WBR0458

Author	[[PageAuthor::Rim Halaby, M.D. [1], (Reviewed by Will Gibson) (Reviewed by Alison Leibowitz)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Hematology, SubCategory::Oncology
Prompt	[[Prompt::A 24-year-old male patient to the physician’s office with complaints of fatigue, unremitting fever, and easy bruisability upon minor trauma. His vital signs demonstrate a temperature of 38.6 °C, heart rate of 98 beats per minute, and blood pressure measuring 116/82 mmHg. Upon physical examination, you observe pallor, bleeding gums, and purpura. An image of the patient’s peripheral blood smear is displayed below. Cytogenetics show a t(15;17) translocation. Following the initiation of appropriate treatment, the patient suffers a complication. Which of the following best characterizes the patient’s complication? ]]
Answer A	AnswerA::Activation of hemostasis and fibrinolysis that leads to formation of thrombin and plasmin
Answer A Explanation	AnswerAExp::Disseminated Intravascular Coagulation (DIC) is a potentially fatal complication of chemotherapeutic treatment of AML M3.
Answer B	AnswerB::Autoimmune antibodies against platelets
Answer B Explanation	[[AnswerBExp::Idiopathic thrombocytopenic purpura (ITP) is characterized by the presence of autoimmune antibodies against platelets. ITP typically occurs following a viral illness.]]
Answer C	AnswerC::Systemic deposition of platelet thrombi with abundant von Willebrand factor (vWF) in arterioles and capillaries
Answer C Explanation	[[AnswerCExp::Thrombotic thrombocytopenic purpura (TTP) is characterized by the systemic deposition of platelet thrombi with abundant von Willebrand factor (vWF) in arterioles and capillaries.]]
Answer D	AnswerD::Increased ristocetin sensitivity
Answer D Explanation	[[AnswerDExp::Due to an unknown mechanism, exposure to the antibiotic ristocetin induces von-Willebrand factor dependent platelet aggregation. von Willebrand disease (vWD) is diagnosed by decreased platelet aggregation in a ristocetin platelet aggregation assay. vWD is the most common inherited coagulopathy, in which patients exhibit increased bleeding due to impaired platelet aggregation. vWD is distinguished from the hemophilias by the distribution of bleeding sites. vWD patients mostly experience increased rates of nosebleeds or bleeding gums, whereas hemophiliacs experience higher rates of internal bleeding and joint bleeding (hemoarthroses).]]
Answer E	AnswerE::Monoclonal gammopathy of undetermined significance
Answer E Explanation	[[AnswerEExp::Monoclonal gammopathy of undetermined significance (MGUS), a hematologic condition, is characterized by the presence of monoclonal antibodies without clinical symptoms, or radiological and laboratory signs. The disease is similar to multiple myeloma (MM), but the number of monoclonal plasma cells in MGUS is lower, constituting less than 10% of bone marrow biopsy findings. MGUS requires no treatment, but the rate of MM development is approximately 1-2% in patients with MGUS.]]
Right Answer	RightAnswer::A
Explanation	[[Explanation:: The patient in this scenario is likely presenting with acute promyelocytic leukemia (APML) or AML M3. Symptoms of AML M3 are typically unremitting fever with signs of pancytopenia, such as anemia as manifested by pallor, thrombocytopenia as manifested by easy bruisibility and purpura, and leucopenia as manifested by sore throat, pneumonia, or other infections. On peripheral smear, AML M3 is frequently characterized by Auer rods. The image above displays one circled Auer rod, as well as several others that are not circled. The presence of Auer rods alone is specific for AML, but alone is not sufficient to establish the diagnosis of APML. The t(15;17) translocation reflects the translocation of the retinoic acid receptor (chr17) with the PML (promyelocytic leukemia) gene (chr15) and is highly specific for APML. Treatment of AML M3 by all-trans retinoic acid leads to the release of Auer rods and potentially results in disseminted intravascular coagulation (DIC). DIC, a complication of several diseases including AML M3, occurs following treatment and is characterized by activation of the hemostasis system, with the release of tissue factor usually from endothelial cells. Normally, the inhibitor system compensates for the tissue factor release, but with the eventual consumption of inhibitors more coagulation ensues in a process called “consumptive coagulopathy”. As a result, the entire hemostasis pathway becomes unbalanced and breaks down. DIC frequently manifests with profuse bleeding and upon blood work-up, low fibrinogen levels, elevated levels of D-dimer, and fibrinogen split products (FSP), suggesting the generation of plasmin. Consumptive coagulopathy is corrected with cryoprecipitate, platelet concentrations, and fresh frozen plasma (FFP), which reduces the tendency to bleed. Educational Objective: AML M3 is frequently characterized by pancytopenia and fever, with a peripheral blood smear displaying plasma cells containing Auer rods. DIC is a common complication following treatment of AML M3, due to the release of Auer rods. DIC, a consumptive coagulopathy, is caused by the imbalance of the hemostasis and fibrinolytic systems. References: Mammen EF. Disseminated intravascular coagulation (DIC). Clin Lab Sci. 2000;13(4):239-45 ]]
Approved	Approved::Yes
Keyword	WBRKeyword::AML M3, WBRKeyword::AML, WBRKeyword::Cancer, WBRKeyword::DIC, WBRKeyword::Disseminated intravascular coagulation, WBRKeyword::Acute myelocytic leukemia, WBRKeyword::Acute promyelocytic leukemia, WBRKeyword::Monoclonal gammopathy, WBRKeyword::Fibrinogen, WBRKeyword::Disseminated intravascular coagulation
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