Continuous Platelet Transfusion Increases Platelet Increment in Refractory Hemato-Oncological Patients – a Single Center Experience

Background: Refractoriness to platelet transfusion is prevalent among 15-25% of hemato-oncology patients. Refractoriness has been linked to inferior clinical outcomes, including bleeding and mortality, as well as higher health care costs. Suggested etiologies to refractoriness include both non-immune and immune causes. Methods to manage refractoriness include leuko-reduction, HLA- and HPA- matched platelets, use of ABO compatible transfusions and platelet cross-matching. Leuko-reduction has been proven to decrease the rates of allo-immunization and is widely used in hemato-oncology units. Other methods have demonstrated modest effectiveness in some studies, but some of these (HLA- and HPA- matched platelets) are not widely available. There are only a few reports in the literature of continuous platelet transfusion (CPT) as an alternative method for increasing post-transfusion platelet increments. Those reports prompted the current analysis of CPT in platelet refractory patients.

Aim: To evaluate the effectiveness of CPT in producing satisfactory platelet increments in refractory patients compared to the standard care of routinely prepared single donor platelet transfusions.

Patients and Methods: Patients included in this study were treated for hematological malignancies in our Institution between January 2007 and December 2013. A retrospective analysis of the increment of platelets achieved in refractory patients was performed. Refractoriness was defined as a corrected calculated increment (CCI) less than 10,000 platelets per micro-liter following two successive platelet transfusions. The CCI was calculated as PPI (post-transfusion platelet count minus pre-transfusion platelet count) x BSA (body surface area measured in square meters m2) x 10¹¹/number of platelets transfused. All refractory patients included in this analysis received single donor platelet transfusions. The practice of CPT was adopted by us in March 2008. All refractory patients who received CPT between March 2008 and December 2013 were included. These patients received a continuous 24 hour transfusion of single donor platelet units, each dose given over 4 to 6 hours, comprising of 1.5 x 10¹¹ platelets and equaling to half a single donor platelet unit. Their outcome was compared with that of our refractory patients treated with single donor transfusions in the routine manner, between January 2007 and March 2008 (i.e. before the introduction of CPT). The CCI was used to monitor the effectiveness of each platelet unit at 12 and 24 hours post-transfusion intervals. To account for prior antigen-exposure of the patients, we chose to include for each patient the 11^th consecutive platelet transfusion. Factors known to contribute to the development of refractoriness, such as infection, disseminated intravascular coagulation (DIC) and splenomegaly were evaluated for impact on the CCI. The statistical analysis was generated using SAS Software, Version 9.4. Continuous variables were presented as mean ± STD, Categorical variables were presented by (N, %). t-tests and non-parametric Wilcoxon tests were used to compare the value of continuous variables between study groups.

Results: Twenty eight patients with hematologic malignancies received at least eleven single-donor platelet transfusions during 2007-2013. Twenty one of the 28 patients received CPT due to refractoriness and seven patients were treated before the introduction of this approach. CPT resulted in a significantly higher post-transfusion mean increment at 24 hours (1.16 vs. 0.37, p<0.05). Increments were higher, albeit not significantly, at 12 hours post-transfusion in the CPT group (2.45 vs. 0.36, p=0.058). Patient's gender, age (younger than 35 years old versus older), renal failure, high grade fever, infection and DIC, splenomegaly or donor-recipient ABO compatibility were not found to significantly influence the increment.

Conclusions: CPT results in significantly higher increments at 24 hours post-transfusion, and therefore suggest an effective approach to the treatment of platelet refractoriness in patients treated for hematological malignancies.