Platelet Transfusion-Sparing Regimens for Severe Thrombocytopenia in Patients Undergoing Autologous Stem Cell Transplantation - a Comparative Retrospective Analysis

Background

Severe pancytopenia requiring transfusion support is often seen in patients with multiple myeloma, Hodgkin Lymphoma and non-Hodgkin Lymphoma following high dose chemotherapy and autologous stem cell transplant (ASCT). Certain patients do not accept blood products for various medical, ethical or religious reasons, therefore safe alternatives to transfusions are necessary. While there are studies evaluating the efficacy of alternative regimens used along with prophylactic and therapeutic platelet transfusion to control bleeding events, there are not many studies investigating the use of transfusion-sparing regimens alone in ASCT patients. We compared the incidence of bleeding and thrombotic events between transfusion-supported (TS) patients and transfusion-free (TF) patients (who did not accept blood products). This is to assess the efficacy of alternative therapies like antifibrinolytics and Vitamin K in comparison with platelet transfusion regimens in patients who received ASCT for various malignancies.

Methods

This is a retrospective analysis including adult patients who underwent ASCT at Pennsylvania Hospital of the University of Pennsylvania from 2016 to 2024. Data was extracted through chart review. TS patients received prophylactic and therapeutic platelet transfusions as per standard guidelines. TF patients were managed with supplemental vitamin K, and antifibrinolytics like IV/oral aminocaproic acid or tranexamic acid as primary measures, along with GI prophylaxis, stool softeners and holding anticoagulation/antiplatelet when platelets are <30,000/uL. Secondary measures including cryoprecipitate, desmopressin, and/or nasal vasoconstrictors were occasionally used in case of refractory bleeding. Bleeding events were evaluated using CTCAE (C) grading schema. A chi-square test was used to compare bleeding frequencies between the two groups. Statistical analysis to identify differences was set at α=0.05 or less. Maximum type I error rate of p=0.05 was used.

Results

A total of 100 patients who underwent ASCT were included. Out of the 100 patients, 50 were TS patients and 50 were TF patients. The median platelet count for all patients was 12x103/µL. For the TS group, median platelet count was 17.5x103/µL and median platelet nadir was 12x103/µL. For the TF group, median platelet count was 9x103/µL and platelet nadir was <4x103/µL.

Four out of 50 patients in the TS group (8% of TS) and seven out of 50 patients in the TF group (14% of TF) had bleeding events greater than or equal to CTCAE grade 1 and were not statistically different (p=0.33; α=0.05).Most of these bleeding events were spontaneous, however there were 4 instances in which the bleeding events were provoked by either traumatic foley placement/removal, peripheral intravenous catheter insertion or mechanical fall. Bleeding events in the TS group included spontaneous petechiae (C1), spontaneous epistaxis requiring ENT intervention with nasal packing (C3) or requiring topical vasoconstrictors (C2) and subdural hematoma post mechanical fall (C3). Bleeding events in the TF group included spontaneous microscopic hematuria (C1), traumatic macroscopic hematuria (C1), spontaneous petechiae/ecchymoses (C1-2), subconjunctival hemorrhage (C1), hematemesis (C2), vaginal (C1) and rectal bleeding (C1). Transplant related mortality occurred in 1 patient in the TF group due to delayed engraftment and septic shock due to typhlitis. Eight patients in the TF group (16% of TF) developed deep vein thrombosis (DVT) associated with peripherally inserted central catheters which were treated without further complications.

Conclusion

Our study demonstrates the effectiveness of platelet transfusion-sparing regimens in ASCT. The overall bleeding outcomes with transfusion regimens (TS group) are similar to the transfusion-sparing regimens alone (TF group). While an increased incidence of provoked DVT is noted in the TF group, these cases were managed uneventfully with conventional anticoagulation. With adequate resources at experienced centers, thrombocytopenia in ASCT can be safely managed with appropriate use of transfusion-sparing regimens in patients who refuse the use of blood products. Similarly, use of alternative regimens may be considered as an effective therapy to prevent bleeding in patients with platelet transfusion refractoriness. Future research to investigate should be considered.