Chemoprophylaxis Use and Risk of Venous Thromboembolism and Death in Adult Patients following Orthotopic Liver Transplantation.

BACKGROUND: Coagulation abnormalities in end-stage liver disease may preclude patients from receiving venous thromboembolism (VTE) prophylaxis immediately following orthotopic liver transplantation. METHODS: To identify risk factors for VTE and death following liver transplantation, a retrospective chart review was conducted in adult liver transplant recipients from January 1, 2001, to October 1, 2011. RESULTS: In 716 transplantations in 701 patients, the overall incidence of VTE was 2.1%. The incidence was 3.6% in patients who received chemoprophylaxis compared to 1.4% in those without chemoprophylaxis (P = .06). Most patients (69.5%) did not receive chemoprophylaxis postsurgery during their hospitalization. Multivariate logistic regression modeling revealed no association between the use of chemoprophylaxis (adjusted odds ratio [OR] 1.5 [0.45-4.7], P = .53) and VTE. A significant positive association was observed between the use of chemoprophylaxis (adjusted OR 3.2 [1.3-8.0], P = .01) and death. CONCLUSION: Use of chemoprophylaxis and increasing amounts of blood products following orthotopic liver transplant was associated with increased mortality. A significant positive association was observed between blood product administration and VTE, while chemoprophylaxis use was not significantly associated with VTE. Larger prospective studies are necessary to further examine the significance of this finding.

Clinically significant venous thromboembolic complications in burn patients receiving unfractionated heparin or enoxaparin as prophylaxis.

The aim of the study is to examine the comparative effectiveness of unfractionated heparin 5000 units given subcutaneously two or three times daily and enoxaparin given 30 mg subcutaneously twice daily or 40 mg daily for the prevention of venous thromboembolism in burn patients. This is a retrospective cohort study conducted in adult burn patients admitted between January 1, 1998, and September 30, 2008, who received only one agent for prophylaxis against venous thromboembolism during their admission. The primary outcome was a symptomatic venous thromboembolism, defined as any lower extremity deep venous thrombosis or pulmonary embolism. A total of 1111 patients were included; 600 received heparin and 511 received enoxaparin. Five patients (0.45%) experienced a symptomatic venous thromboembolic event. All five events occurred in the heparin group (P = .07). Heparin patients were older, had a larger TBSA burned, and a longer length of stay. No incidences of heparin-induced thrombocytopenia were identified. In this retrospective study of burned patients, the authors report a low incidence of symptomatic venous thromboembolic events. All events occurred in patients receiving unfractionated heparin as prophylaxis; however, the number of risk factors for venous thromboembolism was also greater in this group. Future prospective studies are needed to determine definitive conclusions regarding appropriate chemical VTE prophylaxis and dosing regimens for burn patients.

Review of a large clinical series: once- versus twice-daily enoxaparin for venous thromboembolism prophylaxis in high-risk trauma patients.

BACKGROUND: Consensus guidelines support the use of low-molecular-weight heparin for venous thromboembolism (VTE) prophylaxis in high-risk trauma patients but do not recommend a specific regimen. The current study compared the effectiveness and safety of enoxaparin 40 mg once-daily versus enoxaparin 30 mg twice-daily for VTE prophylaxis in high-risk trauma patients. METHODS: A retrospective chart review was conducted of all trauma patients older than 18 years of age admitted to Shands at the University of Florida between July 1, 2005 and June 30, 2007, who received either dosing regimen. Excluded were patients with Injury Severity Score <9, surviving <2 days, hospital length of stay <2 days, receipt of >1 agent, and/or dosing regimen for VTE prophylaxis during hospitalization, interruption in therapy, pregnancy, or diagnosis of a VTE within 24 hours of admission. RESULTS: A total of 409 patients were treated with once-daily dosing and 278 patients were treated with twice-daily dosing. The overall rate of VTE was 2.9% (95% confidence interval, 1.52, 5.07) in the once-daily group and 1.1% in the twice-daily group (95% confidence interval, 0.22, 3.12; P = .118). Major bleeding occurred in 11 patients in the once-daily group and 5 patients in the twice-daily group (1.8% vs 2.7%; P = .608). CONCLUSION: Enoxaparin 30 mg twice-daily may be more effective than enoxaparin 40 mg once-daily for prevention of VTE in high-risk trauma patients; however, statistical significance was not achieved. There were no statistically significant differences observed in clinically significant bleeding. Further study is needed to clarify which dosing regimen of enoxaparin is superior with regard to safety and effectiveness.

The use of anti-Xa assay to monitor intravenous unfractionated heparin therapy.

Continuous infusion unfractionated heparin (UH) has traditionally been monitored using the activated partial thromboplastin time (aPTT). The use of this test to monitor heparin therapy is not based on randomized controlled clinical trials, and the test is associated with significant intra- and inter-patient variability that is not related to circulating blood heparin activity. Due to these and other limitations, the use of aPTT alone to monitor UF has been questioned. Many laboratories are now transitioning to monitoring actual heparin activity (by anti-factor Xa analysis). In this review, we discuss the limitations of using the aPTT to monitor UH therapy and additionally the limitations of solely using heparin activity to monitor therapy. We also include a discussion of the challenges with monitoring heparin therapy in the pediatric population.

Current practice of thromboprophylaxis in the burn population: a survey study of 84 US burn centers.

While there is limited prospective data on the incidence of venous thromboembolism (VTE) in the burn population, there are no prospective studies on the efficacy and safety of VTE prophylaxis in these patients. Despite lack of such data, we hypothesized that most burn centers practice some form of prophylaxis. Eighty-four US burn centers were contacted regarding their modality of VTE prophylaxis, if any. Of the 84 US burn centers, 71 were enrolled in this survey. 76.1% centers reported routine VTE prophylaxis. Modalities included sequential compression device (SCD) (33), subcutaneous heparin (31), enoxaparin (13), dalteparin (3), and intravenous heparin infusion (1). Twenty-one reported combined modalities of SCD and subcutaneous heparin (19), SCD and enoxaparin (1), or SCD and dalteparin (1). Survey results underscore the need to definitively establish risk factors for VTE in the burn population and to prospectively define an evidence-based standard of care in prophylaxis for those patients.

Methemoglobinemia secondary to topical benzocaine use in a lung transplant patient.

OBJECTIVE: To report a case of methemoglobinemia secondary to the administration of topical benzocaine spray in an anemic patient who had previously undergone a lung transplant. CASE SUMMARY: A 40-year-old white man with a past medical history significant for lung transplant acutely decompensated following oropharyngeal administration of topical benzocaine spray. Subsequent blood analysis revealed a methemoglobin concentration of 51.2%. Following the administration of a single dose of methylene blue 2 mg/kg intravenously, the patient's respiratory status dramatically improved and stabilized. DISCUSSION: Methemoglobinemia is a rare but potentially fatal condition that may be either acquired or congenital; however, the disorder is most commonly acquired secondary to exposure to oxidizing chemicals, which are often routinely prescribed medications, including benzocaine. Benzocaine can react with hemoglobin to form methemoglobin at a rate that exceeds reduction capabilities, which may result in oxygenation difficulty and respiratory distress. In severe or symptomatic methemoglobinemia, the treatment of choice is methylene blue. CONCLUSIONS: Application of the Naranjo probability scale established a highly probable relationship between topical benzocaine spray and methemoglobinemia and associated respiratory compromise. The risks of palliative use of topical benzocaine in patients with preexisting disorders that compromise oxygen delivery may outweigh any benefit. In our patient, anemia and lung disease increased his risk for clinically significant adverse respiratory events secondary to deficiencies or interferences in oxygen delivery. Topical benzocaine should be administered with caution and careful monitoring in such patient populations.

Rash associated with piperacillin/tazobactam administration in infectious mononucleosis.

OBJECTIVE: To report a case of piperacillin/tazobactam-induced rash in a patient with infectious mononucleosis. CASE SUMMARY: A 25-year-old white man developed a rash while receiving piperacillin/tazobactam 3.375 g intravenously every 6 hours and gentamicin for osteomyelitis complicating a left femur fracture secondary to a motorcycle accident. Due to progression of the rash following additional doses of piperacillin/tazobactam during hospitalization, the patient's antimicrobial regimen was changed to vancomycin and meropenem. Subsequently, a mononucleosis spot test was positive, and both Epstein-Barr virus (EBV) immunoglobulin (Ig) G and IgM antibodies were positive. The rash rapidly resolved with the discontinuation of piperacillin/tazobactam. DISCUSSION: Although the development of rash following the administration of several different antimicrobials, especially ampicillin, has been previously reported, this is the first report of piperacillin/tazobactam-induced rash in infectious mononucleosis. The rash is generally self-limiting and usually resolves within days of discontinuing the causative antimicrobial agent. An altered drug metabolism or an immune-mediated process has been suggested as the potential mechanism for rash development. CONCLUSIONS: Prior reports of antimicrobial-induced rash in infectious mononucleosis and a positive laboratory diagnosis of EBV in our patient with no history of penicillin allergy support the identification of piperacillin/tazobactam as the inducer of the rash. According to the Naranjo probability scale, the association of piperacillin/tazobactam with the rash was classified as probable.