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Biomedical subjects

John A Heit

Publications and source records attributed to John A Heit.

At least 19 recordsLinked to original sources
PubMed2006

Estrogen therapy and thrombotic risk.

Post-menopausal hormone therapy increases the risk for venous thrombosis, and possibly myocardial infarction (MI) and ischemic stroke. However, most women using hormone therapy do not suffer thrombosis, and to date our ability to identify women at risk is limited. Thrombosis, arterial or venous, has 2 requisites: a vascular anomaly and a response of the hemostasis system to the anomaly. Consequently, experimental approaches to understand the pathophysiology of thrombosis require definition of vascular anatomy and function as well as characteristics of the blood within the context of genetic background, lifestyle choices and environmental exposures, which influence gene expression. Defining interactions among factors that affect individual propensity to thrombosis will allow physicians to better identify at-risk individuals, for example a woman contemplating estrogen therapy for symptoms of menopause, and prevent adverse thrombotic events.

Arteries↗
PubMed2006

The epidemiology of venous thromboembolism in the community: implications for prevention and management.

The epidemiology of venous thromboembolism (VTE) in the community has important implications for VTE prevention and management. This review describes the incidence, survival, recurrence, complications and risk factors for deep vein thrombosis and pulmonary embolism occurring in the community. VTE incidence among whites of European origin exceeds 1 per 1000; the incidence among persons of African and Asian origin may be higher and lower, respectively. VTE incidence over recent time remains unchanged. Survival after VTE is worse than expected, especially for pulmonary embolism where one-quarter of patients present as sudden death. Of those patients who survive, 30% develop VTE recurrence and venous stasis syndrome within 10 and 20 years, respectively. Common independent VTE risk factors include surgery, hospitalization for acute medical illness, nursing home confinement, trauma, active cancer, neurologic disease with extremity paresis, superficial vein thrombosis, central venous catheter/transvenous pacemaker, and among women, oral contraceptives, pregnancy and the puerperium, and hormone and SERM therapy. Exposures can identify populations at risk but have a low predictive value for the individual person. An acquired or familial thrombophilia may predict the subset of exposed persons who actually develop symptomatic VTE. In conclusion, VTE is a common, lethal disease that recurs frequently and causes serious long-term complications. To improve survival and prevent complications, VTE occurrence must be reduced. Better individual risk stratification is needed in order to modify exposures and target primary and secondary prophylaxis to the person who would benefit most.

Epilepsy, Tonic-Clonic↗
PubMed2005

Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study.

OBJECTIVES: We sought to determine the association between patent foramen ovale (PFO), atrial septal aneurysm (ASA), and stroke prospectively in a unselected population sample. BACKGROUND: The disputed relationship between PFO and stroke reflects methodologic weaknesses in studies using invalid controls, unblinded transesophageal echocardiography examinations, and data that are unadjusted for age or comorbidity. METHODS: The use of transesophageal echocardiography to identify PFO was performed by a single echocardiographer using standardized definitions in 585 randomly sampled, Olmsted County (Minnesota) subjects age 45 years or older participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. RESULTS: A PFO was identified in 140 (24.3%) subjects and ASA in 11 (1.9%) subjects. Of the 140 subjects with PFO, 6 (4.3%) had an ASA; of the 437 subjects without PFO, 5 had an ASA (1.1%, two-sided Fisher exact test, p = 0.028). During a median follow-up of 5.1 years, cerebrovascular events (cerebrovascular disease-related death, ischemic stroke, transient ischemic attack) occurred in 41 subjects. After adjustment for age and comorbidity, PFO was not a significant independent predictor of stroke (hazard ratio 1.46, 95% confidence interval 0.74 to 2.88, p = 0.28). The risk of a cerebrovascular event among subjects with ASA was nearly four times higher than that in those without ASA (hazard ratio 3.72, 95% confidence interval 0.88 to 15.71, p = 0.074). CONCLUSIONS: These prospective population-based data suggest that, after correction for age and comorbidity, PFO is not an independent risk factor for future cerebrovascular events in the general population. A larger study is required to test the putative stroke risk associated with ASA.

Aged↗
PubMed2005

Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study.

BACKGROUND: The risk for venous thromboembolism during pregnancy or postpartum is uncertain. OBJECTIVES: To estimate the relative and absolute risk for deep venous thrombosis and pulmonary embolism during pregnancy and postpartum and to describe trends in incidence. DESIGN: Population-based inception cohort study using the resources of the Rochester Epidemiology Project. SETTING: Olmsted County, Minnesota. PATIENTS: Women with deep venous thrombosis or pulmonary embolism first diagnosed between 1966 and 1995, including women with venous thromboembolism during pregnancy or the postpartum period (defined as delivery of a newborn no more than 3 months before the deep venous thrombosis or pulmonary embolism event date, including delivery of a stillborn infant after the first trimester). MEASUREMENTS: The authors obtained yearly counts of live births in Olmsted County between 1966 and 1995 from the Minnesota Department of Health. RESULTS: The relative risk (standardized incidence ratio) for venous thromboembolism among pregnant or postpartum women was 4.29 (95% CI, 3.49 to 5.22;P < 0.001), and the overall incidence of venous thromboembolism (absolute risk) was 199.7 per 100,000 woman-years. The annual incidence was 5 times higher among postpartum women than pregnant women (511.2 vs. 95.8 per 100,000), and the incidence of deep venous thrombosis was 3 times higher than that of pulmonary embolism (151.8 vs. 47.9 per 100,000). Pulmonary embolism was relatively uncommon during pregnancy versus the postpartum period (10.6 vs. 159.7 per 100,000). Over the 30-year study period, the incidence of venous thromboembolism during pregnancy remained relatively constant whereas the postpartum incidence of pulmonary embolism decreased more than 2-fold. LIMITATIONS: Because the Olmsted County population was 98% white and of non-Hispanic ethnicity, the results may not be generalizable to other ethnicities. CONCLUSIONS: Among pregnant women, the highest risk period for venous thromboembolism and pulmonary embolism in particular is during the postpartum period. Any prophylaxis against these events should be particularly targeted to postpartum women. Although the incidence of pulmonary embolism has decreased over time, the incidence of deep venous thrombosis remains unchanged, indicating the need to better identify pregnant women at increased risk.

Adolescent↗
PubMed2005

The clinical challenge of bridging anticoagulation with low-molecular-weight heparin in patients with mechanical prosthetic heart valves: an evidence-based comparative review focusing on anticoagulation options in pregnant and nonpregnant patients.

BACKGROUND: Recent labeling changes for enoxaparin, a low-molecular-weight heparin (LMWH), have prompted a reexamination of its role in patients with mechanical prosthetic heart valves (MPHVs). Healthcare providers are faced with the challenge of weighing favorable trial results with LMWHs and balancing their clinical experiences with these agents as a bridge to oral anticoagulation in patients with prosthetic heart valves. This review will provide evidence-based guidance on issues surrounding the use of LMWH that require bridging anticoagulant therapy in the setting of cardiac surgery (MPHVs), cardiovascular disease, and during temporary interruption of oral anticoagulants in patients requiring periprocedural bridging therapy. METHODS: A Medline search was conducted of articles appearing in the medical literature published in English between 1992 and 2004. Approximately 120 clinical trials, case reports, editorials, and/or guideline statements were retrieved and reviewed by the authors as to their relevance for the subject under review, ie, bridging anticoagulation in patients with MPHVs. Approximately 80 of these publications were selected for detailed review, analysis, and discussion in a consensus format. RESULTS: This review addresses the controversy surrounding the divergence between the new labeling recommending against the use of LMWH in patients with MPHVs as well as the ongoing clinical experience and evidence in the medical literature. The clinical challenges in the use of LMWH and unfractioned heparin (UFH) in pregnant patients with MPHVs are presented; the evidence for LMWHs in nonpregnant patients with prosthetic valves is described; and the role of LMWH for bridging immediately after mechanical valve surgery and its periprocedural and perioperative uses are discussed. Based on an expert consensus panel, clinical algorithms for the use of LMWH in pregnant and nonpregnant patients with MPHVs are also illustrated. CONCLUSIONS: Based on the available data sets, clinical trials, reviews, and registry data, the evidence suggests that LMWH compared to UFH may be a safe and effective agent in patients with MPHVs. Future large-scale, randomized trials are warranted.

Anticoagulants↗
PubMed2005

Thrombomodulin gene polymorphisms or haplotypes as potential risk factors for venous thromboembolism: a population-based case-control study.

Dysfunction of the protein C anticoagulant system is associated with venous thromboembolism (VTE) and thrombomodulin (TM) is a critical cofactor within the protein C system. The aim of this study was to test the hypotheses that polymorphisms or haplotypes within the TM gene are common risk factors for VTE. We screened the TM putative promoter, exon and 3'-untranslated region for sequence variations in a random sample (n = 266) of consecutive idiopathic, objectively confirmed non-Olmsted County VTE patients referred to the Mayo Clinic. We then genotyped a sample of Olmsted County, MN residents with a first lifetime, objectively confirmed VTE in the 25-year period, 1966-90 (n = 223), and a sample of Olmsted County residents without VTE (n = 237) for polymorphisms either discovered in the screening population or previously published, and tested for an association of VTE with TM genotype or haplotypes using unconditional logistic regression and generalized linear models, respectively. We also genotyped these Olmsted County cases and controls at 20 'null' genetic maker loci and tested for population admixture. Nine novel and three previously described mutations were identified in the screening population. Mutations within the TM promoter, EGF(1-5), serine/threonine-rich, transmembrane, and cytoplasm regions were absent or uncommon. TM845G-->A (Ala25Thr; lectin region), TM2136T-->C (Ala455Val; EGF(6) region), TM2470C deletion (3'-untranslated region), and 4363A-->G (3'-flanking region) were more common, but were not associated with VTE by genotype or haplotype. Null genetic marker allele frequencies did not differ significantly among cases and controls. We conclude that polymorphisms or haplotypes within the TM gene are not common risk factors for incident VTE.

Adult↗
PubMed2004

Thromboembolism in adults with acute lymphoblastic leukemia during induction with L-asparaginase-containing multi-agent regimens: incidence, risk factors, and possible role of antithrombin.

Thromboembolism (TE) is a known complication of L-asparaginase (ASP) therapy of acute lymphoblastic leukemia (ALL), possibly attributable to reduced synthesis of natural anticoagulants, in particular antithrombin (AT). This retrospective single institution study was performed to determine the TE incidence among adults undergoing induction with contemporary, ASP-containing regimens. Ten of 54 (18.5%) consecutive adults developed symptomatic, objectively confirmed TE, at a median of 5.5 days after the first ASP dose. These were notable for CNS and upper extremity localization, varied significantly according to ALL immunophenotype (precursor B: 11% vs. T cell: 33%), without apparent effect of schedule or total dose of ASP. Median baseline AT level was 94% and fell to a nadir of 47% (P < 0.0001) during ASP therapy. Prophylactic AT had been given to 17 during ASP therapy. None of these developed TE vs. 10/37 (27%) without replacement (P = 0.021). These observations merit further study to gain insight into disease and/or therapy-specific pathogenesis of TE in this population and call for the prospective evaluation of appropriate prophylactic interventions.

Adolescent↗
PubMed2004

Thrombophilia and new anticoagulant drugs.

Venous thromboembolism, which includes deep vein thrombosis and pulmonary embolism, is the result of an imbalance among procoagulant, anticoagulant and profibrinolytic processes. This imbalance reflects a complex interplay between genetic and environmental or acquired risk factors. Genetic thrombophilic defects influence the risk of a first episode of thrombosis. How these defects influence the risk of recurrence in patients whose first episode of venous thromboembolism was unprovoked is less certain. Thus, when anticoagulants are stopped, patients with unprovoked venous thromboembolism have a risk of recurrence of at least 7% to 10% per year, even in the absence of an underlying thrombophilic defect. Consequently, there is a trend toward longer durations of anticoagulation therapy for these patients, which is problematic given the limitation of existing anticoagulants. This chapter provides an overview of the thrombophilic defects and how they influence the risk of venous thromboembolism. The chapter also details advances in anticoagulant therapy, focusing on new inhibitors of factor Xa and thrombin. In Section I, Dr. Saskia Middeldorp describes the various thrombophilic defects and reviews their relative importance in the pathogenesis of a first episode of venous thromboembolism. She then discusses the influence of these defects on the risk of recurrent thrombotic events in patients with unprovoked venous thromboembolism and in those whose thrombosis occurred in association with a known risk factor, such as surgery. In Section II, Dr. William Geerts reviews the pharmacology of new parenteral and oral factor Xa inhibitors and describes the results of the Phase II and III clinical trials with these agents. He then provides perspective on the potential advantages and drawbacks of these drugs for the prevention and treatment of venous thromboembolism. In Section III, Dr. John Heit focuses on direct thrombin inhibitors. He discusses their mechanism of action and compares and contrasts their pharmacological profiles prior to describing the results of Phase II and III clinical trials. Dr. Heit then provides perspective on the potential advantages and limitations of these drugs relative to existing anticoagulants.

Anticoagulants↗
PubMed2004

Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

This article discusses the prevention of venous thromboembolism (VTE) and is part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. Grade 1 recommendations are strong and indicate that the benefits do, or do not, outweigh risks, burden, and costs. Grade 2 suggests that individual patients' values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this chapter are the following. We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A). For moderate-risk general surgery patients, we recommend prophylaxis with low-dose unfractionated heparin (LDUH) (5,000 U bid) or low-molecular-weight heparin (LMWH) [< or = 3,400 U once daily] (both Grade 1A). For higher risk general surgery patients, we recommend thromboprophylaxis with LDUH (5,000 U tid) or LMWH (> 3,400 U daily) [both Grade 1A]. For high-risk general surgery patients with multiple risk factors, we recommend combining pharmacologic methods (LDUH three times daily or LMWH, > 3,400 U daily) with the use of graduated compression stockings and/or intermittent pneumatic compression devices (Grade 1C+). We recommend that thromboprophylaxis be used in all patients undergoing major gynecologic surgery (Grade 1A) or major, open urologic procedures, and we recommend prophylaxis with LDUH two times or three times daily (Grade 1A). For patients undergoing elective total hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or adjusted-dose vitamin K antagonist (VKA) [international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0] (all Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1C+), VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 2B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty, or HFS receive thromboprophylaxis for at least 10 days (Grade 1A). We recommend that all trauma patients with at least one risk factor for VTE receive thromboprophylaxis (Grade 1A). In acutely ill medical patients who have been admitted to the hospital with congestive heart failure or severe respiratory disease, or who are confined to bed and have one or more additional risk factors, we recommend prophylaxis with LDUH (Grade 1A) or LMWH (Grade 1A). We recommend, on admission to the intensive care unit, all patients be assessed for their risk of VTE. Accordingly, most patients should receive thromboprophylaxis (Grade 1A).

Anticoagulants↗
PubMed2004

Sensitivity and specificity of the semiquantitative latex agglutination D-dimer assay for the diagnosis of acute pulmonary embolism as defined by computed tomographic angiography.

OBJECTIVE: To determine the sensitivity and specificity of the semiquantitative latex agglutination plasma fibrin D-dimer assay for the diagnosis of acute pulmonary embolism by using computed tomographic (CT) angiography as the diagnostic reference standard. PATIENTS AND METHODS: From January 1, 1998, to June 26, 2000, patients who had both semiquantitative latex agglutination plasma fibrin D-dimer testing and CT angiography for suspected acute pulmonary embolism were selected for the study. A D-dimer value greater than 250 ng/mL was considered positive for thromboembolic disease. Diagnosis of acute pulmonary embolism was based solely on the interpretation of the CT angiogram. The D-dimer assay results were then compared with the CT angiographic diagnoses. RESULTS: Of 946 CT studies, 172 (18%) were positive for acute pulmonary embolism. The D-dimer assay was positive for 612 (65%) of the 946 patients. For acute pulmonary embolism, the D-dimer assay had a sensitivity of 0.83 (95% confidence interval [CI], 0.76-0.88), a specificity of 039 (95% CI, 036-0.43), a negative likelihood ratio of 0.44 (95 % CI, 032-0.62), and a negative predictive value of 0.91 (95% CI, 0.87-0.94). CONCLUSIONS: The semiquantitative latex agglutination plasma fibrin D-dimer assay had moderate sensitivity and low specificity for the diagnosis of acute pulmonary embolism. When used alone, the results of this test were insufficient to exclude this serious and potentially fatal disorder. Approximately two thirds of our patients had positive D-dimer assays and required further evaluation to exclude acute pulmonary embolism.

Adolescent↗
PubMed2004

Clinical importance of positive test results for lupus anticoagulant and anticardiolipin antibodies.

OBJECTIVES: To assess the performance of 4 clotting assays for lupus anticoagulant (LA) detection, to determine the prevalence of LA and anticardiolipin antibodies (aCL), and to correlate LA and aCL prevalence with systemic disease and thrombosis. PATIENTS AND METHODS: We studied 664 consecutive patients at the Mayo Clinic in Rochester, Minn, who were referred for laboratory testing because of a clinical suspicion of LA or thrombophilia between June 25, 1990, and July 1, 1991. RESULTS: Of 664 patients tested for LA, 584 also were tested for aCL. Of patients tested for both LA and aCL, 137 (235%) had positive results for one or both tests (13 [95%], LA-positive only; 76 [555%], aCL-positive only; and 48 [35.0%], positive for both). The dilute Russell viper venom time (DRVVT) was the most frequently positive LA assay (74% of the 61 patients with positive results for LA). Twenty-two patients (36.1% of the 61) had positive results for all 4 LA assays, whereas 21 (34.4% of the 61) had positive results for only 1 LA assay: activated partial thromboplastin time (3 patients [4.9%]), plasma clot time (5 patients [8.2%]), kaolin clot time (5 patients [8.2%]), or DRVVT (8 patients [13.1%]). Thromboembolism prevalence was not definitely associated with positive test results (LA only, aCL only, or LA plus aCL), nor was it strongly associated with aCL isotype or titer. Furthermore, thromboembolism prevalence was not increased when all LA assays were positive, although a history of deep venous thrombosis or pulmonary embolism was nonsignificantly associated with positive results for all 4 LA tests. The likelihood of having both LA- and aCL-positive test results was higher among patients with systemic lupus erythematosus (26 [19.0%] of 137 patients with positive results for one or both tests), but they had no more thrombotic events or fetal loss than other patients in our study group. CONCLUSIONS: The DRVVT identified more patients with LA than the other LA tests, but more than 1 LA test was required to identify all patients with LA. Positive results were much more common for aCL than for LA. No single LA test or anticardiolipin isotype correlated with thrombosis or systemic disease in this population.

Antibodies, Anticardiolipin↗
PubMed2003

Risk factors for venous thromboembolism.

Venous thromboembolism is a common and potentially lethal disease. Patients who have pulmonary embolism are at especially high risk for death. Death owing to pulmonary embolism is independent of other comorbid conditions (e.g., cancer, chronic heart disease, or lung disease). Sudden death is often the first clinical manifestation. Only a reduction in the incidence of venous thromboembolism can reduce sudden death owing to pulmonary embolism and venous stasis syndrome owing to deep vein thrombosis. The incidence of venous thromboembolism has been relatively constant since about 1980. Improvement in the incidence of venous thromboembolism will require better recognition of persons at risk, improved estimates of the magnitude of risk, the avoidance of risk exposure when possible, more widespread use of safe and effective prophylaxis when risk is unavoidable, and targeting of prophylaxis to those persons who will benefit most. Recognition of venous thromboembolism as a multifactorial disease with genetic and genetic-environmental interaction has provided significant insights into its epidemiology and offers the possibility of improved identification of persons at risk for incident and recurrent venous thromboembolism.

Humans↗
PubMed2003

Venous stasis syndrome: the long-term burden of deep vein thrombosis.

Currently there is no cure for venous stasis syndrome, a common complication of deep vein thrombosis. Prophylaxis with anticoagulant agents, including new drugs presently under investigation, may decrease the incidence and costs associated with this condition.

Factor Xa Inhibitors↗
PubMed2003

The potential role of direct thrombin inhibitors in the prevention and treatment of venous thromboembolism.

Venous thromboembolism (VTE) is a common and potentially lethal disease that recurs frequently and is associated with long-term impairment and suffering. Despite a great deal of effort, the incidence of VTE has not changed substantially in the last 20 years. Independent risk factors include hospitalization (either for surgery or for acute medical illness), trauma, malignant neoplasm, central venous catheters or transvenous pacemakers, superficial vein thrombosis, and extremity paresis. Of these, hospitalization accounts for almost 60% of all VTE occurring in the community. Thus, universal effective prophylaxis of hospitalized patients would significantly reduce the incidence of VTE. Parenteral direct thrombin inhibitors are safe and effective for both prevention and treatment of acute VTE, and do not require laboratory monitoring or dose adjustment. Oral direct thrombin inhibitors may also be safe and effective, and offer enhanced convenience without diet or drug-drug interactions.

Humans↗
PubMed2002

Venous thromboembolism hospitalizations among American Indians and Alaska Natives.

Cardiovascular disease (CVD) has been reported to be on the increase in the American Indian/Alaska Native (AI/AN) population. The Indian Health Service (IHS) hospital discharge database was used to describe venous thromboembolism (VTE)-associated hospitalizations among patients receiving IHS-reported medical care in the United States from 1980 through 1996. The average overall VTE-associated hospitalization rate in the AI/AN population during 1980-1996 was 33.1 per 100,000, however, the rate significantly decreased from 38.4 per 100,000 AI/ANs in 1980-1982 to 33.2 in 1994-1996. The average age at hospitalization was 50.4 years, which was consistent during the 17-year period. The overall annual VTE hospitalization rate was higher for females than for males (38.0 versus 27.7 per 100,000). The female VTE hospitalization rates decreased significantly from 46.1 per 100,000 in 1980-1982 to 36.7 per 100,000 in 1994-1996 (risk ratio: RR=1.3; 95% confidence interval: CI=1.1-1.4), while the rates for males remained unchanged. The VTE hospitalization rates also varied by geographic region. The hospitalization rate was highest in the East region (52.2 per 100,000) and lowest in the Alaska region (16.1 per 100,000). These data indicate that the overall VTE rate for AI/ANs may not have only decreased, but appears lower than the reported rate for Caucasians.

Adolescent↗