A 59-year-old woman comes to the emergency department due to right leg swelling and pain for 2 days. The patient was started on hemodialysis 2 months ago for end-stage renal disease from poorly controlled hypertension and type 2 diabetes mellitus. Duplex ultrasound shows a right popliteal vein thrombosis. The patient is started on intravenous heparin infusion and admitted to the medical floor. On the third day of hospitalization, the right leg is more swollen and painful. Repeat ultrasound shows an extension of thrombus to the right femoral vein. Laboratory results are as follows: Which of the following is the most likely cause of this patient's worsening condition?

Question

A 59-year-old woman comes to the emergency department due to right leg swelling and pain for 2 days.  The patient was started on hemodialysis 2 months ago for end-stage renal disease from poorly controlled hypertension and type 2 diabetes mellitus.  Duplex ultrasound shows a right popliteal vein thrombosis.  The patient is started on intravenous heparin infusion and admitted to the medical floor.  On the third day of hospitalization, the right leg is more swollen and painful.  Repeat ultrasound shows an extension of thrombus to the right femoral vein.  Laboratory results are as follows:  Which of the following is the most likely cause of this patient's worsening condition?

Quizplus · Accepted Answer

Explanation: 11ec25c8_d419_cbff_bc81_1197b1633766_MD0003_00 This patient with thrombocytopenia and thrombus progression 3 days into heparin therapy likely has type 2 heparin-induced thrombocytopenia (HIT). Heparin induces a conformational change to a platelet surface protein (platelet factor 4 [PF4]), which exposes a neoantigen. In patients with type 2 HIT, the immune system responds by forming an IgG autoantibody (HIT antibody) that then coats the surface of platelets and forms complexes (heparin-PF4-HIT antibody), resulting in: Thrombocytopenia - the reticuloendothelial system (largely the spleen) removes antibody-coated platelets, causing a mild to moderate thrombocytopenia (rarely <20,000/mm³). Arterial and venous thrombus - HIT antibodies activate platelets, resulting in platelet aggregation and the release of procoagulant factors. The risk of thrombus is as high as 50% in untreated HIT. Typically, type 2 HIT manifests with a >50% drop in platelets 5-10 days after the initiation of heparin, but it may occur earlier (sometimes <1 day) in patients previously exposed. This patient with end-stage renal disease likely receives heparin with hemodialysis. If HIT is suspected, all heparin products should be discontinued immediately and anticoagulation should be initiated with an alternate anticoagulant (eg, argatroban, fondaparinux). Heparin works by binding antithrombin, which inactivates factor Xa; this prolongs activated partial thromboplastin time. (Choice B) Impaired bone marrow platelet production is seen with malignant infiltration or myelodysplastic syndrome. Typically, the other cell lines are also affected (eg, leukocytosis, pancytopenia). (Choice C) Acute disseminated intravascular coagulation is usually characterized by bleeding, end-organ dysfunction (renal, pulmonary, liver), and shock. Trauma, infection, and malignancy are the most common causes and patients tend to be acutely ill. In this patient on heparin with thrombocytopenia and thrombus progression alone, HIT is far more likely. (Choice D) Type 1 HIT is marked by nonimmune-mediated platelet aggregation. It results in mild thrombocytopenia (platelets rarely <100,000/mm³), usually within 2 days of heparin initiation. Type 1 HIT does not require intervention and does not cause ill effects; the thrombocytopenia resolves without cessation of heparin. ³ (Choice E) Splenomegaly may cause platelet sequestration and redistribution. It is associated with thrombocytopenia but does not increase thrombus risk. Educational objective: In type 2 heparin-induced thrombocytopenia (HIT), heparin induces a conformational change in a platelet surface protein which exposes a neoantigen. Antibodies are formed and bind to the surface of platelets, resulting in platelet activation, thrombocytopenia, and a prothrombotic state. Type 2 HIT typically occurs 5-10 days after heparin initiation but may occur sooner in patients previously exposed to heparin. References: Stroke in patients with heparin-induced thrombocytopenia and the effect of argatroban therapy. (http://www.ncbi.nlm.nih.gov/pubmed/15071388)

A 59-Year-Old Woman Comes to the Emergency Department Due to Right