Platelet refractoriness (noun): 

     

     The failure to achieve a desired increase in the

 

     platelet count following the administration of a unit

 

     of platelets on 2 separate occasions. 

Generally speaking, the platelet count is expected to increase ~50,000/uL at 10-60 min and 40,000/uL at 18-24 h after transfusion of 1 unit of platelets (using apheresis platelets).

Pathologists (especially those in Transfusion Medicine/Blood Bank) are often consulted if a patient does not appear to have an adequate response to platelet transfusion.

 

The first thing to do is to rule out a non-immune cause for the patient's PR by looking at the clinical history and other laboratory tests.

Non-immune causes of Platelet Refractoriness:

  • Fever/ Infection/ Sepsis

  • Bleeding

  • Accelerated platelet consumption (DIC, microangiopathic hemolytic anemia or TTP)

  • Drugs (amphotericin B, vancomycin, ATG, interferons)

  • Splenic sequestration) 

  • GVHD

  • Poor platelet quality

If a non-immune cause cannot be identified to explain the patient's inadequate response to platelet transfusion, immune refractoriness can be suspected,

 

Immune-mediated causes of Platelet Refractoriness:

  • HLA or auto-antibodies against platelets

  • ABO mismatched platelets

To assess whether the patient is refractory due to an immune-mediated response, the corrected count increment (CCI) can be used.

NOTE: Our hospital uses apheresis platelets which is approximately 3x10^11 for the calculator below!

CORRECTED COUNT INCREMENT (CCI)

If the patient has an adequate CCI (>7500), then the cause of the platelet refractoriness is likely due to a non-immune mediated condition and the clinical history should be further explored. The patient can continue to receive stock platelets without further platelet testing workups required.

Platelet refractoriness due to an immune-mediated response (antibodies against the platelets) is defined as a CCI less than 7500 (or 5000 according to some sources) on at least two sequential platelet transfusions. 

 

If immune refractoriness is suspected, you can proceed with a workup to determine the cause of the patient's refractoriness or to find units that may give a better response. This involves special testing (costly), thus we tend to use the following algorithm when dealing with refractory patients.

 

1. Order crossmatched platelets.

Random units of platelets are tested against the patient's serum to determine the extent of the incompatibility of platelet transfusions with the patient's body. 

 

Example: Let's say 10 units of platelets were tested, and a majority of them were compatible with the patient's serum (meaning the platelets were not destroyed). In this case, we may consider giving the patient stock platelets in the future. This is because as it seems most platelet units would work fine and not be destroyed by the patient's immune system.

Example: If only a few of the 10 units tested were compatible with the patient's serum we typically will order those crossmatched units for the patient and resassess their CCI using theses special platelets for the patient. If CCI is still inadequate, move on to next step.

 

2. Consider platelet HLA-Ab testing or Platelet Antibody Specificity prediction tests.

In patients with autoimmune diseases, there can be auto-antibodies that cause the destruction of the platelets within the patient. If present, you can attempt to find donors that have a similar HLA (or antibody type) as the patient to reduce the chances of there being an antibody in the donor's platelets.

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