WBR0080

Author	[[PageAuthor::William J Gibson (reviewed by Rim Halaby, M.D. [1], Jad Al Danaf, Yazan Daaboul)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Hematology
Prompt	[[Prompt::A 5-year-old boy is brought to the emergency department (ED) by his parents for severe right knee pain and swelling that started a few hours ago. The parents explain that approximately 12 hours ago, the patient hit his knee on a table in his room when jumping off of his bed. Since then, his knee has swollen severely. On physical examination, the right knee is tender to palpation; and pain is elicited with both active and passive flexion of the right knee. Initial work-up shows the following lab results: PT:12 seconds (normal: 9.5-13.5) PTT: 65 seconds (normal: 25-40 seconds) Platelet count: 250,000/μl (normal: 150,000-400,000/μl) In the ED, the patient is infused with cryoprecipitate, after which 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 Syndrome (BSS). Patients typically experience cutaneous and mucosal bleeding. The alternative name of the disease is "Giant Platelet Syndrome" because it is characterized by the presence of abnormally large platelets, along with thrombocytopenia.]]
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 accounts for more than 80% of hemophilia cases. It is thus more common than hemophilia B.]]
Answer D	AnswerD::Factor IX
Answer D Explanation	[[AnswerDExp::Factor XI deficiency is responsible for hemophilia B. It is less common than hemophilia A.]]
Answer E	AnswerE::von Willebrand Factor (vWF)
Answer E Explanation	[[AnswerEExp::vWF deficiency causes von Willebrand’s disease, a common bleeding disorder. In contrast to hemophilia, vWDis a mixed coagulation and platelet dysfunction disorder. Patients typically experience cutaneous and mucosal bleeding. vWD 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 hemarthrosis (joint bleeding) and elevated PTT. Hemophilia is an X-linked recessive bleeding disorder caused by deficiency of specific clotting factors. Hemophilia A: It accounts for more than 80% of cases. The disease is caused by deficiency of factor VIII Hemophilia B: It accounts for less than 20% of cases. The disease is caused by deficiency of factor IX. Hemophilia C: It is a rare disease found mostly in Ashkenazi Jews. It is characterized by less bleeding than other types of hemophilias. The disease is caused by deficiency of factor XI. In both hemophilias A and B, spontaneous hemarthrosis is characteristic. It is accompanied by inflammatory synovial changes that demonstrate iron deposits, resulting in hemophilic arthropathy. On laboratory testing, these patients have a normal bleeding time, normal prothrombin time (PT), normal thrombin time, but prolonged partial thromboplastin time (PTT). 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: Roosendaal G, Vianen ME, Wenting MJ, et al. Iron deposits and catabolic properties of synovial tissue from patients with haemophilia. J Bone Joint Surg Br. 1998;80(3):540-5. First Aid 2014 page 389,]]
Approved	Approved::Yes
Keyword	WBRKeyword::Hemophilia, WBRKeyword::Haemophilia, WBRKeyword::Bleed, WBRKeyword::Bleeding, WBRKeyword::Blood, WBRKeyword::Coagulation
Linked Question	Linked::
Order in Linked Questions	LinkedOrder::