Practical-Manual-Scores-Algorithms-Haemostasis-Thrombosis

Practical manualScores and Algorithmsin Haemostasisand ThrombosisJosé A. Páramo (coordinator)Henri BounameauxMarcel LeviGregory YH LipPascual MarcoJoan Carles ReverterAlberto Tosetto

© Text: the authors© Edition: Grupo Acción Médica. Madrid, 2014Email: publicaciones@accionmedica.comThis 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 boardHenri BounameauxDivision of Angiology and HaemostasisUniversity Hospital of Geneva, SwitzerlandMarcel LeviAcademic Medical Center, University of AmsterdamAmsterdam, The NetherlandsGregory YH LipCentre for Cardiovascular Sciences - City HospitalUniversity of Birmingham, United KingdomPascual MarcoHematology ServiceUniversity General Hospital of Alicante, SpainJosé A. PáramoHematology ServiceUniversity Hospital of Navarra - Pamplona, SpainJoan Carles ReverterHemotherapy and Hemostasis Service. CDBHospital Clínic of Barcelona, SpainAlberto TosettoHemophilia and Thrombosis CenterHematology DepartmentSan Bortolo Hospital, Vicenza, Italy3

SummaryPrologue .............................................................................................................. 7Deep Vein Thrombosis and Pulmonary EmbolismClinical probability model for deep vein thrombosis ......................................... 9Clinical probability models for Pulmonary Embolism ....................................... 10Diagnostic algorithm for deep vein Thrombosis and Pulmonary Embolism .... 12Prognostic scores in pulmonary embolism ...................................................... 14Prediction of recurrent deep vein thrombosis or Pulmonary Embolism ......... 17Outpatient versus inpatient care in venous thromboembolism ....................... 19Assessment of post-thrombotic syndrome ..................................................... 21PregnancyDiagnostic algorithm in suspected deep vein thrombosis during pregnancy . 22Diagnostic algorithm in suspected pulmonary embolism during pregnancy ... 23Atrial FibrillationPrediction of stroke risk in patients with atrial fibrillation ................................ 25Bleeding risk in anticoagulated patients with atrial fibrillation ......................... 28Predicting the likelihood of achieving good anticoagulation control in a newlydiagnosed non-anticoagulated patient with atrial fibrillation ........................... 30Other thrombotic conditionsCancerRisk of Venous thromboembolism in Cancer Patients .................................... 32Medical patientsRisk assessment models in hospitalized Medical Patients .............................. 35Antiphospholipid syndromeDiagnosis of the antiphospholipid syndrome ................................................... 38Diagnosis of Disseminated Intravascular Coagulation .................................... 40OthersDiagnosis of Thrombotic Thrombocytopenic Purpura (TTP) ............................ 43Acute Intestinal Ischemia / Thrombosis ........................................................... 445

SummaryBleedingISTH bleeding assessment tool for the evaluation of bleeding severity .......... 46Pediatric bleeding assessment tool for the evaluation of bleedingseverity in children ........................................................................................... 50Bleeding assessment tool for the evaluation of bleeding severityin immune thrombocytopenia: the SMOG system ........................................... 53Anticoagulant therapyDiagnostic and therapeutic algorithm of Heparin-InducedThrombocytopenia (HIT syndrome) ................................................................. 59Bridging strategies in patients on anticoagulants who needto undergo invasive procedures ....................................................................... 616

PrologueEvidence-based medicine provides guidelines to physicians aimed at improvingefficacy and safety of patient management. This approach is to a great extentbased on the use of clinical scores and diagnosis algorithms that, in combinationwith patient clinical examination and laboratory tests, improve diagnosis accuracyand patient stratification. This approach also offers a better standardization of patientmanagement across centres and improves patient care reliability.For doctors who see patients with thrombotic and bleeding problems, or whose clinicalworkload 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 managementof such cases.The use of score calculators and algorithms can facilitate decision making inboth diagnosis and treatment of thrombotic and bleeding problems. However,considering the multiplicity of these tools in recent years, it becomes necessary touse 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 andsimple way, most recognized and useful clinical scores and diagnosis algorithms in thefield of thrombosis and haemostasis: deep venous thrombosis, pulmonary embolism,pregnancy, cancer, DIC, antiphospholipid syndrome, atrial fibrillation, and bleedingrisk. Each algorithm includes the indication and a brief interpretation emphasisingthe most relevant aspects of each one followed by some representative references.We hope this algorithm booklet may guide the clinician in the most appropriatediagnostic and therapeutic strategy, answering some of the questions that may arisewhen treating thrombotic and bleeding problems.The authors7

Clinical probability model for deep vein thrombosisIndicationClinically suspected deep vein thrombosis (DVT)FeatureWells’ scoreActive cancer (treatment ongoing, within previous 6 months, or palliative) 1Paralysis, paresis, or recent plaster immobilization of the lower extremities 1Recently bedridden ≥ 3 days or major surgery(within the previous 12 weeks requiring general or regional anesthesia)Localized tenderness along the distribution of the deep venous system 1Entire leg swollen 1Calf swelling by ≥ 3 cm than that on the asymptomatic leg(measured 10 cm below tibial tuberosity)Pitting oedema* (confined to the symptomatic leg) 1Collateral superficial veins (non-varicose) 1Previously documented DVT 1ScoreAlternative diagnosis at least as likely as DVT –211Deep Vein Thrombosis and Pulmonary EmbolismClinical probabilityLow 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 aD-dimer test result below a validated threshold and/or a negative ultrasound, alow 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 probabilityof deep-vein thrombosis in clinical management. Lancet. 1997;350:1795-8.9

Deep Vein Thrombosis and Pulmonary EmbolismClinical probability models for Pulmonary EmbolismIndicationClinically suspected Pulmonary Embolism (PE).FeatureWells’ scoreScorePrevious 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 3Clinical probabilityPE unlikely ≤ 4PE likely > 410

FeatureGeneva scoresPoints(revised dichotomized score)Points(simplified score)Previous DVT or PE 3 1Heart rate:75-94 bpm≥ 95 bpm3512Surgery or fracture < 1 month 2 1Hemoptysis 2 1Active malignancy 2 1Unilateral lower limb pain 3 1Pain on lower limb deep venous palpationor unilateral oedema4 1Age > 65 1 1Clinical probabilityPE unlikely ≤ 5 ≤ 2PE likely > 5 > 2Deep Vein Thrombosis and Pulmonary EmbolismInterpretationThese models are very useful when incorporated into algorithms, to optimizepatient management in clinically suspected PE. Combined with a D-dimertest result below a validated threshold and/or an objective imaging test, a lowclinical probability can safely rule out the presence of PE.References• Ceriani E, Combescure C, Le Gal G, et al. Clinical prediction rules for pulmonaryembolism: 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 scorefor 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 EmergencyDepartment: The Revised Geneva Score. Ann Intern Med. 2006;144:165-71.• Lucassen W, Geersing GJ, Erkens PM, et al. Clinical decision rules for excludingpulmonary 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 tocategorize patients probability of pulmonary embolism: increasing the models utilitywith the SimpliRED D-dimer. Thromb Haemost. 2000;83:416-20.11

Deep Vein Thrombosis and Pulmonary EmbolismDiagnostic algorithm of deep vein Thrombosisand Pulmonary EmbolismIndicationClinically suspected deep vein thrombosis (DVT) or non-massive PulmonaryEmbolism (PE), to decide therapeutic approach.UnlikelyClinical probabilityLikelyD-dimerBelow cut-offAbove cut-offCUS or MDCTANegativePositiveNo anticoagulant therapyAnticoagulant therapy12

InterpretationClinical decision rule with sequential diagnostic steps in clinically suspectedDVT or PE, based on the clinical probability, assessed by the diagnosticscores (see corresponding chapters), DD (D-dimer measurement) andimaging (CUS: compression ultrasonography in suspected DVT, MDCTA:multidetector CT angiography in suspected PE). When using highly sensitiveDD assays, the cut-off is usually set at 500 ng/mL. Recently, the utility of theDD 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 futureprospects. 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 forexclusion 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. SeminThromb Hemost. 2012;38:691-701.• Prisco D, Grifoni E. The role of D-dimer testing in patients with suspected venousthromboembolism. Semin Thromb Hemost. 2009;35:50-9.• Righini M, van Es J, Den Exter PL, et al. Age-adjusted D-dimer cut-off levels torule 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-dimerconcentration and non-high pretest probability score is a safe strategy to excludedeep venous thrombosis. Circulation. 2003;107:593-7.• Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis ofsuspected deep-vein thrombosis. N Engl J Med. 2003;349:1227-35.Deep Vein Thrombosis and Pulmonary Embolism13

Deep Vein Thrombosis and Pulmonary EmbolismPrognostic scores in pulmonary embolismIndicationPredictive scoring system for patients with pulmonary embolism (PE) usingPESI (the Pulmonary Embolism Severity Index) and Geneva score calculators.PESIFeaturesPointsOriginal version Simplified versionAge Years > 80 =1Male +10History of cancer +30 1History of heart failure +10History of chronic lung disease +10} 1 aPulse ≥ 110 bpm +20 1Systolic BP < 100 mmHg +30 1Respiratory rate ≥ 30/min +20Temperature < 36 ºC +20Altered mental status +60Arterial oxygen saturation < 90% +20 1Risk evaluationClass I (very low)≤ 65 pointsClass II (low)66-85 pointsClass III (intermediate)86-105 points Low: 0High: ≥ 1Class IV (high)106-125 pointsClass V (very high)> 125 pointsaVariables combined into a single category of chronic cardiopulmonary diseaseInterpretationThe PESI score includes 11 clinical features and provides an estimation of therisk of mortality at 30 days after hospitalization in patients with PE. A significantproportion of low-risk patients (negative predictive value 99%) are identified aspotential candidates for ambulatory treatment. The simplified version includes14

6 features with a similar validity. The RIETE study shows that mortality was1% amongst 36% of the classified low-risk patients, against 10.9% in high-riskpatients. The PESI has been used to identify patients that may be treated in anoutpatient setting.FeatureGeneva prognostic scorePointsHistory of cancer 2History of heart failure 1Previous DVT 1DVT on ultrasound 1PAS < 100 mmHg 2PaO 2< 8 kPa 1Deep Vein Thrombosis and Pulmonary EmbolismClinical probabilityLow risk ≤ 2High risk ≥ 2InterpretationPredictive risk value of low-mortality-risk patients, recurrent VTE or increasingbleeding at 3 months. Patients with ≤ 2 points are considered low-level riskpatients. This stratification might help identifying patients who could be treatedin an outpatient setting.15

Deep Vein Thrombosis and Pulmonary EmbolismReferences• Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognosticmodel 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 forpatients 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 EmbolismSeverity 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 thepulmonary embolism severity index for prognostication in patients with acutesymptomatic pulmonary embolism. Arch Intern Med. 2010;170:1383-9.• Wicki J, Perrier A, Perneger TV, et al. Predicting adverse outcome in patients withacute pulmonary embolism: a risk score. Thromb Haemost. 2000;84:548-52.16

Prediction of recurrent deep vein Thrombosisor Pulmonary EmbolismIndicationAssessment of risk of recurrence after a first DVT or PE. Presentation of twomethods: the Vienna nomogram and the DASH score.PointsGenderVienna Nomogram0 10 20 30 40 50 60 70 80 90 100FemaleMaleDeep Vein Thrombosis and Pulmonary EmbolismLocationDistal DVTProximal DVTPED-dimer(ng/mL)100 150 200 250 400 500 750 1.000 1.500 2.000Total points0 50 100 150 200 250 300 3501 year cumulativerecurrence rate0.02 0.04 0.06 0.08 0.1 0.12 0.155 year cumulativerecurrence rate0.1 0.2 0.3 0.4 0.5InterpretationThe nomogram aims at estimating the recurrence risk following DVT or PE.Clinical (type of thrombosis and gender) and analytical (D-dimer measured at thetime 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, locationand D-dimer). The sum of the three responses is born on a line called Total, from17

Deep Vein Thrombosis and Pulmonary Embolismwhich a perpendicular line is drawn to this value, which gives the cumulated riskat one year and, by drawing another perpendicular line, the cumulative risk atfive years. For example: A man with a proximal DVT and a D-dimer of 400 μg/Lwill score 60 points for gender, 70 for proximal thrombosis and 46 points forD-dimer, totalizing 176 points, which corresponds to a probability of recurrenceof 5.1% and 18.5%, at one and five years, respectively.DASH scoreFeatureScoreAbnormal D-dimer(measured one month after stopping anticoagulation)+2Age ≤ 50 +1Male +1Hormonal therapy at onset of VTE (among women) –2ProbabilityLow ≤ 1High > 1DASH: D-dimer, Age, Sex, HormonesInterpretationThis model classifies DVT or PE recurrence risk as low (annual incidencearound 3%) if the score is 0 or 1, or high (annual incidence around 9%) if it ishigher than 1. Of note, D-dimer measurement is performed after withdrawal ofanticoagulation (≅ 30 days).References• Eichinger S, Heinze G, Jandeck LM, et al. Risk assessment of recurrence inpatients with unprovoked deep-vein thrombosis or pulmonary embolism: theVienna prediction model. Circulation. 2010;121:1630-6.• Tosetto A, Iorio A, Marcucci M, et al. Predicting disease recurrence in patientswith previous unprovoked venous thromboembolism: a proposed prediction score(DASH). J Thromb Haemost. 2012;10:1019-25.18

Outpatient versus inpatient care in venousthromboembolismIndicationTo identify patients with VTE that can safely be treated as outpatients.Is the patient hemodynamically unstable?*Hestia criteriaIs thrombolysis or embolectomy necessary?Active bleeding or high risk for bleeding?**More than 24 hours of oxygen supply to maintain oxygen saturation > 90%?Is pulmonary embolism diagnosed during anticoagulant treatment?Severe pain needing intravenous pain medication for more than 24 hours?Medical or social reason for treatment in the hospital for more than 24 hours(infection, malignancy, no support system, etc.)?Does the patient have a creatinine clearance of less than 30 mL/min?***Does the patient have severe liver impairment?****Is the patient pregnant?yesnoyesnoyesnoyesnoyesnoyesnoyesnoyesnoyesnoyesnoDeep Vein Thrombosis and Pulmonary EmbolismDoes the patient have a documented history of heparin-inducedthrombocytopenia (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/mm 3 ), uncontrolled hypertension (SAP > 180 ordiastolic arterial pressure [DAP] > 110 mmHg)*** Calculated applying Cockcroft-Gault formula**** As per medical assessment19

Deep Vein Thrombosis and Pulmonary EmbolismInterpretationAnswering yes to any of the questions means that the patient should probablybe hospitalized for treatment. Of note, the PESI and the Geneva PrognosticScore (see corresponding chapters) that stratify patients in low and highrisk of mortality or adverse outcome, respectively, have also been used forthat purpose.References• Zondag W, Hiddinga BI, Crobach MJ, et al.; Hestia Study Investigators. Hestia criteriacan 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. Outpatienttreatment in patients with acute pulmonary embolism: the Hestia Study. J ThrombHaemost. 2011;9:1500-7.20

Assessment of post-thrombotic syndromeIndicationScore of post-thrombotic syndrome (PTS) severitySymptoms• Pain• Cramps• Heaviness• Paresthesia• ItchingSigns• Pretibial oedema• Skin induration• Hyperpigmentation• Redness• Venous ectasia• Calf painon pressureVillalta scoreVenous ulcer Absence PresenceNone Light Moderate Severe00000000000111111111112222222222233333333333Deep Vein Thrombosis and Pulmonary EmbolismInterpretationThe 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 ≥ 15References• Kahn SR, Partsch H, Vedantham S, et al.; Subcommittee on Control of Anticoagulationof the Scientific and Standardization Committee of the International Society onThrombosis and Haemostasis. Definition of post-thrombotic syndrome of the legfor use in clinical investigations: a recommendation for standardization. J ThrombHaemost. 2009;7:879-83.• Prandoni P, Villalta S, Polistena P, et al. Symptomatic deep-vein thrombosis and thepost-thrombotic syndrome. Haematologica. 1995;80(Suppl 2):42-8.• Villalta S, Bagatella P, Piccioli A, et al. Assessment of validity and reproducibility of aclinical scale for the post-thrombotic syndrome. Haemostasis. 1994;24(suppl 1):158a.21

PregnancyDiagnostic algorithm in suspected deep veinthrombosis during pregnancyIndicationClinically suspected DVT during pregnancy.Clinically suspected DVTSerial compression ultrasoundDVT no confirmedDVT confirmedClinically suspected iliac DVT*Start treatmentNoYesSerial compressionultrasound after 1 weekDuplex DopplerNormal Abnormal Flow absent Flow presentDVT excludedDVT confirmedConsider magneticresonance imageStart treatment* The clinical suspicion of iliac vein thrombosis is based on pain located at the back of the thigh orbuttocks and swelling in the upper part of the lower extremity.InterpretationClinical decision rule using sequential steps in clinically suspected DVT ina pregnant woman. D-dimer measurement is usually skipped due to lack ofspecificity in this condition, though a value below the threshold allows ruling outthe condition.22

Diagnostic algorithm in suspected pulmonaryembolism during pregnancyPregnancyIndicationClinically suspected PE during pregnancy.Clinically suspected PESymptomatic DVTNoYesSerial compressionultrasoundDVT noconfirmedDVT confirmedStart treatmentVentilation/perfusion scanComputed tomographyNormalHighprobabilityPEexcludedPEconfirmedNondiagnosticNondiagnosticPEexcludedPEconfirmedComputedtomographyStart treatmentVentilation/perfusion scanStart treatment23

PregnancyInterpretationClinical decision rule using sequential steps in clinically suspected PE in apregnant woman. Again, D-dimer measurement is usually skipped duringpregnancy, though a value below the threshold allows ruling out the condition.In case of detecting a symptomatic DVT, anticoagulation therapy should bestarted without additional imaging tests.References• Chan WS, Ginsberg JS. Diagnosis of deep-vein thrombosis and pulmonaryembolism in pregnancy. Thromb Res. 2002;107:85-91.• Le Gal G, Kercret G, Ben Yahmed K, et al. Diagnostic value of single completecompression ultrasonography in pregnant and postpartum women with suspecteddeep vein thrombosis: prospective study. BMJ. 2012;344:e2635.• Tan M, Huisman MV. The diagnostic management of acute venousthromboembolism during pregnancy: recent advancements and unresolvedissues. Thromb Res. 2011;127:S13-6.24

Prediction of stroke risk in patientswith atrial fibrillationIndicationAtrial fibrillation (AF) is the most common arrhythmia in the population, and is amajor cause of stroke and systemic thromboembolism. Whilst the risk of strokein AF is increased 5-fold, stroke risk in AF is not homogeneous.Atrial FibrillationThe CHADS 2and CHA 2DS 2-VASc stroke risk score calculators have beenused to aid risk stratifying of patients, and to help decision making forthromboprophylaxis. The CHA 2DS 2-VASc score is now recommended bymany international guidelines, including those from the ESC, AHA/ACC/HRS,APHRS, SIGN and NICE guidelines.InterpretationLow risk = 0Moderate risk = 1High risk ≥ 2CHADS 2risk scoreRisk factorScoreCongestive heart failure 1Hypertension 1Age ≥ 75 years 1Diabetes mellitus 1Prior Stroke or TIA or Thromboembolism 2The CHADS 2score has been replaced by the CHA 2DS 2-VASc score in thelatest guidelines from the ESC, AHA/ACC/HRS, NICE, etc. Older guidelines(e.g. the 2006 ACC/AHA/ESC guidelines) recommended the following:CHADS 2scoreAntithrombotic therapy recommendation> 1 OAC (vitamin K antagonist or dabigatran)1 OAC or ASA 75-325 mg/day0 ASAOAC: oral anticoagulant; NOAC: Non-VKA Oral AntiCoagulants (previously called New or novel OACs);ASA: Acetylsalicylic Acid25

Atrial FibrillationCHA 2DS 2-VASc risk scoreRisk factorScoreCongestive heart failure 1Hypertension 1Age ≥ 75 years 2Diabetes 1Prior Stroke or TIA or Thromboembolism 2Vascular disease(peripheral artery disease, myocardial infarction, aortic plaque)1Age between 65 and 74 years 1Sex category (i.e. female gender) 1Maximum score 9InterpretationLow risk = 0 (males) or 1 (females)Moderate risk = 1 (males)High risk ≥ 2The ESC guidelines de-emphasises the ‘traditional’ (but artificial) low,moderate and high risk stratification and recommends a risk factor-basedapproach 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 isessentially a CHA 2DS 2-VASc score = 0 (males) or 1 (females). Such ‘lowrisk’ patients do not need any antithrombotic therapy.After this initial decision step, patients with AF and ≥ 1 stroke risk factors canbe offered effective stroke prevention, which is oral anticoagulation (OAC).The latter can be delivered either as well controlled VKA (as reflected byaverage Time in Therapeutic Range [TTR] ≥ 70%) or one of the NOACs.26

References• Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelinesfor the management of atrial fibrillation: An update of the 2010 ESC Guidelines forthe management of atrial fibrillation. Eur Heart J. 2012;33:2719-47.• De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heartdisease: Current status and perspectives (section III). Position paper of the escworking 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, andwhy? Eur Heart J. 2013;34:1041-9.• Lip GY, Nieuwlaat R, Pisters R, et al. Refining clinical risk stratification for predictingstroke and thromboembolism in atrial fibrillation using a novel risk factor-basedapproach: 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.Atrial Fibrillation27

Atrial FibrillationBleeding risk in anticoagulated patientswith atrial fibrillationIndicationMajor complication in anticoagulated patients is bleeding, intracranialhaemorrhage being the most severe manifestation (0.8-1%/patients/year).In the ESC guidelines, bleeding risk assessment is also recommended usingthe HAS-BLED score. The HAS-BLED score is validated for VKA and non-VKAanticoagulants, and is the only bleeding risk score predictive for intracranialhaemorrhage. Other studies have validated HAS-BLED in atrial fibrillation (AF)and non-AF patients, those undergoing bridging therapy, and in bleeding relatedto PCI/stenting.HAS-BLED scoreHAS-BLEDScoreHypertension i.e. uncontrolled Blood Pressure 1Abnormal renal/liver function 1 or 2Stroke 1Bleeding tendency or predisposition 1Labile INR 1Elderly (e.g., > 65, frail condition) 1Drugs (e.g. concomitant aspirin or NSAIDs) or alcohol excess or abuse 19InterpretationA high HAS-BLED score (≥ 3) should not be used as a reason for withholdingOAC but is indicative of the need for regular review and follow-up. A highHAS-BLED score also makes us consider the potentially reversible riskfactors for bleeding, for example, the H in HAS-BLED stands for uncontrolledblood pressure (so to reduce risk, BP should be controlled), the L stands forlabile INRs, and D for concomitant use of aspirin/NSAIDs in anticoagulatedpatients, etc. Those patients with a high HAS-BLED score derive a higher netclinical benefit when balancing ischaemic stroke and intracranial bleeding.28

References• Friberg L, Rosenqvist M, Lip G. Net clinical benefit of warfarin in patients withatrial 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. ExecutiveSummary of a Position Document from the European Heart Rhythm Association[EHRA], endorsed by the European Society of Cardiology [ESC] Working Group onThrombosis. Thromb Haemost. 2011;106:997-1011.• Pisters R, Lane DA, Nieuwlaat R, et al. A novel user-friendly score (has-bled) toassess 1-year risk of major bleeding in patients with atrial fibrillation: The EuroHeart Survey. Chest. 2010;138:1093-100.Atrial Fibrillation29

Atrial FibrillationPredicting the likelihood of achieving goodanticoagulation control in a newly diagnosednon-anticoagulated patient with atrial fibrillationIndicationA clinical management dilemma is how to predict those newly diagnosednon-anticoagulated AF patients who are likely to do well on warfarin withhigh TTR, especially since costs of NOACs are high, and since the relativebenefits of NOACs over the VKAs may be small in those who achievegood-quality anticoagulation control, with high TTRs (> 70%).An ESC Working Group on Thrombosis Anticoagulation Task Force Positionpaper recommends that the use of the new SAMe-TT 2R 2score should beconsidered to aid decision making when assessing such patients. This is auser-friendly validated score based on simple clinical variables.Definition of the SAMe-TT 2R 2scoreAcronym Definitions ScoreS Sex (female) 1A Age (less than 60 years) 1Me Medical history* 1Treatment1T(interacting Rx e.g., amiodarone for rhythm control)T Tobacco use (within 2 years) 2R Race (non-Caucasian) 2Maximum points 8Definition of the SAMe-TT 2R 2score* 2 of the following: hypertension, diabetes melitus, coronary artery disease /myocardial infraction, PAD, coronary heart failure, previous stroke, pulmonarydisease, hepatic or renal disease.30

InterpretationThis score identifies those Atrial Fibrillation patients likely to do well on warfarin(SAMe-TT 2R 2score 0-1) or those more likely to have poor anticoagulationcontrol (SAMe-TT 2R 2score > 2).Atrial FibrillationIf the SAMe-TT 2R 2score is > 2, such patients could be better off being startedon NOACs as initial therapy, or having more aggressive efforts to improveanticoagulation control.References• Apostolakis S, Sullivan RM, Olshansky B, et al. Factors affecting quality ofanticoagulation control among patients with atrial fibrillation on warfarin: TheSAME-TT2R2 score. Chest. 2013;144:1555-63.• Boriani G. Predicting the quality of anticoagulation during warfarin therapy: thebasis for an individualized approach. Chest. 2013;144:1437-8.• De Caterina R, Husted S, Wallentin L, et al. Vitamin K antagonists in heartdisease: Current status and perspectives (section III). Position paper of the ESCworking 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 bleedingand mortality in patients with atrial fibrillation. Chest. 2014 Apr 10. doi: 10.1378/chest.13-2976. [Epub ahead of print].31

Other thrombotic conditionsRisk of venous thromboembolism in cancer PatientsIndicationAssessing the risk of DVT or PE in outpatients with cancer on chemotherapy(Khorana model), the prediction of recurrence (Ay and Ottawa models) andthe risk of DVT in patients with multiple myeloma treated with thalidomide orlenalidomide.Khorana model: for outpatients with cancer on chemotherapyFeatureSite of cancer (origin)• High risk (pancreas, stomach)• Low risk (lung, lymphoma, gynaecologic, bladder, testicular)PointsPlatelet count ≥ 350 × 10 9 /L 1Haemoglobin level < 100 g/L or use of red cell growth factor 1Leukocyte count > 11 × 10 9 /L 1BMI ≥ 35 kg/m 2 1Probability• Low risk 0• Intermediate risk 1-2• High risk > 321InterpretationThe risk of thrombosis was 0.3-0.8% for low-risk patients; 1.8-2.0% forintermediate-risk patients and 6.7-7.1% for high-risk patients; in the latterthromboprophylaxis should be considered.32

Vienna score (Ay Model): DVT or PE risk scoringFeaturePointsKhorana Model scoring (0 to 6)D-dimer ≥ 1.44 μg/mL 1P-selectin ≥ 53.1 mg/mL 1ProbabilityLow risk 0Intermediate risk 1-2High risk ≥ 3Other thrombotic conditionsInterpretationThe risk of DVT or PE at 6 months was 17.7% in high-risk patients, 9.6% inintermediate-risk patients and 3.8% in low-risk patients.Ottawa scoreRecurrence risk in patients with thrombosis associated with neoplasiaFeaturePointsFemale 1Lung Cancer 1Breast Cancer –1Status (TNM*) –2Previous DVT or PE 1ProbabilityLow risk ≤ 0High risk ≥ 1* TNM: Tumor-Node-Metastasis levelInterpretationThe DVT or PE recurrence risk was ≤ 4.5% for low-risk patients and ≥ 19% forhigh-risk patients.33

Other thrombotic conditionsDVT riskfactorsIndividual andmyeloma-relatedfactorsMyelomatherapyDVT risk scoring in patients with myeloma treatedwith thalidomide or lenalidomideCategoryProphylaxis• BMI ≥ 30 kg/m 2• Previous DVT or PTE• Central venous catheter or pacemaker• Concomitant disease (cardiac, chronicrenal, diabetes, acute infection,immobilization)• Medications (EPO)• Clotting disorders• HyperviscosityHigh dose of dexamethasone,doxorubicin, polychemotherapy≤ 1 risk factor:• Aspirin(80-300 mg/d)≥ 2 factors:• LMWH (equivalentto enoxaparin40 mg/d) or• VKA (INR = 2-3)HBPM (e.g., enoxaparin40 mg/d) or VKA(INR = 2-3)BMI: Body Mass Index; EPO: Erythropoietin; LMWH: Low-Molecular-Weight Heparin; INR: InternationalNormalized Ratio; VKA: Vitamin K antagnonistsInterpretationThe risk of thrombosis is high in patients with multiple myeloma, especially in thosereceiving thalidomide or lenalidomide combined with dexamethasone. In thesepatients antithrombotic prophylaxis should be considered, according to the risk.References• Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancerpatients. Blood. 2010;116:5377-82.• Farge D, Debourdeau P, Beckers M, et al. International clinical practice guidelines forthe 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 predictivemodel for chemotherapy-associated thrombosis. Blood. 2008;111:4902-7.• Louzada ML, Carrier M, Lazo-Langner A, et al. Development of a clinical prediction rulefor 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 WorkingGroup. Prevention of thalidomide- and lenalidomide-associated thrombosis inmyeloma. Leukemia. 2008;22:414-23.34

Risk assessment modelsin hospitalized Medical PatientsIndicationRisk Assessment Model (RAM) for DVT or PE in patients hospitalized formedical conditions.Other thrombotic conditionsPadua prediction scoreFeaturePointsActive cancer* 3Previous DVT or PE (excluding superficial vein thrombosis) 3Reduced mobility** 3Already-known thrombophilic condition*** 3Recent (≤ 1 month) trauma and/or surgery 2Age ≥ 70 years 1Heart and/or respiratory failure 1Acute myocardial infarction or ischemic stroke 1Acute infection and/or rheumatologic disorder 1Obesity (BMI ≥ 30 kg/m 2 ) 1Ongoing hormonal treatment**** 1ProbabilityHigh > 4* Patients with local or distant metastases and/or in whom chemotherapy or radiotherapy have beengiven 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 genemutation, antiphospholipid syndrome**** Hormone replacement therapy or oral contraceptivesInterpretationAmong patients who did not receive prophylaxis, VTE occurred in 11% of thehigh-risk group against 0.3% in the low-risk group. The prevalence of DVT andPE were 6.7% and 3.9% respectively in the high-risk group.35

Other thrombotic conditionsReferences• Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identificationof hospitalized medical patients at risk for venous thromboembolism: the PaduaPrediction 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 Preventionof Thrombosis, 9th ed: American College of Chest Physicians Evidence-BasedClinical Practice Guidelines. Chest. 2012;141(Suppl 2):e195S-226.Geneva prediction scoreFeaturePointsCardiac failure 2Respiratory failure 2Recent stroke 2Recent myocardial infarction 2Acute infectious disease 2Acute rheumatic disease 2Malignancy 2Myeloproliferative syndrome 2Nephrotic syndrome 2History of VTE 2Known hypercoagulability state 2Immobilisation 1Travel > 6hs 1Age > 60 1Obesity (BMI > 30) 1Chronic venous insufficiency 1Pregnancy 1Hormonal therapy 1Dehydration 1InterpretationIndication for thromboprophylaxis if the score is ≥ 3.36

References• Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patientsrequiring thromboprophylaxis. J Thromb Haemost. 2006;4:915-6.• Nendaz M, Spirk D, Kucher N, et al. Multicenter validation of the Geneva riskscore for hospitalized medical patients at risk of venous thromboembolism.Explicit ASsessment of Thromboembolic risk and prophylaxis for Medical Patientsin Switzerland (ESTIMATE). Thromb Haemost. 2014;111:531-8.Other thrombotic conditions37

Other thrombotic conditionsDiagnosis of the antiphospholipid syndromeIndicationAccording to the 2006 Sydney criteria, both clinical and biological featuresshould be associated in the diagnosis of the antiphospholipid antibody syndrome(APS).Diagnostic criteria for APSClinical features aOne or more episodes of venousor arterial thrombosis• Presence of small-vein thrombosisin any organ system• Confirmed by imaging tests(such as ultrasound or Doppler)• Histopathology confirmation: to excludein case of inflammation• Superficial venous thrombosis excludedPregnancy-related complications• One or more unexplained deaths of amorphologically normal foetus at or after10 weeks of gestation, evidenced byultrasound or direct examination of thefoetus• One or more premature births ofmorphologically normal neonate(s) at orbefore 34 weeks gestation associatedwith severe preeclampsia or eclampsia orsevere placenta insufficiency• Three or more unexplained consecutivemiscarriages at or before 10 weeksgestation, with anatomic, genetic andhormonal causes excludedHaemostasis laboratory criteria b1) Lupus anticoagulant:• Prolonged result of a phospholipiddependentclotting assay (e.g., aPTT,dRVVT)• Mixing study: evidence of the LAinhibitory effect• Evidence of phospholipiddependency: Correction by addingphospholipids into coagulation assay(exclusion of specific inhibitors against acoagulation factor)2) Anticardiolipin antibodies:• Normalised ELISA system• Titre > 40 UGPL/UMPL or > 99 thpercentile. IgG and IgM antibodies3) Anti-β 2glycoprotein I antibodies:• Normalised ELISA system• Titre > 99 th percentile. IgG and IgMantibodiesaAPS diagnosis criteria: both clinical and laboratory criteria are requiredbBiological tests should be confirmed at two occasions separated at least by 12 weeks38

Recommendations for the determination of Lupus Anticoagulant1) 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 beforeusing• DO NOT work with filtrated plasmaOther thrombotic conditions2) 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 99 th percentile. Avoid average ± 2 SD• Mixing study– Use a 1:1 proportion between the patient plasma and the normal plasma (poolor commercially certified plasma). NO pre-incubation of sample and activator. Ifusing pool plasma, make sure that the platelet count is lower than 10,000/μL.Cut off value by 99 th percentile or Rosner Index• Confirmation tests: Addition of phospholipids– In dRVVT: generics. In Staclot-LA: hexagonal structureReferences• 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 anupdate 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 theInternational Society on Thrombosis and Haemostasis.Update of the guidelinesfor lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee ofthe International Society on Thrombosis and Haemostasis. J Thromb Haemost.2009;7:1737-40.39

Other thrombotic conditionsDiagnosis of Disseminated Intravascular CoagulationIndicationDisseminated intravascular coagulation (DIC) is a clinical syndromecharacterized 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 andHaemostasis (ISTH)1) Clinical risk assessmentDoes the patient have a disease knownto be associated with DIC? (see table on p. 42)Continue the algorithm onlyif the answer is yes2) Perform a global coagulation evaluationScore global coagulation test results• platelet count (> 100 × 10 9 /L = 0; < 100 × 10 9 /L = 1; < 50 × 10 9 /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 scoreThe scoring system can only be used if an underlying disorder, known to beassociated with DIC, has been diagnosed. The cut-off values for the fibrin-relatedmarker are dependent on the test used. A moderate increase was defined asabove the upper limit of normal and a strong increase as above 5 times theupper limit of normal. A total score of ≥ 5 is compatible with DIC.40

Template for scoring system for non-overt DIC1. Risk assessment: Does the patient have an underlying disorder known to beassociated with DIC (see table on page 42)?yes = 2, no = 0score2. Major criteriaOther thrombotic conditionsplatelet > 100 × 10 9 /L = 0 < 100 × 10 9 /L = 1 rising = –1 stable = 0 falling = 1count +PT < 3 sec = 0 > 3 sec = 1 falling = –1 stable = 0 rising = 1prolongation* +soluble fibrin normal raised falling = –1 stable = 0 rising = 1or FDP’s +3. Specific criteriaantithrombin normal = –1 low = 1protein C normal = –1 low = 14. Calculate scoreA score of 5 or higher is compatibe with non-overt DIC.The score should be repeated daily.41

Other thrombotic conditionsTable 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 rejectionReferences• 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 DisseminatedIntravascular Coagulation (DIC) of the International Society on Thrombosis andHaemostasis (ISTH). Towards definition, clinical and laboratory criteria, and ascoring system for disseminated intravascular coagulation. Thromb Haemost.2001;86:1327-30.• Toh CH, Downey C. Performance and prognostic importance of a new clinical andlaboratory scoring system for identifying non-overt disseminated intravascularcoagulation. Blood Coagul Fibrinolysis. 2005;16:69-74.42

Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP)IndicationTTP is an acute, rare life-threatening thrombotic microangiopathy that requiresrapid diagnosis and treatment.Diagnostic features of thrombotic microangiopathies1. Thrombocytopenia2. Hemolytic anemia3. Renal insufficiency4. Cerebral symptoms5. FeverOther thrombotic conditionsADAMTS13-related parameters in TMAsCongenital TTP Acquired TTP Other TMAsAntigen Very low or absent Low or variable Normal or moderately decreasedActivity ≤ 5% ≤ 5% or variable 30-100%Inhibitor No Mostly yes NoInterpretationTTP results from a deficiency of ADAMTS-13, a serine metalloproteinaserequired for the cleavage of von Willebrand factor.Reference• Shenkman B, Einav Y. Thrombotic thrombocytopenic purpura and other thromboticmicroangiopathic hemolytic anemias: Diagnosis and classification. AutoimmunRev. 2014;13:584-6.43

Other thrombotic conditionsAcute Intestinal Ischemia / ThrombosisManagement of suspected mesenteric ischemiaSuspected mesenteric ischemia (arterial)PeritonitisNo peritonitisLaparotomyCT/CT angiographyRemainingintestinetoo shortRemainingintestinesufficientCentralPeripheralSuspectedNOMINo resectionResectionInterventionalradiologySurgeryInterventionalradiologyInterventionalradiologyCatheterembolectomyand lysis,possibly stentEmbolectomyLysis,vasodilationVasodilation(alsopostsurgeryfollowingrecection)44

Management of patientswith occlusion of the superior mesenteric arteryCT-verified acute SMA occlusionOther thrombotic conditionsNo peritonitisPeritonitisEmbolusThrombosisStentingExploratorylaparotomyNo contraindicationto thrombolysisAspiration ±pharmacologicalthrombolysis ±endovascularmechanicalembolectomyContraindicationto thrombolysisAspiration ±endovascularmechanicalembolectomyOpenembolectomy +completionangiographyEmbolusOpenembolectomy +completionangiography +damagecontrol surgeryThrombosisStenting +damagecontrol surgeryReferences• 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

BleedingISTH bleeding assessment tool for the evaluationof bleeding severityIndicationQuantitative assessment of the severity of bleeding symptoms in patients referredfor the evaluation of a suspected congenital bleeding disorder. Correlation ofclinical 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 beenendorsed by the International Society of Haemostasis and Thrombosis as theresult of experts’ consensus. The bleeding questionnaire allows to accuratelyrecord the worst-ever presentation for each bleeding symptom. The bleedingquestionnaire 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 developedtogether 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 arestrongly encouraged to join the ISTH-BATR initiative, which is provided as afreely available service for the scientific community.Please visit http://www.isth.org/members/group.aspx?id=100549 orhttps://bh.rockefeller.edu/ISTH-BATR/ for full information on how to join theinitiative.2. Bleeding score: The severity of symptoms collected with the bleedingquestionnaire is scored and all obtained values are summed together. The finalresult is the Bleeding Score, an index of the overall severity of the bleedingphenotype.46

Symptoms(up to the time of diagnosis)Bleeding Assessment ToolScoreEpistaxis No / trivial • > 5/year or• more than10 minutesCutaneous No / trivial For bruises 5or more (> 1 cm)in exposed areasBleeding from minorwounds0 1 2 3 4No / trivial • > 5/year or• more than10 minutesConsultation only Packing or cauterizationor antifibrinolyticBlood transfusion or replacement therapy(use of hemostatic blood componentsand rFVIIa) or desmopressinConsultation only Extensive Spontaneous hematoma requiring bloodtransfusionConsultation only Surgical haemostasis Blood transfusion, replacement therapy,or desmopressinOral cavity No / trivial Present Consultation only Surgical haemostasisor antifibrinolyticGastrointestinalbleedingNo / trivial Present(not associatedwith ulcer, portalhypertension,hemorrhoids,angiodysplasia)Hematuria No / trivial Present(macroscopic)Tooth extraction No / trivialor nonedoneSurgery No / trivialor nonedoneReported in ≤ 25%of all procedures,no interventionReported in ≤ 25%of all procedures,no interventionConsultation only Surgical haemostasis,antifibrinolyticConsultation only Surgical haemostasis,iron therapyReported in > 25%of all procedures,no interventionReported in > 25%of all procedures,no interventionBlood transfusion, replacement therapyor desmopressinBlood transfusion, replacement therapyor desmopressinBlood transfusion, replacement therapyor desmopressinResuturing or packing Blood transfusion, replacement therapyor desmopressinSurgical haemostasisor antifibrinolyticBlood transfusion, replacement therapyor desmopressinBleeding47

Symptoms(up to the time of diagnosis)Bleeding Assessment Tool (cont.)ScoreMenorrhagia No / trivial Consultationonly or• Changing padsmore frequentlythan every 2hours or• Clot and floodingor• PBAC score >100Post-partumhemorrhageNo / trivialor nodeliveries0 1 2 3 4Consultationonly or• Use of syntocin or• Lochia > 6 weeksMuscle hematomas Never Post trauma,no therapyHemarthrosis Never Post trauma,no therapy• Time off work/school >2/year or• Requiringantifibrinolytics orhormonal or irontherapy• Iron therapy or• AntifibrinolyticsSpontaneous,no therapySpontaneous,no therapy• Requiring combinedtreatment withantifibrinolytics andhormonal therapy or• Present sincemenarche and > 12monthsRequiring bloodtransfusion, replacementtherapy, desmopressinor requiring examinationunder anaesthesia and/orthe use of uterin balloon/package to tamponadethe uterusSpontaneous ortraumatic, requiringdesmopressinor replacement therapySpontaneous ortraumatic, requiringdesmopressinor replacement therapy• Acute menorrhagia requiring hospitaladmission and emergency treatment orrequiring blood transfusion, replacementtherapy, desmopressin, or• Requiring dilatation & curretage orendometrial ablation or hysterectomyAny procedure requiring critical careor surgical intervention(e.g., hysterectomy, internal iliac artery legation,uterine artery embolization, uterine brace sutures)Spontaneous or traumatic, requiring surgicalintervention or blood transfusionSpontaneous or traumatic, requiring surgicalintervention or blood transfusionCNS bleeding Never Subdural, any intervention Intracerebral, any interventionOther bleedings No / trivial Present Consultation only Surgical haemostasis,antifibrinolyticsBlood transfusion or replacement therapyor desmopressinBleeding48

InterpretationA bleeding score > 3 is considered suggestive for the presence of a bleedingdisorder, warranting a detailed laboratory investigation, whereas a bleedingscore ≤ 3 has negative predictive value of 99.2% in excluding a congenitalbleeding disorder. In a multicentre study using a very similar quantitation ofbleeding symptoms, a bleeding score > 3 in males or > 5 in females showeda sensitivity and specificity for the diagnosis of von Willebrand’s disease of64.2% and 99.1%, respectively.BleedingReferences• Rodeghiero F, Castaman G, Tosetto A, et al. The discriminant power of bleedinghistory 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: astandardized questionnaire and a proposal for a new bleeding score for inheritedbleeding disorders. J Thromb Haemost. 2010;8:2063-5.• Tosetto A, Castaman G, Plug I, et al. Prospective evaluation of the clinical utilityof quantitative bleeding severity assessment in patients referred for hemostaticevaluation. J Thromb Haemost. 2011;9:1143-8.49

BleedingPediatric bleeding assessment tool for the evaluationof bleeding severity in childrenIndicationQuantitative assessment of the severity of bleeding symptoms in young patientsreferred for the evaluation of a suspected congenital bleeding disorder.The Pediatric Bleeding Assessment is formed by two components: the PediatricBleeding Questionnaire (PBQ) and the Bleeding Score, essentially derived fromthe one used by the European Study on type 1 VWD. The Pediatric BleedingAssessment tool was originally developed to evaluate address pediatric-specificbleeding symptoms, and all its items in the questionnaire are now representedalso in the ISTH Bleeding Assessment Tool. The PBQ is however presentedsince many studies in children used this score.1. Pediatric Bleeding Questionnaire (PBQ): The bleeding questionnaireallows to accurately record the worst-ever presentation for each bleedingsymptom. 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 isscored according to the following table and all obtained values are summedtogether. The final result is the Pediatric Bleeding Score, an index of the overallseverity 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 bleedingdisorder. The sensitivity, specificity, positive predictive value and negativepredictive value of the PBQ are 83%, 79%, 0.14, and 0.99 respectively for thediagnosis of von Willebrand’s disease in a secondary care setting. The PBQ isconsistently elevated in children with platelet function disorders.References• Biss TT, Blanchette VS, Clark DS, et al. Quantitation of bleeding symptoms in childrenwith 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 bleedingquestionnaire to assess mucocutaneous bleeding symptoms in children with a plateletfunction disorder. J Thromb Haemost 2010;8:1416-9.• Bowman M, Riddel J, Rand ML, et al. Evaluation of the diagnostic utility for von Willebranddisease of a pediatric bleeding questionnaire. J Thromb Haemost. 2009;7:1418-21.50

Pediatric Bleeding scoreSymptoms ScoreEpistaxis No or trivial(≤ 5 per year)Cutaneous No or trivial(≤ 1 cm)Minour wounds No or trivial(≤ 5 per year)–1 0 1 2 3 4> 5 per year OR> 10 minutesduration> 1 cm ANDno trauma> 5 per yearOR > 5 minutesdurationOral cavity No Reportedat least onceGastrointestinaltractTooth extraction No bleedingin at least2 extractionsSurgery No bleedingin at least2 surgeriesConsultationonlyConsultationonlyConsultationonly orSteristreapsConsultationonlyNo Identified cause ConsultationorspontaneuousNonedone or nobleeding in1 extractionNone doneor nobleedingin 1 surgeryReported,no consultationReported,no consultationConsultationonlyConsultationonlyPacking, cauterizationor antifibrinolyticsSurgical haemostasisor antifibrinolyticsSurgical haemostasisor antifibrinolyticsSurgical haemostasis,antifibrinolytics, bloodtransfusion, replacementetherapy or demopressinResuturing, repackingor antifibrinolyticsSurgical haemostasisor antifibrinolyticsBlood transfusion,replacement therapyor desmopressinBlood transfusion,replacement therapyor desmopressinBlood transfusion,replacement therapyor desmopressinBlood transfusion,replacement therapyor desmopressinBlood transfusion,replacement therapyor desmopressinBleeding51

BleedingPediatric Bleeding score (cont.)Symptoms Score–1 0 1 2 3 4Menorrhagia No Reported orconsultation onlyPost-partum No bleedingin at least2 deliveriesMusclehematomaNo deliveriesor nobleedingin 1 deliveryReported orconsultation onlyNever Post-trauma,no therapyHemarthrosis Never Post-trauma,no therapyCentral nervioussystemAntifibronolyticsor contraceptivepill useD&C or irontherapy orantifibronolyticsSpontaneus,no therapySpontaneus,no therapyD&C or iron therapy Blood transfusion,replacement therapy,desmopressinor hysterectomyBlood transfusion,replacement therapyor desmopressinSpontaneus or traumatic,requiring replacementtherapy or desmopressinSpontaneus or traumatic,requiring replacementtherapy or desmopressinSpontaneusor traumatic, requiringsurgical interventionor blood transfusionSpontaneusor traumatic, requiringsurgical interventionor blood transfusionNever Subdural, any intervention Intracerebral,any interventionOther No Reported Consultation only Surgical haemostasis,antifibrinolytics oriron therapyBlood transfusion,replacement therapyor desmopressin52

Bleeding assessment tool for the evaluationof bleeding severity in immune thrombocytopenia:the SMOG systemBleedingIndicationQuantitative assessment of the severity of bleeding symptoms in patients withimmune 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 standardizedefinitions of bleeding, and to grade symptom-specific and domain-specificbleedings. Bleeding signs/symptoms are grouped according to three majordomains: 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 (gumbleeding, hemorrhagic bullae/blisters, bleeding from bites to lips & tongue or afterdeciduous 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 (SMOGsystem): each bleeding manifestation should be assessed at the time ofexamination. Its severity is graded from 0 to 4. Appreciation of bleeding basedon history only, without supporting medical documentation, will be given agrade 1 designation. Within each domain, the same grading is assigned to thesymptoms judged to have similar clinical relevance. For each symptom, theworst ever episode during the observation period is graded and then the worstepisode within the domain is recorded. For example if the highest grade is 2 forskin, 3 for mucosae and 2 for organs, SMOG is S2M3O2. The index producedby summing the worst ever grade in the 3 domains represents the final score forthat 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 bleedingassessment in immune thrombocytopenia: report from the International WorkingGroup. Blood. 2013;121:2596-606.53

The SMOG systemType of bleeding Grades based on the worst incident episode since last visitPetechiae(does not includesteroid-inducedor senile purpura)SKIN 0 1 2 3 4Ecchymoses None or up to 2in the same bodyarea, but smallerthan a patient’spalm-sized area, if:• spontaneous or• disproportionateto trauma/constrictionSubcutaneoushematomasBleeding from minorwoundsNo • Less than or equal to 10in a patient’s palm-sizedarea in the most affectedbody area• Any number if reportedby the patient• 3 or more in the same bodyarea, but all smaller than apatient’s palm-sized area, if:– spontaneous or– disproportionate to trauma/constriction• At least 2 in two differentbody areas, smaller than apatient’s palm-sized area, if:– spontaneous or– disproportionate to trauma/constriction• Any number and size ifreported by the patientNo • 1 smaller than a patient’spalm-sized area• Any number and size ifreported by the patientNo • Lasting < 5 min• Any episode if reported bythe patientMore than 10 in a patient’spalm-sized area or more than5 in at least 2 patient’s palmsizedareas located in at least2 different body areas, oneabove and one below the belt(in the most affected body areas)From 1 to 5 larger than apatient’s palm-sized area, if:• spontaneous or• disproportionate to trauma/constriction with or withoutsmaller ones• 2 smaller than a patient’spalm-sized area,spontaneous• 2 smaller than a patient’spalm-sized area,disproportionate to traumaLasting > 5 min or interferingwith daily activitiesMore than 50, if scattered bothabove and below the beltMore than 5 larger than apatient’s palm-sized area, if:• spontaneous or• disproportionateto trauma/constriction• More than 2 smaller or at least1 larger than a patient’spalm-sized area, spontaneous• More than 2 smaller or at least1 larger than a patient’spalm-sized area,disproportionate to trauma• Requiring protracted medicalobservation at the timeof this visit• Medical report describingpatient’s evaluationby a physicianBleeding54

The SMOG system (cont.)Type of bleeding Grades based on the worst incident episode since last visitMUCOSAL 0 1 2 3 4Epistaxis No • Lasting < 5 min• Any episode if reportedby the patientOral cavity(gum bleeding)Oral cavity(hemorrhagic bullae or blisters)Oral cavity(bleeding from bites to lips& tongue or after deciduousteeth loss)Subconjunctivalhemorrhage(not due to conjunctivaldisease)No • Lasting < 5 min• Any episode if reportedby the patientNo • Less than 3• Any number if reportedby the patientNo • Lasting < 5 min• Any episode if reportedby the patientNo • Petechiae/hemorrhagepartially involving one eye• Any episode if reportedby the patientLasting > 5 min or interferingwith daily activitiesLasting > 5 min or interferingwith daily activitiesFrom 3 to 10 but no difficultywith masticationLasting > 5 min or interferingwith daily activitiesPetechiae/hemorrhagepartially involving both eyes,or diffuse hemorrhage inone eye• Packing or cauterization orin-hospital evaluationat the time of this visit• Medical report describingpacking or cauterization orin-hospital evaluation• Requiring protracted medicalobservation at the time of thisvisit• Medical report describingpatient’s evaluationby a physicianMore than 10 or more than 5 ifdifficulty with mastication• Interventions to ensurehaemostasis or in-hospitalevaluation at the timeof this visit• Medical report describinginterventions to ensurehaemostasis or in-hospitalevaluationDiffuse hemorrhage in both eyesRBC transfusion or Hbdrop > 2 g/dLBleeding55

BleedingThe SMOG system (cont.)Type of bleeding Grades based on the worst incident episode since last visitORGAN(and internal mucosae)Gastrointestinal bleedingnot explained by visible mucosalbleeding or lesion:• Hematemesis,• Melena,• Hematochezia,• RectorrhagiaLung bleeding• Hemoptysis• Tracheobronchial bleeding0 1 2 3 4No Any episode if reportedby the patientNo Any episode if reportedby the patientHematuria No • Any episode if reportedby the patient• Microscopic (lab analysis)Menorrhagia(compared to pre-ITP or to a phaseof disease with normal platelet count)No • Doubling nr. of pads ortampons in last cyclecompared to pre-ITP orto a phase of diseasewith normal platelet count• Score > 100 using PBACin the last cycle, if normalscore in pre-ITP cycles orin a phase of disease withnormal platelet count• Present at this visit• Described in a medicalreport• Present at this visit• Described in a medicalreport• Macroscopic• Described in a medicalreport• Changing pads morefrequently than every 2 hrs.or clot and flooding• Requiring combinedtreatment withantifibrinolytics and hormonaltherapy or gynecologicalinvestigation(either at this visit or describedin a medical report)• Requiring endoscopy or othertherapeutic procedures or inhospitalevaluation at the timeof this visit• Medical report prescribingendoscopy or other therapeuticprocedures or in-hospitalevaluation• Requiring bronchoscopy orother therapeutic procedures orin-hospital evaluation at the timeof this visit• An equivalent episode ifdescribedin a medical report• Macroscopic, and requiringcystoscopy or other therapeuticprocedures or in-hospitalevaluation at the time of this visit• An equivalent episode ifdescribedin a medical reportAcute menorrhagia requiringhospital admissionor endometrial ablation(either at this visit or describedin a medical report)RBC transfusion orHb drop > 2 g/dLRBC transfusion orHb drop > 2 g/dLRBC transfusion orHb drop > 2 g/dLRBC transfusion orHb drop > 2 g/dL56

The SMOG system (cont.)Type of bleeding Grades based on the worst incident episode since last visitORGAN(and internal mucosae)Intramuscular hematomas(only if diagnosed by a physicianwith an objective method)Hemarthrosis(only if diagnosed by a physicianwith an objective method)Ocular bleeding(only if diagnosed by a physicianwith an objective method)0 1 2 3 4No • Post trauma, diagnosedat this visit, if judgeddisproportionate to trauma• An equivalent episodeif described in a medicalreportNo • Post trauma, diagnosedat this visit, functionconserved or minimallyimpaired, if judgeddisproportionate to trauma• An equivalent episode ifdescribed in a medicalreport• Spontaneous, diagnosed atthis visit• An equivalent episodeif described in a medicalreport• Spontaneous, diagnosedat this visit, functionconserved or minimallyimpaired• An equivalent episode ifdescribedin a medical reportNo • Any post trauma vitreousor retinal hemorrhageinvolving one or both eyeswith or without impaired/blurred vision presentat this visit if judgeddisproportionate to trauma• An equivalent episode ifdescribed in a medicalreport• Spontaneous or post trauma(if judged disproportionate to trauma)diagnosed at this visit andrequiring hospital admission orsurgical intervention• An equivalent episode ifdescribed in a medical report• Spontaneous or post trauma(if judged disproportionate totrauma),diagnosed at this visitand requiring immobilization orjoint aspiration• An equivalent episode ifdescribed in a medical report• Spontaneous vitreousor retinal hemorrhage involvingone or both eyes with impaired/blurred vision present at this visit• An equivalent episode ifdescribed in a medical reportRBC transfusion orHb drop > 2 g/dL• Spontaneous orpost trauma (if judgeddisproportionate to trauma)diagnosed at this visitand requiring surgicalintervention• An equivalent episode ifdescribed in a medicalreport• Spontaneous vitreous orretinal hemorrhagewith loss of vision in oneor both eyes presentat this visit• An equivalent episode ifdescribed in a medicalreportBleeding57

BleedingThe SMOG system (cont.)Type of bleeding Grades based on the worst incident episode since last visitORGAN(and internal mucosae)Intracranial bleeding:intracerebral, intraventricular,subarachnoidal, subdural, extradural(only if diagnosed with an objectivemethod at the visit or described in amedical report provided by the patient)Other internal bleeding:hemoperitoneum, hemopericardium,hemothorax retroperitoneal bleeding,hepatic and splenic peliosis withorgan rupture retroorbital bleeding,metrorrhagia, etc.(only if diagnosed with an objectivemethod at the visit or described in amedical report provided by the patient)0 1 2 3 4No • Any post trauma eventrequiring hospitalizationAny spontaneous event requiringhospitalization in presenceof an underlying intracranial lesionNo Any event requiring hospitalization< 48 hrs.Any spontaneous eventrequiring hospitalizationwithout an underlyingintracranial lesionAny event requiringhospitalization > 48 hrs.or RBC transfusionor Hb drop > 2 g/dL58

Diagnostic and therapeutic algorithm ofHeparin-Induced Thrombocytopenia (HIT syndrome)IndicationHeparin-Induced Thrombocytopenia (HIT) is a serious complication ofanticoagulant therapy with unfractionated heparin and, less frequently, lowmolecular weight heparin, with the formation of abnormal antibodies againstthe heparin/platelet factor-4 (PF4) complex. The syndrome is characterized bythe occurrence of a drop in platelet count associated with venous or arterialthrombotic complications initiated after 5-10 days of treatment with heparin. Inpatients that were earlier exposed to heparin the complication may occur in ashorter time after initiation of heparin treatment.Anticoagulant therapyHIT clinical probability algorithm4T scoreThrombocytopenia• Decrease > 50% and platelets nadir ≥ 20 × 10 9 /L• Decrease 30-50% or platelets nadir = 10-19 × 10 9 /L• Decrease < 30% or platelets nadir < 10 × 10 9 /LTiming 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 1after previous exposition to heparin in day 30-100• Decrease < 4 days with no recent expositionThrombosis or other sequelae• New thrombosis (confirmed); cutaneous necrosis; acute systemicreaction after heparin bolus• Progressive or recurrent thrombosis; non-necrotic cutaneous lesions;suspicion of thrombosis• NoneThrombocytopenia due to other causes• Apparently none• Possible• YesScore21021021021059

Anticoagulant therapyInterpretationAccording to the 4T rule, 3 levels of clinical probability can be defined:• High = 6-8 points• Intermediate = 4-5 points• Low = ≤ 3 pointsOnce the pre-test probabilities are assumed, the HIT diagnostic / therapeuticalgorithm can proceed.Thrombocytopenia in a patientreceiving heparin or LMWHApply clinical scoring systemHigh clinical suspicion(4T’s = 6-8)Discontinue heparin:start alternative therapyImmunoassayIntermediate (4T’s = 4-5)Discontinue heparin:start alternative therapyImmunoassayLow clinicalsuspicionfor HIT(4T’s ≤ 3)Continueheparin therapyPositive HITconfirmed(post-test probabilityof HIT > 95%)Negative HITHIT unlikely(post-test probabilityof HIT~ 3-16%)Positive HITpossible(post-test probabilityof HIT ~ 60%)Negative HITHIT unlikely(post-test probabilityof HIT< 0,5%)ConsiderfunctionalassayPresence ofhigh IgG OD/titerand/or plateletactivating antibodiesincrease HIT likelihood(post-test probability of HIT ~ 65%)Presence oflow IgG OD/titeror lack plateletactivating antibodiesdecrease HIT likelihood(post-test probability of HIT ~ 40%)References• Crowther MA, Cook DJ, Albert M, et al.; Canadian Critical Care Trials Group. The4Ts scoring system for heparin-induced thrombocytopenia in medical-surgicalintensive 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 HematolEduc Program. 2011:143-9.• Warkentin TE, Greinacher A, Koster A, et al.; American College of ChestPhysicians. 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

Bridging strategies in patients on anticoagulantswho need to undergo invasive proceduresIndicationFor patients on vitamin K antagonists requiring a surgical or invasiveprocedure, the question of whether or not to bridge and how to bridge iscommonly encountered in clinical practice.Anticoagulant therapyRisk assessment of thrombosisArterial thrombosisHigh • Atrial fibrillation with CHADS 2score: 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 thrombosisIntermediate • Atrial fibrillation with CHADS 2score: 2-3• Mechanical aortic heart valve without any other risk• Recurrent TIA• Ischemic brain infarct without cardiac embolismLow • Atrial fibrillation with CHADS 2score: 0-1• Cerebrovascular disease without recurrent TIA/infarctionVenous thromboembolismHigh• Recent (< 3 months) venous thromboembolism• Thromboembolism with known thrombophilia• Recurrent idiopathic venous thromboembolismIntermediate Venous thromboembolism 3-6 months agoLowVenous thromboembolism > 6 months ago61

Anticoagulant therapyRisk of thromboembolismHighLowManagement strategy based on risk assessment• Consult withsurgeon 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 LMWH24 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• 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)LowHighRisk of peri-operative bleedingVKA: Vitamin K antagonists; UFH: Unfractionated Heparin; LMWH: Low Molecular Weight Heparin;INR: International Normalized RatioInterpretationPerioperative interruption and bridging strategy based on risk of thromboembolismand risk of perioperative bleeding. Patients with an intermediate risk ofthromboembolism are treated according to the low risk stratum, althoughindividual exceptions may be made based on patient characteristics andpreferences of patients and doctors.References:• Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin asbridginganticoagulation during interruption of warfarin: assessment of astandardized periprocedural anticoagulation regimen. Arch Intern Med.2004;164:1319-26.• Levi M, Eerenberg E, Kamphuisen PW. Periprocedural reversal and bridging ofanticoagulant treatment. Neth J Med. 2011;69:268-73.62

Practical manualof scores and algorithms inhemostasis and thrombosisDiagnostica Stago - 05/2014 - ref.: 28111This booklet was produced with the help ofwww.stago.com