The abnormality you have chosen is:
an elevated PROTHROMBIN TIME (PT). This test measures the time for clot formation to occur once clotting has been initiated with thromboplastin via factor VII and tests the common pathway of the clotting cascade. Prolongation may occur when there is a deficiency of any of the clotting factors of the common pathway. Deficiencies of these clotting factors occur when absorption of vitamin K is impaired (vitamin K is needed for the synthesis of these factors) or when liver disease is severe enough to cause impaired hepatic synthesis (all clotting factors except a portion of factor VIII are synthesized in the liver). The PT may also be prolonged in patients who are vitamin K deficient (often seen with hospitalized patients unable to eat and on antibiotics), have concomitant erythrocytosis, or in patients with the lupus anticoagulant.
The acquired coagulopathy secondary to liver disease is mainly due to impaired synthesis of clotting factors but is also influenced by the release of abnormal clotting factors and an inability of the diseased liver to clear certain coagulation-related proteins from the blood. If the abnormal PT is not associated with an increased bleeding tendency, then no treatment is necessary other than correction of the underlying liver disease. Once hemorrhaging complicates the patients condition, replacement of the missing clotting factors becomes essential. Fresh frozen plasma is the most effective way to replace all clotting factors. Cryoprecipitate may also be administered to replace fibrinogen, factor VIII and von Willebrand factor. Other supportive measures include platelet transfusions in patients with concomitant thrombocytopenia.
The evaluation for a prolonged PT not secondary to coumadin therapy begins with a mixing study. If the PT normalizes, then there is an underlying factor deficiency (factors II, V, VII, or X or a deficiency or fibrinogen). Acquired factor II, V, VII, or X deficiencies are often seen in hospitalized patients on antibiotics who become vitamin K deficient when they are in a prolonged fasting state or in patients with severe liver disease. If the PT fails to correct with a mixing study, then an inhibitor is present. Inhibitors will usually cause a concomitant prolongation of the aPTT.
The prothrombin time is also used to monitor patients receiving warfarin (Coumadin) therapy. Since wide variations in the PT occur depending on which thromboplastins are used as reagents, most laboratories now report PT values as the International Normalized Ratio (INR). The INR is a standardized value; therefore, it serves as an accurate assessment of the PT despite which reagent is used in the determination. Warfarin functions as an anticoagulant by interfering with hepatic biosynthesis of the vitamin K dependent clotting factors (II, VII, IX and X) Of note, warfarin also serves to decrease the anticoagulation proteins, C and S. Therefore, during the initiation of warfarin therapy when proteins C and S decrease more rapidly than the clotting factors, there is potentially a hypercoaguable state which may manifest as warfarin induced skin necrosis. Although, this is rarely seen clinically except in patients with deficiencies of proteins C and S prior to initiation of warfarin therapy. This complication may be avoided by administering concomitant intravenous heparin therapy during the initiation of warfarin therapy.
When using the INR to adjust warfarin therapy, the dosage should be adjusted for a target INR between 2 to 3. In patients who prove to be hypercoaguable despite conventional warfarin therapy and in patients with prosthetic mechanical cardiac valves, the target range for the INR is 2.5 to 3.5. Warfarin therapy is often started after the patient has been effectively heparinized. Once the warfarin therapy has been started in these patients and the INR becomes therapeutic, heparin therapy should be continued for another 3 days. The reason for the prolonged heparinization despite a therapeutic INR is that the initial change in the INR may actually reflect a decrease in only factor VII, which is not an effective state of anticoagulation. Once patients are on a proper dose, chronic warfarin therapy may be monitored by serial measurements of the INR. If the INR is stable, representing a therapeutic warfarin dose, surveillance of the INR can be continued at intervals of 4 to 8 weeks.
When a patient is over-anticoagulated, as evidenced by an excessively high INR, bleeding becomes a major concern. If patients are not actively bleeding, warfarin therapy may be decreased in dose or discontinued for 1 to 2 days and then reinitiated with a dosage adjustment to bring the INR into the therapeutic range. In patients with widely variable INRs despite dosage adjustments, compliance with therapy, variable dietary intake of foods rich in vitamin K or concomitant ingestion of medications which interfere with the effectiveness of warfarin may be the underlying problem. When the INR is excessively elevated and the patient is bleeding, therapy is warranted. If the hemorrhaging is not life threatening (minor epistaxis or microscopic hematuria) 1 to 2 mg of vitamin K administered orally or subcutaneously should bring the PT into the therapeutic range within 6 to 8 hours. Intravenous vitamin K at a dose of 10 mg along with fresh frozen plasma should be administered when severe life-threatening hemorrhaging is associated with excessive anticoagulation with warfarin.