warfarin and Spinal-Fractures

Anticoagulant therapy in patients with atrial fibrillation requires careful evaluation because its benefits i.e. prevention of thromboembolism, must be greater than the risk of bleeding. Patients at higher risk of thrombosis are evaluated through specific scores, such as the CHA(2)DS(2)VASc, coupled with scoring systems for assessing bleeding risks, such as the HAS-BLED score. In addition to bleeding, other risks have been associated with the use of warfarin, including an increased susceptibility to vascular calcifications and fractures caused by a reduction in the levels of vitamin K dependent carboxylated enzymes, matrix Gla-protein (MGP) and bone Gla-protein or osteocalcin (BGP). In fact, while on one side warfarin is used to prevent embolism, on the other hand acting as a vitamin K antagonist it blocks the inhibitory effect of MGP on vascular calcification. Similarly, patients treated with warfarin carry a greater risk of developing osteoporosis and fractures, due to reduced BGP activity. Recently, a new generation of anticoagulant drugs has been developed, such as dabigatran, a direct thrombin inhibitor, and rivaroxaban, a direct factor-Xa inhibitor. They offer an interesting alternative to warfarin, because they do not require frequent blood tests for monitoring while offering similar results in terms of efficacy. Lacking the inhibitory effect on the vitamin K cycle, the consequent side effects can be avoided. If, compared to warfarin treated patients, a lower incidence of vascular calcifications and fractures will be demonstrated, the advantages over warfarin may be even greater, leading to further benefits in terms of morbidity and mortality.

Topics: Animals; Anticoagulants; Atrial Fibrillation; Drug Design; Drug Monitoring; Hemorrhage; Humans; Spinal Fractures; Thromboembolism; Vascular Calcification; Vitamin K; Warfarin

It is unclear whether anticoagulant type is associated with the risk for osteoporotic fracture, a deleterious complication of anticoagulants among patients with atrial fibrillation (AF).. To compare the risk for osteoporotic fracture between anticoagulants.. Population-based cohort study.. Territory-wide electronic health record database of the Hong Kong Hospital Authority.. Patients newly diagnosed with AF between 2010 and 2017 who received a new prescription for warfarin or a direct oral anticoagulant (DOAC) (apixaban, dabigatran, or rivaroxaban). Follow-up ended on 31 December 2018.. Osteoporotic hip and vertebral fractures in anticoagulant users were compared using propensity score-weighted cumulative incidence differences (CIDs).. There were 23 515 patients identified (3241 apixaban users, 6867 dabigatran users, 3866 rivaroxaban users, and 9541 warfarin users). Overall mean age was 74.4 years (SD, 10.8), ranging from 73.1 years (warfarin) to 77.9 years (apixaban). Over a median follow-up of 423 days, 401 fractures were identified (crude event number [weighted rate per 100 patient-years]: apixaban, 53 [0.82]; dabigatran, 95 [0.76]; rivaroxaban, 57 [0.67]; and warfarin, 196 [1.11]). After 24-month follow-up, DOAC use was associated with a lower risk for fracture than warfarin use (apixaban CID, -0.88% [95% CI, -1.66% to -0.21%]; dabigatran CID, -0.81% [CI, -1.34% to -0.23%]; and rivaroxaban CID, -1.13% [CI, -1.67% to -0.53%]). No differences were seen in all head-to-head comparisons between DOACs at 24 months (apixaban vs. dabigatran CID, -0.06% [CI, -0.69% to 0.49%]; rivaroxaban vs. dabigatran CID, -0.32% [CI, -0.84% to 0.18%]; and rivaroxaban vs. apixaban CID, -0.25% [CI, -0.86% to 0.40%]).. Residual confounding is possible.. Among patients with AF, DOAC use may result in a lower risk for osteoporotic fracture compared with warfarin use. Fracture risk does not seem to be altered by the choice of DOAC. These findings may help inform the benefit-risk assessment when choosing between anticoagulants.. The University of Hong Kong and University College London Strategic Partnership Fund.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Cohort Studies; Dabigatran; Female; Follow-Up Studies; Hip Fractures; Hong Kong; Humans; Male; Osteoporotic Fractures; Pyrazoles; Pyridones; Rivaroxaban; Spinal Fractures; Stroke; Warfarin

The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown.. To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF.. Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016.. Dabigatran or warfarin use during the study period.. Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated.. Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean [SD] age, 74 [11] years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users [1.0%]; 72 warfarin users [1.5%]). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, -0.68 [95% CI, -0.38 to -0.86]; IRR, 0.38 [95% CI, 0.22 to 0.66]). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, -3.15 [95% CI, -2.40 to -3.45]; IRR, 0.12 [95% CI, 0.04 to 0.33]), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, -0.04 [95% CI, 0.67 to -0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (P value for interaction, <.001).. Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.

Topics: Accidental Falls; Aged; Anticoagulants; Antithrombins; Atrial Fibrillation; Dabigatran; Databases, Factual; Female; Hip Fractures; Hong Kong; Humans; Male; Osteoporotic Fractures; Poisson Distribution; Propensity Score; Retrospective Studies; Risk; Spinal Fractures; Stroke; Warfarin

Warfarin inhibits vitamin-K dependent proteins involved in bone mineralization and the prevention of vascular calcification (bone Gla protein BGP, matrix Gla protein MGP). In this multicenter, cross-sectional study with 3-year follow-up, data from 387 patients on hemodialysis for ≥1 year at 18 dialysis units were analyzed. Patients on warfarin treatment for > 1 year (11.9% of the population) were compared with the remaining cohort for vertebral fractures, vascular calcifications and mortality. Vertebral fractures and vascular calcifications were sought in L-L vertebral X-rays (D5 to L4). Compared with controls, warfarin-treated male patients had more vertebral fractures (77.8 vs. 57.7%, p<0.04), but not females (42.1% vs. 48.4%, p=0.6); total BGP was significantly reduced (82.35 vs. 202 µg/L, p<0.0001), with lower levels in treated men (69.5 vs. women 117.0 µg/L, p=0.03). In multivariate logistic regression analyses, the use of warfarin was associated with increased odds of aortic (OR 2.58, p<0.001) and iliac calcifications (OR 2.86, p<0.001); identified confounders were age, atrial fibrillation, angina, PPI use and total BGP. Seventy-seven patients died during a 2.7±0.5 year follow-up. In univariate Cox regression analysis, patients on warfarin had a higher risk of all-cause mortality (HR 2.42, 95% CI 1.42-4.16, p=0.001) when compared with those untreated and data adjustment for confounders attenuated but confirmed the significant warfarin-mortality link (HR: 1.97, 95% CI: 1.02-3.84, P=0.046). In hemodialysis patients, additional studies are warranted to verify the risk/benefit ratio of warfarin, which appears to be associated with significant morbidity and increased mortality.

Topics: Aged; Aged, 80 and over; Anticoagulants; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Italy; Kaplan-Meier Estimate; Kidney Diseases; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Prevalence; Proportional Hazards Models; Renal Dialysis; Risk Factors; Sex Factors; Spinal Fractures; Time Factors; Vascular Calcification; Warfarin

Association between warfarin use and fracture risk is unclear. We examined the association between long-term warfarin use and fracture risk at the hip, spine, and wrist in elders. No significant association was found between long-term warfarin use and fracture risk, despite biological plausibility.. Prior studies examining the association of warfarin use and osteoporotic fractures have been conflicting, potentially related to methodological limitations. Thus, we examined the association of long-term warfarin use with risk of hip, spine, and wrist fractures among older adults with atrial fibrillation, attempting to address prior methodologic challenges.. We included men and women ≥ 65 years of age with incident atrial fibrillation and without prior history of fractures from The Health Improvement Network followed between 2000 and 2010. Long-term warfarin use was defined in two ways: (1) warfarin use ≥ 1 year; (2) warfarin use ≥ 3 years. Propensity-score matched cohorts of warfarin users and nonusers were created to evaluate the association between long-term warfarin use and risk of hip, spine, and wrist fractures separately as well as combined, using Cox-proportional hazards regression models.. Among >20,000 participants with incident atrial fibrillation, the hazard ratios (HR) for hip fracture with warfarin use ≥ 1 and ≥ 3 years, respectively, were 1.08 (95%CI 0.87, 1.35) and 1.13 (95% CI 0.84, 1.50). Similarly, no significant associations were observed between long-term warfarin use and risk of spine or wrist fracture. When risk of any fracture was assessed with warfarin use, no association was found [HR for warfarin use ≥ 1 year 0.92 (95%CI 0.77, 1.10); HR for warfarin use ≥ 3 years 1.12 (95%CI 0.88, 1.43)].. Long-term warfarin use among elders with atrial fibrillation was not associated with increased risk of osteoporotic fractures and therefore does not appear to necessitate additional surveillance or prophylaxis.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Databases, Factual; Drug Administration Schedule; Drug Utilization; Female; Hip Fractures; Humans; Incidence; Male; Osteoporotic Fractures; Propensity Score; Risk Assessment; Spinal Fractures; United Kingdom; Warfarin; Wrist Injuries

Vertebral artery injury (VAI) associated with cervical trauma is being increasingly recognized with more aggressive screening. Disparate results from previous literature have led to uncertainty of the significance, natural history, and optimal therapy for VAI.. To understand the natural history and treatment outcomes from our experience, we performed a retrospective, single-center review from a level I trauma center for the previous 10 years of all VAI. Injuries were identified from search of an administrative trauma database, a resident-run working database, and all radiology dictations for the same period. All VAI were classified according to segmental involvement, Denver grading scale, and laterality. Analysis of associated injuries, demographics, neurologic outcome, mortality, length of stay, treatment plan, and follow-up imaging was also performed.. Fifty-one patients with VAI were identified from 2001 to 2011 from a total of 36,942 trauma admissions (0.13% incidence). Associated injuries were significant with an average New Injury Severity Score of 29.6. Penetrating trauma occurred in 14%. Cervical spine fracture was present in 88% with VAI. Diagnosis was obtained with computed tomographic angiography (CTA) in 95%. Screening was prompted by injury pattern or high-risk mechanism in all cases. Injuries classified according to the Denver grading scale were grade I = 24%, grade II = 35%, grade III = 4%, grade IV = 35%, and grade V = 2%. Distribution across segments included V1 = 18%, V2 = 67%, V3 = 31%, and V4 = 6%. Only one posterior circulation stroke was attributable to VAI. Overall mortality was 8%, with each mortality being associated with significant other organ injuries. Treatment rendered for VAI was antiplatelet therapy (50%), observation (31%), warfarin (17%), and stent (2%). There were no significant differences between treatment groups on any variable with the exception of body mass index (P = .047). Follow-up was obtained for 13% (n = 6) of survivors. The CTA demonstrated injury stability in four patients and resolution in two patients. Accuracy of the administrative trauma database was 53% compared with 96% for the resident-run working database.. Neurologic sequelae attributable to VAI were rare. Grade of VAI or vertebral artery segment did not correlate with morbidity. We did not observe any differences in short-term outcomes between systemic anticoagulation and antiplatelet therapy. Of those patients seen at follow-up, injury resolution or stability was documented by CTA. A conservative approach with either observation or antithrombotic therapy is suggested. If the natural history of VAI includes a very low stroke rate, then therapies with a lower therapeutic index, such as systemic anticoagulation, in the severely injured trauma patient are not supported. Our search strategy urges awareness of the limitations of administrative databases for retrospective vascular study.

Topics: Adult; Anticoagulants; Cervical Vertebrae; Chi-Square Distribution; Endovascular Procedures; Female; Humans; Injury Severity Score; Male; Middle Aged; Multiple Trauma; Odds Ratio; Platelet Aggregation Inhibitors; Predictive Value of Tests; Retrospective Studies; Risk Factors; Spinal Fractures; Stents; Stroke; Tennessee; Time Factors; Tomography, X-Ray Computed; Trauma Centers; Treatment Outcome; Vascular System Injuries; Vertebral Artery; Warfarin; Wounds, Penetrating; Young Adult

We report the first case of acute subdural hematoma (SDH) developing after tightening the halo of an osteoporotic 61-year-old woman on warfarin therapy for bilateral traumatic vertebral artery dissection. We discuss literature relevant to this case with an emphasis on identifying warning signs, including recurrent pin loosening, especially in patients with compromised bone structure and high risk of bleeding. Our 61-year-old patient presented to neurosurgery clinic for a 2-month follow-up of a type-III odontoid fracture sustained in a motor vehicle accident. The patient had repeatedly loosened halo pins, and shortly after the pins were tightened, the patient had a syncopal event and struck her head. An emergent computed tomography scan revealed acute SDH requiring emergent craniotomy and evacuation. SDH following pin penetration in a patient with bilateral vertebral artery dissection, osteoporosis, and anticoagulation has not been reported as a complication of the use of the halo vest for stabilization of the cervical spine. The risk of this serious complication can be minimized by giving special consideration to patients with comorbidities and by repositioning problematic pins. This case demonstrates the importance of special attention to bone strength, bleeding risk, and recurrent minor complaints with use of the halo vest.

Topics: Accidental Falls; Accidents, Traffic; Anticoagulants; Bone Nails; Craniocerebral Trauma; Craniotomy; Device Removal; Equipment Failure; Female; Hematoma, Subdural, Acute; Hemorrhagic Disorders; Humans; Immobilization; Middle Aged; Odontoid Process; Osteoporosis, Postmenopausal; Risk Factors; Spinal Fractures; Syncope; Tomography, X-Ray Computed; Vertebral Artery Dissection; Warfarin

To describe a complication of placement of an inferior vena cava (IVC) filter in a man with paraplegia.. Case report.. A 48-year-old man with T11 paraplegia secondary to an L1 burst fracture underwent thoracic spinal fusion. The postoperative course was complicated by deep vein thrombosis (DVT) of the right common femoral vein, which was treated with warfarin.. During rehabilitation, the hematocrit declined, and fluctuance was noted along the surgical site. Computed tomographic scan suggested a hematoma in the paraspinal and latissimus dorsi muscles. Warfarin was discontinued, and an IVC filter was placed. He subsequently developed severe leg pain, followed by hypotension, acute renal failure, and compartment syndrome in bilateral lower extremities requiring fasciotomies. Ultrasound and computed tomographic angiogram showed extensive bilateral lower extremity DVTs and pulmonary emboli. The diagnosis of cerulea dolens was made. Mechanical and pharmacological thrombectomy was aborted secondary to bleeding complications and hypotension. The patient died shortly after care was withdrawn at the family's request. The autopsy revealed multiple thrombi in IVC, bilateral pelvic and femoral veins, and left pulmonary artery embolus, consistent with phlegmasia cerulea dolens.. Inferior vena cava filters may prevent pulmonary embolism but do not affect the underlying thrombotic process. An IVC filter should be recognized as a possible thrombogenic nidus in patients with spinal cord injury who have known DVT.

Topics: Anticoagulants; Fatal Outcome; Humans; Male; Middle Aged; Paraplegia; Pulmonary Embolism; Spinal Cord Injuries; Spinal Fractures; Thrombophlebitis; Tomography, X-Ray Computed; Vena Cava Filters; Venous Thrombosis; Warfarin

A case of inferior vena cava syndrome following percutaneous vertebroplasty is described herein.. To alert clinicians to the potential occurrence of inferior vena cava syndrome following percutaneous vertebroplasty.. Vertebroplasty is a less invasive treatment solution for the osteoporotic compression fracture. There complications of the cement leakage would appear to have been rather infrequent. We report a case of inferior vena cava syndrome related to the cement leakage.. A 59-year-old woman underwent percutaneous vertebroplasty for painful T11, L1, L2, and L3 compression fractures, under general anesthesia at a community hospital. A contralateral transpedicular approach was made in order to inject polymethylmethacrylate resin into the fractured vertebra.. Just subsequent to surgery, this patient developed dyspnea, arthralgia, myalgia, and progressive right lower-limb pain, redness, and swelling., conservative treatment being then undertaken, albeit in vain. One week after the attempted remediation of this patient's condition, she was transferred to our hospital for further management. After admission, radiography of the patient's lumbar spine (lateral view) revealed multiple cement leakage in the area of the posterior longitudinal ligament and also in the anterior paravertebral area. The abdominal and pelvic CT scan and venography revealed vertebroplasty cement leakage into the lumbar vein, the left renal vein, and the inferior vena cava. Thrombosis at the left common iliac vein and left femoral vein were noted with extension into the inferior part of the inferior vena cava. Intravenous heparin was then administered to our patient for the ensuing 20 days, at which time heparin was replaced by warfarin, in order to attempt to prevent progressive venous thrombosis. The patient's leg edema appeared to improve 10 weeks subsequent to her surgery, she then being able to perambulate using a rigid walker.. This case illustrates the need for clinicians to be critically aware of the potential occurrence of inferior vena cava syndrome among patients who have undergone percutaneous vertebroplasty, especially when multiple levels of vertebra are injected as part of the vertebroplasty procedure.

Topics: Anticoagulants; Bone Cements; Female; Fractures, Compression; Heparin; Humans; Lumbar Vertebrae; Middle Aged; Phlebography; Polymethyl Methacrylate; Spinal Fractures; Syndrome; Thoracic Vertebrae; Tomography, X-Ray Computed; Treatment Outcome; Vena Cava, Inferior; Venous Thrombosis; Vertebroplasty; Warfarin