Impact of thromboprophylaxis guidelines on clinical outcomes following total hip and total knee replacement

Background

The American College of Chest Physicians (ACCP) guidelines recommends thromboprophylaxis for total hip replacement (THR) and total knee replacement (TKR) patients. We examined alignment with ACCP thromboprophylaxis guidelines among THR/TKR patients, and compared symptomatic venous thromboembolism (VTE), bleeding event rates and risk factors for VTE between patients receiving ACCP-recommended thromboprophylaxis (‘ACCP’) and those who did not (‘non-ACCP’).

Methods

This retrospective observational study used a large US health plan claims database that was linked to an inpatient database containing detailed inpatient medication use and a database containing date-of-death information. Patients who had THR/TKR surgery between April 01, 2004 and December 31, 2006 were included. Comparisons of VTE and bleeding events between ACCP and non-ACCP patients were analyzed using chi-squared tests and multivariate logistic regression.

Results

Of 3,497 linked patients, 1,395 (40%) received ACCP recommended thromboprophylaxis. Of the patients who received non-ACCP recommended prophylaxis the majority (81%) received shorter than the recommended minimum 10 day prophylaxis and 118 (5.6%) of patients received no prophylaxis. Overall, non-ACCP patients were almost twice as likely to experience an incident DVT (3.76% versus 2.01%, p = 0.003) and more than eight times as likely to experience an incident PE (1.19% versus 0.14%, p = 0.001) relative to ACCP patients; there were no statistically significant difference in bleeding rates. Multivariate logistic regression indicated that the odds of a VTE event were significantly lower for ACCP patients (DVT: OR = 0.54; p = 0.006; PE: OR = 0.12; p = 0.004).

Conclusions

This study offers a unique perspective on ‘real-world’ thromboprophylaxis patterns and associated outcomes in THR and TKR patients in the US. It suggests that only 40% of THR/TKR patients receive ACCP-recommended thromboprophylaxis and that not receiving ACCP thromboprophylaxis is an independent risk factor for both DVT and PE.     

Who are at risk for thromboembolism after arthroplasty? A systematic review and meta-analysis

Background

Thromboembolism, including deep venous thrombosis and pulmonary embolism, is a grave threat to patients undergoing total joint replacement. Using a systematic review and meta-analysis we asked whether gene mutations or polymorphisms could be risk factors for thrombosis after arthroplasty.

Methods

We performed a comprehensive search of Medline, PubMed, Embase, Cochrane databases, China National Knowledge Infrastructure (CNKI), and Google Scholar, and identified 19 studies detailing genetic investigations of patients with thromboembolism following joint replacement.

Results

Our meta-analyses included 5149 patients who underwent arthroplasty surgery. Significant associations with venous thromboembolism were identified for factor G1691A (odds ratio (OR) 1.41, 95% confidence interval (CI) 1.03 - 1.94, p = 0.03), prothrombin G20210A (OR 2.16, 95% CI, 1.27- 3.69, p = 0.005), and MTHFR/C677T/TT (OR 2.36, 95% CI 1.03 - 5.42, p = 0.04) in Caucasian populations. No significant gene mutation was identified in Asian populations.

Conclusion

This study suggests a way to identify patients scheduled for arthroplasty who are at higher risk of thrombosis, enabling individualized treatment.     

Thromboprophylaxis patterns,risk factors,and outcomes of care in the medically ill patient population

Introduction

Medically ill, hospitalized patients are at increased risk for venous thromboembolism (VTE) after discharge. This study aimed to examine thromboprophylaxis patterns, risk factors, and post-discharge outcomes.

Methods

This was a retrospective claims analysis involving administrative claims data and in-patient data abstracted from a sample of hospital charts. Patients aged ≥ 40 years hospitalized for ≥ 2 days for nonsurgical reasons between 2005 and 2009 were included. Hospital chart data were abstracted for a random sample of patients without evidence of anticoagulant use at 30 days post-discharge. The combined data determined whether in-patient thromboprophylaxis (anticoagulant or mechanical prophylaxis) reduces risk of VTE at 90 days post-discharge. Hazard ratios (HR) and odds ratios (OR) were calculated using Cox proportional hazard models and logistic regression.

Results

Of 141,628 patients in the claims analysis, 3.9% received anticoagulants (3.6% warfarin). VTE, rehospitalization, and mortality rates were 1.9%, 17.2%, and 6.2%, respectively. The strongest predictors of post-discharge VTE were history of VTE (HR = 4.0, 95% confidence interval [CI]: 3.3-4.8), and rehospitalization (HR = 3.9, 95% CI: 3.6-4.3). Of 504 medical charts, 209 (41.5%) reported in-patient thromboprophylaxis. There was no statistically significant difference in post-discharge VTE rates between patients who did and did not receive in-patient thromboprophylaxis. All-cause mortality was greater among patients without use of VTE prophylaxis.

Conclusion

Utilization rates of in-hospital and post-discharge VTE prophylaxis were low. In-hospital VTE prophylaxis did not reduce the risk of post-discharge VTE in the absence of post-discharge anticoagulation. Combined in-patient and post-discharge thromboprophylaxis lowered the odds of short-term, all-cause post-discharge mortality.     

Safety and Efficacy of Edoxaban,an Oral Factor Xa Inhibitor,Versus Enoxaparin for Thromboprophylaxis After Total Knee Arthroplasty: The STARS E-3 Trial

Introduction

This phase 3 trial compared the safety and efficacy of edoxaban, an oral direct factor Xa inhibitor, with enoxaparin sodium (enoxaparin) for thromboprophylaxis after total knee arthroplasty (TKA) in patients in Japan and Taiwan.

Materials and methods

In this randomized, double-blind, double-dummy study, patients received oral edoxaban 30 mg once daily beginning 6 to 24 hours postsurgery or enoxaparin 2000 IU (equivalent to 20 mg) subcutaneously twice daily beginning 24 to 36 hours postsurgery for 11 to 14 days. The primary efficacy endpoint was the composite of symptomatic pulmonary embolism and symptomatic and asymptomatic deep vein thrombosis. Safety endpoints included the incidence of major bleeding, clinically relevant non-major (CRNM) bleeding, major bleeding or CRNM bleeding, all bleeding events, adverse events, and adverse drug reactions.

Results

Of 716 patients enrolled, 360 and 356 were randomized to receive edoxaban or enoxaparin, respectively. The primary efficacy outcome occurred in 22/299 (7.4%) and 41/295 (13.9%) patients in the edoxaban and enoxaparin groups, respectively (relative risk reduction = 46.8%), indicating non-inferiority (P < 0.001) and superiority (P = 0.010) of edoxaban versus enoxaparin. In the edoxaban and enoxaparin groups, major bleeding occurred in 4/354 (1.1%) versus 1/349 (0.3%) patients (P = 0.373); major or CRNM bleeding occurred in 22/354 (6.2%) versus 13/349 (3.7%) patients (P = 0.129), respectively.

Conclusions

Edoxaban 30 mg once daily was more effective for thromboprophylaxis than subcutaneous enoxaparin 2000 IU twice daily following TKA and demonstrated a similar incidence of bleeding events.     

Has the incidence of deep vein thrombosis in patients undergoing total hip/knee arthroplasty changed over time? A systematic review of randomized controlled trials

Background

There is a perception in the orthopaedic and thromboembolism community that the incidence of deep vein thrombosis (DVT) has decreased in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).

Objectives

To assess the incidence of DVT with warfarin thromboprophylaxis over time in patients undergoing elective TKA or THA.

Methods

The MEDLINE, EMBASE, and Cochrane Library databases were searched to October 2006, supplemented by a manual search of reference lists. Two reviewers independently extracted data on study characteristics, quality and the frequency of total, symptomatic and proximal DVT.

Results

Fourteen studies (4,423 patients) were included. Total and proximal DVT after TKA declined over time (r = − 0.75, p = 0.031; r = − 0.86, p = 0.007 respectively). Total and proximal DVT after THA did not change. The risk of developing DVT after TKA was significantly higher than after THA (OR 1.85, 95% CI 1.6 - 2.14; p < 0.0001). The risk of developing symptomatic DVT after THA was significantly higher than after TKA (OR 2.18, 95% CI 1.11 - 4.27; p = 0.012).

Conclusions

The incidence of DVT in patients undergoing elective TKA appears to have declined in patients receiving warfarin thromboprophylaxis.     

Incidence and risk factors of symptomatic venous thromboembolism related to implanted ports in cancer patients

Introduction

The true incidence of symptomatic implanted port related venous thromboembolism (VTE) in cancer patients is unclear and there is very limited data on its associated risk factors.

Materials and methods

We performed a retrospective cohort study of consecutive cancer outpatients who received an ultrasound guided implanted port insertion for the administration of chemotherapy. The primary outcome measure was symptomatic VTE. Univariable and multivariable logistic regression analyses were used to identify risk factors for symptomatic VTE.

Results

A total of 400 cancer patients with a newly inserted implanted port for deliverance of chemotherapy were included in the study. Median age was 58 years (range of 21 to 85 years) and 120 (30%) were males. Patients were followed for a median of 12 months and none received thrombophrophylaxis. Of the 400 patients included in the analysis, 34 patients (8.5%; 95% CI: 6.0 to 11.7%) had symptomatic VTE (16 DVTs, 16 PEs, and 2 with both). In the univariate analyses, metastatic disease, male gender and right sided implanted port insertion were significantly associated with the risk of VTE. In the multiple-variable analysis, male gender (OR 2.17, p = 0.04) and presence of metastases (OR 8.22, p < 0.01) were the two significant independent predictors of implanted port related VTE.

Conclusion

Symptomatic VTE is a frequent complication in cancer patients with implanted port receiving chemotherapy. Gender and presence of metastatic disease are independent risk factors for symptomatic VTE. Future trials assessing the role of thromboprophylaxis among these higher risk patients are needed.     

Efficacy of postoperative anticoagulation therapy with enoxaparin for portal vein thrombosis after hepatic resection in patients with liver cancer

Backgrounds

Enoxaparin, low-molecular-weight heparin, has become a routine thromboprophylaxis in general surgery.

Study design

A retrospective cohort study was performed in 281 patients who underwent hepatic resections for liver cancers from 2011 to 2013. These patients were divided into two groups; an enoxaparin (-) group (n = 228) and an enoxaparin (+) group (n = 53). Short-term surgical results including venous thromboembolism (VTE) and portal vein thrombosis (PVT) were compared.

Results

In the enoxaparin (+) group, the patients’ age (65 vs. 69 years; p = 0.01) and BMI (22.9 vs. 24.4; p < 0.01) were significantly higher. According to the symptomatic VTE, symptomatic pulmonary embolism occurred in one patient (0.4%) in the enoxaparin (-) group, but the complication rate was not significantly different (p = 0.63). The complication rate of PVT was significantly lower in the enoxaparin (+) group (10 vs. 2%; p = 0.04). The independent risk factors for PVT were an operation time ≥ 300 minutes (Odds ratio 6.66) and non-treatment with enoxaparin (Odds ratio 2.49).

Conclusions

Postoperative anticoagulant therapy with enoxaparin could prevent PVT in patients who underwent hepatic resection for liver cancers.     

Risk-assessment and pharmacological prophylaxis of venous thromboembolism in hospitalized patients with chronic liver disease

Introduction

There is a lack of evidence regarding the need for thromboprophylaxis in hospitalized patients with liver disease. The purpose of this study was to evaluate the Padua Predictor Score (PPS) as a risk-stratification tool for the development of venous thromboembolism (VTE) in patients with chronic liver disease.

Methods

This was a retrospective cohort study conducted in an academic medical center in the United States. Consecutive adult patients admitted with chronic liver disease were included. Patients were categorized into two groups based on whether they developed a VTE or not. The risk for VTE in each patient was evaluated using the Padua Predictor Score (PPS). Patients were risk stratified using the PPS score as high-risk (score ≥ 4) and low-risk (score < 4). The risk of VTE based on PPS categorization was evaluated using logistic regression.

Results

A total of 163 patients with liver disease were included in the study cohort. Of these, 18 (11%) developed VTE. Mean PPS was significantly greater in the VTE group than the non-VTE group (5.8 ± 2.0 versus 3.0 ± 2.1, respectively; p < 0.001). In high-risk patients 22% (n = 16/72) developed VTE and in low-risk patients 2% (2/91) developed VTE (p < 0.001). High-risk patients were more likely to have VTE (OR 12.7, 95% CI 2.8 to 57.4, p = 0.001).

Conclusion

The PPS is an effective risk assessment tool for VTE in patients hospitalized with chronic liver disease.     

Clinical predictors of recurrent venous thromboembolism: a single institute experience in Korea

Introduction

Racial disparities in incidence rate as well as risk factors for venous thromboembolism (VTE) exist between Asian and Western populations. Moreover, predictors for recurrent VTE were not identified in Asians. Thus, this study was undertaken to investigate risk factors for recurrent VTE events in Korean people.

Materials and Methods

Three hundred-three patients newly diagnosed as VTE were enrolled from Seoul National University Hospital. Recurrence rate based on risk factors for VTE were investigated. Cumulative incidence of recurrent VTE was calculated by the Kaplan and Meier method. Independent predictors for VTE were determined using Cox proportional hazards model.

Results

After a median follow-up of 44 months, 24 (8%) of 303 patients relapsed for a total observation time of 1,217 patient-year. Cumulative incidences of recurrent VTE were 3% at 1 year, 10% at 5 years, and 18% at 8 years. Independent predictors for recurrent VTE were presence of residual thrombosis (hazard ratio [HR] = 3.1, 95% confidence interval [CI] 1.0-9.3; p = 0.044), antiphospholipid syndrome (APS) (HR = 4.3, 95% CI 1.0-19.0; p = 0.052), and age 50 years or younger (HR = 2.5, 95% CI 1.0-6.6; p = 0.053) by multivariate analysis. Residual thrombosis and APS remained predictive of recurrence by the anticoagulation-period stratified analysis.

Conclusions

In contrast to Western populations, Korean patients with VTE had the lower recurrent rate. Extended anticoagulation is necessary for Korean patients with residual thrombosis or APS.     

Risk factors for inpatient venous thromboembolism despite thromboprophylaxis

Introduction

Venous thromboembolism (VTE) is the most common preventable cause of morbidity and mortality in the hospital. Adequate thromboprophylaxis has reduced the rate of hospital-acquired VTE substantially; however, some inpatients still develop VTE even when they are prescribed thromboprophylaxis. Predictors associated with thromboprophylaxis failure are unclear. In this study, we aimed to identify risk factors for inpatient VTE despite thromboprophylaxis.

Materials and methods

We conducted a case–control study to identify independent predictors for inpatient VTE. Among patients discharged from the BJC HealthCare system between January 2010 and May 2011, we matched 94 cases who developed in-hospital VTE while taking thromboprophylaxis to 272 controls who did not develop VTE. Matching was done by hospital, patient age, month and year of discharge. We used multivariate conditional logistic regression to develop a VTE prediction model.

Results

We identified five independent risk factors for in-hospital VTE despite thromboprophylaxis: hospitalization for cranial surgery, intensive care unit admission, admission leukocyte count > 13,000/mm³, presence of an indwelling central venous catheter, and admission from a long-term care facility.

Conclusions

We identified five risk factors associated with the development of VTE despite thromboprophylaxis in the hospital setting. By recognizing these high-risk patients, clinicians can prescribe aggressive VTE prophylaxis judiciously and remain vigilant for signs or symptoms of VTE.     

Inhibitory effects of bortezomib on platelet aggregation in patients with multiple myeloma

Introduction

Multiple myeloma (MM) therapy affects prothrombotic and anticoagulant processes. Patients receiving thalidomide, especially in combination with steroids, are at increased risk of venous thromboembolism (VTE), while the incidence of VTE on bortezomib is low. In vitro studies indicate that bortezomib causes a reduction in ADP-induced platelet aggregation.

Objectives

To analyse the influence of bortezomib on platelet aggregation induced by various agonists in patients with MM.

Patients and Methods

A total of 30 patients (median age 57.5 years) with relapsed/refractory MM receiving bortezomib-based regimens were analysed. Optical platelet aggregometry was performed with the agonists collagen, ADP and ristocetin and measured over two 21-day cycles. The results from two groups: those treated with bortezomib and thalidomide (BT group, n = 11) and those without thalidomide (B group, n = 19) were analysed.

Results

During the second cycle, significantly decreased platelet aggregation was observed in the B group: 5 μM ADP (p = 0.0285, day 1 versus 8); 3.5 μM ADP (p = 0.0005, day 1 versus 8 and day 1 versus 11), collagen (p = 0.0014, day 4 versus 8, day 4 versus 11), 1.25 mg/ml ristocetin (p = 0.0017, day 1 versus 8 and day 1 versus 11). Agonist-induced platelet aggregation tended to be reduced over time during the 1st cycle in group B. In the thalidomide group, significant platelet aggregation inhibition by collagen only was found. Transient reduction in platelet count was observed in all patients, but more prominently in group B.

Conclusion

The inhibitory effects of prolonged exposure of bortezomib on platelet aggregation were demonstrated in relapsed/refractory MM patients, but antithrombotic activity of bortezomib should be clarified in further prospective studies.     

Use of antifibrinolytic therapy to reduce transfusion in patients undergoing orthopedic surgery: A systematic review of randomized trials

Background

Minimizing bleeding and transfusion is desirable given its cost, complexity and potential for adverse events. Concerns have been heightened by recent data demonstrating that bleeding events may predict worse outcomes and by warnings about the safety of erythropoietic stimulating agents. Prior small studies suggest that antifibrinolytic agents may reduce bleeding and transfusion need in patients undergoing total hip replacement (THR) or total knee arthroplasty (TKA). However, no single study has been large enough to definitively determine if these agents are safe and effective. To address this issue we performed a systematic review of randomized trials describing the use of tranexamic acid, epsilon aminocaproic acid, or aprotinin administration in the perioperative setting.

Methods

MEDLINE, EMBASE, CINAHL and the Cochrane databases were searched for relevant trials. Two independent reviewers abstracted total blood loss, transfusion requirements, and venous thromboembolism (VTE) rates. Data were combined using the Mantel-Haenszel method and dichotomous data expressed as relative risk (RR) with 95% confidence intervals (CI).

Results

Patients receiving antifibrinolytic agents had reduced transfusion need (RR 0.52; 95% CI, 0.42 to 0.64; P < 0.00001), reduced blood loss and no increase in the risk of VTE (RR 0.95% CI, 0.80 to 1.10, I² = 0%, P = 0.531).

Conclusions

We conclude that antifibrinolytic agents may reduce bleeding and transfusion in patients undergoing THR or TKA who receive appropriate antithrombotic prophylaxis. There is a need for a large, adequately powered prospective study to carefully examine the safety and efficacy of these agents.     

Effectiveness of vitamin K in anticoagulation reversal for hip fracture surgery – A prospective observational study

Introduction

Vitamin K antagonists are often used for anticoagulant treatment in hip fracture patients. The optimal handling with such anticoagulants is unclear.We aimed to determine when anticoagulation reversal occurred after vitamin K administration and how often prothrombin complex concentrates (PCCs) were administered. We compared patients’ treatments and outcomes with those of a control group not receiving treatment for anticoagulation.

Patients and Methods

A total of 402 geriatric hip fracture patients were included in this observational study. We collected data on treatment for anticoagulation, time to surgery, and reasons for delay of surgery. In patients taking vitamin K antagonists, we measured the INR (international normalized ratio) on admission and prior to surgery, along with the frequency of PCC administration. Finally, we compared in-hospital mortality and complications between patient groups.

Results

A total of 62 (15%) patients received phenprocoumon prior to their fractures. Surgery was delayed in these patients compared to controls (27 h; 95%CI 23–31 vs. 16 h; 95%CI 19–19; p = 0.001), but surgery delay > 48 h (n = 5; 8%) was not due to a failure of INR reversal. The main reason for these delays was a lack of capacity for surgery. The average INR on admission was 2.1 (± 0.7; range 1.0-3.5) in patients taking phenprocoumon, which decreased to 1.3 (± 0.3; range 1.0-1.6) until surgery. PCCs were administered to 19% of patients. We found no differences in the in-hospital mortality (6.2% vs. 8.1%, p = 0.575) or complication rates (12.9% vs. 9.4%, p = 0.364).

Conclusion

The use of vitamin K seemed to be sufficient for anticoagulation reversal in geriatric hip fracture patients, and it generally led to timely surgery; despite this success, PCCs were sometimes administered for logistical reasons.     

New cerebral microbleeds in ischemic stroke patients on warfarin treatment: Two-year follow-up

Objective

Cerebral microbleeds (CMBs) are known to be indicative of bleeding-prone microangiopathy. Little is known about the significance of CMBs in anticoagulated patients. We determined the frequency of new CMBs in ischemic stroke patients who had been receiving warfarin treatment for 2 years.

Methods

A total of 204 ischemic stroke patients on warfarin therapy for 2 years underwent a repeat MRI. We compared demographic features, vascular risk factors, and radiological findings of patients with and without new CMBs.

Results

New CMBs on gradient-echo MRI were found in 29 of 204 patients (10%). Of 35 patients who had CMBs in the original study, 9 developed new CMBs after 2 years (26%), compared with 20 of the 169 patients (12%) who did not have CMBs at baseline (p = 0.03). Patients with new CMBs were older than patients without CMBs (p = 0.04), and the frequency of leukoaraiosis was significantly higher (p = 0.02). The mean duration of warfarin treatment was not significantly different between the patients with and without new CMBs (p = 0.28).

Conclusion

This longitudinal study suggested that the presence of CMBs at baseline increased the frequency of new CMBs in patients on warfarin therapy.     

Sticker reminders improve thromboprophylaxis appropriateness in hospitalized patients

Background

Venous thromboembolism (VTE) is a major health problem. Even though effective thromboprophylaxis measures exist to prevent VTE, close adherence to guidelines is missing. We assessed the effects of pasting VTE prophylaxis sticker reminders, on the appropriateness of thromboprophylaxis and prophylaxis underutilization.

Methods

Thromboprophylaxis reception was sought prospectively in two time points before and two time points after pasting sticker reminders in hospitalized patients of Masih Daneshvari Medical Center, Tehran, Iran. Thromboprophylaxis reception appropriateness was evaluated by the eighth American College of Chest Physicians (ACCP) guidelines on antithrombotic and thrombolytic therapy. Co-morbidities and conditions considered to affect the risk of venous thromboembolism were also recorded.

Results

Prophylaxis reception and appropriateness were studied in 298 patients before and 306 patients after the intervention. Based on the ACCP guidelines, overall thromboprophylaxis appropriateness was improved after the intervention (70.4% before, and 78.1% after the intervention, P = 0.03). Prophylaxis underutilization, and prophylaxis initiation delay in those who needed thromboprophylaxis, were also reduced (P = 0.03, and P = 0.011 respectively). The intervention did not result in an increased rate of overprophylaxis (P = 0.45).

Conclusion

Sticker reminders could be safely and effectively incorporated into strategies to improve VTE prophylaxis and prophylaxis appropriateness, particularly in healthcare settings where electronic alert systems are not available.     

Statins are Associated with Low Risk of Venous Thromboembolism in Patients with Cancer: A Prospective and Observational Cohort Study

Introduction

Patients with cancer are at risk of venous thromboembolism (VTE). Statin-use has been shown to be associated with low risk of VTE in patients without cancer, but data in cancer patients is scarce. The objective of this study was to evaluate the association of statins with risk of VTE in cancer patients in a prospective observational cohort study.

Materials and Methods

Patients with newly diagnosed cancer or progression of disease after remission were included and prospectively followed for a maximum of 2 years. Study endpoint was occurrence of symptomatic VTE.

Results

Patients (n = 1434) were followed over a median observation period of 729 days. VTE occurred in 107 (7.5%) patients. At study inclusion, 170 (11.9%) patients took statins. Simvastatin (n = 96) and atorvastatin (n = 48) were the most frequently prescribed statins. VTE occurred in 6 (3.5%) patients with statins. Patients with statins had a lower risk of VTE than patients without (subhazard ratio 0.43, 95% confidence interval 0.19 to 0.98; p = 0.04). In competing risk analysis, the cumulative probability of VTE in patients with statins was 2.94% after 12 months and 3.54% after 24 months, compared to 7.13% and 8.13% in the group without statins (Gray’s test: p = 0.04).

Conclusion

This study provides observational evidence for an association between statin use and low risk of VTE in patients with cancer. The role of statins for prevention of cancer-associated VTE needs to be confirmed in randomized, controlled trials.     

Atorvastatin favorably modulates proinflammatory cytokine profile in patients following deep vein thrombosis

Background

Venous thromboembolism (VTE) has been shown to be associated with inflammation. Statins that might reduce VTE risk have been found to exert anti-inflammatory properties in patients at cardiovascular risk. We sought to investigate whether anti-inflammatory effects of atorvastatin can be observed in VTE patients.

Materials and Methods

Atorvastatin 40 mg/d was given for 3 days to 26 consecutive VTE patients following discontinuation of anticoagulant therapy and 25 controls. We evaluated interleukin (IL)-1b, IL-6, IL-8, IL-10, soluble P-selectin and von Willebrand factor (vWF) antigen in peripheral venous blood.

Results

The VTE patients displayed higher C-reactive protein (p = 0.013), IL-1b (p = 0.03), IL-8 (p = 0.03) and vWF (p < 0.0001) compared with the controls. In VTE patients atorvastatin decreased IL-6 (p = 0.0003), IL-8 (p = 0.003) and P-selectin (p < 0.0001), but increased IL-10 (p = 0.001), with no association with C-reactive protein or cholesterol-lowering effects. Atorvastatin reduced IL-1b (p = 0.01), IL-6 (p = 0.03) and P-selectin (p = 0.002) in controls. Residual venous thrombosis was associated with elevated IL-6 and P-selectin, whereas patients with proximal deep vein thrombosis showed elevated P-selecitn prior to and following statin administration (all p < 0.05).

Conclusion

A 3-day administration of atorvastatin reduces inflammation without decrease in C-reactive protein in VTE patients.     

Influence of coronary artery disease-associated genetic variants on risk of venous thromboembolism

Introduction

We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case–control study (n = 2753) from Sweden.

Materials and Methods

39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression.

Results

Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181).

Conclusions

It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.     

The loudness dependence of the auditory evoked potential (LDAEP) in schizophrenia,bipolar disorder,major depressive disorder,anxiety disorder,and healthy controls

Background

Serotonergic dysfunction in schizophrenia, bipolar disorder, major depressive disorder, anxiety disorder, and healthy controls was evaluated by measuring the activity of the loudness dependence of the auditory evoked potential (LDAEP).

Methods

The 357 subjects who were evaluated comprised 55 normal controls, 123 patients with major depressive disorder, 37 with bipolar disorder, 46 with schizophrenia, 37 with panic disorder (PD), 31 with generalized anxiety disorder (GAD), and 28 with post-traumatic stress disorder (PTSD).

Results

LDAEP was significantly stronger in healthy controls than in patients with either bipolar disorder (p = 0.025) or schizophrenia (p = 0.008), and significantly stronger in patients with major depressive disorder than in those with bipolar disorder (p = 0.01) or schizophrenia (p = 0.03). LDAEP did not differ significantly between patients with major depressive disorder and healthy control subjects (p = 0.667), or between healthy control subjects and patients with anxiety disorder, including PD (p = 0.469), GAD (p = 0.664), and PTSD (p = 0.167).

Conclusion

The findings of the present study reveal that patients with major psychiatric disorders exhibit different strengths of LDAEP according to their serotonin-related pathology. Studies controlled for psychotropic medication, menstruation cycle, and smoking are needed.