A case‐control analysis of hyperhemolysis syndrome in adults and laboratory correlates of complement involvement

Abstract

BACKGROUND: Hyperhemolysis syndrome (HS) is a poorly understood, severe hemolytic anemia provoked by transfusion. Both host and donor RBCs are destroyed in HS; thus, transfusion paradoxically worsens anemia. Risk factors and mechanism of HS are unknown. STUDY DESIGN AND METHODS:A retrospective case-control analysis was performed on adults with HS. Patients with HS were matched 1:1 with matched, transfused controls, and HS risk factors were analyzed with multivariable logistic regression. HS samples were analyzed for complement deposition by flow cytometry, and an in vitro model of bystander hemolysis was developed. ABBREVIATIONS: ACS = acute chest syndrome; DAT = direct antiglobulin test; HS = hyperhemolysis syndrome; IAT = indirect antiglobulin test; IVIG = intravenous immunoglobulin; LDH = lactate dehydrogenase; SCD = sickle cell disease.

A case of hyperhaemolysis syndrome in a pregnant Chinese woman with β‐thalassemia during perinatal transfusion

“…It indicated that a marked reticulocytopenia (a significant decrease from the patient's usual absolute reticulocyte level) during haemolysis and recovery manifested by reticulocytosis and gradual improvement in Hb level were also diagnostic features of HHS. Reticulocyte production is not impaired, and macrophages in the reticuloendothelial system may play a key role in reticulocyte haemolysis 1,8 . The reticulocyte detected during the onset of HHS in this patient was within the biological reference interval; unfortunately, the serial reticulocyte counts, including the data before the onset of HHS, were not available for comparison.//…”

“…However, not all HHS is associated with red blood cell alloimmune antibodies, and red blood cell autoantibodies and other haemolytic factors may also be involved in the development of HHS 19 . Pregnancy, acute inflammation and viral infection may prompt the production of red blood cell alloimmune antibodies in the recipient, and viral infection may also induce autoimmunity; alloimmune immunity and infection are independent risk factors for HHS 1,7,20,21 . The persistence of free heme produced by chronic haemolysis may lead to abnormal immune function 10 .…”

“…The diagnostic criteria for HHS 1 in SCD patients include three prerequisites: (1) an unexplained decrease of Hb after transfusion to a lower level than that before transfusion occurs; (2) haemoglobinuria occurring after transfusion or becoming worse than that before transfusion and associated with a higher LDH or TBIL than that before transfusion; and (3) the symptoms appear within 21 days after transfusion. In this case, β‐thalassemia gene analysis revealed a pure mutation in CD 41–42 (‐TTCT), and the MCV and MCH were significantly lower than the biological reference interval; thus, the diagnosis of β‐thalassemia was confirmed 13 .…”

“…The mechanism of HHS is still not completely clarified; it usually occurs once the alloimmune red blood cell antibody titre is lower than the detectable level or after the disappearance and re‐exposure to the corresponding red blood cell blood‐type antigen, rapid antibody elevation or recurrent immune response to produce new antibodies. The occurrence of delayed immune haemolytic transfusion reaction (DIHTR) further aggravates haemolysis, so the donor and recipient red blood cells show accelerated destruction 1 . However, not all HHS is associated with red blood cell alloimmune antibodies, and red blood cell autoantibodies and other haemolytic factors may also be involved in the development of HHS 19 .…”

“…Hyperhaemolysis syndrome (HHS) involves the accelerated destruction of red blood cells of the donor and recipient after blood transfusion, thus resulting in severe haemolytic anaemia syndrome in the recipient 1 . HHS is very rare, and most reported cases of HHS occur in patients with sickle cell disease (SCD) receiving transfusion treatment, 2‐5 whereas only a few cases have been reported in the patients with thalassemia 6‐8 and non‐haemoglobinopathy receiving transfusion treatment 9‐11 .…”