Platelet transfusion

Contamination of blood products with lymphocytes can lead to transfusion-induced reactions ranging from a mild fever to severe reactions such as alloimmunization and graft versus host disease (GvHD), in which the transfused lymphocytes (graft) survive the defensive immune reaction of the patient (host) and start a reaction which destroys the cells of the host. The patient also may develop an immune response to the human leukocyte antigen (HLA) type of the graft s cells and reject all platelet transfusions that do not match their own HLA system. The HLA system, found on blood platelets and lymphocytes, is more compHcated than, but similar to, the ABO blood group system of red cells. 

They release adenosine diphosphate [58-64-0 (ADP) and thromboxane [57576-52-0] which results in vascular contraction and, indirectiy, in the formation of fibrin clot. Platelet transfusions are indicated for patients with thrombocytopenia, ie, a shortage of healthy platelets or thrombocytopathy, ie, platelet malignancy associated with spontaneous hemorrhages. 

Transfusion-induced autoimmune disease has been a significant complication in the treatment of patients who require multiple platelet transfusions. Platelets and lymphocytes carry their own blood group system, ie, the human leukocyte antigen (HLA) system, and it can be difficult to find an HLA matched donor. A mismatched platelet transfusion does not induce immediate adverse reactions, but may cause the patient to become refractory to the HLA type of the transfused platelets. The next time platelets with an HLA type similar to that of the transfused platelets are transfused, they are rejected by the patient and thus have no clinical efficacy. Exposure to platelets originating from different donors is minimized by the use of apheresis platelets. One transfusable dose (unit) of apheresis platelets contains 3-5 x 10 platelets. An equal dose of platelets from whole blood donation requires platelets from six to eight units of whole blood. Furthermore, platelets can be donated every 10 days, versus 10 weeks for whole blood donations. 

J. P. Dutcher, "Platelet Transfusion Therapy in Patients with Malignancy," in J. P. Dutcher, ed.. Modem Transfusion Therapy, CRC Press, Boca Raton, Ha., 1990. 

Thrombocytopenia is another dose-limiting side effect of chemotherapy. The primary treatment for thrombocytopenia is platelet transfusions. The risk of bleeding is significant when platelet counts are less than 10,000/mm3 (10 x 109/L) ... 

Platelet transfusions are used to prevent hemorrhage. Patients with uncomplicated thrombocytopenia can be transfused when the platelet count falls below 10,000/pL (10 x 109/L). Patients who are either highly febrile or actively bleeding may require transfusions at higher levels. Red blood cell transfusions generally are not necessary for a hemoglobin concentration greater than 8 g/dL (80 g/L, 4.96 mmol/L). 

Severe thrombocytopenia and reduction of the need for platelet transfusions Chemotherapy-induced thrombocytopenia Nov. 1997... 

Prolonged bleeding time is normalized within 2 hours after administration of 20 mg methylprednisolone IV. Platelet transfusions also may be used to reverse the effect of ticlopidine on bleeding. If possible, avoid platelet transfusions because they may accelerate thrombosis in patients with TTP on ticlopidine. 

E. Therapeutic response The primary end point of one randomized, placebo-controUed trial was whether the patient required one or more platelet transfusions in the subsequent chemotherapy cycle. More patients avoided platelet transfusion in the Neumega arm (28%) than in the placebo arm (7%). 

F. Role in therapy According to Micro-medex, treatment of severe chemotherapy-related thrombocytopenia is hmited to platelet transfusions. There is a need for an alternative, especially due to the frequent use of myeloid colony-stimulating factors (G-CSF, GM-CSF) to reduce febrile neutropenia although effective, their use increases the risk of acute and prolonged thrombocytopenia, and the need for platelet transfusions. Other cytokines, such as interleukin-1 and interleukin-6, have been investigated as a means of ameliorating chemotherapy-induced thrombocytopenia, but results have been equivocal. 

In a very early study, Shaffer et al. (1945) administered single oral doses of 5 and 10 g di(2-ethylhexyl) phthalate to two human subjects and reported that approximately 4.5% of the dose was excreted in the urine within 24 h. Schmid and Schlatter (1985) also administered di(2-ethylhexyl) phthalate orally to two human subjects, but at the much lower dose of 30 mg per person. These authors reported that 11-15% of the dose was excreted in the urine and a urinary elimination half-life of about 12 h can be estimated from the data. In the same study, the two volunteers also received 10 mg di(2-ethylhexyl) phthalate daily for four days, there being no evidence of accumulation, with 11 and 33 % of the dose recovered each day in the urine. In contrast, Rubin and Schififer (1976) reported data from two patients receiving platelet transfusions from bags containing di(2-ethylhexyl) phthalate, who excreted between 60 and 90% of the infused dose in the urine collected for 24 h after transfusion. 

Interleukin-11 is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for treatment of nonmyeloid cancers. Clinical trials show that it reduces the number of platelet transfusions required by... 

Patients with thrombocytopenia have a high risk of hemorrhage. While platelet transfusion is... 

Interleukin-11 is the first growth factor to gain FDA approval for treatment of thrombocytopenia. It is approved for the secondary prevention of thrombocytopenia in patients receiving cytotoxic chemotherapy for treatment of nonmyeloid cancers. Clinical trials show that it reduces the number of platelet transfusions required by patients who experienced severe thrombocytopenia after a previous cycle of chemotherapy. Although IL-11 has broad stimulatory effects on hematopoietic cell lineages in vitro, it does not appear to have significant effects on the leukopenia or neutropenia caused by myelosuppressive chemotherapy. Interleukin-11 is given by subcutaneous injection at a dose of 50 g/kg/d. It is started 6-24 hours after completion of chemotherapy and continued for 14-21 days or until the platelet count passes the nadir and rises to > 50,000 cells/ L. 

The bleeding potential is similar among the agents. However, thrombocytopenia, particularly profound thrombocytopenia (platelet count <50,000 mrrT3) occurs with a two-to four-fold higher frequency with abciximab (0.4— 1.0%) compared with eptifibatide (0-0.2%) or tirofiban (0,1 —0.3%) (6), The exact mechanism of this difference is not clear, However, immune complex-mediated reaction (due to an anamnestic response to the humanized chimeric antibody) may contribute to rapid precipitation of thrombocytopenia with abciximab (6), Platelet counts should, therefore, be measured early (within the first one to four hours) after administration of these agents and followed for the duration of therapy. Platelet transfusion should be considered for profound thrombocytopenia with or without serious bleeding (6). 

The main concern with the use of Gp llb/llla inhibitors is the risk of hemorrhage and thrombocytopenia. On meta-analysis, major hemorrhage was significantly more likely with abciximab than with either tirofiban (standard regimen) or eptifibatide (33), The TARGET trial demonstrated abciximab to predispose to thrombocytopenia when compared to tirofiban (35), Regardless, thrombocytopenia (platelet count <20,000/ jJ) is rare (<3%) and can often be treated conservatively, without the need for platelet transfusions,... 

Antidote Vitamin K, (1) Platelet transfusion (2) Protamine (3) Protamine (4) Protamine (5) Protamine None (6) None (11) None None... 

Consider platelet transfusions if platelet count is low or in case of bleeding. 

Ikeda H, Mitani T, Okuma M, Haga H, Ohtzuka S, Kato T, Nakase T, SdcigucU S A new platelet specific antigen Nak(a) involved in the refiactoriness t HLA-matched platelet transfusion. Vox Sang 57 213-217,1989... 

Castillo R, Memteagudo J, Escolar G, Ordinas A, Magallon M, Martin Villar J Hemostatic effect of ncamal platelet transfusion in severe von Willebrand disease p ents. Blood 77 1901-1905,1991. 

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