Risk of bleeding and use of platelet transfusions in patients with hematologic malignancies: recurrent event analysis

Abstract

This study is a further analysis of the TOPPS trial data and assesses patients' baseline characteristics at enrolment, burden of thrombocytopenia, presence of fever and presence of minor hemorrhage as potential risk factors for WHO grade 2 to 4 bleeding. Recurrent event analyses have been used to allow assessment of bleeding over the 30-day trial period and to account for multiple bleeds per patient. MethodsDetails of the UK and Australian TOPPS randomized trial have been published previously .2,8,10 Six hundred patients were randomized to receive either prophylactic platelet transfusions if the platelet count was <10x10 9 /L (n=299), or no prophylaxis (n=301). The trial was approved by independent ethics committees. Although the median number of days with complete data was 30, bleeding data were not complete for all 30 days for all patients. The vast majority of bleeds were inpatient bleeds 8 and, as incomplete records often related to when the patient was at home, no bleeding was assumed on days for which no data were reported.Bleeding types were grouped to describe characteristics of bleeding: skin bruising included petechiae, purpura, and bruising; gastrointestinal bleeding included blood in the stool, melena and hematemesis; mouth bleeding included oral blood blisters and oropharyngeal bleeding; and other included musculoskeletal or deep tissue bleeding, eyes and visual impairment, pleural tap, and cerebral bleeds.For the modeling (Figure 1), patients were grouped by treatment plan [autologous hematopoietic stem cell transplant (HSCT) and chemotherapy (induction and consolidation)/allogeneic HSCT (myeloablative and reduced intensity)] and diagnosis [acute myeloid leukemia (AML), myeloma, lymphoma and other diagnoses]. In contrast to the TOPPS analysis, only the first day of consecutive bruising or petechiae was counted as a bleed, unless bleeding on the subsequent day was worse. Modeling analysisNegative binomial regression 11 was used to model baseline characteristics associated with the number of days of grade 2-4 bleeding (analysis 1). The risk factors considered are shown in Table 1. Previous HSCT (defined as any prior transplant) and relapsed disease were also considered.Recurrent event analysis 12 was used to model the hazard of a grade 2-4 bleed on any one day, accounting for previous bleeds (analyses 2a, 2b and 2c). Robust sandwich variance estimates 12 were used for the hazard confidence intervals. Analysis 2a was the main recurrent event analysis. Analysis 2b was performed on a subset of bleeding records in which the platelet count from all 3 previous days was reported. Analysis 2c was a further subset analysis in which patients' temperature from all 3 previous days Risk factors for bleeding and platelet transfusion haematologica | 2015; 100(6) 741 Figure 1. Shows the number of patients (Np) and number of bleeding records (Nr) included in each part of the analysis.Eight of the 600 patients in the TOPPS trial dataset were not included in the analyses described in this paper: two patients w...

Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial

“…As described, increased overall risk for bleeding correlated with treatment stratum, profoundly low platelet counts (#5 3 10 9 /L), hematocrit of #25%, INR .1.2, and aPTT .30 seconds. The findings echo those reported by others in demonstrating that a large percentage of patients with hypoproliferative thrombocytopenia experience grade 2A bleeding 16 and a minority experience grade 3 and/or 4 bleeding. Given the attendant risks of platelet transfusion (adverse reactions, including septic transfusion reactions), further exploration of the impact of treatment-related risk factors, and careful assessment of posttransfusion impact on bleeding is encouraged.…”

“…5,6,16 Our secondary analysis demonstrated that patients in the AUTO stratum had lower risk for bleeding and thus represent a patient population for which a therapeutic-only platelet transfusion approach could be considered. However, even patients in the AUTO stratum had a high risk of bleeding at platelet counts #5 3 10 9 /L.…”

The association between haemorrhage and markers of endothelial insufficiency and inflammation in patients with hypoproliferative thrombocytopenia: a cohort study

“…Spontaneous extravasation of red cells occurred in patients with prolonged deep thrombocytopenia. In agreement with this finding, a secondary analysis of the TOPPS study revealed that a greater number of days with a platelet count <10 9 10 9 /l is associated with haemorrhage (Stanworth et al, 2015b). However, although a disturbed vascular lining is apparently an important risk for bleeding, surprisingly, laboratory tests do not take vascular integrity into account for transfusion management.…”

Is there a role for proton pump inhibitor prophylaxis in haematology patients?

“…26,28,29 The risk of bleeding is increased in patients taking ibrutinib in combination with aspirin and new oral anticoagulants, and concurrent warfarin therapy is contraindicated. 30 To our knowledge there are no data supporting the use of PPI prophylaxis in patients on ibrutinib and EviQ guidelines do not mention PPI use in these patients.…”

“…Minor bleeding on ibrutinib is common, but grade 3 or higher bleeding rates attributable to the drug are low, and the incidence of GI bleeding specifically is not well documented . The risk of bleeding is increased in patients taking ibrutinib in combination with aspirin and new oral anticoagulants, and concurrent warfarin therapy is contraindicated . To our knowledge there are no data supporting the use of PPI prophylaxis in patients on ibrutinib and EviQ guidelines do not mention PPI use in these patients.…”