How I safely transfuse patients with sickle-cell disease and manage delayed hemolytic transfusion reactions

Abstract

Transfusions can be a life-saving treatment of patients with sickle-cell disease (SCD). However, availability of matched units can be limiting because of distinctive blood group polymorphisms in patients of African descent. Development of antibodies against the transfused red blood cells (RBCs), resulting in delayed hemolytic transfusion reactions (DHTRs), can be life-threatening and pose unique challenges for this population with regard to treatment strategies and transfusion management protocols. In cases where the transfused cells and the patient's own RBCs are destroyed, diagnosis of DHTR can be difficult because symptoms may mimic vaso-occlusive crisis, and frequently, antibodies are undetectable. Guidelines are needed for early diagnosis of DHTR because treatment may need to include temporarily withholding any new transfusions to avoid further hemolysis. Also needed are case-control studies to optimally tailor treatments based on the severity of DHTR and develop preventive transfusion strategies for patients at DHTR risk. Here, we will review gaps in knowledge and describe through case studies our recommended approach to prevent alloimmunization and to diagnose and treat symptomatic DHTRs for which complementary mechanistic studies to understand their pathogenesis are sorely needed.

Complement activation during intravascular hemolysis: Implication for sickle cell disease and hemolytic transfusion reactions

“…DHTR is classically caused by a secondary immune reaction where alloantibodies undetectable at the time of transfusion rebound following exposure to the corresponding RBC antigens, leading to the RBC destruction. DHTR occurs between 3 and 22 days after RBC transfusion (69), in around 3-8% of transfused SCD patients (70)(71)(72), which in 4-12% of DHTR can be fatal (69,71,73,74). It remains poorly recognized, mostly because it mimics an acute painful crisis.…”

“…Regarding preventive treatment, rituximab has been recently used with success in hyperimmunized patients considered to be at high risk of developing DHTRs (73,130,131). A potential role of prophylactic Eculizumab needs to be assessed, in particular in patients with recurrent antibodynegative DHTR.…”

Two Consecutive Episodes of Severe Delayed Hemolytic Transfusion Reaction in a Sickle Cell Disease Patient

“…is is important also because patients may be treated at different institutions over the course of a lifetime, and without universal medical records, they may receive transfusions of blood with antibodies "lost to follow-up". Moreover, follow-up screenings at regular intervals following a diagnosed DHTR will increase the likelihood of detecting new alloantibodies [9].…”

Successful management of the potentially fatal hyperhaemolysis syndrome of sickle cell anaemia with a regimen including bortezomib and Hemopure

“…5 Activation of cytokine and complement pathways has also been implicated 2,3 Since the immune system is thought to be a key player in the haemolytic process, immunosuppressive strategies have been applied including the use of steroids, intravenous immune globulin, rituximab and eculizumab. [7][8][9][10] However, responses to these treatments have not been uniform and optimal treatment of HHS has not been clearly defined. Because of the rarity of this syndrome, large clinical trials have not been performed.…”