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.

We report a case of a 22-year-old female with antiphospholipid antibody (APLA) syndrome who presented with severe dyspnea. Diagnostic imaging confirmed pulmonary embolism (PE), and treatment comprised unfractionated heparin and apixaban. APLA syndrome was diagnosed based on clinical, serological, and radiological findings. During evaluation, the patient developed cardiogenic shock necessitating catheter-directed thrombolysis, followed by veno-arterial extracorporeal membrane oxygenation (VA-ECMO) due to deteriorating condition and suspected heparin-induced thrombocytopenia (HIT). Surgical embolectomy with bivalirudin use followed, and a hybrid veno-arterial-venous (VAV) ECMO setup was implemented. Postoperatively, the patient improved, transitioning to veno-venous (VV) ECMO and eventually ECMO withdrawal. ECMO is a valuable tool for managing complex cardiorespiratory cases like PE. In the context of HIT and APLA syndrome, prompt anticoagulant transition is vital, and bivalirudin is an effective heparin alternative. Our study highlights the challenges involved in managing patients needing ECMO support with immunothrombotic conditions like HIT and APLA syndrome.

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.

UNASSIGNED: There were controversial opinions on the use of bivalirudin versus heparin for anticoagulant therapy in extracorporeal membrane oxygenation. The aim of our present study is to evaluate the efficacy and safety of bivalirudin versus heparin for the maintenance of systemic anticoagulation during adult veno-venous extracorporeal membrane oxygenation (V-V ECMO).
UNASSIGNED: Adult patients who received V-V ECMO support in our center between February 2018and February 2022 were retrospectively recruited. We analyzed their ECMO support time, platelet count, coagulation indicators, blood product infusion volume, the incidence of thrombosis and bleeding, probability of successful weaning of ECMO, and in-hospital mortality.
UNASSIGNED: A total of 58 patients received V-V ECMO support. Thirty-four patients were finally included according to the exclusion and inclusion criteria, 14 and 20 accepted bivalirudin and heparin for anticoagulant therapy, respectively. The Minimum platelet value (98.50 × 109/L (85.50, 123.75) vs 49.50 × 109/L (31.25, 83.00), p = 0.002) and mean platelet value (149.90 × 109/L (127.40, 164.80) vs 74.55 × 109/L (62.45, 131.60), p = 0.03) and the ratio of successful weaning of ECMO (92.8% vs 60.0%, p = 0.033) in bivalirudin group were significantly higher than those in heparin group. The red blood cell infusion volume (7.00 U (3.00, 13.25) vs 13.75 U (7.25, 22.63), p = 0.039), platelet infusion volume (0.00 mL (0.00, 75.00) vs 300 mL (0.00, 825.00), p = 0.027), and the incidence of major bleeding (0.00% vs 30%, p = 0.024) in bivalirudin group were significantly lower than those in heparin group.
UNASSIGNED: In V-V ECMO-supported adult patients, systemic anticoagulation with bivalirudin has achieved the same anticoagulation targets as heparin with less frequency of major bleeding events and lower requirement for blood products without significantly increased risk of thrombosis. Bivalirudin most likely is a safe and effective anticoagulation method for adult patients supported by V-V ECMO.

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.

Percutaneous coronary intervention (PCI) is one of the most frequently performed invasive therapeutic procedures and plays a key role in the long-term survival of patients with ischemic heart disease. Over 965,000 angioplasties are performed annually in the United States alone. While the technique and equipment have undergone significant revisions and improvement, the medical community will still benefit from more data and guidance on the optimal selection of mandatory peri-operation anticoagulation in specific, high-risk populations. Many of these procedures are performed on high-risk individuals who have an inherently higher risk of hemorrhage or thrombosis. Unfractionated heparin is the most popular choice in the general population, however, its use carries certain limitations. Here we will describe the use of an uncommonly used anticoagulant in a patient being actively treated for leukemia. We will also discuss the unique properties and benefits of the four most frequently used anticoagulants during a cardiac angioplasty. Our team describes the successful use of bivalirudin during an urgent PCI in a 71-year-old female with eight previous stents that was followed by an uncomplicated recovery period. Our experience contributes to a small, but growing, body of evidence that bivalirudin may be a safe choice to use in lieu of unfractionated heparin in patients with underlying oncological disease. Our patient had several comorbidities that significantly increased their risk of bleeding. We will also review the clinical trials that compared the four most commonly used anticoagulants during cardiac catheterization.

As patients transition between dialysis modalities, and from the intra- to the inter-dialytic period, medications with a narrow therapeutic index that are cleared in dialysis may require dose adjustments and close monitoring. Three cases of patients receiving bivalirudin while converting from continuous to prolonged intermittent renal replacement therapy are reported. Details provided include flow rates and ultrafiltrate volume. In these cases, it appears pre-emptive dose adjustments may be unwarranted, and clinicians should be aware of potential rebound after cessation of dialysis.

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.

Extracorporeal membrane oxygenation (ECMO) can provide respiratory and cardiac support to patients in reversible devastated conditions. Heparin is the mainstay for anticoagulation during ECMO. Bivalirudin, a direct thrombin blocker, may represent an effective alternative for patients suffering from heparin-induced thrombocytopenia (HIT). We present the first case of a Chinese patient who experienced HIT and received bivalirudin anticoagulation during ECMO. In addition, we present a systematic review for this topic. We searched PubMed, EMBASE, and Cochrane Library (up to April 20, 2020) for studies that included patients undergoing ECMO, presenting with HIT, requiring bivalirudin treatment, and reporting relevant outcomes. The literature review yielded 15 studies involving 123 patients, amongst whom 58 patients were confirmed or suspected HIT patients, and 76 patients received bivalirudin as an anticoagulant for ECMO. Twelve studies were included for quantitative synthesis, and 46 patients were retrieved. The mean age of these patients was 46 years, and 30 patients were males. The average maintenance rate of bivalirudin was 0.27 ± 0.37 mg/kg/h, in order to maintain a target of activated clotting time (ACT) of 160-220 s. Additionally, bivalirudin doses in patients with continuous renal replacement therapies (CRRT) and patients without CRRT were 0.15 ± 0.06 mg/kg/h vs 0.28 ± 0.36 mg/kg/h, respectively (p=0.15). Most of the patients with confirmed HIT improved platelet counts in 3.3 ± 2.8 days after switching to bivalirudin anticoagulation. The patient-level data showed that 29 cases survived, 1 reported major bleeding, and 4 reported thrombotic events. Bivalirudin might be a promising optimal choice for ECMO anticoagulation in patients with HIT. A tailored protocol for management of bivalirudin treatment during ECMO should be developed with caution. Further prospective studies are necessary to standardise the use of bivalirudin.
UNASSIGNED: PROSPERO, identifier CRD42020160907.