Risk factors for bleeding in haemato-oncology patients-a nested case-control study: The BITE study protocol (Bleeding In Thrombocytopenia Explained)

Abstract

Introduction: Haemato-oncological patients often receive platelet count driven prophylactic platelet transfusions to prevent bleeding. However, many prophylactically transfused patients still bleed. More knowledge on risk factors for bleeding is therefore needed. This will enable identification of bleeding risk profiles on which future transfusion policy can be optimised. The present BITE study (Bleeding In Thrombocytopenia Explained) aims to identify clinical conditions and biomarkers that are associated with clinically relevant bleeding events.

Methods and analysis: A matched case-control study nested in a cohort of haemato-oncological patients in the Netherlands. We collect a limited number of variables from all eligible patients, who together form the source population. These patients are followed for the occurrence of clinically relevant bleeding. Consenting patients of the source population form the cohort. Cases from the cohort are frequency matched to selected control patients for the nested case-control study. Of both case and control patients more detailed clinical data is collected.

Study population: Adult haemato-oncological patients, who are admitted for intensive chemotherapeutic treatment or stem cell transplantation, or who received such treatments in the past and are readmitted for disease or treatment-related adverse events.

Statistical analysis: Bleeding incidences will be calculated for the total source population, as well as for different subgroups. The association between potential risk factors and the occurrence of bleeding will be analysed using conditional logistic regression, to account for matching of case and control patients.

Ethics and dissemination: The study was approved by the Medical Research Ethics Committee Leiden Den Haag and Delft, and the Radboudumc Committee on Research Involving Human Subjects. Approval in seven other centres is foreseen. Patients will be asked for written informed consent and data is coded before analyses, according to Dutch privacy law. Results will be published in peer-reviewed journals.

Trial registration number: NL62499.058.17. NCT03505086; Pre-results.

Keywords: haemato-oncology; haemorrhage; platelet transfusion; risk factors.

Conflict of interest statement

Competing interests: JJZ reports that the Leiden University Medical Center, his employer, is structurally compensated for his work on blood transfusion medicine by Dutch Blood Supply organisation Sanquin, also during the conduct of the study. The other authors declare no conflicts of interest.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

The source population consists of all patients fulfilling the eligibility criteria. The source population will be used for calculation of incidence rates. For this purpose, minimal data are collected. The cohort population consists of all consenting patients in the source population. Case identification and control selection is performed from the cohort population. The case–control study is performed with consenting patients who have clinically relevant bleeding during admission (cases) and one to four matched controls per case. This population will be used for estimating rate ratios for different potential risk factors and the occurrence of clinically relevant bleeding and developing a prediction score. For these purposes, extensive data collection is performed.

Figure 2

Graphic explaining the index period used for data collection. t0=first day of treatment or day of admission, tn=index day: treatment day or admission day and bleeding day for cases. Matching was performed for hospital of admission, diagnosis and admission indication.

Figure 3

Lines indicate the number of cases needed to achieve 80% power to detect a statistically significant difference (ie, type 1 error rate smaller than 5%), at different exposure prevalences, if the true relative risk is 2. Ratio indicates the ratio of cases to controls. At a ratio of 1:4 fewer cases will always be needed to achieve the same power, compared with the other rate ratios causing the 1:4 line to be entirely below the 1:1, 1:2 and 1:3 lines. The more controls per case, the fewer cases we need to achieve this power.