Delayed haemolytic transfusion reactions (DHTR)

When to suspect this adverse reaction?

This normally manifests between 2 to 14 days after transfusion of a red cell component. Signs and symptoms are similar to an acute transfusion reaction but are less severe.

The patient may have fever, inadequate rise in Hb, jaundice, high LDH, reticulocytosis, spherocytosis, positive antibody screen and a positive Direct Antiglobulin Test (DAT).(1,2)

It occurs with estimates of approximately 1:2500 of transfusions but is found more frequently in sickle cell patients who have received frequent blood transfusions.(1,2)

Usual causes?

After transfusion, transplantation or pregnancy, a patient may make an antibody to a red cell antigen that they lack. This antibody may fall to a very low level and therefore not detected during pretransfusion screening. If the patient is later exposed to a red cell transfusion which expresses the same antigen, an anamnestic response may occur where the antibody level rises rapidly and hence lead to DHTR.

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.(1)


Request a Direct Antiglobulin Test (DAT), antibody screen, liver function tests (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.(2)

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

For patients who frequently receive blood transfusion such as patients with sickle cell disease and those with thalassaemia, patients should have extended red cell phenotyping and receive red cells matched for at least ABO, Rh (D,C,c,E,e) and Kell antigens.(3)

  1. Fung MK (ed). Non-infectious complications of blood transfusion. Chapter 27, AABB Technical Manual, 18th edition. AABB Bethesda, 2014.
  2. Delaney M, Wendel S, Bercovitz R, Cid J, Cohn C, Dunbar D,et al.  Transfusion reactions:prevention, diagnosis and treatment.  BJH 2016; 388: 2825-36.

  3. Gardner K, Hoppe C, Mijovic A, Thein S L.  How we treat delayed haemolytic transfusion reactions in patients with sickle cell disease.  BJH 2015; 170: 745-756.