Independent Risk Factor For Thromboembolism Research Articles

Preterm preeclampsia as an independent risk factor for thromboembolism in a large national cohort

BackgroundPreterm preeclampsia, a product of vascular dysfunction, is associated with prolonged hospital admission and proteinuria, significant risk factors for thromboembolism in pregnancy. The risk of thromboembolism in preterm preeclampsia warrants further investigation. ObjectivesTo determine the relationship between preterm preeclampsia and thromboembolic risk. We hypothesize that preterm preeclampsia is an independent risk factor for thromboembolism in pregnancy. Study DesignThis is a retrospective cohort study using the National Inpatient Sample database via HCUP-AHRQ from 2017-2019. All subjects with an ICD-10 code for pregnancy or peripartum encounter were included. Subjects were excluded if gestational age at delivery was less than 20 weeks or if they had a history of thromboembolism, inherited thrombophilia, or antiphospholipid syndrome. Patients with preterm (delivered less than 37 weeks) preeclampsia and term (delivered 37 weeks or greater) preeclampsia were compared to those without preeclampsia. The primary outcome was a composite of any thromboembolic event, including pulmonary embolism, deep vein thrombosis, cerebral thrombosis/transient ischemic attack (TIA), or other thromboses. The secondary outcomes were rates of each individual type of thromboembolic event. The groups were compared via analysis of variance, chi-squared, and logistic regression analyses. The logistic regression included those variables that differed between groups with p<0.05. ResultsOf individuals in the database more than 2.2 million met inclusion criteria. A total of 56,446 (2.7%) had preterm preeclampsia and 86,152 (6.7%) had term preeclampsia. Those with preterm preeclampsia were more likely to be older, identify as non-Hispanic black, be obese, have chronic hypertension among other chronic diseases, and be in the lowest quartile of income (p<0.001). Among patients with preterm preeclampsia, 0.32% experienced thromboembolism while those with term preeclampsia and without preeclampsia experienced thromboembolism 0.10% and 0.09%, respectively. After controlling for confounders that differed between groups with p<0.05, preterm preeclampsia remained independently associated with any thromboembolic event (aOR 2.21 95%CI 1.84-2.65) as well as each individual type of thromboembolism. Term preeclampsia was not associated with an increased risk of thromboembolism (aOR 1.18, 95%CI 0.94-1.48). ConclusionPreterm preeclampsia is independently associated with an increased risk of thromboembolic events.

Hormone replacement therapy does not increase thrombosis risk following THA: a national database study

PurposeHormone replacement therapy (HRT) causes a significant increase in the risk of venous thrombosis. The risk of medical and surgery-related complications among women taking HRT following total hip arthroplasty (THA) is poorly understood, and there are currently no guidelines in place regarding venous thromboembolism prophylaxis in this patient population. The purpose of this study was to evaluate the frequency of early medical and surgery-related complications following THA among women taking HRT.MethodsWomen aged > 40 years of age who underwent primary THA were identified from a retrospective database review. A control group of non-HRT users was matched using propensity scoring to HRT users. Rates of 90-day medical complications and 1-year surgery-related complications were compared between cohorts using odds ratios. Postoperative anticoagulation regimens were also compared.ResultsThere were 3,936 patients in the HRT cohort who were matched to 39,360 patients not taking HRT. There were no significant differences in rates of DVT (OR 0.94, p = 0.6601) or PE (OR 0.80, p = 0.4102) between cohorts. Patients on HRT were more likely to sustain a dislocation (OR 1.35, p = 0.0269) or undergo revision surgery (OR 1.23, p = 0.0105). HRT patients were more likely to be prescribed warfarin (OR 1.21, p = 0.0001) or enoxaparin (OR 1.18, p = 0.0022) and less likely to be prescribed rivaroxaban (OR 0.62, p < 0.0001) compared to controls.ConclusionsHRT was not found to be an independent risk factor for thromboembolism following THA. Further research is warranted to better delineate the ideal perioperative medical management of HRT users undergoing THA.

Left Atrial Diameter and the Risk of Thromboembolism in Patients with Left Ventricular Noncompaction.

Aims: Patients with left ventricular noncompaction (LVNC) are at risk of thromboembolism. The relationship between left atrial diameter (LAD), a robust predictor for thrombosis, and LVNC is unclear. The purpose of this study was to explore the effect of LAD on the thrombotic risk in LVNC. Methods: In this retrospective cohort study, 320 patients with imaging characteristics of LVNC were included for statistical analysis. The primary endpoint was a composite event of intracardiac thrombi and stroke or transient ischemic attack (TIA). The secondary endpoints were intracardiac thrombi and stroke/TIA. Results: The 320 included patients (211 [65.9%] men, median age: 45 years [interquartile range: 30−57]) were divided into LAD1 (<43 mm, n = 157) and LAD2 (≥43 mm, n = 163) groups based on the median LAD. Throughout the median follow-up of 34 months, the incidence of thromboembolism among them was 7.2%: 11 (3.4%) patients had stroke/TIA and 14 (4.4%) had intracardiac thrombi. The rate of thromboembolism in the LAD2 group was higher than that of patients in the LAD1 group (11.0% vs. 3.2%, p = 0.007). Kaplan−Meier survival curves suggested that a LAD ≥ 43 mm was associated with a higher risk of thromboembolism and intracardiac thrombi (log-rank test, all p < 0.05). After adjusting for potential risk factors, LAD ≥ 43 mm was found to be an independent risk factor for thromboembolism (p = 0.013) and stroke (p = 0.024). The area under the receiver operating characteristic curve of LAD for predicting thromboembolism reached 0.696 at 1 year, 0.635 at 2 years, and 0.660 at 3 years. Conclusions: A larger LAD was related to a higher risk of thromboembolism in patients with LVNC. The LAD may be a useful predictor for thrombotic risk stratification among such patients.

Perioperative parenteral fish oil supplementation improves postoperative coagulation function and outcomes in patients undergoing colectomy for ulcerative colitis.

Ulcerative colitis (UC) is an independent risk factor for thromboembolism, especially during the perioperative period. This study aimed to determine the effects of perioperative parenteral nutrition (PN) supplemented with fish oil (FO) on coagulation function and postoperative outcomes in patients with UC. This retrospective cohort included 92 consecutive patients who underwent colectomy for UC. Postoperative coagulation indices and outcomes, including thromboelastography (TEG) findings and comprehensive complication index (CCI), were compared. The relative change in serum D-dimer (ΔD-dimer) levels and maximal amplitude (ΔMA) on TEG were also determined. Patients receiving PN supplemented with FO (n = 48) had lower D-dimer (P = .036) levels on postoperative day (POD) 5 and a higher MA (P < 0.001) on POD 1 than those who did not receive it (n = 44). A lower ΔD-dimer level (P = .048) and ΔMA (P < 0.001) were also observed in patients receiving FO. The incidence of major postoperative complications (6.3 vs 22.7%; P = .017) and CCI (20.9 vs 23.4%; P = .044) were significantly lower in patients receiving FO. In multivariate analysis, FO (odds ratio, 0.231; 95% confidence interval, 0.055-0.971; P = .046) was a positive protector of major postoperative complications. Perioperative PN supplemented with FO improved coagulation function and reduced major postoperative complications in patients with UC requiring colectomy. These results may provide cues in formulating management strategies for preventing thromboembolisms and postoperative complications in patients with UC.

Risk factors for systemic and venous thromboembolism, mortality and bleeding risks in 1125 patients with COVID-19: relationship with anticoagulation status.

Aim: Coronavirus disease 2019 (COVID-19) has been associated with increased mortality and morbidity from thromboembolism, especially venous thromboembolism. There are more limited data for systemic thromboembolism. The present study aimed to investigate the prevalence of systemic and venous thromboembolism as well as major bleeding and mortality in relation to underlying risk factors and the impact of anticoagulation use in hospitalized patients with COVID-19.Methods and results: Patients with COVID-19 admitted to Union Hospital, Wuhan, Hubei, China between January 08, 2020 and April 7, 2020 were enrolled in this retrospective study. Cox proportional hazard models were utilized to determine associated risk factors for clinical events, adjusting for the severity of COVID-19 infection, drug therapies, comorbidities, surgery, and use of antithrombotic drugs.There were 1125 patients (49.9% male; mean age 58 years (standard deviation, SD, 15 years)) with a mean follow-up of 21 (SD 13) days. Approximately 25 (30%) patients with thromboembolism also suffered bleeding events.Age was an independent risk factor for thromboembolism, bleeding events, and death (all p<0.05). After adjusting for the severity of COVID-19 infection, comorbidities, surgery, antiviral drugs, immunomodulators, Chinese herbs, and antithrombotic drugs, low lymphocyte counts (hazard ratio, HR, 95% confidence interval (CI), 1.03, 1.01-1.05, p=0.01) and surgery (HR 2.80, 1.08-7.29, p=0.03) independently predicted the risk for major bleeding, whereas liver dysfunction (HR 4.13, 1.30-13.1, p=0.02) was an independent risk factor for patients with both thromboembolism and bleeding events.Conclusions: Patients with COVID-19 were at high risk for thromboembolic and bleeding events as well as mortality. The use of anticoagulants, especially parenteral anticoagulants, significantly reduced the risk for composite outcomes of thromboembolism, bleeding events, and death. The presence of AF was a contributor to systemic thromboembolism in COVID-19 patients.

Vitamin B12 deficiency, an independent risk factor for thromboembolism

Vitamin B12 deficiency, an independent risk factor for thromboembolism

Safety and efficacy of anterior communicating artery compromise during endovascular coil embolization of adjoining aneurysms.

In the presence of symmetric A1 flow, the safety and efficacy of compromising the anterior communicating artery (ACoA) during coil embolization of ACoA aneurysms has yet to be evaluated. Herein, the authors describe their experience, focusing on procedural safety. Between October 2012 and July 2017, 285 ACoA aneurysms with symmetric A1 flows were treated at the authors' institution by endovascular coil embolization. Clinical and angiographic outcome data were subjected to binary logistic regression analysis. ACoA compromise was chosen in the treatment of 71 aneurysms (24.9%), which were completely (n = 15) or incompletely (n = 56) compromised. In the remaining 214 lesions, the ACoA was preserved. Although 9 patients (3.2%) experienced procedure-related thromboembolisms (compromised, 4; preserved, 5), all but 1 patient (with ACoA compromise) were asymptomatic. In multivariate analysis, subarachnoid hemorrhage at presentation was the sole independent risk factor for thromboembolism (OR 15.98, p < 0.01), with ACoA compromise being statistically unrelated. In 276 aneurysms (96.8%) with follow-up of > 6 months (mean 20.9 ± 13.1 months, range 6-54 months), recanalization was confirmed in 21 (minor, 15; major, 6). A narrow (≤ 4 mm) saccular neck (p < 0.01) and ACoA compromise (p = 0.04) were independently linked to prevention of recanalization. During coil embolization of ACoA aneurysms, the ACoA may be compromised without serious complications if A1 flows are symmetric. This approach may also confer some long-term protection from recanalization, serving as a valid treatment option for such lesions.

Effect of hypertrophic cardiomyopathy on the prediction of thromboembolism in patients with nonvalvular atrial fibrillation

Anticoagulation is recommended for hypertrophic cardiomyopathy (HCM) with nonvalvular atrial fibrillation (NVAF) according to European and American guidelines. However, it is unclear whether HCM is a risk factor for thromboembolism in NVAF in Japan, and the management for NVAF with HCM is not established. We studied the impact of concomitant HCM on predicting thromboembolism in NVAF. We retrospectively studied consecutive 2374 Japanese patients with NVAF (1682 men, 70.9%; mean age 71±10 years). Clinical factors were evaluated using the Cox proportional hazards model. We also investigated whether adding HCM to CHADS2 or CHA2DS2-VASc score improved the prediction of thromboembolism. Thromboembolism was observed in 122 patients (5.1%) during the median follow-up of 2.4 years (interquartile range 2.0-3.2 years). The Cox proportional hazards model showed that HCM was significantly associated with thromboembolism after adjustment for CHADS2 or CHA2DS2-VASc score (hazard ratio 3.41; 95% confidence interval [CI] 1.98-5.73; P<.0001 and hazard ratio 3.38; 95% CI 1.97-5.64; P<.0001, respectively). NVAF with HCM had significantly higher thromboembolism rates, even in those with a CHADS2 or CHA2DS2-VASc score of 1 or 0-1, respectively. Based on the comparison of C-statistics, the addition of HCM to CHADS2 or CHA2DS2-VASc score significantly improved the prediction of thromboembolism (C-statistics 0.75 vs 0.71; P=.003 and C-statistics 0.77 vs 0.71; P=.0001, respectively). HCM is an independent risk factor for thromboembolism in patients with NVAF. A markedly high incidence of thromboembolism is observed in NVAF patients with HCM with CHA2DS2-VASc score of both ≥2 and 0-1, and anticoagulation therapy is recommended for them.

Female Sex as a Risk Factor for Ischemic Stroke and Systemic Embolism in Chinese Patients With Atrial Fibrillation: A Report From the China-AF Study.

BackgroundPrevious studies have provided conflicting results as to whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation (AF). We investigated whether women with AF were at higher risk of ischemic stroke in the China‐AF (China Atrial Fibrillation Registry) Study.Methods and ResultsA total of 19 515 patients were prospectively enrolled between August 2011 and December 2016 in the China‐AF Study. After exclusion of patients receiving anticoagulation or ablation therapy, 6239 patients (2574 women) with results from at least 6 months of follow‐up were used for the analysis. Cox proportional hazards models were performed to evaluate whether female sex was an independent risk factor for thromboembolism after multivariate adjustment. The primary outcome was the time to the first occurrence of ischemic stroke or systemic embolism. After a mean follow‐up of 2.81±1.46 years, 152 female patients reached the primary outcome, as compared with 172 male patients. Crude incidence rates of thromboembolism between women and men were of borderline statistical significance (2.08 versus 1.68 per 100 patient‐years, P=0.058). After multivariable analysis, female sex was not independently associated with an increased thromboembolism risk (hazard ratio 1.09, 95% confidence interval 0.86‐1.39). There was no significant difference in thromboembolism risk by sex stratified by age and presence or absence of risk factors (P for interaction all >0.1).ConclusionsAlthough crude incidence rates of thromboembolism were higher in Chinese female patients with AF compared with male patients, female sex did not emerge as an independent risk factor for thromboembolism on multivariate analysis.Clinical Trial Registration URL: http://www.chictr.org.cn/. Unique identifier: ChiCTR‐OCH‐13003729.

Impact of Blood Pressure Control on Thromboembolism and Major Hemorrhage in Patients With Nonvalvular Atrial Fibrillation: ASubanalysis of the J-RHYTHM Registry.

BackgroundTo clarify the influence of hypertension and blood pressure (BP) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed.Methods and ResultsA consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P=0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P=0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, <114; Q2, 114–125; Q3, 126–135; and Q4, ≥136 mm Hg), odds ratios for both events were significantly higher in Q4 than in Q1 (thromboembolism, odds ratio 2.88, 95% CI 1.75–4.74, P<0.001; major hemorrhage, odds ratio 1.61, 95% CI 1.02–2.53, P=0.041) after adjustment for components of CHA 2 DS 2‐VASc score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage.Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation.Clinical Trial Registration URL: http://www.umin.ac.jp/ctr. Unique identifier: UMIN000001569.

Incidental Aortic Thrombus in a Patient With Crohn’s Disease

Introduction: Thromboembolism is a well-known complication of inflammatory bowel disease (IBD). Patients with IBD are at least 3 times more likely to experience thromboembolism than general population. They are most often venous in origin than arterial with deep venous thrombosis/pulmonary embolism being the most common. A total of 13 cases were reported in literature with aortic mural thrombus. We are presenting a case of Crohn’s disease with incidental aortic thrombus detected on imaging which was done to evaluate disease flare. Case Report: A 34-year-old female with Crohn’s disease for past 10 years came to our hospital with rectal bleeding and abdominal pain for past 1 week. She has been taking IBD medications intermittently when she has flares. Past medical history is significant for pulmonary embolism diagnosed 5 years ago. Vital signs were unremarkable except for mild tachycardia. Exam revealed diffuse mild tenderness in all quadrants with no guarding, rigidity or organomegaly. Rest of the exam was unremarkable including good distal extremity pulses. Lab tests were significant for mild leukocytosis and significant thrombocytosis with platelet count of 1.1 million/dL. CT scan of abdomen and pelvis showed acute exacerbation of Crohn’s disease and incidental detected infra renal aortic thrombus occupying 50% of the lumen. Heparin drip was initiated and patient was monitored in-house for few more days. Decision was made to manage medically as she did not have any vascular compromise and hence discharged on enoxaparin. Complete hypercoagulable work up was sent, which was negative. Patient had repeat imaging 4 weeks later which showed complete resolution of thrombus. Discussion: Several studies have confirmed the fact about IBD being an independent risk factor for thromboembolism. Probable pathogenetic mechanisms include increased pro inflammatory cytokines, circulating immune complexes, and decreased fibrinolysis all of which activate coagulation cascade. Most important risk factors in IBD patients are active disease, post-operative status, and steroid use. Inherited risk factors for thrombosis have same incidence in IBD patients compared to non IBD controls as shown in cohort studies. It is still remains unclear if there is a role for extensive hypercoagulable work up in these patients. Management of aortic thrombus remains controversial due to rarity of this complication. Medical management is preferable due to ease of administration with surgical intervention reserved for patients with end organ ischemia from thrombus embolization. We conclude that clinicians should be aware of this complication in IBD patients as it can cause fatal outcomes.

Evaluation of the relationship between serum apelin levels and vitamin D and mean platelet volume in diabetic patients

ObjectivesIt was reported that Vitamin D deficiency was associated with a greater risk of cardiometabolic diseases, obesity, impaired glucose tolerance and diabetes mellitus type 2, arterial hypertension, and dyslipidemia. Apelin is an adipocytokine suspected to have a role in skeletal muscle glucose utilization and glycemic regulation which may be a promising treatment modality for diabetes. It was recently reported that increased mean platelet volume (MPV) was emerging as an independent risk factor for thromboembolism, stroke, and myocardial infarction. In patients with diabetes, MPV was higher compared with the normal glycemic controls; in addition, it has been proposed that an increase in MPV may play a role in the micro- and macro-vascular complications related to diabetes. We postulated that deficiency in Vitamin D levels might be associated with higher MPV and lower serum apelin levels leading a further increase in insulin resistance in diabetic patients. So, we aimed to investigate Vitamin D levels, MPV and serum apelin levels in diabetic patients and their correlations between each other. Materials and methodThis is a cross-sectional study design. Seventy-eight patients with Diabetes Mellitus type 2, admitted to our outpatient clinic of internal medicine department at Bezmialem Vakif University, were included in our study. Forty-one patients were female; 37 patients were male. Serum apelin levels, fasting glucose levels, urea, creatinine, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting serum insulin level, HbA1c, free T3, free T4, TSH, vitamin D (25-OH Vitamin D) and complete blood counts were analyzed in all subjects. ResultsEach sex was analyzed separately. We found that a positive correlation existed between serum apelin levels and BMI in female patients. (r: 0.380, P: 0.014) There was also a significant positive correlation between MPV and HbA1c and fasting glucose levels and a negative correlation between MPV and PLT. (r: 0.377, P: 0.021; r: 0.395, P: 0.014; r: −0.401, P: 0.011; respectively) We failed to show a significant relationship between serum vitamin D levels, serum apelin levels and MPV in patients with diabetes mellitus type 2. ConclusionWe failed to show an association between vitamin D, apelin and MPV higher volumes of which may have a role in cardiovascular complications related to diabetes by increasing platelet activation.

Female sex as an independent risk factor for stroke in atrial fibrillation: Possible mechanisms

Atrial fibrillation (AF) is an independent risk factor for thromboembolism and stroke. Women with AF are at a higher overall risk for thromboembolic stroke when compared to men with AF. Recent evidence suggests that female sex, after adjusting for stroke risk profile and sex differences in utilisation of anticoagulation, is an independent stroke risk factor in AF. The inclusion of female sex has improved the accuracy of the CHADS2 stroke risk stratification schema (Congestive heart failure, Hypertension, Age 75 years or greater, Diabetes mellitus, and prior Stroke or TIA). The newly revised and validated schema, CHA2DS2-VASc, dichotomises age and incorporates female sex and vascular disease history. The pathophysiological mechanisms to explain this increased risk in women are not well understood. According to Virchow's triad, thrombosis that leads to stroke in AF should arise from three co-existing phenomena: structural abnormalities, blood stasis, and a hypercoagulable state. Herein, we explore the sex differences in the biological processes that lead to thrombus formation as applied to Virchow's Triad. The objective of this review is to describe the potential mechanisms behind the increased risk of stroke in AF associated with female sex.

Distinct contractile and molecular differences between two goat models of atrial dysfunction: AV block-induced atrial dilatation and atrial fibrillation

Atrial dilatation is an independent risk factor for thromboembolism in patients with and without atrial fibrillation (AF). In many patients, atrial dilatation goes along with depressed contractile function of the dilated atria. While some mechanisms causing atrial contractile dysfunction in fibrillating atria have been addressed previously, the cellular and molecular mechanisms of atrial contractile remodeling in dilated atria are unknown. This study characterized in vivo atrial contractile function in a goat model of atrial dilatation and compared it to a goat model of AF. Differences in the underlying mechanisms were elucidated by studying contractile function, electrophysiology and sarcoplasmic reticulum (SR) Ca 2+ load in atrial muscle bundles and by analyzing expression and phosphorylation levels of key Ca 2+-handling proteins, myofilaments and the expression and activity of their upstream regulators. In 7 chronically instrumented, awake goats atrial contractile dysfunction was monitored during 3 weeks of progressive atrial dilatation after AV-node ablation (AV block goats (AVB)). In open chest experiments atrial work index (AWI) and refractoriness were measured (10 goats with AVB, 5 goats with ten days of AF induced by repetitive atrial burst pacing (AF), 10 controls). Isometric force of contraction (FC), transmembrane action potentials (APs) and rapid cooling contractures (RCC, a measure of SR Ca 2+ load) were studied in right atrial muscle bundles. Total and phosphorylated Ca 2+-handling and myofilament protein levels were quantified by Western blot. In AVB goats, atrial size increased by 18% (from 26.6 ± 4.4 to 31.6 ± 5.5 mm, n = 7 p < 0.01) while atrial fractional shortening (AFS) decreased (from 18.4 ± 1.7 to 12.8 ± 4.0% at 400 ms, n = 7, p < 0.01). In open chest experiments, AWI was reduced in AVB and in AF goats compared to controls (at 400 ms: 8.4 ±0.9, n = 7, and 3.2 ± 1.8, n = 5, vs 18.9 ± 5.3 mm×mmHg, n = 7, respectively, p < 0.05 vs control). FC of isolated right atrial muscle bundles was reduced in AVB ( n = 8) and in AF ( n = 5) goats compared to controls ( n = 9) (at 2 Hz: 2.3 ± 0.5 and 0.7 ± 0.2 vs 5.5 ± 1.0 mN/mm 2, respectively, p < 0.05). APs were shorter in AF, but unchanged in AVB goats. RCCs were reduced in AVB and AF versus control (AVB, 3.4 ± 0.5 and AF, 4.1 ± 1.4 vs 12.2 ± 3.2 mN/mm 2, p < 0.05). Protein levels of protein kinase A (PKA) phosphorylated phospholamban (PLB) were reduced in AVB ( n = 8) and AF ( n = 8) vs control ( n = 7) by 37.9 ± 12.4% and 29.7 ± 10.1%, respectively ( p < 0.01), whereas calmodulin-dependent protein kinase II (CaMKII) phosphorylated ryanodine channels (RyR2) were increased by 166 ± 55% in AVB ( n = 8) and by 146 ± 56% in AF ( n = 8) goats ( p < 0.01). PKA-phosphorylated myosin-binding protein-C and troponin-I were reduced exclusively in AVB goat atria (by 75 ± 10% and 55 ± 15%, respectively, n = 8, p < 0.05). Atrial dilatation developing during slow ventricular rhythm after complete AV block as well as AF-induced remodeling are associated with atrial contractile dysfunction. Both AVB and AF goat atria show decreased SR Ca 2+ load, likely caused by PLB dephosphorylation and RYR2 hyperphosphorylation. While shorter APs further compromise contractility in AF goat atria, reduced myofilament phosphorylation may impair contractility in AVB goat atria. Thus, atrial hypocontractility appears to have distinct molecular contributors in different types of atrial remodeling.

Plasma total homocysteine in the active stage of ulcerative colitis

Homocysteine, an independent risk factor for thromboembolism, has been recently shown to be elevated in ulcerative colitis (UC). However, its relation to the activity of the disease remain unclear. Two groups were studied: group consisted of 1-30 patients with UC (17 men, 13 women, mean age 50.3 +/- 14.7 years), including 15 patients with active disease. Group 2 (controls) consisted of 21 age-, sex-, bodyweight-matched healthy persons (12 men, nine women, mean age 53.1 +/- 12.8 years). Total plasma homocysteine (tHcy) and serum folate and vitamin B12 as well as selected coagulation parameters were assessed. Mean tHcy in UC patients was significantly higher than in healthy controls: 10.8 +/- 3.1 mmol/L versus 6.8 +/- 2.5 mmol/L (P < 0.001). Patients with active disease had higher tHcy than patients in remission: 11.2 +/- 3.5 mmol/L versus 9.0 +/- 2.3 mmol/L (P = 0.048). Patients with > or =4 recurrences of the disease had also higher tHcy than the others: 11.5 +/- 3.6 mmol/L versus 9.0 +/- 2.1 mmol/L (P = 0.035). The tHcy correlated with duration of disease: r = 0.6632 (P < 0.05). Folate and B12 levels were within their reference ranges in all subjects. However, in the patients with active disease the platelet count, fibrinogen and D-dimer were significantly higher than in the patients in remission and the controls. Ulcerative colitis is associated with elevated tHcy concentration, particularly in the active stage, and in more recurrent types of the disease; this elevation does not seem to be prevented by a normal folate status and might have an enhancing effect on the procoagulation blood profile.

Accumulation of Risk Factors Increases Risk of Thromboembolic Events in Patients With Nonvalvular Atrial Fibrillation

Accumulation of risk factors could increase thromboembolic event rates in patients with nonvalvular atrial fibrillation (NVAF). To validate this hypothesis, a post hoc analysis was performed to determine the relationship of risk levels and thromboembolic events in patients with NVAF from our previous prospective study. Risk levels were quantified using the CHADS2 index in 509 patients with NVAF (66.3+/-10.3 years old). One point each was given for patients with advanced age (>or=75 years), hypertension, congestive heart failure, and diabetes mellitus, and 2 points, to those with prior ischemic stroke or transient ischemic attack. Patients with a CHADS2 score of 0 were classified as low risk, 1 to 2 a moderate risk and 3 or more were high risk. Because hypertrophic cardiomyopathy had emerged as an independent risk factor for thromboembolism, the original CHADS2 score was modified by adding 1 point to patients with hypertrophic cardiomyopathy. Warfarin was given to 263 patients (mean international normalized ratio (INR) at enrollment, 1.86), antiplatelets (aspirin or ticlopidine) to 163 patients and no antithrombotic therapy to 83. During a mean follow-up period of 2 years, 31 thromboembolic events occurred. As the risk level (modified CHADS2 score) increased, the event rate increased for both the patient groups receiving warfarin (p=0.035) and those not receiving warfarin (p=0.048). When a thromboembolic event occurred in patients who had been treated with warfarin, the mean INR level was 1.41. Twelve (75%) of 16 patients complicated with thromboembolism during warfarin treatment had INR levels below the optimal levels (1.6-2.6) for Japanese patients. Accumulation of risk factors could increase risk of thromboembolic events in patients with NVAF. Adherence to the guidelines for anticoagulation therapy is recommended.

Management of Venous Thromboembolism in the Elderly

In this review the authors discuss the use of oral and parenteral anticoagulants for the prevention and treatment of venous thromboembolism (VTE) in the elderly. The use of anticoagulant agents in VTE prophylaxis and treatment in the elderly is complicated by an increase with age in the presence of multiple risk factors and co-morbidities that may increase the risk of both VTE and bleeding. Age itself is identified as an independent risk factor for thromboembolism. VTE is underdiagnosed in the elderly population, and routine prophylaxis frequently falls short of the levels required according to level of risk. Although appropriate anticoagulation of at-risk patients offers a means of reducing the significant VTE burden in this population, concerns have been raised over the use of anticoagulants in a patient group in whom multiple risk factors are common. Bleeding in the elderly can be exacerbated by reduced renal clearance and hypersensitivity to oral anticoagulants that may lead to over-anticoagulation. Although bleeding due to anticoagulant therapy is a serious issue in the elderly, it is often overemphasized, given the therapeutic value otherwise observed in treating this patient group. Warfarin is still used in VTE prophylaxis after orthopaedic surgery and for long-term VTE treatment. Unfractionated and low-molecular-weight heparins (LMWHs) have been shown to be safe and effective in the prophylaxis of VTE, and are now being shown to be as effective as warfarin in the initial and long-term treatment of VTE. LMWHs confer the advantage over unfractionated heparin of subcutaneous once-daily administration with no requirement for laboratory monitoring of their anticoagulant effect, which allows for the convenience of outpatient therapy. New anticoagulants that may be of potential benefit in this patient population include fondaparinux sodium, but clinical experience of this drug in the elderly remains limited.

Gender Differences in the Risk of Ischemic Stroke and Peripheral Embolism in Atrial Fibrillation

Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation (AF). We examined data from a large contemporary cohort of AF patients to address this question. We prospectively studied 13,559 adults with AF and recorded data on patients' clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke, peripheral embolism, and major hemorrhagic events through searching validated computerized databases and medical record review. We compared event rates by patient sex using multivariable log-linear regression, adjusting for clinical risk factors for stroke, and stratifying by warfarin use. We identified 394 ischemic stroke and peripheral embolic events during 15,494 person-years of follow-up off warfarin. After multivariable analysis, women had higher annual rates of thromboembolism off warfarin than did men (3.5% versus 1.8%; adjusted rate ratio [RR], 1.6; 95% CI, 1.3 to 1.9). There was no significant difference by sex in 30-day mortality after thromboembolism (23% for both). Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men (RR, 0.4; 95% CI, 0.3 to 0.5; and RR, 0.6; 95% CI, 0.5 to 0.8, respectively), with similar annual rates of major hemorrhage (1.0% and 1.1%, respectively). Women are at higher risk than men for AF-related thromboembolism off warfarin. Warfarin therapy appears be as effective in women, if not more so, than in men, with similar rates of major hemorrhage. Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF.

Incidence and Risk Factors for Thromboembolism in Patients with Hematologic Malignancies Undergoing Allogeneic and Autologous Stem Cell Transplantation.

Background: Thromboembolism (TE) is a common complication of hospitalized non-transplant cancer patients. To date, the extent and impact of TE in stem cell transplant patients is unknown, in part because it is considered a low risk group given the high prevalence of thrombocytopenia. The purpose of this study is to evaluate the incidence of and risk factors for TE in cancer patients undergoing stem cell transplantation.Methods: We conducted a retrospective analysis of all discharge summaries from the 115 US academic health centers reporting to the University HealthSystem Consortium from 1995 to 2002. We identified a total of 7,087 patients with hematologic malignancies undergoing allogeneic and autologous stem cell transplantation. The incidence of and risk factors for venous and arterial TE was analyzed in univariate and multivariate logistic regression analysis with adjusted odds ratios as estimates of relative risk.Results: TE was reported in 389 (5.5%) transplant patients with 4.8% patients developing venous and 0.7% arterial TE. The incidence of TE was greater in allogeneic (6.8%) compared to autologous (4.8%) transplant patients (p<0.0001). Among those receiving allogeneic transplantations, BMT patients experienced a higher rate of TE than PBSC patients (7.5% vs 5.6%; p<0.05). In multivariate logistic regression analysis, the following clinical variables were significantly associated with TE in stem call transplant patients with hematologic malignancies: gram negative sepsis (OR=1.76; 1.02–3.02; p=0.04), gram positive sepsis (OR=1.75; 1.25–2.45; p=0.001), line infections (OR=1.48; 1.11–1.97; p=0.008), central venous catheters (OR=1.74; 1.39–2.17; P<0.0001), pulmonary disease (OR=1.87; 1.47–2.37; p<0.0001), liver disease (OR=1.31; 1.01–1.70; p=0.04) and length of stay >30 days (OR=1.66; 1.30–2.13; p<0.0001). Hodgkin's disease (OR= 0.59; 0.37–0.94; p=0.026) was associated with a lower risk of TE. In multivariate analysis, the type of transplant failed to remain an independent risk factor for TE after controlling for other transplant complications.Conclusions: This is the first substantive report on the incidence of thromboembolism in stem cell transplant patients. We found that thromboembolic events are a frequent complication in patients with hematologic malignancies undergoing stem cell transplantation. The incidence of TE is high among most subgroups studied. Prospective studies are needed to evaluate the efficacy and safety of thromboprophylaxis in this high-risk population.

Thrombin formation in platelet-rich plasma after oral methionine loading: Preliminary report

Homocysteine, an intermediate of methionine metabolism, has been found to be an independent risk factor for thromboembolism [1]. Various mechanisms have been proposed to explain possible homocysteine-induced thrombogenicity, including endothelial damage, enhanced lipid peroxidation, impaired activity of the anticoagulant protein C system and increased expression of tissue factor [1–5]. Relevance of these findings in vivo remains controversial. Much less is known on the effects of homocysteine on platelet function [6]. In patients with homocystinuria, homocysteine might increase thromboxane A2 production [7] and stimulate platelet aggregation [8], though the effect of homocysteine on platelet survival is less evident [6]. Oxidative stress might lead to homocysteine oxidation, enhanced platelet activation and increased prothrombotic potential in hyperhomocysteinemia [9]. Methionine loading test is recognized as a method to induce a transient acute hyperhomocysteinemia and helps to identify individuals with abnormal methionine metabolism [10,11]. It remains to be determined whether in mild hyperhomocysteinemia platelet-mediated prothrombotic effects might be of importance. The aim of the study was to evaluate potential alterations in thrombin formation in platelet-rich plasma after oral methionine loading in healthy subjects. 2. Materials and methods