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Afibrinogenemia is a rare disorder characterized by the absence of detectable fibrinogen due to genetic mutations.1 The common presentation is spontaneous or unusual bleedingwithminor trauma. But the recent case report and review by Santoro et al highlights that many patients present with thrombosis with or without bleeding, representing challenging clinical situations.2 Here, we add insight into management of these patients with a case of a patient with afibrinogenemia who developed recurrent arterial stenosis refractory to dual antiplatelet therapy and fibrinogen replacement treated with the novel protease-activated receptor 1 (PAR-1) antagonist vorapaxar. Fibrinogen is a glycoprotein that is produced in the liver and stored in platelet α granules after uptake from plasma.1 Fibrinogen functions in fibrin clot formation, thrombin regulation, platelet aggregation, and fibrinolysis. Afibrinogenemia is an autosomal recessive disorder associatedwith a quantitative deficiency of fibrinogen and a prevalence of 1 in 1,000,000.3 The clinical manifestations of afibrinogenemia include umbilical cord hemorrhage and bleeding in the gastrointestinal (GI) tract, genitourinary tract, mucosa, skin, and the central nervous system.4 Approximately 30% of patients with afibrinogenemia may also have thrombotic complications due to the antithrombin function of fibrinogen. Rarely patients may have both bleeding and thrombotic complications related to the disease.5,6 Treatment for hemorrhage includes antifibrinolytics and/or fibrinogen replacement therapy with fresh frozen plasma, cryoprecipitate, and plasma-derived fibrinogen concentrate.7 In the setting of a thrombotic phenotype, there is no clear consensus, but treatment with low molecular weight heparin, antiplatelet agents, vasodilators, lepirudin, and direct thrombin inhibitors with fibrinogen replacement therapy has been used.8 We present a case of a patient with bleeding and thrombotic complications associated with congenital afibrinogenemia treated with the novel PAR-1 antagonist vorapaxar (Zontivity, Aralez Pharmaceuticals Inc.) and fibrinogen replacement therapy (►Fig. 1). The patient is a 34-year-old Hispanic woman with a past medical history of sensorineural hearing loss, type 1 renal tubular acidosis, GI bleed, and congenital afibrinogenemia. The patient’s history of afibrinogenemiawas associatedwith episodes of gingival bleeding, hemarthrosis, menorrhagia, and hematemesis. She was treated with on-demand infusions of cryoprecipitate for many years with control of symptoms. In April 2010, she began having recurrent painful edema in her right great toe that progressed to her other digits and foot and was relieved with cryoprecipitate infusions. Over the next year, the pain became more persistent. Evaluation for ischemia with an angiogram demonstrated stenosis of the infrarenal aorta and narrowing of the dorsalis pedis artery. In June 2011, she was started on fibrinogen concentrate infusion to reduce the risk of bleeding intraoperatively and underwent endovascular aortic repair with endoprosthetic stents placed to dilate the distal aortic stenosis. She was treated with clopidogrel 75 mg orally (PO) once daily (QD), aspirin 81 mg PO QD, and prophylactic fibrinogen concentrate infusions 2000 mg IV (intravenous) once weekly due to the history of GI bleeding. She developed recurrent microembolic phenomena after cessation of clopidogrel, which was restarted. In July 2016, she presented with complaints of cramping lower extremity pain on exertion that had progressed to pain at rest and was admitted for critical limb ischemia. Angiogram of the infrarenal abdominal aorta revealed multifocal hypodense plaques in the proximal third of the stents bilaterally consistent with mild-to-moderate in-stent stenosis (►Figs. 2 and 3). She then underwent bilateral common femoral artery exploration with kissing balloon angioplasty with resolution of the stenosis and patent bilateral lower extremities postprocedure. After discharge from the hospital, there was grave concern that she had developed in-stent stenosis while on

The Novel Protease-Activated Receptor 1 Antagonist Vorapaxar as a Treatment for Thrombosis in Afibrinogenemia