Delayed haemolytic transfusion reactions (DHTR)

Notes

1. QLD data is unavailable for 2012–13.
2. Sex and facility location data is unavailable for NSW.
3. Time of transfusion data is unavailable for NSW and SA.
4. Data is unavailable for WA.
5. Uncategorised refers to those reports where no data was provided.

In contrast to AHTR, delayed haemolytic transfusion reactions (DHTR) are triggered by the production or re‑emergence of antibodies following transfusion and therefore are not generally detectable at the time of pre‑transfusion compatibility testing. From 2011–12 to 2012–13, there were 23 reports of DHTR to the National Haemovigilance Program, accounting for 2.2% of all reports (1,044) for this period.

In the five financial years to 2012–13:

• The number of DHTRs increased from 4 in 2008–09 to 17 in 2011–12 and then dropped to 6 in 2012–13 (mainly due to the unavailability of QLD data).
• The majority of cases were related to red cell transfusion.
• The majority of affected patients were females.

DHTR are relatively common when compared with acute haemolytic transfusion reactions, but may be difficult to diagnose and easily missed as presentation may be remote (in time and place) from the causal transfusion. UK data has suggested that DHTR were responsible for 10.2% of all serious transfusion‑related hazards between 1996 and 2003.^[21] Researchers have observed that DHTRs are probably under‑reported and under‑recognised in the UK.^[22]

The current figures for Australia imply that DHTR may be severely under‑recognised and/or under‑reported. The National Haemovigilance Program does not currently gather data on the specific antibodies associated with haemolytic transfusion reactions.

Current national level haemovigilance reporting in Australia does not consider the delay period between the transfusion and the reaction. This may be addressed in future reporting. UK data reported the interval in days between the implicated transfusion and clinical signs or symptoms of a DHTR to have a median of 8 days with a range of 2 to 18 days. Anti‑Jk(a) is the single most common red cell specifically implicated in both acute and delayed reactions.^[23] Treatment of DHTR remains challenging. Immunosuppressive medication has been reported to be useful by some but not by others. The mainstay of treatment is to minimise RBC transfusions as much as possible.^[24]

Clinical recommendation

The Blood Service provides guidance on the recognition, investigation and management of DHTRs.^[25]

• When to suspect these adverse reactions?
  

  Patients may present with unexplained fever and anaemia usually 2 to 14 days after transfusion of a red cell component.

  The patient may also have jaundice, high bilirubin, high liver function tests (LDH), reticulocytosis, spherocytosis, positive antibody screen and a positive DAT.

  It occurs in 1:2,500 to 1:11,000 of transfusions.

• Usual causes?
  

  After transfusion, transplantation or pregnancy, a patient may make an antibody to a red cell antigen that they lack. If the patient is later exposed to a red cell transfusion which expresses this antigen a DHTR may occur.

  DHTRs may also occur with transfusion transmitted malaria and babesiosis.

  The clinical severity of a DHTR depends on the immunogenicity or dose of the antigen. Blood group antibodies associated with DHTRs include those of the Kidd, Duffy, Kell and MNS systems, in order of decreasing frequency.

• Investigation
  

  Request a DAT, antibody screen, LDH and markers of haemolysis (eg serum haptoglobin, bilirubin).

• What to do?
  

  Most delayed haemolytic reactions have a benign course and require no treatment however life threatening haemolysis with severe anaemia and renal failure may occur.

  If an antibody is identified, you may request antigen-negative blood if further transfusion is needed.