Platelet transfusion refractoriness

Platelet transfusion refractoriness is the repeated failure to achieve the desired level of blood platelets in a patient following a platelet transfusion. The cause of refractoriness may be either immune or nonimmune based. Among immune-related refractoriness, antibodies against HLA antigens are the primary cause. Non-immune causes include splenomegaly (enlargement of the spleen), fever, and sepsis.

Cause

Platelet refractoriness can be due to immune causes or non-immune causes. Non-immune causes account for over 80% of cases of platelet refractoriness, and sepsis is one of the most common non-immune causes. HLA alloimmunization is the commonest immune cause of platelet refractoriness.

Non-immune causes

• Sepsis

• Fever

• Disseminated intravascular coagulation

• Splenomegaly

• Treatment of infection, antibiotics (vancomycin), antifungals (amphotericin B)

• Graft-versus-host disease

• Hepatic veno-occlusive disease

• Bleeding

Immune causes

• Alloantibodies to platelet antigens
  • Human leucocyte antigen (HLA) antibodies
  • Human platelet antigen (HPA) antibodies

• Immune complexes

• Other antibodies
  • Drug-related antibodies

Diagnosis

Platelet transfusion refractoriness can be defined in several different ways. All measures of platelet refractoriness are defined by the timing of the post-transfusion platelet count, usually 1 hour post transfusion or 24 hours post transfusion or both.

Platelet increment (PI)

This is the simplest method, and only requires data on the platelet count before and after the transfusion.

PI = post-transfusion platelet count - pre-transfusion platelet count

However, it is affected by the number of platelets given in the transfusion (platelet dose) and the patient’s blood volume. Larger patients and smaller platelet doses decrease the platelet increment. These factors are adjusted for in the other methods of defining platelet refractoriness.

Percentage platelet recovery (PPR)

Requires data on the platelet increment (PI), the patient’s total blood volume (TBV) - estimated using the patient’s weight multiplied by 0.075, and the number of platelets transfused (platelet dose)

PPR = ((PI x TBV)/PD) x 100

At 1 hour post-transfusion, a PPR < 20% is considered evidence of platelet refractoriness. At 16 hours post-transfusion a PPR < 10% is considered evidence of platelet refractoriness.

Percentage platelet increment

Is very similar to the percentage platelet recovery (PPR) but the patient’s total blood volume is estimated using the patient’s weight multiplied by 0.07, and there has been an additional adjustment for splenic pooling of platelets (multiplied by 2/3)

PPI = ((PI x TBV x 0.67)/PD) x 100

Corrected count increment (CCI)

This requires data on the platelet increment (PI), the patient’s Body surface area (BSA), and the number of platelets transfused (PD).

CCI = ((PI x BSA)/PD

Some blood banks maintain records of the estimated number of platelets in each unit. Current requirements in the US stipulate that a unit of apheresis platelets must contain at least 3.0 x10¹¹ platelets.

The CCI is calculated as follows: CCI= (Post-transfusion platelet count - Pre-transfusion platelet count)(BSA) ÷ (number of platelets transfused).

A CCI greater than 7500 indicates a sufficient post-transfusion increment, whereas a CCI less than 7500 is considered diagnostic of platelet refractoriness.

Immune-mediated refractoriness usually shows little or no increment in the immediate post-transfusion platelet count. Non-immune refractoriness may show an initial rise in platelet count, but a subsequent 8-hour or 12-hour post-transfusion sample shows a return to the baseline platelet count.