WBR0254

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::An 86-year-old man is brought by EMS to the emergency department (ED) with an altered mental state. Blood work-up is remarkable for leukocytosis and elevated CRP. Chest-xray demonstrates consolidation in the left lower lobe. In the ED, the patient desaturates and requires mechanical intubation. The patient is admitted to the intensive care unit for antimicrobial therapy. A few days later, the patient develops subcutaneous ecchymoses. His lab tests reveal prolonged INR and aPTT at the upper limit of normal. The mechanism of the patient's clotting abnormality is similar to which of the following bleeding conditions?]]
Answer A	AnswerA::Factor V Leiden
Answer A Explanation	[[AnswerAExp::Factor V may be mutated to a pro-thrombotic isoform termed Factor V Leiden. The disorder is the most common cause of hereditary prothrombotic syndrome. The Factor V Leiden mutation produces a gene product that cannot be degraded by protein C, resulting in increased Factor V levels. The vitamin K deficiency of this patient results in decreased coagulability by decreasing the levels of coagulation factors II, VII, IX, as well as proteins C and S.]]
Answer B	AnswerB::Glanzmann’s thrombasthenia
Answer B Explanation	[[AnswerBExp::While Glanzmann’s thrombasthenia may cause increased bleeding, it is an abnormality of platelet function and not of the coagulation cascade (like vitamin K deficiency).]]
Answer C	AnswerC::Hemophilia A
Answer C Explanation	[[AnswerCExp::Hemophilia A is caused by a deficiency of factor VIII, which is not a vitamin K-dependent clotting factor.]]
Answer D	AnswerD::Hemophilia B
Answer D Explanation	[[AnswerDExp::Hemophilia B is caused by a deficiency of factor IX, which is a vitamin K-dependent clotting factor that is decreased in vitamin K deficiency.]]
Answer E	AnswerE::Isolated protein C deficiency
Answer E Explanation	AnswerEExp::While Protein C is decreased by vitamin K deficiency, the main feature of vitamin K deficiency is a decrease in coabulability. Isolated protein C deficiency causes hypercoagulability.
Right Answer	RightAnswer::C
Explanation	[[Explanation::Vitamin K deficiency is associated with the development of coagulation defects. The patient in this vignette has most probably developed vitamin K deficiency secondary a combination of malnutrition and antibiotic use. While malnutrition depletes vitamin K stores in the body, antibiotics alter the GI microflora that normally produce vitamin K necessary for coagulation pathway reactions. Vitamin K is a co-factor in gamma-carboxylation of glutamic acid residues in prothrombin precursor reactions that occur in the liver. Vitamin K-dependent clotting factors are factors II, VII, IX, and X, along with synthesis of protein C and protein S. When vitamin K is deficient, the synthesis of these short-lived clotting factors is diminished. Therefore, Vitamin K deficiency manifests with bleeding in a similar mechanism to the bleeding observed in hemophilia B, which is caused by factor IX deficiency. Clinical features of vitamin K deficiency include subcutaneous bleeding events, along with a prolonged prothrombin time (PT or INR) followed by a prolonged activated partial thromboplastin time (aPTT). Characteristically, platelets are not involved in vitamin K deficiency, and bleeding time is usually normal. Hemophilia is an X-linked recessive genetic disorder characterized by bleeding due to factor deficiency. Hemophilia A is caused by factor VIII deficiency, hemophilia B is caused by factor IX deficiency, and the less common hemophilia C is caused by factor XI deficiency. In both hemophilia A and B, spontaneous bleeding is common, which usually manifests as hemarthrosis in children. On laboratory testing, these patients have a normal bleeding time, normal prothrombin time (PT and INR), but prolonged activated partial thromboplastin time (aPTT). Educational Objective: Both hemophilia and vitamin K deficiency are characterized by deficiency of clotting factors and bleeding tendency. Hemophilia B is caused by a deficiency of factor IX, which is a vitamin K-dependent clotting factor that is decreased in vitamin K deficiency. References: Mann KG, Nesheim ME, Church WR, et al. Surface-dependent reactions of the vitamin K-dependent enzyme complexes. Blood. 1990;76(1):1-16. First Aid 2014 page 389]]
Approved	Approved::Yes
Keyword	WBRKeyword::Vitamin K deficiency, WBRKeyword::Vitamin K, WBRKeyword::Gamma-carboxylation, WBRKeyword::PT, WBRKeyword::aPTT, WBRKeyword::INR, WBRKeyword::Bleeding, WBRKeyword::Subcutaneous ecchymosis, WBRKeyword::Malnutrition, WBRKeyword::Antibiotics, WBRKeyword::Microflora, WBRKeyword::Clotting factors, WBRKeyword::Hemophilia, WBRKeyword::Factor IX, WBRKeyword::Bleeding
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