The Typical Timeline of a Delayed Transfusion Reaction
Delayed transfusion reactions, unlike acute reactions, appear after 24 hours. Delayed hemolytic transfusion reactions (DHTR), the most common type, typically show evidence of hemolysis between 3 and 10 days after transfusion, but can occur up to 28 days later. Other delayed reactions, such as transfusion-associated graft-versus-host disease (TA-GVHD), may take several weeks to appear. Symptoms can be mild, potentially leading to a delayed diagnosis.
The Underlying Immune Mechanism: An Anamnestic Response
A delayed reaction is caused by an anamnestic, or secondary, immune response. This occurs when a patient has prior exposure to foreign red blood cell (RBC) antigens from a previous transfusion, pregnancy, or transplantation. The initial exposure leads to the development of antibodies that may become undetectable over time. A subsequent transfusion with RBCs containing the same antigen triggers a rapid increase in these antibodies. These antibodies then target the transfused RBCs for destruction, primarily in the spleen and liver, a process called extravascular hemolysis. The Kidd, Rh, Duffy, and Kell blood groups are commonly involved in DHTR. Reactions can range from mild to severe, particularly in patients with conditions like sickle cell disease.
Recognizing the Symptoms and Signs
Symptoms of a delayed transfusion reaction are often less pronounced than acute reactions. They can include:
- Unexplained fever.
- Worsening anemia, or a failure of hemoglobin levels to rise as expected after transfusion.
- Jaundice, due to increased bilirubin from RBC breakdown.
- Dark urine, which can indicate hemoglobinuria.
- General malaise and fatigue.
Comparing Acute vs. Delayed Transfusion Reactions
| Feature | Acute Transfusion Reaction | Delayed Transfusion Reaction |
|---|---|---|
| Timing of Onset | During or within 24 hours of transfusion | After 24 hours, typically 3 to 28 days post-transfusion |
| Mechanism | Pre-existing antibodies rapidly destroy transfused RBCs | Anamnestic (secondary) immune response to a previously encountered antigen |
| Severity | Often more severe, with potential for life-threatening complications | Generally less severe and more gradual, though life-threatening cases occur |
| Common Symptoms | Fever, chills, chest/back pain, dyspnea, hypotension | Fever, worsening anemia, jaundice, fatigue, hemoglobinuria |
| Primary Treatment | Immediate cessation of transfusion, supportive care for shock and renal function | Supportive care, monitoring for worsening hemolysis; may require immunosuppressants |
Diagnosis and Management
Diagnosis involves clinical suspicion and lab tests. Repeat blood tests are performed when a reaction is suspected. Lab findings for DHTR include a positive direct antiglobulin test (DAT) and the identification of a new alloantibody. Other indicators of RBC destruction, such as increased LDH, elevated bilirubin, and decreased haptoglobin, may also be present.
Management is primarily supportive. Mild cases may only need monitoring. Severe hemolysis might require hydration to protect kidney function. In very severe cases, such as hyperhemolysis, especially in sickle cell patients, immunosuppressive therapy with steroids or IVIg might be needed. A critical step after diagnosis is flagging the patient's record to prevent future transfusions with antigen-positive blood.
Conclusion
A delayed transfusion reaction, commonly DHTR, typically manifests 3 to 10 days after transfusion, but can occur up to 28 days later. This delay is due to an anamnestic immune response triggered by re-exposure to a foreign blood antigen. The subtle nature of the symptoms requires a high level of clinical suspicion for timely diagnosis. Supportive care and preventative measures are key to safe management. Understanding the immune mechanism explains the delayed onset and helps prevent future complications. For more detailed information, consult authoritative resources such as the National Institutes of Health website. https://www.ncbi.nlm.nih.gov/books/NBK448158/
