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Question 4#

A 38-year-old woman with no prior medical history presents to the ED with altered mental status and a temperature of 38.3°C. Physical examination reveals petechiae on both arms but is otherwise unremarkable. Her vital signs are normal and labs are significant for:

What is the most likely diagnosis?

A. Heparin induced thrombocytopenia (HIT)
B. Idiopathic thrombocytopenic purpura (ITP)
C. Disseminated intravascular coagulation (DIC)
D. Thrombotic thrombocytopenic purpura (TTP)

Correct Answer is D


Correct Answer: D

TTP is a thrombotic microangiopathy caused by platelet binding to abnormal von Willebrand factor on the microvascular endothelium. The classic pentad presentation includes: fever, altered mental status, acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. Diagnosis requires thrombocytopenia and microangiopathic hemolytic anemia (as evidenced by schistocytes on peripheral smear). It can be distinguished from DIC since INR, aPTT, and fibrinogen levels are normal. Treatment is early plasma exchange until platelet count is over 50,000 for at least 48 hours and avoidance of platelet transfusions because it can lead to further thrombosis. Left untreated, TTP is almost always fatal.

HIT occurs when heparin binds to platelet factor 4 and triggers the formation of IgG antibodies that bind to platelets and causes the promotion of thrombosis. It generally occurs 5 to 10 days after the first heparin exposure but can appear in 1 day if heparin exposure occurred within the prior 30 days. Venous thrombosis is more common than arterial thrombosis. Diagnosis requires high clinical score on the 4T score and a positive antibody test. Treatment includes discontinuing all heparin and heparin-containing products and anticoagulation with a direct thrombin inhibitor such as argatroban.

ITP is caused by autoantibody-mediated platelet clearance and usually results in a severe thrombocytopenia. Physical examination can reveal petechiae and the peripheral smear may show large platelets. Treatment of ITP includes glucocorticoids, IVIG, and rituximab in those who are unresponsive to initial corticosteroid therapy.

DIC is caused by release of tissue factor that activates clotting factors that lead to widespread microvascular thrombosis and consumption of platelets and clotting factors. Clinically, DIC can lead to multiorgan failure along with bleeding. Laboratory test results will show an elevation of INR and aPTT, low fibrinogen, and elevated D-dimer, whereas a peripheral smear will show schistocytes. Treatment is primarily supportive and addressing the underlying cause inciting DIC.


  1. Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158(3):323-335.