Blood Product Selection and Administration

Fresh Frozen Plasma

Plasma is removed from whole blood and frozen below 55˚F to make FFP. It contains all of the coagulation factors but is not a concentrate. Fresh frozen plasma contains both stable and labile components of the fibrinolytic, coagulation, and complement systems, as well as proteins that maintain oncotic pressure. Unlike PRBC, where type O is the universal donor, in FFP, AB type is the universal donor for transfusion. In the ED, FFP is used for the reversal of coagulopathy in bleeding patients and for replacement of coagulation factors when specific factors are unavailable. It is also given to patients requiring large volumes of blood components (ie, massive blood transfusion protocol).¹⁰

A typical FFP unit is approximately 250 mL and is administered within 6 hours of thawing. Every 1 mL/kg of body weight of FFP raises clotting factors by 1%. For warfarin reversal, 5 to 8 mL/kg of FFP should be administered IV. One milliliter of FFP has 1 U of activity of all coagulation factors; 15 mL/kg of FFP achieves approximately 30% of plasma factor concentration.^10,11

Patients with active bleeding and documented liver disease, congenital factor deficiency, or mass transfusion recipients are candidates for FFP in the ED. Patients with TTP should also receive FFP with plasma exchange. When FFP is administered for emergent reversal in life-threatening bleeding or intracranial hemorrhage, it is given in conjunction with IV vitamin K and either Factor VIIa or prothrombin.¹²

Cryoprecipitate

Cryoprecipitate contains factor VIII, von Willebrand factor (vWF), and fibrinogen with some amounts of factor XIII and fibronectin. Actively bleeding patients with hypofibrinogenemia (<100 mg/dL fibrin) are candidates for cryoprecipitate. Cryoprecipitate is used in the therapeutic management of hemophilia A (factor VIII deficiency) when factor VIII concentrates are not available. Cryoprecipitate is given as type ABO compatible when possible and, like FFP, type AB is the universal donor. Each unit of cryoprecipitate raises fibrinogen 75 mg/dL, with a typical dose being 10 U or 1 U per 5 kg of patient body weight.^13,14

Factor VIII, Von Willebrand Factor, and Factor IX

Patients with hemophilia typically present to the ED with bleeding episodes ranging from benign abrasion to life-threatening epidural hematomas. Factor VIII concentrates are purified from plasma to treat bleeding patients with hemophilia A or von Willebrand disease (VWD). For emergent use, the amount of factor VIII should be calculated as follows: estimated dose = weight (kg) x 0.5 x desired factor (%) increase. The targeted factor VIII increase is typically 80% to 100% for severe bleeding in patients with hemophilia A.

Another component of factor VIII is vWF activity (factor VIII/vWF). Von Willebrand disease is characterized by the lack of factor VIII/vWF, resulting in normal platelet counts and morphologies, but with impaired adhesion ability. Humate-P and Alphanate SD/HT, are factor VIII replacement therapies with significant amounts of vWF, and are approved for use in patients with hemophilia A and vWD. The initial dose of Humate-P for severe bleeding episodes is 40 to 60 U/kg IV. An administered dose of 50 IU/kg of Alphanate is expected to increase circulating FVIII levels to 100% of normal.

Factor IX (FIX) concentrates are used to treat patients with hemophilia B, a condition in which patients lack factor IX, a vitamin K-dependent glycoprotein. The FIX concentrates may also benefit patients with factor X or prothrombin deficiency. In the United States, since 1992, commercially available FIX is produced from genetically engineered recombinant factor replacement (rFIX). Second-generation rFIX and monoclonal antibody solvents do not contain human plasma and are free of viral contaminants, including parvovirus B19.¹⁵

Etiology and Treatment

Gastrointestinal Bleeding

Sources of GI bleeding vary from hemorrhoids to Mallory-Weiss tears. The heterogeneous population of patients with GI bleeds complicates the identification of high-risk patients needing transfusion. Bleeding is traditionally characterized as either upper GI bleeding (UGIB) or lower GI bleeding (LGIB)—the former requiring endoscopy, the latter colonoscopy or other expensive strategies to differentiate one form from the other.

In patients with LGIB, the differential diagnosis is broad, ranging from hemorrhoidal bleeding, cancer, or life-threatening diverticular hemorrhage. Prompt volume replacement with isotonic crystalloid IV fluids must be initiated. In nonvariceal UGIB, blood transfusions should be initiated for Hgb levels <70g/L.¹⁶

Clinical prediction rules for acute GI bleeding can help identify those patients who require transfusions. One study collected data on seven established independent predictors of severe LGIB, including heart rate, systolic blood pressure (SBP), syncope, nontender abdomen, rectal bleeding in the first 4 hours of evaluation, aspirin use, and more than two comorbid conditions. A nontender abdomen was the best predictor of severe bleeding, likely due to the fact that vascular disorders, such as diverticulitis, result in brisk bleeding without tenderness; whereas inflammatory processes, such as ischemic colitis, are associated with less severe bleeding and abdominal tenderness. Patients with one or more of the seven risk factors were stratified into low (0-7 risk factors), moderate (1-3 risk factors), and high-risk groups (>3 risk factors). Low-risk patients had a ≤ 9% risk of a severe LGIB, moderate-risk patients had a 43% risk, and high-risk patients had >79% likelihood of bleeding. The high-risk patients were more likely to require early transfusion of PRBCs. Tachycardia, hypotension, syncope, nontender abdomen, and rectal bleeding were identified as the most significant predictors of patients requiring 4 or more units of PRBC in the first 24 hours. Such clinical prediction rules may aid in the initial triage of patients with acute LGIB and identify those most likely to require transfusion in the ED.¹⁷