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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor=William J Gibson
|QuestionAuthor=William J Gibson (reviewed by  {{Rim}}, [[user: Jad Al Danaf|Jad Al Danaf]], Yazan Daaboul)
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Genetics
|MainCategory=Pathophysiology
|SubCategory=Hematology
|SubCategory=Hematology
|MainCategory=Genetics
|MainCategory=Pathophysiology
|SubCategory=Hematology
|SubCategory=Hematology
|MainCategory=Genetics
|MainCategory=Pathophysiology
|SubCategory=Hematology
|SubCategory=Hematology
|MainCategory=Genetics
|MainCategory=Pathophysiology
|MainCategory=Genetics
|MainCategory=Pathophysiology
|MainCategory=Pathophysiology
|SubCategory=Hematology
|SubCategory=Hematology
|MainCategory=Genetics
|MainCategory=Pathophysiology
|SubCategory=Hematology
|SubCategory=Hematology
|MainCategory=Genetics
|MainCategory=Pathophysiology
|SubCategory=Hematology
|SubCategory=Hematology
|MainCategory=Genetics
|MainCategory=Pathophysiology
|SubCategory=Hematology
|SubCategory=Hematology
|MainCategory=Genetics
|MainCategory=Pathophysiology
|MainCategory=Genetics
|MainCategory=Pathophysiology
|SubCategory=Hematology
|SubCategory=Hematology
|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: <br>
|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: <br>
PT:13 seconds (normal: 11-15) <br>
PT:12 seconds (normal: 9.5-13.5) <br>
PTT: 65 seconds (normal: 25-40 seconds) <br>
PTT: 65 seconds (normal: 25-40 seconds) <br>
Platelet count:  250,000 per microliter (normal: 150,000-400,000 per microliter) <br>
Platelet count:  250,000/μl (normal: 150,000-400,000/μl) <br>
The patient is infused with cryoprecipitate and his bleeding resolves. Which of the following proteins is most likely deficient in this patient?
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?
|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]].   
|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 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.
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 vW.  The newly released vWF binds to and stabilizes factor VIII, thereby increasing its half life in serum.
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.
|AnswerA=GpIb
|AnswerA=GpIb
|AnswerAExp=[[GPIb]] is deficient in [[Bernard-Soulier disease]].
|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.
|AnswerB=Factor V
|AnswerB=Factor V
|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.
|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.
|AnswerC=Factor VIII
|AnswerC=Factor VIII
|AnswerCExp=Factor VIII deficiency is responsible for [[hemophilia A]]. [[Hemophilia A]] (80%) is more common than [[hemophilia B]] (20%).
|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]].
|AnswerD=Factor IX
|AnswerD=Factor IX
|AnswerDExp=[[Factor XI]] deficiency is responsible for [[hemophilia B]].
|AnswerDExp=[[Factor XI]] deficiency is responsible for [[hemophilia B]]. It is less common than hemophilia A.
|AnswerE=von Willebrand Factor (vWF)
|AnswerE=von Willebrand Factor (vWF)
|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.
|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.
|EducationalObjectives=[[Hemophilia A]] is the most common form of hemophilia and is caused by a deficiency of [[Factor VIII]].
|EducationalObjectives=[[Hemophilia A]] is the most common form of hemophilia and is caused by a deficiency of [[factor VIII]].
|References=First Aid 2014 page 389,
|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 2012 page 387, [http://www.youtube.com/watch?v=cPLZcrq9Vm8 video tutorial]
First Aid 2014 page 389,
|RightAnswer=C
|RightAnswer=C
|WBRKeyword=Hemophilia, Haemophilia, Bleed, Bleeding, Blood, Coagulation
|WBRKeyword=Hemophilia, Haemophilia, Bleed, Bleeding, Blood, Coagulation
|Approved=Yes
|Approved=Yes
}}
}}

Latest revision as of 23:16, 27 October 2020

 
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::