Anti-thrombotic Prophylaxis Regimens Research Articles

Venous thrombosis risk factors in pregnant women.

Venous thromboembolism (VTE) is the third most common cause of death on Earth after myocardial infarctions and strokes, according to the World Health Organization (WHO). Pregnancy is a unique condition of woman, when enormous changes occur in functioning of the most important systems of homeostasis in a relatively short time. These are physiological hypercoagulation, slowing of blood flow, increase in circulating blood volume, etc. However, while being physiological, these changes increase the risks of venous thromboembolism by almost 6 times. In some cases, there appears an imbalance or dissociation between the functioning of natural antithrombotic systems and the activation of coagulation as aconsequence of genetically or acquired determined causes (genetic thrombophilia, antiphospholipid syndrome, comorbidities, obstetric complications and other exogenous and endogenous factors). Accordingly, identification of risk factors, their systematization, and determination of VTE risks in pregnancy and puerperium is one of the mostimportant tasks of clinical medicine. Various recommendations have appeared for practitioners during the last 10-15 years on the basis of the risk factors analysis in order to prevent VTE in pregnant women more effectively. Nevertheless, none of these recommendations can yet take into account all risk factors, although convenient scoring systems have emerged for risk assessment and clear recommendations on anti-thrombotic prophylaxis regimens in risk groups in recent years. This article will review historical understanding of thrombosis in pregnant women, progress in understanding VTE risk factors in pregnant women, and available reserves in identifying new risk factors during pregnancy and puerperium in order to stratify risks more efficiently.

Venous thrombosis risk factors in pregnant women.

Assess all risk factors of venous thromboembolism (VTE) in pregnancy and puerperium. Different guidelines for VTE prevention have been analyzed. Various recommendations have appeared for practitioners during the last 10-15 years on the basis of the risk factors analysis in order to prevent VTE in pregnant women more effectively. Nevertheless, none of these recommendations can yet take into account all risk factors, although convenient scoring systems have emerged for risk assessment and clear recommendations on anti-thrombotic prophylaxis regimens in risk groups in recent years. VTE is the third most common cause of death on Earth after myocardial infarctions and strokes, according to the World Health Organization. Pregnancy is a unique condition of woman, when enormous changes occur in functioning of the most important systems of homeostasis in a relatively short time. These are physiological hypercoagulation, slowing of blood flow, increase in circulating blood volume, etc. However, while being physiological, these changes increase the risks of venous thromboembolism by almost six times. In some cases, there appears an imbalance or dissociation between the functioning of natural antithrombotic systems and the activation of coagulation as a consequence of genetically or acquired determined causes (genetic thrombophilia, antiphospholipid syndrome, comorbidities, obstetric complications and other exogenous and endogenous factors). Accordingly, identification of risk factors, their systematization, and determination of VTE risks in pregnancy and puerperium is one of the most important tasks of clinical medicine. This article will review historical understanding of thrombosis in pregnant women, progress in understanding VTE risk factors in pregnant women, and available reserves in identifying new risk factors during pregnancy and puerperium in order to stratify risks more efficiently.

Venous Thromboembolism Prophylaxis among Elderly Heart Failure Patients and 60-Day Outcomes: An Analysis from ADHERE Linked to Medicare Claims

Background: Hospitalized medically ill patients are at increased risk for venous thromboembolism (VTE). While antithrombotic prophylaxis regimens have reduced VTE risk in medically ill patients, their effectiveness for post-discharge outcomes among HF patients is unknown. Methods: We used ADHERE registry data linked to Medicare claims. We included patients hospitalized from 2001 to 2004, discharged alive. Patients on warfarin or IV heparin were excluded. We estimated observed 60-day rates of mortality, thromboembolic events, major adverse cardiovascular events (MACE), and rehospitalization for HF using estimates based on the cumulative incidence function.

Risk Factors for Venous Thromboembolism and the Use of Antithrombotic Prophylaxis in Multiple Myeloma Patients Treated with Lenalidomide and Dexamethasone Combination Regimens.

Abstract 1385Poster Board I-407 Background:Lenalidomide and dexamethasone combination therapy (LEN/DEX) is efficacious in the treatment of multiple myeloma (MM). Venous thrombotic events (VTE) have been associated with LEN/DEX regimens in patients who may also have individual and disease-specific risk factors for VTE (Palumbo et al., Leukemia 2008). Fewer VTE events have been reported among patients receiving low-dose corticosteroids (Menon et al., 2008; Jacobus et al., 2008). Antithrombotic prophylaxis (AP) strategies based on risk factors have been proposed. Objectives:To assess the relationship between known VTE risk factors and the probability of prescription AP in a community-based cohort of MM patients receiving concomitant LEN/DEX therapy and to evaluate secular trends in prescribing patterns (exclusive of over-the-counter [OTC] aspirin). Methods:An analysis of MM patients treated with LEN/DEX from January 1, 2006 – April 30, 2008 (1H2008) was performed using the Integrated Healthcare Information Services (IHCIS) National Managed Care Benchmark Database from Ingenix, Inc. Diagnoses, procedures, and prescription medications were evaluated using ICD-9-CM, CPT, HCPCS, and NDC codes (IHCIS does not capture OTC drugs). VTE risk factors among MM patients were evaluated. The proportion of patients receiving AP regimens and the proportion of patients receiving high- (cumulative dose ≥ 480 mg over the initial 28 day cycle) or medium-dose (cumulative dose ≤ 480 mg, but > 160 mg) dexamethasone vs. low-dose dexamethasone (cumulative dose ≤ 160 mg) were also evaluated. AP prophylaxis was assessed during the first 120 days of LEN/DEX therapy or prior to VTE event in patients who experienced VTE within the first 120 days of therapy. Risk factors present prior to the initial LEN/DEX prescription included age, gender, previous VTE, other peripheral vascular disease, congestive heart failure, atrial fibrillation, diabetes, chronic renal disease, respiratory failure, use of central venous catheter, recent (≤ past 90 days) stroke, recent infection, recent surgery, recent hospitalization, recent chemotherapy, recent use of erythropoietin-stimulating agents and number of risk factors (>2 vs. 0-2). Outcomes of interest included secular trends by half-year in the proportion of patients receiving AP regimens in combination with LEN/DEX and in the proportion of patients receiving high/medium vs. low dose dexamethasone regimens. Odds ratios (OR) with 95% confidence intervals (CI) were estimated from a multivariate logistic regression model of AP use as a function of identified risk factors with a p-value ≤ 0.10 for selection into the model. Results:Among 570 patients receiving LEN/DEX between 2006 – 1H2008, 14.0% received prescription AP. Among patients receiving high/medium DEX, 16.3% received AP; among patients receiving low DEX 12.2% received AP. No secular trend in the overall proportion of LEN/DEX patients receiving prophylaxis was observed. Nearly half (47.7%) of the patients had >2 risk factors; among these higher risk patients, 20% received prescription AP. For the half years 1H2007, 2H2007, and 1H2008, the proportion of all patients starting LEN/DEX regimens with low-dose dexamethasone increased from 55.6% to 76.3% to 81.5%, respectively.Independent positive predictors of prescription AP use include prior chemotherapy (OR=2.71; CI=1.49, 4.90), recent infection (OR=2.16; CI=0.88, 5.32), renal failure (OR=1.72; CI=0.97, 3.05), high/medium dexamethasone dose (OR=1.64; CI=0.98, 2.75), and >2 risk factors (OR=1.63; CI=0.89, 2.99). Patients with respiratory failure (OR=0.23; CI 0.05, 1.01) were less likely to receive AP therapy. Conclusions:The likelihood of prescription AP is increased by the presence and the number of several VTE risk factors. Recent prescribing trends favoring the use of low-dose dexamethasone among community MM patients may enhance the risk-benefit ratio of LEN/DEX therapy through reduction in VTE events. Disclosures:Brandenburg: Celgene Corporation: Employment, Equity Ownership. Knight: Covance, Inc: Employment, Equity Ownership; Celgene Corporation: Consultancy. Vassilev: Covance, Inc: Employment, Equity Ownership; Celgene Corporation: Consultancy. Knight: Celgene Corporation: Employment.

Evaluation of the Relationship Between Venous Thromboembolism Risk Factors and the Use of Antithrombotic Prophylaxis in Multiple Myeloma Patients Treated with Thalidomide and Dexamethasone Combination Regimens

Background: The efficacy of the thalidomide and dexamethasone combination regimens (T+D) in the treatment of multiple myeloma (MM) has been documented. Venous thrombotic events (VTE) have been associated with T+D regimens in patients who may also have individual and disease-specific risk factors for VTE. Antithrombotic prophylaxis (AP) strategies based upon risk factors recently have been proposed (Palumbo et al., Leukemia 2007).Objectives: To assess the relationship between known VTE risk factors on the probability of prescription antithrombotic prophylaxis (AP) in a community-based cohort of MM patients receiving T+D and to evaluate secular trends in prescribing patterns (exclusive of over-the-counter (OTC) aspirin).Methods: An analysis of MM patients treated with T+D from 2004–2007 was performed using the IHCIS National Managed Care Benchmark Database from Ingenix, Inc. Diagnoses, procedures and medications were evaluated using ICD-9-CM, CPT, HCPCS and NDC codes. VTE risk factors among MM patients were evaluated as were secular trends in the proportion of patients receiving AP regimens (exclusive of OTC aspirin therapy) and the proportion of patients receiving high-dose (cumulative dose ≥480 mg over the initial 28 day cycle) vs. low-dose dexamethasone (cumulative dose ≤ 160 mg). Risk factors present prior to T+D therapy (as identified by Palumbo et al.) included age, congestive heart failure, atrial fibrillation, recent (≤ past 90 days) stroke, other peripheral vascular disease, diabetes, infection, chronic renal disease, recent surgery, recent hospitalization, use of central venous catheter, chemotherapy, and use of erythropoietin-stimulating agents (ESA). Outcomes of interest included secular trends by half-year in the proportion of patients receiving AP regimens in combination with T+D and in the proportion of patients receiving high vs. low dose dexamethasone regimens. Odds ratios (OR) with 95% confidence intervals (CI) were estimated from a multivariate logistic regression model of AP use as a function of identified risk factors with a p-value ≤ 0.10 for retention in the model.Results: Among 1732 patients first receiving T+D between 2004–2007, 12.4% received prescription AP simultaneously with T+D, and no secular trend in the overall proportion of T+D patients receiving prophylaxis was observed. In 2007, the proportion of all patients starting T+D regimens with low-dose dexamethasone was 35.9% in the first half of the year in contrast to 58.7% in the second half of the year. Among all patients, 66.3% had at least one risk factor. Among patients with at least two risk factors (N=837; 48.3%), 14.7% received prescription AP simultaneously with T+D. Independent predictors of prescription AP use include age (OR=0.98; CI= 0.97, 1.00), stroke (OR=3.06; CI=0.88, 10.66), peripheral vascular disease (OR=2.69; CI=1.47, 4.93), recent surgery (OR=1.93; CI=1.42, 2.62), and concomitant ESA use (OR=1.67; CI=1.19, 2.34).Conclusions: While the likelihood of thromboprophylaxis is increased in the presence of several well-known risk factors, additional consideration of thromboprophylaxis among patients with recognized VTE risk factors may be clinically warranted. Further reductions in VTE events may be anticipated should recent prescribing patterns of T+D employing low-dose dexamethasone continue.

Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery.

A point mutation in coagulation factor V (A1691G) is associated with increased risk for venous thrombosis. However, limited information is available about the prospective risk for deep venous thrombosis in specific high-risk clinical settings. To determine whether the factor V Leiden mutation is associated with an increased occurrence of deep venous thrombosis in patients undergoing hip or knee replacement surgery. Retrospective analysis of plasma samples obtained during six prospective clinical trials that compared different antithrombotic prophylaxis regimens in patients undergoing hip or knee replacement surgery. Inpatients at the University of Rochester Medical Center, McMaster University Medical Center, Hamilton Civic Hospitals, and the Genesee Hospital. 825 patients hospitalized for hip or knee replacement surgery. Venographically diagnosed postoperative deep venous thrombosis was correlated with factor V genotype. The factor V Leiden mutation was not associated with a significantly increased risk for venographically detected deep venous thrombosis. The absolute incidence of deep venous thrombosis was 31% (95% CI, 15% to 47%) in patients with the mutation and 26% (CI, 22% to 29%) in patients without the mutation (relative risk, 1.2 [CI, 0.6 to 2.9]). The factor V Leiden mutation was not significantly associated with deep venous thrombosis in subgroups of patients receiving warfarin or heparin. The incidence of clinical hemorrhage was similar in patients with (10%) and without (8%) the mutation. The factor V Leiden mutation is not a significant risk factor for acute deep venous thrombosis in this group of patients. Current data do not justify routine preoperative screening for this mutation or intensified perioperative prophylaxis in patients with the factor V Leiden mutation who are undergoing hip or knee joint replacement surgery and are receiving effective antithrombotic prophylaxis.