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José A. Páramo (coordinator)
Henri Bounameaux
Marcel Levi
Gregory YH Lip
Pascual Marco
Joan Carles Reverter
Alberto Tosetto
Practical manual
Scores and Algorithms in Haemostasis and Thrombosis
© Text: the authors© Edition: Grupo Acción Médica. Madrid, 2014Email: [email protected]
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
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Scientific board
Henri BounameauxDivision of Angiology and Haemostasis University Hospital of Geneva, Switzerland
Marcel LeviAcademic 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 TosettoHemophilia and Thrombosis CenterHematology DepartmentSan Bortolo Hospital, Vicenza, Italy
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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
Summary
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
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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
Prologue
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Clinical probability model for Deep Vein Thrombosis
IndicationClinically 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) ≤ 1Intermediate/high probability (likely) ≥ 2
* The most symptomatic extremity is used in patients with symptoms in both legs.
InterpretationUseful 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• Wells 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.
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Clinical probability models for Pulmonary Embolism
IndicationClinically suspected Pulmonary Embolism (PE).
Wells’ score
Feature Score
Previous DVT or PE 1.5Heart rate > 100 bpm 1.5Surgery or bedridden < 4 weeks 1.5Hemoptysis 1Active malignancy 1Clinical symptoms of DVT 3Alternative diagnosis less likely than PE 3
Clinical probability
PE unlikely ≤ 4PE likely > 4
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InterpretationThese 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• Ceriani 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.
Geneva scores
Feature Points(revised dichotomized score)
Points(simplified score)
Previous DVT or PE 3 1Heart rate:
75-94 bpm≥ 95 bpm
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Surgery or fracture < 1 month 2 1Hemoptysis 2 1Active malignancy 2 1Unilateral lower limb pain 3 1Pain on lower limb deep venous palpation or unilateral oedema 4 1
Age > 65 1 1
Clinical probabilityPE unlikely ≤ 5 ≤ 2PE likely > 5 > 2
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Diagnostic algorithm of Deep Vein Thrombosis and Pulmonary Embolism
IndicationClinically suspected Deep Vein thrombosis (DVT) or non-massive Pulmonary Embolism (PE), to decide therapeutic approach.
Clinical probability
No anticoagulant therapy Anticoagulant therapy
Unlikely
Negative Positive
Below cut-off Above cut-off
CUS or MDCTA
D-dimer
Likely
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InterpretationClinical 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.
References• Adam 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.
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Prognostic scores in Pulmonary Embolism
IndicationPredictive scoring system for patients with Pulmonary Embolism (PE) using PESI (the Pulmonary Embolism Severity Index) and Geneva score calculators.
InterpretationThe 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
PESI
FeaturesPoints
Original version Simplified version
Age Years > 80 =1Male +10History of cancer +30 1History of heart failure +10 } 1aHistory of chronic lung disease +10Pulse ≥ 110 bpm +20 1Systolic BP < 100 mmHg +30 1Respiratory rate ≥ 30/min +20Temperature < 36 ºC +20Altered mental status +60Arterial oxygen saturation < 90% +20 1
Risk evaluation
Class I (very low) ≤ 65 points
Low: 0High: ≥ 1
Class II (low) 66-85 pointsClass III (intermediate) 86-105 pointsClass IV (high) 106-125 points
Class V (very high) > 125 pointsa Variables combined into a single category of chronic cardiopulmonary disease
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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.
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
InterpretationPredictive 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.
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References• Aujesky 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.
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Prediction of recurrent Deep Vein Thrombosis or Pulmonary Embolism
IndicationAssessment of risk of recurrence after a first DVT or PE. Presentation of two methods: the Vienna nomogram and the DASH score.
Vienna Nomogram
InterpretationThe 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
0 10 20 30 40 50 60 70 80 90 100
Female Female
Male Male
Distal DVT PE Distal DVT PE
Proximal DVTProximal DVT
100 150 200 250 400 500 750 1.000 1.500 2.000 100 150 200 250 400 500 750 1.000 1.500 2.000
0 50 100 150 200 250 300 350
0.02 0.04 0.06 0.08 0.1 0.12 0.15 0.02 0.04 0.06 0.08 0.1 0.12 0.15
0.1 0.2 0.3 0.4 0.5 0.1 0.2 0.3 0.4 0.5
Gender
Location
D-dimer(ng/mL)
1 year cumulativerecurrence rate
5 year cumulativerecurrence rate
Points
Total points
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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.
InterpretationThis 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• Eichinger 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.
DASH score
Feature ScoreAbnormal D-dimer (measured one month after stopping anticoagulation)
+2
Age ≤ 50 +1Male +1Hormonal therapy at onset of VTE (among women) –2
ProbabilityLow ≤ 1High > 1
DASH: D-dimer, Age, Sex, Hormones
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Outpatient versus inpatient care in Venous Thromboembolism
IndicationTo identify patients with VTE that can safely be treated as outpatients.
Hestia criteria
Is the patient hemodynamically unstable?* yesno
Is thrombolysis or embolectomy necessary? yesno
Active bleeding or high risk for bleeding?** yesno
More than 24 hours of oxygen supply to maintain oxygen saturation > 90%? yesno
Is pulmonary embolism diagnosed during anticoagulant treatment? yesno
Severe pain needing intravenous pain medication for more than 24 hours? yesno
Medical or social reason for treatment in the hospital for more than 24 hours (infection, malignancy, no support system, etc.)?
yesno
Does the patient have a creatinine clearance of less than 30 mL/min?*** yesno
Does the patient have severe liver impairment?**** yesno
Is the patient pregnant? yesno
Does the patient have a documented history of heparin-induced thrombocytopenia (HIT)?
yesno
* 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
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InterpretationAnswering 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• Zondag 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.
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Assessment of Post-Thrombotic Syndrome
IndicationScore of post-thrombotic syndrome (PTS) severity
InterpretationThe 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• Kahn 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.
Villalta score
None Light Moderate Severe
Symptoms• Pain• Cramps• Heaviness• Paresthesia• Itching
00000
11111
22222
33333
Signs• Pretibial oedema• Skin induration• Hyperpigmentation• Redness• Venous ectasia• Calf pain
on pressure
000000
111111
222222
333333
Venous ulcer Absence Presence
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Diagnostic algorithm in suspected Deep Vein Thrombosis during pregnancy
IndicationClinically suspected DVT during pregnancy.
InterpretationClinical 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.
Clinically suspected DVT
Clinically suspected iliac DVT*
Serial compression ultrasound
Duplex Doppler
DVT no confirmed DVT confirmed
Start treatment
No
Normal Abnormal Flow absent Flow present
Yes
Start treatment
DVT confirmed Consider magnetic resonance image
DVT excluded
Serial compression ultrasound after 1 week
* 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.
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Diagnostic algorithm in suspected Pulmonary Embolism during pregnancy
IndicationClinically suspected PE during pregnancy.
Symptomatic DVT
No Yes
Normal
PEexcluded
PEconfirmed
Computedtomography
Computed tomography
Highprobability
Non-diagnostic
PEconfirmed
Non-diagnostic
Clinically suspected PE
Serial compression ultrasound
DVT no confirmed
DVT confirmed
Ventilation/perfusion scan
Ventilation/perfusion scan
Start treatment
Start treatment
Start treatment
PEexcluded
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InterpretationClinical 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• Chan 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.
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Prediction of stroke risk in patients with Atrial Fibrillation
IndicationAtrial 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 CHA
2DS
2-VASc stroke risk score calculators have been
used to aid risk stratifying of patients, and to help decision making for thromboprophylaxis. The CHA
2DS
2-VASc score is now recommended by
many international guidelines, including those from the ESC, AHA/ACC/HRS, APHRS, SIGN and NICE guidelines.
InterpretationLow risk = 0Moderate risk = 1High risk ≥ 2
The CHADS2 score has been replaced by the CHA
2DS
2-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 Antithrombotic therapy recommendation> 1 OAC (vitamin K antagonist or dabigatran)1 OAC or ASA 75-325 mg/day
0 ASA
OAC: oral anticoagulant; NOAC: Non-VKA Oral AntiCoagulants (previously called New or novel OACs); ASA: Acetylsalicylic Acid
CHADS2 risk score
Risk factor Score
Congestive heart failure 1
Hypertension 1
Age ≥ 75 years 1
Diabetes mellitus 1
Prior Stroke or TIA or Thromboembolism 2
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InterpretationLow 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 ‘CHA
2DS
2-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 CHA
2DS
2-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.
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 (peripheral artery disease, myocardial infarction, aortic plaque)
1
Age between 65 and 74 years 1
Sex category (i.e. female gender) 1
Maximum score 9
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References• Camm 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.
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Bleeding risk in anticoagulated patients with Atrial Fibrillation
IndicationMajor 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.
InterpretationA high HAS-BLED score (≥ 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.
HAS-BLED score
HAS-BLED Score
Hypertension i.e. uncontrolled Blood Pressure 1
Abnormal renal/liver function 1 or 2
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
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References• Friberg 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.
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Predicting the likelihood of achieving good anticoagulation control in a newly diagnosed non-anticoagulated patient with Atrial Fibrillation
IndicationA 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-TT
2R
2 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* 2 of the following: hypertension, diabetes melitus, coronary artery disease / myocardial infraction, PAD, coronary heart failure, previous stroke, pulmonary disease, hepatic or renal disease.
Definition of the SAMe-TT2R2 score
Acronym Definitions Score
S Sex (female) 1
A Age (less than 60 years) 1
Me Medical history* 1
TTreatment (interacting Rx e.g., amiodarone for rhythm control)
1
T Tobacco use (within 2 years) 2
R Race (non-Caucasian) 2
Maximum points 8
31
Atr
ial F
ibril
latio
n
InterpretationThis score identifies those Atrial Fibrillation patients likely to do well on warfarin (SAMe-TT
2R
2 score 0-1) or those more likely to have poor anticoagulation
control (SAMe-TT2R
2 score > 2).
If the SAMe-TT2R
2 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• Apostolakis 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 SAME-TT2R2 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].
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Risk of Venous Thromboembolism in Cancer Patients
IndicationAssessing 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.
InterpretationThe 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.
Khorana model: for outpatients with cancer on chemotherapy
Feature PointsSite of cancer (origin)
• High risk (pancreas, stomach)• Low risk (lung, lymphoma, gynaecologic, bladder, testicular)
21
Platelet count ≥ 350 × 109/L 1
Haemoglobin level < 100 g/L or use of red cell growth factor 1
Leukocyte count > 11 × 109/L 1
BMI ≥ 35 kg/m2 1
Probability• Low risk 0
• Intermediate risk 1-2
• High risk > 3
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InterpretationThe 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.
Vienna score (Ay Model): DVT or PE risk scoring
Feature Points Khorana Model scoring (0 to 6)
D-dimer ≥ 1.44 μg/mL 1
P-Selectin ≥ 53.1 mg/mL 1
ProbabilityLow risk 0
Intermediate risk 1-2
High risk ≥ 3
Ottawa scoreRecurrence risk in patients with thrombosis associated with neoplasia
Feature Points female 1
Lung Cancer 1
Breast Cancer –1
Status (TNM*) –2
Previous DVT or PE 1
ProbabilityLow risk ≤ 0
High risk ≥ 1* TNM: Tumor-Node-Metastasis level
InterpretationThe DVT or PE recurrence risk was ≤ 4.5% for low-risk patients and ≥ 19% for high-risk patients.
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DVT risk scoring in patients with myeloma treated with thalidomide or lenalidomide
DVT risk factors
Category Prophylaxis
Individual and myeloma-related factors
• BMI ≥ 30 kg/m2
• Previous DVT or PTE• Central venous catheter or pacemaker• Concomitant disease (cardiac, chronic
renal, diabetes, acute infection, immobilization)
• Medications (EPO)• Clotting disorders• Hyperviscosity
≤ 1 risk factor:• Aspirin
(80-300 mg/d)
≥ 2 factors:• LMWH (equivalent
to enoxaparin 40 mg/d) or
• VKA (INR = 2-3)
Myeloma therapy
High dose of dexamethasone, doxorubicin, polychemotherapy
HBPM (e.g., enoxaparin 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
InterpretationThe 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• Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer
patients. Blood. 2010;116:5377-82.• Farge 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.
• Palumbo 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.
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Risk assessment models in hospitalized Medical Patients
IndicationRisk Assessment Model (RAM) for DVT or PE in patients hospitalized for medical conditions.
InterpretationAmong 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.
Padua prediction score
Feature Points Active cancer* 3
Previous DVT or PE (excluding superficial vein thrombosis) 3
Reduced mobility** 3
Already-known thrombophilic condition*** 3
Recent (≤ 1 month) trauma and/or surgery 2
Age ≥ 70 years 1
Heart and/or respiratory failure 1
Acute myocardial infarction or ischemic stroke 1
Acute infection and/or rheumatologic disorder 1
Obesity (BMI ≥ 30 kg/m2) 1
Ongoing hormonal treatment**** 1
ProbabilityHigh > 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
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References• Barbar 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.
InterpretationIndication for thromboprophylaxis if the score is ≥ 3.
Geneva prediction score
Feature PointsCardiac failure 2Respiratory failure 2 Recent stroke 2 Recent myocardial infarction 2 Acute infectious disease 2 Acute rheumatic disease 2
Malignancy 2 Myeloproliferative syndrome 2 Nephrotic syndrome 2 History of VTE 2 Known hypercoagulability state 2 Immobilisation 1 Travel > 6hs 1 Age > 60 1 Obesity (BMI > 30) 1 Chronic venous insufficiency 1 Pregnancy 1 Hormonal therapy 1 Dehydration 1
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References• Chopard 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.
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Diagnosis of the Antiphospholipid Syndrome
IndicationAccording 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 phospholipid-
dependent 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
3) Anti-β2 Glycoprotein I Antibodies:
• Normalised ELISA system• Titre > 99th percentile. IgG and IgM
antibodies
a ApS diagnosis criteria: both clinical and laboratory criteria are requiredb Biological tests should be confirmed at two occasions separated at least by 12 weeks
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References• Devreese 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.
Recommendations for the determination of Lupus Anticoagulant
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
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Diagnosis of Disseminated Intravascular Coagulation
IndicationDisseminated 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)
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.
1) Clinical risk assessmentDoes the patient have a disease known
to be associated with DIC? (see table on p. 42)
2) Perform a global coagulation evaluation
Continue the algorithm only if the answer is yes
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Template for scoring system for non-overt DIC
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 normal raised falling = –1 stable = 0 rising = 1 or FDP’s +
3. Specific criteria
antithrombin normal = –1 low = 1 protein C normal = –1 low = 1
4. Calculate score
A score of 5 or higher is compatibe with non-overt DIC.The score should be repeated daily.
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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.
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Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP)
IndicationTTP is an acute, rare life-threatening thrombotic microangiopathy that requires rapid diagnosis and treatment.
Diagnostic features of thrombotic microangiopathies1. Thrombocytopenia2. Hemolytic anemia3. Renal insufficiency4. Cerebral symptoms5. Fever
InterpretationTTP 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.
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
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Acute Intestinal Ischemia / Thrombosis
Management of suspected mesenteric ischemia
Suspected mesenteric ischemia (arterial)
Peritonitis
Laparotomy
Remainingintestine too short
Remainingintestine sufficient
No peritonitis
Central
Surgery
Embolectomy
Interventionalradiology
Catheterembolectomy
and lysis,possibly stent
Vasodilation(also
postsurgeryfollowing
recection)
Interventionalradiology
Lysis,vasodilation
Interventionalradiology
Peripheral SuspectedNOMI
No resection Resection
CT/CT angiography
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Management of patients with occlusion of the superior mesenteric artery
References• 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.
Suspected mesenteric ischemia (arterial)
Peritonitis
Laparotomy
Remainingintestine too short
Remainingintestine sufficient
No peritonitis
Central
Surgery
Embolectomy
Interventionalradiology
Catheterembolectomy
and lysis,possibly stent
Vasodilation(also
postsurgeryfollowingrecection)
Interventionalradiology
Lysis,vasodilation
Interventionalradiology
Peripheral SuspectedNOMI
No resection Resection
CT/CT angiography
Peritonitis
CT-verified acute SMA occlusion
No peritonitis
Exploratorylaparotomy
Embolus
No contraindicationto thrombolysis
Aspiration ±pharmacological
thrombolysis ±endovascularmechanical
embolectomy
Aspiration ±endovascularmechanical
embolectomy
Openembolectomy +
completionangiography
Openembolectomy +
completionangiography +
damage control surgery
Contraindicationto thrombolysis
Thrombosis
Embolus Thrombosis
Stenting
Stenting +damage
control surgery
46
Blee
ding
ISTH bleeding assessment tool for the evaluation of bleeding severity
IndicationQuantitative 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 experts’ 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.pdfA 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 patients’ 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.
47
Blee
ding
Ble
edin
g A
sses
smen
t Too
lSy
mpt
oms
(up
to th
e tim
e of
dia
gnos
is)Sc
ore
01
23
4
Epis
taxi
sN
o / t
rivia
l• >
5/y
ear o
r• m
ore
than
10
min
utes
Con
sulta
tion
only
Pack
ing
or c
aute
rizat
ion
or a
ntifi
brin
olyt
icBl
ood
trans
fusi
on o
r rep
lace
men
t the
rapy
(u
se o
f hem
osta
tic b
lood
com
pone
nts
an
d rF
VIIa
) or d
esm
opre
ssin
Cut
aneo
usN
o / t
rivia
lFo
r bru
ises
5
or m
ore
(> 1
cm
) in
exp
osed
are
as
Con
sulta
tion
only
Exte
nsiv
e Sp
onta
neou
s he
mat
oma
requ
iring
blo
od
trans
fusi
on
Ble
edin
g fr
om m
inor
w
ound
sN
o / t
rivia
l• >
5/y
ear o
r• m
ore
than
10
min
utes
Con
sulta
tion
only
Surg
ical
hae
mos
tasi
sBl
ood
trans
fusi
on, r
epla
cem
ent t
hera
py,
or d
esm
opre
ssin
Ora
l cav
ityN
o / t
rivia
lPr
esen
tC
onsu
ltatio
n on
lySu
rgic
al h
aem
osta
sis
or
ant
ifibr
inol
ytic
Bloo
d tra
nsfu
sion
, rep
lace
men
t the
rapy
or
des
mop
ress
in
Gas
troi
ntes
tinal
bl
eedi
ngN
o / t
rivia
lPr
esen
t (n
ot a
ssoc
iate
d w
ith u
lcer
, por
tal
hype
rtens
ion,
he
mor
rhoi
ds,
angi
odys
plas
ia)
Con
sulta
tion
only
Surg
ical
hae
mos
tasi
s,
antifi
brin
olyt
icBl
ood
trans
fusi
on, r
epla
cem
ent t
hera
py
or d
esm
opre
ssin
Hem
atur
iaN
o / t
rivia
lPr
esen
t (m
acro
scop
ic)
Con
sulta
tion
only
Surg
ical
hae
mos
tasi
s,
iron
ther
apy
Bloo
d tra
nsfu
sion
, rep
lace
men
t the
rapy
or
des
mop
ress
in
Toot
h ex
trac
tion
No
/ triv
ial
or n
one
done
Rep
orte
d in
≤ 2
5%
of a
ll pr
oced
ures
, no
inte
rven
tion
Rep
orte
d in
> 2
5%
of a
ll pr
oced
ures
, no
inte
rven
tion
Res
utur
ing
or p
acki
ngBl
ood
trans
fusi
on, r
epla
cem
ent t
hera
py
or d
esm
opre
ssin
Surg
ery
No
/ triv
ial
or n
one
done
Rep
orte
d in
≤ 2
5%
of a
ll pr
oced
ures
, no
inte
rven
tion
Rep
orte
d in
> 2
5%
of a
ll pr
oced
ures
, no
inte
rven
tion
Surg
ical
hae
mos
tasi
s
or a
ntifi
brin
olyt
icBl
ood
trans
fusi
on, r
epla
cem
ent t
hera
py
or d
esm
opre
ssin
48
Blee
ding
Ble
edin
g A
sses
smen
t Too
l (co
nt.)
Sym
ptom
s (u
p to
the
time
of d
iagn
osis)
Scor
e
01
23
4
Men
orrh
agia
No
/ triv
ial
Con
sulta
tion
only
or
• Cha
ngin
g pa
ds
mor
e fre
quen
tly
than
eve
ry 2
ho
urs
or
• Clo
t and
floo
ding
or • P
BAC
sco
re >
10
0
• Tim
e of
f wor
k/sc
hool
>
2/ye
ar o
r• R
equi
ring
antifi
brin
olyt
ics
or
horm
onal
or i
ron
ther
apy
• Req
uirin
g co
mbi
ned
treat
men
t with
an
tifibr
inol
ytic
s an
d ho
rmon
al th
erap
y or
• Pre
sent
sin
ce
men
arch
e an
d >
12
mon
ths
• Acu
te m
enor
rhag
ia re
quiri
ng h
ospi
tal
adm
issi
on a
nd e
mer
genc
y tre
atm
ent o
r re
quiri
ng b
lood
tran
sfus
ion,
repl
acem
ent
ther
apy,
des
mop
ress
in, o
r• R
equi
ring
dila
tatio
n &
curre
tage
or
endo
met
rial a
blat
ion
or h
yste
rect
omy
Post
-par
tum
he
mor
rhag
eN
o / t
rivia
l or
no
deliv
erie
s
Con
sulta
tion
only
or
• Use
of s
ynto
cin
or• L
ochi
a >
6 w
eeks
• Iro
n th
erap
y or
• Ant
ifibr
inol
ytic
sRe
quirin
g bl
ood
trans
fusio
n, re
plac
emen
t th
erap
y, de
smop
ress
in
or re
quirin
g ex
amin
atio
n un
der a
naes
thes
ia a
nd/o
r th
e us
e of
ute
rin b
allo
on/
pack
age
to ta
mpo
nade
th
e ut
erus
Any
proc
edur
e re
quiri
ng c
ritic
al c
are
or
sur
gica
l int
erve
ntio
n
(e.g
., hy
ster
ecto
my,
inte
rnal
ilia
c ar
tery
lega
tion,
ut
erin
e ar
tery
em
boliz
atio
n, u
terin
e br
ace
sutu
res)
Mus
cle
hem
atom
asN
ever
Post
trau
ma,
no
ther
apy
Spon
tane
ous,
no
ther
apy
Spon
tane
ous
or
traum
atic
, req
uirin
g de
smop
ress
in
or re
plac
emen
t the
rapy
Spon
tane
ous
or tr
aum
atic
, req
uirin
g su
rgic
al
inte
rven
tion
or b
lood
tran
sfus
ion
Hem
arth
rosi
sN
ever
Post
trau
ma,
no
ther
apy
Spon
tane
ous,
no
ther
apy
Spon
tane
ous
or
traum
atic
, req
uirin
g de
smop
ress
in
or re
plac
emen
t the
rapy
Spon
tane
ous
or tr
aum
atic
, req
uirin
g su
rgic
al
inte
rven
tion
or b
lood
tran
sfus
ion
CN
S bl
eedi
ngN
ever
Subd
ural,
any
inte
rven
tion
Intra
cere
bral
, any
inte
rven
tion
Oth
er b
leed
ings
No
/ triv
ial
Pres
ent
Con
sulta
tion
only
Surg
ical h
aem
osta
sis,
antifi
brino
lytics
Bloo
d tra
nsfu
sion
or r
epla
cem
ent t
hera
py
or d
esm
opre
ssin
49
Blee
ding
Ble
edin
g A
sses
smen
t Too
l (co
nt.)
Sym
ptom
s (u
p to
the
time
of d
iagn
osis)
Scor
e
01
23
4
Men
orrh
agia
No
/ triv
ial
Con
sulta
tion
only
or
• Cha
ngin
g pa
ds
mor
e fre
quen
tly
than
eve
ry 2
ho
urs
or
• Clo
t and
floo
ding
or • P
BAC
sco
re >
10
0
• Tim
e of
f wor
k/sc
hool
>
2/ye
ar o
r• R
equi
ring
antifi
brin
olyt
ics
or
horm
onal
or i
ron
ther
apy
• Req
uirin
g co
mbi
ned
treat
men
t with
an
tifibr
inol
ytic
s an
d ho
rmon
al th
erap
y or
• Pre
sent
sin
ce
men
arch
e an
d >
12
mon
ths
• Acu
te m
enor
rhag
ia re
quiri
ng h
ospi
tal
adm
issi
on a
nd e
mer
genc
y tre
atm
ent o
r re
quiri
ng b
lood
tran
sfus
ion,
repl
acem
ent
ther
apy,
des
mop
ress
in, o
r• R
equi
ring
dila
tatio
n &
curre
tage
or
endo
met
rial a
blat
ion
or h
yste
rect
omy
Post
-par
tum
he
mor
rhag
eN
o / t
rivia
l or
no
deliv
erie
s
Con
sulta
tion
only
or
• Use
of s
ynto
cin
or• L
ochi
a >
6 w
eeks
• Iro
n th
erap
y or
• Ant
ifibr
inol
ytic
sRe
quirin
g bl
ood
trans
fusio
n, re
plac
emen
t th
erap
y, de
smop
ress
in
or re
quirin
g ex
amin
atio
n un
der a
naes
thes
ia a
nd/o
r th
e us
e of
ute
rin b
allo
on/
pack
age
to ta
mpo
nade
th
e ut
erus
Any
proc
edur
e re
quiri
ng c
ritic
al c
are
or
sur
gica
l int
erve
ntio
n
(e.g
., hy
ster
ecto
my,
inte
rnal
ilia
c ar
tery
lega
tion,
ut
erin
e ar
tery
em
boliz
atio
n, u
terin
e br
ace
sutu
res)
Mus
cle
hem
atom
asN
ever
Post
trau
ma,
no
ther
apy
Spon
tane
ous,
no
ther
apy
Spon
tane
ous
or
traum
atic
, req
uirin
g de
smop
ress
in
or re
plac
emen
t the
rapy
Spon
tane
ous
or tr
aum
atic
, req
uirin
g su
rgic
al
inte
rven
tion
or b
lood
tran
sfus
ion
Hem
arth
rosi
sN
ever
Post
trau
ma,
no
ther
apy
Spon
tane
ous,
no
ther
apy
Spon
tane
ous
or
traum
atic
, req
uirin
g de
smop
ress
in
or re
plac
emen
t the
rapy
Spon
tane
ous
or tr
aum
atic
, req
uirin
g su
rgic
al
inte
rven
tion
or b
lood
tran
sfus
ion
CN
S bl
eedi
ngN
ever
Subd
ural,
any
inte
rven
tion
Intra
cere
bral
, any
inte
rven
tion
Oth
er b
leed
ings
No
/ triv
ial
Pres
ent
Con
sulta
tion
only
Surg
ical h
aem
osta
sis,
antifi
brino
lytics
Bloo
d tra
nsfu
sion
or r
epla
cem
ent t
hera
py
or d
esm
opre
ssin
InterpretationA 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.
References• Rodeghiero 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.
50
Blee
ding
Pediatric bleeding assessment tool for the evaluation of bleeding severity in children
IndicationQuantitative 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/fullThere 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• Biss 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.
51
Blee
ding
Pedi
atric
Ble
edin
g sc
ore
Sym
ptom
sSc
ore
–10
12
34
Epis
taxi
sN
o or
triv
ial
(≤ 5
per
yea
r)>
5 pe
r yea
r OR
>
10 m
inut
es
dura
tion
Con
sulta
tion
only
Pack
ing,
cau
teriz
atio
n
or a
ntifi
brin
olyt
ics
Bloo
d tra
nsfu
sion
, re
plac
emen
t the
rapy
or
des
mop
ress
in
Cut
aneo
usN
o or
triv
ial
(≤ 1
cm
)>
1 cm
AN
D
no tr
aum
aC
onsu
ltatio
n on
ly
Min
our w
ound
sN
o or
triv
ial
(≤ 5
per
yea
r)>
5 pe
r yea
r O
R >
5 m
inut
es
dura
tion
Con
sulta
tion
only
or
Ster
istre
aps
Surg
ical
hae
mos
tasi
s
or a
ntifi
brin
olyt
ics
Bloo
d tra
nsfu
sion
, re
plac
emen
t the
rapy
or
des
mop
ress
in
Ora
l cav
ityN
oR
epor
ted
at
leas
t onc
eC
onsu
ltatio
n on
lySu
rgic
al h
aem
osta
sis
or
ant
ifibr
inol
ytic
sBl
ood
trans
fusi
on,
repl
acem
ent t
hera
py
or d
esm
opre
ssin
Gas
troin
test
inal
tra
ctN
oId
entifi
ed c
ause
Con
sulta
tion
or
sp
onta
neuo
us
Surg
ical
hae
mos
tasi
s,
antifi
brin
olyt
ics,
blo
od
trans
fusi
on, r
epla
cem
ente
th
erap
y or
dem
opre
ssin
Toot
h ex
tract
ion
No
blee
ding
in
at l
east
2
extra
ctio
ns
Non
e do
ne o
r no
blee
ding
in
1 ex
tract
ion
Rep
orte
d,
no c
onsu
ltatio
nC
onsu
ltatio
n on
lyR
esut
urin
g, re
pack
ing
or
ant
ifibr
inol
ytic
sBl
ood
trans
fusi
on,
repl
acem
ent t
hera
py
or d
esm
opre
ssin
Surg
ery
No
blee
ding
in
at l
east
2
surg
erie
s
Non
e do
ne
or n
o bl
eedi
ng
in 1
sur
gery
Rep
orte
d,
no c
onsu
ltatio
nC
onsu
ltatio
n on
lySu
rgic
al h
aem
osta
sis
or
ant
ifibr
inol
ytic
sBl
ood
trans
fusi
on,
repl
acem
ent t
hera
py
or d
esm
opre
ssin
52
Blee
ding
Pedi
atric
Ble
edin
g sc
ore
(con
t.)Sy
mpt
oms
Scor
e–1
01
23
4
Men
orrh
agia
No
Rep
orte
d or
co
nsul
tatio
n on
lyAn
tifibr
onol
ytic
s or
con
trace
ptiv
e pi
ll us
e
D&C
or i
ron
ther
apy
Bloo
d tra
nsfu
sion
, re
plac
emen
t the
rapy
, de
smop
ress
in
or h
yste
rect
omy
Post
-par
tum
No
blee
ding
in
at l
east
2
deliv
erie
s
No
deliv
erie
s or
no
blee
ding
in
1 d
eliv
ery
Rep
orte
d or
co
nsul
tatio
n on
lyD
&C o
r iro
n th
erap
y or
an
tifibr
onol
ytic
s
Bloo
d tra
nsfu
sion
, re
plac
emen
t the
rapy
or
des
mop
ress
in
Mus
cle
hem
atom
aN
ever
Post
-trau
ma,
no
ther
apy
Spon
tane
us,
no th
erap
ySp
onta
neus
or t
raum
atic
, re
quiri
ng re
plac
emen
t th
erap
y or
des
mop
ress
in
Spon
tane
us
or tr
aum
atic
, req
uirin
g su
rgic
al in
terv
entio
n
or b
lood
tran
sfus
ion
Hem
arth
rosi
sN
ever
Post
-trau
ma,
no
ther
apy
Spon
tane
us,
no th
erap
ySp
onta
neus
or t
raum
atic
, re
quiri
ng re
plac
emen
t th
erap
y or
des
mop
ress
in
Spon
tane
us
or tr
aum
atic
, req
uirin
g su
rgic
al in
terv
entio
n
or b
lood
tran
sfus
ion
Cen
tral
ner
viou
s sy
stem
Nev
erSu
bdur
al, a
ny in
terv
entio
nIn
trace
rebr
al,
any
inte
rven
tion
Oth
erN
oR
epor
ted
Con
sulta
tion
only
Surg
ical
hae
mos
tasi
s,
antifi
brin
olyt
ics
or
iron
ther
apy
Bloo
d tra
nsfu
sion
, re
plac
emen
t the
rapy
or
des
mop
ress
in
53
Blee
ding
Bleeding assessment tool for the evaluation of bleeding severity in immune thrombocytopenia: the SMOG system
IndicationQuantitative 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• 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.
54
Blee
ding
The
SMO
G s
yste
m
Type
of b
leed
ing
Gra
des
base
d on
the
wor
st in
cide
nt e
piso
de s
ince
last
vis
itSK
IN0
12
34
Pete
chia
e (d
oes
not i
nclu
de
ster
oid-
indu
ced
or
sen
ile p
urpu
ra)
No
• Le
ss th
an o
r equ
al to
10
in a
pat
ient
’s p
alm
-siz
ed
area
in th
e m
ost a
ffect
ed
body
are
a•
Any
num
ber i
f rep
orte
d by
the
patie
nt
Mor
e th
an 1
0 in
a p
atie
nt’s
pa
lm-s
ized
are
a or
mor
e th
an
5 in
at l
east
2 p
atie
nt’s
pal
m-
size
d ar
eas
loca
ted
in a
t lea
st
2 di
ffere
nt b
ody
area
s, o
ne
abov
e an
d on
e be
low
the
belt
(in th
e m
ost a
ffect
ed b
ody
area
s)
Mor
e th
an 5
0, if
sca
ttere
d bo
th
abov
e an
d be
low
the
belt
Ecch
ymos
esN
one
or u
p to
2
in th
e sa
me
body
ar
ea, b
ut s
mal
ler
than
a p
atie
nt’s
pa
lm-s
ized
are
a, if
:• s
pont
aneo
us o
r • d
ispro
porti
onat
e to
trau
ma/
cons
trict
ion
• 3
or m
ore
in th
e sa
me
body
ar
ea, b
ut a
ll sm
alle
r tha
n a
patie
nt’s
palm
-siz
ed a
rea,
if:
– sp
onta
neou
s or
–
disp
ropo
rtion
ate
to tr
aum
a/co
nstri
ctio
n•
At le
ast 2
in tw
o di
ffere
nt
body
are
as, s
mal
ler t
han
a pa
tient
’s pa
lm-s
ized
are
a, if
:–
spon
tane
ous
or
– di
spro
porti
onat
e to
trau
ma/
cons
trict
ion
• An
y nu
mbe
r and
siz
e if
repo
rted
by th
e pa
tient
From
1 to
5 la
rger
than
a
patie
nt’s
pal
m-s
ized
are
a, if
:• s
pont
aneo
us o
r • d
ispr
opor
tiona
te to
trau
ma/
cons
trict
ion
with
or w
ithou
t sm
alle
r one
s
Mor
e th
an 5
larg
er th
an a
pa
tient
’s p
alm
-siz
ed a
rea,
if:
• spo
ntan
eous
or
• dis
prop
ortio
nate
to
trau
ma/
cons
trict
ion
Subc
utan
eous
he
mat
omas
No
• 1
smal
ler t
han
a pa
tient
’s
palm
-siz
ed a
rea
• An
y nu
mbe
r and
siz
e if
repo
rted
by th
e pa
tient
• 2
smal
ler t
han
a pa
tient
’s
palm
-siz
ed a
rea,
sp
onta
neou
s •
2 sm
alle
r tha
n a
patie
nt’s
pa
lm-s
ized
are
a,
disp
ropo
rtion
ate
to tr
aum
a
• M
ore
than
2 s
mal
ler o
r at l
east
1
larg
er th
an a
pat
ient
’s
palm
-siz
ed a
rea,
spo
ntan
eous
• M
ore
than
2 s
mal
ler o
r at l
east
1
larg
er th
an a
pat
ient
’s
palm
-siz
ed a
rea,
di
spro
porti
onat
e to
trau
ma
Ble
edin
g fr
om m
inor
w
ound
s N
o•
Last
ing
< 5
min
• An
y ep
isod
e if
repo
rted
by
the
patie
nt
Last
ing
> 5
min
or i
nter
ferin
g w
ith d
aily
act
iviti
es•
Req
uirin
g pr
otra
cted
med
ical
ob
serv
atio
n at
the
time
of
this
vis
it•
Med
ical
repo
rt de
scrib
ing
patie
nt’s
eva
luat
ion
by
a p
hysi
cian
55
Blee
ding
The
SMO
G s
yste
m (c
ont.)
Type
of b
leed
ing
Gra
des
base
d on
the
wor
st in
cide
nt e
piso
de s
ince
last
vis
itM
UCO
SAL
01
23
4
Epis
taxi
sN
o•
Last
ing
< 5
min
• An
y ep
isod
e if
repo
rted
by
the
patie
nt
Last
ing
> 5
min
or i
nter
ferin
g w
ith d
aily
act
iviti
es•
Pack
ing
or c
aute
rizat
ion
or
in-h
ospi
tal e
valu
atio
n
at th
e tim
e of
this
vis
it•
Med
ical
repo
rt de
scrib
ing
pack
ing
or c
aute
rizat
ion
or
in-h
ospi
tal e
valu
atio
n
RBC
tran
sfus
ion
or H
b dr
op >
2 g
/dL
Ora
l cav
ity
(gum
ble
edin
g)
No
• La
stin
g <
5 m
in•
Any
epis
ode
if re
porte
d
by th
e pa
tient
Last
ing
> 5
min
or i
nter
ferin
g w
ith d
aily
act
iviti
es•
Req
uirin
g pr
otra
cted
med
ical
ob
serv
atio
n at
the
time
of th
is
visi
t•
Med
ical
repo
rt de
scrib
ing
patie
nt’s
eva
luat
ion
by
a p
hysi
cian
Ora
l cav
ity
(hem
orrh
agic
bul
lae
or b
liste
rs)
No
• Le
ss th
an 3
• An
y nu
mbe
r if r
epor
ted
by
the
patie
nt
From
3 to
10
but n
o di
fficu
lty
with
mas
ticat
ion
Mor
e th
an 1
0 or
mor
e th
an 5
if
diffi
culty
with
mas
ticat
ion
Ora
l cav
ity
(ble
edin
g fro
m b
ites
to li
ps
& to
ngue
or a
fter d
ecid
uous
te
eth
loss
)
No
• La
stin
g <
5 m
in•
Any
epis
ode
if re
porte
d
by th
e pa
tient
Last
ing
> 5
min
or i
nter
ferin
g
with
dai
ly a
ctiv
ities
• In
terv
entio
ns to
ens
ure
haem
osta
sis
or in
-hos
pita
l ev
alua
tion
at th
e tim
e
of th
is v
isit
• M
edic
al re
port
desc
ribin
g in
terv
entio
ns to
ens
ure
haem
osta
sis
or in
-hos
pita
l ev
alua
tion
Subc
onju
nctiv
al
hem
orrh
age
(n
ot d
ue to
con
junc
tival
di
seas
e)
No
• Pe
tech
iae/
hem
orrh
age
parti
ally
invo
lvin
g on
e ey
e•
Any
epis
ode
if re
porte
d
by th
e pa
tient
Pete
chia
e/he
mor
rhag
e pa
rtial
ly in
volv
ing
both
eye
s,
or d
iffus
e he
mor
rhag
e in
on
e ey
e
Diff
use
hem
orrh
age
in b
oth
eyes
56
Blee
ding
The
SMO
G s
yste
m (c
ont.)
Type
of b
leed
ing
Gra
des
base
d on
the
wor
st in
cide
nt e
piso
de s
ince
last
vis
itO
RG
AN
(a
nd in
tern
al m
ucos
ae)
01
23
4
Gas
troi
ntes
tinal
ble
edin
g
not e
xpla
ined
by
visi
ble
muc
osal
bl
eedi
ng o
r les
ion:
• Hem
atem
esis
,• M
elen
a,• H
emat
oche
zia,
• Rec
torrh
agia
No
Any
epis
ode
if re
porte
d
by th
e pa
tient
• Pr
esen
t at t
his
visi
t•
Des
crib
ed in
a m
edic
al
repo
rt
• R
equi
ring
endo
scop
y or
oth
er
ther
apeu
tic p
roce
dure
s or
in-
hosp
ital e
valu
atio
n at
the
time
of th
is v
isit
• M
edic
al re
port
pres
crib
ing
endo
scop
y or
oth
er th
erap
eutic
pr
oced
ures
or i
n-ho
spita
l ev
alua
tion
RBC
tran
sfus
ion
or
Hb
drop
> 2
g/d
L
Lung
ble
edin
g• H
emop
tysi
s• T
rach
eobr
onch
ial b
leed
ing
No
Any
epis
ode
if re
porte
d
by th
e pa
tient
• Pr
esen
t at t
his
visi
t•
Des
crib
ed in
a m
edic
al
repo
rt
• R
equi
ring
bron
chos
copy
or
othe
r the
rape
utic
pro
cedu
res
or
in-h
ospi
tal e
valu
atio
n at
the
time
of th
is v
isit
• An
equ
ival
ent e
piso
de if
de
scrib
ed
in a
med
ical
repo
rt
RBC
tran
sfus
ion
or
Hb
drop
> 2
g/d
L
Hem
atur
ia
No
• An
y ep
isod
e if
repo
rted
by
the
patie
nt•
Mic
rosc
opic
(lab
ana
lysi
s)
• M
acro
scop
ic•
Des
crib
ed in
a m
edic
al
repo
rt
• M
acro
scop
ic, a
nd re
quiri
ng
cyst
osco
py o
r oth
er th
erap
eutic
pr
oced
ures
or i
n-ho
spita
l ev
alua
tion
at th
e tim
e of
this
vis
it•
An e
quiv
alen
t epi
sode
if
desc
ribed
in
a m
edic
al re
port
RBC
tran
sfus
ion
or
Hb
drop
> 2
g/d
L
Men
orrh
agia
(c
ompa
red
to p
re-IT
P or
to a
pha
se
of d
isea
se w
ith n
orm
al p
late
let c
ount
)
No
• D
oubl
ing
nr. o
f pad
s or
ta
mpo
ns in
last
cyc
le
com
pare
d to
pre
-ITP
or
to a
pha
se o
f dis
ease
w
ith n
orm
al p
late
let c
ount
• Sc
ore
> 10
0 us
ing
PBAC
in
the
last
cyc
le, i
f nor
mal
sc
ore
in p
re-IT
P cy
cles
or
in a
pha
se o
f dis
ease
with
no
rmal
pla
tele
t cou
nt
• C
hang
ing
pads
mor
e fre
quen
tly th
an e
very
2 h
rs.
or c
lot a
nd fl
oodi
ng•
Req
uirin
g co
mbi
ned
treat
men
t with
an
tifibr
inol
ytic
s an
d ho
rmon
al
ther
apy
or g
ynec
olog
ical
in
vest
igat
ion
(e
ither
at t
his
visi
t or d
escr
ibed
in
a m
edic
al re
port)
Acut
e m
enor
rhag
ia re
quiri
ng
hosp
ital a
dmis
sion
or
end
omet
rial a
blat
ion
(e
ither
at t
his
visi
t or d
escr
ibed
in
a m
edic
al re
port)
RBC
tran
sfus
ion
or
Hb
drop
> 2
g/d
L
57
Blee
ding
The
SMO
G s
yste
m (c
ont.)
Type
of b
leed
ing
Gra
des
base
d on
the
wor
st in
cide
nt e
piso
de s
ince
last
vis
itO
RG
AN
(a
nd in
tern
al m
ucos
ae)
01
23
4
Intr
amus
cula
r hem
atom
as
(onl
y if
diag
nose
d by
a p
hysi
cian
w
ith a
n ob
ject
ive
met
hod)
No
• Po
st tr
aum
a, d
iagn
osed
at
this
vis
it, if
judg
ed
disp
ropo
rtion
ate
to tr
aum
a•
An e
quiv
alen
t epi
sode
if
desc
ribed
in a
med
ical
re
port
• Sp
onta
neou
s, d
iagn
osed
at
this
vis
it •
An e
quiv
alen
t epi
sode
if
desc
ribed
in a
med
ical
re
port
• Sp
onta
neou
s or
pos
t tra
uma
(if
judg
ed d
ispr
opor
tiona
te to
trau
ma)
di
agno
sed
at th
is v
isit
and
requ
iring
hos
pita
l adm
issi
on o
r su
rgic
al in
terv
entio
n•
An e
quiv
alen
t epi
sode
if
desc
ribed
in a
med
ical
repo
rt
RBC
tran
sfus
ion
or
Hb
drop
> 2
g/d
L
Hem
arth
rosi
s
(onl
y if
diag
nose
d by
a p
hysi
cian
w
ith a
n ob
ject
ive
met
hod)
No
• Po
st tr
aum
a, d
iagn
osed
at
this
vis
it, fu
nctio
n co
nser
ved
or m
inim
ally
im
paire
d, if
judg
ed
disp
ropo
rtion
ate
to tr
aum
a•
An e
quiv
alen
t epi
sode
if
desc
ribed
in a
med
ical
re
port
• Sp
onta
neou
s, d
iagn
osed
at
this
vis
it, fu
nctio
n co
nser
ved
or m
inim
ally
im
paire
d•
An e
quiv
alen
t epi
sode
if
desc
ribed
in
a m
edic
al re
port
• Sp
onta
neou
s or
pos
t tra
uma
(if ju
dged
dis
prop
ortio
nate
to
traum
a),d
iagn
osed
at t
his
visi
t an
d re
quiri
ng im
mob
ilizat
ion
or
join
t asp
iratio
n•
An e
quiv
alen
t epi
sode
if
desc
ribed
in a
med
ical
repo
rt
• Sp
onta
neou
s or
po
st tr
aum
a (if
judg
ed
disp
ropo
rtion
ate
to tr
aum
a)
diag
nose
d at
this
vis
it an
d re
quiri
ng s
urgi
cal
inte
rven
tion
• An
equ
ival
ent e
piso
de if
de
scrib
ed in
a m
edic
al
repo
rt
Ocu
lar b
leed
ing
(onl
y if
diag
nose
d by
a p
hysi
cian
w
ith a
n ob
ject
ive
met
hod)
No
• An
y po
st tr
aum
a vi
treou
s or
retin
al h
emor
rhag
e in
volv
ing
one
or b
oth
eyes
w
ith o
r with
out i
mpa
ired/
blur
red
visi
on p
rese
nt
at th
is v
isit
if ju
dged
di
spro
porti
onat
e to
trau
ma
• An
equ
ival
ent e
piso
de if
de
scrib
ed in
a m
edic
al
repo
rt
• Sp
onta
neou
s vi
treou
s
or re
tinal
hem
orrh
age
invo
lvin
g on
e or
bot
h ey
es w
ith im
paire
d/bl
urre
d vi
sion
pre
sent
at t
his
visi
t•
An e
quiv
alen
t epi
sode
if
desc
ribed
in a
med
ical
repo
rt
• Sp
onta
neou
s vi
treou
s or
re
tinal
hem
orrh
age
w
ith lo
ss o
f vis
ion
in o
ne
or b
oth
eyes
pre
sent
at
this
vis
it•
An e
quiv
alen
t epi
sode
if
desc
ribed
in a
med
ical
re
port
58
Blee
ding
The
SMO
G s
yste
m (c
ont.)
Type
of b
leed
ing
Gra
des
base
d on
the
wor
st in
cide
nt e
piso
de s
ince
last
vis
itO
RG
AN
(a
nd in
tern
al m
ucos
ae)
01
23
4
Intr
acra
nial
ble
edin
g:
intra
cere
bral
, int
rave
ntric
ular
, su
bara
chno
idal
, sub
dura
l, ex
tradu
ral
(onl
y if
diag
nose
d w
ith a
n ob
ject
ive
met
hod
at th
e vi
sit o
r des
crib
ed in
a
med
ical
repo
rt pr
ovid
ed b
y th
e pa
tient
)
No
• An
y po
st tr
aum
a ev
ent
requ
iring
hos
pita
lizat
ion
Any
spon
tane
ous
even
t req
uirin
g ho
spita
lizat
ion
in p
rese
nce
of
an
unde
rlyin
g in
tracr
ania
l les
ion
Any
spon
tane
ous
even
t re
quiri
ng h
ospi
taliz
atio
n w
ithou
t an
unde
rlyin
g in
tracr
ania
l les
ion
Oth
er in
tern
al b
leed
ing:
he
mop
erito
neum
, hem
oper
icar
dium
, he
mot
hora
x re
trope
riton
eal b
leed
ing,
he
patic
and
spl
enic
pel
iosi
s w
ith
orga
n ru
ptur
e re
troor
bita
l ble
edin
g,
met
rorrh
agia
, etc
. (o
nly
if di
agno
sed
with
an
obje
ctiv
e m
etho
d at
the
visi
t or d
escr
ibed
in a
m
edic
al re
port
prov
ided
by
the
patie
nt)
No
Any
even
t req
uirin
g ho
spita
lizat
ion
<
48 h
rs.
Any
even
t req
uirin
g ho
spita
lizat
ion
> 48
hrs
. or
RBC
tran
sfus
ion
or
Hb
drop
> 2
g/d
L
59
Ant
icoa
gula
nt th
erap
y
Diagnostic and therapeutic algorithm of Heparin-Induced Thrombocytopenia (HIT syndrome)
IndicationHeparin-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
210
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
10
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
2
10
Thrombocytopenia due to other causes• Apparently none• Possible• Yes
210
60
Ant
icoa
gula
nt th
erap
y
InterpretationAccording 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.
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.
Thrombocytopenia in a patientreceiving heparin or LMWH
Apply clinical scoring system
Immunoassay
Considerfunctional
assay
Positive HITconfirmed
(post-test probabilityof HIT > 95%)
Negative HITHIT unlikely
(post-test probabilityof HIT~ 3-16%)
Immunoassay
High clinical suspicion(4T’s = 6-8)
Discontinue heparin:start alternative therapy
Low clinical suspicion
for HIT(4T’s ≤ 3)Continue
heparin therapy
Intermediate (4T’s = 4-5)Discontinue heparin:
start alternative therapy
Positive HITpossible
(post-test probabilityof HIT ~ 60%)
Negative HITHIT unlikely
(post-test probabilityof HIT< 0,5%)
Presence ofhigh IgG OD/titerand/or platelet
activating antibodiesincrease HIT likelihood
(post-test probability of HIT ~ 65%)
Presence oflow IgG OD/titeror lack platelet
activating antibodiesdecrease HIT likelihood
(post-test probability of HIT ~ 40%)
61
Ant
icoa
gula
nt th
erap
y
Bridging strategies in patients on anticoagulants who need to undergo invasive procedures
IndicationFor 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 thromboembolismHigh • 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
62
Ant
icoa
gula
nt th
erap
y
InterpretationPerioperative 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.
Management strategy based on risk assessmentR
isk
of th
rom
boem
bolis
m
High
• Consult with surgeon or operator
• Continue VKA• Monitor INR• Target INR 1.5-2.0
• Stop treatment with VKA (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
(if no bleeding)
• Restart VKA 1-2 days postoperatively (if no bleeding)
• Stop heparin when INR is in therapeutic range
Low • 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
Practical manual of scores and algorithms in hemostasis and thrombosis
This booklet was produced with the help ofwww.stago.com
Dia
gnos
tica
Stag
o - 0
5/20
14 -
ref.:
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11
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