What is the cause of a delayed hemolytic transfusion reaction (DHTR)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: May 5, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

Delayed transfusion reactions should be managed promptly with immunosuppressive therapy, including first-line agents such as IVIg and high-dose steroids, to prevent life-threatening hemolysis and improve patient outcomes. The management of delayed transfusion reactions involves a comprehensive approach, including stopping any ongoing transfusions, obtaining blood samples for laboratory testing, and providing supportive care 1. Patients with delayed transfusion reactions often present with a significant drop in hemoglobin within 21 days posttransfusion, associated with new red cell alloantibody, hemoglobinuria, or accelerated HbS% increase 1.

Key considerations in the management of delayed transfusion reactions include:

  • Initiating immunosuppressive therapy promptly in patients with life-threatening hemolysis 1
  • Using first-line immunosuppressive agents such as IVIg and high-dose steroids 1
  • Considering second-line agents such as eculizumab 1
  • Avoiding further transfusion unless patients are experiencing life-threatening anemia with ongoing hemolysis 1
  • Providing supportive care, including erythropoietin with or without IV iron 1

The pathophysiology of delayed transfusion reactions involves the development of antibodies against minor blood group antigens present in the donor blood, which can lead to significant hemolysis 1. Prevention strategies include careful cross-matching and maintaining detailed transfusion records to avoid future exposure to incompatible blood products 1. Patients with a history of delayed transfusion reactions should receive leukocyte-reduced blood products and be monitored closely during subsequent transfusions 1.

In terms of specific treatment, a dose of 375 mg of rituximab/m2 repeated after 2 weeks, methylprednisolone or prednisone at 1 to 4 mg/kg per day, and IVIg at 0.4 to 1 g/kg per day for 3 to 5 days have been used to treat hemolytic transfusion reactions 1. However, the optimal treatment approach may vary depending on the individual patient's circumstances and the severity of the reaction. A shared decision-making process is critical in the management of delayed transfusion reactions, taking into account the potential benefits and harms associated with specific immunosuppressive therapies 1.

From the Research

Definition and Symptoms of Delayed Transfusion Reactions

  • Delayed hemolytic transfusion reactions (DHTRs) are defined as immune-mediated hemolysis of allogeneic donor red cells that occurs approximately 3 to 5 days after transfusion 2
  • Symptoms of DHTRs may include a drop in hemoglobin and hematocrit, fever, jaundice, and renal insufficiency 2
  • Delayed serologic transfusion reactions (DSTRs) are characterized by serologic findings consistent with DHTRs but no clinical evidence of hemolysis 2, 3

Incidence and Risk Factors

  • The incidence of DSTRs is estimated to be 1 (0.66%) of 151 recipients with posttransfusion samples available for testing, while the incidence of DHTRs is only 1 (0.12%) of 854 patients tested 3
  • Risk factors for DHTRs include high alloantibody evanescence rates among both general patient groups and those with sickle cell disease (SCD) 4
  • Transfusion record fragmentation can also hamper antibody detection and contribute to the risk of DHTRs 4

Treatment and Prevention

  • Automated red blood cell exchange (ARE) can be used to limit hemolysis associated with an emerging DHTR 5
  • Novel immunosuppressive agents may be used to prevent or treat hyperhaemolytic DHTRs, particularly in patients with SCD 4
  • Implementing practical preventive strategies, such as enhancing antibody detection and improving transfusion record management, is a priority for reducing the risk of delayed transfusion reactions 4

Pathophysiology and Clinical Significance

  • DHTRs are mediated by blood group antibodies that undergo anamnestic increases following antigen reexposure 2, 5
  • The persistence of a positive direct antiglobulin test (DAT) after DSTR or DHTR may involve several immunologic mechanisms, including the development of posttransfusion autoantibodies 3
  • Delayed serologic and haemolytic reactions remain important and highly relevant transfusion-associated adverse events, and further research is needed to understand their basic mechanisms and develop evidence-based approaches for treatment and prevention 4

Related Questions

What is the best next step in evaluating a suspected allergic transfusion reaction in a patient with idiopathic aplastic anemia, who developed a diffuse urticarial rash and received diphenhydramine (benzhydramine)?
What are the management strategies for adverse reactions to blood transfusion?
What is the most likely blood transfusion reaction in a patient who develops pain at the intravenous (IV) site, difficulty breathing, and fever after 10 minutes of blood transfusion?
Why did the patient experience pruritus, tachycardia, and nausea after receiving Tranexamic Acid (TXA) and blood?
What is the most adverse effect that can occur after a massive blood transfusion of cold blood, such as Hypocalcemia, Febrile Non-Haemolytic Transfusion Reaction (FNHTR), or Haemolytic Transfusion Reaction (HTR)?
What is the most likely diagnosis for a 33-year-old patient with a history of Hepatitis B (HB) surface antigen (HBsAg) positivity, presenting with fatigue, nausea, vomiting, and jaundice, and laboratory results showing HBsAg positivity, Hepatitis B e-antigen (HBeAg) negativity, elevated Alanine Transaminase (ALT), and undetectable Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels?
What is the treatment for dysuria without evidence of Urinary Tract Infection (UTI)?
What are the recommended profile restrictions following a comminuted nasal bone fracture with maxillary spine fracture and anterior maxillary wall fracture for a military member (Member of the Armed Forces)?
How is vitamin D insufficiency treated in an uninsured patient with a vitamin D level of 26 ng/mL (nanograms per milliliter)?
What medication can be prescribed to calm a patient experiencing anxiety and distress after the death of her two-week-old grandchild, presenting with symptoms of emotional upset and tremors?
What are the treatment options for wrist pain resulting from physical exercise (Physical Activity)?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.