warfarin and Aneurysm--Ruptured

Background and Purpose- The effects of anticoagulation therapy and elevated international normalized ratio (INR) values on the risk of aneurysmal subarachnoid hemorrhage are unknown. We aimed to investigate the association between anticoagulation therapy, elevated INR values, and rupture of intracranial aneurysms. Methods- We conducted a case-control study of 4696 patients with 6403 intracranial aneurysms, including 1198 prospective patients, diagnosed at the Massachusetts General Hospital and the Brigham and Women's Hospital between 1990 and 2016 who were on no anticoagulant therapy or on warfarin for anticoagulation. Patients were divided into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to evaluate the association of anticoagulation therapy, INR values, and presentation with a ruptured intracranial aneurysm, taking into account the interaction between anticoagulant use and INR. Inverse probability weighting using propensity scores was used to minimize differences in baseline demographics characteristics. The marginal effects of anticoagulant use on rupture risk stratified by INR values were calculated. Results- In unweighted and weighted multivariable analyses, elevated INR values were significantly associated with rupture status among patients who were not anticoagulated (unweighted odds ratio, 22.78; 95% CI, 10.85-47.81 and weighted odds ratio, 28.16; 95% CI, 12.44-63.77). In anticoagulated patients, warfarin use interacts significantly with INR when INR ≥1.2 by decreasing the effects of INR on rupture risk. Conclusions- INR elevation is associated with intracranial aneurysm rupture, but the effects may be moderated by warfarin. INR values should, therefore, be taken into consideration when counseling patients with intracranial aneurysms.

Topics: Adult; Aged; Aneurysm, Ruptured; Anticoagulants; Case-Control Studies; Female; Humans; International Normalized Ratio; Intracranial Aneurysm; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Propensity Score; Risk Factors; Rupture, Spontaneous; Subarachnoid Hemorrhage; Warfarin

Topics: Adult; Aneurysm, False; Aneurysm, Ruptured; Drug Overdose; Dyspnea; Echocardiography, Doppler, Color; Humans; Leg Ulcer; Lupus Coagulation Inhibitor; Lupus Erythematosus, Systemic; Male; Treatment Outcome; Venous Thrombosis; Ventricular Dysfunction, Left; Warfarin

There is evidence that vitamin K-deficiency during human pregnancy can be caused by the therapeutic use of warfarin or phenytoin. The pregnancy histories of three cases of Binder's syndrome are reported. One was associated with warfarin exposure, one with phenytoin exposure and one with alcohol abuse. It is proposed that Binder's syndrome can be caused by prenatal exposure to agents that cause vitamin K-deficiency. Sprague-Dawley rats were treated from postnatal day 1 to 12 weeks with daily doses of warfarin (100 mg/kg) and concurrent vitamin K1 (10 mg/kg). This regimen creates a net extra-hepatic vitamin K-deficiency. The treated rats developed with a distinct facial appearance characterized by a markedly reduced snout. Histological examination showed that the normally non-calcified septal cartilage was extensively calcified. It is proposed that normal growth of the septal cartilage is necessary for the development of the profile of the nose and midface and that normal growth will only take place while the septal cartilage is uncalcified.

Topics: Adolescent; Alcoholism; Aneurysm, Ruptured; Animals; Cartilage; Child, Preschool; Female; Humans; Infant; Intracranial Aneurysm; Male; Maxilla; Nasal Bone; Nasal Septum; Phenytoin; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Thrombophlebitis; Vitamin K; Vitamin K Deficiency; Warfarin