A 66-year-old woman is brought to the emergency department due to left leg pain. Five days ago, the patient underwent elective right hip arthroplasty for advanced osteoarthritis. She had been recovering well at an acute rehabilitation facility until she woke today with severe left calf pain and swelling. The patient has taken daily subcutaneous, low-molecular-weight heparin and as-needed acetaminophen since the surgery. She has no other medical conditions. Temperature is 37 C (98.6 F), blood pressure is 130/70 mm Hg, and pulse is 92/min. The surgical incision over her right hip is healing well. Her left posterior calf is tender and swollen to the knee. Three days ago, complete blood count was normal, but platelet count is now 70,000/mm³. Peripheral blood smear shows decreased platelet number but no other abnormalities. Which of the following is the most likely cause of this patient's thrombocytopenia?

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11ec160b_3af3_08c6_9249_59f56148ff0e_MD0001_00 This patient on low-molecular-weight heparin developed thrombocytopenia and deep venous thrombosis (calf pain/swelling), raising strong suspicion for heparin-induced thrombocytopenia (HIT) type 2. In HIT type 2, heparin induces a conformational change in platelet-factor 4, leading to the formation of a neoantigen. IgG antibodies form against the neoantigen (heparin-platelet factor 4), which results in antibody aggregation on the platelet surface. Patients generally develop manifestations 5-10 days after heparin initiation. Thrombocytopenia is the hallmark feature due to the clearance of antibody-coated platelets by splenic macrophages. Antibody aggregation on the platelet surface also results in wide-spread platelet aggregation, which worsens the thrombocytopenia and significantly increases the risk of venous and arterial thrombosis. Patients with HIT-type 2 should immediately stop heparin and be initiated on a nonheparin anticoagulant (eg, argatroban) to help prevent/treat thrombosis. (Choice A) Although bone marrow suppression can cause thrombocytopenia, it most often occurs in the setting of malignant invasion of the bone marrow (eg, leukemia) or chemical toxicity (eg, chemotherapy, excessive alcohol). Thrombosis is uncommon. (Choices B and E) Mechanical destruction of platelets can be seen with a mechanical prosthetic heart valve or in disseminated intravascular coagulation, a condition marked by the excessive activation of the coagulation cascade. In both of these conditions, thrombocytopenia is accompanied by schistocytes on peripheral blood smear. (Choice C) HIT type 1 is a non-immune-mediated condition caused by platelet clumping. Thrombocytopenia is typically mild (nadir ~100,000/mm³), and most cases arise within 2 days of heparin administration. It does not cause thrombosis and is not considered clinically significant; therefore, heparin can be continued. Educational objective: Heparin-induced thrombocytopenia type 2 results from the formation of IgG antibodies to complexes of heparin and endogenous platelet factor 4. The major manifestation is thrombocytopenia, which typically occurs 5-10 days after heparin initiation due to the destruction of antibody-coated platelets by splenic macrophages. Widespread intravascular platelet activation also results in a high risk of arterial and venous thrombosis. __________ References: Heparin-induced thrombocytopenia. (http://www.ncbi.nlm.nih.gov/pubmed/19630757)

A 66-Year-Old Woman Is Brought to the Emergency Department Due