Pathophysiology

  • Refractoriness is defined as the failure to obtain a satisfactory response to transfusion of unselected platelet components.
  • One adult therapeutic dose (ATD) of platelets (four random pools or a single apheresis unit) typically raises the platelet count by 20-40×109/L.
    • A platelet count increment of <10×109/L between 1-24 hours after transfusion of 1 ATD on two separate occasions is indicative of refractoriness.
  • Universal leukodepletion in the UK has dropped the incidence of alloimmunisation from 50% to 10-25% (the residual number of alloimmunised people is largely due to women exposed in pregnancy).
    • Approximately 25-30% of patients who are alloimmunised become refractory to platelet transfusion (TRAPS study)
    • Leukodepletion was shown in the TRAPS study to be the most effective way of reducing the risk of alloimmunisation.
    • Leukodepleted components cause primary HLA immunisation in <3% of recipients.
    • Leukodepletion is best performed at the point of component preparation.
  • Usually the result of increased destruction. Causes are:
    • Immune
      • Alloimmune
        • Anti-HLA (human leukocyte antigen) class I antibodies
        • Anti-HPA (human platelet antigen) antibodies
      • Autoimmune
        • Immune thrombocytopaenic purpura (ITP)
        • Drug-induced ITP
    • Non-immune
      • Consumptive coagulopathy
        • Sepsis
        • Bleeding
      • Disseminated intravascular coagulation
      • Microangiopathic haemolytic anaemia
      • Hypersplenism

Investigation

  • If a patient has proven platelet refractoriness, then blood should be sent to look for HLA antibodies.
  • While awaiting confirmation, patients should be transfused with ABO-matched, fresh (<3 days old) platelets.
  • If a patient has HLA antibodies, then HLA-matched platelets should be used and the response to platelet transfusion assessed. Patients with a good response should continue HLA-matched product transfusion.
  • If a patient has a poor response to HLA-matched platelets, ensure that the HLA match is grade A. If it is and the response is still poor, test for HPA antibodies. Patients with both HLA and HPA antibodies should be provided with both HLA and HPA-matched platelets.

Management of HLA antibodies

  • Patients should be transfused with irradiated, HLA-matched platelets.
  • Ideally, platelets should be “A” matched (donor antigens fully matched with recipient antigens).
  • Grading of HLA matching:
    • A: donor and recipient antigens fully matched.
    • B1: donor expresses one antigens that the recipient does not, but no antigens against which HLA-antibodies are directed.
    • B2: donor expresses two antigens that the recipient does not, but no antigens against which HLA-antibodies are directed.
    • B3: donor expresses three antigens that the recipient does not, but no antigens against which HLA-antibodies are directed.
    • B4: donor expresses four antigens that the recipient does not, but no antigens against which HLA-antibodies are directed.
    • C: donor expresses antigens against which recipient HLA antibodies are directed. These should be avoided.

Inherited Thrombocytopathies (Glanzmann thrombasthenia or Bernard-Soulier syndrome)

  • These patients have platelet function defects which increase their bleeding risk even when the platelet count is normal or near-normal.
  • They may require platelet transfusion when bleeding.
  • Platelet products for such individuals should be ABO-compatible, HLA-matched and irradiated to prevent alloimmunisation. 
  • Insofar as possible, patients should receive alternatives to platelet transfusion (e.g. rFVIIa) to prevent alloimmunisation against GPIIb/IIIa (Glanzmann) or GPIb-IX-V (BSS).