Thromb Haemost 2019; 119(01): 163-174
DOI: 10.1055/s-0038-1676520
Atherosclerosis and Ischaemic Disease
Georg Thieme Verlag KG Stuttgart · New York

Managing Anti-Platelet Therapy in Thrombocytopaenic Patients with Haematological Malignancy: A Multinational Clinical Vignette-Based Experiment

Avi Leader
1   Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
2   Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel
3   Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Vincent Ten Cate
4   Department of Epidemiology, Maastricht University, Maastricht, The Netherlands
,
Arina J. Ten Cate-Hoek
1   Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
5   Thrombosis Expert Center, Maastricht University Medical Center, Maastricht, The Netherlands
,
Galia Spectre
2   Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel
3   Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Erik A. M. Beckers
6   Department of Hematology, Maastricht University Medical Center, Maastricht University, Maastricht, The Netherlands
,
Pia Raanani
2   Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel
3   Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
,
Cinzia Giaccherini
7   Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
David Pereg
3   Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
8   Department of Cardiology, Meir Medical Center, Kfar Saba, Israel
,
Harry C. Schouten
6   Department of Hematology, Maastricht University Medical Center, Maastricht University, Maastricht, The Netherlands
,
Anna Falanga
7   Department of Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Hugo Ten Cate
1   Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
5   Thrombosis Expert Center, Maastricht University Medical Center, Maastricht, The Netherlands
› Author Affiliations
Further Information

Publication History

13 July 2018

25 October 2018

Publication Date:
31 December 2018 (online)

Abstract

Data on anti-platelet therapy (APT) for prevention of atherothrombotic events in thrombocytopaenic cancer patients is lacking. We aimed to identify patient and physician characteristics associated with APT management in thrombocytopaenic patients with haematological malignancy. A clinical vignette-based experiment was designed. Eleven haematologists were interviewed, identifying five variable categories. Next, 18 hypothetical vignettes were generated. Each physician received three vignettes and chose to: hold all APT; continue APT without platelet transfusion support; or continue APT with platelet transfusion support. The survey was distributed to haematologists and thrombosis specialists in three countries. Multivariate cluster robust Poisson regression models were used to calculate relative risks (RRs) of using one management option (over the other) for each variable in comparison to a reference variable. A total of 145 physicians answered 434 cases. Clinicians were more likely to hold APT in case of 20,000/µL platelets (vs. 40,000/µL; RR for continuing: 0.82 [95% confidence interval: 0.75–0.91]), recent major gastrointestinal bleeding (vs. none; RR 0.81 [0.72–0.92]) and when the physician worked at a university-affiliated community hospital (vs. non-academic community hospital; RR 0.84 [0.72–0.98]). Clinicians were more likely to continue APT in ST elevation myocardial infarction with dual APT (vs. unstable angina with single APT; RR 1.31 [1.18–1.45]) and when there were institutional protocols guiding management (vs. none; RR 1.15 [1.03–1.27]). When APT was continued, increased platelet transfusion targets were used in 34%. In summary, the decision process is complex and affected by multiple patient and physician characteristics. Platelet transfusions were frequently chosen to support APT, although no evidence supports this practice.

Supplementary Material

 
  • References

  • 1 Bhatnagar P, Wickramasinghe K, Williams J, Rayner M, Townsend N. The epidemiology of cardiovascular disease in the UK 2014. Heart 2015; 101 (15) 1182-1189
  • 2 Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65 (02) 87-108
  • 3 Vinholt PJ, Alnor A, Nybo M, Hvas AM. Prediction of bleeding and prophylactic platelet transfusions in cancer patients with thrombocytopenia. Platelets 2016; 27 (06) 547-554
  • 4 Ng FH, Wong SY, Chang CM. , et al. High incidence of clopidogrel-associated gastrointestinal bleeding in patients with previous peptic ulcer disease. Aliment Pharmacol Ther 2003; 18 (04) 443-449
  • 5 Ng W, Wong WM, Chen WH. , et al. Incidence and predictors of upper gastrointestinal bleeding in patients receiving low-dose aspirin for secondary prevention of cardiovascular events in patients with coronary artery disease. World J Gastroenterol 2006; 12 (18) 2923-2927
  • 6 Généreux P, Giustino G, Witzenbichler B. , et al. Incidence, predictors, and impact of post-discharge bleeding after percutaneous coronary intervention. J Am Coll Cardiol 2015; 66 (09) 1036-1045
  • 7 Liebman HA. Thrombocytopenia in cancer patients. Thromb Res 2014; 133 (Suppl. 02) S63-S69
  • 8 Stanworth SJ, Estcourt LJ, Powter G. , et al; TOPPS Investigators. A no-prophylaxis platelet-transfusion strategy for hematologic cancers. N Engl J Med 2013; 368 (19) 1771-1780
  • 9 Velders MA, Boden H, Hofma SH. , et al. Outcome after ST elevation myocardial infarction in patients with cancer treated with primary percutaneous coronary intervention. Am J Cardiol 2013; 112 (12) 1867-1872
  • 10 Navi BB, Reiner AS, Kamel H. , et al. Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol 2017; 70 (08) 926-938
  • 11 Del Prete C, Kim T, Lansigan F, Shatzel J, Friedman H. The epidemiology and clinical associations of stroke in patients with acute myeloid leukemia: a review of 10,972 admissions from the 2012 national inpatient sample. Clin Lymphoma Myeloma Leuk 2018; 18 (01) 74-77
  • 12 Feher A, Kampaktsis PN, Parameswaran R, Stein EM, Steingart R, Gupta D. Aspirin is associated with improved survival in severely thrombocytopenic cancer patients with acute myocardial infarction. Oncologist 2017; 22 (02) 213-221
  • 13 McCarthy CP, Steg G, Bhatt DL. The management of antiplatelet therapy in acute coronary syndrome patients with thrombocytopenia: a clinical conundrum. Eur Heart J 2017; 38 (47) 3488-3492
  • 14 Bhatt DL, Stone GW, Mahaffey KW. , et al; CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med 2013; 368 (14) 1303-1313
  • 15 Aspirin in patients with myocardial infarction and thrombocytopenia - full text view - ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT00501345 . Accessed January 25, 2018
  • 16 Sarkiss MG, Yusuf SW, Warneke CL. , et al. Impact of aspirin therapy in cancer patients with thrombocytopenia and acute coronary syndromes. Cancer 2007; 109 (03) 621-627
  • 17 O'Gara PT, Kushner FG, Ascheim DD. , et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 61: 78
  • 18 Amsterdam EA, Wenger NK, Brindis RG. , et al; ACC/AHA Task Force Members; Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130 (25) 2354-2394
  • 19 Kernan WN, Ovbiagele B, Black HR. , et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2014; 45 (07) 2160-2236
  • 20 Iliescu C, Grines CL, Herrmann J. , et al. SCAI expert consensus statement: evaluation, management, and special considerations of cardio-oncology patients in the cardiac catheterization laboratory (Endorsed by the Cardiological Society of India, and Sociedad Latino Americana de Cardiologıa Intervencionista). Catheter Cardiovasc Interv 2016; 87 (05) 895-899
  • 21 Chalayer E, Cavalieri D, Martignoles JA, Genthon A, Tavernier E, Tardy B. Antithrombotic therapy and platelet transfusions in hematologic malignancy patients presenting chemotherapy-induced thrombocytopenia: a French survey. Transfusion 2017; 57 (07) 1717-1723
  • 22 Evans SC, Roberts MC, Keeley JW. , et al. Vignette methodologies for studying clinicians' decision-making: validity, utility, and application in ICD-11 field studies. Int J Clin Health Psychol 2015; 15: 160-170
  • 23 Ten Cate V, Essers BA, Prins MH. Determinants of treatment duration in the prevention of recurrent venous thromboembolism: a protocol for a balanced vignette experiment. BMJ Open 2017; 7 (05) e015231
  • 24 Zou GY, Donner A. Extension of the modified Poisson regression model to prospective studies with correlated binary data. Stat Methods Med Res 2013; 22 (06) 661-670
  • 25 Yusuf SW, Daraban N, Abbasi N, Lei X, Durand JB, Daher IN. Treatment and outcomes of acute coronary syndrome in the cancer population. Clin Cardiol 2012; 35 (07) 443-450
  • 26 Levine GN, Bates ER, Bittl JA. , et al. 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation 2016; 134 (10) e123-e155
  • 27 Urban P, Meredith IT, Abizaid A. , et al; LEADERS FREE Investigators. Polymer-free drug-coated coronary stents in patients at high bleeding risk. N Engl J Med 2015; 373 (21) 2038-2047
  • 28 Valgimigli M, Patialiakas A, Thury A. , et al; ZEUS Investigators. Zotarolimus-eluting versus bare-metal stents in uncertain drug-eluting stent candidates. J Am Coll Cardiol 2015; 65 (08) 805-815
  • 29 Schiffer CA, Bohlke K, Delaney M. , et al. Platelet transfusion for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2018; 36 (03) 283-299
  • 30 Houghton DE, Key NS, Zakai NA, Laux JP, Shea TC, Moll S. Analysis of anticoagulation strategies for venous thromboembolism during severe thrombocytopenia in patients with hematologic malignancies: a retrospective cohort. Leuk Lymphoma 2017; 58 (11) 2573-2581
  • 31 Li A, Davis C, Wu Q. , et al. Management of venous thromboembolism during thrombocytopenia after autologous hematopoietic cell transplantation. Blood Adv 2017; 1 (12) 707-714
  • 32 Samuelson Bannow BT, Walter RB, Gernsheimer TB, Garcia DA. Patients treated for acute VTE during periods of treatment-related thrombocytopenia have high rates of recurrent thrombosis and transfusion-related adverse outcomes. J Thromb Thrombolysis 2017; 44 (04) 442-447
  • 33 Khorana AA, Francis CW, Blumberg N, Culakova E, Refaai MA, Lyman GH. Blood transfusions, thrombosis, and mortality in hospitalized patients with cancer. Arch Intern Med 2008; 168 (21) 2377-2381
  • 34 Baaten CCFMJ, Moenen FCJI, Henskens YMC. , et al. Impaired mitochondrial activity explains platelet dysfunction in thrombocytopenic cancer patients undergoing chemotherapy. Haematologica 2018; 103 (09) 1557-1567
  • 35 Management and outcomes of anti-thrombotic medication use in thrombocytopenia - full text view - ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/show/NCT03288441 . Accessed January 25, 2018
  • 36 Uhl L, Assmann SF, Hamza TH, Harrison RW, Gernsheimer T, Slichter SJ. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood 2017; 130 (10) 1247-1258
  • 37 Roe MT, Messenger JC, Weintraub WS. , et al. Treatments, trends, and outcomes of acute myocardial infarction and percutaneous coronary intervention. J Am Coll Cardiol 2010; 56 (04) 254-263
  • 38 Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. ; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345 (07) 494-502
  • 39 Bhatt DL, Hulot JS, Moliterno DJ, Harrington RA. Antiplatelet and anticoagulation therapy for acute coronary syndromes. Circ Res 2014; 114 (12) 1929-1943
  • 40 Udell JA, Bonaca MP, Collet JP. , et al. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J 2016; 37 (04) 390-399
  • 41 Eikelboom JW, Connolly SJ, Bosch J. , et al; COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017; 377 (14) 1319-1330
  • 42 Vries MJA, van der Meijden PE, Henskens YM, ten Cate-Hoek AJ, ten Cate H. Assessment of bleeding risk in patients with coronary artery disease on dual antiplatelet therapy. A systematic review. Thromb Haemost 2016; 115 (01) 7-24