Challenges in the treatment and prevention of delayed hemolytic transfusion reactions with hyperhemolysis in sickle cell disease patients

Abstract

BACKGROUND Delayed hemolytic transfusion reactions (DHTRs) are serious complications of RBC transfusion that can occur in previously alloimmunized patients. Patients who require episodic transfusions during heightened inflammatory states, such as patients with sickle cell disease (SCD), are particularly prone to alloimmunization and developing DHTRs with hyperhemolysis. While efforts to mitigate these hemolytic episodes via immunosuppressive drugs can be employed, the relative efficacy of various treatment options remains incompletely understood. CASE REPORTS In this study, we explored five patients with SCD and multiple RBC alloantibodies who received various forms of immunosuppressive therapy in an attempt to prevent or treat severe DHTRs. RESULTS The clinical course for these five patients provides insight into the difficulty of effectively treating and preventing DHTRs in patients with SCD with currently available immunosuppressive therapies. CONCLUSION Based on our experience, and the current literature, it is difficult to predict the potential impact of various immunosuppressive therapies when seeking to prevent or treat DHTRs. Future mechanistic studies are needed to identify the optimal treatment options for DHTRs in the presence or absence of distinct alloantibodies in patients with SCD.

Peripartum hyperhemolysis prophylaxis and management in sickle cell disease: A case report and narrative review

“…9 HS is unique among DHTRs as both transfused and native RBCs are consumed by hemolysis. 2 HS is a complex entity and its pathophysiology is poorly understood. Suspected mechanisms include activated macrophages consuming RBCs with exposed phosphatidylserine domains, excessive complement activation, and concomitant reticulocytopenia.…”

“…Immunosuppressive agents that have been used successfully for HS treatment include corticosteroids, IVIG, rituximab, eculizumab, bortezomib, and tocilizumab. 2,4,33,34 In many published cases of HS, multiple agents were used in combination. Data on the use of immunosuppressants for the prevention of DHTR/HS in SCD are sparse, but rituximab and bortezomib have been used successfully in case reports/series outside of pregnancy.…”

“…Data on the use of immunosuppressants for the prevention of DHTR/HS in SCD are sparse, but rituximab and bortezomib have been used successfully in case reports/series outside of pregnancy. 2,6 Mechanistically rituximab may have utility in cases where a new alloantibody has been detected, while bortezomib may be beneficial in antibody-negative cases of DHTR/HS. 2 Data on the use and safety of rituximab and eculizumab for any indication during pregnancy are limited, with only case series and cohort studies.…”

“…Hyperhemolysis syndrome (HS) is the most severe form of DHTR in patients with SCD, in which both transfused and native red blood cells (RBCs) are destroyed. 1,2 Further transfusions are relatively contraindicated after a history of HS. Immunomodulatory agents can be used as prophylaxis against life-threatening hemolysis when transfusion is necessary.…”

“…Immunomodulatory agents can be used as prophylaxis against life-threatening hemolysis when transfusion is necessary. [2][3][4] There is a paucity of evidence for the use of HS prophylaxis before transfusions, the continuation of hydroxyurea (HU) in lieu of chronic transfusion, and the use of erythropoiesisstimulating agents (ESA) in pregnant SCD patients. We present a case of a pregnant patient with SCD and a previous history of HS and the multidisciplinary approach to management that was applied.…”