Anti‐N and anti‐Do^a immunoglobulin G alloantibody–mediated delayed hemolytic transfusion reaction with hyperhemolysis in sickle cell disease treated with eculizumab and HBOC‐201: case report and review of the literature

Abstract

BACKGROUND Delayed hemolytic transfusion reaction (DHTR) with hyperhemolysis is a potentially fatal complication resulting from alloimmunization that can cause severe hemolysis of both transfused and intrinsic red blood cells (RBCs). Patients with sickle cell disease often receive multiple RBC units during their lifetime and thus are likely to develop alloantibodies that increase the risk for DHTR. Treatment to decrease hemolysis includes intravenous immunoglobulin (IVIG), steroids, eculizumab, rituximab, and plasmapheresis in addition to erythropoietin (EPO), intravenous (IV) iron, vitamin B12, and folate to support erythropoiesis. RBC transfusion is preferably avoided in DHTR due to an increased risk of exacerbating the hemolysis. CASE REPORT We report a rare case of anti‐N and anti‐Doa immunoglobulin (Ig)G alloantibody–mediated life‐threatening DHTR with hyperhemolysis in a patient with hemoglobin SS after RBC transfusion for acute chest syndrome who was successfully treated with eculizumab and HBOC‐201 (Hemopure) in addition to steroids, IVIG, EPO, IV iron, and vitamin B12. HBOC‐201 (Hemopure) was successfully used as a RBC alternative in this patient. CONCLUSION Anti‐N and anti‐Doa IgG alloantibodies can rarely cause severe life‐threatening DHTR with hyperhemolysis. HBOC‐201 (Hemopure) can be a lifesaving alternative in this scenario. Our report also supports the use of eculizumab in DHTR; however, prospective studies are needed to determine the appropriate dose and sequence of eculizumab administration.

Red cell transfusion and alloimmunization in sickle cell disease

“…84,85 Eculizumab, a monoclonal anti-C5 antibody targeting terminal complement activation, has been used as salvage therapy in cases of severe DHTR and hyperhemolysis. [85][86][87][88][89][90][91][92] Case reports have also described treatment of hyperhemolysis with tocilizumab, a monoclonal antibody against the interleukin-6 receptor. [93][94][95] These cases showed marked improvement after targeted antiinterleukin-6 receptor therapy, suggesting that blockade of macrophage activation may be an effective treatment strategy.…”

Hemoglobin-Based Oxygen Carriers: Potential Applications in Solid Organ Preservation

“…This is possible because methemoglobin is washed out of the perfusion fluid before transplantation, making the amount of methemoglobin that eventually reaches the recipient's circulation negligible. Moreover, supplementation with additional HBOC-201, glutathione, vitamin C, and methylene blue also corrected or slowed the increased percentage of methemoglobin caused by HBOCs (de Vries et al, 2019;Mackenzie et al, 2010;Unnikrishnan et al, 2019). Therefore, applying conventional preservation solutions with added HBOCs to the preservation of isolated organs can adequately improve the oxygenation of tissues with fewer side effects.…”

Anti-C5 antibody treatment for delayed hemolytic transfusion reactions in sickle cell disease

“…1,7 Other teams have also treated DHTR in patients with and without detectable allo-or auto-antibody formation with Eculizumab, with promising results. [8][9][10][11] The American Society of Hematology (ASH) guidelines include a conditional recommendation for the use of anti-C5 antibodies in patients with SCD presenting DHTR and ongoing hyperhemolysis, based on currently very low levels of certainty. 12 This retrospective study focuses on the biological and clinical findings and the effects of anti-C5 therapy on DHTR, for patients treated between 2013 and 2019 who experienced particularly severe DHTR.…”

“…Aline Floch, 1 Alexandre Morel, 2 Fabian Zanchetta-Balint, 2 Catherine Cordonnier-Jourdin, 3 Slimane Allali, 4 Maximilien Grall, 5 Ghislaine Ithier, 6 Benjamin Carpentier, 7 Sadaf Pakdaman, 1 Jean-Claude Merle, 8 Radjiv Goulabchand, 9 Tackwa Khalifeh, 10 Ana Berceanu, 11 Cećile Helmer, 12 Christelle Chantalat-Auger, 13 Véronique Frémeaux-Bacchi, 14 Marc Michel, 15 Mariane de Montalembert, 4 Armand Mekontso- Dessap, 16 France Pirenne, 1…”