Intensive therapies producing severe and sustained thrombocytopenia are used routinely in patients with hematologic malignancies and are being applied to many patients with solid tumors as well.

Platelet Products

Platelets for transfusion can be prepared either by separation of units of platelet concentrates (PCs) from whole blood, which are pooled before administration, or by apheresis from single donors. Comparative studies have shown that the posttransfusion increments, hemostatic benefit, and side effects are similar with either product. Thus, in routine circumstances, they can be used interchangeably.

Both preparations can be store for up 5 days after collection at 20℃ to 24℃ with good maintenance of platelet viability.

PCs, which can also be called random donor platelets, are prepared by centrifugation of standard units of whole blood. With the separate technology, PCs contain approximately 0.5 to 0.75 × 1011 platelets/unit or approximately 60% to 75% of the platelets from the original unit of whole blood. However, PCs also contain 108 to 109 WBCs or approximately 50% or more of the leukocytes from original unit of whole blood. Because the PCs are centrifuged from whole blood, the volume of plasma in might be too large for pediatric patients or recipients require severe volume restriction.

Single-donor platelets are produced by apheresis. Donor usually undergo two venipunctures. Blood pumped from one vein passes through a blood-cell separator centrifugation system with removal of the platelets or other cellular components and return of the plasma and RBCs to the donor's other arm.

Plateletpheresis usually requires approximately 11/2 to 2 hours and involves processing 4,000 to 5,000 mL of the donor's blood. This results in a plateletpheresis product that contains the number of platelets equivalent to six to nine units of PC prepared from whole blood. Some centers have recently begun to split their apheresis collections into two products so that the dose may actually be more equivalent to four to five units of PC.

Single-donor platelets contain at least 3 × 1011 platelets in each bag of apheresis. Each apheresis product has a volume of approximately 200 mL and contains few red cells, so that red cell crossmatching is not necessary. The WBC content varies, but most plateletpheresis products now contain less than 5 × 106 leukocytes and can be considered to be leukocyte reduced.

Prophylactic VS Therapeutic Platelet Transfusion

It is recommended that prophylactic platelet transfusion be administered to patients with thrombocytopenia resulting from impaired bone marrow function to reduce the risk of hemorrhage when the platelet count falls below a predefined threshold level. This threshold level for transfusion varies according to the patient's diagnosis, clinical condition, and treatment modality. For example, if the patient has a clinical condition believed to be associated with increased risks of bleeding, it should be provisioned that the threshold might be set greater.

Why prophylactic transfusion? In 1966, Han et al reported that the 63% incidence of hemorrhagic deaths occurring in leukemia patients in the yeaer before the implementation of a prophylactic platelet transfusion policy decreased to 15% in the following year. A similar reduction was observed in a small double-blinded randomized clinical trial performed by Higby et al in 21 patients with acute leukemia.

Prevention of Alloimmunization to RhD Antigens

Platelets do not express Rh antigens on their surface, but the quantity of RBCs in platelet preparations is sufficient to induce Rh sensitization, even in immunosuppressed cancer patients. Different studies have documented that anti-D antibodies can be detected in 7.8% to 19% of heterogeneous groups of RhD-negative cancer patients exposed to RhD antigens via transfusion. Two small studies have demonstrated that RhD immunoprophylaxis can prevent the development of anti-D in this setting.

Thus, if platelets from an Rh-positive donor or platelets from a donor of unknown Rh phenotype are given to an Rh-negative recipient, administration of Rh immunoprophylaxis should be considered, especially for younger female patients who might become pregnant after successful treatment.

The amount of anti-D immunoglobulin necessary to prevent sensitization depends on the number of contaminating RBCs in the PCs. Extrapolating from guidelines used to prevent maternal sensitization after fetal-maternal hemorrhage, a dose of 25 mcg (125 IU) of anti-D immunoglobulin will protect aganist 1mL of RBCs. If possible, the immunoglobulin should be given before or immediately after the transfusion, although, as in the obstetrical setting, it may still be efficacious if given within 72 hours of exposure to the RhD-positive RBCs.

Prevention of Alloimmunization Using Leukoreduced Blood Products

Alloimmunization against histocompatibility antigens occurs in many recipients of multiple random donor platelet transfusions and is the most important long-term complication of platelet transfusion. Recent experience suggests that between 25% and 35% of newly diagnosed patients with AML will produce lymphocytotoxic antibody and become alloimmunized and refractory to nonhistocompatible platelet transfusion. There is evidence from murine and canine models that the leukocytes contaminating platelet preparations are the primary stimulus for alloimmunization and the alloimmunization due to leukocytes will mediate refractoriness to platelet transfusion.

The methods to remove leukocytes include filtration or modification of the antigen presenting capacity of the leukocyte. It has been shown that ultraviolet B irradiation can abolish reactivity in mixed lymphocyte reactions and do not affect platelet function in vitro.

Despite greater understanding of factors that influence the results of transfusion from HLA-selected donors, as many as 40% to 60% of apparently histocompatible platelet transfusions administered to alloimmunized patients are unsuccessful. So the elimination of alloimmunization would greatly simplify platelet transfusion therapy and increase the safety of intensive postremission therapy administered to patients with leukemia.

The incidence of alloantibody mediated refractoriness to platelet transfusion can be decreased in patients with acute myeloid leukemia receiving induction chemotherapy when both platelet and RBC products are leukoreduced by filtration before transfusion. Although randomized trials have not been conducted in other patients groups, it is likely that alloimmunization can also be decreased in patients with other types of leukemia and in other cancer patients receiving chemotherapy. But there are no data in patients who are not receiving chemotherapy in the same time periods that the transfusion are being administered (e.g., aplastic anemia, myelodysplasia), however, the consensus of opinion of American Society of Clinical Oncology (ASCO) would favor its use in these patients as well.

Because leukoreduction ads appreciably to the costs of transfusion, it should be used only for patients expected to require multiple or long-term platelet transfusions during their treatment courses and is not indicated for patients with cancer receiving RBCs or therapies that do not produce significant and sustained thrombocytopenia. However, because the antibodies often developed after 3 to 4 weeks, at a time when the patients may no longer have require platelet transfusion during induction, the major impact of prevention of alloimmunization may be noted in patients receiving intensive consolidation.

Update on Oct 9th 2016

From the perspective of critical care medicine.

There are two main indications for platelet transfusion: to promote hemostasis in bleeding patients with thrombocytopenia or functional platelet disorders and to prevent bleeding in patients with profound thrombocytopenia. Indications for platelet transfusion are related to 1) the underlying disease, 2) presence or absence of active bleeding, 3) anticipation of invasive procedures, and 4) platelet count. In general, patients with active life-threatening bleeding, intracranial hemorrhage, or undergoing neurological or vascular surgery should receive platelet transfusion to maintain concentrations over 100 x 109/L. For most bleeding situations, general surgical procedures, and routine endoscopies with biopsies; however, lower thresholds (50 x 109/L) are adequate; 20 x 109/L is an adequate platelet threshold for most bedside, needle-based procedures including central venous catheterization and lumbar puncture. While the role of prophylactic platelet transfusion in patients with hematologic malignancy has been debated, there appears to be some benefit when a transfusion threshold of 10 x 109/L is used.

In clinical practice, each unit of pooled, random donor platelets increases the circulating platelet count by 5 to 10 x 109/L in patients with average body size. For this reason, random donor platelets are pooled and typically given as a "six pack". By comparsion, one single-donor pheresis platelet unit may increase the platelet count by 30 to 60 x 109/L and these are administered singly. Routine monitoring of platelet transfusion should include posttransfusion platelet count to determine transfusion responsiveness. Failure of the circulating platelet count to increase may result from destruction of the transfused platelets or consumption of the platelets at sites of injury or clot activation. Risks for ineffective platelet transfusion include ITP, presence of antiplatelet antibodies, DIC, drug-induced thrombocytopenia, and sepsis. In general, platelet transfusions are ineffective if the cause of thrombocytopenia is enhanced destruction, since the transfused platelets are destroyed through the same mechanism.