BACKGROUND: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome is a severe adverse drug reaction marked by delayed hypersensitivity reactions causing skin and systemic complications. DRESS diagnosis is challenging due to the variety of clinical presentations and symptom overlap with other conditions. The perioperative period in these patients requires precise pharmacological strategies to prevent complications associated with this syndrome. The treatment of DRESS induced by unfractionated heparin during cardiopulmonary bypass (CPB) surgery presents some challenges that must be considered when selecting an anticoagulant to avoid side effects. In this case, bivalirudin, a direct thrombin inhibitor, is indicated as an alternative to heparin in patients undergoing CPB. However, in contrast to heparin/protamine, there is no direct reversal agent for bivalirudin.
METHODS: We report the case of an 11-year-old male diagnosed with native aortic valve endocarditis and thrombosis in his left lower extremity. During valvular replacement surgery, systemic unfractionated heparin was administered. Postoperatively, the patient developed fever, eosinophilia and pruritic rash. Warm shock and elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels followed, leading to the diagnosis of DRESS syndrome. Treatment with methylprednisolone resulted in complete resolution of symptoms. Seven years later, the patient was readmitted due to insufficient anticoagulation and a thrombus in the prosthetic aortic valve, presenting a recurrent DRESS episode due to the administration of unfractionated heparin, which was later replaced with low-molecular-weight heparin during hospitalization. Treatment with corticosteroids and antihistamines was initiated, resulting in the resolution of this episode. Ultimately, the patient required the Ross procedure. During this intervention the anticoagulation strategy was modified, unfractionated heparin was replaced with bivalirudin during the procedure and fondaparinux was administered during the postoperative period. This resulted in stable transaminases levels and no eosinophilia.
CONCLUSIONS: The severity of DRESS Syndrome underscores the importance of early recognition, heightened monitoring, and a comprehensive approach tailored to each patient\'s needs. This particular case highlights the significance of this approach and may have a substantial clinical impact since it provides alternatives to heparin, such as bivalirudin and fondaparinux, in the anticoagulation strategy of CPB for patients who have a hypersensibility reaction to this medication; thus, enhancing clinical outcomes by minimizing risks linked to adverse drug reactions.

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A growing body of evidence supports the use of bivalirudin as an alternative to unfractionated heparin (UFH) for the prevention of thrombotic events in patients on venovenous (VV) extracorporeal membrane oxygenation (ECMO). However, data in patients bridged to lung transplantation are limited. In this case series, we describe the outcomes of six patients who were transitioned from UFH to bivalirudin during their course of VV ECMO support as a bridge to lung transplantation. All six patients were on VV ECMO support until transplant, with a median duration of 73 days. Bivalirudin demonstrated a shorter time to first therapeutic activated thromboplastin time (aPTT) level. Additionally, time in therapeutic range was longer while patients were receiving bivalirudin compared to UFH (median 92.9% vs. 74.6%). However, major bleeding and thrombotic events occurred while patients were receiving either anticoagulant. Based on our experience, bivalirudin appears to be a viable option for anticoagulation in VV ECMO patients bridged to lung transplantation. Larger studies evaluating the optimal anticoagulation strategy in patients bridged to transplant are needed.

OBJECTIVE: To describe the intraoperative use of bivalirudin during lower extremity revascularization in the setting of heparin-induced thrombocytopenia (HIT).
METHODS: A 65 year-old man presented with left common iliac, external iliac, and femoral artery occlusion necessitating revascularization with left femoral endarterectomy and common and external iliac stent angioplasty. Three months before the femoral endarterectomy, the patient was hospitalized for a coronary artery bypass procedure. During this admission, the patient tested positive for the presence of heparin-PF4 antibody complexes. With the patient\'s recent history of HIT, bivalirudin was selected as the optimal agent for intraoperative anticoagulation. Bivalirudin was administered as a 50 mg bolus, followed by a continuous infusion initiated at 1.75 mg/kg/hr. Repeated bivalirudin boluses were necessary to maintain an activated clotting time (ACT) necessary for the revascularization procedures and recurrent subacute thrombi despite appropriate ACT values.
CONCLUSIONS: Bivalirudin has been utilized for cardiopulmonary bypass and carotid endarterectomy (CEA), but data for dosing in lower extremity revascularization are lacking. As the risk for thrombosis with HIT continues for months after diagnosis, it is important to elucidate optimal dosing of non-heparin anticoagulant options, such as the direct thrombin inhibitor, bivalirudin. The absence of validated dosing strategies for bivalirudin can result in prolonged operative times, increased risk of bleeding, and inadequate anticoagulation.
CONCLUSIONS: Bivalirudin is an appropriate agent for intraoperative anticoagulation in lower extremity revascularization. However, further investigation into the optimal intraoperative bivalirudin dosing regimen is necessary.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with thrombosis. Clinical scoring systems and the presence of anti-platelet factor 4 (anti-PF4)/heparin antibodies determine the diagnosis.
METHODS: A 57-year-old man who was treated with acenocoumarol due to a chronic left ventricular thrombus was admitted to the hospital for severe SARS-CoV-2 pneumonia and pulmonary embolism. The patient was started on bemiparin and discharged. Left lower limb acute arterial ischemia and thrombocytopenia were diagnosed 18 days later. Computed tomography angiography revealed a large left ventricular thrombus and multiple arterial thrombi. Left femoral-popliteal thromboembolectomy was performed. Anti-PF4/heparin antibodies confirmed an HIT diagnosis. Fondaparinux (7.5 mg/24 h) was initiated, but cardiac surgery was necessary. Bivalirudin was used during surgery, with an initial load (1.25 mg/kg) and maintenance infusion (2.5 mg/kg/h). The cardiac thrombus was extracted, but the patient experienced a postsurgical myocardial infarction. Percutaneous cardiovascular intervention (PCI) required a bivalirudin load (0.75 mg/kg) and maintenance infusion (1.75 mg/kg/h). No coronary lesions were detected, and argatroban was started afterwards (0.5 µg/kg/min). When the platelet count exceeded 100 × 109/L, acenocoumarol was initiated. Thereupon, acetylsalicylic acid (100 mg/24 h) was added. No other complications have been reported to date.
CONCLUSIONS: The clinical presentation of intraventricular and multiple arterial thrombi is remarkable. SARS-CoV-2 infection likely contributed to a hypercoagulable state. The management of patients with HIT undergoing cardiac surgery is challenging. If surgery cannot be delayed, then treatment with bivalirudin is recommended. Additionally, this drug is recommended for PCI. Bivalirudin is safe and well-tolerated in both procedures.

The Impella device is a percutaneous ventricular assist devices that requires administration of heparin via a continuous purge solution. Patients on Impella device support may experience hemolysis with accompanying thrombocytopenia generating suspicion for heparin-induced thrombocytopenia (HIT). However, data and recommendations for use of non-heparin anticoagulants with Impella device are lacking. Therefore, we performed a retrospective cohort analysis of patients requiring bivalirudin during Impella device support to describe the safety and efficacy of bivalirudin as an alternative anticoagulant during Impella device support. Nine patients were included in the evaluation which analyzed Impella device purge flow and purge pressure along with bivalirudin dosing requirements, incidence of thrombosis, and incidence of pump failure. All patients had a positive platelet factor-4 IgG ELISA test, and the serotonin release assay was positive in four patients. After initiation of bivalirudin, the median (15th, 85th percentile) nadir purge flow decreased by 76% (5%, 88%) and the median (15th, 85th percentile) peak purge pressure increased by 86% (21%, 143%). At the time of bivalirudin discontinuation, the median final purge flow and pressure were 2.4 mL/h (74% decrease) and 969 mmHg (89% increase), respectively. Zero patients experienced catastrophic pump failure. Adding low concentration bivalirudin to the purge solution along with systemic bivalirudin may be a reasonable approach.

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Venous thromboembolism has increasing significance in hospitalized pediatric patients. Patients who have life-threatening or limb-threatening thrombotic events require thrombolysis in addition to anticoagulation. In patients who show signs of heparin resistance or heparin-induced thrombocytopenia, it is imperative to identify alternative therapeutic options. We present a child in whom bivalirudin was used for systemic anticoagulation during catheter-directed thrombolysis along with tissue plasminogen activator (Alteplase® ) for the treatment of a near-occlusive organ-threatening thrombus. We also review the currently available literature on the use of combination therapy of an intravenous direct thrombin inhibitor with alteplase.

Bivalirudin is a direct thrombin inhibitor that is used as a procedural anticoagulant during percutaneous coronary interventions and cardiac surgery for patients with heparin-resistant thrombosis or heparin-induced thrombocytopenia. There is a robust literature describing its safety and efficacy in adults; however, its use in the pediatric population is relatively rare, with dosing extrapolated from adult data. In this case report, we describe a 4-year-old with complex congenital heart disease and history of heparin-induced thrombocytopenia who required bivalirudin dose uptitration during cardiac catheterization.

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