Low-dose oral vitamin K to normalize the international normalized ratio prior to surgery in patients who require temporary interruption of warfarin

Background In patients who require warfarin interruption before surgery and have an elevated international normalized ratio (INR) before surgery, low-dose vitamin K may normalize the INR in time for surgery. Patients and methods In a retrospective cohort study, we assessed the efficacy of 1 mg oral vitamin K to normalize the INR for surgery and whether resistance to re-anticoagulation occurs when warfarin is restarted after surgery. We studied a cohort of patients with an INR 1.4–1.9 on the day before surgery who received 1 mg oral vitamin K (vitamin K group), and a comparator group of patients with a normal INR (≤1.3) on the day before surgery who did not receive vitamin K (no vitamin K group). In both patient groups, we determined the proportion of patients with a normalized INR on the day of surgery and compared the mean INR after surgery when warfarin was resumed. Results Of 43 patients in the vitamin K group, the INR was normalized (≤1.3) in 33 patients (76.6; 95% confidence interval [CI]: 64.1–89.4), and the INR was normal or near-normal (≤1.4) in 39 patients (90.7; 95% CI: 82.0–99.4) on the day of surgery. The mean (standard deviation) INR in the vitamin K and no vitamin K group 4–8 days after surgery was 1.75 (0.34) and 1.59 (0.36), respectively (P = 0.56). Conclusions In patients requiring interruption of warfarin for surgery, 1 mg oral vitamin K on the day before surgery can normalize the INR by the day of surgery and may not confer resistance to warfarin re-anticoagulation after surgery.     

Postpartum management of women at increased risk of thrombosis--results of a Canadian pilot survey

OBJECTIVE: To determine current practice patterns in the postpartum management of women at increased risk of thrombosis. METHODS: Physicians affiliated with the University of Toronto departments of Obstetrics and Gynecology, Rheumatology, Hematology, and Obstetric Medicine who provide care to pregnant women were mailed a questionnaire that presented 6 clinical scenarios involving postpartum management of a woman at risk for thrombosis, with (1) recurrent pregnancy loss and antiphospholipid antibody syndrome (APS) treated with aspirin (ASA) in the pregnancy; (2) 2 pregnancy losses and a low titer antiphospholipid antibody (aPL) treated with ASA and low molecular weight (LMW) heparin with placental insufficiency; (3) known APS and pregnancy loss treated with LMW heparin and delivered by cesarean section; (4) a previous 17 week fetal death and aPL; (5) a previous deep vein thrombosis while on oral contraception; and (6) systemic lupus erythematosus and secondary APS with a history of a stillbirth. Physicians were asked whether they would recommend postpartum coagulation, and if so to choose from a list of treatment options. RESULTS: Of the 71 questionnaires mailed, 44 were returned (62%). Three physicians replied that their practices do not include patients similar to those presented in the cases and chose not to respond to the clinical scenarios. Percentages of responders recommending treatment in each scenario were 29% for Case 1, 49% for Case 2, 63% for Case 3, 41% for Case 4, 51% for Case 5, and 58% for Case 6. Recommendation for treatment differed among medical specialties, with rheumatologists being less likely to treat in all cases. Prophylactic heparin was selected as the treatment of choice most frequently by those recommending anticoagulation 70% (84/120). CONCLUSION: Postpartum treatment recommendations for women at increased risk of thrombosis are variable across different practitioner specializations demonstrating clinical equipoise regarding therapy. More definitive research is needed and broader study of physicians involved in the care of these patients is planned to more accurately describe and understand the decision to treat these patients.     

Prevention and treatment of venous thromboembolism in the elderly patient

Venous thromboembolism (VTE) is a common complication among hospitalized patients. Pharmacological thromboprophylaxis has emerged as the cornerstone for VTE prevention. As trials on thromboprophylaxis in medical patients have proven the efficacy of both low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH), all acutely medical ill patients should be considered for pharmacological thromboprophylaxis. Unlike in the surgical setting where the risk of associated VTE attributable to surgery is well recognized, and where widespread use of pharmacological thromboprophylaxis and early mobilization has resulted in significant reductions in the risk of VTE, appropriate VTE prophylaxis is under-used in medical patients. Many reasons for this under-use have been identified, including low perceived risk of VTE in medical patients, absence of optimal tools for risk assessment, heterogeneity of patients and their diseases, and fear of bleeding complications. A consistent group among hospitalized medical patients is composed of elderly patients with impaired renal function, a condition potentially associated with bleeding. How these patients should be managed is discussed in this review. Particular attention is devoted to LMWHs and fondaparinux and to measures to improve the safety and the efficacy of their use.     

Systematic assessment of inflammation by magnetic resonance imaging in the posterior elements of the spine in ankylosing spondylitis

Objective

Magnetic resonance imaging (MRI) is sensitive for scoring inflammatory lesions in the spine, but attention has primarily focused on vertebral bodies, and no study has systematically examined the posterior elements. We aimed to systematically determine the frequency and distribution of inflammatory changes in the posterior elements of the spine using MRI, and to assess the reliability of their detection and their impact on discrimination of spinal MRI.

Methods

We scanned 32 patients recruited to placebo‐controlled trials of anti–tumor necrosis factor therapy. Inflammatory lesions were detected by systematic review of consecutive sagittal STIR slices of the entire spine. Two readers evaluated pretreatment and posttreatment scans, blinded to treatment and time point. Inflammation was scored dichotomously (present/absent) in each posterior structure. Reproducibility was assessed by calculating random model variance components and generalizability coefficients, and discrimination by using Guyatt's effect size.

Results

Most patients (87.5%) had ≥1 lesion in the posterior elements (mean ± SD number of affected spinal levels per patient 6.7 ± 5.3), and they were detected most frequently in the thoracic spine. Interobserver reproducibility for total lesion count was very good to excellent for lesions in the thoracic spine and transverse and spinous processes. The addition of a simple dichotomous method for scoring posterior element inflammation substantially enhanced the discrimination observed using established MRI methods for scoring vertebral body inflammation.

Conclusion

Inflammatory lesions in the posterior elements were present in the majority of patients with AS, and standard MRI protocols of the spine should be modified to ensure adequate visualization of posterolateral structures.     

Is impaired renal function a contraindication to the use of low-molecular-weight heparin?

BACKGROUND: Because of the risk of accumulation of anticoagulant effect, it has been suggested that patients with a creatinine clearance of 30 mL/min or less (< or =0.50 mL/s) should be excluded from treatment with low-molecular-weight (LMW) heparin, or have anti-factor Xa heparin level monitoring performed. OBJECTIVE: To assess the appropriateness of this recommendation. METHODS: We performed a systematic search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts to identify prospective articles comparing differences in the pharmacokinetics of LMW heparins in nondialyzed patients with varying degrees of renal function. Reference lists of retrieved reports were checked for additional articles. RESULTS: Three single-dose pharmacokinetic trials and 2 multiple-dose deep vein thrombosis (treatment trials met our selection criteria. The 3 trials that could address our primary objective did not support the use of a 30-mL/min (0.50-mL/s) cutoff of creatinine clearance to select individuals at risk of accumulation when LMW heparin is used. Four of the 5 trials support the notion that anti-factor Xa activity of some LMW heparin preparations accumulates in patients with impaired creatinine clearance. Tinzaparin sodium, an LMW heparin with a higher-than-average molecular weight distribution, appears to be the exception, since it did not exhibit accumulation in patients with creatinine clearances as low as 20 mL/min (0.33 mL/s). CONCLUSIONS: The use of a 30-mL/min (0.50-mL/s) cutoff is not justified, on the basis of currently available evidence, to select individuals at increased risk of accumulation when LMW heparin is used. The pharmacokinetic response to impaired renal function may differ among LMW heparin preparations.     

Bleeding risk and the management of bleeding complications in patients undergoing anticoagulant therapy: focus on new anticoagulant agents

For more than 60 years, heparin and coumarin have been mainstays of anticoagulation therapy. They are widely available, inexpensive, effective, and have specific antidotes but are regarded as problematic because of their need for careful monitoring. In addition, coumarin has a delayed onset of action, interacts with many medications, has a narrow therapeutic window, and is paradoxically prothrombotic in certain settings (ie, can precipitate "coumarin necrosis"). Heparin may require monitoring of its therapeutic effect and can also cause thrombosis (heparin-induced thrombocytopenia/thrombosis syndrome). These limitations have led to the development of new anticoagulants with the potential to replace current agents. These newer agents fall into 2 classes, based on whether they are antithrombin dependent (low-molecular-weight heparin, fondaparinux) or antithrombin independent (direct inhibitors of factor Xa and thrombin [factor IIa]). This paper addresses newer anticoagulants, reviewing their efficacy and limitations, and focuses on the risk of major bleeding that may complicate their use. In contrast to heparin and coumarin, none of these newer agents has a specific antidote that completely reverses its anticoagulant effect. Available data on the efficacy and safety of current and experimental agents for anticoagulant reversal are reviewed, and a plan for management of anticoagulant-induced bleeding is presented.     

Short-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of prospective studies investigating symptomatic outcomes

BACKGROUND: The prevalence of asymptomatic deep vein thrombosis diagnosed by venography after hip or knee replacement remains high despite 7 to 10 days of anticoagulant prophylaxis. However, the risk of symptomatic events in such patients is unclear. We performed a meta-analysis to provide reliable estimates of the risk of symptomatic venous thromboembolism occurring within 3 months of hip or knee replacement in patients who received short-duration (7-10 days) anticoagulant prophylaxis. METHODS: The MEDLINE, EMBASE, and Cochrane databases were searched from January 1993 to March 2001, supplemented by a manual search of bibliographies and conference abstracts, to identify prospective studies of patients undergoing hip or knee replacement who received short-duration prophylaxis (ie, 7-10 days of fixed-dose low-molecular-weight heparin or adjusted-dose warfarin, with a target international normalized ratio of 2.0-3.0). Studies were classified as clinical outcome studies if the outcome was symptomatic venous thromboembolism or as venographic outcome studies if the outcome was asymptomatic deep vein thrombosis diagnosed after bilateral venography. RESULTS: There were 4 clinical outcome studies with 6089 patients who had 3 months of follow-up, and 13 venographic outcome studies with 7080 patients who had venography 7 to 10 days after surgery. In clinical outcome studies, the 3-month incidence of nonfatal venous thromboembolism was 3.2% (95% confidence interval [CI], 2.0%-4.4%), and the 3-month incidence of fatal pulmonary embolism was 0.10% (95% CI, 0.02%-0.20%). The postprophylaxis incidence of nonfatal venous thromboembolism was 2.2% (95% CI, 1.4%-3.0%), and the incidence of fatal pulmonary embolism was 0.05% (95% CI, 0%-0.12%). The postprophylaxis incidence of symptomatic venous thromboembolism was higher after hip than after knee replacement (2.5% vs 1.4%; P=.02). In venographic outcome studies, the prevalence of deep vein thrombosis (total and proximal) was higher after knee than after hip replacement (total: 38.8% vs 16.4%; P<.001; proximal: 7.6% vs 3.8%; P<.001). CONCLUSIONS: In patients who undergo hip or knee replacement and receive short-duration anticoagulant prophylaxis, symptomatic nonfatal venous thromboembolism will occur in about 1 of 32 patients and fatal pulmonary embolism will occur in about 1 of 1000 patients within 3 months of the surgery. Although the prevalence of asymptomatic deep vein thrombosis is more than 2-fold higher after knee replacement than after hip replacement 7 to 10 days after surgery, in the subsequent 3 months, symptomatic venous thromboembolism is more likely to occur after hip replacement.     

A comparison of two methods of assessing orthodontic treatment need in the mixed dentition: DAI and IOTN

This paper assesses the unmet orthodontic treatment need in a random sample of 10-year-old schoolchildren, using two indices: the Dental Aesthetic Index (DAI) and the Index of Orthodontic Treatment Need (IOTN). The DAI scores were adjusted by omitting the missing teeth component of the index because many children were in the mixed dentition with unerupted permanent teeth. Although both indices assessed the same number of children with malocclusions requiring orthodontic treatment, not all were ranked similarly by each index.     

Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors

The new oral anticoagulants dabigatran, rivaroxaban and apixaban have advantages over warfarin which include no need for laboratory monitoring, less drug-drug interactions and less food-drug interactions. However, there is no established antidote for patients who are bleeding or require emergent surgery and there is a paucity of evidence to guide the clinical care during these situations. Members of thrombosis and anticoagulation groups participating in the Thrombosis and Hemostasis Summit of North America formulated expert opinion guidance for reversing the anticoagulant effect of the new oral anticoagulants and suggest: routine supportive care, activated charcoal if drug ingestion was within a couple of hours, and hemodialysis if feasible for dabigatran. Also, the pros and cons of the possible use of four factor prothrombin complex concentrate are discussed.