Prescribing of anticoagulation is increasing worldwide. This is partly reflective of an aging population with cardiovascular comorbidities such as arrhythmias and prosthetic heart valves, alongside improvements in cancer treatments and survival. In this review, we discuss three common challenges faced by clinicians. These concern the management of patients with thrombosis and thrombocytopenia, resumption of anticoagulation in patients with a history of gastrointestinal or intracranial haemorrhage, and how to approach and treat a patient with recurrent thrombosis on anticoagulation. We consider the available evidence including relevant published recommendations and propose practical management suggestions to aid clinicians faced with these dilemmas.
HoKHvan HoveMLengG.Trends in anticoagulant prescribing: a review of local policies in English primary care. BMC Health Serv Res2020; 20: 279.
2.
CortelezziAMoiaMFalangaAet al. Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: a prospective multicentre study. Br J Haematol2005; 129: 811–7.
3.
KhoranaAAKudererNMCulakovaEet al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood2008; 111: 4902–7.
4.
KopolovicILeeAYWuC.Management and outcomes of cancer-associated venous thromboembolism in patients with concomitant thrombocytopenia: a retrospective cohort study. Ann Hematol2015; 94: 329–36.
5.
Samuelson BannowBTLeeAKhoranaAAet al. Management of cancer-associated thrombosis in patients with thrombocytopenia: guidance from the SSC of the ISTH. J Thromb Haemost2018; 16: 1246–9.
6.
KansuE.Thrombosis in stem cell transplantation. Hematology2012; 17: S159–62.
7.
RodeghieroF.Is ITP a thrombophilic disorder?Am J Hematol2016; 91: 39–45.
8.
RuggeriMTosettoAPalandriFet al. Thrombotic risk in patients with primary immune thrombocytopenia is only mildly increased and explained by personal and treatment-related risk factors. J Thromb Haemost2014; 12: 1266–73.
9.
SarpatwariABennettDLogieJWet al. Thromboembolic events among adult patients with primary immune thrombocytopenia in the United Kingdom General Practice Research Database. Haematologica2010; 95: 1167–75.
10.
SeverinsenMTEngebjergMCFarkasDKet al. Risk of venous thromboembolism in patients with primary chronic immune thrombocytopenia: a Danish population-based cohort study. Br J Haematol2011; 152: 360–2.
11.
SwanDNewlandARodegheiroFet al. Thrombosis in immune thrombocytopenia — current status and future perspectives. Br J Haematol2021; 194: 822–34.
12.
ArepallyGMPadmanabhanA.Heparin-induced thrombocytopenia: a focus on thrombosis. Arterioscler Thromb Vasc Biol2021; 41: 141–52.
13.
WatsonHDavidsonSKeelingD.Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol2012; 159: 528–40.
14.
GreinacherAThieleTWarkentinTEet al. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med2021; 384: 2092–101.
15.
MendolicchioGLRuggeriZM.New perspectives on von Willebrand factor functions in hemostasis and thrombosis. Semin Hematol2005; 42: 5–14.
16.
ScullyMHuntBJBenjaminSet al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. B J Haematol2012; 158: 323–35.
17.
Samuelson BannowBRLeeAYKhoranaAAet al. Management of anticoagulation for cancer-associated thrombosis in patients with thrombocytopenia: a systematic review. Res Pract Thromb Haemost2018; 2: 664–9.
18.
NapolitanoMSacculloGMariettaMet al. Platelet cut-off for anticoagulant therapy in thrombocytopenic patients with blood cancer and venous thromboembolism: an expert consensus. Blood Transfus2019; 17: 171–80.
19.
AgnelliGBecattiniCMeyerGet al. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med2020; 382: 1599–607.
20.
RaskobGEvan EsNVerhammePet al. Edoxaban for the treatment of cancer-associated venous thromboembolism. N Engl J Med2017; 378: 615–24.
21.
YoungAMMarshallAThirlwallJet al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol2018; 36: 2017–23.
22.
RubboliABecattiniCVerheugtFW.Incidence, clinical impact and risk of bleeding during oral anticoagulation therapy. World J Cardiol2011; 3: 351–8.
23.
KhanalNBociekRGChenBet al. Venous thromboembolism in patients with hematologic malignancy and thrombocytopenia. Am J Hematol2016; 91: E468–72.
24.
OaklandKChadwickGEastJEet al. Diagnosis and management of acute lower gastrointestinal bleeding: guidelines from the British Society of Gastroenterology. Gut2019; 68: 776–89.
25.
StrateLLGralnekIM.ACG clinical guideline: management of patients with acute lower gastrointestinal bleeding. Am J Gastroenterol2016; 111: 459–74.
26.
ChristensenHCordonnierCKõrvJet al. European stroke organisation guideline on reversal of oral anticoagulants in acute intracerebral haemorrhage. Eur Stroke J2019; 4: 294–306.
27.
RadaelliFDentaliFRepiciAet al. Management of anticoagulation in patients with acute gastrointestinal bleeding. Dig Liver Dis2015; 47: 621–7.
28.
RuffCTGiuglianoRPBraunwaldEet al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet2014; 383: 955–62.
29.
GrangerCBAlexanderJHMcMurrayJJet al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med2011; 365: 981–92.
30.
GiuglianoRPRuffCTBraunwaldEet al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med2013; 369: 2093–104.
31.
AgenoWVedovatiMCCohenAet al. Bleeding with apixaban and dalteparin in patients with cancer-associated venous thromboembolism: results from the caravaggio study. Thromb Haemost2021; 121: 616–24.
32.
LaneDALipGY.Use of the CHA(2)DS(2)-VASc and HAS-BLED scores to aid decision making for thromboprophylaxis in nonvalvular atrial fibrillation. Circulation2012; 126: 860–5.
33.
WittDMDelateTGarciaDAet al. Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for gastrointestinal tract bleeding. Arch Intern Med2012; 172: 1484–91.
34.
QureshiWMittalCPatsiasIet al. Restarting anticoagulation and outcomes after major gastrointestinal bleeding in atrial fibrillation. Am J Cardiol2014; 113: 662–8.
35.
PatsiasIMittalCElbattaMet al. Optimal duration to restart warfarin after discontinuation of therapy in atrial fibrillation patients that developed gastrointestinal bleeding. J Am Coll Cardiol2013; 61: E342.
36.
SenguptaNFeuersteinJDPatwardhanVRet al. The risks of thromboembolism vs. recurrent gastrointestinal bleeding after interruption of systemic anticoagulation in hospitalized inpatients with gastrointestinal bleeding: a prospective study. Am J Gastroenterol2015; 110: 328–35.
37.
LaineLBarkunANSaltzmanJRet al. ACG clinical guideline: upper gastrointestinal and ulcer bleeding. J Am Gastroenterol2021; 116: 899–917.
38.
SchulmanSBeythRJKearonCet al. Hemorrhagic complications of anticoagulant and thrombolytic treatment: american college of chest physicians evidence-based clinical practice guidelines (8th edition). Chest2008; 133: 257S–98S.
39.
WilsonDSeiffgeDJTraenkaCet al. Outcome of intracerebral hemorrhage associated with different oral anticoagulants. Neurology2017; 88: 1693–700.
40.
SeiffgeDJGoeldlinMBTatlisumakTet al. Meta-analysis of haematoma volume, haematoma expansion and mortality in intracerebral haemorrhage associated with oral anticoagulant use. J Neurol2019; 266: 3126–35.
41.
NielsenPBLarsenTBSkjøthFet al. Outcomes associated with resuming warfarin treatment after hemorrhagic stroke or traumatic intracranial hemorrhage in patients with atrial fibrillation. JAMA Intern Med2017; 177: 563–70.
42.
Al-Shahi SalmanRKeerieCStephenJet al. Effects of oral anticoagulation for atrial fibrillation after spontaneous intracranial haemorrhage in the UK: a randomised, open-label, assessor-masked, pilot-phase, non-inferiority trial. Lancet Neurol2021; 20: 842–53.
43.
HawrylukGWAustinJWFurlanJCet al. Management of anticoagulation following central nervous system hemorrhage in patients with high thromboembolic risk. J Thromb Haemost2010; 8: 1500–8.
44.
MajeedAKimYKRobertsRSet al. Optimal timing of resumption of warfarin after intracranial hemorrhage. Stroke2010; 41: 2860–6.
45.
SteinerTAl-Shahi SalmanRBeerRet al. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke2014; 9: 840–55.
46.
KirchhofPBenussiSKotechaDet al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J2016; 37: 2893–962.
47.
HemphillJCGreenbergSMAndersonCSet al. Guidelines for the management of spontaneous intracerebral hemorrhage. Stroke2015; 46: 2032–60.
48.
LoboJLJiménezDTeresa OrueMet al. Recurrent venous thromboembolism during coumarin therapy. Data from the computerised registry of patients with venous thromboembolism. Br J Haematol2007; 138: 400–3.
49.
KiladjianJJCervantesFLeebeekFWet al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood2008; 111: 4922–9.
50.
HillAKellyRJHillmenP.Thrombosis in paroxysmal nocturnal hemoglobinuria. Blood2013; 121: 4985–96.
51.
ThachilJ.Recurrent venous thromboembolism while on anticoagulant therapy. Blood Rev2012; 26: 175–81.
52.
LeeAYLevineMNBakerRIet al. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med2003; 349: 146–53.
53.
AgnelliGBecattiniCBauersachsRet al. Apixaban versus dalteparin for the treatment of acute venous thromboembolism in patients with cancer: the caravaggio study. Thromb Haemost2018; 118: 1668–78.
54.
KeyNSKhoranaAAKudererNMet al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol2020; 38: 496–520.
55.
WangTFZwickerJIAyCet al. The use of direct oral anticoagulants for primary thromboprophylaxis in ambulatory cancer patients: guidance from the SSC of the ISTH. J Thromb Haemost2019; 17: 1772–8.
56.
PengoVHoxhaAAndreoliLet al. Trial of rivaroxaban in antiPhospholipid syndrome (TRAPS): two-year outcomes after the study closure. J Thromb Haemost2021; 19: 531–5.
57.
KubitzaDBeckaMZuehlsdorfMet al. Effect of food, an antacid, and the H2 antagonist ranitidine on the absorption of BAY 59-7939 (rivaroxaban), an oral, direct factor Xa inhibitor, in healthy subjects. J Clin Pharmacol2006; 46: 549–58.
58.
MartinKALeeCRFarrellTMet al. Oral anticoagulant use after bariatric surgery: a literature review and clinical guidance. Am J Med2017; 130: 517–24.
59.
KeelingDBaglinTTaitCet al. Guidelines on oral anticoagulation with warfarin – fourth edition. Br J Haematol2011; 154: 311–24.
60.
CarrierMLe GalGChoRet al. Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients. J Thromb Haemost2009; 7: 760–5.
