Exploring the components of bleeding outcomes in transfusion trials for patients with hematologic malignancy

Department of Oncology, Division of Malignant Hematology, Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada. Department of Medicine, McMaster Centre for Transfusion Research, McMaster University, Hamilton, Ontario, Canada. Department of Product and Process Development, Sanquin Blood Bank, Amsterdam, the Netherlands. Department of Hematology, Haga Teaching Hospital, The Hague, the Netherlands. Department of Medicine, Division of Hematology, McMaster University, Hamilton, Ontario, Canada. Canadian Blood Services, Hamilton, Ontario, Canada.

Transfusion. 2020
PICO Summary

Population

Patients with haematologic malignancies and chemotherapy-induced thrombocytopenia (3 randomised controlled trials (RCTs), n= 315).

Intervention

Less severe bleeds (WHO Grades 1 and 2).

Comparison

More severe bleeds (WHO Grades 3 and 4).

Outcome

The total data aggregated from the 3 RCTs was 5476 daily bleeding assessments, 61.8% with a bleed documented. A total of 98.3% were Grade 1 and 2 bleeds and 1.7% were Grades 3 and 4. Grade 1 and 2 bleeds were composed of 20 different bleeding signs and symptoms. Haematuria was associated with incident Grade 3 or 4 bleeds. In patients with hematologic malignancy, only haematuria was associated with more severe incident bleeds.
Abstract
Clinically significant bleeding in patients with hematologic malignancies is a heterogeneous composite outcome currently defined as World Health Organization (WHO) bleeding Grades 2, 3, and 4. However, the clinical significance of some minor bleeds categorized as WHO Grades 1 and 2 remains controversial. We analyzed the number and frequency of individual signs and symptoms of WHO Grades 1 and 2 bleeds and explored their association with more severe incident bleeds graded as WHO Grades 3 and 4. STUDY DESIGN AND METHODS We aggregated daily bleeding assessment data from three randomized controlled trials conducted in patients with hematologic malignancies that used bleeding as an outcome. Cox proportional hazard regression analysis was used to identify signs and symptoms categorized as WHO Grades 1 and 2 bleeds that were associated with more severe bleeds (Grades 3 and 4). RESULTS We collected data from 315 patients (n = 5476 daily bleeding assessments; 3383 [61.8%] with a bleed documented). A total of 98.3% (3326/3383) were Grade 1 and 2 bleeds and 1.7% (57/3383) were Grades 3 and 4. Grade 1 and 2 bleeds were composed of 20 different bleeding signs and symptoms. Hematuria (hazard ratio, 16.1; 95% confidence interval, 4.4-59.2; P < .0001) was associated with incident Grade 3 or 4 bleeds. CONCLUSION In patients with hematologic malignancy, only hematuria (microscopic and/or macroscopic) was associated with more severe incident bleeds. This findings require validation in independent data sets.
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine