Weight-adjusted tinzaparin for venous thromboembolism prophylaxis in bariatric surgery patients weighing 160 kg or more.

INTRODUCTION: Bariatric surgery patients experience an increased risk of venous thromboembolism (VTE), however, the optimal dose of low-molecular-weight heparin for VTE prophylaxis remains uncertain. Currently, St. Joseph's Healthcare Hamilton utilizes a weight-adjusted tinzaparin dosage (50 to 75 units/kg rounded to nearest pre-filled syringe) for postoperative VTE prophylaxis. OBJECTIVES: This study analyzed the safety of weight-adjusted tinzaparin for VTE prophylaxis in bariatric surgery patients weighing ≥160 kg. METHODS: This was a retrospective study involving patients weighing ≥160 kg that underwent bariatric surgery from September 2015 to September 2019. Patients received a single dose of weight-adjusted subcutaneous unfractionated heparin (UFH) [5000 or 7500 IU] immediately prior to surgery, subcutaneous UFH [5000 IU, 7500 IU, or unspecified] immediately postoperatively, and either 10,000 or 14,000 IU of tinzaparin, beginning on the day after surgery, for 10 days. Intra-operative sequential compression devices could be used at the attending surgeon's discretion. Occurrence of VTE and major bleeding within 30 days of surgery were assessed. RESULTS: A total of 389 patients were included for analysis, all patients received in-hospital follow-up while 349 patients had also 30-day follow-up. For the primary safety and efficacy analysis of in-hospital events, VTE and major bleeding rates were 0.26% [95% CI 0.01%-1.44%] (1/389) and 0.77% [95% CI 0.21%-2.24%] (3/389) respectively. For patients with 30-day follow-up VTE and major bleeding rates were 0.57% [95% CI 0.1%-2.07%] (2/349) and 1.43% [95% CI 0.61%-3.3%] (5/349) respectively. CONCLUSIONS: Weight-adjusted tinzaparin was associated with a low risk of bleeding and VTE events, supporting its use for VTE prophylaxis for patients weighing ≥160 kg.

Resumption of anticoagulant therapy after anticoagulant-related gastrointestinal bleeding: A systematic review and meta-analysis.

INTRODUCTION: Oral anticoagulation (OAC) is permanently discontinued in up to 50% of patients following a gastrointestinal (GI) bleed. A previous meta-analysis showed a reduced risk of thromboembolism and death, and a non-statistically significant increased risk of re-bleeding associated with resumption. We conducted an updated meta-analysis to determine the risks of recurrent GI bleeding, thromboembolism, and death in patients who resumed OAC compared to those who did not. MATERIALS AND METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials for new references from January 2014 to September 2017. Randomized controlled trials and observational studies involving adults with OAC-related GI bleeding were included. Risk of bias was assessed using the Cochrane Collaboration's ROBINS-I tool. Pooled relative risk (RR) ratios were calculated using a random-effects model. RESULTS: We identified 12 observational studies involving 3098 patients. There was an increased risk of recurrent GI bleeding (RR 1.91, 95% CI 1.47-2.48, I2 = 0%, 11 studies), and a reduced risk of thromboembolism (RR 0.30, 95% CI 0.13-0.68, I2 = 59.8%, 9 studies) and death (RR 0.51, 95% CI 0.38-0.70, I2 = 71.8%, 8 studies) in patients who resumed OAC compared to those who did not. Eleven studies were judged to be at serious risk of bias due to confounding. CONCLUSIONS: Resuming OAC after OAC-related GI bleeding appears to be associated with an increase in recurrent GI bleeding, but a reduction in thromboembolism and death. Further prospective data are needed to identify patients for whom the net clinical benefit favours OAC resumption and the optimal timing of resumption.

Weight-adjusted tinzaparin for the prevention of venous thromboembolism after bariatric surgery.

Essentials The optimal dose and duration of thromboprophylaxis after bariatric surgery are unclear. We evaluated the safety of weight-adjusted tinzaparin prophylaxis in 1212 patients. In-hospital rates of venous thromboembolism and major bleeding were 0.2% and 1.8% respectively. In a sub-set of patients, trough anti-Xa levels did not show excessive anticoagulant activity. SUMMARY: Background Patients undergoing bariatric surgery are at moderate to high risk of venous thromboembolism (VTE). The optimal dose and duration of anticoagulant prophylaxis is uncertain. Objective To evaluate the safety of extended-duration weight-adjusted tinzaparin after bariatric surgery. Patients/methods We conducted a single-center retrospective cohort study of consecutive patients undergoing bariatric surgery who received weight-adjusted tinzaparin 4500-14 000 IU daily (75 IU kg-1 rounded to the nearest prefilled syringe) for 10 days after surgery (7-9 days post-hospital discharge). Primary safety outcomes were the frequency of VTE and major bleeding within 30 days of surgery in patients receiving at least one dose of tinzaparin. Results A total of 1279 patients undergoing bariatric surgery between July 2009 and December 2012 were reviewed, of whom 1212 received weight-adjusted tinzaparin. Safety outcomes were collected for 819 patients at 30 days, and for 1212 patients in-hospital only. The median age was 45.0 years, median weight was 130.0 kg and 98.8% of patients underwent gastric bypass or sleeve gastrectomy. In patients completing 30 days of follow-up, VTE occurred in 4/819 (0.5%) and major bleeding occurred in 13/819 patients (1.6%). In-hospital rates of VTE and major bleeding during surgical admission were 3/1212 (0.2%) and 22/1212 (1.8%), respectively. Conclusions Extended thromboprophylaxis with weight-adjusted tinzaparin appears to be a safe strategy after bariatric surgery, with low rates of postoperative VTE and major bleeding.

Anticoagulants in cancer.

Cancer patients are at high risk for venous thromboembolism (VTE), which results in substantial morbidity and mortality. In this narrative review, we present evidence for the use of anticoagulants in the treatment and prevention of VTE in cancer patients. The benefit of perioperative anticoagulant prophylaxis following cancer surgery is well established. However, the risk-benefit trade-offs in non-surgical hospitalized cancer patients and among outpatients receiving chemotherapy are more complex. Emerging evidence suggests that the use of low molecular weight heparin (LMWH) may confer a small survival benefit in cancer patients without VTE. However, specific patient populations that may derive the most benefit have yet to be defined. Guidelines endorse LMWH as the preferred treatment for acute VTE, on the basis of high-quality clinical trial data, but the optimal duration of treatment remains unclear, and practical issues may limit its use outside the clinical trial setting. Novel oral anticoagulants may provide additional treatment and prophylaxis options, but their efficacy and safety in this population have not been established. Despite the significant impact of VTE on the lives of cancer patients and the large body of existing literature regarding treatment and prevention, important unanswered clinical questions remain, emphasizing the need for additional high-quality clinical trial data.

Liver-kidney transplantation in primary hyperoxaluria type-1: case report and literature review.

Primary hyperoxaluria type-1 (PH1) is a rare inherited autosomal recessive disorder in which a deficiency of the hepatic enzyme alanine-glyoxylate aminotransferase leads to endogenous oxalate overproduction, renal failure, systemic oxalate deposition and death. As hemodialysis provides insufficient oxalate clearance, patients ultimately require both liver and kidney transplantation for correction of the metabolic abnormality and oxalate excretion. Herein, we describe a young adult male with end-stage renal disease and systemic oxalosis causing progressive disabling multi-organ dysfunction while awaiting transplantation. We review the literature regarding liver-kidney transplantation and suggest that for patients with PH1, a standardized assessment of organ dysfunction and functional impairment may improve identification of patients requiring urgent transplantation thereby reducing the morbidity and mortality that can occur with delayed transplantation.

Graft-versus-host disease following marrow transplantation for aplastic anemia: different impact of two GVHD prevention strategies.

Prevention of GVHD is one of the most desirable goals of BMT in aplastic anemia (AA). We reviewed the medical records of 24 consecutive patients treated with BMT for acquired AA using two different GVHD prevention strategies. Ten patients were given alemtuzumab-based GVHD prophylaxis (50-60 mg in three divided doses on days -8, -7 and -6), and 14 patients were given conventional GVHD prophylaxis with calcineurin inhibitors plus MTX before the introduction of the alemtuzumab-based protocols. The incidence of acute, chronic and 'serious GVHD' was significantly reduced in alemtuzumab-treated patients compared to conventionally treated patients [11 vs 64% (P=0.03), 0 vs 78% (P=0.002) and 0 vs 57% (P=0.007), respectively]. Engraftment time and rates of graft failure appeared similar in the two groups. A significantly higher proportion of alemtuzumab-treated patients developed CMV reactivation compared to control patients (83 vs 12%; P=0.03); none developed CMV disease. The rates of other infectious complications did not appear significantly different. Our data suggest that 50-60 mg of alemtuzumab given according to the current schedule significantly reduces the risk of GVHD without increasing the risk of graft failure or serious infections.

Invasive pneumococcal disease in adult hematopoietic stem cell transplant recipients: a decade of prospective population-based surveillance.

Prospective population-based surveillance to assess the epidemiology of invasive pneumococcal disease (IPD) in hematopoietic stem cell transplant (HSCT) patients is limited and a comparison to the general population is lacking. By using a population-based Invasive Bacterial Diseases Network surveillance program, we studied the incidence, clinical significance, serotypes and antimicrobial resistance of IPD in a large cohort of adult HSCT patients and the general population. Streptococcus pneumoniae isolates and patient data were collected prospectively from 1995 to 2004. We identified 14 cases of IPD (based on sterile site isolates) in our HSCT population over a 10-year period. This translated to an incidence rate of 347 infections per 100 000 persons per year. This compared to an incidence of 11.5 per 100 000 persons per year in the general population (regression ratio=30.2; 95% confidence interval (CI) 17.8-50.8, P<0.00001). If nonsterile site isolates (respiratory tract) were included, the incidence rate in transplant patients was 446 per 100 000 persons per year. Serotypes 23F and 6B were most common; 100 and 69.2% of isolates were a serotype included in the pneumococcal polysaccharide and conjugate vaccines, respectively. The antimicrobial resistance rates were high, especially for trimethoprim/sulfamethoxazole. HSCT recipients are at significantly greater risk for IPD than the general population. Preventative strategies are necessary.

Invasive pneumococcal disease in solid organ transplant recipients--10-year prospective population surveillance.

Prospective population-based surveillance to assess the incidence and impact of invasive pneumococcal disease (IPD) in organ transplant patients is lacking. By using a population-based Invasive Bacterial Diseases Network surveillance program, we studied the incidence, clinical significance, serotypes and antimicrobial resistance pattern of IPD in a large cohort of adult transplant patients and the general population. Streptococcus pneumoniae isolates and patient data were collected prospectively from 1995 to 2004. We identified 21 cases of IPD (based on sterile-site isolates) in our organ transplant population over a 10-year period. This translated to an incidence rate of 146 infections per 100,000 persons per year. This compared to an incidence of 11.5 per 100,000 persons per year in the general population (R(R)=12.8; 95% CI 8.1-19.9, p<0.00001). If nonsterile-site isolates (respiratory tract) were included, the incidence rate in transplant patients was 419 of 100 000 persons per year. Serotypes 23F and 22F were most common, and 85.0% had a serotype included in the 23-valent pneumococcal vaccine. The antimicrobial resistance rates were high, especially for penicillin and trimethoprim-sulfamethoxazole (TMP/SMX), but were not significantly different from the general population. Solid organ transplant recipients are at significantly greater risk for IPD than the general population. Preventative strategies are necessary.

Immunogenicity of pneumococcal vaccine in renal transplant recipients--three year follow-up of a randomized trial.

Routine pneumococcal vaccination is recommended at regular intervals posttransplant. However, there is limited data on durability of vaccine response and the impact of vaccine type on antibody persistence. We determined the durability of response for patients enrolled in a randomized trial of conjugate (PCV7) versus polysaccharide (PPV23) pneumococcal vaccination. Response was defined as a twofold increase from baseline and a titer > or =0.35 microg/mL using a pneumococcal ELISA for seven serotypes (measured at 8 weeks and 3 years). Forty-seven patients were evaluated and had received either PPV23 (n = 24) or PCV7 (n = 23). Response rates and geometric mean titers varied by serotype but declined significantly at 3-years for 6 of 7 serotypes (p < 0.001). No significant difference in durability was found in patients that had received PPV23 versus PCV7. Compared to the 8-week response, 20.6% fewer patients had a response to at least one serotype by 3 years. The largest relative declines were seen for serotype 4 (response dropped from 40.4% at 8 weeks to 17.0% at 3 years) and serotype 9V (44.7% dropping to 21.3%). The only factor predictive of response durability was a strong multiserotype initial response (p < 0.001). In conclusion, vaccine responses decline significantly by 3 years and conjugate vaccine does not improve the durability of response.

Clinical and electrophysiological assessments in ALS patients.

Since the relationships between traditional assessments in ALS patients have not been defined, three clinical and four electrophysiological assessments were performed in a cross-sectional study of 87 ALS patients. The clinical assessments produced Norris ALS scores, muscle strength scores and illness durations (DUR). The electrophysiological assessments produced scores for motor unit interference pattern, denervation potentials, compound muscle action potential, and fasciculations. The individual muscle scores were averaged to produce mean scores, and Spearman rank correlations were performed on the mean scores. The association between Norris ALS and mean muscle strength (MMS) scores is significant (p less than .001, rs = 0.84), and these scores are significantly correlated with mean interference pattern (0.77, 0.82), mean denervation potential (-0.63, -0.70), and mean compound muscle action potential scores (0.55, 0.60), respectively. Correlations between IP and DP scores (-0.71), IP and CMAP scores (0.62), and DP and CMAP (-0.56) scores are also significant. Scatterplots of the data and regression lines suggest linear relationships between each of these assessments. Illness duration and fasciculation scores are not strongly correlated (rs less than 0.55) with any of the other clinical or electrophysiological assessments.