pathology

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Interpreting Blood Tests and Investigations Maureen Cox

RCN Conference January 2009


AIM To explore the role of the nurse in assisting, carrying out and assessing the results of blood tests and investigations To discuss the most commonly used investigations in the diagnosis of rheumatological conditions To explore the investigations commonly used for the ongoing monitoring of therapies used in the treatment of rheumatological conditions To look at normal values ( and ranges) and begin to recognise the significance of the results RCN Conference January 2009


The Nurses Role in Blood Tests and Investigations

To provide safe, informed care. To request investigations that are timely and appropriate Support the patient Provide explanation of need for tests Carry them out safely for both patient and nurse Correct labelling and transportation Interpretation of results Action taken on abnormal values Explain results to patient and how this will influence treatment. RCN Conference January 2009


Diagnosis- Commonly used blood tests

Full blood count Urea and electrolytes Liver function tests

ESR Plasma Viscosity C-Reactive Protein Rheumatoid factor Anti CCP

Uric acid Creatinine Kinase Antinuclear antibodies Compliment levels

RCN Conference January 2009


FULL BLOOD COUNT This is used to monitor disease activity, to assess the effects of drug treatment, to exclude dietary deficiency. IMPORTANT VALUES MEASURED Haemoglobin (Hb) White cell count (WCC or WBC) Neutrophils/Granulocytes Eosinophils Platelets Mean cell volume (MCV) RCN Conference January 2009


HAEMOGLOBIN (Hb) Normal value Male Female

13 -18 g dL-1 11.5-15.5 g dL-1

Low haemoglobin, can be due to the increased disease activity.

A sudden fall in Hb should be checked as this can

indicate blood loss, e.g from anti-inflammatory drugs. Check FOB’s (Faeces for occult blood)

Low HB ? Poor Nutrition. Assess function / mobility RCN Conference January 2009


WHITE CELL COUNT

Normal value 4-11x109/l These are the cells which “gobble” up infection A raised white cell count is suggestive of infection. White cell count also is elevated when patients are on or have had steroids. A low white cell count (below 3.5) can occur as a side effect to drug treatments. Patients with SLE and Felty’s often have a low white cell countRCN Conference January 2009


NEUTROPHILS (Neuts /Grans) Specific type of white cell. Normal value 2 - 7.5 x 109/l (absolute value) Same as WCC, up with infection,steroids, also inflammation Down (below 2) side effect of drug treatment, SLE flare, viral infections, severe bacterial infection 1 - 1.5 no significant risk 0.5 - 1 some increased risk < 0.5 major risk of infection Also lower in some races - black Africans -”Negro neutropaenia” RCN Conference January 2009


Eosinophils (EOS) Another specific type of white cell. Normal value up to 0.4 (absolute value) Elevation may indicate: Allergy to either a drug i.e Methotrexate pneumonitis or asthma. Particularly important with Myocrisin (Gold Injection) as may herald allergic reaction. Seen in certain conditions – Churg Struass syndrome – worm infestations. RCN Conference January 2009


PLATELETS Normal value 150 - 400x109/l These are the cells which help the blood to clot Platelets often elevated in active disease (thrombocytosis) due to inflammation. A low platelet count ( thrombocytopaenia) can occur – – –

as a side effect of drug treatment, in patients with active SLE, Felty’s viral infections RCN Conference January 2009


MEAN CELL VOLUME (MCV) Normal value 78 - 104 Reduced MCV(<78) can indicate: – Anaemia of chronic disease – Iron deficiency anaemia (? Need to check Ferritin levels)

Elevated MCV (>104) can indicate: – – – – –

Vitamin B12 deficiency Folate deficiency Thyroid problems Liver problems Marrow dysplasia /Aplastic anaemia RCN Conference January 2009


FERRITIN Serum ferritin is an acute phase protein. It goes up with inflammation. Ferritin is used as a test to check for iron deficiency anaemia in patients with a low Hb and low MCV. In active disease a Ferritin below 90 can indicate iron deficiency. If patients are treated with iron supplements they need to take for at least 3 months then have Ferritin rechecked before stopping treatment RCN Conference January 2009


B12 and Folate Should be measured in patients with macrocytosis ie elevated MCV Macrocytosis seen with some DMARD’s especially Azathioprine, Sulphasalazine and Methotrexate May also herald aplastic anaemia – so don’t ignore!!

RCN Conference January 2009


UREA AND ELECTROLYTES Blood biochemistry is used to check for abnormalities in the body chemistry. Abnormal renal or liver function may occur as a result of organ involvement in multisystem inflammatory diseases, or a side effect of drug treatment.

RCN Conference January 2009


LIVER FUNCTION TESTS ALT – Alanine Transaminase (15-45) Elevated as a side effect of some drugs Alcohol Hepatitis and liver damage Alkaline Phosphatase (up to 300) Elevated when bony activity, flare, fractures Also as side effect of drugs Malignancy RCN Conference January 2009


Inflammatory Markers Commonly used to assess disease activity in RA – Erythrocyte sedimentation rate (ESR) – Plasma viscosity ( PV) – C reactive protein (CRP)

RCN Conference January 2009


Erythrocyte Sedimentation Rate (ESR) Erythrocyte sedimentation rate measures the rate at which the red cells settle. The higher the value the more inflammation. Therefore elevated in active arthritic disorders such as Rheumatoid Arthritis, Lupus, vasculitis, polymyalgia rheumatica Also malignancies. NORMAL VALUES 0-10mm/hr in men aged 18-65 years 1-20mm/hr in women aged 18-65 years Over 65 can go up by 5-10mm/hr RCN Conference January 2009


Plasma Viscosity Used in some hospitals in preference to ESR Reacts in the same way as ESR – elevated with disease activity due to an increase in protein concentration. In same way as ESR elevated in malignancy and paraproteinuraemias Normal range 1.5 - 1.72cp RCN Conference January 2009


C REACTIVE PROTEIN An acute phase protein This is a sensitive and quantitative measurement used for evaluating severity and course of an inflammatory process Considered more accurate than ESR by some. Normal range 0-8mg/l NB Oral contraceptives may affect CRP levels RCN Conference January 2009


RHEUMATOID FACTOR This test measures the presence of rheumatoid factor - the circulating immunoglobulin IgM / IgG It is not a specific test Rheumatoid factor is positive in 4-6% of population Can be negative - Sero- negative inflammatory disease ( AS, PSA) Present in 70% of patients with RA Highest titres found in patients with severe disease It can also be found in patients with cirrhosis, TB, infection and cancer RCN Conference January 2009


RHEUMATOID FACTOR 2 Three tests: RA latex fixation test >1:40 or higher is significant Rose-Waaler – Positive at titre of 1:32 or more Particle agglutination test – Normal range 0-40 In all tests, antibodies cause agglutination of sheep red cells, bacteria or latex, which has been coated with IgG fraction RCN Conference January 2009


RCN Conference January 2009


Anti CCP

Anti Cyclic Citrullinated Peptide Antibody Used in diagnosis of RA Used as an indicator of potential severity of disease

Normal Levels: < 11 negative > 11 Positive, the higher the positivity the greater the potential for errosive disease RCN Conference January 2009


SERUM URIC ACID Uric acid produced as a by-product of purine metabolism. This is the test used if gout is suspected. Normal value Male – 210-480 umol/l Female – 170-420 umol/l NB Women do not get gout prior to the menopause. Commonly seen in diuretic use. Men. RCN Conference January 2009


URIC ACID In addition to this test, aspiration of a swollen joint and the fluid looked at for uric acid crystals under the microscope can confirm Gout.

RCN Conference January 2009


MUSCLE ENZYMES - Creatine Kinase (CK) This is an enzyme released when muscle is damaged. Often done in post MI to measure for heart muscle damage. It is a useful test for muscle disorders such as Myositis (inflammation of the muscles) In Myositis the CK level is often elevated into the 1000’s (Normal 24-190) RCN Conference January 2009


ANTINUCLEAR ANTIBODIES Antinuclear antibodies are found in several rheumatic diseases. It is a useful screening test for SLE, most patients with SLE have +ve ANA, but it is also found in RA, scleroderma, juvenile arthritis and mixed connective tissue diseases. This is a sensitive, but not specific test. Low titres can be found in 1 - 5% of healthy population, titres rise with age. RCN Conference January 2009


ANTINUCLEAR ANTIBODIES 2 The test measures and differentiates antinuclear antibodies. The immunoglobulins IgM, IgG and IgA are the antibodies which react with the nuclear part of leucocytes forming antibodies to DNA and RNA. Test uses immunoflorescence to detect their presence RCN Conference January 2009


ANTINUCLEAR ANTIBODIES 3

RCN Conference January 2009


Complement – C3 and C4 Useful to diagnose immune complex disease. The complement system activated by IgM and IgG and concerned with the mediation of inflammation. Once system has been activated C3 and C4 act as enzymes. Elevate C3 and normal C4 indicates an acute phase response Raised or normal C4 occurs in RA Low C3 and /or C4 suggests SLE, RA or a CTD Normal values C3 - 0.63- 1.7g/l, C4 - 0.11- 0.45g/l RCN Conference January 2009


TPMT Assay 1:33 individuals lack thiopurine s-methyltransferase (TPMT) which helps the body remove drugs such as azathioprine form the body when they are present above therapeutic levels. Assessment of TPMT helps to determine if a patient is going suffer from adverse reactions for Thiopurine drugs such as Azathioprine Individuals with no TPMT enzyme can become severely ill with normal doses of thiopurine drugs because toxic levels of the drug accumulate, leading to bone marrow suppression, a reduction in blood cell production, with subsequent increase in risk of infection and abnormal bleeding RCN Conference January 2009


Ongoing Monitoring of rheumatological conditions Clear evidence from randomised placebo controlled trials that DMARD’s: – – – – –

Reduce symptoms Improve function Improve global well being Improve function Improve long term outcome and survival

Mode of action poorly understood All have the potential to cause adverse effects – Require safety monitoring RCN Conference January 2009


Monitoring of DMARD’s All DMARD’s present some risk to the patient, and require regular monitoring to: – Monitor disease activity – Monitor the patients general health – Detect any adverse effects occurring as a result of the medication

Patients are cautioned that medication will not be prescribed if blood monitoring is not undertaken. RCN Conference January 2009


Current Monitoring Regimes Revised Guidelines Published by BSR 2008 BSR Website www.rheumatology.org At commencement of medication – FBC, U& E’s, LFT’s and CPR every 2 weeks for 3 months then monthly – After 6 months, if stable rheumatologist will advise 6 weekly testing. With the exception of Sulphasalazine which can be every 3 months.

If a second DMARD is prescribed in addition to an established medication, monitoring should revert to 2 weekly for 3 months, and continue monthly

RCN Conference January 2009


Methotrexate Dose 7.5 mg –25mg WEEKLY(2.5 mg tabs) If oral dose is not effective or causes intolerance consider subcutaneous Folic acid (5mg weekly)to be taken day after methotrexate Monthly monitoring for at least 12 months, decrease frequency, based on clinical judgement if disease / dose stable Alcohol-limit within national recommendations

RCN Conference January 2009


Methotrexate (2) Pulmonary toxicity (1:108 pt yrs) – – –

Potentially fatal hypersensitivity Usually seen within 12 months of treatment Incidence may be higher in pre existing lung disease

Pregnancy– Adequate contraception- withdraw mtx for 3 months before conception for both men and women. Avoid breast feeding

Infection-do not withdraw pre operatively

RCN Conference January 2009


Leflunomide Monitoring – BP if>140/90 X 2 occasions 2 weeks apart, treat hypertension before commencement – Weight -pre treatment and on each monitoring visit – FBC and LFT’s monthly for 6 months, then if stable, 2 monthly.

SPC states caution if used with MTX although combination therapy is used. Monitor monthly

RCN Conference January 2009


Leflunomide (2) Pregnancy – Teratogenic, requires adequate contraception. – Females planning conception, withdraw treatment for 2 years or use washout procedure. Avoid Breast feeding – Men should continue adequate contraception for 3 months after discontinuation of treatment.

Alcohol limit to within national limits (4-8 units week) Treat hypertension

RCN Conference January 2009


Sulfasalazine

Time to response minimum 3/12 Transient reversible oligospermia Can be prescribed in pregnancy – Assess risk to mother /baby – Prescribe folic acid supplement when trying to conceive and during pregnancy – Small amounts excreted in breast milk, not thought to be a risk

RCN Conference January 2009


Sulfasalazine (2) Monitoring – FBC and LFT monthly for 3 months then 3 monthly. If following the first year, dose and blood results have been stable -6 monthly for 2nd yr of treatment. Thereafter monitoring can be discontinued – Pts should be asked about the presence of rash or oral ulceration at each visit

RCN Conference January 2009


Other Investigations

Plain x-rays MRI CT Ultrasound Thermography Arthrogram Arthroscopy Capilliary microscopy Nerve conduction studies

Pulmonary function tests Biopsy – Muscle Skin Synovial Bone scans DEXA Synovial fluid analysis Urine testing –Stick Bence Jones 24 hr collections

RCN Conference January 2009


Urinalysis Routine dipstick urinalysis – should never be underestimated Can detect: Blood, protein, bilirubin Indicated possible infection, active disease in Lupus, other organ involvement – kidney or liver Used for drug monitoring – Gold, Penicillamine, cyclophoshamide, ciclosporin, biologic therapies Should be done routinely for all new admissions/clinic attenders Is a case for urinalysis at every visit RCN Conference January 2009


Urine specimens and 24hr collections Bence Jones protein – A protein of low molecular weight found in the urine of patients with multiple myeloma, other bone tumours, amyloidosis and metastatic disease. 24 hour collection Creatinine clearance Urinary protein Used to assess disease and damage, for example in Lupus. Also as a baseline prior to commencing therapy RCN Conference January 2009


Conclusion Multiple investigations available to health professional A full history will give a preliminary diagnosis in 70% of cases Investigations assist us in not only diagnosis, but monitoring and assessing disease process and effect of treatment. Biomechanical measurement is only a small part of assessment of disease –remember assessment of pain, anxiety, depression, function, QOL RCN Conference January 2009


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