0006 heamatology notes 2015

Introduction and general aspects 387 The red cell 389 Anaemia 392 Microcytic anaemia 393 Normocytic anaemia 397 Macrocytic anaemias 397 Megaloblastic anaemia 397 Macrocytosis without megaloblastic changes 401 Anaemia due to marrow failure (aplastic anaemia) 402 Haemolytic anaemias: an introduction 403 Inherited haemolytic anaemia 404 Red cell membrane defects 404 Haemoglobin abnormalities 406 The thalassaemias 407 Sickle syndromes 409 Metabolic disorders of the red cell 412 Acquired haemolytic anaemia 414 Autoimmune haemolytic anaemias 415 Drug-induced immune haemolytic anaemia 417 Alloimmune haemolytic anaemia 417 Non-immune haemolytic anaemia 418 Mechanical haemolytic anaemia 41 Myeloproliferative disorders 419 Polycythaemia 419 Myelofibrosis (myelosclerosis) 421 Myelodysplasia (MDS) 422 The spleen 422 Splenomegaly 423 Blood transfusion 423 Blood groups 424 Procedure for blood transfusion 424 Complications of blood transfusion 425 Blood, blood components and blood products 428 The white cell 430 Neutrophils 430 Eosinophils 431 Basophils 431 Monocytes 431 Lymphocytes 431 Haemostasis and thrombosis 431 Haemostasis 431 Vascular disorders 435 Platelet disorders 435 Inherited coagulation disorders 438 Acquired coagulation disorders 440 Thrombosis 442

1

Iron metabolism Absorption  upper small intestine  about 10% of dietary iron absorbed  Fe2+ (ferrous iron) much better absorbed than Fe3+ (ferric iron)  absorption is regulated according to body's need  increased by vitamin C, gastric acid  decreased by proton pump inhibitors, gastric achlorhydia, tetracycline, tannin (found in tea) Distribution in body:  total body iron = 4g  haemoglobin = 70%  ferritin and haemosiderin = 25%  myoglobin = 4%  plasma iron = 0.1% Transport  carried in plasma as Fe3+ bound to transferrin Storage  stored as ferritin in tissues Excretion  lost via intestinal tract following desquamination

Iron studies Serum iron Total iron binding capacity (TIBC)  transferrin  raised in iron deficiency anaemia (IDA)  raised in pregnancy and by oestrogen Transferrin saturation:  calculated by serum iron / TIBC Ferritin:  raised in inflammatory disorders  low in IDA Rarer tests:  transferrin receptors increased in IDA Anaemia of chronic disease  normochromic/hypochromic, normocytic anaemia  reduced serum and TIBC  normal or raised ferritin 2

Folate metabolism Drugs which interfere with metabolism  trimethoprim  methotrexate  pyrimethamine Drugs which can reduce absorption  phenytoin

Methaemoglobinaemia 





Methaemoglobinaemia describes haemoglobin which has been oxidised from Fe2+ (ferrous iron) to Fe3+ (ferric iron).

This is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin resulting in the reduction of methaemoglobin to haemoglobin.

There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left

Congenital causes 1) haemoglobin chain variants: HbM, HbH 2) NADH methaemoglobin reductase deficiency Acquired causes 1) drugs: 1. sulphonamides, 2. nitrates, sodium nitroprusside, 3. primaquine 4. dapsone 2) chemicals: aniline dyes Features: 1) dyspnoea, anxiety, headache 2) 'chocolate' cyanosis 3) severe: acidosis, arrhythmias, seizures, coma 4) normal pO2 but decreased oxygen saturation Management: 1) NADH - methaemoglobinaemia reductase deficiency: ascorbic acid 2) IV methylene blue if acquired

3

Sideroblastic anaemia:   

A condition where red cells fail to completely form haem, whose biosynthesis takes place partly in the mitochondrion.

This leads to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast.

It may be congenital or acquired

A) Congenital cause: delta-aminolevulinate synthase-2 deficiency B) Acquired causes 1) 2) 3) 4)

myelodysplasia alcohol lead anti-TB medications

Investigations: 1) hypochromic microcytic anaemia (more so in congenital) 2) bone marrow: sideroblasts and increased iron stores Management: 1) supportive 2) treat any underlying cause 3) pyridoxine may help

4

Porphyrias Overview  abnormality in enzymes responsible for the biosynthesis of haem  results in overproduction of intermediate compounds (porphyrins)  may be acute or non-acute

Acute intermittent porphyria:  a rare autosomal dominant condition  caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem.  This results in the toxic accumulation of delta aminolaevulinic acid and porphobilinogen.  It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40 year olds.  AIP is more common in females (5:1) Features: 1) abdominal: abdominal pain, vomiting 2) neurological: motor neuropathy 3) psychiatric: e.g. depression 4) hypertension and tachycardia are common Diagnosis: 1) classically urine turns deep red on standing 2) raised urinary porphobilinogen (Elevated between attacks and to a greater extent during acute attacks) 3) assay of red cells for porphobilinogen deaminase 4) raised serum levels of delta aminolaevulinic acid and porphobilinogen Drugs which may precipitate attack 1) barbiturates 2) benzodiazepines 3) halothane 4) alcohol 5) oral contraceptive pill 6) sulphonamides 5

Drugs considered safe to use 1) paracetamol 2) aspirin 3) codeine 4) morphine 5) chlorpromazine 6) beta-blockers 7) penicillin 8) metformin Porphyria cutanea tarda (PCT):  most common hepatic porphyria  defect in uroporphyrinogen decarboxylase  may be caused by hepatocyte damage e.g. alcohol, oestrogens  classically photosensitive rash with bullae, skin fragility on face and dorsal aspect of hands  urine: elevated uroporphyrinogen and pink fluorescence of urine under Wood's lamp  manage with chloroquine Variegate porphyria:  autosomal dominant  defect in protoporphyrinogen oxidase  photosensitive blistering rash  abdominal and neurological symptoms  more common in South Africans

6

Haemochromatosis:  

Haemochromatosis is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation.

It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6*.

Epidemiology:  

1 in 10 people of European descent carry a mutation genes affecting iron metabolism, mainly HFE prevalence in people of European descent = 1 in 200

Presenting features: 1) early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands) 2) 'bronze' skin pigmentation 3) diabetes mellitus 4) liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition) 5) cardiac failure (2nd to dilated cardiomyopathy) 6) hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism) 7) arthritis (especially of the hands) Questions have previously been asked regarding which features are reversible with treatment: Reversible complications Irreversible complications  Liver cirrhosis**  Cardiomyopathy  Diabetes mellitus  Skin pigmentation  Hypogonadotrophic hypogonadism  Arthropathy **whilst elevated liver function tests and hepatomegaly may be reversible, cirrhosis is not Investigation:  The British Committee for Standards in Haematology (BCSH) published guidelines for the investigation and management of haemochromatosis in 2000  There is continued debate about the best investigation to screen for haemochromatosis.  The 2000 BCSH guidelines suggest: 1) General population:  Transferrin saturation is considered the most useful marker.  Ferritin should also be measured but is not usually abnormal in the early stages of iron accumulation 2) Testing family members: genetic testing for HFE mutation. 

These guidelines may change as HFE gene analysis become less expensive

Diagnostic tests: 1) molecular genetic testing for the C282Y and H63D mutations 2) liver biopsy: Perl's stain 7

Typical iron study profile in patient with haemochromatosis 1) transferrin saturation:  > 55% in men or  > 50% in women 2) raised ferritin (e.g. > 500 ug/l) and iron 3) low TIBC Monitoring adequacy of venesection:  BSCH recommend 'transferrin saturation should be kept below 50% and the serum ferritin concentration below 50 ug/l' Joint x-rays characteristically show chondrocalcinosis *there are rare cases of families with classic features of genetic haemochromatosis but no mutation in the HFE gene

8

Anaemia 392 Microcytic anaemia 393 Normocytic anaemia 397 Macrocytic anaemias 397 Megaloblastic anaemia 397 Macrocytosis without megaloblastic changes 401

Microcytic anaemia: Causes 1) iron-deficiency anaemia 2) thalassaemia: in beta-thalassaemia minor the microcytosis is often disproportionate to the anaemia 3) congenital sideroblastic anaemia 4) lead poisoning 5) anaemia of chronic disease (more commonly a normocytic, normochromic picture) A question sometimes seen in exams gives a history of a normal haemoglobin level associated with a microcytosis. In patients not at risk of thalassaemia, this should raise the possibility of polycythaemia rubra Vera which may cause an iron-deficiency secondary to bleeding.

Iron deficiency anaemia: Features: 1) koilonychia ‫تقعر األظفار‬ 2) atrophic glossitis 3) post-cricoid webs 4) angular stomatitis

Blood film: 1) target cells 2) 'pencil' poikilocytes 3) if combined with B12/folate deficiency a dimorphic film occurs with mixed microcytic and macrocytic cells

Macrocytic anaemia: Macrocytic anaemia can be divided into causes associated with a megaloblastic bone marrow and those with a normoblastic bone marrow Megaloblastic causes 1) vitamin B12 deficiency 2) folate deficiency

Normoblastic causes 1) 2) 3) 4) 5) 6) 7)

alcohol liver disease hypothyroidism pregnancy reticulocytosis myelodysplasia drugs: cytotoxics 9

Pernicious anaemia investigation: Investigation:  anti gastric parietal cell antibodies in 90% (but low specificity)  anti intrinsic factor antibodies in 50% (specific for pernicious anaemia)  macrocytic anaemia  low WCC and platelets  LDH may be raised due to ineffective erythropoiesis  also low serum B12, hypersegmented polymorphs on film, megaloblasts in marrow  Schilling test Schilling test  radiolabelled B12 given on two occasions  first on its own  second with oral IF  urine B12 levels measured

10

Anaemia due to marrow failure (aplastic anaemia)

Aplastic anaemia:  

Characterised by pancytopaenia and a hypoplastic bone marrow Peak incidence of acquired = 30 years old Features: 1) normochromic, normocytic anaemia 2) leukopenia, with lymphocytes relatively spared 3) thrombocytopenia 4) may be the presenting feature acute lymphoblastic or myeloid leukaemia 5) a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia Causes: 1) idiopathic 2) congenital: Fanconi anaemia, dyskeratosis congenita 3) drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold 4) toxins: benzene 5) infections: parvovirus, hepatitis 6) radiation Management: 1) Supportive:  blood products  prevention and treatment of infection 2) Anti-thymocyte globulin (ATG) and anti-lymphocyte globulin (ALG)  prepared in animals (e.g. rabbits or horses) by injecting human lymphocytes  is highly allergenic and may cause serum sickness (fever, rash, arthralgia), therefore steroid cover usually given 3) immunosuppression using agents such as ciclosporin may also be given 4) Stem cell transplantation:  allogeneic transplants have a success rate of up to 80%

Fanconi anaemia Autosomal recessive Features  aplastic anaemia  increased risk of AML  neurological & skeletal abnormalities  skin pigmentation

Drug-induced pancytopaenia Drug causes of pancytopaenia 1) cytotoxics 2) antibiotics: trimethoprim, chloramphenicol 3) anti-rheumatoid: gold, penicillamine 4) carbimazole: causes both agranulocytosis and pancytopaenia 5) anti-epileptics: carbamazepine 6) sulphonylureas: tolbutamide 11

Haemolytic anaemias: by site In intravascular haemolysis:  Free haemoglobin is released which binds to haptoglobin.  As haptoglobin becomes saturated haemoglobin binds to albumin forming methaemalbumin (detected by Schumm's test).  Free haemoglobin is excreted in the urine as haemoglobinuria, haemosiderinuria

Intravascular haemolysis: causes: 1) 2) 3) 4) 5)

mismatched blood transfusion G6PD deficiency* red cell fragmentation: heart valves, TTP, DIC, HUS paroxysmal nocturnal haemoglobinuria cold autoimmune haemolytic anaemia

*strictly speaking there is an element of extravascular haemolysis in G6PD as well, although it is usually classified as a intravascular cause

Extravascular haemolysis: causes 1) 2) 3) 4)

haemoglobinopathies: sickle cell, thalassaemia hereditary spherocytosis haemolytic disease of newborn warm autoimmune haemolytic anaemia

12

13

14

Causes of haemolytic anaemia Inherited

Acquired

Red cell membrane defect 1) Hereditary spherocytosis 2) Hereditary elliptocytosis

Immune 1) Autoimmune  Warm  Cold 2) Alloimmune  Haemolytic transfusion reactions  Haemolytic disease of the newborn  After allogeneic bone marrow or organ transplantation 3) Drug-induced

Haemoglobin abnormalities 1) Thalassaemia 2) Sickle cell disease Metabolic defects 1) Glucose-6-phosphate dehydrogenase deficiency 2) Pyruvate kinase deficiency 3) Pyrimidine kinase deficiency Miscellaneous 1) Infections, e.g. malaria, mycoplasma Clostridium welchii, 2) generalized sepsis 3) Drugs and chemicals causing damage to the red cell membrane or oxidative haemolysis 4) Hypersplenism 5) Burns

Non-immune 1) Acquired membrane defects: Paroxysmal nocturnal haemoglobinuria 2) Mechanical:  Microangiopathic haemolytic anaemia  Valve prosthesis  March haemoglobinuria 3) Secondary to systemic disease Renal and liver failure

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Red cell membrane defect 1) Hereditary spherocytosis 2) Hereditary elliptocytosis

Hereditary spherocytosis Basics  most common hereditary haemolytic anaemia in people of northern European descent  autosomal dominant defect of red blood cell cytoskeleton  the normal biconcave disc shape is replaced by a sphere-shaped red blood cell  red blood cell survival reduced as destroyed by the spleen Presentation: 1) failure to thrive 2) jaundice, gallstones 3) splenomegaly 4) aplastic crisis precipitated by parvovirus infection 5) degree of haemolysis variable 6) MCHC elevated Diagnosis:  osmotic fragility test Management: 1) folate replacement 2) splenectomy Comparing G6PD deficiency to hereditary spherocytosis G6PD deficiency

Hereditary spherocytosis

Gender

Male (X-linked recessive)

Male + female (autosomal dominant)

Ethnicity

African + Mediterranean descent

Northern European descent

Typical history



Neonatal jaundice



Neonatal jaundice



Infection/ drugs precipitate haemolysis



Chronic symptoms although haemolytic crises may be precipitated by infection



Gallstones



Gallstones Splenomegaly is common Extravascular Heamolysis

 



Intravascular Heamolysis

Blood film

Heinz bodies

Spherocytes (round, lack of central pallor)

Diagnostic test

Measure enzyme activity of G6PD

Osmotic fragility test

16

Haemoglobin Abnormalities 1) Thalassaemia 2) Sickle Cell Disease

Thalassaemia 

The thalassaemias are a group of genetic disorders characterised by a reduced production rate of either alpha or beta chains.

17

Alpha-thalassaemia: Alpha-thalassaemia is due to a deficiency of alpha chains in haemoglobin Overview:  2 separate alpha-globulin genes are located on each chromosome 16  Clinical severity depends on the number of alpha chains present  If 1 or 2 alpha chains are absent

 

the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal

 Loss of 3 alpha chains results in

 

Hypochromic microcytic anaemia with splenomegaly.

This is known as Hb H disease

 If all 4 alpha chains absent (i.e. homozygote) then



death in utero (hydrops fetalis, Bart's hydrops)

Beta-thalassaemia trait:   

Beta-thalassaemia trait is an autosomal recessive condition Characterised by a mild hypochromic, microcytic anaemia.

It is usually asymptomatic

Features: 1) mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia 2) HbA2 raised (> 3.5%) normally it is 2%

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Haemoglobin abnormalities 1) Thalassaemia 2) Sickle cell disease

Sickle-cell crises:  

Sickle cell anaemia is characterised by periods of good health with intervening crises Four main types of crises are recognised: 1) thrombotic, 'painful crises' 2) sequestration 3) aplastic 4) haemolytic

A) Thrombotic crises:  



also known as painful crises or vaso-occlusive crises precipitated by: 1) infection, 2) dehydration, 3) deoxygenation infarcts occur in various organs including: 1) the bones e.g. avascular necrosis of hip, 2) hand-foot syndrome in children, 3) lungs, spleen and brain

B) Sequestration crises:  

sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia acute chest syndrome: 1) dyspnoea, 2) chest pain, 3) pulmonary infiltrates, 4) low pO2 5) the most common cause of death after childhood

C) Aplastic crises  

caused by infection with parvovirus sudden fall in haemoglobin

D) Haemolytic crises:  

rare fall in haemoglobin due an increased rate of haemolysis

Sickle cell anemia cause nephrogenic Diabetes Insipidus

19

G6PD deficiency 

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect.  It is more common in people from the Mediterranean and Africa  Inherited in a X-linked recessive fashion.  Many drugs can precipitate a crisis as well as infections and broad (fava) beans Pathophysiology:  ↓ G6PD → ↓ glutathione → increased red cell susceptibility to oxidative stress Features: 1) neonatal jaundice is often seen 2) intravascular haemolysis 3) gallstones are common 4) splenomegaly may be present 5) Heinz bodies on blood films Diagnosis is made by using a G6PD enzyme assay Some drugs causing haemolysis: 1) anti-malarials: primaquine 2) ciprofloxacin 3) sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas Some drugs thought to be safe 1) penicillins 2) cephalosporins 3) macrolides 4) tetracyclines 5) trimethoprim Comparing G6PD deficiency to hereditary spherocytosis G6PD deficiency

Hereditary spherocytosis

Gender

Male (X-linked recessive)

Male + female (autosomal dominant)

Ethnicity

African + Mediterranean descent

Northern European descent

Typical history

• Neonatal jaundice • Infection/drugs precipitate haemolysis • Gallstones

• Neonatal jaundice • Chronic symptoms although haemolytic crises may be precipitated by infection • Gallstones • Splenomegaly is common

Blood film

Heinz bodies

Spherocytes (round, lack of central pallor)

Diagnostic test

Measure enzyme activity of G6PD

Osmotic fragility test

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Acquired haemolytic anaemia Causes of immune destruction of red cells  Autoimmune haemolytic anaemias  Drug-induced immune haemolytic anaemia  Alloimmune haemolytic anaemia Causes of non-immune destruction of red cells  Acquired membrane defects (e.g. paroxysmal nocturnal haemoglobinuria).  Mechanical factors (e.g. prosthetic heart valves, or microangiopathic haemolytic anaemia)  Secondary to systemic disease (e.g. renal and liver disease).

Autoimmune haemolytic anaemia   

Autoimmune haemolytic anaemia (AIHA) may be divided in to 'warm' and 'cold' types, according to at what temperature the antibodies best cause haemolysis.

It is most commonly idiopathic but may be secondary to a lymphoproliferative disorder, infection or drugs.

AIHA is characterised by a positive direct antiglobulin test (Coombs' test)

A) Warm AIHA:    

In warm AIHA the antibody is usually IgG causes haemolysis best at body temperature Haemolysis tends to occur in extravascular sites, for example the spleen.

Management options include steroids, immunosuppression and splenectomy

Causes of warm AIHA 1) autoimmune disease: e.g. systemic lupus erythematosus* 2) neoplasia: e.g. lymphoma, CLL 3) drugs: e.g. methyldopa *systemic lupus erythematosus can rarely be associated with a mixed-type autoimmune haemolytic anaemia

B) Cold AIHA:     

The antibody in cold AIHA is usually IgM Causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular.

Features may include symptoms of Raynaud's and acrocynaosis.

Patients respond less well to steroids

Causes of cold AIHA: 1) neoplasia: e.g. lymphoma 2) infections: e.g. mycoplasma, EBV

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Drug-induced haemolytic anaemia: Drug-induced haemolytic anaemia can be classified according to three different mechanisms: Type I:  antibody against drug-red cell membrane complex  penicillin Type II:  deposition of complement via a drug-protein-antibody complex onto the red cell membrane  quinidine  rifampicin Type III:  true autoimmune haemolytic anaemia - role of drug not known  methyldopa  L-dopa  mefanamic acid

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Paroxysmal nocturnal haemoglobinuria: (PNH)   

An acquired disorder leading to haemolysis (mainly intravascular) of haematological cells.

It is thought to be caused by increased sensitivity of cell membranes to complement (see below) due to a lack of glycoprotein glycosyl-phosphatidylinositol (GPI).

Patients are more prone to venous thrombosis

Pathophysiology:  GPI can be thought of as an anchor which attaches surface proteins to the cell membrane  complement-regulating surface proteins, e.g. decay-accelerating factor (DAF), are not properly bound to the cell membrane due a lack of GPI  thrombosis is thought to be caused by a lack of CD59 on platelet membranes predisposing to platelet aggregation Features: 1) haemolytic anaemia 2) red blood cells, white blood cells, platelets or stem cells may be affected therefore pancytopaenia may be present 3) haemoglobinuria: classically dark-coloured urine in the morning (although has been shown to occur throughout the day) 4) thrombosis e.g. Budd-Chiari syndrome 5) aplastic anaemia may develop in some patients Diagnosis:  flow cytometry of blood to detect low levels of CD59 and CD55 has now replaced Ham's test as the gold standard investigation in PNH  Ham's test: acid-induced haemolysis (normal red cells would not) Management: 1) blood product replacement 2) anticoagulation 3) Eculizumab:  a monoclonal antibody directed against terminal protein C5,  is currently being trialled and is showing promise in reducing intravascular haemolysis 4) stem cell transplantation

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Myeloproliferative disorders 419 Polycythaemia 419 Myelofibrosis (myelosclerosis) 421 Myelodysplasia (MDS) 422

Polycythaemia: Polycythaemia may be relative, primary (polycythaemia rubra vera) or secondary Relative causes: 1) dehydration 2) stress: Gaisbock syndrome Primary:  polycythaemia rubra vera Secondary causes: 1) COPD 2) altitude 3) obstructive sleep apnoea 4) excessive erythropoietin:  cerebellar haemangioma,  hypernephroma,  hepatoma,  uterine fibroids: uterine fibroids may cause menorrhagia which in turn leads to blood loss - polycythaemia is rarely a clinical problem  

To differentiate between true (primary or secondary) polycythaemia and relative polycythaemia red cell mass studies are sometimes used.

In true polycythaemia the total red cell mass in males > 35 ml/kg and in women > 32 ml/kg

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Polycythaemia Rubra Vera:    

(PRV) A myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume.

Often accompanied by overproduction of neutrophils and platelets.

It has recently been established that a mutation in JAK2 is present in approximately 95% of patients with PRV and this has resulted in significant changes to the diagnostic criteria.

The incidence of PRV peaks in the sixth decade.

Features: 1) hyperviscosity 2) pruritus, typically after a hot bath 3) splenomegaly 4) haemorrhage (secondary to abnormal platelet function) 5) plethoric appearance 6) hypertension in a third of patients 7) Other features that may be seen in PRV include a low ESR and a raised leukocyte alkaline phosphotase Following history and examination, the British Committee for Standards in Haematology (BCSH) recommends the following tests are performed: 1) full blood count/film (raised haematocrit; neutrophils, basophils, platelets raised in half of patients) 2) JAK2 mutation 3) serum ferritin 4) renal and liver function tests If the JAK2 mutation is negative and there is no obvious secondary causes the BCSH suggest the following tests: 1) red cell mass 2) arterial oxygen saturation 3) abdominal ultrasound 4) serum erythropoietin level 5) bone marrow aspirate and trephine 6) cytogenetic analysis 7) erythroid burst-forming unit (BFU-E) culture

25

The diagnostic criteria for PRV have recently been updated by the BCSH. This replaces the previous PRV Study Group criteria.

JAK2-positive PRV - diagnosis requires both criteria to be present Criteria

Notes

A1

 

A2

Mutation in JAK2

High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted)

JAK2-negative PRV - diagnosis requires A1 + A2 + A3 + either another A or two B criteria Criteria

Notes

A1

 

A2

Absence of mutation in JAK2

A3

No cause of secondary erythrocytosis

A4

Palpable splenomegaly

A5

Presence of an acquired genetic abnormality (excluding BCRABL) in the haematopoietic cells

B1

Thrombocytosis (platelet count >450 * 109/l)

B2

Neutrophil leucocytosis (neutrophil count > 10 * 109/l in non-smokers; > 12.5*109/l in smokers)

B3

Radiological evidence of splenomegaly

B4

 

haematocrit >0.60 in men, >0.56 in women OR Raised red cell mass (>25% above predicted)

Endogenous erythroid colonies or low serum erythropoietin

Polycythaemia rubra Vera management: 1) venesection - first line treatment 2) aspirin 3) hydroxyurea -slight increased risk of secondary leukaemia 4) phosphorus-32 therapy Prognosis:  thrombotic events are a significant cause of morbidity and mortality  5-15% of patients progress to myelofibrosis  5-15% of patients progress to acute myeloid leukaemia (risk increased with chemotherapy treatment) 26

Myeloproliferative disorders 419 Polycythaemia 419 Myelofibrosis (myelosclerosis) 421 Myelodysplasia (MDS) 422

Myelofibrosis: Overview:  a myeloproliferative disorder  thought to be caused by hyperplasia of abnormal megakaryocytes  the resultant release of platelet derived growth factor is thought to stimulate fibroblasts  haematopoiesis develops in the liver and spleen Features: 1) e.g. elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom) 2) massive splenomegaly 3) hypermetabolic symptoms: weight loss, night sweats etc Laboratory findings: 1) anaemia 2) high WBC and platelet count early in the disease 3) 'tear-drop' poikilocytes on blood film 4) unobtainable bone marrow biopsy - 'dry tap' therefore trephine biopsy needed 5) high urate and LDH (reflect increased cell turnover)

27

Thrombocytosis: Thrombocytosis is an abnormally high platelet count, usually > 400 * 109/l.

Causes of thrombocytosis A) reactive: platelets are an acute phase reactant - platelet count can increase in response to stress such as a severe infection or surgery B) malignancy C) essential thrombocytosis (see below), or as part of another myeloproliferative disorder such as chronic myeloid leukaemia or polycythaemia rubra vera D) hyposplenism

Essential Thrombocytosis  

Essential thrombocytosis is one of the myeloproliferative disorders which overlaps with chronic myeloid leukaemia, polycythaemia rubra vera and myelofibrosis.

Megakaryocyte proliferation results in an overproduction of platelets.

Features: 1) platelet count > 600 * 109/l 2) both thrombosis (venous or arterial) and haemorrhage can be seen 3) a characteristic symptom is a burning sensation in the hands 4) a JAK2 mutation is found in around 50% of patients Management 1) hydroxyurea (hydroxycarbamide) is widely used to reduce the platelet count 2) interferon-Îą is also used in younger patients 3) low-dose aspirin may be used to reduce the thrombotic risk

28

Hyposplenism: Causes: 1) splenectomy 2) sickle-cell 3) coeliac disease, dermatitis herpetiformis 4) Graves' disease 5) systemic lupus erythematosus 6) amyloid Features: 1) Howell-Jolly bodies 2) siderocytes

Blood product transfusion complications 1) haemolytic: immediate or delayed 2) febrile reactions 3) transmission of viruses, bacteria, parasites As platelet concentrates are generally stored at room temperature they provide a more favourable environment for bacterial contamination than other blood products.

4) hyperkalaemia 5) iron overload 6) ARDS 7) clotting abnormalities 8) Massive blood tx may cause hypocalcemia

Immediate haemolytic reaction 

E.g. ABO mismatch massive intravascular haemolysis

Febrile reactions:  

due to white blood cell HLA antibodies often the result of sensitization by previous pregnancies or transfusions

Causes a degree of immunosuppression 

e.g. patients with colorectal cancer who have blood transfusions have a worse outcome than those who do not

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The white cell

Eosinophilia Causes of eosinophilia may be divided into pulmonary, infective and other Pulmonary causes: 1) asthma 2) allergic bronchopulmonary aspergillosis 3) Churg-Strauss syndrome 4) Loffler's syndrome 5) tropical pulmonary eosinophilia 6) eosinophilic pneumonia 7) hypereosinophilic syndrome Infective causes: 1) schistosomiasis 2) nematodes: Toxocara, Ascaris, Strongyloides 3) cestodes: Echinococcus Other causes 1) drugs: sulfasalazine, nitrofurantoin 2) psoriasis/eczema 3) eosinophilic leukaemia (very rare)

Neutropenic sepsis 

Neutropenic sepsis is a relatively common complication of cancer therapy, usually as a consequence of chemotherapy.  It may be defined as a neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:  a temperature higher than 38C or  other signs or symptoms consistent with clinically significant sepsis Prophylaxis: 9  if it is anticipated that patients are likely to have a neutrophil count of < 0.5 * 10 as a consequence of their treatment they should be offered a fluoroquinolone Management: 1) antibiotics must be started immediately, do not wait for the WBC 2) NICE recommend starting empirical antibiotic therapy with piperacillin with tazobactam (Tazocin) immediately 3) many units add vancomycin if the patient has central venous access but NICE do not support this approach 4) following this initial treatment patients are usually assessed by a specialist and risk-stratified to see if they may be able to have outpatient treatment 5) if patients are still febrile and unwell after 48 hours an alternative antibiotic such as meropenem is often prescribed +/- vancomycin 6) if patients are not responding after 4-6 days the Christie guidelines suggest ordering investigations for fungal infections (e.g. HRCT), rather than just starting therapy antifungal therapy blindly 7) there may be a role for G-CSF in selected patients 30

Blood films: typical pictures Hyposplenism e.g. post-splenectomy 1) target cells 2) Howell-Jolly bodies 3) Pappenheimer bodies 4) siderotic granules 5) acanthocytes Iron-deficiency anaemia: 1) target cells 2) 'pencil' poikilocytes 3) if combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells Myelofibrosis:  'tear-drop' poikilocytes Intravascular haemolysis:  schistocytes Megaloblastic anaemia:  hypersegmented neutrophils Blood films: pathological cell forms Pathological red cell forms Abnormality

Associated condition(s)

Target cells

   

'Tear-drop' poikilocytes

Myelofibrosis

Spherocytes

 

Appearance

Sickle-cell/thalassaemia Iron-deficiency anaemia Hyposplenism Liver disease

Hereditary spherocytosis Autoimmune hemolytic anaemia

31

Abnormality

Associated condition(s)

Basophilic stippling

 

Howell-Jolly bodies

Hyposplenism

Heinz bodies

 

G6PD deficiency Alpha-thalassaemia

Schistocytes ('helmet cells')

  

Intravascular haemolysis Mechanical heart valve DIC

'Pencil' poikilocytes

Iron defiency anaemia

Burr cells (echinocytes)

 

Acanthocytes

Abetalipoproteinemia

Appearance

Lead poisoning Thalassaemia

Uraemia Pyruvate kinase deficiency

Other blood film abnormalities:  hypersegmented neutrophils: megaloblastic anaemia

32

Leucocyte alkaline phosphatase: Rose in:  pregnancy, oral contraceptive pill  infections  leukaemoid reactions  myelofibrosis  polycythaemia rubra vera  steroids, Cushing's syndrome Low in:  chronic myeloid leukaemia  pernicious anaemia  paroxysmal nocturnal haemoglobinuria  infectious mononucleosis

Leukaemoid reaction:  

The leukaemoid reaction describes the presence of immature cells such as myeloblasts, promyelocytes and nucleated red cells in the peripheral blood.

This may be due to: 1. infiltration of the bone marrow causing the immature cells to be 'pushed out' or 2. sudden demand for new cells

Causes: 1) severe infection 2) severe haemolysis 3) massive haemorrhage 4) metastatic cancer with bone marrow infiltration A relatively common clinical problem is differentiating chronic myeloid leukaemia from a leukaemoid reaction. The following differences may help: Leukaemoid reaction  high leucocyte alkaline phosphatase score  toxic granulation (Dohle bodies) in the white cells  'left shift' of neutrophils i.e. three or less segments of the nucleus

Chronic myeloid leukaemia  low leucocyte alkaline phosphatase score

33

Haematological Malignancies: Genetics: Below is a brief summary of the common translocations associated with haematological malignancies

t(9;22) - Philadelphia chromosome:  present in > 95% of patients with CML  this results in part of the Abelson proto-oncogene being moved to the BCR gene on chromosome 22  the resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal  poor prognostic indicator in ALL t(15;17):  seen in acute promyelocytic leukaemia (M3)  fusion of PML and RAR-alpha genes t(8;14):  seen in Burkitt's lymphoma  MYC oncogene is translocated to an immunoglobulin gene t(11;14)  Mantle cell lymphoma  deregulation of the cyclin D1 (BCL-1) gene

Haematological malignancies: Infections: Viruses:  EBV: Hodgkin's and Burkitt's lymphoma, nasopharyngeal carcinoma  HTLV-1: Adult T-cell leukaemia/lymphoma  HIV-1: High-grade B-cell lymphoma Bacteria:  Helicobacter pylori: gastric lymphoma (MALT) Protozoa:  malaria: Burkitt's lymphoma

34

Acute myeloid leukaemia:  

Acute myeloid leukaemia is the more common form of acute leukaemia in adults.

It may occur as a primary disease or following a secondary transformation of a myeloproliferative disorder.

Poor prognostic features: 1) > 60 years 2) > 20% blasts after first course of chemo 3) cytogenetics: deletions of chromosome 5 or 7

Acute promyelocytic leukaemia:   

Acute promyelocytic leukaemia (APML) is the M3 subtype of AML. The importance of identifying APML lies in both the presentation (classically disseminated intravascular coagulation) and management APML is associated with the t(15;17) translocation which causes fusion of the PML and RARalpha genes.

Features: 1) presents younger than other types of AML (average = 25 years old) 2) DIC or thrombocytopenia often at presentation 3) good prognosis 4) Auer rods (seen with myeloperoxidase stain) Classification - French-American-British (FAB)  MO - undifferentiated  M1 - without maturation  M2 - with granulocytic maturation  M3 - acute promyelocytic  M4 - granulocytic and monocytic maturation  M5 - monocytic  M6 - erythroleukaemia  M7 - megakaryoblastic

Gingival hyperplasia Drug causes of gingival hyperplasia 1) phenytoin 2) ciclosporin 3) calcium channel blockers (especially nifedipine) Other causes of gingival hyperplasia include  acute myeloid leukaemia (myelomonocytic and monocytic types)

35

Chronic myeloid leukaemia: 

The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML).  It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11).  This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22.  The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal Presentation (40-50 years): 1) middle-age 2) anaemia, weight loss, abdo discomfort 3) splenomegaly may be marked 4) spectrum of myeloid cells seen in peripheral blood 5) decreased leukocyte alkaline phosphatase 6) May undergo blast transformation (AML in 80%, ALL in 20%) Management: 1) imatinib is now considered first-line treatment 2) hydroxyurea 3) interferon-alpha 4) allogenic bone marrow transplant

Imatinib: 1) inhibitor of the tyrosine kinase associated with the BCR-ABL defect 2) very high response rate in chronic phase CML

Hairy cell leukaemia:  

Hairy cell leukaemia is a rare malignant proliferation disorder of B cells.

It is more common in males (4:1) Features: 1) pancytopenia 2) splenomegaly 3) skin vasculitis in 1/3 patients 4) 'dry tap' despite bone marrow hypercellularity 5) tartrate resistant acid phosphotase (TRAP) stain positive Management: 1) chemotherapy is first-line: cladribine, pentostatin 2) immunotherapy is second-line: rituximab, interferon-alpha

Interferons (IFN)  

 

These Are cytokines released by the body in response to viral infections and neoplasia.

They are classified according to cellular origin and the type of receptor they bind to: 1) IFN-alpha and IFN-beta bind to type 1 receptors whilst 2) IFN-gamma binds only to type 2 receptors.

IFN-alpha is produced by leucocytes and has an antiviral action.

It has been shown to be useful in the management of hepatitis B & C, Kaposi's sarcoma, metastatic renal cell cancer and hairy cell leukaemia 36

Acute lymphoblastic leukaemia: Prognostic features Good prognostic factors: 1) French-American-British (FAB) L1 type 2) common ALL 3) pre-B phenotype 4) low initial WBC 5) del(9p) Poor prognostic factors: 1) FAB L3 type 2) T or B cell surface markers 3) Philadelphia translocation, t(9;22) 4) age < 2 years or > 10 years 5) male sex 6) CNS involvement 7) high initial WBC (e.g. > 100 * 109/l) 8) non-Caucasian

37

Chronic lymphocytic leukaemia: 

Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of welldifferentiated lymphocytes which are almost always B-cells (99%) Features: 1) often none 2) constitutional: anorexia, weight loss 3) bleeding, infections 4) lymphadenopathy more marked than CML Complications: 1) hypogammaglobulinaemia leading to recurrent infections 2) warm autoimmune haemolytic anaemia in 10-15% of patients 3) transformation to high-grade lymphoma (Richter's transformation) Investigations: 1) blood film: smudge cells 2) immunophenotyping Prognostic factors Poor prognostic factors: (median survival 3-5 years) 1) male sex 2) age > 70 years 3) lymphocyte count > 50 4) prolymphocytes comprising more than 10% of blood lymphocytes 5) lymphocyte doubling time < 12 months 6) raised LDH 7) CD38 expression positive Chromosomal changes: A) Deletion of the long arm of chromosome 13 (del 13q) :  It is the most common abnormality, being seen in around 50% of patients.  It is associated with a good prognosis B) deletions of part of the short arm of chromosome 17 (del 17p)  These are seen in around 5-10% of patients  associated with a poor prognosis Indications for treatment 1) progressive marrow failure: the development or worsening of anaemia and/or thrombocytopenia 2) massive (>10 cm) or progressive lymphadenopathy 3) massive (>6 cm) or progressive splenomegaly 4) progressive lymphocytosis: > 50% increase over 2 months or lymphocyte doubling time < 6months 5) systemic symptoms:  weight loss > 10% in previous 6 months,  fever >38 C for > 2 weeks,  extreme fatigue, night sweats 6) autoimmune cytopaenias e.g. ITP Management: 1) patients who have no indications for treatment are monitored with regular blood counts 2) fludarabine, cyclophosphamide and rituximab (FCR) has now emerged as the initial treatment of choice for the majority of patients 38

Hodgkin's lymphoma  

Malignant proliferation of lymphocytes Characterised by the presence of the Reed-Sternberg cell.

It has a bimodal age distributions being most common in the third and seventh decades Features: 1) lymphadenopathy (75%) - painless, non-tender, asymmetrical 2) systemic (25%): weight loss, pruritus, night sweats, fever (Pel-Ebstein) 3) alcohol pain in HL 4) normocytic anaemia, eosinophilia 5) LDH raised Histological classification: Type

Frequency

Prognosis

Notes

Nodular sclerosing

Most common (around 70%)

Good prognosis

 

Mixed cellularity

Around 20%

Good prognosis

Associated with a large number of Reed-Sternberg cells

Lymphocyte predominant

Around 5%

Best prognosis

Lymphocyte depleted

Rare

Worst prognosis

More common in women.

Associated with lacunar cells

'B' symptoms also imply a poor prognosis 1) weight loss > 10% in last 6 months 2) fever > 38 C 3) night sweats Other factors associated with a poor prognosis identified in a 1998 NEJM paper included: 1) age > 45 years 2) male 3) stage IV disease 4) haemoglobin < 10.5 g/dl 5) white blood count > 15,000/�l 6) lymphocyte count < 600/�l or < 8% 7) albumin < 40 g/l *Reed-Sternberg cells with nuclei surrounded by a clear space Hodgkin's lymphoma: staging: Ann-Arbor staging of Hodgkin's lymphoma  I: single lymph node  II: 2 or more lymph nodes/regions on same side of diaphragm  III: nodes on both sides of diaphragm  IV: spread beyond lymph nodes Each stage may be subdivided into A or B  A = no systemic symptoms other than pruritus  B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis) 39

Burkitt's lymphoma  

Burkitt's lymphoma is a high-grade B-cell neoplasm.

There are two major forms: 1) Endemic (African) form: typically involves maxilla or mandible

2) Sporadic form:  Abdominal (e.g. ileo-caecal) tumours are the most common form.  More common in patients with HIV  

Burkitt's lymphoma is associated with the c-myc gene translocation, usually t(8:14).

The Epstein-Barr virus (EBV) is strongly implicated in the development of the African form of Burkitt's lymphoma and to a lesser extent the sporadic form.

Management: 1) Is with chemotherapy.

1) This tends to produce a rapid response which may cause 'tumour lysis syndrome'.

2) Rasburicase :  A recombinant version of urate oxidase,  An enzyme which catalyses the conversion of uric acid to allantoin is often given before the chemotherapy to reduce the risk of 'tumour lysis syndrome'.  allantoin is 5-10 times more soluble than uric acid, so renal excretion is more effective Complications of tumour lysis syndrome: 1) hyperuricaemia 2) hyperkalaemia 3) hyperphosphataemia 4) hypocalcaemia 5) acute renal failure

40

Paraproteinaemia: Causes of paraproteinaemia: 1) myeloma 2) monoclonal gammopathy of uncertain significance (MGUS) 3) benign monoclonal gammopathy 4) Waldenstrom's macroglobulinaemia 5) amyloidosis 6) CLL, lymphoma 7) heavy chain disease 8) POEMS Benign monoclonal gammopathy: 1) non-lymphoid malignancy (e.g. colon, breast) 2) infections (CMV, hepatitis) 3) autoimmune disorders (RA, SLE)

41

Myeloma Overview:  neoplastic proliferation of bone marrow plasma cells  peak age = 60-70 years  equal sex ratio Monoclonal products produced  IgG (50-60%)  IgA (20-30%)  Light chain disease (20%) Clinical features: 1) bone disease:  bone pain,  osteoporosis + pathological fractures (typically vertebral),  osteolytic lesions 2) lethargy 3) infection 4) hypercalcaemia (see below) 5) renal failure 6) amyloidosis e.g. Macroglossia, 7) carpal tunnel syndrome; 8) neuropathy; 9) hyperviscosity Diagnosis is based on: 2 of the following 3 1) monoclonal proteins in the serum and urine (Bence Jones proteins) 2) Increased plasma cells in the bone marrow (> 20%) 3) bone lesions on the skeletal survey Hypercalcaemia in myeloma 1) primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells 2) much less common contributing factors: 1. impaired renal function, 2. increased renal tubular calcium reabsorption and 3. elevated PTH-rP levels Myeloma prognosis: 1) B2-microglobulin is a useful marker of prognosis - raised levels imply poor prognosis.

2) Low levels of albumin are also associated with a poor prognosis International prognostic index Stage

Criteria

Median survival (months)

I

B2 microglobulin < 3.5 mg/l Albumin > 35 g/l

62

II

Not I or III

45

III

B2 microglobulin > 5.5 mg/l

29 42

MGUS:    

Monoclonal gammopathy of undetermined significance (MGUS) also known as benign paraproteinaemia and monoclonal gammopathy.

It is a common condition that causes a paraproteinaemia and is often mistaken for myeloma.

Differentiating features are listed below.

Around 10% of patients eventually develop myeloma at 5 years, with 50% at 15 years

Features: 1) usually asymptomatic 2) no bone pain or increased risk of infections 3) around 10-30% of patients have a demyelinating neuropathy Differentiating features from myeloma 1) normal immune function 2) normal beta-2 microglobulin levels 3) lower level of paraproteinaemia than myeloma (e.g. < 30g/l IgG, or < 20g/l IgA) 4) stable level of paraproteinaemia 5) no clinical features of myeloma (e.g. lytic lesions on x-rays or renal disease)

Waldenstrom's macroglobulinaemia  

An uncommon condition seen in older men.

It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein

Features: 1) monoclonal IgM paraproteinaemia 2) systemic upset: weight loss, lethargy 3) hyperviscosity syndrome e.g. visual disturbance 4) hepatosplenomegaly 5) lymphadenopathy 6) cryoglobulinaemia e.g. Raynaud's

43

Amyloidosis Overview  amyloidosis is a term which describes the extracellular deposition of an insoluble fibrillar protein termed amyloid  amyloid is derived from many different precursor proteins: A) fibrillar component B) non-fibrillary protein: 1) amyloid-P component, derived from the acute phase protein serum amyloid P 2) apolipoprotein E and 3) heparan sulphate proteoglycans 

the accumulation of amyloid fibrils leads to tissue/organ dysfunction

Classification:  systemic or localized  further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments) Diagnosis:  Congo red staining: apple-green birefringence  serum amyloid precursor (SAP) scan  biopsy of rectal tissue

Renal amyloid with congo red staining - apple-green birefringence

Renal amyloid with congo red staining - apple-green birefringence

44

Congo red staining. Amyloid deposits are seen in both the arteries/arterioles and within the glomerulus. The deposit of amyloid within the mesangium is not dissimilar to the nodular lesions seen in diabetic nephropathy

Amyloidosis: types A) AL amyloid:  L for immunoglobulin Light chain fragment  due to myeloma, Waldenstrom's, MGUS  features include: cardiac and neurological involvement, macroglossia, periorbital eccymoses B) AA amyloid:  A for precursor serum amyloid A protein, an acute phase reactant  seen in chronic infection/inflammation  e.g. TB, bronchiectasis, rheumatoid arthritis  features: renal involvement most common feature C) Beta-2 microglobulin amyloidosis:  precursor protein is beta-2 microglobulin, part of the major histocompatibility complex  associated with patients on renal dialysis

45

Haemostasis and thrombosis 431 Haemostasis 431 Vascular disorders 435 Platelet disorders 435 Inherited coagulation disorders 438 Acquired coagulation disorders 440 Thrombosis 442

Thrombocytopenia: Causes of severe thrombocytopenia 1) ITP 2) DIC 3) TTP 4) haematological malignancy Causes of moderate thrombocytopenia: 1) heparin induced thrombocytopenia (HIT) 2) drug-induced (e.g. quinine, diuretics, sulphonamides, aspirin, thiazides) 3) alcohol 4) liver disease 5) hypersplenism 6) viral infection (EBV, HIV, hepatitis) 7) pregnancy 8) SLE/antiphospholipid syndrome 9) vitamin B12 deficiency

ITP 

Idiopathic thrombocytopenic purpura (ITP) is an immune mediated reduction in the platelet count.  Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.  ITP can be divided into acute and chronic forms: Acute ITP:  more commonly seen in children  equal sex incidence  may follow an infection or vaccination  usually runs a self-limiting course over 1-2 weeks Chronic ITP:  more common in young/middle-aged women  tends to run a relapsing-remitting course Investigations: 1) antiplatelet autoantibodies (usually IgG) 2) Bone marrow aspiration shows megakaryocytes in the marrow. This should be carried out prior to the commencement of steroids in order to rule out leukaemia Management: 1) oral prednisolone (80% of patients respond) 2) splenectomy if platelets < 30 after 3 months of steroid therapy 3) IV immunoglobulins 4) immunosuppressive drugs e.g. cyclophosphamide Evan's syndrome: ITP in association with autoimmune haemolytic anaemia (AIHA) 46

Thrombotic thrombocytopenic purpura: Pathogenesis of thrombotic thrombocytopenic purpura (TTP) 1) abnormally large and sticky multimers of von Willebrand's factor cause platelets to clump within vessels 2) in TTP there is a deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns large multimers of von Willebrand's factor 3) overlaps with haemolytic uraemic syndrome (HUS) Features: 1) rare, typically adult females 2) fever 3) fluctuating neuro signs (microemboli) 4) microangiopathic haemolytic anaemia 5) thrombocytopenia 6) renal failure Causes: 1) post-infection e.g. urinary, gastrointestinal 2) pregnancy 3) drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir 4) tumours 5) SLE 6) HIV Management: 1) no antibiotics - may worsen outcome 2) plasma exchange is the treatment of choice 3) steroids, immunosuppressants 4) vincristine

47

Haemolytic uraemic syndrome Haemolytic uraemic syndrome is generally seen in young children and produces a triad of:   

acute renal failure microangiopathic haemolytic anaemia thrombocytopenia

Causes  post-dysentery - classically E coli 0157:H7 ('verotoxigenic', 'enterohaemorrhagic')  tumours  pregnancy  ciclosporin, the Pill  systemic lupus erythematosus  HIV Investigations  full blood count: anaemia, thrombocytopaenia, fragmented blood film  U&E: acute renal failure  stool culture Management  treatment is supportive e.g. Fluids, blood transfusion and dialysis if required  there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients  The indications for plasma exchange in HUS are complicated. As a general rule plasma exchange is reserved for severe cases of HUS not associated with diarrhoea

Heparin-induced thrombocytopaenia (HIT)   

immune mediated - antibodies form which cause the activation of platelets usually does not develop until after 5-10 days of treatment despite being associated with low platelets HIT is actually a prothrombotic condition

Features: 1) a greater than 50% reduction in platelets, 2) thrombosis and 3) skin allergy Treatment options include Alternative anticoagulants such as lepirudin and danaparoid

48

Haemophilia  

Haemophilia is X-linked recessive disorder of coagulation.

Up to 30% of patients have no family history of the condition.

A) Haemophilia A 1) It is due to a deficiency of factor VIII 2) accounts for 90% of cases of haemophilia B) haemophilia B (Christmas disease) there is a lack of factor IX Features: 1) haemoarthroses, haematomas 2) prolonged bleeding after surgery or trauma Blood tests: 1) prolonged APTT 2) bleeding time, thrombin time, prothrombin time normal 3) Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment A normal factor VIIIc activity points to a diagnosis of haemophilia B (lack of factor IX).

Von Willebrand's disease   

The most common inherited bleeding disorder.

The majority of cases are inherited in an autosomal dominant fashion characteristically behaves like a platelet disorder i.e:  epistaxis and menorrhagia are common whilst  haemoarthroses and muscle haematomas are rare Role of von Willebrand factor:  large glycoprotein which forms massive multimers up to 1,000,000 Da in size  promotes platelet adhesion to damaged endothelium  carrier molecule for factor VIII Types: Type 1: partial reduction in vWF (80% of patients) Type 2: abnormal form of vWF Type 3: total lack of vWF (most severe form) autosomal recessive Investigation: 1) prolonged bleeding time 2) APTT may be prolonged 3) factor VIII levels may be moderately reduced 4) defective platelet aggregation with ristocetin Management: 1) tranexamic acid for mild bleeding 2) desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from WeibelPalade bodies in endothelial cells 3) factor VIII concentrate A grossly elevated APTT may be caused by: 1) heparin therapy, 2) haemophilia or 3) Antiphospholipid syndrome.

49

Thrombophilia: Causes: Inherited A) activated protein C resistance (factor V Leiden) B) antithrombin III deficiency C) protein C deficiency D) protein S deficiency Acquired: A) antiphospholipid syndrome B) the Pill

A) Activated protein C resistance:  

(factor V Leiden) The most common inherited thrombophilia.

It is due to Factor V Leiden mutation.

Heterozygotes have a 5-fold risk of venous thrombosis whilst Homozygotes have a 50-fold increased risk

B) Protein C deficiency An autosomal codominant condition which causes an increased risk of thrombosis Features: 1) venous thromboembolism 2) skin necrosis following the commencement of warfarin:  When warfarin is first started biosynthesis of protein C is reduced.  This results in a temporary procoagulant state after initially starting warfarin,  Normally avoided by concurrent heparin administration.  Thrombosis may occur in venules leading to skin necrosis

C) Antithrombin III deficiency:   

autosomal dominant An inherited cause of thrombophilia occurring in approximately 1:2,000 of the population.

Antithrombin III inhibits several clotting factors, primarily thrombin, factor X and factor IX. It mediates the effects of heparin  Antithrombin III deficiency comprises a heterogeneous group of disorders: 1) some patients having a deficiency of normal antithrombin III whilst 2) others produce abnormal antithrombin III Features: 1) recurrent venous thromboses 2) arterial thromboses do occur but is uncommon Management: 1) thromboembolic events are treated with lifelong warfarinisation 2) heparinisation during pregnancy* 3) antithrombin III concentrates (often using during surgery or childbirth) *as patients with antithrombin III deficiency have a degree of resistance to heparin anti-Xa levels should be monitored carefully to ensure adequate anticoagulation 50

Antiphospholipid syndrome: pregnancy  an acquired disorder  Characterised by: 1) A predisposition to both venous and arterial thromboses, 2) recurrent fetal loss and 3) Thrombocytopenia.  It may occur as a primary disorder or secondary to other conditions, most commonly SLE. In pregnancy the following complications may occur: 1) recurrent miscarriage 2) IUGR 3) pre-eclampsia 4) placental abruption 5) pre-term delivery 6) venous thromboembolism Management: 1) low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing 2) Low molecular weight heparin:  Started once a fetal heart is seen on ultrasound.  discontinued at 34 weeks gestation These interventions increase the live birth rate seven-fold

Superficial Thrombophlebitis

51

Venous thromboembolism Risk factors: Common predisposing factors include: 1) malignancy, 2) pregnancy and 3) the period following an operation The comprehensive list below is partly based on the 2010 SIGN venous thromboembolism (VTE) guidelines: General: 1) pregnancy (especially puerperium) 2) increased risk with advancing age 3) obesity 4) family history of VTE 5) immobility 6) hospitalisation 7) anaesthesia 8) central venous catheter: femoral >> subclavian Underlying conditions: 1) malignancy 2) thrombophilia: e.g. Activated protein C resistance, protein C and S deficiency 3) heart failure 4) antiphospholipid syndrome 5) Behcet's 6) polycythaemia 7) nephrotic syndrome 8) sickle cell disease 9) paroxysmal nocturnal haemoglobinuria 10) hyperviscosity syndrome 11) homocystinuria Medication 1) combined oral contraceptive pill: 3rd generation more than 2nd generation 2) hormone replacement therapy: the risk of VTE is higher in women taking oestrogen + progestogen preparations compared to those taking oestrogen only preparations 3) raloxifene and tamoxifen 4) antipsychotics (especially olanzapine) have recently been shown to be a risk factor It should be remembered however that around 40% of patients diagnosed with a PE have no major risk factors.

52

Deep vein thrombosis: diagnosis and management Diagnosis  NICE published guidelines in 2012 relating to the investigation and management of DVT.  If a patient is suspected of having a DVT a two-level DVT Wells score should be performed: Two-level DVT Wells score Clinical feature

Points

Active cancer (treatment ongoing, within 6 months, or palliative)

1

Paralysis, paresis or recent plaster immobilisation of the lower extremities

1

 

1

Recently bedridden for 3 days or more or major surgery within 12 weeks requiring general or regional anaesthesia

Localised tenderness along the distribution of the deep venous system

1

Entire leg swollen

1

Calf swelling at least 3 cm larger than asymptomatic side

1

Pitting oedema confined to the symptomatic leg

1

Collateral superficial veins (non-varicose)

1

Previously documented DVT

1

An alternative diagnosis is at least as likely as DVT

-2

Clinical probability simplified score  DVT likely: 2 points or more  DVT unlikely: 1 point or less A) If a DVT is 'likely' (2 points or more):  a proximal leg vein ultrasound scan should be carried out within 4 hours and, if the result is negative, a D-dimer test  if a proximal leg vein ultrasound scan cannot be carried out within 4 hours a D-dimer test should be performed and low-molecular weight heparin administered whilst waiting for the proximal leg vein ultrasound scan (which should be performed within 24 hours) B) If a DVT is 'unlikely' (1 point or less)  perform a D-dimer test and if it is positive arrange:  a proximal leg vein ultrasound scan within 4 hours  if a proximal leg vein ultrasound scan cannot be carried out within 4 hours low-molecular weight heparin should be administered whilst waiting for the proximal leg vein ultrasound scan (which should be performed within 24 hours) 53

Management: Venous thromoboembolism - length of warfarin treatment  provoked (e.g. recent surgery): 3 months  unprovoked: 6 months  Cancer patients with VTE - 6 months of LMWH  Low molecular weight heparin (LMWH) or fondaparinux should be given initially after a DVT is diagnosed.  a vitamin K antagonist (i.e. warfarin) should be given within 24 hours of the diagnosis  the LMWH or fondaparinux should be continued for at least 5 days or until the international normalised ratio (INR) is 2.0 or above for at least 24 hours, whichever is longer, i.e. LMWH or fondaparinux is given at the same time as warfarin until the INR is in the therapeutic range  warfarin:  should be continued for at least 3 months.  At 3 months, NICE advise that clinicians should 'assess the risks and benefits of extending treatment'  NICE add 'consider extending warfarin beyond 3 months for patients withunprovoked proximal DVT if their risk of VTE recurrence is high and there is no additional risk of major bleeding'.  This essentially means that if there was no obvious cause or provoking factor (surgery, trauma, significant immobility) it may imply the patient has a tendency to thrombosis and should be given treatment longer than the norm of 3 months.  In practice most clinicians give 6 months of warfarin for patients with an unprovoked DVT/PE  for patients with active cancer NICE recommend using LMWH for 6 months Further investigations and thrombophilia screening  As both malignancy and thrombophilia are obvious risk factors for deep vein thrombosis NICE make recommendations on how to investigate patients with unprovoked clots.

Investigations for cancer: 1) a physical examination (guided by the patient's full history) and 2) a chest X-ray and 3) Blood tests (full blood count, serum calcium and liver function tests) and urinalysis.

4) Consider further investigations for cancer with an abdomino-pelvic CT scan (and a mammogram for women) in all patients aged over 40 years with a first unprovoked DVT or PE Thrombophilia screening  not offered if patients will be on lifelong warfarin (i.e. won't alter management)  consider testing for antiphospholipid antibodies  consider testing for hereditary thrombophilia in patients who have had unprovoked DVT or PE and who have a first-degree relative who has had DVT or PE

54

55

Pregnancy: DVT/PE Overview  pregnancy is a hypercoagulable state  majority occur in last trimester Pathophysiology 1) increase in factors VII, VIII, X and fibrinogen 2) decrease in protein S 3) uterus presses on IVC causing venous stasis in legs Management 1) warfarin contraindicated 2) S/C low-molecular weight heparin preferred to IV heparin (less bleeding and thrombocytopenia)

Superior vena cava obstruction:  

Superior vena cava (SVC) obstruction is an oncological emergency caused by compression of the SVC. It is most commonly associated with lung cancer.

Features: 1) dyspnoea is the most common symptom 2) swelling of the face, neck and arms - conjunctival and periorbital oedema may be seen 3) headache 4) visual disturbance 5) pulseless jugular venous distension Causes: 1) common malignancies: small cell lung cancer, lymphoma 2) other malignancies: metastatic seminoma, Kaposi's sarcoma, breast cancer 3) aortic aneurysm 4) mediastinal fibrosis 5) goitre 6) SVC thrombosis Management: 1) general: dexamethasone, balloon venoplasty, stenting 2) small cell: chemotherapy + radiotherapy 3) non-small cell: radiotherapy

56

Heparin    

There are two main types of heparin - unfractionated, 'standard' heparin or low molecular weight heparin (LMWH).

Heparins generally act by activating antithrombin III. Unfractionated heparin forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa. LMWH however only increases the action of antithrombin III on factor Xa The table below shows the differences between standard heparin and LMWH: Standard heparin

Low molecular weight heparin

Administration

Intravenous

Subcutaneous

Duration of action

Short

Long

Mechanism of action

 

Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa

 

Activates antithrombin III. Forms a complex that inhibits factor Xa

Side-effects

  

Bleeding HIT Osteoporosis

 

Bleeding Lower risk of HIT and osteoporosis with LMWH

Monitoring

Activated partial thromboplastin time (APTT)

Anti-Factor Xa (although routine monitoring is not required)

Useful in situations where there is a high risk of bleeding as anticoagulation can be terminated rapidly

Now standard in the management of venous thromboembolism treatment and prophylaxis and acute coronary syndromes

Notes

  

Both unfractionated and low-molecular weight heparin can cause hyperkalaemia.

This is thought to be caused by inhibition of aldosterone secretion.

Heparin overdose may be reversed by protamine sulphate, although this only partially reverses the effect of LMWH.

57

Warfarin 

Warfarin is an oral anticoagulant which inhibits the reduction of vitamin K to its active hydroquinone form, which in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X (mnemonic = 1972) and protein C.

Indications: 1) venous thromboembolism: target INR = 2.5, if recurrent 3.5 2) atrial fibrillation, target INR = 2.5 3) Mechanical heart valves, target INR depends on the valve type and location. Mitral valves generally require a higher INR than aortic valves.   

Patients on warfarin are monitored using the INR (international normalised ration), the ratio of the prothrombin time for the patient over the normal prothrombin time.

Warfarin has a long half-life and achieving a stable INR may take several days.

There a variety of loading regimes and computer software is now often used to alter the dose.

Factors that may potentiate warfarin: 1) liver disease 2) P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin 3) cranberry juice 4) drugs which displace warfarin from plasma albumin, e.g. NSAIDs 5) inhibit platelet function: NSAIDs Side-effects: 1) haemorrhage 2) teratogenic, although can be used in breast-feeding mothers 3) Skin necrosis: when warfarin is first started biosynthesis of protein C is reduced. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis 4) purple toes

58

Warfarin overdose ď&#x201A;ˇ ď&#x201A;ˇ

The following is based on the BNF guidelines, which in turn take into account the British Committee for Standards in Haematology (BCSH) guidelines.

A 2005 update of the BCSH guidelines emphasised the preference of prothrombin complex concentrate over FFP in major bleeding.

Situation

Management

Major bleeding

1) Stop warfarin 2) Give intravenous vitamin K 5mg 3) Prothrombin complex concentrate - if not available then FFP*

INR > 8.0 Minor bleeding

1) 2) 3) 4)

INR > 8.0 No bleeding

1) Stop warfarin 2) Give vitamin K 1-5mg by mouth, using the intravenous preparation orally 3) Repeat dose of vitamin K if INR still too high after 24 hours 4) Restart when INR < 5.0

INR 5.0-8.0 Minor bleeding

1) Stop warfarin 2) Give intravenous vitamin K 1-3mg 3) Restart when INR < 5.0

INR 5.0-8.0 No bleeding

1) Withhold 1 or 2 doses of warfarin 2) Reduce subsequent maintenance dose

Stop warfarin Give intravenous vitamin K 1-3mg Repeat dose of vitamin K if INR still too high after 24 hours Restart warfarin when INR < 5.0

*as FFP can take time to defrost prothrombin complex concentrate should be considered in cases of intracranial haemorrhage

59

Hereditary haemorrhagic telangiectasia  



Also known as Osler-Weber-Rendu syndrome, Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition characterised by (as the name suggests) multiple telangiectasia over the skin and mucous membranes.

20% of cases occur spontaneously without prior family history.

There are 4 main diagnostic criteria: 1) epistaxis : spontaneous, recurrent nose bleeds 2) telangiectases: multiple at characteristic sites (lips, oral cavity, fingers, nose) 3) visceral lesions: for example  gastrointestinal telangiectasia (with or without bleeding),  pulmonary arteriovenous malformations (AVM),  hepatic AVM,  cerebral AVM,  spinal AVM 4) family history: a first-degree relative with HHT  If the patient has 2 then they are said to have a possible diagnosis of HHT.  If they meet 3 or more of the criteria they are said to have a definite diagnosis of HHT:

The chest x-ray shows multiple pulmonary nodules representing arteriovenous malformations, the largest in the right mid-zone.

The CT scan shows multiple hepatic arteriovenous malformations

60

‫الروهينجا ‪ ..‬حاكية شعب بال وطن‬

‫كلمة "روهنجيا" مأخوذة من "روهانج" اسم دولة أراكان القديم وتطلق على المسلمين المواطنين األصليين في أراكان المحتلة من‬ ‫قبل دولة ميانمار(بورما)‪ ،‬وهم أقلية مسلمة مضطهدة تعيش مأساة حقيقية‪ .‬و للغوص في أعماق تاريخ هذه البالد وانتمائها إلى‬ ‫الحضارة اإلسالمية فيمكننا القول أن أراكان كانت في ما مضى دولة إسالمية مستقلة حرة في جنوب شرق آسيا‪ ،‬استمرت في‬ ‫الوجود عدة قرون قبل أن تحتل من بورما عام ‪4871‬م فأصبحت بعد ذلك واحدة من ‪ 41‬والية ومقاطعة التحاد بورما – ميانمار حاليا‪.‬‬ ‫أما من حيث الجغرافيا فإن إقليم أراكان يقع في الجنوب الغربي لميانمار على ساحل خليج البنغال‪ ،‬والشريط الحدودي مع‬ ‫بنغالديش‪ ،‬وتبلغ مساحة اإلقليم حوالي خمسين ألف كيلومتر مربع أي عشر مساحة ميانمار تقريبا‪ .‬وتقع ميانمار حاليا في الجنوب‬ ‫الشرقي لقارة آسيا‪ ،‬ويحدُّها من الشمال الصين والهند‪ ،‬ومن الجنوب خليج البنغال والهند وبنغالديش‬ ‫يتخذ هذا اإلقليم من مدينة اكياب عاصمة له‪ ،‬أما عاصمة ميانمار فهي رانجون‪ .‬أما التقسيم الديمغرافي للسكان فيأتي كالتالي‪-:‬‬ ‫‪ )4‬عدد سكان ميانمار ‪ )1544(08،999،75‬ونسبة المسلمين تبلغ ‪ %15‬بحدود ‪ 45‬مليون نسمة حسب منظمة تضامن الروهنجيا‬ ‫التي تدافع عن حقوق أبناء اراكان منذ ‪ 4978‬وهناك بعض المصادر تبالغ في تقليص عددهم فبحسب ‪ CIA Fact Book‬فإن نسبة‬ ‫المسلمين تبلغ ‪.%1‬‬ ‫‪ )1‬عدد سكان منطقة أراكان حوالي ‪ 0.0‬ماليين ونسبة المسلمين فيها ‪ 1 %95‬ويعيش منهم مليونان داخل ميانمار‪ ،‬أما اآلخرون‬ ‫فهاجروا إلى خارج البالد بسبب االضطهاد الذي تمارسه هذه الدولة ضدهم‪.‬‬ ‫‪ )8‬وتنحدر أصول مسلمي ميانمار من أصول مختلفة مثل البنغالية والعرب والمورو واألتراك والفرس والمنغول والباتان ومعظمهم يشبه‬ ‫أهل القارة الهندية شكال ولونا‪.‬‬ ‫اللغة ‪:‬‬ ‫تسمى لهجة مسلمي أراكان "الروهنجيان" و هي مؤلفة من كلمات و تعبيرات من اللغة العربية و الفارسية و األردية و البنغالية‪،‬‬ ‫وهي ليست مكتوبة لحد اآلن‪.‬‬

‫‪61‬‬

‫ويرجع دخول اإلسالم إلى أراكان في القرن السابع الميالدي مع قدوم التجار العرب المسلمين إليها‪ ،‬ثم تتابعت الوفود اإلسالمية‬ ‫إليها من أنحاء المعمورة‪ .‬فأقبل عدد كبير من األهالي على اعتناق اإلسالم‪ ،‬وك َّون شعب الروهنجيا مملكة دام حكمها ‪ 805‬عاما من‬ ‫‪4185‬م إلى عام ‪4871‬م‪ ،‬فقد شكلت أول دولة إسالمية في عام ‪4185‬م بقيادة الملك سليمان شاه‪ ،‬وحكم بعده (‪ )17‬ملكا مسلما‬ ‫على التوالي‪ ،‬وكان لهم عمالت نقدية تتضمن شعارات إسالمية مثل كلمة التوحيد‪ .‬ومما يدل على قِ َدم وجود المسلمين في هذه‬ ‫الدولة أيضا بعض اآلثار التاريخية كمسجد (بدر مقام) في (أكياب) عاصمة (أراكان)‪( ،‬مسجد سندي خان) الذي بني منذ ‪ 065‬عاما‪،‬‬ ‫ومسجد (الديوان موسى) الذي ُبني عام ‪4107‬م‪ ،‬ومسجد (ولي خان) الذي بني في القرن الخامس عشر الميالدي‪.‬‬ ‫واحتلت أراكان من قِبَل الملك البوذي (بوداباي) عام ‪4871‬م الذي قام بضم اإلقليم إلى ميانمار خوفا من انتشار اإلسالم في‬ ‫ُ‬ ‫المنطقة‪ ،‬واستمر البوذيون البورميون في اضطهاد المسلمين ونهب خيراتهم وتشجيع البوذيين الماغ (أصل هندي) على ذلك طِوال‬ ‫فترة احتاللهم‪.‬‬ ‫في عام ‪4711‬م احتلت بريطانيا ميانمار‪ ،‬وضمتها إلى حكومة الهند البريطانية االستعمارية‪ .‬وفي عام ‪4988‬م جعلت بريطانيا ميانمار‬ ‫وعرفت بحكومة‬ ‫مع أراكان مستعمرة مستقلة عن حكومة الهند البريطانية االستعمارية كباقي مستعمراتها في اإلمبراطورية آنذاك‪ُ ،‬‬ ‫ميانمار البريطانية‪.‬‬ ‫واجه المسلمون االستعمار اإلنجليزي بقوة مما جعل بريطانيا تخشاهم‪ ،‬فبدأت حملتها للتخلص من نفوذ المسلمين باعتماد‬ ‫م َدت على تحريض البوذيين ضد المسلمين‪ ،‬وأمدتهم بالسالح حتى أوقعوا بالمسلمين مذبحة‬ ‫سد) ف َع َ‬ ‫فرق تَ ُ‬ ‫سياساتها المعروفة ( ِ‬ ‫عام م‪ 4911‬فتكوا خاللها بحوالي مائة ألف مسلم في أراكان!‬ ‫وفي عام ‪4917‬م‪ ،‬منحت بريطانيا االستقالل لميانمار شريطة أن تمنح لكل العرقيات االستقالل عنها بعد عشر سنوات إذا رغبت في‬ ‫ذلك‪ ،‬ولكن ما أن حصلوا على االستقالل حتى نقضوا عهودهم‪ ،‬ونكثوا وعودهم‪ ،‬واستمروا في احتالل أراكان بدون رغبة سكانها من‬ ‫المسلمين (الروهنجيا) والبوذيين (الماغ) أيضا‪ ،‬وقاموا بأبشع الممارسات ضد المسلمين‪.‬‬

‫‪62‬‬

63

‫عذابات مسلمي الروهنجيا‬ ‫لم تتغير أحوال المسلمين الروهنجيا‪ ،‬بعد االنتخابات التي جرت في نوفمبر ‪1545‬م‪ ،‬حيث مازال مخطط إخراج المسلمين من أراكان‬ ‫موجودا‪ ،‬رغم إعالن حكومة ميانمار تغيير نظام الدولة من نظام عسكري إلى نظام ديمقراطي‪ ،‬لكن هذا إعالن ال عالقة له بالحقيقة‪،‬‬ ‫ولم يقبل العالم واألمم المتحدة إعالنهم ونتائج انتخاباتهم‪ .‬ويقول «د‪.‬محمد يونس» رئيس منظمة تضامن الروهنجيا‪« :‬إن بورما تخطط‬ ‫إلخراج المسلمين من أراكان وجعلها مستوطنة للبوذيين الجبليين‪ ،‬ولن يحدث التغيير باالنتخابات التي تم إجراؤها تحت التهديد‬ ‫العسكري‪ ،‬ولن ينال المسلمون الروهنجيا حقوقهم إال بأحد طريقين‪ :‬إما أن تكون أراكان دولة إسالمية مستقلة‪ ،‬وإما أن ُتجرى‬ ‫انتخابات في أراكان تحت رعاية األمم المتحدة»‪.‬‬ ‫وقد تحولت معاناة المسلمين الروهنجيا إلى اتجاه جديد بعد تطبيق قانون الجنسية الجديد في ميانمار عام ‪4971‬م‪ ،‬فبموجب هذا‬ ‫القانون المزعوم تم حرمانهم من تملك العقارات وممارسة أعمال التجارة وتقلد الوظائف في الجيش والهيئات الحكومية‪ ،‬كما تم‬ ‫حرمانهم من جميع الحقوق اإلنسانية الطبيعية واألساسية مثل حق التصويت في االنتخابات البرلمانية‪ ،‬وتأسيس المنظمات‬ ‫وممارسة النشاطات السياسية‪ .‬ولم تتخذ سلطات االحتالل البورمية الخطوات الجديدة ضد المسلمين في أراكان منذ ذلك التاريخ‬ ‫فحسب‪ ،‬بل ما زالت تواصل تطبيق الخطط القديمة ضد المسلمين؛ إلرغامهم على ترك العقيدة اإلسالمية‪ ،‬وإجبارهم على مغادرة‬ ‫بلدهم‪.‬‬ ‫الصعوبات واإلطضهاااات التي تواجه المسلمين‪.‬‬ ‫و يتعرض المسلمون في ميانمار وخصوصا في أراكان لسلسلة ال تنتهي من أعمال الشغب التي يذهب ضحيتها األرواح والممتلكات‪،‬‬ ‫ولم تتخذ السلطات أية إجراءات أمنية لحماية المسلمين‪.‬‬ ‫ويقول شهود عيان إن الجنود الميانماريون وهيئات التنفيذ القضائي وسفاحو (الماغ) البوذيين يطوفون بأنحاء القرى المسلمة ويقومون‬ ‫بإذالل كبار السن وضرب الشباب المسلم ودخول المنازل وسلب الممتلكات‪.‬‬

‫‪64‬‬

‫و من الفظائع التي تمارس على المسلمين هناك أن الحكومة العسكرية تجبرهم على تقديم األرز والدواجن والماعز وحطب النار‬ ‫ومواد البناء بالمجان طِوال العام إلى الجنود وهيئات التنفيذ القانونية ‪ .‬كما يتم إجبار السكان على العمل القسري لدى الجيش أثناء‬ ‫التنقالت أو بناء ثكنات عسكرية أو شق طرق وغير ذلك من األعمال الحكومية أو في بناء الطرق والسدود سخرة دون مقابل وذلك‬ ‫ضمن سياسة االكتفاء الذاتي التي يعتمدها الجيش‪.‬‬ ‫أما على الصعيد السكاني فإن الحكومة ما زالت تقوم بإحداث تغييرات جذرية في التركيبة السكانية لمناطق المسلمين‪ ،‬فال توجد‬ ‫أي قرية أو منطقة إال وأنشأت فيها منازل للمستوطنين البوذيين سلمتهم السلطة فيها‪ .‬ومنذ عام ‪4977‬م قامت الحكومة بإنشاء ما‬ ‫سر البوذيين على االستيطان في هذه المناطق‪.‬‬ ‫يسمى بـ"القرى النموذجية" في شمال أراكان‪ ،‬حتى يتسنى تشجيع ُأ َ‬ ‫وتفرض الحكومة شروط معينة على ما يخص الزواج من المسلمين أو بينهم‪ ،‬فهناك قانون الزواج الذي يشترط موافقة الدولة على‬ ‫الزواج وبدفع مبلغ عال مقابل وغالبا ما تدفع الرشاوى لقاء هذا اإلذن‪ ،‬وقد يتأخر اإلذن لسنوات‪ ،‬وتصل عقوبة الزواج بغير إذن إلى ‪45‬‬ ‫سنوات سجن‪.‬‬ ‫ومن عذابات المسلمين هناك عدم السماح للعائلة إال بمولودين فقط ومن يولد له أكثر من ولدين يوضع أوالده على القائمة السوداء‬ ‫وهي تعني أنهم غير معترف بهم وليس لهم حقوق ويعرض العائلة للعقوبة مما يضطر العائلة في أحيان كثيرة إلى إخفاء أوالدهم‬ ‫عند التعداد السكاني وكثيرا ما يسجل أوالد القائمة السوداء باسم جداتهم وأقاربهم خوفا عليهم‪.‬‬ ‫فيمنع منعا باتا‪ ،‬ويعتبر جريمة‬ ‫كما ال يسمح لهم باستضافة أحد في بيوتهم ولو كانوا أشقاء أو أقارب إال بإذن مسبق‪ ،‬أما ال َ‬ ‫مبيت ُ‬ ‫ب عليها بهدم منزله أو اعتقاله أو طرده من البالد هو وأسرته‪.‬‬ ‫كبرى ربما يعا َق ُ‬ ‫ويحرم كذلك أبناء المسلمين من مواصلة التعلُّم في الكليات والجامعات‪ ،‬ومن يذهب للخارج ُيطوى قيده من سجالت القرية‪ ،‬أما إذا‬ ‫ويرمى به في غياهب السجون‪ ،‬ويتم إرغام الطالب المسلمين في المدارس الحكومية على االنحناء لل َعلَم‬ ‫فيعتقل عند عودته‪ُ ،‬‬ ‫عاد ُ‬ ‫البورمي‪ .‬وال يسمح للمسلمين باالنتقال من مكان إلى آخر دون تصريح‪ ،‬والذي يَص ُعب الحصول عليه‪ .‬كما يتم حجز جوازات السفر‬ ‫ويعتبر السفر إلى عاصمة الدولة (رانجون) أو أية‬ ‫الخاصة بالمسلمين لدى الحكومة وال ُيسمح لهم بالسفر للخارج إال بإذن رسمي‪ُ ،‬‬ ‫مدينة أخرى جريمة ُيعاقب عليها‪.‬‬ ‫وتمارس الحكومة بمليشياتها عمليات طرد وتهجير جماعي متكررة تستهدف المسلمين وعائلتهم إلبعادهم عن البالد‪ ،‬وخير دليل‬ ‫على ذلك ما حصل في األعوام التالية‪ :‬عام ‪4961‬م عقب االنقالب العسكري حيث طرد أكثر من ‪ 855.555‬مسلم إلى بنغالديش‪.‬‬ ‫وفي عام ‪4987‬م طرد أكثر من (‪ )055.555‬أي نصف مليون مسلم‪ ،‬في أوضاع قاسية جدا‪ ،‬مات منهم قرابة ‪ 15.555‬من الشيوخ‬ ‫والنساء واألطفال حسب إحصائية وكالة غوث الالجئين التابعة لألمم المتحدة‪ .‬وفي عام ‪4977‬م تم طرد أكثر من ‪ 405.555‬مسلم‪،‬‬ ‫بسبب بناء القرى النموذجية للبوذيين في محاولة للتغيير الديموغرافي‪ .‬وفي عام ‪4994‬م تم طرد قرابة (‪ )055.555‬أي نصف مليون‬ ‫مسلم‪ ،‬وذلك عقب إلغاء نتائج االنتخابات العامة التي فازت فيها المعارضة بأغلبية ساحقة‪ ،‬انتقاما من المسلمين ألنهم صوتوا مع‬ ‫عامة أهل البالد لصالح الحزب الوطني الديمقراطي‪.‬‬

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‫قسم المواطنين كما يلي‪:‬‬ ‫وبحسب قانون الجنسية الجديد الذي صدر عام ‪ 2891‬وهو ُي‬ ‫ّ‬ ‫أ‪ -‬مواطنون من الدرجة األولى وهم‪( :‬الكارينون والشائيون والباهييون والصينيون والكامينيون)‪.‬‬ ‫ب‪ -‬مواطنون من الدرجة الثانية وهم‪ :‬خليط من أجناس الدرجة األولى‪.‬‬ ‫صنِفوا على أنهم أجانب دخلوا بورما الجئين أثناء االحتالل البريطاني حسب‬ ‫ج‪ -‬مواطنون من الدرجة الثالثة وهم‪ :‬المسلمون حيث ُ‬ ‫وحرموا من كل األعمال وصار بإمكان الحكومة ترحيلهم متى شاءت‪.‬‬ ‫مزاعم الحكومة‬ ‫فسحبت جنسيات المسلمين وصاروا بال هوية ُ‬ ‫ُ‬ ‫وتفرض الحكومة كذلك مجموعة من العقوبات الدينية واالقتصادية على السكان المسلمين في إقليم "أراكان" ومن أهما ‪-:‬‬ ‫الناحية االقتصااية‪:‬‬ ‫‪ )4‬تصادر الحكومة الميانمارية أراضي المسلمين وقوارب صيد السمك دون سبب واضح‪.‬‬ ‫‪ )1‬فرض الضرائب الباهظة على كل شيء‪ ،‬والغرامات المالية‪ ،‬ومنع بيع المحاصيل إال للعسكر أو من ُيمثلُهم بسعر زهيد بهدف إبقاء‬ ‫المسلمين فقراء‪ ،‬أو إلجبارهم على ترك الديار‪.‬‬ ‫‪ )8‬منع المسلمين من شراء اآلالت الزراعية الحديثة لتطوير مشاريعهم الزراعية‪.‬‬ ‫‪ )1‬إلغاء العمالت المتدا َولة بين وقت وآخر من دون تعويض‪ ،‬ودون إنذار مسبق‪.‬‬ ‫‪ )0‬إحراق محاصيل المسلمين الزراعية وقتل مواشيهم‪.‬‬ ‫‪ )6‬عدم السماح للمسلمين بالعمل ضمن القطاع الصناعي في أراكان‪.‬‬ ‫الناحية الدينية‪:‬‬ ‫‪ )4‬ال تسمح الحكومة بطباعة الكتب الدينية وإصدار المطبوعات اإلسالمية إال بعد إجازتها من الجهات الحكومية وهذا أمر صعب جدا‪.‬‬ ‫هم أو لبس الزي اإلسالمي في أماكن عملهم‪.‬‬ ‫‪ )1‬عدم السماح للمسلمين بإطالق لِحا ُ‬ ‫‪ )8‬تصادر الحكومة ممتلكات األوقاف والمقابر المخصصة لدفن المسلمين وتُوزعها على غيرهم أو وتحولها إلى مراحيض عامة أو‬ ‫حظائر للخنازير والمواشي!!‬ ‫‪ )1‬يتعرض كبار رجال الدين لالمتهان والضرب ويتم إرغامهم على العمل في معسكرات االعتقال‪.‬‬ ‫‪ُ )0‬يمنع استخدام مكبرات الصوت إلطالق أذان الصالة‪ ،‬وقد ُمنع األذان للصالة بعد رمضان ‪ 4158‬هـ (‪4978‬م)‪.‬‬ ‫‪ )6‬تتدخل الحكومة بطريقة غير مشروعة في إدارة المساجد والمدارس بهدف فرض إرادتها عليها‪.‬‬ ‫‪ُ )8‬يمنع المسلمون من أداء فريضة الحج باستثناء قلة من األفراد الذين تعرفهم الحكومة وترضى عن سلوكهم‪.‬‬

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‫‪ )7‬منع ذبح األضاحي‪.‬‬ ‫س َكن أو تحويلها إلى مستودعات وثكنات عسكرية ومتنزهات عامة‪ ،‬ومصادرة‬ ‫ودور َ‬ ‫‪ )9‬هدم المساجد وتحويلها إلى مراقص وخمارات ُ‬ ‫األراضي والعقارات الخاصة باألوقاف اإلسالمية وتوزيعها على الماغ البوذيين‪ .‬وقد قال نائب رئيس اتحاد الطالب المسلمين في إقليم‬ ‫أراكان إبراهي محمد عتيق الرحمن في حديث لـ"وكالة األنباء اإلسالمية ـ إينا"‪ :‬إن حكومة ميانمار قامت خالل عام ‪1554‬م بتدمير‬ ‫نحو ‪ 81‬مسجدا وذلك بموجب قانون أصدرته منعت بموجبه بناء المساجد الجديدة أو ترميم وإصالح المساجد القديمة‪ ،‬كما أن هذا‬ ‫ي خالل العشر سنوات األخيرة‪.‬‬ ‫القانون ينص على هدم أي مسجد ُب ِن َ‬ ‫‪ )45‬حمالت التنصير وخاصة بعد إعصار نرجس الذي ضرب بورما عام ‪ 1557‬حيث بلغ عدد ضحايا هذا اإلعصار على األقل ‪ 87‬ألف قتيل‬ ‫و‪ 06‬ألف مفقود وماليين المشردين‪.‬‬ ‫‪ )44‬المحاوالت المستميتة لطمس الثقافة اإلسالمية وتذويب المسلمين في المجتمع البوذي البورمي قسرا‪ ،‬فلقد فرضوا الثقافة‬ ‫البوذية والزواج من البوذيات وعدم لبس الحجاب للبنات المسلمات والتسمي بأسماء بوذية‪.‬‬ ‫‪ )41‬طمس الهوية واآلثار اإلسالمية‪ :‬وذلك بتدمير اآلثار اإلسالمية من مساجد ومدارس تاريخية‪ ،‬وما بقي ُيمنع منعا باتا من الترميم‬ ‫ودور لأليتام وغيرها‪ ،‬وبعضها تهوي على‬ ‫فضال عن إعادة البناء أو بناء أي شيء جديد لـه عالقة بالدين من مساجد ومدارس ومكتبات ُ‬ ‫رؤوس الناس بسبب مرور الزمن‪ ،‬والمدارس اإلسالمية ُتمنع من التطوير أو االعتراف الحكومي والمصادقة لشهاداتها أو خريجيها‪.‬‬ ‫وطضع المرأة المسلمة‬ ‫أما حينما نتحدث عن عذابات المرأة المسلمة في " أركان" فإن الحكومة لكي تحد من إرتفاع نسبة السكان في صفوف المسلمين‬ ‫قامت برفع سن الزواج للفتيات لـ ‪ 10‬عاما والرجال ‪ 85‬عاما‪،‬ومنعت عقود النكاح إال بعد إجراءات طويلة وإذن من السلطات‪ ،‬وإعطاء‬ ‫حقَن مانعة للحمل للنساء المسلمات في حاالت كثيرة‪ ،‬منع التعدد منعا باتا مهما كان السبب‪ ،‬منع الزواج مرة أخرى للمطلق أو‬ ‫ُ‬ ‫األرمل إال بعد مرور سنة‪ ،‬ومن يخالف ذلك ُيعرض نفسه للسجن والغرامات الباهظة أو الطرد من البلد‪ .‬والهدف من كل ذلك هو القضاء‬ ‫عليهم أو تقليل أعدادهم‪.‬‬ ‫ملَت الزوجة فال بد من ذهابها طِبقا لقرار السلطات الحاكمة إلى إدارة قوات األمن‬ ‫ح َ‬ ‫و فرضت إجراءات تعسفية منها أيضا أنه إذا َ‬ ‫الحدودية "ناساكا" ألخذ صورتها الملونة كاشفة بطنها بعد مرور كل شهر حتى تضع حملها‪ ،‬وفي كل مرة ال بد من دفع الرسوم بمبلغ‬ ‫كبير‪ ،‬وذلك للتأكد كما تدعي السلطة من سالمة الجنين‪ ،‬ولتسهيل إحصائية المولود بعد الوالدة‪.‬‬ ‫كما يتم أخذ النساء َعنوة من منازلهن وإجبارهن على العمل في معسكرات الجيش دون مقابل‪ .‬باإلضافة إلى إجبار الفتيات‬ ‫المسلمات على الزواج من البوذيين‪ .‬وتلزم القوانين هناك الفتيات المسلمات غير المتزوجات بالحضور اإلجباري إلى قيادة القوات‬ ‫المسلحة والعمل لمدة ‪ 6‬أشهر تحت إشراف أفراد قوات حرس الحدود‪ ،‬كما تجبر المسلمات على خلع الحجاب وتنتهك حرمات الكثير‬ ‫منهن‪.‬‬

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‫الاجرة والالجئين‬ ‫بسبب المعاناة الكبيرة التي تعرض لها مسلموا الروهنجيا فقد قامت هجرات جماعية كان أكبرها في العام ‪ 4987‬و ‪ 4994‬حيث هاجر‬ ‫معظم الروهنجيين إلى بنجالديش و دول أخرى مثل‪ :‬السعودية‪ ،‬وباكستان‪ ،‬وماليزيا‪ ،‬وليبيا‪ ،‬وتايالند‪ ،‬واإلمارات العربية المتحدة‪،‬‬ ‫وغيرها‪ ،‬وما زالت الهجرة والهروب عبر الحدود يتم بشكل دائم‪ .‬والمحظوظون من يصلوا إلى بنجالديش عبر النهر الفاصل بينهم أو من‬ ‫خالل السياج الحدودي ولكن من يقومون بالهرب بالقوارب من خالل الخليج فقد يتم قذفهم إلى تايالند والتي تقوم بقذفهم ثانية إلى‬ ‫المحيط ولكن بعد فصل محركات القوارب ليواجهوا الموت المحقق في المحيط‪.‬‬ ‫ويقدر عدد الالجئين األراكانيين في بنجالديش بنحو ‪ 155.555‬إلى ‪ ،155.555‬وفي تايالند حسب ما تعتبره السلطات التايالندية‬ ‫أنهم مهاجرون غير شرعيين فيبلغ عددهم حوالي ‪ 15.555‬شخص‪ ،‬ووفقا التحاد حدود تايالند ‪ -‬بورما‪ ،‬وهو مجموعة من المنظمات‬ ‫اإلنسانية الدولية العاملة على طول الحدود البالغة ‪ 4،755‬كيلومتر‪ ،‬يعيش نحو ‪ 411.555‬الجئ بورمي في تسعة مخيمات تديرها‬ ‫الحكومة أما مفوضية األمم المتحدة لشؤون الالجئين فقد قامت حتى اآلن بتسجيل ‪ 455.555‬الجئ بورمي في تايالند‪ .‬أما في‬ ‫ماليزيا فتقدر لجنة حماية حقوق عمال بورما ومقرها كوااللمبور عدد المهاجرين من ميانمار المسجلين وغير المسجلين في ماليزيا‬ ‫بحوالي ‪( 055.555‬ايرين)‪ .‬أما في السعودية فيقدر عددهم نحو نصف مليون‪ ،‬وفي باكستان ‪ 805‬ألفا‪.‬‬ ‫وعندما ازداد عدد الالجئين في بنجالدش‪ ،‬بادرت كثير من المنظمات اإلسالمية بالوقوف بجانب إخوانهم األراكانيين بالدعم‬ ‫والمساعدات الغذائية والطبية وغيرها‪ .‬ولكن‪ ،‬بعد أحداث الحادي عشر من سبتمبر ‪1554‬م بالواليات المتحدة‪ ،‬منعت الحكومة‬ ‫البنغالية المنظمات اإلسالمية من العمل في مخيمات الالجئين الروهنجيا على الحدود‪.‬‬ ‫جلة لدى حكومة بنجالديش ولدى المفوضية العليا لشؤون‬ ‫مخيمات الالجئين البورماويين في بنجالدش نوعان؛ فهناك مخيمات مس َّ‬ ‫الالجئين التابعة لألمم المتحدة‪ ،‬حيث يوجد ‪ 17.555‬روهينجيا مسجال لدى المفوضية فقط‪ 44.555 ،‬منهم يقيمون في مخيم‬ ‫كوتوبالونج لالجئين خارج كوكس بازار و‪ 48.555‬غيرهم في مخيم نايابار الذي يقع على مسافة أبعد جنوبا‪.‬‬ ‫وهؤالء يجدون بعض المواد الغذائية والعالج من منظمات األمم المتحدة‪ ،‬رغم أنها مساعدات ضئيلة جدا مقارنة باحتياجات وعدد‬ ‫جلة (غير رسمية)‪ ،‬ويوجد بها أكثر من مائتي ألف نسمة‪ ،‬يعيشون في مخيمات‬ ‫الالجئين الروهنجيا أما المخيمات األخرى غير مس َّ‬ ‫الالجئين على الحدود بين بنجالديش وبورما‪ ،‬في أوضاع مأساوية تنذر بكارثة إنسانية‪ ،‬فال ماء وال غذاء وال دواء وال حياة لهم إال في‬ ‫خيام بالستيكية‪ .‬وقد تقيدت كل المحاوالت للخروج من المخيم بسبب االعتقال التعسفي والطرد القسري من قبل السلطات‬ ‫البنغالية‪ ،‬ويتعرض الالجئون ألنواع شتى من األوبئة واألمراض الفتاكة‪ ،‬مثل الحمى والمالريا واألمراض الجلدية واإلسهال المزمن‪،‬‬ ‫ويموت عدد كبير من األطفال بسبب األمراض الخطيرة‪ ،‬كما يموت عدد من النساء بسبب الوالدة المتعثرة لعدم وجود مستشفى غير‬ ‫ح ُقوق اإلنسان األمريكيَّة (أطباء من أجل حقوق اإلنسان)‪ ،‬في تقرير لها أن ‪ 155‬ألف روهنجي في‬ ‫الرسمي‪ ،‬فقد حذرت منظم ُة ُ‬ ‫السلَع‬ ‫بنجالديش ُيعانون من حالة ُمتدهورة من الناحية اإلنسانية‪ ،‬وأن مسلمي روهينجا سيَ َت َع َّرضون لخطر المجاعة إذا لَم يتم زيادة‬ ‫ِ‬ ‫سوء تغذية حاد‪.‬‬ ‫الغذائية‪ ،‬وتقول المنظمة‪ :‬إنَّ ‪ % 47‬من األطفال ُيعانون بالفعل من ُ‬

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‫ومن جهة أخرى تقوم السلطات في بنجالدش بحمالت دعائية عبر وسائل اإلعالم المحلية لبث الكراهية والتحريض ضد الالجئين‬ ‫الروهنجيين وتقوم أيضا بتهديد القرويين باالعتقال إذا لم يقوموا بدورهم في إبالغ السلطة عن جيرانهم الروهنجيا‪.‬‬ ‫وهنالك كثير من األنباء التي تتحدث عن معاناة بعض الجئي الروهنجيا في تايالند الذين دفعت بهم القوات البحرية التايالندية في‬ ‫قوارب دون محركات وسط األمواج البحرية العالية‪.‬‬ ‫قرارات األمم المتحدة المتعلقة بالروهنجيا‬ ‫• (‪ ) 1545/ 45‬عقدت الدورة ال ‪ 40‬لمنظمة حقوق اإلنسان التابعة لألمم المتحدة في جنيف وتم مناقشة قضية الروهنجيا فيها‬ ‫وكانت توصياتها‪:‬‬ ‫حث المجتمع الدولي إلنشاء لجنة للتحقيق في الجرائم ضد االنسانية التي يرتكبها النظام البورمي ضد الروهنجيا في بورما‪ ،‬ودعوة‬ ‫مجلس الدولة في بورما إلى رفع جميع القيود المفروضة على المجتمع الروهنجي‪ ،‬وتقديم المساعدات اإلنسانية والتعليم والرعاية‬ ‫الصحية للمجتمع الروهنجي في والية أراكان والالجئين الروهنجيا في بنغالديش والسعودية وماليزيا والبحث عن حل جذري‬ ‫لمشكلة معاناة الالجئين الروهنجيا‪ ،‬والدعوة إلنشاء بعثة لتقصي الحقائق والتحقيق في جميع انتهاكات حقوق اإلنسان ضد‬ ‫الروهنجيا في أراكان وبورما‪.‬‬ ‫(‪)Rohingya issues discuss in 15th UN Human Rights Council session in Geneva‬‬ ‫• قرار األمم المتحدة ( ‪) 1545/ 0‬‬ ‫دعا الكونجرس األمريكي النظام البورمي لالعتراف بالروهنجيا كمواطنين لهم الحقوق الكاملة والمتساوية في بورماورفع جميع القيود‬ ‫المفروضة على الزواج‪ ،‬والتنقل والتعليم ويدعو القرار أيضا إلى وضع حد لحملة النظام من االضطهاد الديني والعرقي‪.‬‬ ‫(‪)Recognize Rohingya as “full and equal” citizens of Burma: US Congress‬‬ ‫مهالب مسلمي الروهنجيا‬ ‫‪ )4‬دعوة الدول والمنظمات اإلسالمية للضغط على حكومة ميانمار العسكرية‪.‬‬ ‫‪ )1‬تقديم الدعم والمساعدة الكاملة سياسيا ومعنويا وماديا للصمود حتى ينالوا حقوقهم المشروعة‪.‬‬ ‫‪ )8‬تكثيف وزيادة الدعم المادي واإلغاثي من قبل المنظمات والهيئات الخيرية واإلسالمية العالمية ‪.‬‬ ‫‪ )1‬تكثيف الجهود اإلعالمية‪ ،‬والتواصل مع كبريات وسائل اإلعالم العربية والغربية‪ ،‬وتخصيص أوقات معينة في تلك القنوات للتعريف‬ ‫بالقضية والوضع الراهن‪ ،‬وفتح قنوات فضائية تبث بعدة لغات‪ ،‬وإجراء حوارات مع الحقوقيين الدوليين المعنيين بهذه القضية‪ ،‬لممارسة‬ ‫مزيد من الضغط على السلطات البوذية‪ ،‬وفضح ممارساتها أمام العالم أجمع‪.‬‬

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‫‪ )0‬توفير المعونات اإلغاثة الغذاء والدواء والرعاية الصحية والتعليمية لالجئي أراكان خاصة في بنجالديش وباكستان وإطالق نداء عاجل‬ ‫إلى الدول المانحة من أجل اإلغاثة اإلنسانية وحماية الفئة من الالجئين غير المعترف بها في بنغالديش‪ ،‬والضغط على حكومة‬ ‫بنغالديش للسماح الفوري بإيصال المساعدات اإلنسانية لالجئين من السكان المعرضين للخطر‪.‬‬ ‫‪ )6‬على الدول اإلسالمية التي يوجد بها الجئون من مسلمي أراكان تقديم التسهيالت التي يحتاجونها مثل التعليم والعمل واإلقامة‬ ‫كما ينبغي بناء المؤسسات التعليمية للمسلمين الروهنجيا في أماكن تواجدهم في العالم‪ ،‬ويدرس فيها مادة "الدراسة الوطنية‬ ‫ألراكان" كما يدرس تاريخهم وثقافتهم ولغتهم القومية كمواد أساسية لتلبية ضروراتهم ومراعاة لمتطلباتهم‪ ،‬حتى تستمر رابطتهم‬ ‫مع الوطن وينشأ فيهم الحماس والروح واالرتباط العاطفي والشعور بالمسئولية تجاه الوطن والمواطنين بداخل أراكان وخارجها‪.‬‬ ‫‪ )8‬تقديم المساعدة الضرورية للحفاظ على المعاهد الدينية واألنشطة الدعوية وتنمية البرامج التعليمية في اراكان‪.‬‬ ‫‪ )7‬وينبغي تأليف الكتب وترجمتها إلى اللغة الروهنجية‪ ،‬فبقدر ما تنشر الكتب بهذه اللغة يقترب هذا القوم إلى الحرية ويبتعدون عن‬ ‫العبودية‪ .‬فيتأهلون لحل مشاكلهم بأنفسهم مثل األمم األخرى المثقفة‪ ،‬ويكون التعليم سائدا فيما بينهم‪.‬‬

‫‪https://www.facebook.com/j.documentary/videos/548991465153823/‬‬

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Who are the Rohingya?

The Rohingya are a Muslim ethnic minority living in northern Arakan/Rakhine State in western Burma. They have faced severe persecution and violence at the hands of the state and national governments for decades.

There are approximately 1.33 million Rohingya in Burma, but the country's 1982 Citizenship Law denies them citizenship in spite of the fact that Rohingya have lived in Burma for generations. Burmese President Thein Sein outright denies the existence of the Rohingya as an ethnic group of Burma, calling them "Bengali" instead. Labeling the Rohingya "Bengali" is a discriminatory, xenophobic way of erroneously implying that Rohingya are illegal immigrants from Bangladesh.

photo: Anadolu Agency

A Current Crisis On January 13, 2014, Rakhine mobs and security forces entered Du Chee Yar Tan, Maungdaw Township, and slaughtered over 40 Rohingya. A UN report confirms the gruesome deaths – severed heads of at least 10 Rohingya, some children, were found bobbing in a water tank.

The international community has called on the Burmese government to commission an independent investigation. But Burmese Presidential Spokesman Ye Htut rebuked the UN for calling for an investigation: “It was sad to see a statement issued by the UN…These accusations are unacceptable. By acting like this, it will mean the local people will have more concerns, doubts and less trust in the UN.”

71

The government also vehemently refused the USâ&#x20AC;&#x2122; request to allow international officials to sit on an investigation into the incidents at Du Chee Yar Tan village. The government did eventually consent to commission two internal investigations, but these severely biased investigations concluded that no massacre had taken place whatsoever, and deliberately permitted perpetrators to go uncharged.

The governmentâ&#x20AC;&#x2122;s insistence that there were no Rohingya deaths in Du Chee Yar Tan in January 2014 is just one recent example of the Governmentâ&#x20AC;&#x2122;s complicity in religious violence. Publicly rejecting UN counsel, the Government has refused to hold perpetrators to account or provide legal redress to the many displaced, imprisoned, raped, and murdered Muslims who have become victims of an avoidable, manmade humanitarian crisis.

Stranded at Sea UNHCR estimates that 130,000 Rohingya have fled Bangladesh and western Arakan state since the outbreak of violence in 2012. As a result, the Burmese Navy and local security forces are profiting off the ethnic cleansing of the Rohingya in western Burma by demanding payments from smugglers who devlier Rohingya to human traffickers, as well as Rohingya desperately seeking passage.

Forced to venture by boat to trafficking camps on remote Thai islands, the Rohingya are faced with violence, lack of food and water (often forced to drink their own urine), and those who have fallen victim to disease are thrown overboard if dead or close to dying. In Thailand Rohingya are held in internment camps until they can either pay thousands to human traffickers to be released or be sold as slaves to the highest bidder. Often Rohingya must resort to soliciting funds from their personal networks, and if successful, they are pushed back out to sea. Those who are unable to pay become slaves: women and young girls are forced into marriages and lifelong indentured servitude, and men sold to Thai fishermen.

Recently, mass graves, mostly Rohingya, have been uncovered in Thailand. Now, ASEAN countries (specifically Thailand, Indonesia and Malaysia) are refusing to allow Rohingya refugees to seek assylum. They instruct their respective military to take them back to sea, effectively abandoning the vulnerable Rohingya. It is suspected that thousands have died making the deadly voyage to escape the ethnic cleansing they face in Burma.

Escalating Violence Since June 2012, several hundred Rohingya have been killed because of their religion and ethnicity in widespread, systematic attacks led by Rakhine Buddhists. Over 140,000 Rohingya have been displaced in inhumane internment camps, and thousands have fled the country. Hundreds more, mostly men and boys, have been arrested on false charges.

In June 2012, a Rakhine Buddhist woman was allegedly raped and murdered by three Rohingya Muslim men, and the western Rakhine state subsequently broke out in violence. Refugees accumulated from both sides of the violence, leaving thousands displaced and villages burned and abandoned. The Burmese military was called in to stop the violence by means of further violence, firing tear gas and shooting at the mobs. The fury was temporarily subdued.

In October 2012, a more targeted surge occured against the Rohingya Muslim population. Rakhine Buddhist communities formulated vigilante mobs, surrounding homes and razing them to flames, and Rohingya villagers fled.

Many Rohingya attempted to escape by boat to Bangladesh; some boats capsized leaving many missing, and some reached the Bangladesh shore where they were told to immediately return to Burma.

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Most alarming is the direct involvement of the local, state, and national government in the violence. Government officials have enforced explicitly racist policies for decades, and have failed to intervene and even participated in violent attacks against Rohingya. The government has been accused of implementing the crime against humanity of persecution against the Rohingya, and Rohingya are increasingly considered to be targets of potential acts of genocide.

But Government officials and security forces have refused to implement impartial investigations into the violence. They have instead subjected Rohingya and other Muslims to discriminatory restrictions and policies of apartheid and ethnic cleansing. Rohingya internally displaced persons (IDPs) in Arakan State are now languishing in what UN officials have called the most dismal and under-served IDP camps in the world.

Government persecution has enabled Rakhine Buddhist nationalists to implement a reign of terror against the Rohingya with impunity. Hate speech directed against Rohingya Muslims appears regularly in state-run media, and some Buddhist monks have instigated vitriolic rumors and discrimination against the minority group. Hate speech has helped fuel waves of violence and systematic arson attacks in Rakhine State.

Of the hundreds of thousands of Rohingya that have fled to Bangladesh, Thailand, and Malaysia to escape persecution and adversity, approximately 300,000 Rohingya live in squalid conditions in Bangladesh where they are denied access to food supplies, medical aid, and education. In essence, the Rohingya are â&#x20AC;&#x153;Exiled to Nowhere.â&#x20AC;?

Take action with us and demand that the Rohingya Muslims be given citizenship, are treated with dignity as determined by the Universal Declaration of Human Rights, and insist on an international investigation into systems of violence and impunity encouraged by the Burmese government.

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