Fresh frozen plasma is indicated for the deficiency of coagulation factors with abnormal coagulation tests in the presence of active bleeding. FFP is also indicated for a planned surgery or invasive procedure in the presence of abnormal coagulation tests, reversal of warfarin in the presence of active bleeding or planned procedure when vitamin K is inadequate to reverse the warfarin effect, thrombotic thrombocytopenic purpura, and congenital or acquired factor deficiency with no alternative therapy. Other more specific recommendations for FFP based on systematic review include trauma patients requiring massive transfusion and warfarin-related intracranial hemorrhage. Other situations where the administration of FFP cannot be recommended for or against based on systematic review include FFP transfusion at a plasma-to-RBC ratio of 1:3 or more in trauma patients with massive transfusion. Conditions that cause the deficiency of multiple coagulation factors and may require the administration of FFP include liver disease and disseminated intravascular coagulation. FFP transfusion may not be tolerated in patients with liver disease as patients may not be able to tolerate the infusion volumes necessary to achieve adequate hemostatic levels of coagulation factors.
Fresh frozen plasma is the fluid portion of a unit of whole blood that is frozen in a designated time frame, usually within 8 hours. FFP contains all coagulation factors except platelets. FFP contains fibrinogen (400 to 900 mg/unit), albumin, protein C, protein S, antithrombin, tissue factor pathway inhibitor. It is free of erythrocytes and leukocytes. FFP corrects coagulopathy by replacing or supplying plasma proteins in patients who are deficient in or have defective plasma proteins. A standard dose of 10 to 20 mL/kg (4 to 6 units in adults) will raise factor levels by approximately 20%. An increase of approximately 10% of several factors is enough to effect hemostasis. In addition, FFP provides some volume resuscitation as each unit contains approximately 250 ml.
FFP can only be administered intravenously. FFP must be ABO compatible with the recipient’s red cells. The FFP container and fluid upon visual inspection should have no leakage, clots, or abnormal color. FFP is stored at -30 C. Prior to administration, FFP is thawed in a water bath at 30 to 37 C over 20 to 30 minutes or in an FDA-cleared device as quickly as 2 to 3 minutes. FFP should be administered immediately after thawing. If FFP is not given immediately after thawing, it should be stored at 1 to 6 C. If the thawed FFP is not used in 24 hours, it should be discarded. Once thawed, the activity of clotting factors, particularly factor V and factor VIII, decline gradually. After initial dosage, re-administration may be needed every 6 to 8 hours if there is continued bleeding due to the short half-life of factor VII. Factor VII has a half-life of 2 to 6 hours.
The adverse effects of FFP administration are similar to those that pertain to whole blood and all blood components and can be categorized into non-immunologic complications, immediate immunologic complications, and delayed immunologic complications. FFP’s acellularity spares certain disease transmission and blood immunogenicity: CMV and graft-versus-host disease cannot be transmitted by FFP as there are no viable leukocytes. Non-immunologic complications include the transmission of infectious agents, transfusion-associated circulatory overload (TACO), and metabolic complications like citrate toxicity. Infectious agents that can be transmitted via FFP include HIV and hepatitis B and C. Screening and pathogen inactivation have reduced transmission rates of HIV to 1:7.8 million, hepatitis B virus to 1:153,000, and hepatitis C virus to 1:2.3 million. TACO is caused by cardiogenic pulmonary edema and can occur after transfusion of excessive volumes or volumes at excessive rates. Immediate immunologic complications include hemolytic transfusion reaction, febrile non-hemolytic reaction, allergic reactions, anaphylactoid/anaphylactic reactions, and transfusion-related acute lung injury (TRALI). Hemolytic transfusion reaction occurs from anti-A and anti-B antibodies due to the failure of ABO matching. TRALI is the most common cause of transfusion-related death. TRALI is the acute onset of hypoxemia and non-cardiogenic pulmonary edema in the absence of other causes of acute lung injury or circulatory overload. TRALI occurs secondary to stimuli in blood components (white blood cell antibodies from donors and/or pro-inflammatory molecules that have accumulated in stored blood components) that trigger an inflammatory response resulting in injury to the alveolar capillary membrane causing permeability pulmonary edema. Delayed immunologic complications include alloimmunization to plasma proteins.
FFP is contraindicated when coagulopathy can be corrected more effectively with specific therapy and when blood volume can be adequately replaced with other volume expanders. More specific therapies that can be pursued before FFP administration include vitamin K, cryoprecipitated antihemophilic factor, prothrombin complex concentrates, or specific coagulation factor concentrates like factor VII. In the absence of coagulation deficiencies and active bleeding, FFP should not be used as a volume expander. FFP is contraindicated for the reversal of anticoagulation induced by heparin, direct thrombin inhibitors, or direct factor Xa inhibitors because FFP does not effectively reverse anticoagulation induced by these medications. Antidote treatments for the reversal of direct oral anticoagulants should be pursued instead.
The therapy of FFP is monitored clinically with signs of bleeding and chemically with coagulation studies and fibrinogen levels. Each unit of FFP contains approximately 200 to 250 mL. Apheresis-derived units can contain as much as 400 to 600 mL. Administration of one 250 mL unit should raise the fibrinogen level by 5 to 10 mg/dl. The goal of therapy is a cessation of bleeding. The laboratory value goal is to correct the prothrombin time/activated partial thromboplastin time to less than 1.5 times normal.
The adverse effects of FFP are monitored like any other blood product administration. The patient’s vital signs (temperature, pulse, respirations, and blood pressure) are monitored before, during, and after administration. If a reaction is noted based on signs and symptomology, treatment is guided by the type of transfusion reaction. Usually, administration of the product should be immediately ceased. Life-threatening reactions like TRALI and TACO may require aggressive respiratory support and often mechanical ventilation.
Citrate toxicity can occur with administration of FFP. The majority of citrate in whole blood products is found in FFP and platelets, not packed red blood cells. Citrate chelates calcium. Citrate intoxication causes hypocalcemia. Signs and symptoms of hypocalcemia include hypotension, decreased pulse pressure, arrhythmias, mental status changes, and tetany. Treatment includes calcium administration.
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