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PubMed2005

Systemic thromboembolism in inflammatory bowel disease: mechanisms and clinical applications.

Systemic thromboembolism is an extraintestinal manifestation of inflammatory bowel disease (IBD), and an important cause of patient morbidity and mortality. The underlying basis for the hypercoagulable state in IBD is complex, and involves altered activity of all three components that govern hemostasis: platelets, fibrinolysis, and the coagulation cascade. Currently, there are no distinct guidelines for treating or preventing thromboembolic (TE) events in IBD patients compared with the general population. However, the prothrombotic state in IBD stems, at least in part, from several modifiable factors, such as hyperhomocysteinemia and an active inflammatory state. In this review we summarize the mechanisms that favor thrombosis in IBD, and the principles that need to be applied for the primary and secondary prevention of TE in this selected group of patients.

Autoantibodies↗
PubMed1995

Very low-dose warfarin prophylaxis to prevent thromboembolism in women with metastatic breast cancer receiving chemotherapy: an economic evaluation.

PURPOSE: A recent double-blind, randomized trial demonstrated that very low-dose warfarin (VLDW) reduced the incidence of venous thromboembolism (VTE) without increasing the rate of bleeding in women with metastatic breast cancer receiving chemotherapy. We have evaluated the economic impact on the health care system of using VLDW in such patients. METHODS: The records of patients entered onto the trial and a simultaneous, fully allocated, costing model for a tertiary care hospital in Hamilton, Canada were used to determine the difference in costs associated with the care of patients with and without VLDW. RESULTS: The cost of providing VLDW was $ 21,854 (Canadian dollars) per 100 patients. This therapy led to a reduction in costs of $ 24,297 per 100 patients, thus saving the health care system $ 2,443 per 100 patients. In the sensitivity analysis, VLDW prophylaxis still did not increase health care costs unless the cost of VLDW was greatly increased, the cost of treating thromboembolic episodes was markedly reduced, or the incidence of either VTE or bleeding with VLDW was increased above the rates observed in the trial. CONCLUSION: We conclude that for women receiving chemotherapy for metastatic breast cancer, the benefits of VLDW can be realized without increased health care costs.

Breast Neoplasms↗
PubMed2006

Thromboembolism and delayed cerebral ischemia after subarachnoid hemorrhage: an autopsy study.

OBJECTIVE: Recent findings have cast doubt on vasospasm as the sole cause of delayed cerebral ischemia after subarachnoid hemorrhage. METHODS: We reviewed the medical records of 29 patients who died after subarachnoid hemorrhage. Brain sections were taken from the insula, cingulate gyrus, and hippocampus. Adjacent sections were stained with hematoxylin-eosin and immunostained for thromboemboli. The density (burden) of the latter was calculated blindly and correlated with evidence for ischemia and with the amount of subarachnoid blood. RESULTS: There is a strong correlation between microclot burden and delayed cerebral ischemia. Patients with clinical or radiological evidence of delayed ischemia had mean microclot burdens of 10.0/cm2 (standard deviation [SD], +/-6.6); those without had mean burdens of 2.8 (SD, +/-2.6), a highly significant difference (P = 0.002). There is also significant association (P = 0.001) between microclot burden and histological evidence of ischemia, with the mean burdens being 10.9 in sections exhibiting severe ischemia and 4.1 in those in which ischemia was absent. Microclot burden is high in patients who died within 2 days of hemorrhage, decreasing on Days 3 and 4. In delayed ischemia, the numbers rise again late in the first week and remain high until after the second week. In contrast, the average clot burden is low in patients dying without developing delayed ischemia. The amount of blood on an individual slide influenced the microclot burden on that slide to a highly significant extent (P < 0.001). CONCLUSION: Thromboembolism after subarachnoid hemorrhage may contribute to delayed cerebral ischemia, which parallels that caused by vasospasm. The pathogenesis of thromboembolism is discussed.

Adult↗
PubMed2003

Clinical features of acute pulmonary thromboembolism in younger patients.

The incidence of acute pulmonary thromboembolism (APTE) in younger patients is extremely low compared with older patients, so the clinical features of these younger patients with APTE is unknown. In the present study, 8 patients with APTE who were less than 40 years old (YG) were compared with 40 patients who were more than 41 years of age (OG). All YG patients had coagulopathy compared with 3 patients in the OG (p<0.01). Deep venous thrombosis (DVT) occurred in all 8 patients in the YG compared with 19 patients in the OG (p<0.01). A higher incidence of patients whose symptoms occurred gradually was noted in the YG (p<0.05). There were no significant differences in clinical characteristics, initial symptoms, past history or other predisposing factors for venous thromboembolism between the 2 groups. Residual pulmonary hypertension was not noted in the YG. However, 1 patient in the YG had recurrent APTE, despite good warfarin control. This study demonstrated the frequency of gradual onset, coagulopathy and clinical signs of DVT in the YG and therefore more careful and long-term observation is necessary in such patients.

Acute Disease↗
PubMed2003

Usefulness of a second temporary vena cava filter for preventing acute pulmonary thromboembolism.

The usefulness of a temporary inferior vena cava filter (t-IVC-f) for the prevention of acute pulmonary thromboembolism (APTE) associated with venous thromboembolism (VTE) has been established, but not the requirement for an additional therapeutic method when the t-IVC-f has captured a thrombus. A woman underwent implantation of a t-IVC-f just caudal to the bifurcation of the renal vein immediately before cesarean section (C/S) for VTE that had occurred during the third trimester of pregnancy. After receiving a combination of anticoagulant and fibrinolytic therapies after the C/S, the t-IVC-f was found to contain a thrombus and in order to prevent its dissemination during the removal of the closed filter, another filter was inserted and expanded proximal to the first. Insertion of an additional t-IVC-f may prevent occurrence of APTE during removal of the primary filter containing a friable thrombus after fibrinolytic therapy, and the technique proved useful in the present case of VTE during pregnancy.

Acute Disease↗
PubMed1984

The incidence of thromboembolism and the hemocoagulative background in patients with rheumatic heart disease.

We discussed the existence of a thrombotic tendency and the relationship between the high incidence of thromboembolism and the thrombotic tendency in patients with rheumatic heart disease (RHD). The augmentation of platelet function was detected in all kinds of rheumatic valvular disease from the finding of high values of plasma beta-thromboglobulin (72 ng/ml, normal 29 ng/ml). The existence of hypercoagulation was also detected in patients with mitral stenosis by showing low levels of plasma antithrombin III (AT III), while fibrinolytic reaction remained normal. The degree of hypercoagulation became augmented in the order of cases of mitral stenosis (MS) complicated by both atrial fibrillation and chronic congestive heart failure, MS complicated only atrial fibrillation and MS with normal sinus rhythm (AT III: 19.6, 25.0, 26.7 mg/dl, respectively). On the contrary, hypercoagulation, the degree of which was almost the same as that in the respective MS groups, also existed in comparable controls of non-RHD, accompanied by the acceleration of fibrinolytic reaction as shown by the decrease in activity of plasma alpha 2-plasmin inhibitor. Therefore, it was concluded that thrombotic tendency certainly existed in patients with MS compared to those with non RHD and that it was one of the causes of the significantly high incidence of thromboembolism in comparison with non RHD.

Antithrombin III↗
PubMed1995

Mechanism of atrial fibrillation and increased incidence of thromboembolism in patients with hypertrophic cardiomyopathy.

To elucidate the morphologic characteristics of the left ventricle in patients with hypertrophic cardiomyopathy who developed atrial fibrillation, we studied left ventricular geometry by two-dimensional echocardiography in 92 patients with hypertrophic cardiomyopathy. These patients were divided into two groups; 24 patients with transient or persistent atrial fibrillation (group I) and 68 patients with sinus rhythm (group II). Left ventricular chamber size in group I was significantly smaller than that in group II. Left ventricular chamber size was correlated positively with stroke volume, and was correlated negatively with left ventricular end-diastolic pressure. The incidence of systemic thromboembolism in group I was 7.1% per patient year. In hypertrophic cardiomyopathy, the size of the left ventricle appears to have major pathophysiologic significance in the development of atrial fibrillation. In addition, since patients with hypertrophic cardiomyopathy who develop atrial fibrillation have a potential risk of systemic thromboembolism, prophylactic anticoagulant therapy should be performed in these patients.

Adult↗
PubMed1998

Venous thromboembolic disease.

The advent of spiral CT has encouraged investigation into the diagnosis of venous thromboembolic disease. It has also exposed the limitations of prior methods of investigation and raised questions as to the significance of small pulmonary emboli. This article discusses this new technique, the clinical detection of venous thromboembolic disease and possible current and future strategies in diagnosis.

Humans↗
PubMed1998

Transmural myocardial infarction caused by thromboembolism associated with mitral insufficiency in a dog.

A 10-year-old dog, which had been treated for mitral insufficiency, died suddenly. Transmural myocardial infarction secondary to thromboembolic occlusion of the subsinuosal interventricular branch of the left circumflex artery was noted in the posterior lower half of the left ventricular wall, involving the interventricular septum and a part of right ventricular wall. The mitral valve leaflets were markedly thickened (valvular endocardiosis). These were a patchy area of jet lesion and several mural thrombi on the left-atrial endocardium. The embolus in the subsinuosal interventricular branch was composed of mostly platelets and fibrin, showing the same histologic features as those of the mural thrombi on the left-atrial endocardium. From these findings, it was concluded that dislodgement of part of the mural thrombi on the left-atrial endocardium caused thromboembolism of the subsinuosal interventricular branch.

Animals↗
PubMed2001

Treating venous thromboembolism: enoxaparin.

This article reviews the developments that have occurred in the treatment of venous thromboembolism during the last decade, with emphasis on the establishment of low molecular weight heparin as a therapeutic agent of proven efficacy and examines the evidence that supports the movement from inpatient to outpatient hospital management of venous thromboembolism.

Ambulatory Care↗
PubMed2001

Pathophysiology of venous thromboembolism.

Venous thromboembolism remains an important cause of morbidity and mortality for surgical and non-surgical patients, and its pathophysiology in acutely ill, non-surgical patients is not well understood. The clinically silent nature of thromboembolism makes it a significant threat to hospital patients.

Death, Sudden↗
PubMed2000

Meta-analysis of thromboembolic prophylaxis after total knee arthroplasty.

We performed a meta-analysis of the English literature to assess the efficacy of four common regimes for thromboembolic prophylaxis after total knee arthroplasty: aspirin, warfarin, low-molecular-weight heparin (LMWH) and pneumatic compression. We reviewed 136 articles and abstracts published between January 1980 and December 1997. Papers not using routine venography and a lung scan or angiography to detect deep-venous thrombosis (DVT) and pulmonary emboli (PE) respectively, were excluded. Of the 136 studies, 23 with 6,001 patients were selected. The incidence of DVT was 53% (1,701/3,214) in the aspirin group, 45% (541/1,203) in the warfarin group, 29% (311/1,075) in the LMWH group, and 17% (86/509) in the pneumatic compression device group. Intermittent pneumatic compression devices and LMWH were significantly better than warfarin (p < 0.0001) or aspirin (p < 0.0001) in preventing DVT. The incidence of asymptomatic PE was 11.7% in the aspirin group (222/1,901), 8.2% (101/1,229) in the warfarin group and 6.3% (24/378) in the pneumatic compression group. No studies with LMWH used routine lung scans. Warfarin and pneumatic compression were significantly better than aspirin in preventing asymptomatic PE (p < 0.05). The incidence of symptomatic PE was 1.3% (23/1,800) in the aspirin group, 0.4% (2/559) in the warfarin group, 0.5% (2/416) in the LMWH group and 0% (0/177) in the pneumatic compression group. No statistically significant difference was noted between the above prophylactic regimes due to the very small incidence of symptomatic PE. Prophylaxis for thromboembolic disease in TKA may have to include a combination of some of the above regimes to incorporate their advantages.

Anticoagulants↗
PubMed2001

Argatroban for prevention and treatment of thromboembolism in heparin-induced thrombocytopenia.

OBJECTIVE: To renew the pharmacology, pharmacokinetics, efficacy adverse events, and cost of argatroban in the prevention and treatment of thromboembolism in patients with heparin-induced thrombocytopenia (HIT). DATA SOURCES: A MEDLINE search (1980 to August 2000) of English-language literature was conducted using the search term argatroban to identify pertinent case reports, clinical trials, abstracts, and review articles. Additional reports were identified from the reference lists compiled in the literature reviewed, as well as from the manufacturer. DATA SYNTHESIS: Argatroban is a synthetic direct thrombin inhibitor indicated for parenteral use in the prevention and treatment of thromboembolism in patients with HIT. Its elimination half-life is approximately 40-50 minutes, and it is primarily eliminated by hepatic metabolism and biliary secretion. Compared with historical controls, argatroban-treated patients with HIT or HIT with thrombosis (HITTS) experienced lower rates of the composite end point of death, amputation, and new thrombosis. Dosing is initiated at 2 microg/kg/min and adjusted to maintain the activated partial thromboplastin time at 1.5-3 times the patient's baseline. In Japan, argatroban is approved for use in acute ischemic stroke and chronic peripheral occlusive disease. It has also been used as an alternative to unfractionated heparin (UFH) in patients with a history of HIT or HITTS undergoing percutaneous coronary intervention and other procedures. Additionally, argatroban has been compared with UFH in patients with acute myocardial infarction who were receiving thrombolytic therapy. Hemorrhage is the primary adverse event associated with argatroban. Argatroban increases the prothrombin time, making assessment of the intensity of warfarin therapy during concurrent administration more complex. CONCLUSIONS: The use of argatroban in patients with HIT and HITTS is associated with improvement in clinical outcomes compared with historical controls. Argatroban offers several practical advantages over other available agents with respect to dosing, monitoring, reversibility of effect with discontinuation of the drug, and cost.

Animals↗
PubMed2003

Venous thromboembolism prevention with LMWHs in medical and orthopedic surgery patients.

OBJECTIVE: To discuss the role of low-molecular-weight heparins (LMWHs) in the prevention of venous thromboembolism (VTE) in medical and orthopedic surgery patients. VTE prophylaxis trials in these practice settings establishing the current use of LMWHs marketed in the US are included. An overview is also provided of VTE incidence, risk factors, and prophylaxis consensus guidelines. DATA SOURCES AND STUDY SELECTION: Clinical trials, review articles, and meta-analyses for Food and Drug Administration-approved LMWHs were identified from a MEDLINE search (1980-March 2002). Search terms included dalteparin, enoxaparin, internal medicine, low-molecular-weight heparin, orthopedic surgery, risk factors, tinzaparin, and venous thromboembolism. DATA SYNTHESIS: Consensus guidelines are useful as an initial guide to appropriate VTE prophylaxis; however, a review of the primary literature is needed to identify optimal agents, regimens, or interventions. LMWHs have demonstrated sound efficacy in VTE prevention; however, the quantity and quality of literature are not always comparable for the available agents. CONCLUSIONS: Enoxaparin has demonstrated efficacy and safety in VTE prevention in medical patients, whereas information is limited or lacking for dalteparin and tinzaparin. Total hip replacement (THR) trials have been conducted with all US-marketed LMWHs and have demonstrated the efficacy and safety of each agent. Trials specifically establishing the efficacy of an LMWH in total knee replacement surgery (TKR) have been published for enoxaparin. One combination THR and TKR trial has been published for tinzaparin. These trial outcomes have positioned the LMWHs as key alternatives to adjusted-dose warfarin for VTE prophylaxis in orthopedic surgery. Inherent differences between LMWHs prevent the extrapolation of clinical outcomes from 1 trial to another.

Anticoagulants↗
PubMed2003

Duration of anticoagulant therapy after initial idiopathic venous thromboembolism.

OBJECTIVE: To review the literature investigating the duration of oral anticoagulant therapy following a first event of idiopathic venous thromboembolism (VTE). DATA SOURCE: MEDLINE (1967-April 2003) and bibliographic searches of the English-language literature pertaining to the duration of oral anticoagulant therapy following a first event of idiopathic VTE was conducted. Search terms included venous thromboembolism, anticoagulation, duration of treatment, warfarin, and idiopathic. STUDY SELECTION AND DATA EXTRACTION: The results of all trials and meta-analyses that were obtained are reviewed and critiqued. DATA SYNTHESIS: The risk of recurrent VTE following a first idiopathic event is similar to the risk in patients with a permanent risk factor. Conventional-intensity oral anticoagulant therapy reduces this risk by 80-90%, but at an annual risk of bleeding of approximately 2-3%. According to the PREVENT trial, low-intensity anticoagulation also affords protection against VTE recurrence, but at a lower risk of bleeding. Older trials indicated that longer therapy was superior to shorter therapy; however, data from recent trials have demonstrated that the benefit was maintained only while receiving therapy. CONCLUSIONS: Patients with a first episode of idiopathic proximal VTE should be considered for indefinite anticoagulant therapy. The appropriate intensity of anticoagulation is still controversial; however, it appears that low-intensity treatment would be appropriate in most patients. For patients who will not continue therapy indefinitely, there does not appear to be any long-term benefit to extending the duration of therapy from 3 to 6 months.

Ambulatory Care↗
PubMed2005

Relative thromboembolic risks associated with COX-2 inhibitors.

OBJECTIVE: To evaluate the clinical literature on cyclooxygenase-2 (COX-2) inhibitors to determine whether a greater incidence of thromboembolic events is universal within the drug class. DATA SOURCES: A MEDLINE search was conducted (1996-March 2005) for key articles in the English language assessing the efficacy or safety of these agents. STUDY SELECTION AND DATA EXTRACTION: Randomized, double-blind, and controlled trials, as well as case-control and retrospective cohort studies, that assessed the cardiovascular safety of COX-2 inhibitors were reviewed. DATA SYNTHESIS: Seventeen published studies were reviewed, and the cardiovascular safety data were extracted from each trial. The mechanism by which COX-2 inhibitors may induce a thromboembolic event is likely multifactorial involving (1) COX-2-specific isoform binding affinity, (2) drug dose, (3) duration of therapy, and (4) cardiovascular risk profile of the patient. Evidence supports an association between cardiovascular adverse events and the use of rofecoxib, valdecoxib, and celecoxib. However, this risk is not equally distributed among the drugs. Given the relative paucity of data, lumiracoxib and etoricoxib cardiovascular effects remain uncertain. CONCLUSIONS: Each COX-2 inhibitor has a unique cardiovascular risk profile. Based on the current evidence, celecoxib is the safest COX-2 inhibitor when prescribed appropriately in the lowest possible dose for the shortest duration in the ideal target population.

Case-Control Studies↗
PubMed2024

An insight into the causal relationship between sarcopenia-related traits and venous thromboembolism: A mendelian randomization study.

BACKGROUND: As a geriatric syndrome, sarcopenia has a high prevalence in the old population and represents an impaired state of health with adverse health outcomes. A strong clinical interest in its relationship with venous thromboembolism (VTE), which is a complex trait disease with a heterogeneous annual incidence rate in different countries, has emerged. The relationship between sarcopenia and venous thromboembolism has been reported in observational studies but the causality from sarcopenia to VTE remained unclarified. We aimed to assess the causal effect of sarcopenia on the risk of VTE with the two-sample Mendelian randomization (MR) method. METHODS: Two sets of single-nucleotide polymorphisms (SNPs), derived from two published genome-wide association study (GWAS) meta-analyses and genetically indexing muscle weakness and lean muscle mass separately, were pooled into inverse variance weighted (IVW), weighted median and MR-Egger analyses. RESULTS: No evidence was found for the causal effect of genetically predicted muscle weakness (IVW: OR = 0.90, 95% CI = 0.76-1.06, p = 0.217), whole body lean mass (IVW: OR = 1.01, 95% CI = 0.87-1.17, p = 0.881) and appendicular lean mass (IVW: OR = 1.13, 95% CI = 0.82-1.57, p = 0.445) on the risk of VTE. However, both genetically predicted whole-body lean mass and appendicular lean mass can causally influence diabetes mellitus (IVW of whole-body lean mass: OR = 0.87, 95% CI = 0.78-0.96, p = 0.008; IVW of appendicular lean mass: OR = 0.71, 95% CI = 0.54-0.94, p = 0.014) and hypertension (IVW of whole-body lean mass: OR = 0.92, 95% CI = 0.87-0.98, p = 0.007; IVW of appendicular lean mass: OR = 0.84, 95% CI = 0.73-0.96, p = 0.013). CONCLUSIONS: Genetically predicted sarcopenia does not causally influence VTE directly, but it might still have an indirect effect on VTE incidence via diabetes mellitus and hypertension.

Humans↗
PubMed2005

Acquired activated protein C resistance associated with IgG antibodies against beta2-glycoprotein I and prothrombin as a strong risk factor for venous thromboembolism.

BACKGROUND: Venous thromboembolic events such as deep vein thrombosis and pulmonary embolism are common manifestations of antiphospholipid syndrome. Our aim was to clarify the roles of anti-phospholipid (aPL) antibodies in the pathogenesis of venous thromboembolism (VTE) in patients with systemic lupus erythematosus (SLE). METHODS AND RESULTS: We examined anti-cardiolipin/beta2-glycoprotein I (anti-CL/beta2-GPI) antibody concentrations, anti-phosphatidylserine/prothrombin (anti-PS/PT) antibody concentrations, and lupus anticoagulant (LA) activity in 87 patients with SLE (21 with VTE and 66 without thrombosis). Both anti-CL/beta2-GPI and anti-PS/PT antibodies strongly correlated with LA activity. Multivariate logistic analysis confirmed that both anti-CL/beta2-GPI and anti-PS/PT antibodies were significant independent risk factors for VTE (odds ratios = 4.98 and 7.54, respectively; 95% confidence intervals, 1.51-16.4 and 2.30-24.7, respectively). We therefore studied the in vitro effects of IgG fractions containing anti-CL/beta2-GPI or anti-PS/PT antibodies on the anticoagulant activity of activated protein C (APC) and found that purified IgG containing anti-CL/beta2-GPI or anti-PS/PT antibodies significantly hampered the anticoagulant activity of APC. We also studied the ability of IgG fractions to impede the anticoagulant activity of APC before and after complete removal of anti-CL/beta2-GPI or anti-PS/PT antibodies by adsorption. Removal of anti-CL/beta2-GPI or anti-PS/PT antibodies from all positive IgG samples clearly decreased the inhibitory effect of those samples on APC anticoagulant activity. CONCLUSIONS: Anti-CL/beta2-GPI and anti-PS/PT antibodies independently cause APC resistance, which may contribute to risk of VTE in patients with SLE.

Activated Protein C Resistance↗