WBR0256

Author	PageAuthor::William J Gibson
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics, MainCategory::Pathophysiology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 14 year old female presents to her pediatrician for excessive menstrual bleeding. The young woman is distressed because her periods are very heavy and she fears that she may stain her pants during school. She has a long history of easy bruising, nosebleeds and reports that gums often bleed after brushing her teeth. The physician orders laboratory testing which reveals: PT: 13 seconds (normal: 11-15), PTT: 40 seconds (normal: 25-40 seconds), Platelet count: 200,000 (normal: 150,000-400,000), Bleeding time: 45 minutes (normal: 2-7 minutes). What is the most likely diagnosis?]]
Answer A	AnswerA::Bernard-Soulier Disease
Answer A Explanation	AnswerAExp::While Bernard-Soulier disease is a platelet disorder that could prolong bleeding time, von Willebrand disease is far more common. Bernard Soulier disease also causes a decreased platelet count, wheras this patient has a normal platelet count.
Answer B	AnswerB::Hemophilia A
Answer B Explanation	[[AnswerBExp::Hemophilia A is a bleeding disorder which tends to cause internal bleeds as opposed to the cutaneous and mucosal bleeds observed in this patient with von Willebrand disease. Hemophilia A would should markedly elevated PTT and a normal bleeding time.]]
Answer C	AnswerC::Idiopathic thrombocytopenic purpura
Answer C Explanation	AnswerCExp::Idiopathic thrombocytopenic purpura is a bleeding disorder caused by antibodies against GpIIb/IIIa, which lead to peripheral platelet destruction. The long history of bleeding and normal platelet count argue against ITP in this patient.
Answer D	AnswerD::Thrombotic thrombocytopenic purpura
Answer D Explanation	[[AnswerDExp::Thrombotic thrombocytopenic purpura is a bleeding disorder caused by antibodies against ADAMTS13, a metalloprotease responsible for cleaving vWF into smaller subunits. The increase in circulating multimers of vWB increase platelet adhesion to areas where subendothelial collagen is exposed. The long history of bleeding, and lack of other TTP symptoms such as neurologic or kidney dysfunction argue against TTP in this patient.]]
Answer E	AnswerE::von Willebrand Disease
Answer E Explanation	AnswerEExp::The patient in this vignette has von Willebrand disease, an autosomal dominant bleeding disorder caused by dysfunctional platelet adhesion. von Willebrand disease is the most common bleeding disorder in humans.
Right Answer	RightAnswer::E
Explanation	[[Explanation::The patient in this vignette has von Willebrand Disease, an autosomal dominant disorder caused by mutations in von Willebrand Factor (vWF). vWF is a multimeric protein required for proper platelet adhesion. von Willebrand disease is the most common bleeding disorder in humans, affecting approximately 1% of the population (most are asymptomatic). vWF is primarily active under high flow, high shear rate conditions such as those in small vessels. Therefore, the bleeding of vWD is primarily localized to cutaneous and mucosal areas; internal bleeding is rare. Coagulation studies typically show increased bleeding time, normal PT and normal to prolonged PTT. The prolonged PTT can be observed in some severe vWD cases because vWF normally binds to and protects Factor VIII, thereby prolonging its half life. Educational Objective: Abnormal cutaneous and mucosal bleeding is characteristic of von Willebrand disease, an autosomal dominant bleeding disorder caused by dysfunctional platelet adhesion. References: First Aid 2014 390]]
Approved	Approved::Yes
Keyword	WBRKeyword::Platelet, WBRKeyword::Bleeding, WBRKeyword::Bleed, WBRKeyword::Blood, WBRKeyword::von Willebrand disease, WBRKeyword::Bruise, WBRKeyword::Bruising, WBRKeyword::Blood, WBRKeyword::Hematology, WBRKeyword::Clotting, WBRKeyword::Thrombosis
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