AABB23: Hyperhemolysis Syndrome Presents Challenges

Hyperhemolysis syndrome (HHS) is a rare but life-threatening complication of transfusion characterized by accelerated clearance of transfused as well as autologous red cells. Attendees in the session, “Hyperhemolysis Syndrome: Recognition and Current Management Strategies of a Potentially Fatal Transfusion Complication,” heard two different perspectives on the challenges in HHS.

The Importance of Recognition

Jeremy Jacobs, MD, MHS, fellow in special coagulation at the Mayo Clinic, reviewed of the epidemiologic, clinical and laboratory features of HHS. Because HHS is considered by many to be the most severe form of delayed hemolytic transfusion reaction, a thorough understanding and early recognition of this complication are essential. He noted that the difficulty in diagnosis is complicated because HHS is usually, but not always, associated with a new antibody and HHS usually, but not always, occurs in patients with sickle cell disease (SCD). He identified diagnostic hallmarks, including:

• Hemolysis of both donor and recipient red cells.
• Hemoglobin level decreases below the pretransfusion baseline.
• Presence of reticulocytopenia or an inappropriately low reticulocyte count.

  He also noted data from the Serious Hazards of Transfusion (SHOT) hemovigilance program indicating that 1) HHS is under-reported and 2) cases continue to be reported in patients for whom antibody-negative units are available. He summarized in some detail a recent article [Br J Haematol. 2023;201(6):1025-32] that reviewed reported HHS cases.

Jacobs presented case studies to prompt attendee consideration of the points in his presentation. He closed with a recap of why treatment of HHS patients is challenging:

• HHS is likely under-reported.
• HHS often manifests without evidence of a new antibody.
• It is difficult, but critical, to avoid transfusion of red cells in the face of hemolysis.
• Obstetric patients are particularly challenging because both maternal and fetal survival are involved.

Management Strategies in Use

The second speaker, Ross M. Fasano, MD, associate professor of laboratory medicine and pathology at Emory University in Atlanta, spoke briefly on the pathophysiology and incidence of HHS. He reviewed results of an audit of HHS in SCD patients from Children’s Healthcare of Atlanta and transfusion guidelines for SCD from the American Society of Hematology. Both the audit and the guidelines pointed to a need for quality improvement in the transfusion support of patients with HHS.

Fasano focused the remainder of his comments on the quality improvement initiatives undertaken via creation and use of 1) clinical decision support (CDS) tools for diagnosing HHS and 2) a standard operating procedure (SOP) for treatment of HHS. He shared screen shots of the CDS software alerts and the results of implementation. Those results showed a decrease in the number of SCD patients needing posttransfusion support in the emergency department and a reduction in the number of SCD patients who had declining hemoglobin A levels. The SOP he shared was tabular in format, displaying sequential drug agents and doses used as well as cautionary comments.

He concluded by identifying next steps for the quality initiatives, which include inter-institutional collaboration, and the expected results of those next steps:

• A better way to evaluate the true incidence of HHS in pediatric SCD patients.
• Standardized and timely diagnosis and treatment of HHS in SCD.
• A better understanding of HHS pathophysiology.