Alloimmunization and hyperhemolysis in sickle cell disease

Abstract

Alloimmunization against red blood cell antigens and delayed hemolytic transfusion reaction (DHTR) are major barriers to transfusion in sickle cell disease (SCD). In SCD, DHTR is a potentially life-threatening. Blood group polymorphism in SCD patients, who are of African ancestry and frequently exposed to antigens they do not carry; an inflammatory clinical state; and occasional transfusion in acute situations are risk factors for alloimmunization and DHTR. In patients at risk, the transfusion indication must be balanced against the risk of developing DHTR. However, when transfusion is absolutely necessary, protocols combining the prevention of exposure to immunogenic antigens with immunosuppressive treatments must be implemented, and patients should be carefully monitored during posttransfusion follow-up. This close monitoring makes it possible to diagnose hyperhemolysis as soon as possible; to avoid retransfusion, which can exacerbate hemolysis; and to administer specific treatments, such as anticomplement therapy, in severe cases. Finally, in patients with severe disease, hematopoietic stem cell transplantation may be indicated. However, transfusion is also required in this context, and its management is complex because these risks must be taken into account.

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

“…Simultaneously, the physiological protective mechanisms against free heme become fulminant and the complement system, activated through the classical or alternative pathways, generates extreme hemolysis via the membrane attack complex. As a result, the red blood cells are destroyed as they are not only sensitive to oxidative stress but also to the non-specific binding of activated complement factors [11,[18][19][20][21].…”

“…While HHS requires prompt intervention, evidence to guide optimal therapy is limited. Currently, no guidelines exist for using steroids or IVIG as a first-line treatment, and no evidence-based studies support the use of one over the other [11,14,22]. Based on the evidence presented by previous case-control studies and according to institutional, consensus-based guidelines, we simultaneously administered IVIG and steroid therapy.…”

“…Delayed hemolytic transfusion reaction (DHTR) occurs in about 4% of adult patients receiving occasional transfusions [10]. DHTR is an umbrella term, primarily caused by RBC alloimmunization due to differences in blood groups between donors of Caucasian origin and recipients of African ancestry [11]. However, many cases have been described in the literature with no detectable antibodies, which raises uncertainty regarding the underlying pathogenesis [12].…”

“…The most severe form of DHTR is hyperhemolysis or hyperhemolytic syndrome (HHS), which clinically presents with fever, acute pain, and jaundice. In HHS, there is an acute increase in total bilirubin and/or lactate dehydrogenase (LDH) levels, a decrease in hemoglobin levels following RBC transfusion, and acute reticulocytopenia followed by marked reticulocytosis [11]. HHS can be classified as acute and delayed forms; the acute form occurs within 7 days of transfusion without alloantibody formation and the DAT test is negative.…”

“…The role of RBC transfusions in HHS is controversial [11][12][13][14][15]. Treatment of HHS is avoiding the use of transfusions; if transfusions are still necessary, then premedication with corticosteroids or intravenous immunoglobulin (IVIG) could be used.…”