WBR0256
| Author | [[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D.)]] |
|---|---|
| Exam Type | ExamType::USMLE Step 1 |
| Main Category | MainCategory::Genetics, MainCategory::Pathophysiology |
| Sub Category | SubCategory::Hematology |
| Prompt | [[Prompt::A 14-year-old girl is brought to her pediatrician's office for excessive menstrual bleeding. The patient 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 bruisability and nosebleeds, and she reports that her gums often bleed excessively after brushing her teeth. The physician orders laboratory tests which reveal the following findings: prothrombin time (PT) = 13 seconds (normal: 11-15); activated partial thromboplastin time (aPTT) = 70 seconds (normal: 30-50 seconds); platelet count = 287 x 109/L (normal: 150-400 x 109/L); and bleeding time = 22 minutes (normal: 2-15 minutes). What is this patient's most likely diagnosis?]] |
| Answer A | AnswerA::Bernard-Soulier syndrome |
| Answer A Explanation | [[AnswerAExp::While Bernard-Soulier syndrome (BSS) is a platelet disorder characterized by a defect in platelet adhesion to von Willebrand factor. BSS may result in a bleeding disorder and prolongation of bleeding time. However, patients usually have thrombocytopenia, which is not present in this patient.]] |
| Answer B | AnswerB::Hemophilia A |
| Answer B Explanation | AnswerBExp::Hemophilia A is an X-linked bleeding disorder characterized by internal bleeds as opposed to the cutaneous and mucosal bleeds observed in this patient. Labs in hemophilia reveal a marked elevation in aPTT and a normal bleeding time. |
| Answer C | AnswerC::Idiopathic thrombocytopenic purpura |
| Answer C Explanation | [[AnswerCExp::Idiopathic thrombocytopenic purpura (ITP) is an acquired bleeding disorder caused by decreased production and increased destruction of platelets due to formation of auto-antibodies against GpIIb/IIIa. ITP is associated with several environmental exposures, including hematological malignancies, HIV infection, HCV infection, and lupus erythematosus. The long history of bleeding and normal platelet counts make ITP a less likely diagnosis in this patient.]] |
| Answer D | AnswerD::Thrombotic thrombocytopenic purpura (TTP) |
| Answer D Explanation | [[AnswerDExp::Thrombotic thrombocytopenic purpura is a bleeding disorder that may be inherited (deficiency of ADAMTS13) or acquired (auto-antibodies against ADAMTS13). ADAMTS13 is a metalloprotease responsible for cleaving vWF into smaller subunits. Acquired TTP is common in pregnancy and the early post-partum period. In TTP, the circulating multimers of vWF increases platelet adhesion to areas where subendothelial collagen is exposed. TTP is characterized by pentad of manifestations: Microangiopathic hemolysis, thrombocytopenia, fever, neurological symptoms, and renal disease. The lack of other TTP signs and symptoms make the diagnosis of TTP unlikely in this patient.]] |
| Answer E | AnswerE::von Willebrand disease |
| Answer E Explanation | [[AnswerEExp::von Willebrand disease is an autosomal dominant bleeding disorder caused by dysfunctional platelet adhesion. Patients with von Willebrand disease may present similarly to the patient in the vignette. Typically, patients with VWD have a prolonged bleeding time, normal/prolonged aPTT, and normal PTT and platelet count.]] |
| Right Answer | RightAnswer::E |
| Explanation | [[Explanation::von Willebrand's disease (VWD) is an autosomal dominant inherited disorder caused by mutations in von Willebrand's factor (vWF). VWD is the most common bleeding disorder with a prevalence that approximately reaches 1%. The disease is characterized by either a quantitative or a qualitative defect of vWF. There are 3 major types of VWD:
vWF is synthesized by the endothelial cells and megakaryocytes. Physiologically, it binds to GP1b glycoprotein at the platelet surface and collagen at the endothelial surface to promote platelet adhesion. In addition, vWF has a role in binding to factor VIII, a clotting factor of the intrinsic coagulation pathway, and in protecting it against degradation. vWF is active under high flow, high shear rate conditions such as those in small vessels. Therefore, the bleeding of vWD is often localized to cutaneous and mucosal areas, while internal bleeding is rare. Coagulation studies typically show increased bleeding time, normal PT and normal/prolonged aPTT. The prolonged aPTT can be observed in some severe vWD cases because vWF normally binds to and protects factor VIII, thereby prolonging its half life. In the absence of vWF, the half-life of factor VIII will be shortened, and aPTT will be prolonged. The diagnosis of VWD may be confirmed by ristocetin cofactor assay, which demonstrates a decrease in platelet agglutination. For the majority of patients, treatment of VWD includes vasopressin (DDAVP), which has demonstrated efficacy in increasing the concentration of circulatory VWF by inducing the release of VWF stored in the endothelium. Notably, VWD is not necessarily an inherited disease. Development of acquired VWD is associated with systemic diseases, such as malignancies, thyroid disease, and other lymphoproliferative and myeloproliferative disorders. Acquired VWD is also associated with aortic stenosis due to the breakdown of vWF under high shear stress around the aortic valve (Heyde's syndrome), leading to a functional defect of vWF and predisposition to the development of colonic angiodysplasia and GI bleeding. |
| Approved | Approved::Yes |
| Keyword | WBRKeyword::von Willebrand's disease, WBRKeyword::von Willebrand disease, WBRKeyword::von Willebrand factor, WBRKeyword::Bleeding, WBRKeyword::Heavy menses, WBRKeyword::Autosomal dominant, WBRKeyword::VWD, WBRKeyword::VWF |
| Linked Question | Linked:: |
| Order in Linked Questions | LinkedOrder:: |