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in Red Blood Cell Transfusion Leukoreduction in Red Blood Cell Transfusion By Dr. Amr Mohamed Mahmoud

Etymology The name "white blood cell“ is derived from the fact that after centrifugation of a blood sample, the white cells are found in the buffy coat, a thin, typically white layer of nucleated cells between the sedimented red blood cells and the blood plasma. The scientific term leukocyte directly reflects this description, derived from Ancient Greek λευκό (white), and κύτταρο (cell).

During blood component preparation : Leukocyte content of whole blood averages two billion ( 2 x109 ) leukocytes per 500 mL of whole blood. During blood component preparation : 90% of leukocytes fractionate with the red blood cells (RBCs). 8% is retained within Platelet concentrates. 2% are present in the plasma before freezing.

Leukocyte reduction can be achieved by various techniques, including : Centrifugation Leukocyte filtration Sedimentation Washing Freeze-thawing Apheresis

Leukocyte Reduction Filters Purpose Mechanism Pore Size Generation No leukocyte filtration; “standard” blood filter Screen filter 170–260 um First Micro-aggregate filter; leukocyte filtration, 90% 20–49 um Second Adsorption filter; leukocyte filtration 99.9% Adhesion filter Not applicable Third

Leukocyte Filters

Adverse Effects Associated with Donor Leukocytes Nonhemolytic febrile transfusion reactions Transmission of leukocyte-associated viruses cytomegalovirus Alloimmunization Immunomodulatory effects Cancer recurrence Postoperative infections Transfusion storage time for red blood cells Transfusion storage time for platelets Transfusion-related acute lung injury Transfusion-associated graft-versus-host disease

1. Febrile Nonhemolytic Transfusion Reactions Definition : as a temperature increase of 1°C after an allogeneic blood transfusion. Cause : alloantibodies in the recipient’s plasma against antigens present on donor leukocytes and/or platelets Incidence: 0.5% in patients receiving a first transfusion 60% in Chronically transfused patients

2. Transmission of leukocyte-associated viruses (e.g.cytomegalovirus) Transfusion-associated CMV infection is a significant cause of morbidity and mortality in immuno-compromised patients and especially in organ transplant recipients. After either kidney or liver transplants, more than 60% of patients develop antibodies against CMV.

3. Platelet Refractoriness and Alloimmunization Alloimmunization can reduce the clinical effectiveness of platelet transfusions by 50%. Especially prevalent among those : - Patients receiving pooled random donor platelet concentrates. - Who are Pregnant.

4. Immunomodulation and Postoperative Infectious Complications Contaminating leukocytes in RBC transfusions might be responsible for down-regulation of : Natural-killer (NK) cell activity, T cell proliferation T lymphocyte antitumor activity CD-4 helper to CD-8 suppressor ratio Lymphocyte blastogenesis

5. Cancer Recurrence An association between allogeneic blood transfusion and colorectal cancer recurrence after surgery. Blood transfusions in colorectal surgery patients have been reported to increase cancer recurrence by 37%also have been associated with increased recurrence of breast, lung, kidney, prostate, stomach, cervical, laryngeal, soft tissue, and bone malignancies.

6. Postoperative infections Transfusion of blood components containing bacteria may lead to potentially fatal sepsis. Cause : inadequate skin preparation before venipuncture. Common pathogens : include Gram-negative endotoxin producing organisms such as Yersinia enterocolitica, pseudomonas and enterobacter

6. Postoperative infections Optimal storage time before filtration to allow for maximal leukocyte ingestion of bacteria appeared to be between 2 and 12 hours. The beneficial effect of leukocyte reduction may lie in removal of leukocytes containing ingested bacteria.

7. Transfusion storage time for red blood cells Decrease ATP. Glucose consumption. Increase lactate and k+ production. The presence of leukocytes in blood components reduces glucose availability. leukocyte lysis leads to release of cytokines that reduce RBC survival.

8. Transfusion storage time for platelets Decreases in pH Increases in glucose consumption Lactate production Lactic dehydrogenase release Platelets stored with leukocytes express decreased quantities of glycoprotein Ib (GPIb) receptor, resulting in a bleeding disorders.

9. Transfusion-related acute lung injury Stored blood contains micro-aggregates of degenerated leukocytes, platelets and fibrin These micro-aggregates have been associated with pulmonary insufficiency due to agglutination of donor leukocytes by recipient antibodies. C/P : severe dyspnea, non-cardiogenic pulmonary edema.

10. Transfusion-associated graft-versus-host disease (GVHD) GVHD is a potentially lethal condition. Cause : donor T lymphocytes. Mechanism : immunocompromised recipients, host defense mechanisms fail to suppress viable transfused donor lymphocytes, which engraft within the recipient’s marrow, ultimately resulting in death. Occurrence : 1. when the donor and recipient share an HLA haplotype. 2. Use of directed-donor blood from first degree relatives. Prophylaxis : gamma-irradiation.

Adverse Effects of Leukocyte Reduction Few side effects have been reported Hypotension : due to release of bradykinin like vasoactive substance esp. in patients receiving ACEI prolong intravascular half life of bradykinin : by decreasing bradykinin degradation. Complement activation and formation of platelets aggregate 2%-8% decrease in potency of cellular components of blood.

3. Red eye syndrome ( allergic conjunctivitis). - Erythema 100%. - Periorbital edema 16% - Eye pain 15% - Itching Symptoms resolve 48 hours but erythema may require up to 3 weeks.