Practical manual algorithms final version

Practical manual

Scores and Algorithms in Haemostasis and Thrombosis

JosĂŠ A. PĂĄramo (coordinator) Henri Bounameaux Marcel Levi Gregory YH Lip Pascual Marco Joan Carles Reverter Alberto Tosetto

© Text: the authors © Edition: Grupo Acción Médica. Madrid, 2014 Email: publicaciones@accionmedica.com This work is subject to copyright. All rights, be they related to all or part of the material, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks reserved.

ISBN: 978-84-15226-29-1 • Legal Deposit: M-13411-2014

Scientific board Henri Bounameaux Division of Angiology and Haemostasis University Hospital of Geneva, Switzerland Marcel Levi Academic Medical Center, University of Amsterdam Amsterdam, The Netherlands Gregory YH Lip Centre for Cardiovascular Sciences - City Hospital University of Birmingham, United Kingdom Pascual Marco Hematology Service University General Hospital of Alicante, Spain José A. Páramo Hematology Service University Hospital of Navarra - Pamplona, Spain Joan Carles Reverter Hemotherapy and Hemostasis Service. CDB Hospital Clínic of Barcelona, Spain Alberto Tosetto Hemophilia and Thrombosis Center Hematology Department San Bortolo Hospital, Vicenza, Italy

3

Summary

Prologue .............................................................................................................. 7 Deep Vein Thrombosis and Pulmonary Embolism Clinical probability model for deep vein thrombosis ......................................... 9 Clinical probability models for Pulmonary Embolism ....................................... 10 Diagnostic algorithm for deep vein Thrombosis and Pulmonary Embolism .... 12 Prognostic scores in pulmonary embolism ...................................................... 14 Prediction of recurrent deep vein thrombosis or Pulmonary Embolism ......... 17 Outpatient versus inpatient care in venous thromboembolism ....................... 19 Assessment of post-thrombotic syndrome ..................................................... 21

Pregnancy Diagnostic algorithm in suspected deep vein thrombosis during pregnancy . 22 Diagnostic algorithm in suspected pulmonary embolism during pregnancy ... 23

Atrial Fibrillation Prediction of stroke risk in patients with atrial fibrillation ................................ 25 Bleeding risk in anticoagulated patients with atrial fibrillation ......................... 28 Predicting the likelihood of achieving good anticoagulation control in a newly diagnosed non-anticoagulated patient with atrial fibrillation ........................... 30

Other thrombotic conditions Cancer Risk of Venous thromboembolism in Cancer Patients .................................... 32 Medical patients Risk assessment models in hospitalized Medical Patients .............................. 35 Antiphospholipid syndrome Diagnosis of the antiphospholipid syndrome ................................................... 38 Diagnosis of Disseminated Intravascular Coagulation .................................... 40 Others Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP) ............................ 43 Acute Intestinal Ischemia / Thrombosis ........................................................... 44

5

Summary

Bleeding ISTH bleeding assessment tool for the evaluation of bleeding severity .......... 46 Pediatric bleeding assessment tool for the evaluation of bleeding severity in children ........................................................................................... 50 Bleeding assessment tool for the evaluation of bleeding severity in immune thrombocytopenia: the SMOG system ........................................... 53

Anticoagulant therapy Diagnostic and therapeutic algorithm of Heparin-Induced Thrombocytopenia (HIT syndrome) ................................................................. 59 Bridging strategies in patients on anticoagulants who need to undergo invasive procedures ....................................................................... 61

6

Prologue

Evidence-based medicine provides guidelines to physicians aimed at improving efficacy and safety of patient management. This approach is to a great extent based on the use of clinical scores and diagnosis algorithms that, in combination with patient clinical examination and laboratory tests, improve diagnosis accuracy and patient stratification. This approach also offers a better standardization of patient management across centres and improves patient care reliability.

For doctors who see patients with thrombotic and bleeding problems, or whose clinical workload makes it difficult to keep up with developments in the field of haemostasis, it is hoped that this algorithm booklet may be of some help in the management of such cases.

The use of score calculators and algorithms can facilitate decision making in both diagnosis and treatment of thrombotic and bleeding problems. However, considering the multiplicity of these tools in recent years, it becomes necessary to use a comprehensive manual, without referring to the original sources in every case.

An international expert panel has developed a booklet that compiles, in a clear and simple way, most recognized and useful clinical scores and diagnosis algorithms in the field of thrombosis and haemostasis: deep venous thrombosis, pulmonary embolism, pregnancy, cancer, DIC, antiphospholipid syndrome, atrial fibrillation, and bleeding risk. Each algorithm includes the indication and a brief interpretation emphasising the most relevant aspects of each one followed by some representative references.

We hope this algorithm booklet may guide the clinician in the most appropriate diagnostic and therapeutic strategy, answering some of the questions that may arise when treating thrombotic and bleeding problems.

The authors

7

Indication Clinically suspected deep vein thrombosis (DVT)

Wells’ score Feature

Score

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

1

Paralysis, paresis, or recent plaster immobilization of the lower extremities

1

Recently bedridden ≥ 3 days or major surgery (within the previous 12 weeks requiring general or regional anesthesia)

1

Localized tenderness along the distribution of the deep venous system

1

Entire leg swollen

1

Calf swelling by ≥ 3 cm than that on the asymptomatic leg (measured 10 cm below tibial tuberosity)

1

Pitting oedema* (confined to the symptomatic leg)

1

Collateral superficial veins (non-varicose)

1

Previously documented DVT

1

Alternative diagnosis at least as likely as DVT

–2

Clinical probability Low probability (unlikely) Intermediate/high probability (likely)

≤1 ≥2

* The most symptomatic extremity is used in patients with symptoms in both legs.

Interpretation Useful clinical decision rule if incorporated into the algorithm. Combined with a D-dimer test result below a validated threshold and/or a negative ultrasound, a low clinical probability can safely exclude the presence of DVT. References • W ells PS. Integrated strategies for the diagnosis of venous thromboembolism.

J Thromb Haemost. 2007;5(Suppl 1):41-50.

• Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet. 1997;350:1795-8.

9

Deep Vein Thrombosis and Pulmonary Embolism

Clinical probability model for deep vein thrombosis

Deep Vein Thrombosis and Pulmonary Embolism

Clinical probability models for Pulmonary Embolism Indication Clinically suspected Pulmonary Embolism (PE).

Wells’ score Feature

Score

Previous DVT or PE Heart rate > 100 bpm Surgery or bedridden < 4 weeks Hemoptysis Active malignancy Clinical symptoms of DVT Alternative diagnosis less likely than PE

1.5 1.5 1.5 1 1 3 3

Clinical probability PE unlikely PE likely

â&#x2030;¤4 >4

10

Feature

Points

Points

(revised dichotomized score)

(simplified score)

3

1

3 5 2 2 2 3

1 2 1 1 1 1

4

1

1

1

≤5 >5

≤2 >2

Previous DVT or PE Heart rate: 75-94 bpm ≥ 95 bpm Surgery or fracture < 1 month Hemoptysis Active malignancy Unilateral lower limb pain Pain on lower limb deep venous palpation or unilateral oedema Age > 65

Clinical probability PE unlikely PE likely

Interpretation These models are very useful when incorporated into algorithms, to optimize patient management in clinically suspected PE. Combined with a D-dimer test result below a validated threshold and/or an objective imaging test, a low clinical probability can safely rule out the presence of PE. References

• C eriani E, Combescure C, Le Gal G, et al. Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis. J Thromb Haemost. 2010;8:957-70.

• Klok FA, Mos IC, Nijkeuter M, et al. Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism. Arch Intern Med. 2008;168:2131-6.

• Le Gal G, Righini M, Roy PM, et al. Prediction of Pulmonary Embolism in the Emergency Department: The Revised Geneva Score. Ann Intern Med. 2006;144:165-71.

• Lucassen W, Geersing GJ, Erkens PM, et al. Clinical decision rules for excluding pulmonary embolism: a meta-analysis. Ann Int Med. 2011;155:448-60.

• Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83:416-20.

11

Deep Vein Thrombosis and Pulmonary Embolism

Geneva scores

Deep Vein Thrombosis and Pulmonary Embolism

Diagnostic algorithm of deep vein Thrombosis and Pulmonary Embolism Indication Clinically suspected deep vein thrombosis (DVT) or non-massive Pulmonary Embolism (PE), to decide therapeutic approach.

Clinical probability

Unlikely

Likely

D-dimer

Below cut-off

Above cut-off

CUS or MDCTA

Negative

Positive

No anticoagulant therapy

Anticoagulant therapy

12

References

• A dam SS, Key NS, Greenberg CS. D-dimer antigen: current concepts and future prospects. Blood. 2009;113:2878-87.

• Agnelli G, Becattini C. Acute pulmonary embolism. N Engl J Med. 2010;363: 266-74.

• Aguilar C, del Villar V. Combined D-dimer and clinical probability are useful for exclusion of recurrent deep venous thrombosis. Am J Hematol. 2007;82:41-4.

• Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis.

Lancet. 2012;379:1835-6.

• Hogg K, Wells PS, Gandara E. The diagnosis of venous thromboembolism. Semin Thromb Hemost. 2012;38:691-701.

• Prisco D, Grifoni E. The role of D-dimer testing in patients with suspected venous thromboembolism. Semin Thromb Hemost. 2009;35:50-9.

• Righini M, van Es J, Den Exter PL, et al. Age-adjusted D-dimer cut-off levels to rule out pulmonary embolism: a prospective outcome study: the ADJUST-PE study.

JAMA. 2014;111:1117-24.

• Schutgens RE, Ackermark P, Hass FJ, et al. Combination of a normal D-dimer concentration and non-high pretest probability score is a safe strategy to exclude deep venous thrombosis. Circulation. 2003;107:593-7.

• Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003;349:1227-35.

13

Deep Vein Thrombosis and Pulmonary Embolism

Interpretation Clinical decision rule with sequential diagnostic steps in clinically suspected DVT or PE, based on the clinical probability, assessed by the diagnostic scores (see corresponding chapters), DD (D-dimer measurement) and imaging (CUS: compression ultrasonography in suspected DVT, MDCTA: multidetector CT angiography in suspected PE). When using highly sensitive DD assays, the cut-off is usually set at 500 ng/mL. Recently, the utility of the DD step was shown to be greatly improved by using an age-adjusted cut-off, defined as patient’s age times 10 in patients aged 50 years or more.

Deep Vein Thrombosis and Pulmonary Embolism

Prognostic scores in pulmonary embolism Indication Predictive scoring system for patients with pulmonary embolism (PE) using PESI (the Pulmonary Embolism Severity Index) and Geneva score calculators.

PESI Points Original version Simplified version

Features Age Male History of cancer History of heart failure History of chronic lung disease Pulse ≥ 110 bpm Systolic BP < 100 mmHg Respiratory rate ≥ 30/min Temperature < 36 ºC Altered mental status Arterial oxygen saturation < 90%

Years +10 +30 +10 +10 +20 +30 +20 +20 +60 +20

> 80 =1 1

}

1a 1 1

1

Risk evaluation

a

Class I (very low) Class II (low) Class III (intermediate) Class IV (high)

≤ 65 points 66-85 points 86-105 points 106-125 points

Class V (very high)

> 125 points

Low: 0 High: ≥ 1

Variables combined into a single category of chronic cardiopulmonary disease

Interpretation The PESI score includes 11 clinical features and provides an estimation of the risk of mortality at 30 days after hospitalization in patients with PE. A significant proportion of low-risk patients (negative predictive value 99%) are identified as potential candidates for ambulatory treatment. The simplified version includes

14

Geneva prognostic score Feature

Points

History of cancer

2

History of heart failure

1

Previous DVT

1

DVT on ultrasound

1

PAS < 100 mmHg

2

PaO2 < 8 kPa

1

Clinical probability Low risk

≤2

High risk

≥2

Interpretation Predictive risk value of low-mortality-risk patients, recurrent VTE or increasing bleeding at 3 months. Patients with ≤ 2 points are considered low-level risk patients. This stratification might help identifying patients who could be treated in an outpatient setting.

15

Deep Vein Thrombosis and Pulmonary Embolism

6 features with a similar validity. The RIETE study shows that mortality was 1% amongst 36% of the classified low-risk patients, against 10.9% in high-risk patients. The PESI has been used to identify patients that may be treated in an outpatient setting.

Deep Vein Thrombosis and Pulmonary Embolism

References

• A ujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med. 2005;172:1041-6.

• Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. 2011;378:41-8.

• Donzé J, Le Gal G, Fine MJ, et al. Prospective validation of the Pulmonary Embolism Severity Index. A clinical prognostic model for pulmonary embolism. Thromb Haemost.

2008;100:943-8.

• Jiménez D, Aujesky D, Moores L, et al. RIETE Investigators. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med. 2010;170:1383-9.

• Wicki J, Perrier A, Perneger TV, et al. Predicting adverse outcome in patients with acute pulmonary embolism: a risk score. Thromb Haemost. 2000;84:548-52.

16

Indication Assessment of risk of recurrence after a first DVT or PE. Presentation of two methods: the Vienna nomogram and the DASH score.

Vienna Nomogram Points

0

20

30

40

50

60

70

80

90

100

Male

Gender

Location

10

Female

Proximal DVT Distal DVT

D-dimer (ng/mL)

Total points

PE

100

150

0

50

200

250

100

400

500

150

750

200

1.000

250

1.500 2.000

300

350

1 year cumulative recurrence rate

5 year cumulative recurrence rate

0.02

0.04

0.1

0.06

0.2

0.08 0.1 0.12 0.15

0.3

0.4

0.5

Interpretation The nomogram aims at estimating the recurrence risk following DVT or PE. Clinical (type of thrombosis and gender) and analytical (D-dimer measured at the time of the suspension of anticoagulation) variables are taken into consideration.

In practice, a line has to be drawn perpendicular to the top row (called points) that cuts the value of each of the three considered features (gender, location and D-dimer). The sum of the three responses is born on a line called Total, from

17

Deep Vein Thrombosis and Pulmonary Embolism

Prediction of recurrent deep vein Thrombosis or Pulmonary Embolism

Deep Vein Thrombosis and Pulmonary Embolism

which a perpendicular line is drawn to this value, which gives the cumulated risk at one year and, by drawing another perpendicular line, the cumulative risk at five years. For example: A man with a proximal DVT and a D-dimer of 400 μg/L will score 60 points for gender, 70 for proximal thrombosis and 46 points for D-dimer, totalizing 176 points, which corresponds to a probability of recurrence of 5.1% and 18.5%, at one and five years, respectively.

DASH score Feature

Score

Abnormal D-dimer (measured one month after stopping anticoagulation)

Age ≤ 50 Male Hormonal therapy at onset of VTE (among women)

+2 +1 +1 –2

Probability Low High

≤1 >1

DASH: D-dimer, Age, Sex, Hormones

Interpretation This model classifies DVT or PE recurrence risk as low (annual incidence around 3%) if the score is 0 or 1, or high (annual incidence around 9%) if it is higher than 1. Of note, D-dimer measurement is performed after withdrawal of anticoagulation (≅ 30 days).

References

• E ichinger S, Heinze G, Jandeck LM, et al. Risk assessment of recurrence in patients with unprovoked deep-vein thrombosis or pulmonary embolism: the Vienna prediction model. Circulation. 2010;121:1630-6.

• Tosetto A, Iorio A, Marcucci M, et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost. 2012;10:1019-25.

18

Indication To identify patients with VTE that can safely be treated as outpatients.

Hestia criteria yes no yes Is thrombolysis or embolectomy necessary? no yes Active bleeding or high risk for bleeding?** no yes More than 24 hours of oxygen supply to maintain oxygen saturation > 90%? no yes Is pulmonary embolism diagnosed during anticoagulant treatment? no yes Severe pain needing intravenous pain medication for more than 24 hours? no Medical or social reason for treatment in the hospital for more than 24 hours yes (infection, malignancy, no support system, etc.)? no yes Does the patient have a creatinine clearance of less than 30 mL/min?*** no yes Does the patient have severe liver impairment?**** no yes Is the patient pregnant? no Is the patient hemodynamically unstable?*

Does the patient have a documented history of heparin-induced thrombocytopenia (HIT)?

yes no

* Systolic arterial pressure (SAP) < 100 mmHg; pulse > 100 bpm; Intensive Care Unit admission required ** Gastrointestinal bleeding in the previous 14 days, recent ictus (< 4 weeks), recent surgery (> 2 weeks), bleeding diathesis or thrombocytopenia (< 75.000/mm3), uncontrolled hypertension (SAP > 180 or diastolic arterial pressure [DAP] > 110 mmHg) *** Calculated applying Cockcroft-Gault formula **** As per medical assessment

19

Deep Vein Thrombosis and Pulmonary Embolism

Outpatient versus inpatient care in venous thromboembolism

Deep Vein Thrombosis and Pulmonary Embolism

Interpretation Answering yes to any of the questions means that the patient should probably be hospitalized for treatment. Of note, the PESI and the Geneva Prognostic Score (see corresponding chapters) that stratify patients in low and high risk of mortality or adverse outcome, respectively, have also been used for that purpose.

References

• Z ondag W, Hiddinga BI, Crobach MJ, et al.; Hestia Study Investigators. Hestia criteria can discriminate high from low risk patients with pulmonary embolism. Eur Respir J. 2013;41:588-92.

• Zondag W, Mos IC, Creemers-Schild D, et al.; Hestia Study Investigators. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. J Thromb Haemost. 2011;9:1500-7.

20

Indication Score of post-thrombotic syndrome (PTS) severity Villalta score None

Light

Moderate

Severe

Symptoms • Pain • Cramps • Heaviness • Paresthesia • Itching

0 0 0 0 0

1 1 1 1 1

2 2 2 2 2

3 3 3 3 3

Signs • Pretibial oedema • Skin induration • Hyperpigmentation • Redness • Venous ectasia • Calf pain on pressure

0 0 0 0 0 0

1 1 1 1 1 1

2 2 2 2 2 2

3 3 3 3 3 3

Venous ulcer

Absence

Presence

Interpretation The diagnosis of PTS is established when total score (ranking 0-33) is ≥ 5.

Patients with venous ulcer are scored with 15. PTS is stratified in three levels: • Light: 5-9 • Moderate: 10-14 • Severe ≥ 15 References

• K ahn SR, Partsch H, Vedantham S, et al.; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost. 2009;7:879-83.

• Prandoni P, Villalta S, Polistena P, et al. Symptomatic deep-vein thrombosis and the post-thrombotic syndrome. Haematologica. 1995;80(Suppl 2):42-8.

• Villalta S, Bagatella P, Piccioli A, et al. Assessment of validity and reproducibility of a clinical scale for the post-thrombotic syndrome. Haemostasis. 1994;24(suppl 1):158a.

21

Deep Vein Thrombosis and Pulmonary Embolism

Assessment of post-thrombotic syndrome

Pregnancy

Diagnostic algorithm in suspected deep vein thrombosis during pregnancy Indication Clinically suspected DVT during pregnancy.

Clinically suspected DVT Serial compression ultrasound

DVT no confirmed

DVT confirmed

Clinically suspected iliac DVT*

Start treatment

Yes

No

Serial compression ultrasound after 1 week Normal DVT excluded

Abnormal

Duplex Doppler

Flow absent

Flow present

Consider magnetic resonance image

DVT confirmed

Start treatment * The clinical suspicion of iliac vein thrombosis is based on pain located at the back of the thigh or buttocks and swelling in the upper part of the lower extremity.

Interpretation Clinical decision rule using sequential steps in clinically suspected DVT in a pregnant woman. D-dimer measurement is usually skipped due to lack of specificity in this condition, though a value below the threshold allows ruling out the condition.

22

Pregnancy

Diagnostic algorithm in suspected pulmonary embolism during pregnancy Indication Clinically suspected PE during pregnancy.

Clinically suspected PE Symptomatic DVT

No

Yes

Serial compression ultrasound DVT no confirmed

DVT confirmed

Start treatment Ventilation/ perfusion scan

Computed tomography

Normal

High probability

Nondiagnostic

PE excluded

PE confirmed

Computed tomography

PE excluded

PE confirmed Start treatment

Start treatment

23

Nondiagnostic Ventilation/ perfusion scan

Pregnancy

Interpretation Clinical decision rule using sequential steps in clinically suspected PE in a pregnant woman. Again, D-dimer measurement is usually skipped during pregnancy, though a value below the threshold allows ruling out the condition.

In case of detecting a symptomatic DVT, anticoagulation therapy should be started without additional imaging tests.

References

• C han WS, Ginsberg JS. Diagnosis of deep-vein thrombosis and pulmonary embolism in pregnancy. Thromb Res. 2002;107:85-91.

• Le Gal G, Kercret G, Ben Yahmed K, et al. Diagnostic value of single complete compression ultrasonography in pregnant and postpartum women with suspected deep vein thrombosis: prospective study. BMJ. 2012;344:e2635.

• Tan M, Huisman MV. The diagnostic management of acute venous thromboembolism during pregnancy: recent advancements and unresolved issues. Thromb Res. 2011;127:S13-6.

24

Indication Atrial fibrillation (AF) is the most common arrhythmia in the population, and is a major cause of stroke and systemic thromboembolism. Whilst the risk of stroke in AF is increased 5-fold, stroke risk in AF is not homogeneous.

The CHADS2 and CHA2DS2-VASc stroke risk score calculators have been used to aid risk stratifying of patients, and to help decision making for thromboprophylaxis. The CHA2DS2-VASc score is now recommended by many international guidelines, including those from the ESC, AHA/ACC/HRS, APHRS, SIGN and NICE guidelines.

CHADS2 risk score Risk factor

Score

Congestive heart failure

1

Hypertension

1

Age â&#x2030;Ľ 75 years

1

Diabetes mellitus

1

Prior Stroke or TIA or Thromboembolism

2

Interpretation Low risk = 0 Moderate risk = 1 High risk â&#x2030;Ľ 2 The CHADS2 score has been replaced by the CHA2DS2-VASc score in the latest guidelines from the ESC, AHA/ACC/HRS, NICE, etc. Older guidelines (e.g. the 2006 ACC/AHA/ESC guidelines) recommended the following: CHADS2 score >1 1 0

Antithrombotic therapy recommendation OAC (vitamin K antagonist or dabigatran) OAC or ASA 75-325 mg/day ASA

OAC: oral anticoagulant; NOAC: Non-VKA Oral AntiCoagulants (previously called New or novel OACs); ASA: Acetylsalicylic Acid

25

Atrial Fibrillation

Prediction of stroke risk in patients with atrial fibrillation

Atrial Fibrillation

CHA2DS2-VASc risk score Risk factor

Score

Congestive heart failure

1

Hypertension

1

Age ≥ 75 years

2

Diabetes

1

Prior Stroke or TIA or Thromboembolism

2

Vascular disease

1

(peripheral artery disease, myocardial infarction, aortic plaque)

Age between 65 and 74 years

1

Sex category (i.e. female gender)

1

Maximum score

9

Interpretation Low risk = 0 (males) or 1 (females) Moderate risk = 1 (males) High risk ≥ 2 The ESC guidelines de-emphasises the ‘traditional’ (but artificial) low, moderate and high risk stratification and recommends a risk factor-based approach using the ‘CHA2DS2-VASc’ score.

The initial focus is now on identification of ‘truly low-risk’ patients with AF, that is, those ‘age < 65 and lone AF (irrespective of gender)’ – which is essentially a CHA2DS2-VASc score = 0 (males) or 1 (females). Such ‘low risk’ patients do not need any antithrombotic therapy.

After this initial decision step, patients with AF and ≥ 1 stroke risk factors can be offered effective stroke prevention, which is oral anticoagulation (OAC).

The latter can be delivered either as well controlled VKA (as reflected by average Time in Therapeutic Range [TTR] ≥ 70%) or one of the NOACs.

26

• C amm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation. Eur Heart J. 2012;33:2719-47.

• De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heart disease: Current status and perspectives (section III). Position paper of the esc working group on thrombosis - task force on anticoagulants in heart disease.

Thromb Haemost. 2013;110:1087-107.

• Lip GY. Stroke and bleeding risk assessment in atrial fibrillation: When, how, and why? Eur Heart J. 2013;34:1041-9.

• Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest. 2010;137:263-72.

• Pisters R, Lane DA, Marin F, et al. Stroke and thromboembolism in atrial fibrillation.

Circ J. 2012;76:2289-304.

27

Atrial Fibrillation

References

Atrial Fibrillation

Bleeding risk in anticoagulated patients with atrial fibrillation Indication Major complication in anticoagulated patients is bleeding, intracranial haemorrhage being the most severe manifestation (0.8-1%/patients/year).

In the ESC guidelines, bleeding risk assessment is also recommended using the HAS-BLED score. The HAS-BLED score is validated for VKA and non-VKA anticoagulants, and is the only bleeding risk score predictive for intracranial haemorrhage. Other studies have validated HAS-BLED in atrial fibrillation (AF) and non-AF patients, those undergoing bridging therapy, and in bleeding related to PCI/stenting.

HAS-BLED score HAS-BLED

Score

Hypertension i.e. uncontrolled Blood Pressure

1 1 or 2

Abnormal renal/liver function Stroke

1

Bleeding tendency or predisposition

1

Labile INR

1

Elderly (e.g., > 65, frail condition)

1

Drugs (e.g. concomitant aspirin or NSAIDs) or alcohol excess or abuse

1 9

Interpretation A high HAS-BLED score (â&#x2030;Ľ 3) should not be used as a reason for withholding OAC but is indicative of the need for regular review and follow-up. A high HAS-BLED score also makes us consider the potentially reversible risk factors for bleeding, for example, the H in HAS-BLED stands for uncontrolled blood pressure (so to reduce risk, BP should be controlled), the L stands for labile INRs, and D for concomitant use of aspirin/NSAIDs in anticoagulated patients, etc. Those patients with a high HAS-BLED score derive a higher net clinical benefit when balancing ischaemic stroke and intracranial bleeding.

28

• F riberg L, Rosenqvist M, Lip G. Net clinical benefit of warfarin in patients with atrial fibrillation: A report from the Swedish atrial fibrillation cohort study.

Circulation. 2012;125:2298-307.

• Lip GY, Andreotti F, Fauchier L, et al.; European Heart Rhythm Association.

Bleeding risk assessment and management in atrial fibrillation patients. Executive Summary of a Position Document from the European Heart Rhythm Association [EHRA], endorsed by the European Society of Cardiology [ESC] Working Group on Thrombosis. Thromb Haemost. 2011;106:997-1011.

• Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (has-bled) to assess 1-year risk of major bleeding in patients with atrial fibrillation: The Euro Heart Survey. Chest. 2010;138:1093-100.

29

Atrial Fibrillation

References

Atrial Fibrillation

Predicting the likelihood of achieving good anticoagulation control in a newly diagnosed non-anticoagulated patient with atrial fibrillation Indication A clinical management dilemma is how to predict those newly diagnosed non-anticoagulated AF patients who are likely to do well on warfarin with high TTR, especially since costs of NOACs are high, and since the relative benefits of NOACs over the VKAs may be small in those who achieve good-quality anticoagulation control, with high TTRs (> 70%).

An ESC Working Group on Thrombosis Anticoagulation Task Force Position paper recommends that the use of the new SAMe-TT2R2 score should be considered to aid decision making when assessing such patients. This is a user-friendly validated score based on simple clinical variables.

Definition of the SAMe-TT2R2 score Acronym

Definitions

Score

S

Sex (female)

1

A

Age (less than 60 years)

1

Me

Medical history*

1

Treatment

1

T

(interacting Rx e.g., amiodarone for rhythm control)

T

Tobacco use (within 2 years)

2

R

Race (non-Caucasian) Maximum points

2 8

Definition of the SAMe-TT2R2 score * 2 of the following: hypertension, diabetes melitus, coronary artery disease / myocardial infraction, PAD, coronary heart failure, previous stroke, pulmonary disease, hepatic or renal disease.

30

If the SAMe-TT2R2 score is > 2, such patients could be better off being started on NOACs as initial therapy, or having more aggressive efforts to improve anticoagulation control.

References

• A postolakis S, Sullivan RM, Olshansky B, et al. Factors affecting quality of anticoagulation control among patients with atrial fibrillation on warfarin: The SAME-TT2R2 score. Chest. 2013;144:1555-63.

• Boriani G. Predicting the quality of anticoagulation during warfarin therapy: the basis for an individualized approach. Chest. 2013;144:1437-8.

• De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heart disease: Current status and perspectives (section III). Position paper of the ESC working group on thrombosis - task force on anticoagulants in heart disease.

Thromb Haemost. 2013;110:1087-107.

• Lip GY, Haguenoer K, Saint-Etienne C, Fauchier L. Relationship of the SAMETT2R2 score to poor quality anticoagulation, stroke, clinically relevant bleeding and mortality in patients with atrial fibrillation. Chest. 2014 Apr 10. doi: 10.1378/ chest.13-2976. [Epub ahead of print].

31

Atrial Fibrillation

Interpretation This score identifies those Atrial Fibrillation patients likely to do well on warfarin (SAMe-TT2R2 score 0-1) or those more likely to have poor anticoagulation control (SAMe-TT2R2 score > 2).

Other thrombotic conditions

Risk of venous thromboembolism in cancer Patients Indication Assessing the risk of DVT or PE in outpatients with cancer on chemotherapy (Khorana model), the prediction of recurrence (Ay and Ottawa models) and the risk of DVT in patients with multiple myeloma treated with thalidomide or lenalidomide.

Khorana model: for outpatients with cancer on chemotherapy Feature

Points

Site of cancer (origin) • High risk (pancreas, stomach) • Low risk (lung, lymphoma, gynaecologic, bladder, testicular) Platelet count ≥ 350 × 109/L Haemoglobin level < 100 g/L or use of red cell growth factor Leukocyte count > 11 × 109/L BMI ≥ 35 kg/m2

2 1 1 1 1 1

Probability • Low risk • Intermediate risk • High risk

0 1-2 >3

Interpretation The risk of thrombosis was 0.3-0.8% for low-risk patients; 1.8-2.0% for intermediate-risk patients and 6.7-7.1% for high-risk patients; in the latter thromboprophylaxis should be considered.

32

Feature

Points

Khorana D-dimer ≥ 1.44 μg/mL P-selectin ≥ 53.1 mg/mL

Model scoring (0 to 6) 1 1

Probability Low risk Intermediate risk High risk

0 1-2 ≥3

Interpretation The risk of DVT or PE at 6 months was 17.7% in high-risk patients, 9.6% in intermediate-risk patients and 3.8% in low-risk patients.

Ottawa score Recurrence risk in patients with thrombosis associated with neoplasia Feature

Points

Female Lung Cancer Breast Cancer Status (TNM*) Previous DVT or PE

1 1 –1 –2 1

Probability Low risk High risk

≤0 ≥1

* TNM: Tumor-Node-Metastasis level

Interpretation The DVT or PE recurrence risk was ≤ 4.5% for low-risk patients and ≥ 19% for high-risk patients.

33

Other thrombotic conditions

Vienna score (Ay Model): DVT or PE risk scoring

Other thrombotic conditions

DVT risk scoring in patients with myeloma treated with thalidomide or lenalidomide DVT risk factors

Category

Prophylaxis

• BMI ≥ 30 kg/m2 Individual and ≤ 1 risk factor: myeloma-related • Previous DVT or PTE • Aspirin factors • Central venous catheter or pacemaker (80-300 mg/d) • Concomitant disease (cardiac, chronic renal, diabetes, acute infection, ≥ 2 factors: immobilization) • LMWH (equivalent • Medications (EPO) to enoxaparin • Clotting disorders 40 mg/d) or • Hyperviscosity • VKA (INR = 2-3) Myeloma High dose of dexamethasone, HBPM (e.g., enoxaparin therapy doxorubicin, polychemotherapy 40 mg/d) or VKA (INR = 2-3) BMI: Body Mass Index; EPO: Erythropoietin; LMWH: Low-Molecular-Weight Heparin; INR: International Normalized Ratio; VKA: Vitamin K antagnonists

Interpretation The risk of thrombosis is high in patients with multiple myeloma, especially in those receiving thalidomide or lenalidomide combined with dexamethasone. In these patients antithrombotic prophylaxis should be considered, according to the risk.

References

• A y C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood. 2010;116:5377-82.

• F arge D, Debourdeau P, Beckers M, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer.

J Thromb Haemost. 2013;11:56-70.

• Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-7.

• Louzada ML, Carrier M, Lazo-Langner A, et al. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer: Associated Venous Thromboembolism. Circulation. 2012;126:448-54.

• P alumbo A, Rajkumar SV, Dimopoulos MA, et al.; International Myeloma Working Group. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008;22:414-23.

34

Indication Risk Assessment Model (RAM) for DVT or PE in patients hospitalized for medical conditions.

Padua prediction score Feature

Points

Active cancer* Previous DVT or PE (excluding superficial vein thrombosis) Reduced mobility** Already-known thrombophilic condition*** Recent (≤ 1 month) trauma and/or surgery Age ≥ 70 years Heart and/or respiratory failure Acute myocardial infarction or ischemic stroke Acute infection and/or rheumatologic disorder Obesity (BMI ≥ 30 kg/m2) Ongoing hormonal treatment****

3 3 3 3 2 1 1 1 1 1 1

Probability High

>4

* Patients with local or distant metastases and/or in whom chemotherapy or radiotherapy have been given in the previous 6 months ** Bed rest for at least 3 days *** Carrier status for antithrombin or protein C or S defects, factor V Leiden, prothrombin gene mutation, antiphospholipid syndrome **** Hormone replacement therapy or oral contraceptives

Interpretation Among patients who did not receive prophylaxis, VTE occurred in 11% of the high-risk group against 0.3% in the low-risk group. The prevalence of DVT and PE were 6.7% and 3.9% respectively in the high-risk group.

35

Other thrombotic conditions

Risk assessment models in hospitalized Medical Patients

Other thrombotic conditions

References

• B arbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost. 2010;8:2450-7.

• Kahn SR, Lim W, Dunn AS, et al.; American College of Chest Physicians.

Prevention of VTE in non surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(Suppl 2):e195S-226.

Geneva prediction score Feature

Points

Cardiac failure Respiratory failure Recent stroke Recent myocardial infarction Acute infectious disease Acute rheumatic disease Malignancy Myeloproliferative syndrome Nephrotic syndrome History of VTE Known hypercoagulability state Immobilisation Travel > 6hs Age > 60 Obesity (BMI > 30) Chronic venous insufficiency Pregnancy Hormonal therapy Dehydration

2 2 2 2 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1

Interpretation Indication for thromboprophylaxis if the score is ≥ 3.

36

• C hopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost. 2006;4:915-6.

• Nendaz M, Spirk D, Kucher N, et al. Multicenter validation of the Geneva risk score for hospitalized medical patients at risk of venous thromboembolism.

Explicit ASsessment of Thromboembolic risk and prophylaxis for Medical Patients in Switzerland (ESTIMATE). Thromb Haemost. 2014;111:531-8.

37

Other thrombotic conditions

References

Other thrombotic conditions

Diagnosis of the antiphospholipid syndrome Indication According to the 2006 Sydney criteria, both clinical and biological features should be associated in the diagnosis of the antiphospholipid antibody syndrome (APS).

Diagnostic criteria for APS Clinical featuresa

Haemostasis laboratory criteriab

One or more episodes of venous or arterial thrombosis • Presence of small-vein thrombosis in any organ system • Confirmed by imaging tests (such as ultrasound or Doppler) • Histopathology confirmation: to exclude in case of inflammation • Superficial venous thrombosis excluded

1) Lupus anticoagulant: • Prolonged result of a phospholipiddependent clotting assay (e.g., aPTT, dRVVT) • Mixing study: evidence of the LA inhibitory effect • Evidence of phospholipid dependency: Correction by adding phospholipids into coagulation assay (exclusion of specific inhibitors against a coagulation factor)

Pregnancy-related complications • One or more unexplained deaths of a morphologically normal foetus at or after 10 weeks of gestation, evidenced by ultrasound or direct examination of the foetus • One or more premature births of morphologically normal neonate(s) at or before 34 weeks gestation associated with severe preeclampsia or eclampsia or severe placenta insufficiency • Three or more unexplained consecutive miscarriages at or before 10 weeks gestation, with anatomic, genetic and hormonal causes excluded

2) Anticardiolipin antibodies: • Normalised ELISA system • Titre > 40 UGPL/UMPL or > 99th percentile. IgG and IgM antibodies

a b

3) Anti-β2 glycoprotein I antibodies: • Normalised ELISA system • Titre > 99th percentile. IgG and IgM antibodies

APS diagnosis criteria: both clinical and laboratory criteria are required Biological tests should be confirmed at two occasions separated at least by 12 weeks

38

1) Preanalytical • Sodium citrate tube containing 0.109 mol/L citrate, proportion 9 blood to 1 citrate (vol/vol) • Double-spinning centrifuge. Freeze promptly < –70 ºC • Fast defrosting in a water bath at 37 ºC and mix gently by repeated inversion before using • DO NOT work with filtrated plasma

2) Process: Detection, Mixture, Confirmation • Detection tests – Two tests based on different principles: dRVVT and aPTT – Contact activation system. Recommended activator: Silicium-based; NOT Recommended: Kaolin or Ellagic acid – Set up a cut off value by 99th percentile. Avoid average ± 2 SD • Mixing study – Use a 1:1 proportion between the patient plasma and the normal plasma (pool or commercially certified plasma). NO pre-incubation of sample and activator. If using pool plasma, make sure that the platelet count is lower than 10,000/μL. Cut off value by 99th percentile or Rosner Index • Confirmation tests: Addition of phospholipids – In dRVVT: generics. In Staclot-LA: hexagonal structure

References

• D evreese K, Hoylaerts MF. Laboratory diagnosis of the antiphospholipid syndrome: a plethora of obstacles to overcome. Eur J Haematol. 2009;83:1-16.

• Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).

J Thromb Haemost. 2006;4:295-306.

• Pengo V, Tripodi A, Reber G, et al.; Subcommittee on Lupus Anticoagulant/ Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis.Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/ Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost.

2009;7:1737-40.

39

Other thrombotic conditions

Recommendations for the determination of Lupus Anticoagulant

Other thrombotic conditions

Diagnosis of Disseminated Intravascular Coagulation Indication Disseminated intravascular coagulation (DIC) is a clinical syndrome characterized by the intravascular activation of coagulation, of diverse etiology, involving fibrin generation in the microcirculation and organ failure.

Scoring system of the International Society of Thrombosis and Haemostasis (ISTH) 1) Clinical risk assessment Does the patient have a disease known to be associated with DIC? (see table on p. 42)

Continue the algorithm only if the answer is yes 2) Perform a global coagulation evaluation

Score global coagulation test results

• platelet count (> 100 × 109/L = 0; < 100 × 109/L = 1; < 50 × 109/L = 2) • elevated fibrin-related marker (e.g., fibrin degradation products or D-dimer) (no increase: 0; moderate increase: 2; strong increase: 3) • prolonged prothrombin time

(< 3 sec. = 0; > 3 but < 6 sec. = 1; > 6 sec. = 2)*

• fibrinogen level (> 1.0 g/L = 0; < 1.0 g/L = 1) Calculate score The scoring system can only be used if an underlying disorder, known to be associated with DIC, has been diagnosed. The cut-off values for the fibrin-related marker are dependent on the test used. A moderate increase was defined as above the upper limit of normal and a strong increase as above 5 times the upper limit of normal. A total score of ≥ 5 is compatible with DIC. 40

1. Risk assessment: Does the patient have an underlying disorder known to be associated with DIC (see table on page 42)? yes = 2, no = 0 score 2. Major criteria platelet > 100 × 109/L = 0 < 100 × 109/L = 1 rising = –1 stable = 0 falling = 1 count

+

PT < 3 sec = 0 > 3 sec = 1 falling = –1 stable = 0 rising = 1 prolongation*

+

soluble fibrin or FDP’s

normal

raised

+

falling = –1 stable = 0 rising = 1

3. Specific criteria antithrombin

protein C

normal = –1

normal = –1

low = 1 low = 1

4. Calculate score A score of 5 or higher is compatibe with non-overt DIC. The score should be repeated daily.

41

Other thrombotic conditions

Template for scoring system for non-overt DIC

Other thrombotic conditions

Table of diseases known to be associated with DIC • sepsis/severe infection (any micro-organism) • trauma (e.g., polytrauma, neurotrauma, fat embolism) • organ destruction (e.g., severe pancreatitis) • malignancy – solid tumors – myeloproliferative/lymphoproliferative malignancies • obstetrical calamities – amniotic fluid embolism – abruptio placentae • vascular abnormalities – Kasabach-Merrit syndrome – large vascular aneurysms • severe hepatic failure • severe toxic or immunologic reactions – snake bites – recreational drugs – transfusion reactions – transplant rejection

References

• Levi M. Disseminated intravascular coagulation. Crit Care Med. 2007;35:2191-5.

• Páramo JA. Coagulación intravascular diseminada. Med Clin (Barc). 2006;127:785-9.

• Taylor FB Jr, Toh CH, Hoots WK, et al.; Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost.

2001;86:1327-30.

• Toh CH, Downey C. Performance and prognostic importance of a new clinical and laboratory scoring system for identifying non-overt disseminated intravascular coagulation. Blood Coagul Fibrinolysis. 2005;16:69-74.

42

Indication TTP is an acute, rare life-threatening thrombotic microangiopathy that requires rapid diagnosis and treatment.

Diagnostic features of thrombotic microangiopathies

1. Thrombocytopenia 2. Hemolytic anemia 3. Renal insufficiency 4. Cerebral symptoms 5. Fever

ADAMTS13-related parameters in TMAs Congenital TTP

Acquired TTP Other TMAs

Antigen

Very low or absent Low or variable

Normal or moderately decreased

Activity

≤ 5%

≤ 5% or variable 30-100%

Inhibitor

No

Mostly yes

No

Interpretation TTP results from a deficiency of ADAMTS-13, a serine metalloproteinase required for the cleavage of von Willebrand factor.

Reference

• Shenkman B, Einav Y. Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: Diagnosis and classification. Autoimmun Rev. 2014;13:584-6.

43

Other thrombotic conditions

Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP)

Other thrombotic conditions

Acute Intestinal Ischemia / Thrombosis Management of suspected mesenteric ischemia Suspected mesenteric ischemia (arterial)

Peritonitis

No peritonitis

Laparotomy

CT/CT angiography

Remaining intestine too short

Remaining intestine sufficient

No resection

Resection

Central

Peripheral

Suspected NOMI

Interventional radiology

Surgery

Interventional radiology

Interventional radiology

Catheter embolectomy and lysis, possibly stent

Embolectomy

Lysis, vasodilation

Vasodilation (also postsurgery following recection)

44

Other thrombotic conditions

Management of patients with occlusion of the superior mesenteric artery CT-verified acute SMA occlusion

No peritonitis

Embolus

Peritonitis

Thrombosis

Exploratory laparotomy

Stenting No contraindication to thrombolysis

Aspiration ± pharmacological thrombolysis ± endovascular mechanical embolectomy

Contraindication to thrombolysis

Aspiration ± endovascular mechanical embolectomy

Open embolectomy + completion angiography

References

Embolus

Thrombosis

Open embolectomy + completion angiography + damage control surgery

Stenting + damage control surgery

• Acosta S, Björck M. Modern treatment of acute mesenteric ischaemia. Br J Surg.

2014;101:e100-8.

• Sise MJ. Acute mesenteric ischemia. Surg Clin North Am. 2014;94:165-81.

45

Bleeding

ISTH bleeding assessment tool for the evaluation of bleeding severity Indication Quantitative assessment of the severity of bleeding symptoms in patients referred for the evaluation of a suspected congenital bleeding disorder. Correlation of clinical symptoms with biological parameters for research purposes.

The Bleeding Assessment Tool (BAT) is formed by two components: 1. Bleeding questionnaire: a detailed bleeding questionnaire has been endorsed by the International Society of Haemostasis and Thrombosis as the result of expertsâ&#x20AC;&#x2122; consensus. The bleeding questionnaire allows to accurately record the worst-ever presentation for each bleeding symptom. The bleeding questionnaire is available at: http://www.isth.org/resource/resmgr/ssc/isth-ssc_bleeding_assessment.pdf A Web-based version of the questionnaire (ISTH-BATR) has been developed together by ISTH and the Rockefeller University, and it is accessible at: https://bh.rockefeller.edu/bat/ Users willing to keep their patientsâ&#x20AC;&#x2122; information stored in the ISTH-BATR are strongly encouraged to join the ISTH-BATR initiative, which is provided as a freely available service for the scientific community.

Please visit http://www.isth.org/members/group.aspx?id=100549 or https://bh.rockefeller.edu/ISTH-BATR/ for full information on how to join the initiative.

2. Bleeding score: The severity of symptoms collected with the bleeding questionnaire is scored and all obtained values are summed together. The final result is the Bleeding Score, an index of the overall severity of the bleeding phenotype.

46

47

Blood transfusion, replacement therapy or desmopressin Blood transfusion, replacement therapy or desmopressin

Resuturing or packing

Surgical haemostasis or antifibrinolytic

• > 5/year or • more than 10 minutes

Present

Present (not associated with ulcer, portal hypertension, hemorrhoids, angiodysplasia)

Present (macroscopic)

Reported in ≤ 25% Reported in > 25% of all procedures, of all procedures, no intervention no intervention

Reported in ≤ 25% Reported in > 25% of all procedures, of all procedures, no intervention no intervention

No / trivial

No / trivial

No / trivial

No / trivial

No / trivial or none done

No / trivial or none done

Bleeding from minor wounds

Oral cavity

Gastrointestinal bleeding

Hematuria

Tooth extraction

Surgery

Consultation only

Consultation only

Consultation only

Consultation only

Surgical haemostasis, iron therapy

Surgical haemostasis, antifibrinolytic

Surgical haemostasis or antifibrinolytic

Surgical haemostasis

Blood transfusion, replacement therapy or desmopressin

Blood transfusion, replacement therapy or desmopressin

Blood transfusion, replacement therapy or desmopressin

Blood transfusion, replacement therapy, or desmopressin

Spontaneous hematoma requiring blood transfusion

Extensive

Consultation only

For bruises 5 or more (> 1 cm) in exposed areas

4

No / trivial

3 Packing or cauterization Blood transfusion or replacement therapy or antifibrinolytic (use of hemostatic blood components and rFVIIa) or desmopressin

Cutaneous

2 Consultation only

Epistaxis

1

• > 5/year or • more than 10 minutes

0

Score

No / trivial

(up to the time of diagnosis)

Symptoms

Bleeding Assessment Tool

Bleeding

48 Surgical haemostasis, antifibrinolytics

Post trauma, no therapy

Post trauma, no therapy

Never

Never

Never

No / trivial

Muscle hematomas

Hemarthrosis

CNS bleeding

Other bleedings

Present

Subdural, any intervention

• Iron therapy or Consultation only or •A ntifibrinolytics •U se of syntocin or • L ochia > 6 weeks

No / trivial or no deliveries

Post-partum hemorrhage

3

Menorrhagia

2

Consultation only

Spontaneous, no therapy

Spontaneous, no therapy

Spontaneous or traumatic, requiring desmopressin or replacement therapy

Spontaneous or traumatic, requiring desmopressin or replacement therapy

Requiring blood transfusion, replacement therapy, desmopressin or requiring examination under anaesthesia and/or the use of uterin balloon/ package to tamponade the uterus

• Time off work/school > • Requiring combined treatment with 2/year or antifibrinolytics and •R equiring hormonal therapy or antifibrinolytics or • Present since hormonal or iron menarche and > 12 therapy months

1

Consultation only or • Changing pads more frequently than every 2 hours or •C lot and flooding or •P BAC score > 100

0

Score

No / trivial

(up to the time of diagnosis)

Symptoms

Bleeding Assessment Tool (cont.)

4

Blood transfusion or replacement therapy or desmopressin

Intracerebral, any intervention

Spontaneous or traumatic, requiring surgical intervention or blood transfusion

Spontaneous or traumatic, requiring surgical intervention or blood transfusion

(e.g., hysterectomy, internal iliac artery legation, uterine artery embolization, uterine brace sutures)

Any procedure requiring critical care or surgical intervention

• Acute menorrhagia requiring hospital admission and emergency treatment or requiring blood transfusion, replacement therapy, desmopressin, or • Requiring dilatation & curretage or endometrial ablation or hysterectomy

Bleeding

References

• R odeghiero F, Castaman G, Tosetto A, et al. The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study. J Thromb Haemost. 2005;3:2619-26.

• Rodeghiero F, Tosetto A, Abshire T, et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost. 2010;8:2063-5.

• Tosetto A, Castaman G, Plug I, et al. Prospective evaluation of the clinical utility of quantitative bleeding severity assessment in patients referred for hemostatic evaluation. J Thromb Haemost. 2011;9:1143-8.

49

Bleeding

Interpretation A bleeding score > 3 is considered suggestive for the presence of a bleeding disorder, warranting a detailed laboratory investigation, whereas a bleeding score ≤ 3 has negative predictive value of 99.2% in excluding a congenital bleeding disorder. In a multicentre study using a very similar quantitation of bleeding symptoms, a bleeding score > 3 in males or > 5 in females showed a sensitivity and specificity for the diagnosis of von Willebrand’s disease of 64.2% and 99.1%, respectively.

Bleeding

Pediatric bleeding assessment tool for the evaluation of bleeding severity in children Indication Quantitative assessment of the severity of bleeding symptoms in young patients referred for the evaluation of a suspected congenital bleeding disorder.

The Pediatric Bleeding Assessment is formed by two components: the Pediatric Bleeding Questionnaire (PBQ) and the Bleeding Score, essentially derived from the one used by the European Study on type 1 VWD. The Pediatric Bleeding Assessment tool was originally developed to evaluate address pediatric-specific bleeding symptoms, and all its items in the questionnaire are now represented also in the ISTH Bleeding Assessment Tool. The PBQ is however presented since many studies in children used this score.

1. Pediatric Bleeding Questionnaire (PBQ): The bleeding questionnaire allows to accurately record the worst-ever presentation for each bleeding symptom. The bleeding questionnaire is publicly available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2009.03499.x/full There is no electronic version of the questionnaire available so far.

2. Bleeding Score: The severity of symptoms collected with the PBBQ is scored according to the following table and all obtained values are summed together. The final result is the Pediatric Bleeding Score, an index of the overall severity of the bleeding phenotype in children.

Interpretation (see tables on p. 51-52) A Bleeding Score ≥ 2 is considered suggestive for the presence of a bleeding disorder. The sensitivity, specificity, positive predictive value and negative predictive value of the PBQ are 83%, 79%, 0.14, and 0.99 respectively for the diagnosis of von Willebrand’s disease in a secondary care setting. The PBQ is consistently elevated in children with platelet function disorders.

References

• B iss TT, Blanchette VS, Clark DS, et al. Quantitation of bleeding symptoms in children with von Willebrand disease: use of a standardized pediatric bleeding questionnaire.

J Thromb Haemost. 2010;8:950-6.

• Biss TT, Blanchette VS, Clark DS, et al. Use of a quantitative pediatric bleeding questionnaire to assess mucocutaneous bleeding symptoms in children with a platelet function disorder. J Thromb Haemost 2010;8:1416-9.

• Bowman M, Riddel J, Rand ML, et al. Evaluation of the diagnostic utility for von Willebrand disease of a pediatric bleeding questionnaire. J Thromb Haemost. 2009;7:1418-21.

50

51

No

Oral cavity

No bleeding in at least 2 extractions

No bleeding in at least 2 surgeries

Tooth extraction

Surgery

None done or no bleeding in 1 extraction None done or no bleeding in 1 surgery

No

(≤ 5 per year)

(≤ 1 cm)

Reported, no consultation

Reported, no consultation

Identified cause

No or trivial

Minour wounds

Gastrointestinal tract

No or trivial

Cutaneous

(≤ 5 per year)

1

> 5 per year OR > 10 minutes duration > 1 cm AND no trauma > 5 per year OR > 5 minutes duration Reported at least once

0

No or trivial

–1

Epistaxis

Symptoms

Consultation only

Consultation only

Consultation or spontaneuous

Consultation only Consultation only or Steristreaps Consultation only

Consultation only

2

Score

Pediatric Bleeding score 3

Surgical haemostasis or antifibrinolytics

Surgical haemostasis, antifibrinolytics, blood transfusion, replacemente therapy or demopressin Resuturing, repacking or antifibrinolytics

Surgical haemostasis or antifibrinolytics

Surgical haemostasis or antifibrinolytics

Packing, cauterization or antifibrinolytics

4

Bleeding

Blood transfusion, replacement therapy or desmopressin

Blood transfusion, replacement therapy or desmopressin

Blood transfusion, replacement therapy or desmopressin Blood transfusion, replacement therapy or desmopressin

Blood transfusion, replacement therapy or desmopressin

52

3

Surgical haemostasis, antifibrinolytics or iron therapy

Never

No

Central nervious system

Other

Reported

Subdural, any intervention

Post-trauma, no therapy

Consultation only

Spontaneus, no therapy

Spontaneus or traumatic, requiring replacement therapy or desmopressin

Spontaneus or traumatic, requiring replacement therapy or desmopressin

Never

Spontaneus, no therapy

Blood transfusion, replacement therapy or desmopressin

D&C or iron therapy

Hemarthrosis

Muscle hematoma

Post-partum

D&C or iron therapy or antifibronolytics

Antifibronolytics or contraceptive pill use

2

Score

Post-trauma, no therapy

Reported or consultation only

1

Never

No

0

Reported or consultation only

No bleeding in at least 2 deliveries

–1

No deliveries or no bleeding in 1 delivery

Menorrhagia

Symptoms

Pediatric Bleeding score (cont.)

4

Blood transfusion, replacement therapy or desmopressin

Spontaneus or traumatic, requiring surgical intervention or blood transfusion Spontaneus or traumatic, requiring surgical intervention or blood transfusion Intracerebral, any intervention

Blood transfusion, replacement therapy, desmopressin or hysterectomy

Bleeding

Indication Quantitative assessment of the severity of bleeding symptoms in patients with immune thrombocytopenia (ITP), observed at diagnosis or disease relapse.

Proposed as a clinical guidance to drive need for therapy.

The tool was developed by the International Working Group on ITP to standardize definitions of bleeding, and to grade symptom-specific and domain-specific bleedings. Bleeding signs/symptoms are grouped according to three major domains: skin (S), visible mucosae (M) and organs (Og).

Skin (epidermis, dermis and subcutaneous tissues) includes petechiae, ecchymosis (purpuric macula, bruise or contusion), subcutaneous hematomas, bleeding from minor wounds. Visible mucosae include epistaxis, oral cavity (gum bleeding, hemorrhagic bullae/blisters, bleeding from bites to lips & tongue or after deciduous teeth loss/extraction), subconjunctival hemorrhage.

Organs include GI bleeding (hematemesis, melena, hematochezia, rectorrhagia), lung bleeding (hemoptysis), hematuria, menorrhagia, muscle hematoma, hemarthrosis, ocular bleeding, intracranial (intracerebral, intraventricular, subarachnoidal, subdural, extradural). Gradation of bleeding severity (SMOG system): each bleeding manifestation should be assessed at the time of examination. Its severity is graded from 0 to 4. Appreciation of bleeding based on history only, without supporting medical documentation, will be given a grade 1 designation. Within each domain, the same grading is assigned to the symptoms judged to have similar clinical relevance. For each symptom, the worst ever episode during the observation period is graded and then the worst episode within the domain is recorded. For example if the highest grade is 2 for skin, 3 for mucosae and 2 for organs, SMOG is S2M3O2. The index produced by summing the worst ever grade in the 3 domains represents the final score for that particular patient. In the example shown, the final score is 7.

The data collection forms and grading tables are publicly available at: http://itpbat.fondazioneematologia.it/

Reference

â&#x20AC;˘â&#x20AC;&#x192; Rodeghiero F, Michel M, Gernsheimer T, et al. Standardization of bleeding assessment in immune thrombocytopenia: report from the International Working Group. Blood. 2013;121:2596-606.

53

Bleeding

Bleeding assessment tool for the evaluation of bleeding severity in immune thrombocytopenia: the SMOG system

54

SKIN

Bleeding from minor wounds

Subcutaneous hematomas

Ecchymoses

(does not include steroid-induced or senile purpura)

Petechiae

Type of bleeding

0

1 • Less than or equal to 10 in a patient’s palm-sized area in the most affected body area • Any number if reported by the patient

No

• Lasting < 5 min • Any episode if reported by the patient

None or up to 2 • 3 or more in the same body in the same body area, but all smaller than a area, but smaller patient’s palm-sized area, if: than a patient’s – spontaneous or palm-sized area, if: – disproportionate to trauma/ • spontaneous or constriction • disproportionate • At least 2 in two different to trauma/ body areas, smaller than a constriction patient’s palm-sized area, if: – spontaneous or – disproportionate to trauma/ constriction • Any number and size if reported by the patient No • 1 smaller than a patient’s palm-sized area • Any number and size if reported by the patient

No

Lasting > 5 min or interfering with daily activities

• 2 smaller than a patient’s palm-sized area, spontaneous • 2 smaller than a patient’s palm-sized area, disproportionate to trauma

• More than 2 smaller or at least 1 larger than a patient’s palm-sized area, spontaneous • More than 2 smaller or at least 1 larger than a patient’s palm-sized area, disproportionate to trauma • Requiring protracted medical observation at the time of this visit • Medical report describing patient’s evaluation by a physician

From 1 to 5 larger than a More than 5 larger than a patient’s palm-sized area, if: patient’s palm-sized area, if: • spontaneous or • spontaneous or • disproportionate to trauma/ • disproportionate constriction with or without to trauma/constriction smaller ones

(in the most affected body areas)

3

More than 10 in a patient’s More than 50, if scattered both palm-sized area or more than above and below the belt 5 in at least 2 patient’s palmsized areas located in at least 2 different body areas, one above and one below the belt

2

Grades based on the worst incident episode since last visit

The SMOG system 4

Bleeding

55

(not due to conjunctival disease)

Subconjunctival hemorrhage

(bleeding from bites to lips & tongue or after deciduous teeth loss)

Oral cavity

(hemorrhagic bullae or blisters)

Oral cavity

(gum bleeding)

Oral cavity

Epistaxis

MUCOSAL

Type of bleeding

• Petechiae/hemorrhage partially involving one eye • Any episode if reported by the patient

No

No

• Less than 3 • Any number if reported by the patient • Lasting < 5 min • Any episode if reported by the patient

• Lasting < 5 min • Any episode if reported by the patient

No

No

• Lasting < 5 min • Any episode if reported by the patient

1

Petechiae/hemorrhage partially involving both eyes, or diffuse hemorrhage in one eye

Lasting > 5 min or interfering with daily activities

From 3 to 10 but no difficulty with mastication

Lasting > 5 min or interfering with daily activities

Lasting > 5 min or interfering with daily activities

2

• Interventions to ensure haemostasis or in-hospital evaluation at the time of this visit • Medical report describing interventions to ensure haemostasis or in-hospital evaluation Diffuse hemorrhage in both eyes

• Packing or cauterization or in-hospital evaluation at the time of this visit • Medical report describing packing or cauterization or in-hospital evaluation • Requiring protracted medical observation at the time of this visit • Medical report describing patient’s evaluation by a physician More than 10 or more than 5 if difficulty with mastication

3

Grades based on the worst incident episode since last visit

No

0

The SMOG system (cont.)

4

Bleeding

RBC transfusion or Hb drop > 2 g/dL

56

ORGAN

• Doubling nr. of pads or tampons in last cycle compared to pre-ITP or to a phase of disease with normal platelet count • Score > 100 using PBAC in the last cycle, if normal score in pre-ITP cycles or in a phase of disease with normal platelet count

No

Menorrhagia

(compared to pre-ITP or to a phase of disease with normal platelet count)

• Any episode if reported by the patient • Microscopic (lab analysis)

Any episode if reported by the patient

Any episode if reported by the patient

1

No

No

0

Acute menorrhagia requiring hospital admission or endometrial ablation

• Changing pads more frequently than every 2 hrs. or clot and flooding • Requiring combined treatment with antifibrinolytics and hormonal therapy or gynecological investigation

(either at this visit or described in a medical report)

• Macroscopic, and requiring cystoscopy or other therapeutic procedures or in-hospital evaluation at the time of this visit • An equivalent episode if described in a medical report

(either at this visit or described in a medical report)

RBC transfusion or Hb drop > 2 g/dL

4

RBC transfusion or Hb drop > 2 g/dL

RBC transfusion or Hb drop > 2 g/dL

RBC transfusion or • Requiring bronchoscopy or other therapeutic procedures or Hb drop > 2 g/dL in-hospital evaluation at the time of this visit • An equivalent episode if described in a medical report

• Requiring endoscopy or other therapeutic procedures or inhospital evaluation at the time of this visit • Medical report prescribing endoscopy or other therapeutic procedures or in-hospital evaluation

3

• Macroscopic • Described in a medical report

• Present at this visit • Described in a medical report

• Present at this visit • Described in a medical report

2

Grades based on the worst incident episode since last visit

Hematuria

• Hemoptysis • Tracheobronchial bleeding

Lung bleeding

• Hematemesis, • Melena, • Hematochezia, • Rectorrhagia

No Gastrointestinal bleeding not explained by visible mucosal bleeding or lesion:

(and internal mucosae)

Type of bleeding

The SMOG system (cont.)

Bleeding

57

ORGAN

(only if diagnosed by a physician with an objective method)

Ocular bleeding

(only if diagnosed by a physician with an objective method)

Hemarthrosis

(only if diagnosed by a physician with an objective method)

Intramuscular hematomas

(and internal mucosae)

Type of bleeding

• Post trauma, diagnosed at this visit, function conserved or minimally impaired, if judged disproportionate to trauma • An equivalent episode if described in a medical report

No

No

• Post trauma, diagnosed at this visit, if judged disproportionate to trauma • An equivalent episode if described in a medical report

1

No

0

3

4

• Any post trauma vitreous or retinal hemorrhage involving one or both eyes with or without impaired/ blurred vision present at this visit if judged disproportionate to trauma • An equivalent episode if described in a medical report

• Spontaneous, diagnosed at this visit, function conserved or minimally impaired • An equivalent episode if described in a medical report

diagnosed at this visit and requiring surgical intervention • An equivalent episode if described in a medical report

disproportionate to trauma)

• Spontaneous or post trauma (if judged

Bleeding

• Spontaneous vitreous or • Spontaneous vitreous retinal hemorrhage or retinal hemorrhage involving with loss of vision in one one or both eyes with impaired/ or both eyes present blurred vision present at this visit at this visit • An equivalent episode if • An equivalent episode if described in a medical report described in a medical report

and requiring immobilization or joint aspiration • An equivalent episode if described in a medical report

(if judged disproportionate to trauma),diagnosed at this visit

• Spontaneous or post trauma

• Spontaneous, diagnosed at • Spontaneous or post trauma RBC transfusion or this visit (if judged disproportionate to trauma) Hb drop > 2 g/dL diagnosed at this visit and • An equivalent episode requiring hospital admission or if described in a medical surgical intervention report • An equivalent episode if described in a medical report

2

Grades based on the worst incident episode since last visit

The SMOG system (cont.)

58

ORGAN

hemoperitoneum, hemopericardium, hemothorax retroperitoneal bleeding, hepatic and splenic peliosis with organ rupture retroorbital bleeding, metrorrhagia, etc. (only if diagnosed with an objective method at the visit or described in a medical report provided by the patient)

Other internal bleeding:

intracerebral, intraventricular, subarachnoidal, subdural, extradural (only if diagnosed with an objective method at the visit or described in a medical report provided by the patient)

Intracranial bleeding:

(and internal mucosae)

Type of bleeding

No

No

0

1 • Any post trauma event requiring hospitalization

2

4

Any event requiring hospitalization Any event requiring < 48 hrs. hospitalization > 48 hrs. or RBC transfusion or Hb drop > 2 g/dL

Any spontaneous event requiring Any spontaneous event requiring hospitalization hospitalization in presence of an underlying intracranial lesion without an underlying intracranial lesion

3

Grades based on the worst incident episode since last visit

The SMOG system (cont.)

Bleeding

Indication Heparin-Induced Thrombocytopenia (HIT) is a serious complication of anticoagulant therapy with unfractionated heparin and, less frequently, low molecular weight heparin, with the formation of abnormal antibodies against the heparin/platelet factor-4 (PF4) complex. The syndrome is characterized by the occurrence of a drop in platelet count associated with venous or arterial thrombotic complications initiated after 5-10 days of treatment with heparin. In patients that were earlier exposed to heparin the complication may occur in a shorter time after initiation of heparin treatment.

HIT clinical probability algorithm 4T score

Score

Thrombocytopenia

• Decrease > 50% and platelets nadir ≥ 20 × 109/L • Decrease 30-50% or platelets nadir = 10-19 × 109/L • Decrease < 30% or platelets nadir < 10 × 109/L

2 1 0

Timing of platelet count fall • Onset 5-10 days

(or 1 day after previous exposition to heparin in the last month)

• Unclear decrease at 5-10 days; onset after day 10 or day 1 after previous exposition to heparin in day 30-100 • Decrease < 4 days with no recent exposition

2 1 0

Thrombosis or other sequelae

• New thrombosis (confirmed); cutaneous necrosis; acute systemic reaction after heparin bolus • Progressive or recurrent thrombosis; non-necrotic cutaneous lesions; suspicion of thrombosis • None

Thrombocytopenia due to other causes

2 1 0 2 1 0

• Apparently none • Possible • Yes

59

Anticoagulant therapy

Diagnostic and therapeutic algorithm of Heparin-Induced Thrombocytopenia (HIT syndrome)

Anticoagulant therapy

Interpretation According to the 4T rule, 3 levels of clinical probability can be defined: • High = 6-8 points • Intermediate = 4-5 points • Low = ≤ 3 points Once the pre-test probabilities are assumed, the HIT diagnostic / therapeutic algorithm can proceed.

Thrombocytopenia in a patient receiving heparin or LMWH Apply clinical scoring system

High clinical suspicion (4T’s = 6-8) Discontinue heparin: start alternative therapy

Intermediate (4T’s = 4-5) Discontinue heparin: start alternative therapy Immunoassay

Immunoassay

Positive HIT confirmed

Negative HIT HIT unlikely

(post-test probability of HIT > 95%)

(post-test probability of HIT~ 3-16%)

Consider functional assay

Low clinical suspicion for HIT(4T’s ≤ 3) Continue heparin therapy

Positive HIT possible

Negative HIT HIT unlikely

(post-test probability of HIT ~ 60%)

(post-test probability of HIT< 0,5%)

Presence of high IgG OD/titer and/or platelet activating antibodies increase HIT likelihood

Presence of low IgG OD/titer or lack platelet activating antibodies decrease HIT likelihood

(post-test probability of HIT ~ 65%)

(post-test probability of HIT ~ 40%)

References

• Crowther MA, Cook DJ, Albert M, et al.; Canadian Critical Care Trials Group. The 4Ts scoring system for heparin-induced thrombocytopenia in medical-surgical intensive care unit patients. J Crit Care. 2010;25:287-93.

• Greinacher A. Heparin-induced thrombocytopenia. J Thromb Haemost.

2009;7(Suppl 1):9-12.

• Warkentin TE. How I diagnose and manage HIT. Hematology Am Soc Hematol Educ Program. 2011:143-9.

• Warkentin TE, Greinacher A, Koster A, et al.; American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008;133(Suppl 6):340S-380S.

60

Indication For patients on vitamin K antagonists requiring a surgical or invasive procedure, the question of whether or not to bridge and how to bridge is commonly encountered in clinical practice.

Risk assessment of thrombosis Arterial thrombosis High

• Atrial fibrillation with CHADS2 score: 4-6 • Atrial fibrillation and rheumatic heart valve disease • Mechanical mitral valve prosthesis • Recently inserted heart valve prosthesis • Heart valve prosthesis plus additional thrombotic risk • Old type mechanical heart valve (caged ball, tilting disk) • Intracardial thrombosis

Intermediate

• Atrial fibrillation with CHADS2 score: 2-3 • Mechanical aortic heart valve without any other risk • Recurrent TIA • Ischemic brain infarct without cardiac embolism

Low

• Atrial fibrillation with CHADS2 score: 0-1 • Cerebrovascular disease without recurrent TIA/infarction

Venous thromboembolism High

• Recent (< 3 months) venous thromboembolism • Thromboembolism with known thrombophilia • Recurrent idiopathic venous thromboembolism

Intermediate

Venous thromboembolism 3-6 months ago

Low

Venous thromboembolism > 6 months ago

61

Anticoagulant therapy

Bridging strategies in patients on anticoagulants who need to undergo invasive procedures

Anticoagulant therapy

Management strategy based on risk assessment • Stop treatment with VKA

Risk of thromboembolism

High

(warfarin or coumadin 3-4 days, fenprocoumon 5-7 days)

• Start therapeutic UFH or LMWH • Stop UFH 3 hours preoperatively or LMWH 24 hours preoperatively • Restart heparin 12-24 hours postoperatively

Low

• Consult with (if no bleeding) surgeon or operator • Restart VKA 1-2 days postoperatively • Continue VKA (if no bleeding) • Monitor INR • Stop heparin when INR is in therapeutic range • Target INR 1.5-2.0 • Stop treatment with VKA (warfarin or coumadin 3-4 days, fenprocoumon 5-7 days)

• Restart VKA 12-24 hours postoperatively (if no bleeding)

• Usual prophylactic LMWH (prevention of venous thromboembolism)

Low

High Risk of peri-operative bleeding

VKA: Vitamin K antagonists; UFH: Unfractionated Heparin; LMWH: Low Molecular Weight Heparin; INR: International Normalized Ratio

Interpretation Perioperative interruption and bridging strategy based on risk of thromboembolism and risk of perioperative bleeding. Patients with an intermediate risk of thromboembolism are treated according to the low risk stratum, although individual exceptions may be made based on patient characteristics and preferences of patients and doctors.

References:

• Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin as bridginganticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med. 2004;164:1319-26.

• Levi M, Eerenberg E, Kamphuisen PW. Periprocedural reversal and bridging of anticoagulant treatment. Neth J Med. 2011;69:268-73.

62

Diagnostica Stago - 05/2014 - ref.: 28111

Practical manual of scores and algorithms in hemostasis and thrombosis

This booklet was produced with the help of www.stago.com