Platelet Refractoriness

Platelet refractoriness is repeated failure to achieve the expected rise in platelet count after transfusion. It is usually defined as poor increments after at least two consecutive transfusions of ABO compatible, fresh platelets (stored no more than 3 days), given in adequate dose. It leads to bleeding, longer admissions and wasted stock.

Corrected count increment. Corrected count increment equals (post transfusion count minus pre transfusion count, in x 10⁹/L) multiplied by body surface area in square metres, divided by the number of platelets transfused in units of 10¹¹. Count is measured 10 minutes to 1 hour after transfusion, and again at 18 to 24 hours.

Interpretation. A 1 hour value under about 7.5 and a 24 hour value under about 4.5 indicate a poor response. A good 1 hour increment with a poor 24 hour increment suggests consumption or non-immune causes, and a poor increment at both times suggests immune destruction.

Special groups. Patients with haematological malignancy, stem cell transplant recipients, multiparous women and multiply transfused patients are at higher risk of immune refractoriness. In East Africa, HLA typing and platelet crossmatching are available only in a few centres, so early referral is needed.

Causes.

• Non-immune (most common): fever, sepsis, disseminated intravascular coagulation, splenomegaly, ongoing bleeding, hepatic veno-occlusive disease, drugs (for example amphotericin, vancomycin, heparin), old or damaged platelets, and ABO mismatch.

• Immune: HLA class I antibodies (most), human platelet antigen antibodies and ABO incompatibility.

Assessment steps.

1. Confirm the dose and the age of the product, and the count timing.

2. Check ABO compatibility of the product.

3. Look for non-immune causes and treat them.

4. After two poor responses with fresh, compatible products, send blood for HLA antibody screening (panel reactive antibody) and human platelet antigen antibodies, and HLA typing of the patient.

5. Compare increments with ABO identical fresh platelets.

Red flags. Bleeding with poor increments, and a patient needing transplant in whom HLA sensitisation matters.

Non-immune refractoriness. Treat the cause. Use ABO identical, fresh platelets in adequate dose. Transfuse for bleeding, and avoid prophylactic transfusion that has no effect.

Immune refractoriness.

• HLA matched platelets, from donors typed for HLA class I, or crossmatch compatible platelets where available.

• When matched or crossmatched products are not available, use ABO identical fresh platelets for bleeding, with a larger dose if needed.

• Do not use prophylactic transfusion when the increment is absent.

• Antifibrinolytic therapy for mucosal bleeding, and local measures.

• Intravenous immunoglobulin, plasma exchange and immunosuppression have limited and inconsistent benefit.

Prevention. Leucodepleted products reduce HLA alloimmunisation. Avoid unnecessary transfusion and use single donor units in patients likely to need many.

Special groups.

• Children: weight based dose and attention to the same causes.

• Stem cell transplant: HLA matched products may be needed through engraftment.

• Pregnancy: refer early to haematology, and consider neonatal alloimmune thrombocytopenia.

Monitoring. Count 10 minutes to 1 hour and 18 to 24 hours after each transfusion, with calculated corrected count increment, for the first transfusions after the concern arises.

Complications. Bleeding, repeated reactions, transfusion associated graft versus host disease in unirradiated products to related donors, and delay in procedures.

Referral and escalation. Haematology and the transfusion service for HLA and human platelet antigen testing and for matched donors. Refer to a reference laboratory in advance, because turnaround is days.

Disposition. Record the antibody result and tell the transfusion service, so that future requests for platelets are matched.