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Evidence-Based Minireview: Should warfarin or a direct oral anticoagulant be used in patients presenting with thrombosis in the splanchnic or cerebral veins?
Mathew, C, Zumberg, M
Hematology. American Society of Hematology. Education Program. 2021;(1):100-105
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Abstract
Case 1: A 23-year-old female third-year medical student who has no medical history seeks treatment for abdominal distention. She takes an estrogen-containing birth control pill and does not smoke or consume alcohol. Family history is unremarkable. Physical examination is significant for abdominal distention, and an abdominal fluid wave is detected. Complete blood count is normal. Imaging confirms occlusive thrombosis of the main portal vein. On endoscopy, grade 1 to 2 esophageal varices are noted and banded. Unfractionated heparin is begun. Subsequent workup reveals a homozygous factor V Leiden mutation. Long-term anticoagulation is planned, and she asks if warfarin can be avoided given her hectic ward rotations, erratic diet, and need for monitoring. Case 2: A 35-year-old woman who has no medical history seeks treatment for progressively worsening posterior headaches for 1 week. Magnetic resonance imaging of the brain shows dural sinus thrombosis with associated small areas of petechial cerebral hemorrhage. She is started on a continuous unfractionated heparin infusion and admitted to the hospital for further observation. Her grandmother is on warfarin for atrial fibrillation, and the patient would prefer to avoid warfarin because she does not think she can comply with the frequent monitoring that will be required. She inquires about other oral anticoagulant options for her condition.
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Evidence-Based Minireview: Are DOACs an alternative to vitamin K antagonists for treatment of venous thromboembolism in patients with MPN?
Schieppati, F, Falanga, A
Hematology. American Society of Hematology. Education Program. 2021;(1):448-452
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Use of Idarucizumab to reverse the anticoagulant effect of dabigatran in cardiac transplant surgery. A multicentric experience in Spain.
Crespo-Leiro, MG, López-Vilella, R, López Granados, A, Mirabet-Pérez, S, Díez-López, C, Barge-Caballero, E, Segovia-Cubero, J, González-Vilchez, F, Rangel-Sousa, D, Blasco-Peiró, T, et al
Clinical transplantation. 2019;(12):e13748
Abstract
BACKGROUND Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin inhibitor, is increasingly used for anticoagulation in patients with non-valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab. AIM: To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT. METHODS Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery. RESULTS Fifty-three patients were included (81.1% male). 7.5% required re-operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30-day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post-HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post-HT death was associated with bleeding. CONCLUSIONS These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations.
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Pipeline Embolization of an Infectious Basilar Artery Aneurysm in a 2-Year-Old Child: Case Report, Discussion of the Literature and Perioperative Considerations.
Ares, WJ, Tonetti, DA, Greene, S, Sharma, MS, Xavier, F, Jankowitz, BT, Jadhav, A
Operative neurosurgery (Hagerstown, Md.). 2019;(5):E224-E228
Abstract
BACKGROUND AND IMPORTANCE Flow diversion of intracranial aneurysms has been rarely described in the pediatric population. Here we discuss the technical and perioperative complexities inherent in the flow diversion of an infectious basilar apex aneurysm in a 2-yr-old child with significant medical comorbidities. CLINICAL PRESENTATION Following judicious oral administration of dual anti-platelet agents and intra-arterial administration of calcium channel blockers to treat vasospasm, standard endovascular procedures were used to place a flow diverting stent across the neck of a rapidly enlarging infectious aneurysm of the basilar apex.Following the uncomplicated procedure, the patient demonstrated progressive thrombosis of the previously noted basilar apex aneurysm over a 3-mo period. The patient was therefore felt to be safe to proceed with, and eventually underwent, uncomplicated orthotopic heart transplant. CONCLUSION Flow diversion of complex intracranial aneurysms in pediatric patients with significant medical comorbidities is feasible and safe; however, considerations have to be made in the pre- and perioperative care of these patients given the propensity for low-weight and complicated systemic disease processes.
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Acquired haemophilia A in a patient with breast cancer and lung carcinoma: a case report and literature review.
Biesheuvel, V, Hiddema, SM, Levenga, H, Eikenboom, J, van der Deure, WM
The Netherlands journal of medicine. 2019;(4):153-155
Abstract
Acquired haemophilia A is a rare disorder caused by spontaneous formation of auto-antibodies (inhibitors) against coagulation factor VIII. This can lead tolife-threatening haemorrhages. Six to twenty-two percent of patients with acquired haemophilia have an underlying malignancy. We describe a 69-year-old woman with metastatic breast cancer and non-small cell lung carcinoma who presented at the emergency room with spontaneous bruising, and who was using a vitamin K antagonist. She had a prolonged activated partial thromboplastin time (aPTT) due to a coagulation factor VIII deficiency caused by factor VIII antibodies. She was treated with prednisone and cyclophosphamide.
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Extremely low therapeutic doses of acenocoumarol in a patient with CYP2C9*3/*3 and VKORC1-1639A/A genotype.
Chaidaroglou, A, Kanellopoulou, T, Panopoulos, G, Stavridis, G, Degiannis, D
Pharmacogenomics. 2019;(5):311-317
Abstract
Vitamin-K antagonists (VKAs) have remained the mainstay of oral anticoagulant therapy for the treatment and prevention of thromboembolism. The management of treatment with VKAs is challenging due to their narrow therapeutic index and the wide interindividual variation in response to therapy. Variants of the CYP2C9 and the VKORC1 gene account for 30-50% of the variability in dosing requirements, and it has been proposed that genotyping of these loci could facilitate management of VKA therapy and minimize risk of overanticoagulation, even in very low doses. We present the first reported case of a patient with the compounded genotype CYP2C9*3*3 and VKORC1-1639A/A under treatment with acenocoumarol, and review of other reported cases with analogous genotypic profiles but under treatment with warfarin.
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High-dose steroid therapy for CNS inflammatory diseases increases INR in patients taking oral vitamin K antagonist.
Gelibter, S, Orrico, M, Croese, T, Bosco, L, Martinelli, V, Sangalli, F, Filippi, M
Journal of neurology. 2019;(12):3160-3161
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Acute non-cirrhotic portal vein thrombosis : review.
Salembier, A, Verhamme, M, Verhamme, P, Van Moerkercke, W
Acta gastro-enterologica Belgica. 2018;(2):318-322
Abstract
A 35-year-old man with a medical history of myocardial infarction, presenting with fever, general malaise and vague abdominal discomfort, was diagnosed with a portomesenteric venous thrombosis and acute cytomegalovirus (CMV) infection. Thrombophilia screening resulted in detection of heterozygosity for factor II G20210A gene mutation. Low molecular weight heparin in therapeutic dose was started, followed by disappearance of thrombus on imaging CT two months after diagnosis. The multifactorial origin of portal thrombosis and the importance of awareness of the link between CMV infection and an increased risk of thrombosis is emphasized with this case and review of the literature. Identifying CMV infection as a trigger for thrombosis can help to avoid extended anticoagulation. Acute non-cirrhotic PVT is a rare but probably underestimated condition as symptoms may be discrete or non-specific. The origin of portal thrombosis is frequently multifactorial. Recent literature has emphasized the increasing prevalence of CMV-induced PVT in immunocompetent patients. The multifactorial origin of portal thrombosis and the importance of awareness of the link between CMV infection and an increased risk of thrombosis is emphasized with this review of the literature and included case. Identifying CMV infection as a trigger for thrombosis can help to avoid extended anticoagulation.
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The critical interaction between valproate sodium and warfarin: case report and review.
Zhou, C, Sui, Y, Zhao, W, Dong, C, Ren, L, Song, P, Xu, B, Sun, X
BMC pharmacology & toxicology. 2018;(1):60
Abstract
BACKGROUND Valproic acid (VPA) and warfarin are commonly prescribed for patients with epilepsy and concomitant atrial fibrillation (AF). When VPA and warfarin are prescribed together, clinically important interactions may occur. VPA may replace warfarin from the protein binding sites and result in an abnormally increased anticoagulation effect. This is commonly underrecognized. CASE PRESENTATION In our case, we report a 78-year-old woman with a glioma who presented with status epilepticus. The patient was on warfarin to prevent cardiogenic embolism secondary to AF. Intravenous loading dose of VPA was administered, but international normalized ratio (INR) increased significantly to 8.26. Intravenous vitamin K1 was then given and the patient developed no overt bleeding during the hospitalization. CONCLUSION By reviewing the literature and discussing the critical interaction between valproate sodium and warfarin, we conclude that intravenous VPA and the co-administrated warfarin may develop critical but underrecognized complications due to effects on the function of hepatic enzymes and displacement of protein binding sites.
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Warfarin-Associated Nonuremic Calciphylaxis.
Yu, WY, Bhutani, T, Kornik, R, Pincus, LB, Mauro, T, Rosenblum, MD, Fox, LP
JAMA dermatology. 2017;(3):309-314
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Abstract
IMPORTANCE Classic calciphylaxis associated with renal failure is a life-threatening disease. Warfarin-associated calciphylaxis without renal injury has been described, but whether it is a subset of classic calciphylaxis or a different entity remains unknown. We describe 1 case of warfarin-associated calciphylaxis, present data from 2 others from our institution, and review all cases of warfarin-associated calciphylaxis available in the literature. Our review indicates that warfarin-associated calciphylaxis is clinically and pathophysiologically distinct from classic calciphylaxis. OBJECTIVE To review warfarin-associated calciphylaxis and determine its relationship to classic calciphylaxis. DESIGN, SETTING, AND PARTICIPANTS We searched MEDLINE and Ovid without language or date restrictions for case reports of calciphylaxis from the inpatient setting using the terms "calciphylaxis and warfarin," "non-uremic calciphylaxis," and "nonuremic calciphylaxis." We defined nonuremic calciphylaxis as a histopathologic diagnosis of calciphylaxis without severe kidney disease (serum creatinine level >3 mg/dL; glomerular filtration rate <15 mL/min; acute kidney injury requiring dialysis; and renal transplantation). EXPOSURES Each patient had been exposed to warfarin before the onset of calciphylaxis. MAIN OUTCOMES AND MEASURES Patient data were abstracted from published reports. Original patient medical records were requested and reviewed when possible. RESULTS We identified 18 patients with nonuremic calciphylaxis, 15 from the literature, and 3 from our institution. Patients were predominantly female (15 of 18 [83%]) with ages ranging from 19 to 86 years. Duration of warfarin therapy prior to calciphylaxis onset averaged 32 months. Lesions were usually located below the knees (in 12 of 18 [67%]). No cases reported elevated calcium-phosphate products (0 of 17 [0%]). Calcifications were most often noted in the tunica media (n = 8 [44%]) or in the vessel lumen and tunica intima (n = 7 [39%]). The most common treatments included substitution of heparin or low-molecular weight heparin for warfarin (n = 13 [72%]), intravenous sodium thiosulfate (n = 9 [50%]), and hyperbaric oxygen (n = 3 [17%]). The survival rate on hospital discharge was remarkably high, with 15 cases (83%) reporting full recovery and 3 cases ending in death. CONCLUSIONS AND RELEVANCE Warfarin-associated calciphylaxis is distinct from classic calciphylaxis in pathogenesis, course, and, particularly, outcome. This finding should influence clinical management of the disease and informs targeted treatment of the disease.