Transfusion Medicine

Platelet Alloimmunization

Patients exposed to transfused white cells with different HLA antigens can develop antibodies to these antigens.⁸ Anti-HLA antibodies are common in patients who previously have received transfused blood that is not leukodepleted and in patients who have been pregnant. Since platelets carry class I HLA antigens, they will be rapidly destroyed by anti-HLA antibodies when transfused into these patients. In patients transfused for aplastic anemia or myelodysplasia, as many as 90% will become HLA-immunized. The incidence is lower in patients receiving chemotherapy but still can be as high as 60% to 90%.^9,10 Patients who have developed anti-HLA antibodies can respond to transfused platelets matched for HLA antigens. Unfortunately, some patients will either be a rare HLA type or be so heavily immunized that they will not respond to any platelet transfusion.

The significance of alloimmunization centers on 2 concepts: recognition and avoidance. Patients with HLA antibodies will fail to have an increment of their platelet counts with transfusions. Accordingly, patients who do not experience an increase in their count 15 minutes after the transfusion may have HLA antibodies. One can test for the presence of anti-HLA antibodies, although some patients instead have specific antiplatelet antibodies that will not respond to HLA-matched platelets. In patients who have been pregnant or previously transfused and are scheduled to undergo transplant or aggressive chemotherapy, it is wise to test for anti-HLA antibodies in order to plan their transfusion needs. The evidence suggests that transfused white cells are responsible for initiating the anti-HLA response. Trials have shown that giving leukodepleted blood products may reduce the incidence of alloimmunization, so patients who are not HLA-alloimmunized should receive only leukodepleted products.¹¹A difficult problem is bleeding in patients who are refractory to platelet transfusion.¹² Patients who test positive for the presence of anti-HLA antibodies can receive transfusions of HLA-matched platelets.¹³ Unfortunately, matched platelet transfusions are not effective in 20% to 70% of these patients. Also, since some loci are difficult to match, effective products may be unavailable. Finally, as many as 25% of patients have antiplatelet antibodies in which HLA-matched products will be ineffective. Platelet cross-matching can be performed to find compatible units for these patients, but this may not always be successful. In the patient who is totally refractory to platelet transfusion, consider drugs as an etiology of antiplatelet antibodies (especially vancomycin).¹⁴ Use of antifibrinolytic agents such as epsilon-aminocaproic acid or tranexamic acid may decrease the incidence of minor bleeding, but these are ineffective for major bleeding. “Platelet drips”—infusing either a platelet concentrate per hour or 1 plateletpheresis unit every 6 hours—may be given as a continuous infusion, but there is no evidence that this is helpful.¹⁵

FRESH FROZEN PLASMA

FFP is made from 1 unit of donated whole blood, with an average volume of 225 mL per unit. One unit of FFP can increase coagulation factor levels by 5% and fibrinogen by 10 mg/dL in the average stable patient. FFP can take 20 to 30 minutes to thaw before use, so in situations where FFP is needed quickly, the blood bank must be informed to “keep ahead” some units. Units of FFP that have been thawed but not used can be stored refrigerated for 5 days to prevent wasting blood products.

The indications for FFP are limited to several situations. These include a documented coagulation defect that can be corrected by a reasonable amount of FFP, such as factor V deficiency and factor XI deficiency, disseminated intravascular coagulation (DIC), reversal of warfarin, and massive transfusions. FFP is also used for the therapy of thrombotic thrombocytopenic purpura.

There is little justification for FFP transfusion in many of the clinical settings in which it is commonly used. For example, FFP is given for minor elevations of the INR in patients with liver disease, despite literature showing not only that the INR rise is not reflective of coagulation defects, but also that patients with liver disease may even be thrombophilic.^16,17 Reviews of FFP use found limited evidence-based indications for its use.^18,19 Also, several studies have shown that transfusion of FFP is not effective at reversing minor elevations of the INR (1.3–1.8).²⁰ In a meta-analysis, FFP was associated with increased risk for lung injury and a trend toward increased mortality.¹⁸