BITE study

Background

Thrombocytopenic hemato-oncology patients have a risk of minor and major bleeding events. Because of the low platelet count prophylactic transfusions are given frequently, mostly at a trigger of 10x109 platelets/L. Despite the prophylactic transfusion strategies almost half of the patients still experience bleeding of WHO grade >2 [1, 2]. The proportions of grade 3 or 4 bleedings are smaller, though of more clinical relevance because these bleedings lead to more medical interventions and / or lead to more morbidity or mortality.  
The efficiency of a prophylactic transfusion strategy seems to differ in different patient groups, for instance AML patients experience bleeding despite platelet transfusions more often than patients who receive a autologous stem cell transplantation [3].  Subanalysis of the data of the TOPPS trial [2] also fever and female sex seemed to be associated with days of bleeding [4]. The etiology of bleeding in this population is not fully understood and there is little known about other possible risk factors for bleeding. To be able to give efficient prophylactic transfusions to the patients who need it and to withhold transfusions in patients who are not likely to benefit from the prophylactic transfusion strategy, more knowledge is needed of the different risk factors of bleeding in thrombocytopenic hemato-oncology patients.

Objectives

BITE case control study

To assess the different risk factors and their relative contributions for severe bleeding events ( WHO grade 3-4). Potential risk factors included are clinical data, routinely performed laboratory data and additional laboratory tests of biomarkers of hemostatic biomarkers and biomarkers for endothelial damage. 
To be able to identify thrombocytopenic hemato-oncology patients in future who are more likely to experience severe bleeding, and who are more likely to benefit from prophylactic transfusions
Furthermore we plan to set up another part of the BITE study where we want to obtain sequent laboratory measurements of biomarkers of hemostasis, coagulation and endothelial damage to investigate biomarker changes over time during treatment.  (details following)

Study design

We are conducting a multicenter prospective case control study in which patient with grade 3 or 4 bleeding will be matched to two control groups. One control group consists of 4 matched controls per case. The controls will be matched on disease, hospital, treatment phase and proximity in time. The second control group will only focus on admissions for different disease types and treatment phases. The second control group is made to be able to assess the variables on which patients are matched as possible risk factors. First however, a pilot will be performed to assess if given the number of cases and possible controls a case control study will be feasible or if a case cohort study should be performed.

Study population

Thrombocytopenic hemato-oncology patients with grade 3-4 bleeding (cases) and without grade 3-4 bleeding (controls).

Main study outcome

Identification of risk factors for severe bleeding in hemato-oncology patients and quantification of the relative contribution of (combined) risk factors.

Research Staff

• L.L. Cornelissen MD PhD student. ¹
• R.A Middelburg PhD. ^1,2
• Prof JJ Zwaginga MD, PhD ^1,3

1 Center for Clinical Transfusion Research, Sanquin Research, Leiden
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden
Jon J van Rood Center for Clinical Transfusion Research, Sanquin-Leiden University Medical Center, Leiden
2 Department of Clinical Epidemiology, Leiden University Medical Center, Leiden
3 Department of Blood Transfusion Medicine, LUMC, Leiden

 

1. Ypma, PF et al. The observation of bleeding complications in haemato-oncological patients: stringent watching, relevant reporting. Transfus Med. 2012;22(6):426-31.
2. Stanworth SJ et al., A no-prophylaxis platelet-transfusion strategy for hematologic cancers. N Engl J Med. 2013;368(19):1771-80.
3. Stanworth SJ et al. Impact of prophylactic platelet transfusions on bleeding events in patients with hematologic malignancies: a subgroup analysis of a randomized trial. Transfusion. 2014;54(10):2385-93.
4. Stanworth SJ et al. Risk of bleeding and use of platelet transfusions in patients with hematologic malignancies: recurrent event analysis. Haematologica. 2015;100(6):740-7.