View source for WBR0955

 {{WBRQuestion
|QuestionAuthor= {{M.P}}
|ExamType=USMLE Step 3
|MainCategory=Emergency Room
|SubCategory=Hematology
|MainCategory=Emergency Room
|SubCategory=Hematology
|MainCategory=Emergency Room
|SubCategory=Hematology
|MainCategory=Emergency Room
|MainCategory=Emergency Room
|SubCategory=Hematology
|MainCategory=Emergency Room
|SubCategory=Hematology
|MainCategory=Emergency Room
|SubCategory=Hematology
|MainCategory=Emergency Room
|SubCategory=Hematology
|MainCategory=Emergency Room
|MainCategory=Emergency Room
|SubCategory=Hematology
|Prompt=A 50 year old woman comes to the emergency department with complaints of shortness of breath and chest pain.  She has these symptoms for the past one day.  On further review of history she reveals a recent history of travel outside the United States 3 days back.  Her past history is otherwise insignificant and her family history is unremarkable.  She has smoked one pack of cigarette for the past 10 years.  She attained menopause at the age of 48 and not on any medications.  Her vitals are temperature: 36.7 C, blood pressure: 140/80 mmHg, pulse: 80/min and respiration: 15/min.  The patients pulse oximetry shows 95 % on 4-litres of oxygen.  All system examinations are normal.   V/Q scan shows high probablity for pulmonary embolism.  Her laboratory values comes as :
Hb : 13 g/dl
Hct : 38%
RBC’s : 2.5 million/cmm
WBC’s : 6000/cmm
Platelet’s : 300,000/cmm
PT : 13 sec (N 11-15 sec)
INR : 1.03

You start the patient on unfractionated heparin and warfarin.  Her symptoms resolve the next day and a repeat CBC on the second day reveals a platelet count of 160,000/cumm.  What is the most likely cause of her thrombocytopenia?

|Explanation=[[Heparin-induced thrombocytopeni]]a is diagnosed when the platelet count falls by > 50% typically after 5-10 days of heparin therapy and is usually referred to immune mediated phenomenon.  The development of mild to moderate [[thrombocytopenia]] (platelet counts of 50-70,000) in the context of heparin exposure is suggestive of a possible diagnosis of HIT while severe thrombocytopenia and platelet counts less than 20,000 are quite unusual for the syndrome.  There are two types of HIT, type I and type II.  Type I HIT patients characteristically have a transient decrease in platelet count (rarely <100,000) without any further symptoms and can recover even if heparin is continued to be administered.  It occurs in 10-20% of all patients on heparin and is not due to an immune reaction and antibodies are not found upon investigation.  HIT-1 is due to heparin-induced platelet clumping; it is innocuous.  Type II is due to an autoimmune reaction with antibodies formed against platelet factor 4 (PF4), neutrophil-activating peptide 2 (NAP-2) and interleukin 8 (IL8) which form complexes with [[heparin]].  The heparin-PF4 complex, once formed, binds to an activated platelet surface and is recognized by the Fab region of the HIT antibody, forming a heparin-PF4-antibody complex on the platelet surface.  Activated platelets with the heparin-PF4-antibody complex attached to their surface undergo aggregation and are removed prematurely from the circulation leading to thrombocytopenia (HIT); it also leads to the generation of procoagulant platelet-derived microparticles, frequently resulting in thrombin generation and thrombosis and may also activate microvascular endothelial cells, resulting in augmented release of interleukin-6, [[von Willebrand factor]], and other adhesion molecules.  PF4 can also bind [[heparan sulfate]] on vascular endothelial cells; with subsequent injury  to the endothelium and promoting thrombosis.
|AnswerA=Direct effect of heparin on platelet activation


|AnswerAExp=''' Correct ''' : This patient has type I heparin-induced thrombocytopenia that is typically characterized by a slight fall in platelet count (< 50%) within the first two days after heparin initiation and often returns to normal with continued heparin administration.  The mechanism of the thrombocytopenia is nonimmune and appears to be due to a direct effect of heparin on platelet activation.
|AnswerB=Warfarin induced thrombocytopenia

|AnswerBExp=''' Incorrect ''' : [[Warfarin]] which has anticoagulant properties through their inhibition of activated factors VIII and V, also inhibits the vitamin K-dependent gamma-carboxylation of proteins C and S and hence has potentially thrombogenic effects.  Warfarin is not associated with thrombocytopenia.  
|AnswerC=Antibodies against the heparin-platelet factor 4 complex

|AnswerCExp=''' Incorrect ''' : Immune-mediated HIT is associated with a fall in the platelet count of >50 percent that typically occurs 5 to 10 days after the initiation of heparin therapy which is not seen in this patient. 
|AnswerD=Antibodies against GP Ib/V/IX surface glycoprotein

|AnswerDExp=''' Incorrect ''' : Membrane GPIb/IX of phagocytosed platelets are processed, and their digested peptides are presented by macrophages to autoreactive HLA-restricted CD4+ T cells in immune thrombocytopenic purpura.  It is not related to initiation of heparin. 
|AnswerE=Antibodies against GP IIb/IIIa surface glycoprotein
|AnswerEExp=''' Incorrect ''' : Membrane GPIIb/IIIa of phagocytosed platelets are processed, and their digested peptides are presented by macrophages to autoreactive HLA-restricted CD4+ T cells in [[immune thrombocytopenic purpura]].  It is not related to initiation of heparin. 
|RightAnswer=A
|WBRKeyword=Heparin induced thrombocytopenia, Thrombocytopenia, HIT
|Approved=Yes
}}