WBR0080

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 5 year old boy is brought to the emergency room by his parents following severe bleeding after a fall. Approximately 12 hours prior to presentation, the boy hit his knee on a table in his room when jumping off of his bed. Since then, his knee has swollen severely. The knee is tender to palpation and elicits pain with both active and passive flexion. Laboratory testing reveals the following: PT:13 seconds (normal: 11-15) PTT: 65 seconds (normal: 25-40 seconds) Platelet count: 250,000 per microliter (normal: 150,000-400,000 per microliter) The patient is infused with cryoprecipitate and his bleeding resolves. Which of the following proteins is most likely deficient in this patient?]]
Answer A	AnswerA::GpIb
Answer A Explanation	[[AnswerAExp::GPIb is deficient in Bernard-Soulier disease. Patients typically experience cutaneous and mucosal bleeding.]]
Answer B	AnswerB::Factor V
Answer B Explanation	[[AnswerBExp::Factor V can be mutated to a prothrombotic isoform termed Factor V Leiden. This 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.]]
Answer C	AnswerC::Factor VIII
Answer C Explanation	[[AnswerCExp::Factor VIII deficiency is responsible for hemophilia A. Hemophilia A (80%) is more common than hemophilia B (20%).]]
Answer D	AnswerD::Factor IX
Answer D Explanation	[[AnswerDExp::Factor XI deficiency is responsible for hemophilia B.]]
Answer E	AnswerE::von Willebrand Factor (vWF)
Answer E Explanation	[[AnswerEExp::vWF deficiency causes von Willebrand’s disease, the most common bleeding disease. In contrast to hemophilia, von Willebrand’s disease is a mixed coagulation and platelet dysfunction disorder. Patients typically experience cutaneous and mucosal bleeding. Von Willebrand’s disease can be treated with desmopressin, which releases stored vWF from the endothelium. Von Willebrand disease is inherited in an autosomal dominant fashion.]]
Right Answer	RightAnswer::C
Explanation	[[Explanation::The patient in this vignette has hemophilia, as evidenced by his excessive joint bleeding and elevated PTT. Hemophilia is an X-linked recessive bleeding disorder caused by deficiency of certain clotting factors. Hemophilia A (80% of cases) is caused by deficiency of factor VIII, and hemophilia B (20% of cases) is caused by deficiency of factor IX. In both hemophilia A and B, spontaneous bleeding is common. On laboratory testing, these patients have a normal bleeding time, normal prothrombin time, normal thrombin time, but prolonged partial thromboplastin time. The most characteristic type of internal bleed is a joint bleed where blood enters into the joint spaces. Bleeding can be controlled with regular infusions of the deficient clotting factor, i.e. factor VIII in hemophilia A or factor IX in hemophilia B. One complication of factor supplementation is resistance; some patients may develop antibodies to the administered clotting factors. In milder forms of hemophilia A, DDAVP can be used. DDAVP causes endothelial cells to release vWF. The newly released vWF binds to and stabilizes factor VIII, thereby increasing its half life in serum. Educational Objective: Hemophilia A is the most common form of hemophilia and is caused by a deficiency of factor VIII. References: First Aid 2014 page 389, First Aid 2012 page 387, video tutorial]]
Approved	Approved::Yes
Keyword	WBRKeyword::Hemophilia, WBRKeyword::Haemophilia, WBRKeyword::Bleed, WBRKeyword::Bleeding, WBRKeyword::Blood, WBRKeyword::Coagulation
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