September 1999 - Platelet Transfusion Therapy

PLATELET TRANSFUSION THERAPY

Valerie Lyons, M.D., Fellow
Darrell J. Triulzi, M.D., Medical Director, Patient Transfusion Services

INTRODUCTION

Platelet transfusion plays an important role in the support of surgical, hematological, oncological, and transplant patients. Platelet refractoriness continues to challenge clinicians. The threshold for transfusing these platelets to patients continues to stimulate debate.

DESCRIPTION OF COMPONENTS

Platelets are prepared by donor whole blood centrifugation. A single unit of random donor platelets (RDP) contains a minimum of 5.5 x 10¹⁰ platelets suspended in 50 mL of plasma. Single donor platelets (SDP) are collected by apheresis and contain a minimum of 3.0 x 10¹¹platelets suspended in 200-600 mL of plasma. Leukoreduction (filtration) of platelets is frequently performed to remove the white blood cells responsible for alloimmunization and CMV transmission.

Platelet products may be stored for 5 days with continuous agitation. Once pooled, platelets outdate in 4 hours. Unused platelets must be returned to the blood bank within 30 minutes of issue.

COMPATIBILITY

Platelets are ABO and Rh typed. ABO identical or compatible units are preferred, but not required. In adults, ABO incompatible platelets may be used because the volume of plasma in the product is usually not clinically significant. Apheresis units may contain 350 mL of plasma, but passive transfer of antibodies rarely results in hemolysis. Cross-matching is not necessary because the volume of RBCs is <2 mL in each platelet component. However, 1 mL of RBCs is capable of causing alloimmunization to the D antigen. Rh compatibility is therefore recommended in women of childbearing age and children to prevent D antibody formation and potential hemolytic disease of the newborn. When Rh incompatible transfusions are necessary, prophylaxis with Rh Immune Globulin (300m ) should be considered.

DOSAGE

RDP is dosed at 1 unit per 10 kg of body weight. Stable patients who are not refractory to platelet transfusions can be expected to have a platelet count increase between 5,000-7,000 per unit. SDP is dosed at 1 apheresis unit per transfusion episode, which is generally equivalent to 6-8 units of pooled RDP.

INDICATIONS

Platelet transfusions are indicated to control or prevent bleeding associated with thrombocytopenia or platelet dysfunction. Guidelines for transfusing patients with thrombocytopenia include:

stable patients with platelet counts <10,000/m L
patients with platelet counts <20,000/m L associated with minor bleeding, fever or splenomegaly
patients with platelet counts < 50,000/m L with significant bleeding or undergoing an invasive procedure
patients with documented platelet function abnormalities

Patients who have ingested aspirin products 48 hours or longer prior to surgery are not at increased risk for bleeding due to platelet dysfunction.

CONTRAINDICATIONS AND PRECAUTIONS FOR PLATELET TRANSFUSIONS

thrombotic thrombocytopenic purpura

hemolytic uremic syndrome

heparin induced thrombocytopenia

platelet count >100,000/m L without evidence of platelet dysfunction

idiopathic thrombocytopenic purpura, unless bleeding is life threatening

prophylactically following routine cardiac surgery

COMPLICATIONS OF TRANSFUSION

A febrile non-hemolytic transfusion reaction (FNHTR) is the most common complication of platelet transfusion. FNHT reactions occur in approximately 1% of all transfusion reactions. This increases to as much as 30% in patients who have multiple transfusions. This is due to either recipient antibodies to donor WBCs or cytokines, i.e., IL-1, IL-6 and TNF in the platelet components that are released from the WBCs during storage. Symptoms include an increase in temperature, chills/rigors, tachycardia, and dyspnea. The reaction generally subsides within 30 minutes of stopping the transfusion. Most FNHTR do not recur. Patients with recurrent FNHTR may benefit from leukoreduced platelet components, particularly those leukoreduced prior to storage. A preexisting fever is not a contraindication for platelet transfusion.

Allergic reactions occur in approximately 1% of platelet transfusions. These reactions are generally mild and respond to antihistamines. Rare reactions to platelets include bacterial sepsis, transfusion related acute lung injury, and transfusion associated graft vs host disease. Fever and chills may be the presenting symptoms of acute hemolysis, bacterial sepsis, or FNHTR. Therefore, it is important to stop the transfusion and follow hospital policy for reporting transfusion reactions to the blood bank so that an investigation can determine the cause of the reaction.

MANAGEMENT OF PLATELET REFRACTORINESS

Patients exposed to foreign platelet antigens may develop alloantibodies that cause platelet immune refractoriness or alloimmunization. Previous exposure occurs through pregnancy or transfusion. Alloimmunization is most often due to patient antibodies against donor HLA class I antigens on the platelet surface. The risk of alloimmunization is greatly reduced by leukoreduction, with no difference in risk between leukoreduced RDP and SDP. To assess platelet response, a one hour post-platelet count is necessary. Patients with an adequate platelet increment of >10,000-15,000/m L at one hour are unlikely to be alloimmunized and are more likely to have poor platelet survival. This is due to clinical factors such as fever, sepsis, bleeding, or splenomegaly. Such patients may benefit from larger doses or more frequent platelet transfusions. A one hour post-platelet count increment of <10,000-15,000/m L, on two separate occasions, reflects a poor platelet response. This may be due to immune-mediated platelet destruction. Patients suspected of alloimmunization should have an HLA antibody screen. If positive, HLA antigen typing should be performed. In patients who do not respond to HLA matched SDP, a trial of IVIG or AMICAR may be beneficial. These patients may also benefit from ABO identical platelets.

FUTURE CONSIDERATIONS

The trend in transfusion medicine is toward pre-storage leukoreduction of all blood components, including platelets. This advancement should significantly reduce the number of FNHT reactions, as well as alloimmunization.

Although transmission of infectious disease through blood transfusion has been markedly reduced, a small risk remains despite rigorous donor screening and improved viral screening assays. The residual risk is the impetus for the development of virally inactivated blood components and blood substitutes.

A method of viral inactivation used for platelets involves the use of psoralens, a photochemical compound designed to inactivate lipid enveloped viruses. (Photochemical inactivation is ineffective for non-enveloped viruses.) Psoralens react with nucleic acid when exposed to ultraviolet light (UVA), producing an oxygen radical which attacks the viral envelope. After decontamination, psoralen is removed from the component. Preliminary studies have shown platelet yield and function to be adequate. Potential problems include the safety risk associated with residual psoralen in platelet components after treatment because psoralens are known mutagens¹. A novel psoralen, S-59, is currently under phase II clinical trials.

Platelet substitutes include thrombospheres and infusible platelet membranes (IPM). These products improve bleeding times, albeit transiently (48 hours). Their clinical utility seems to be in patients with thrombocytopenia and active bleeding. These products augment the function of normal circulating platelets. They are not thrombogenic. Heat inactivated human plasma is used in the manufacturing process of these products. Therefore, they could theoretically transmit pathogens. However, the potential advantages to these products include minimal viral and bacterial contamination as a result of heat treatment, reduced alloimmunization, prolonged shelf life (36 months), and reduced FNHTR².

REFERENCES

1. Pehtra JC. Laboratory Medicine 1994; 25:2.

2. Alung BM, et al. Transfusion 1997; 34: 866-76