Epidemiological and clinical features, therapeutic strategies and outcomes in patients with hyperhaemolysis: A systematic review

Abstract

Hyperhaemolysis syndrome (HHS), a severe form of delayed haemolytic transfusion reaction most commonly described in patients with sickle cell disease (SCD), involves destruction of both donor and recipient red blood cells (RBCs). As the epidemiology and underlying pathophysiology have yet to be definitively elucidated, recognition can be challenging. We systematically reviewed PubMed and EMBASE to identify all cases of post-transfusion hyperhaemolysis and characterized the epidemiological, clinical and immunohaematological characteristics and treatments of HHS. We identified 51 patients (33 females and 18 males), including 31 patients with SCD (HbSS, HbSC and HbS/β-thalassaemia). The median haemoglobin nadir (3.9 g/dL) occurred a median of 10 days post-transfusion. 32.6% and 45.7% of patients had a negative indirect anti-globulin test and a negative direct anti-globulin test, respectively. The most common therapies included corticosteroids and intravenous immune globulin. 66.0% of patients received ≥1 supportive transfusion, which was associated with a longer median hospital stay/time to recovery (23 days vs. 15 days; p = 0.015) compared to no supportive transfusion. These findings illustrate that HHS that often results in marked anaemia 10 days post-transfusion is not restricted to patients with haemoglobinopathies, and additional transfused RBCs may be associated with a longer time-to-recovery.

Pregnant patients with sickle cell disease and hyperhemolysis requiring intrauterine transfusion: A challenging clinical scenario

“…Although the pathophysiology of HS remains unclear, defining features include a decrease in hemoglobin below the pre-transfusion level and paradoxical reticulocytopenia. 1,2 Autoantibody-mediated RBC destruction or alloantibody-sensitization of antigen-negative RBCs leading to "bystander hemolysis" are two proposed mechanisms. 1,2 Increased complement activation, impaired complement regulation, and modulation of the antibody-independent lectin complement pathway have also been implicated.…”

“…1,2 Autoantibody-mediated RBC destruction or alloantibody-sensitization of antigen-negative RBCs leading to "bystander hemolysis" are two proposed mechanisms. 1,2 Increased complement activation, impaired complement regulation, and modulation of the antibody-independent lectin complement pathway have also been implicated. [1][2][3][4] Finally, alternative pathways of RBC removal have been suggested, including enhanced macrophage activation and increased eroptosis.…”

“…1,2 Increased complement activation, impaired complement regulation, and modulation of the antibody-independent lectin complement pathway have also been implicated. [1][2][3][4] Finally, alternative pathways of RBC removal have been suggested, including enhanced macrophage activation and increased eroptosis. 1,2,5,6 Notably, physiologic alter-ations in pregnancy can exacerbate the pathophysiologic state of SCD.…”

“…[1][2][3][4] Finally, alternative pathways of RBC removal have been suggested, including enhanced macrophage activation and increased eroptosis. 1,2,5,6 Notably, physiologic alter-ations in pregnancy can exacerbate the pathophysiologic state of SCD. 7,8 Moreover, complement activity and a subset of inflammatory monocytes may increase during pregnancy, 9 potentially increasing hyperhemolysis risk.…”

A Case Report of Hyperhemolytic Syndrome in Sickle Cell Disease, with a Special Focus on Avoiding the Use of Transfusions

“…Moreover, it was shown previously that the activation Thalass. Rep. 2024, 14 of coagulation pathways also contributes to vaso-occlusion [2]. The rate of hemolysis is usually stable between crises, but patients with a higher rate of hemolysis are more likely to develop organ dysfunction and vascular stiffness, and the hemolysis itself causes endothelial dysfunction.…”