Thrombosis Journal - Latest articles

Use of rosiglitazone before and after vascular injury in hypercholesterolemic rabbits: assessment of neointimal formation.

2008-08-27

Objectives: To analyse the effects of rosiglitazone administered at different times on neointimal formation in hypercholesterolemic rabbits following vascular injury. Methods: Thirty-nine rabbits on a hypercholesterolemic diet were included. The animals underwent balloon catheter injury to the right iliac artery on day 14. They were divided into three groups as follows: control group, 13 rabbits without rosiglitazone; group I, 13 rabbits treated with rosiglitazone (3 mg/Kg body weight/day) for 28 days after the vascular injury; and group II, 13 rabbits treated with rosiglitazone (3mg/Kg body weight/day) during all the experiment (42 days). Histological analysis was done by an experienced pathologist who was unaware of the rosiglitazone treatment. Histomorphometric parameters were performed by calculation of the luminal and intimal layer area, and intima/media layer area ratio (the area of the intimal layer divided by the area of the medial layer). Results: Intimal area was significantly lower in group II vs. CG (p = 0.024) and group I (p = 0.006). Luminal layer area was higher in group II vs. CG (p < 0.0001) and group I (p < 0.0001). Intima/media layer area ratio was equal between CG and group I. Intima/media layer ratio area was significantly lower in group II vs. control group (p < 0.021) and group I (p < 0.003). There was a significant reduction of 65% and 71% in intima/media layer area ratio in group II vs. control group and group I, respectively. Conclusions: Pretreatment with rosiglitazone in hypercholesterolemic rabbits submitted to vascular injury significantly reduces neointimal formation.

Ischemic stroke risk, smoking, and the genetics of inflammation in a biracial population: the stroke prevention in young women study

2008-08-26

Background: Although cigarette smoking is a well-established risk factor for vascular disease, the genetic mechanisms that link cigarette smoking to an increased incidence of stroke are not well understood. Genetic variations within the genes of the inflammatory pathways are thought to partially mediate this risk. Here we evaluate the association of several inflammatory gene single nucleotide polymorphisms (SNPs) with ischemic stroke risk among young women, further stratified by current cigarette smoking status. Methods: A population-based case-control study of stroke among women aged 15-49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-comparable control subjects (43.1% African-American). Several inflammatory candidate gene SNPs chosen through literature review were genotyped in the study population and assessed for association with stroke and interaction with smoking status. Results: Of the 8 SNPs (across 6 genes) analyzed, only IL6 SNP rs2069832 (allele C, African-American frequency = 92%, Caucasian frequency = 55%) was found to be significantly associated with stroke using an additive model, and this was only among African-Americans (age-adjusted: OR =2.2, 95% CI=1.0-5.0, p=0.049; risk factor adjusted: OR =2.5, 95% CI=1.0-6.5, p=0.05). When stratified by smoking status, two SNPs demonstrated statistically significant gene-environment interactions. First, the T allele (frequency = 5%) of IL6 SNP rs2069830 was found to be protective among non-smokers (OR = 0.30, 95% CI=0.11-.082, p=0.02), but not among smokers (OR = 1.63, 95% CI=0.48-5.58, p=0.43); genotype by smoking interaction (p=0.036). Second, the C allele (frequency = 39%) of CD14 SNP rs2569190 was found to increase risk among smokers (OR = 2.05, 95% CI=1.09-3.86, p=0.03), but not among non-smokers (OR = 0.93, 95% CI=0.62-1.39, p=0.72); genotype by smoking interaction (p=0.039). Conclusions: This study demonstrates that inflammatory gene SNPs are associated with early-onset ischemic stroke among African-American women (IL6) and that cigarette smoking may modulate stroke risk through a gene-environment interaction (IL6 and CD14). Our finding replicates a prior study showing an interaction with smoking and the C allele of CD14 SNP rs2569190.

Risk of myocardial infarction and overall mortality in survivors of venous thromboembolism

2008-08-18

Background: Venous thromboembolism (VTE) and thromboembolic arterial diseases are usually considered to be distinct entities, but there is evidence to suggest that these disorders may be linked. The aim of this study was to determine whether a diagnosis of VTE increases the long-term risk of myocardial infarction (MI). Methods: The incidence rate (IR) and relative risk (RR) of MI in a cohort of patients with a diagnosis of VTE (n = 4890) compared with that of a control cohort without prior VTE (n = 43 382) were evaluated in the UK General Practice Research Database (GPRD). Death during follow-up was also determined. Patients were followed for up to 8 years (mean of 3 years). Results: The IR of MI per 1000 person-years was 4.1 (95% CI: 3.1–5.3) for the VTE cohort and 3.5 (95% CI: 3.2–3.8) for the control cohort. The IR of MI was highest in the first year after the VTE episode, but overall differences between the two cohorts were not significant (RR of MI associated with VTE: 1.2; 95% CI: 0.9–1.6). The risk of death was higher in the VTE cohort than the control cohort, even after adjustment for cancer, heart failure and ischaemic heart disease (RR: 2.4; 95% CI: 2.2–2.6), particularly during the first year after VTE (RR: 3.8; 95% CI: 3.4–4.3). Conclusion: A VTE episode does not significantly increase the risk of MI, but does increase the risk of death, particularly in the first year following VTE diagnosis.

Successful management of acute thromboembolic disease complicated with heparin induced thrombocytopenia type II (HIT II): a case series

2008-07-02

Heparin-induced thrombocytopenia type II (HIT II) is a rare immune-mediated complication of heparin. The diagnosis of HIT is considered in patients exposed to heparin, presenting with thrombocytopenia and thrombosis.We present two cases with massive pulmonary embolism and HIT, successfully treated with the administration of fondaparinux, an alternative anticoagulant, combined with the insertion of an inferior vena cava filter for the prevention of new thromboembolic events. The two cases supplement the available data of the use of fondaparinux in patients with HIT and pulmonary embolism, before further large studies establish its efficacy and safety in this group of patients. Moreover, the management of these patients reveals the need for future evaluation of the combined therapy of alternative anticoagulant agents with the placement of vena cava filters.

Venous thromboembolism prevention post neck of femur fractures – does it make a difference?

Radwane Faroug, Shireesha Konnuru, San S Min, Fazleenah Hussain and George Ampat — 2008-06-26

Neck of femur fractures predispose patients to venous thromboembolism (VTE). NICE has issued guideline 46 to reduce this risk through the use of antithrombic agents. We audited our department's VTE practise by reviewing the clinical notes of 123 consecutive patients with no exclusions. We found our compliance to be a low 6%. We also found that patients were likely to be given low molecular heparin (LMWH) only during their hospital stay. Reasons for the low adherence were probably secondary to confusion caused by the multiple thromboprophylaxis protocols used in our department. The correlation between duration of heparin administration and length of hospital stay was due to logistical difficulty in administering VTE prophylaxis out of hospital setting.

Warfarin dose and INR related to genotypes of CYP2C9 and VKORC1 in patients with myocardial infarction

2008-06-17

Background: Warfarin treatment has a narrow therapeutic range, requiring meticulous monitoring and dosage titration. Individual dosage requirement has recently partly been explained by genetic variation of the warfarin metabolizing enzyme CYP2C9 and the Vitamin K-activating enzyme VKORC1. In the WARIS-II study, comparing three different antithrombotic regimens after myocardial infarction, warfarin treatment reduced thrombotic events, but was associated with more frequent bleeding than use of acetylsalisylic acid (ASA) alone.AimsThe primary aim of the present study was to investigate the relation between genotypes of CYP2C9 and VKORC1 and warfarin maintenance dose in myocardial infarction. The secondary aim was to relate the genotypes to international normalized ratio (INR). Methods: Genotyping was performed in 212 myocardial infarction patients from the WARIS-II study by robotic isolation of DNA from EDTA whole blood (MagNa Pure LC) before PCR amplification (LightCycler) and melting point analysis. Results: The 420 C>T substitution of CYP2C9*2, the 1075 A>C substitution of CYP2C9*3 and the 1173 C>T substitution of VKORC1 had minor allele frequencies of, 11.3%, 5.7% and 36.6% respectively. Warfarin weekly dose varied between 17 mg and 74 mg among the patients. INR did not vary between genotypes. Warfarin dosage requirement was significantly associated with CYP2C9 and VKORC1 genotypes, treatment group and age. The VKORC1 genotype contributed 24.5% to the interindividual variation in warfarin dosage, whereas the combined CYP2C9 genotypes were only responsible for 7.2% of the dose variation. Conclusion: CYP2C9 and VKORC1 genotype frequencies in myocardial infarction patients appear similar to other patient groups and have similar impact on warfarin maintenance dose.

Examining warfarin underutilization rates in patients with atrial fibrillation: Detailed chart review essential to capture contraindications to warfarin therapy

2008-06-03

IntroductionAtrial fibrillation affects an estimated 2.5 million Americans and incurs an average annual stroke risk of 4.5% per year. Despite warfarin reducing stroke risk by approximately 66%, prior studies show warfarin usage rates to be about 50%. However, the methods that define warfarin as "inappropriate underutilization" might not be sensitive enough to pick up relative contraindications. We assessed the inappropriate underutilization of warfarin in atrial fibrillation patients at our hospital by abstracting individual patient charts. Methods: Medical records were reviewed to determine stroke risk factors, warfarin use, and documented contraindications to warfarin use in 364 consecutive patients with atrial fibrillation. Results: Amongst 364 atrial fibrillation patients, 54.6% received warfarin anticoagulation. Overall, 29.5 % of patients had documented reasons for not prescribing warfarin. Primary reasons listed by treating physicians included: gastrointestinal bleed 10.7%, secondary/transient atrial fibrillation 8.2%, and fall risk 6.3%. Only 7.1% of the patients had no documented reasons for the lack of warfarin use. Conclusion: Consistent with previous reports, 45.4% of patients in this atrial fibrillation cohort were not prescribed warfarin. However, after reviewing medical charts for documented reasons why warfarin was not used, the inappropriate underutilization rate was only 7.1%. These findings suggest that studies utilizing administrative database and ICD-9 CM coding might overestimate warfarin underutilization.

The value of D-dimer in the detection of early deep-vein thrombosis after total knee arthroplasty in Asian patients: a cohort study

Chung-Jen Chen, Ching-Jen Wang and Chung-Cheng Huang — 2008-05-28

Background and purposeThe relationship of D-dimer and deep-vein thrombosis (DVT) after total knee arthroplasty (TKA) remains controversial. The purpose of this study was to assess the value of D-dimer in the detection of early DVT after TKA. Methods: The measurements of plasma D-dimer level were obtained preoperatively and at day 7 postoperatively in 78 patients undergoing TKA. Ascending venography was performed in 7 to 10 days after surgery. The plasma D-dimer levels were correlated statistically with the venographic DVT. Results: Venographic DVT was identified in 40% of patients. High plasma D-dimer level >2.0 μg/ml was found in 68% of patients with DVT and 45% without DVT (P < 0.05). Therefore, high D-dimer level greater than 2.0 μg/ml showed 68% sensitivity, 55% specificity, 60% accuracy, 50% positive predictive rate and 72% negative predictive rate in the detection of early DVT after TKA. Conclusion: High plasma D-dimer level is a moderately sensitive, but less specific marker in the detection of early of DVT after TKA. Measurement of serum D-dimer alone is not accurate enough to detect DVT after TKA. Venography is recommended in patients with elevated D-dimer and clinically suspected but asymptomatic DVT after TKA.

Effects of rosiglitazone on contralateral iliac artery after vascular injury in hypercholesterolemic rabbits

2008-05-16

Background: The objective was to evaluate the effects of rosiglitazone on iliac arteries of hypercholesterolemic rabbits undergoing balloon catheter injury in the contralateral iliac arteries. Methods: White male rabbits were fed a hypercholesterolemic diet for 6 weeks and divided into two groups as follows: rosiglitazone group, 14 rabbits treated with rosiglitazone (3 mg/Kg body weight/day) during 6 weeks; and control group, 18 rabbits without rosiglitazone treatment. All animals underwent balloon catheter injury of the right iliac artery on the fourteenth day of the experiment. Results: There was no significant difference in intima/media layer area ratio between the control group and the rosiglitazone group. Rosiglitazone did not reduce the probability of lesions types I, II, or III (72.73% vs. 92.31%; p = 0.30) and types IV or V (27.27% vs. 7.69%; p = 0.30). There were no differences in the extent of collagen type I and III deposition or in the percentage of animals with macrophages in the intima layer. The percentage of rabbits with smooth muscle cells in the intima layer was higher in rosiglitazone group (p = 0.011). Conclusion: These findings demonstrate that rosiglitazone given for 6 weeks did not prevent atherogenesis at a vessel distant from the injury site.

Pleural mesothelioma and venous thrombosis: the eosinophilia link

Paul Richard Julian Ames and Win Win Aye — 2008-04-28

Peripheral blood eosinophilia and vascular occlusions are rare occurrences in patients with pleural mesothelioma whereas eosinophilia may associate with thrombosis. We describe a patient with mesothelioma who developed peripheral blood eosinophilia followed by deep vein thrombosis despite being on low molecular weight heparin prophylaxis. We discuss the genesis of peripheral blood eosinophilia and thrombosis in pleural mesothelioma.