Platelet Transfusion Refractory Patients

Calculation of Refractoriness

Determination of platelet refractoriness is based on evaluating the increase in platelet count after transfusion. Ideally, such an evaluation will examine platelet increases within 1 hour after transfusion of ABO identical or compatible platelets stored for less than 48 hours, on two different occasions. The most commonly used calculation in the United States is the corrected count increment (CCI), although other equations may also be used. The CCI is calculated as follows:

A typical body surface area (BSA) for adult is 2 m ² , and it can be assumed that 3–4 × 10 ¹¹ platelets are in an apheresis unit or that 0.5–0.7 × 10 ¹¹ platelets are in a whole blood–derived random donor platelet concentrate. Generally, CCIs >7500 are considered satisfactory, while a CCI less than 5000 on two occasions is typically considered to be consistent with platelet refractoriness. It is important to note that while a poor CCI indicates that a patient may be platelet refractory, the value itself provides no insight as to the underlying cause of refractoriness; low CCI values prompt further clinical and laboratory investigation.

Nonimmune Refractoriness

Nonimmune causes of platelet refractoriness are listed in Table 57.1 , with two-thirds of platelet refractoriness thought to be due to nonimmune causes.

Immune Refractoriness

The most common immune-mediated cause of platelet refractoriness is antibodies directed against HLA class I antigens (HLA-A or HLA-B), occurring in 30%–40% of cases. These alloantibodies typically form after exposure to the corresponding HLA class I antigens on either platelets or white blood cells; such exposure may occur through transfusion or pregnancy. However, the presence of HLA class I antibodies alone does not mean that these antibodies are responsible for platelet refractoriness. In the Trial to Prevent Alloimmunization to Platelets (TRAP), for example, the incidence of HLA alloantibodies was twofold higher than the incidence of platelet refractoriness.

Antibodies against human glycoprotein platelet antigens (HPAs) have been reported to cause platelet refractoriness on occasion. Patients with Bernard–Soulier syndrome and Glanzmann Thrombasthenia may become broadly immunized to the platelet glycoproteins GPIb/IX/V and GPIIb/IIIa. Patients with auto antibodies against these and similar platelet antigens (e.g., in the setting of immune thrombocytopenia or posttransfusion purpura) will also demonstrate transfusion refractoriness.

Drug-induced antibodies and major mismatched ABO-incompatible transfusions can also lead to antibody-mediated platelet refractoriness. In general, a 20% increase in platelet recovery may be seen after transfusion with ABO identical or compatible units, given the presence of A and B antigens on platelets (e.g., a platelet unit from a group O donor may survive 20% better in a group O recipient than a platelet unit from a group A donor will, given the recipient’s naturally occurring anti-A antibodies).

Recent animal studies suggest that cellular-mediated immune etiologies of platelet refractoriness may exist, although they would not be identified by antibody-based clinical assays.