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	Use of Blood Products Summary of key information and recommendations Principles of post-transfusion graft-versus-host disease (PT-GVHD) prevention in radiation event emergencies Kinds of blood and blood components that should be irradiated Illustration of blood product irradiation Background information about transfusion issues and policies Recipient risk factors associated with PT-GVHD Patient indications for blood irradiation Transfusion guidelines General guidelines for transfusion of blood and blood components Platelet transfusion guidelines Granulocyte transfusion guidelines Summary of key information and recommendation 1, 2 High-dose whole body radiation exposure induces hematopoietic cytopenias potentially requiring transfusion of blood products. Cytopenias requiring transfusion occur typically 2 to 4 weeks after high-dose radiation exposure, although time to nadir varies by patient, exposure dose, and dose rate. Blood loss requiring transfusion may also result from trauma associated with the radiation incident and gastrointestinal losses from a variety of causes. "Cellular" blood products that will be transfused to radiation victims should undergo the following procedures: 25 Gy of external radiation to prevent post-transfusion graft-versus-host disease (PT-GVHD) Leukocyte reduction (except granulocyte transfusions) to diminish the risk of: Febrile non-hemolytic reactions Immunosuppressive effects of blood transfusions Platelet alloimmunization Cytomegalovirus infection In the setting of a mass casualty event, if neither irradiation nor leukocyte reduction is available, lifesaving blood products should NOT be withheld. References: Circular of Information for the Use of Human Blood and Blood Components (PDF - 584 KB) (HHS/FDA, AABB, ABC, ARC, 7/2002) BCSH Blood Transfusion Task Force. Guidelines on gamma irradiation of blood components for the prevention of transfusion-associated graft-versus-host disease. Transfus Med. 1996;6(3):261-71. [PubMed Citation] Asai T et al. Guidelines for irradiation of blood and blood components to prevent post-transfusion graft-vs.-host disease in Japan. Transfus Med. 2000;10(4):315-20. [PubMed Citation] top of page Principles of post-transfusion graft-versus-host disease (PT-GVHD) prevention in radiation event emergencies 2 Avoid unnecessary transfusions. Avoid transfusions from first-degree relatives whenever possible because it increases the risk of PT-GVHD. If no other option is available, this blood must be irradiated. Transfusion of fresh blood, especially that stored for fewer than 3 days, should be avoided whenever possible, except for platelet concentrates. If allogeneic blood transfusion cannot be avoided, prevention of PT-GVHD by irradiation should be considered, especially for fresh blood. If blood transfusion is urgently required, and irradiated blood cannot be obtained immediately, there should be no hesitation about transfusing unirradiated blood or blood components. top of page Kinds of blood and blood components that should be irradiated 2 Whole blood Red blood cells including leuko-reduced red blood cells and frozen red blood cells Platelets Granulocytes (Note: These transfusions "may sometimes be useful for controlling refractory infections during prolonged neutropenia, but such transfusions have not yet been formally evaluated in controlled trials of subjects with radiation injury." 3 Fresh plasma (Note: There has been no confirmed case of PT-GVHD caused by fresh frozen plasma.) top of page Illustration of blood product irradiation top of page Background information about transfusion issues and policies 2, 3 Post-transfusion graft-versus-host disease (PT-GVHD) can be a life-threatening consequence of transfusing blood into certain patients, including those with significant whole body radiation exposure dose. If patients receiving large doses of whole body radiation need blood products for any reason, PT-GVHD must be avoided, as treatment is difficult and rarely successful. In PT-GVHD, donor lymphocytes in transfused blood attack recipient organs and tissues. The donor cells recognize recipient HLA, proliferate via lymphoblastic transformation, and are not eliminated by host immune defenses. The fresher the blood, the higher the risk of PT-GVHD, especially with blood used within 3 days after donation. Typical PT-GVHD presents with fever, generalized erythema 1 or 2 weeks after transfusion, followed by liver dysfunction, diarrhea, and bone marrow failure with pancytopenia. Most patients die of multi-organ failure within 1 month of transfusion. PT-GVHD occurs at a higher rate in patients with no history of blood transfusions and in patients who receive blood from relatives. Leukocyte reduction by filtration is not sufficient to prevent PT-GVHD, but it is recommended because it diminishes the following: Febrile non-hemolytic reactions Immunosuppressive effects of blood transfusions Platelet alloimmunization Cytomegalovirus infection Blood and blood product irradiation will prevent PT-GVHD. Both irradiation and leukocyte reduction are recommended when these are available. top of page Recipient risk factors associated with PT-GVHD 2 Recipients with pre-existing immunodeficiency Congenital immunodeficiency Hematopoietic stem cell or organ transplantation Fetuses, low-birth-weight babies, and newborns Leukemia and malignant lymphomas Patients undergoing treatment with high doses of anticancer drugs, therapeutic radiation, or immunosuppression Recipients with NO pre-existing immunodeficiency Individuals from an HLA one-way matched donor (recipient lacks HLA antigens on donor cells) Patients undergoing surgery for cardiovascular disease and cancer operations Patients receiving accidental high doses of radiation Patients ≥ 65 years of age top of page Patient indications for blood irradiation 2 Cytopenias from whole body radiation exposure Cardiovascular surgery Congenital immunodeficiency Hematopoietic transplantation Fetuses and low birth-weight infants Immunocompromised recipients of organ transplantation Recipient ≥ age 65 years Massive blood loss of severe trauma Malignant lymphomas, leukemias, hematological malignancies Solid tumor undergoing treatment with high-dose chemotherapy or radiation top of page Transfusion guidelines General guidelines for transfusion of blood and blood components Circular of Information for the Use of Human Blood and Blood Components (PDF - 584 KB) (HHS/FDA, AABB, ABC, ARC, 7/2002) Clinical Use of Blood Handbook (PDF - 701 KB) (WHO, 2002) top of page Platelet transfusion guidelines 3, 4 2001 Platelet Transfusion Guidelines from the American Society of Clinical Oncology3 Adapted by Waselenko et al. 3 Platelet products The benefits of pooled platelets or single donor platelets are similar; the two products can be used interchangeably. Single donor platelets from selected donors are preferred when histocompatible platelet transfusions (i.e., HLA-A and HLA-B antigen matched) are needed. Prophylactic platelet transfusion thresholds: Acute leukemia For adult patients, a threshold of 10,000/uL is recommended. Transfusion at higher levels may be necessary in the newborn or in patients with hemorrhage, high fever, hyperleukocytosis, rapid fall in platelet count, or coagulation abnormalities. Hematopoietic cell transplantation Same as for acute leukemia, with similar caveats. Chronic stable severe thrombocytopenia Many patients can be observed without prophylactic transfusion, reserving transfusion for episodes of hemorrhage or during times of active treatment. Solid tumors Evidence supports the benefit of prophylactic transfusion at a threshold of 10,000/uL or less. A threshold of 20,000/uL should be considered for patients receiving aggressive therapy for bladder cancer, as well as those with demonstrated necrotic tumors. Surgical or invasive procedures A platelet count of 40,000 to 50,000/uL is sufficient to perform major invasive procedures safely, in the absence of associated coagulation abnormalities. Certain procedures, such as bone marrow aspiration/biopsy can be performed safely with counts <20,000/uL; lumbar puncture in children is safe at platelet counts >10,000/uL. Prevention of RhD alloimmunization RhD-negative children (especially girls) and women of child-bearing age should be considered for treatment with either the exclusive use of platelets from RhD-negative donors or via anti-D immunoprophylaxis. Prevention of alloimmunization using leuko-reduced blood products It is appropriate to provide leuko-reduced blood products to patients with acute myelocytic leukemia from the time of diagnosis to ameliorate the problem of alloantibody-mediated refractoriness to platelet transfusion. Currently, this is not indicated in patients with cancer receiving RBCs or treatments that do not produce significant and sustained thrombocytopenia. Universal leukocyte reduction of blood products would obviate the need for these decisions in individual patients. Diagnosis of refractoriness to platelet transfusion A corrected count increment (CCI) of ≥5,000 is recommended as a definition of a satisfactory response. A rough estimate of a CCI of 5,000 is an absolute platelet count increment of 2,000/uL per unit of platelet concentrate given to an average-sized adult. For children, an approximate equivalent is an absolute platelet count increment of 3,500/uL per meter squared per transfused unit. A diagnosis of refractoriness should be entertained only when at least two consecutive ABO-compatible transfusions, stored less than 72 hours, result in poor increments. Management of refractoriness to platelet transfusion Patients with alloimmune refractory thrombocytopenia (i.e., poor increments in association with alloantibody detected using lymphocytotoxicity or antiplatelet antibody assays) are best managed with HLA-A and HLA-B antigen selected donors or from compatible donors identified using platelet cross matching techniques. Alloimmunized patients do not benefit from unmatched prophylactic platelet transfusions that fail to raise the platelet count. Such patients should be transfused only for hemorrhagic events. Adapted by Waselenko et al. 3 from American Society of Clinical Oncology4 top of page Granulocyte transfusion guidelines Stanworth SJ, Massey E, Hyde C, Brunskill S, Lucas G, Navarrete C, Marks DI. Granulocyte transfusions for treating infections in patients with neutropenia or neutrophil dysfunction. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD005339. Review. [PubMed Citation] Additional issues/warnings suggested by REMM consultants: Granulocyte transfusions should be considered for severely neutropenic patients (ANC <200/uL) when infection persists despite optimal antimicrobial and supportive therapy. Daily transfusions for a period of several days to weeks are guided by 24-hour WBC determinations and clinical response. Prophylactic transfusions have not been shown to reduce morbidity or mortality. The presence of red cells in granulocyte concentrates requires ABO compatibility, and HLA compatibility may be necessary for alloimmunized donors. Granulocyte transfusions must be irradiated but must NOT be filtered for leukoreduction. Fever, rigors, and respiratory distress during granulocyte transfusion indicate destruction of transfused cells and increased risk to the recipient. The course of transfusions should be terminated unless compatible granulocyte donors can be identified. top of page References BCSH Blood Transfusion Task Force. Guidelines on gamma irradiation of blood components for the prevention of transfusion-associated graft-versus-host disease. Transfus Med. 1996 Sep;6(3):261-71. [PubMed Citation] Asai T et al. Guidelines for irradiation of blood and blood components to prevent post-transfusion graft-vs.-host disease in Japan. Transfus Med. 2000 Dec;10(4):315-20. [PubMed Citation] Waselenko JK, Armitage JO, Dainiak N; Treatment of radiation injury in the adult. www.UpToDate.com (subscription required) Schiffer, CA, et al. Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2001 Mar 1;19(5):1519-38. [PubMed Citation] Anderson K. Broadening the spectrum of patient groups at risk for transfusion-associated GVHD: implications for universal irradiation of cellular blood components. Transfusion. 2003 Dec;43(12):1652-4. [PubMed Citation] Goans RE, Waselenko JK. Medical management of radiological casualties. Health Phys. 2005 Nov;89(5):505-12. [PubMed Citation] Webb IJ, Anderson KC. Transfusion-associated graft-verus-host disease. In: Popovsky MA, editor. Transfusion Reactions. Bethesda, MD: AABB Press, 2001: 171-186 Circular of Information for the Use of Human Blood and Blood Components (PDF - 584 KB) (HHS/FDA, AABB, ABC, ARC, 7/2002) Clinical Use of Blood Handbook (PDF - 701 KB) (WHO, 2002) Stanworth SJ, Massey E, Hyde C, Brunskill S, Lucas G, Navarrete C, Marks DI. Granulocyte transfusions for treating infections in patients with neutropenia or neutrophil dysfunction. Cochrane Database Syst Rev. 2005 Jul 20;(3):CD005339. Review. [PubMed Citation]

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