Hyperhaemolytic Syndrome in Sickle Cell Disease: Clearing the Cobwebs

Abstract

Sickle cell anaemia presents with a dynamic background haemolysis and deepening anaemia. This increases the demand for transfusion if any additional strain on haemopoiesis is encountered due to any other physiological or pathological. Patients with cerebrovascular accident are placed on chronic blood transfusion; those with acute sequestration and acute chest syndrome are likewise managed with blood transfusion. These patients are prone to develop blood transfusion complications including alloimmunization and hyperhaemolytic syndrome (HHS). This term is used to describe haemolysis of both transfused and ‘own’ red cells occurring during or post-transfusion in sickle cell patients. Hyperhaemolysis results in worsening post-transfusion haemoglobin due attendant haemolysis of both transfused and autologous red cells. The mechanism underlying this rare and usually fatal complication of sickle cell has been thought to be secondary to changes in the red cell membrane with associated immunological reactions against exposed cell membrane phospholipids. The predisposition to HHS in sickle cell is also varied and the search for a prediction pattern or value has been evasive. This review to discusses the pathogenesis, risk factors and treatment of hyperhaemolytic syndrome, elaborating what is known of this rare condition.

Acute Hyperhemolysis Syndrome in a Patient with Known Sickle Cell Anemia Refractory to Steroids and IVIG Treated with Tocilizumab and Erythropoietin: A Case Report and Review of Literature

“…This diagnosis of HHS can be made when the ratios of HbS and HbA both decrease concurrently after a transfusion, indicating lysis of autologous and transfused red blood cells. In DHTR, only HbA falls, indicating destruction of transfused red blood cells [ 10 ]. HHS can be further divided into acute and delayed forms, where the acute variant occurs within seven days of transfusion, and the chronic variant occurs after seven days [ 11 ].…”

“…The mechanism of hyperhemolysis syndrome is thought to be due to changes in the red blood cell membrane coupled with immunological reactions against the exposed membrane phospholipids [ 10 ]. There has been no definitive scientifically proven mechanism; the proposed theories include a similar mechanism as bystander hemolysis, suppression of erythropoiesis, and RBC destruction by activated macrophages [ 4 ].…”

“…The pertinent laboratory testing includes direct antibody testing, antibody screening, the ratio of HbA to HbS via either hemoglobin electrophoresis or high-performance liquid chromatography, reticulocyte count compared to baseline, serum bilirubin, serum ferritin, and serum LDH [ 15 ]. The etiology of HHS is varied and includes genetics, previous transfusions, acute chest syndrome, and infections [ 10 ]. HHS is seen most commonly in patients with SCD, which is likely due to its pro-inflammatory state.…”

“…The mainstay of treatment is glucocorticoids and intravenous immunoglobulin, as they are thought to suppress macrophage activation and help shorten the duration of hemolysis [ 18 ]. Erythropoietin has also been utilized in the management of HHS, as it is thought to stimulate erythropoiesis [ 10 ]. Rituximab, a chimeric monoclonal antibody against CD20, has been shown to be effective in promoting reticulocytosis [ 19 ].…”

Hyperhemolytic Crisis Following Transfusion in Sickle Cell Disease With Acute Hepatic Crisis: A Case Report

“…Many theories try to explain how HHS develops in SCD, including "RBC phosphatidylserine exposure," "bystander complement activation," and "suppressed erythropoiesis." Sickled RBCs (owing to osmotic damage, oxidative stress, or ATP depletion) express more phosphatidylserine on their surface, which marks them for clearance by the activated macrophage [6,7]. Bystander hemolysis occurs when both native and donor RBCs are hemolyzed leading to a lower post-transfusion hemoglobin.…”