A 50-year-old man with a long history of alcohol use disorder is admitted to the hospital with difficulty breathing. Blood pressure is 90/40 mm Hg, pulse is 114/min, respirations are 22/min, and pulse oximetry is 92% on room air. Physical examination shows bilateral basal crackles, increased jugular venous pressure, hepatomegaly, ascites, and peripheral pitting edema. Chest x-ray demonstrates cardiomegaly. Scattered ecchymoses are present across each extremity. Laboratory results are as follows: The patient is given intramuscular vitamin K. Two days later, his laboratory results are unchanged. Which of the following is the most likely cause of this patient's laboratory abnormality?

Question

A 50-year-old man with a long history of alcohol use disorder is admitted to the hospital with difficulty breathing.  Blood pressure is 90/40 mm Hg, pulse is 114/min, respirations are 22/min, and pulse oximetry is 92% on room air.  Physical examination shows bilateral basal crackles, increased jugular venous pressure, hepatomegaly, ascites, and peripheral pitting edema.  Chest x-ray demonstrates cardiomegaly.  Scattered ecchymoses are present across each extremity.  Laboratory results are as follows:  The patient is given intramuscular vitamin K.  Two days later, his laboratory results are unchanged.  Which of the following is the most likely cause of this patient's laboratory abnormality?

Quizplus · Accepted Answer

11ec160b_3af0_228b_9249_57a33b246a75_MD0001_00 This patient has liver dysfunction due to alcohol use disorder. The liver synthesizes many proteins, including clotting factors. Chronic alcohol use leads to progressive hepatic fibrosis/cirrhosis, resulting in acquired coagulopathy. Clotting factors II, VII, IX, and X are produced initially by the liver in an inactive form and then activated by vitamin K-dependent carboxylation. Factor VII, part of the extrinsic pathway, has the shortest half-life of all coagulation factors. Prothrombin time (PT) assesses the extrinsic and common pathways of coagulation and is the first to become abnormal in liver disease. This patient's PT prolongation is likely due to factor VII deficiency in the setting of cirrhosis. Because clotting factor synthesis is impaired, PT may not improve with vitamin K supplementation as there are insufficient quantities of clotting factors to undergo vitamin K-dependent carboxylation/activation. The liver also synthesizes albumin, and hypoalbuminemia results in ascites and peripheral edema. In addition, severe cirrhosis causes high-output heart failure due to chronic splanchnic vasodilation and development of mesenteric and intrahepatic arteriovenous shunts. (Choice A) Dietary vitamin K deficiency impairs activation of factors II, VII, IX, and X. Risk factors include severe malnourishment (eg, alcohol use disorder) and long-term antibiotic use (alters vitamin K-producing gut flora). In vitamin K deficiency, supplementation would likely improve PT. (Choice C) In contrast to other coagulation factors, factor VIII is synthesized by endothelial cells. As part of the intrinsic pathway, factor VIII deficiency results in prolonged activated partial thromboplastin time (PTT) with a normal PT. Hemophilia A is an X-linked recessive disorder of factor VIII deficiency. (Choice D) Cirrhosis is associated with intrinsic platelet dysfunction and thrombocytopenia due to decreased hepatic synthesis of thrombopoietin and increased splenic platelet sequestration (secondary to hypersplenism). Platelet dysfunction and significant thrombocytopenia (eg, platelets <50,000/mm³) lead to mucocutaneous bleeding/petechiae and prolonged bleeding time but do not affect PT. (Choice E) Von Willebrand disease causes defects in platelet adhesion and coagulation (due to associated factor VIII deficiency). PTT may be normal or prolonged based on the level of factor VIII deficiency, and platelet aggregation to ristocetin will be abnormal. Education objective: Vitamin K-dependent coagulation factors (II, VII, IX, and X) are synthesized in the liver. Factor VII has the shortest half-life of the coagulation factors. Failure of the prothrombin time to correct with vitamin K supplementation indicates factor VII deficiency, which is often due to underlying liver disease. __________ References: Coagulation abnormalities in the cirrhotic patient. (http://www.ncbi.nlm.nih.gov/pubmed/24018489) Bleeding and bruising: a diagnostic work-up. (http://www.ncbi.nlm.nih.gov/pubmed/18481559)

A 50-Year-Old Man with a Long History of Alcohol Use