Authors: Christopher Busack MD, Chinwe Unegbu MD, and Daniela Perez-Velasco DO – Children’s National Hospital
A 6-month-old male with Hypoplastic Left Heart Syndrome (HLHS) s/p Norwood/Sano modification receives an ABO-incompatible heart transplant secondary to severe tricuspid regurgitation and right ventricular dysfunction. After separation from cardiopulmonary bypass, the patient received 10 mL/kg each of platelets, cryoprecipitate, fresh frozen plasma, and packed red blood cells. Which of the administered blood products carries the HIGHEST RISK of transmitting viral pathogens?
Transfusion of blood products has significant risks and benefits which must be carefully balanced. A recent publication by Faraoni et al. provides evidence-based guidelines for the use of blood products in the perioperative period for children undergoing cardiac surgery.
In the US, to facilitate more targeted transfusion of deficient blood components, whole blood is typically separated into various components. Fresh frozen plasma (FFP) is frozen within 8 hours of collection. Cryoprecipitate, also known as antihemophilic factor, is then prepared from FFP in the following manner. FFP is slowly thawed to 1-6 o C followed by centrifugation. High-molecular-weight plasma proteins form a precipitate during centrifugation known as cryoprecipitate, which is then is collected, resuspended in a small amount of plasma (10-15 mL) and refrozen. Cryoprecipitate has several important coagulation proteins including fibrinogen, antihemophilic factor (factor VIII), von Willebrand factor, fibrin stabilizing factor (factor XIII), fibronectin, and small amounts of other plasma proteins. Cryoprecipitate has higher concentrations of coagulation proteins due to the smaller volume; making this blood product more appropriate for smaller patients in need of an increased concentration of the aforementioned coagulation proteins. Cryoprecipitate doses of 1-2 units per 10 kg of body weight will increase fibrinogen concentration by 60 to 100 mg/dL.
In the 1960’s, cryoprecipitate was used to manage patients with Hemophilia A. The initial preparations of cryoprecipitate had relatively low Factor VIII concentrations. Therefore, Hemophilia A patients required transfusion of multiple bags of cryoprecipitate to achieve an adequate dose of 20-30 IU/kg. Additionally, cryoprecipitate was pooled from large amounts of plasma obtained from multiple donors. Unfortunately, these specimens were often contaminated with hepatitis viruses. It is estimated that in the 1980’s, HIV was transmitted to 50% of people living with Hemophilia A. In current medical practice, cryoprecipitate is used to correct fibrinogen deficiency due to acute blood loss (secondary to trauma, surgery, etc) or qualitative abnormalities of the fibrinogen protein. Currently, there are no widely available commercial methods of inactivating viral pathogens in FFP or cryoprecipitate. As cryoprecipitate is a pooled product, its administration carries the highest risk of the transmission of viral pathogens (Munlemvo et al). Many Western European countries and Canada have banned the use of cryoprecipitate due to concerns about pathogen transmission. Cryoprecipitate is no longer recommended to treat von Willebrand’s Disease or Hemophilia A unless recombinant or viral inactivated products are not available. The availability of highly purified coagulation factor concentrates and recombinant protein preparations has superseded the use of cryoprecipitate for many coagulopathies.
In contrast, platelets are associated with the highest risk of bacterial contamination due to the need for storage at room temperature. Transfusion transmitted infections, although rare, can have serious consequences. Nucleic acid testing (NAT) has increased the sensitivity of detecting infectious agents in donor blood. This form of testing directly tests the donated blood for viruses, whereas previous screening was done by testing antibody response to viral infection. NAT has reduced the risk of infectious transmission to less than 1 in 1,000,000. Donor blood is now screened for many viruses and bacteria such as the following: HIV, hepatitis B, hepatitis C, HTLV, syphilis, West Nile virus, Chagas disease, Zika virus, and babesiosis. Leukoreduction of blood products is also used to decrease the risk of CMV transmission, which can be fatal in newborns and immunocompromised patients.
Transfusion of blood products carries additional risks occurring with greater frequency than infectious transmission. Recent investigations suggest that blood product transfusion during pediatric cardiac surgery may be associated with adverse outcomes such as renal failure, low cardiac output, vascular thrombosis, and alloimmunization leading to increased time to orthotopic transplantation, prolonged hospital stay, and increased mortality. Guidelines have shifted away from recommending specific hemoglobin targets and instead weighing the risk of complications from blood product transfusion versus the risk of complications from inadequate oxygen-carrying capacity, inadequate hemostasis, and/or inadequate intravascular volume.
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