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Platelets for transfusion can be prepared either by separation of platelet concentrates from whole blood or by apheresis from single donors. Comparative studies have shown that post-transfusion increment, platelet survival and hemostatic effect are similar with either product. Random Donor Platelets Platelets prepared from whole blood are often referred to as random donor platelet concentrates. Platelet rich plasma is separated from red blood cells by centrifugation at a low G force within 4 hours after donation. Platelet rich plasma is then centrifuged at higher G force and most of the platelet poor plasma supernatant is removed. The remaining platelet concentrate contains between 5.5 and 8.5 X 1010 platelets suspended in about 50 mL of plasma. This is approximately 70% of the platelets in the original unit of whole blood. Platelets are stored at room temperature using continuous gentle horizontal agitation in plastic bags designed to optimize oxygen and carbon dioxide exchange. Platelets can be preserved for 7 days under these conditions, but their shelf life is limited to 5 days because of potential problems with bacterial contamination. Platelet concentrates are pooled immediately prior to transfusion and can then be stored for 4 hours. One drawback of random donor platelets is that the concentrates contain 108 to 109 white blood cells or approximately 50% of the leukocytes from the original unit of whole blood. Random donor platelets should be transfused through a bedside leukocyte reduction filter. Random donor platelet concentrates may contain up to 0.5 mL of red cells. Different studies have demonstrated that 8 to 19% of Rh negative cancer patients form anti-D antibody if transfused with Rh positive platelet concentrates. Rh negative units should be used for Rh negative female children and women of childbearing age. If this is not possible then one vial of Rh immune globulin may be given before or immediately after transfusion with Rh positive platelets. Because these patients are thrombocytopenic, it is preferable to administer anti-D intravenously. WinRho SDF is the only licensed IV preparation available in the United States. A dose of 25 ug (125 IU) will protect against 1 mL of RBCs. Single Donor Platelets Apheresis platelets are usually called single donor platelets because they are collected from a single donor with an automated cell separator. Donors usually have an IV line in each arm. Blood pumped from one arm passes through a blood cell separator centrifugation system that collects platelets and returns plasma and red cells to the donor's other arm. Between 4000 and 5000 mL of blood are processed over 1.5 to 2 hours. A single donor platelet concentrate contains a minimum of 3.0 X 1011 platelets suspended in approximately 200 mL of plasma, which is the equivalent of 6 to 8 random donor platelet concentrates. They can be stored up to 5 days under the same conditions as random donor platelet concentrates. Five day old apheresis platelets produce the same posttransfusion platelet increment as one day old units. Single donor apheresis platelets contain fewer than 5 x 106 white blood cells and are considered to be leukocyte reduced. Additional leukocyte reduction filtration is not necessary. Rh negative patients do not need Rh immune globulin after transfusion of Rh positive apheresis platelets because they contain so few red blood cells. Single donor platelets offer several advantages over random donor concentrates including:
Platelet ABO Compatibility The term "ABO-compatible" is confusing when thinking about blood components other than RBCs. Red Blood Cell units contain cells carrying the ABO antigens of the donor and plasma carrying soluble ABO antigens and anti-A and anti-B antibodies. The recipient also possesses ABO antigens and antibodies, but in much larger amounts. Group O blood components do not express cellular and soluble A and B antigens, but do contain anti-A and anti-B antibodies, often in higher titer and avidity than in group A or B components. Group O (so-called universal donor) RBCs usually can be safely transfused to group A or B patients, because the volume of residual incompatible plasma (30 - 70 mL) is minimal. In contrast, a single donor (apheresis) platelet or a pool of 10 random donor platelet concentrates is suspended in 200 to 600 mL of donor plasma. If these platelets are not ABO identical, large volumes of incompatible plasma will be infused, often on a daily basis for extended periods. Anti-A and anti-B can bind to RBCs and to soluble A and B antigens. In the latter instance, immune complexes are formed that can initiate inflammation, tissue injury, and immune suppression. Thus, unlike RBC transfusions, there really are no ABO compatible platelet transfusions. Platelet transfusions should be classified as either ABO identical or nonidentical. The most obvious adverse effect of transfusing ABO nonidentical platelets is hemolysis. The risk of an ABO hemolytic reaction is rare after a single transfusion of ABO nonidentical platelets, but increases significantly when large volumes are transfused over a relatively short time period. Hemolysis is unlikely after a single ABO incompatible unit for two reasons. First, transfused plasma (500 mL) is diluted almost 10 fold in the patient's intravascular blood volume (5000 mL). Second, and perhaps most importantly, transfused anti-A and anti-B antibodies are rapidly neutralized by binding to circulating soluble A and B antigens as well as tissue A and B antigens. Transfusion of platelets containing large volumes of ABO incompatible plasma saturates soluble and tissue ABO antigen sites and permits binding of excess anti-A and/or anti-B to red blood cells. When this happens, patients develop a positive direct antiglobulin test (DAT) and possibly hemolysis. Other serious adverse consequences of transfusing ABO nonidentical platelets have also been reported. Chronically transfused patients with hematologic disease who are transfused with nonidentical ABO platelets have lower post-transfusion platelet counts, require almost twice as many platelet transfusions, and develop platelet refractoriness earlier than patients receiving ABO identical platelet transfusions. Transfusion of group A or B platelets to group O recipients results in post-transfusion platelet increments that are 20% less than those obtained with ABO identical platelet transfusions. Decreased platelet survival is due to the binding of recipient anti-A and/or anti-B to the transfused donor platelets. Transfusion of group O platelets to group A or B recipients results in even lower post-transfusion platelet increments, suggesting that incompatible plasma is an even more important risk factor. In this situation, anti-A and anti-B in the transfused plasma forms immune complexes with soluble A and/or B antigens circulating in the recipient's plasma. These complexes circulate for hours to days after incompatible transfusions and can bind to platelets resulting in their activation and premature destruction. Transfusion of ABO nonidentical platelets to transplant patients can have even more deleterious effects. Patients receiving allogeneic marrow or stem cell transplants and patients receiving chemotherapy for acute leukemia have increased mortality due to multi-organ failure and sepsis if they are transfused with ABO nonidentical platelets. ABO antigens, like HLA antigens, are widely expressed on the endothelium lining of blood vessels. Anti-A and/or anti-B antibodies present in ABO incompatible platelets appear to inflict direct damage to organs by binding to endothelial A and B antigens. The formation of anti-A and/or anti-B immune complexes also suppresses cellular immunity, resulting in a predisposition to infection. To provide optimal patient care SLH Blood Bank issues ABO identical apheresis platelets whenever possible. Apheresis platelets are preferred over random donor platelets, because of the lower risks associated with a decreased number of donor exposures. If ABO identical apheresis platelets are not available, it is most important to avoid transfusing substantial amounts of anti-A and/or anti-B to patients expressing those antigens. Therefore, the second best choice is to provide random donor ABO identical platelets with a bedside leukocyte reduction filter. When neither apheresis nor random donor ABO identical platelets are available, the ordering physician should be consulted to see if the transfusion could be delayed until ABO identical platelets become available. If immediate transfusion is necessary, the following Table should be consulted for additional choices. Platelet Transfusions for All Patients except ABO Mismatched Allogeneic Blood & Marrow Transplant Recipients
The Transfusion Service should also refrain from infusing substantial amounts of soluble or cell associated A and/or B antigens to patients with detectable levels of the corresponding antibody. The most common example is the transfusion of Group A or B platelets to a group O recipient. This practice is permissible if a patient is hemorrhaging and has a platelet count below 100,000 and neither group O random nor single donor platelets are available. Summary
The dose of platelets should be individualized. A number of simple rules can be used to calculate the appropriate dose.
The most common reasons for transfusing platelets are:
A. Decreased platelet production
Premature infants < 37 weeks gestation
Cryoprecipitate transiently corrects uremic platelet defects. Reversal of a qualitative platelet defect requires 10 units of cryoprecipitate. Improvement in platelet function may not be evident for up to 4 hours and lasts approximately 24 hours. Repeat doses of cryoprecipitate are less beneficial. Dialysis also corrects the uremic qualitative platelet defect. Thus, the use of cryoprecipitate to correct a qualitative platelet defect should be reserved for life-threatening hemorrhage or prior to an invasive procedure. Alternatively, desmopressin (DDAVP) or dialysis can be used to correct the uremic platelet defect. DDAVP can be used for both acquired and congenital platelet defects. The recommended dose is 0.3 mg/Kg given intravenously over a period of 15 to 30 minutes. If used preoperatively, the dose should be given 30 minutes prior to the scheduled procedure. Repeat use may result in tachyphylaxis, which can be overcome by waiting 24 to 48 hours before the second dose. Monitoring The Effectiveness Of Platelet Transfusions
Most platelet transfusions are given prophylactically. This means that platelets are transfused to a patient who has thrombocytopenia, but is not bleeding. In stable patients without other factors that increase the risk of bleeding, the goal is to continuously maintain the platelet count above 10 to 20,000/uL. The immediate posttransfusion platelet count should be >20,000/uL and the platelet count obtained 24 hours later should still be >10,000/uL. In more unstable patients with other risk factors for bleeding (e.g. medications, liver disease, renal failure, prolonged PT &/or PTT, sepsis, DIC), it is more desirable for the immediate posttransfusion platelet count to be >30,000/uL and the 24 hour platelet count to be >20,000/uL. Overt bleeding will be controlled in nearly all thrombocytopenic patients if the posttransfusion platelet count is 40,000/uL or higher. In contrast, bleeding diminishes in only about one third of patients when the posttransfusion platelet count remains < 20,000/uL. If the posttransfusion platelet count is not sustained, bleeding will resume when the platelet count falls below 10,000/uL. Therefore, the platelet count needs to be maintained above 10,000 to 20,000/uL for at least 24 hours. Refractoriness Alloimmunization against histocompatibility antigens occurs in 25 to 35% of patients with acute leukemia who are transfused with multiple random donor platelet transfusions and in 4 to 5% transfused with apheresis platelets. This is the most important long-term complication of platelet transfusions because patients become refractory to future platelet transfusions.
If the platelet antibody test is positive, a refractory patient is best managed by transfusion of crossmatch compatible apheresis platelets. There is no evidence that alloimmunized patients benefit from continued prophylactic transfusion of incompatible platelets that do not produce an increase in posttransfusion platelet count. If there is an inadequate post transfusion platelet count increment following 4 consecutive crossmatch compatible single donor platelets, it is reasonable to revert to the use of randomly selected products. It is important to obtain platelet counts 10 minutes to 1 hour following each transfusion of compatible platelets since a useful but temporary post transfusion increment may occur but be missed if platelet counts are not obtained until the next morning. Bleeding patients, for whom compatible platelet donors cannot be found in a timely manner, may benefit from repeated transfusions of pooled random donor platelets (10 or more concentrates per pool). Large numbers of random platelets may adsorb much of the platelet antibody and fortuitously include some compatible units. Intravenous immune globulin and plasma exchanges are not effective in reducing the refractory state. If the platelet antibody screening test is negative, refractoriness is probably due to clinical factors rather than alloimmunization and crossmatched platelets will not be beneficial . |
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