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PubMed2004

Anti-prothrombin antibodies as a potential risk factor of recurrent venous thromboembolism.

The role of antiprothrombin (aPT) antibodies in the development of venous thromboembolism (VTE) is still uncertain. The aim of this study was to evaluate the potential role of aPT antibodies in the development of recurrent thromboembolism. Out of 236 consecutive symptomatic patients with an episode of acute VTE, antiphospholipid antibodies were found in 85 (36.0%), of whom 24 were carriers of aPT antibodies (10.2% of the entire cohort). A history of previous thromboembolism was identified in 56 patients (23.7%). The prevalence of previous thromboembolism was significantly higher in carriers than in non-carriers of antiphospholipid antibodies (OR=2.4; 95% CI, 1.3 to 4.4). Of the 24 patients with aPT antibodies, 12 had a history of previous thromboembolism. In a multivariate logistic regression analysis, in which the other categories of antiphospholipid antibodies were taken into account, as well as the patient's age, sex, and the modality of clinical presentation, it was found that the presence of aPT antibodies was significantly associated with the prevalence of prior thromboembolism (OR=3.3; 95% CI, 1.3 to 8.6). Since aPT antibodies are more commonly identifiable in patients with multiple thrombotic episodes, they are a likely risk factor for recurrent thromboembolism.

Adult↗
PubMed2002

Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): prednisone versus dexamethasone administration.

Alterations in hemostasis leading to symptomatic thromboembolism have been observed in patients with acute lymphoblastic leukemia (ALL) receiving Escherichia coli asparaginase (CASP) combined with steroids. Moreover, hereditary prothrombotic risk factors are associated with an increased risk for venous thromboembolism in pediatric ALL patients treated according to the BFM 90/95 protocols (including CASP combined with prednisone during induction therapy). To assess whether the thromboembolic risk associated with established prothrombotic risk factors is modified by treatment modalities (prednisone or dexamethasone), the present analysis was performed. Three hundred thirty-six consecutively recruited leukemic children treated according to different BFM protocols (PRED group, n = 280, 60 mg/m(2) prednisone; DEXA group, n = 56, 10 mg/m(2) dexamethasone during induction therapy) were studied. Study end point was the onset of symptomatic vascular accidents during induction therapy. Cumulative thromboembolism-free survival was significantly reduced in children in the PRED group (thrombosis frequency, 10.4%) compared with children in the DEXA group (thrombosis frequency, 1.8%; P =.028). Although no significant difference was found in the overall prevalence of prothrombotic risk factors, 46.5% of patients in the PRED group who experienced thromboembolic events were carriers of a prothrombotic risk factor, whereas no carrier in the DEXA group had a thromboembolism. At the time of maximum CASP activity, fibrinogen and activities of antithrombin, plasminogen, and protein S were significantly reduced in the PRED group. No significant correlation could be found between CASP activity and levels of coagulation factors. In conclusion, the use of dexamethasone instead of prednisone, administered with CASP, significantly reduced the onset of venous thromboembolism.

Adolescent↗
PubMed2006

Accumulation of risk factors increases risk of thromboembolic events in patients with nonvalvular atrial fibrillation.

BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSION: Accumulation of risk factors could increase risk of thromboembolic events in patients with NVAF. Adherence to the guidelines for anticoagulation therapy is recommended.

Aged↗
PubMed2005

A feasibility study of continuing dose-reduced warfarin for invasive procedures in patients with high thromboembolic risk.

BACKGROUND: The management of perioperative anticoagulation therapy for patients having a high risk of thromboembolism who are receiving long-term oral anticoagulant therapy is uncertain. The prevalent approach is to discontinue oral anticoagulation therapy and initiate heparin therapy. Another potential strategy is to continue oral anticoagulation therapy with a temporary adjustment of warfarin intensity to a preoperative international normalized ratio (INR) of 1.5 to 2.0. Such moderate-dose anticoagulation therapy with warfarin has been shown to be hemostatically safe yet effective in the prevention of thromboembolism after hip or knee replacement. METHODS: Over an 11-year period (ie, 1993 to 2003), our hemostatic consultative service prospectively identified 100 consecutive patients for whom we continued warfarin therapy at adjusted doses during the perioperative period, targeting a goal for the INR of 1.5 to 2.0. Patients were assigned a score for venous thromboembolic risk as well as overall surgical risk using published instruments. Score assignment was based on what was deemed to be extremely high risk for thromboembolism in patients who were receiving long-term warfarin therapy. Although the patients were accrued prospectively, the final retrospective analysis was made after all patients were treated. RESULTS: The most common indication (62%) for high-risk assignment was a thromboembolic event within the past 6 months. The second most prevalent reason was prior postoperative venous thromboembolism (VTE) [11%]. Indications for long-term anticoagulation therapy were recent VTE (62%), inherited thrombophilia (7%), antiphospholipid syndrome (13%), mechanical heart valves (18%), and prior cerebrovascular accident (4%). The prevalence of inherited thrombophilia probably has been grossly underestimated, as neither factor V Leiden mutation nor prothrombin 20210 mutation had been described during the bulk of the accrual time. Most surgical procedures (58%) were significantly invasive (Johns Hopkins category 3 to 5). The mean INR values were 2.1 on the day prior to surgery (SD, 0.9594; range, 1.2 to 6.5; n = 65), 1.8 on the day of surgery (SD, 0.4899; range, 1.2 to 4.9; n = 75), and 1.8 on the first postoperative day (SD, 0.4436; range, 1.1 to 3.3; n = 70). Two patients had major bleeding, and four patients had minor bleeding. One patient developed deep venous thrombosis. Several weeks after surgery, one patient with a prosthetic heart valve died from an embolic stroke, which was associated with a failure to increase his anticoagulation to therapeutic levels. CONCLUSIONS: Moderate-intensity anticoagulant therapy with warfarin, targeting a goal INR of 1.5 to 2.0, appears to be a safe and feasible method for preventing thromboembolic complications in high-risk surgical patients who are receiving long-term oral anticoagulant therapy. This may be considered a reasonable method to afford thromboprophylaxis in highly selected patients who are occasionally seen in clinical practice. This observational study does not prove equality, let alone superiority, to other proposed methods of anticoagulation therapy.

Administration, Oral↗
PubMed2006

Incidence and economic implications of heparin-induced thrombocytopenia in medical patients receiving prophylaxis for venous thromboembolism.

STUDY OBJECTIVES: To determine the incidence of heparin-induced thrombocytopenia (HIT) in patients admitted to a medical service who were given unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) to prevent venous thromboembolism, the incremental cost of developing HIT, and the cost consequences of using LMWH to prevent venous thromboembolism in medical patients. DESIGN: Retrospective analysis with a nested case-control. SETTING: University-affiliated tertiary-care hospital. PATIENTS: A total of 10,121 adult medical patients admitted between August 1, 2000, and November 2, 2004, received UFH or LMWH to prevent venous thromboembolism during their admission. From these, patients with immune-mediated HIT were identified and served as case patients, and 3-5 matched control patients were identified for each case patient. MEASUREMENTS AND MAIN RESULTS: The development of HIT was determined for patients who received LMWH and for patients who received UFH. Costs were compared between the patients with HIT and the matched control patients. The cost of using LMWH to prevent venous thromboembolism was compared with the cost of using UFH. In patients receiving UFH and those receiving LMWH, the incidence of HIT was 0.51% (43/8420) and 0.084% (1/1189), respectively (p=0.037), with an overall incidence of 0.43% (44/10,121). Admissions that included development of HIT incurred an average cost of 56,364 dollars compared with 15,231 dollars (p<0.001) for admissions without HIT. Using LMWH to prevent venous thromboembolism in medical patients cost 13.88 dollars less per patient than using UFH. CONCLUSIONS: For the prophylaxis of venous thromboembolism, LMWH was associated with a lower incidence of HIT than UFH in medical patients. An admission during which the patient develops HIT costs significantly more than an admission during which the patient does not develop HIT. Low-molecular-weight heparin is cost-effective for prevention of venous thromboembolism in medical patients.

Anticoagulants↗
PubMedDate not supplied

Activated protein C resistance: the most common risk factor for venous thromboembolism.

BACKGROUND: Venous thromboembolism is a major cause of morbidity and mortality. Although activated protein C resistance (APC-R) is the most commonly recognized inherited risk factor for venous thromboembolism, little is known about its long-term implications on health. METHODS: MEDLINE was searched from January 1989 through August 1999 using the key words "thromboembolism," "thrombosis," "activated protein C resistance," and "factor V Leiden." RESULTS: One in 1000 people in the United States is affected by venous thromboembolism annually. APC-R is now understood to be responsible for up to 64% of these cases. APC-R, which occurs widely in some ethnic groups and is nearly absent in others, is due to a single point mutation in the gene for clotting factor V. As a result, inactivation of factor V by activated protein C is impaired, leading to a hypercoagulable state. This condition creates a lifelong increased risk of thrombosis and, possibly, anticoagulant therapy.. CONCLUSION: Family physicians have a new tool for assessing risks for venous thromboembolism. Recognizing that up to 64% of patients with venous thromboembolism can have APC-R and treating this disorder with prophylactic and therapeutic anticoagulation might reduce patient morbidity and mortality from venous thromboembolism. Screening high-risk patients might now be indicated.

Activated Protein C Resistance↗
PubMed1992

Predictors of thromboembolism in atrial fibrillation: I. Clinical features of patients at risk. The Stroke Prevention in Atrial Fibrillation Investigators.

OBJECTIVE: To identify those patients with nonrheumatic atrial fibrillation who are at high risk and those at low risk for arterial thromboembolism. DESIGN: Cohort study of patients assigned to placebo in a randomized clinical trial. SETTING: Five hundred sixty-eight inpatients and outpatients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study. Patients were followed for a mean of 1.3 years. MEASUREMENTS: Clinical variables were assessed at study entry and correlated with subsequent ischemic stroke and systemic embolism by multivariate analysis. MAIN RESULTS: Recent (within 3 months) congestive heart failure, a history of hypertension, and previous arterial thromboembolism were each significantly and independently associated with a substantial risk for thromboembolism (greater than 7% per year; P less than or equal to 0.05). The presence of these three independent clinical predictors (recent congestive heart failure, history of hypertension, previous thromboembolism of 2.5% per year (no risk factors), 7.2% per year (one risk factor), and 17.6% per year (two or three risk factors). Nondiabetic patients without these risk factors, comprising 38% of the cohort, had a low risk for thromboembolism (1.4% per year; 95% Cl, 0.05% to 3.7%). Patients without clinical risk factors who were under 60 years of age had no thromboembolic events. CONCLUSION: Patients with atrial fibrillation at high risk (greater than 7% per year) and low risk (less than 3% per year) for thromboembolism can be identified by readily available clinical variables.

Aged↗
PubMed1992

Predictors of thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk. The Stroke Prevention in Atrial Fibrillation Investigators.

OBJECTIVE: To identify echocardiographic predictors of arterial thromboembolism in patients with nonrheumatic atrial fibrillation and to determine whether these add to clinical variables for risk stratification. DESIGN: Cohort study of patients assigned to placebo in a randomized clinical trial. SETTING: Five hundred sixty-eight inpatients and outpatients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study. Patients were followed for a mean of 1.3 years. MEASUREMENTS: M-mode and two-dimensional (2-D) echocardiograms performed at study entry and interpreted by local cardiologists. The predictive value of 14 echocardiographic variables for later ischemic stroke or systemic embolism was assessed by multivariate analysis. MAIN RESULTS: Left ventricular dysfunction from 2-D echocardiograms (P = 0.003) and the size of the left atrium from M-mode echocardiograms (P = 0.02) were the strongest independent predictors of later thromboembolism. Multivariate analysis of these two independent echocardiographic predictors with the three independent clinical predictors of thromboembolism (history of hypertension, recent congestive heart failure, previous thromboembolism) identified 26% of the cohort with a low risk for thromboembolism (1.0% per year; 95% Cl, 0.2% to 4.0%). Compared with risk stratification using clinical variables alone, echocardiographic results altered thromboembolic risk stratification in 18% of the entire cohort and in 38% of those without clinical risk factors. CONCLUSIONS: Both left ventricular and left atrial variables are significant predictors of thromboembolism in patients with nonvalvular atrial fibrillation. Our results challenge traditional views of the pathogenesis of ischemic stroke in patients with atrial fibrillation and suggest that standard echocardiography contributes to risk stratification, differentiating the one third of patients without clinical risk factors who are at increased risk for stroke from the remainder who may not need antithrombotic prophylaxis.

Aged↗
PubMed1997

Risk for clinical thromboembolism associated with conversion to sinus rhythm in patients with atrial fibrillation lasting less than 48 hours.

BACKGROUND: It has been assumed that cardioversion in patients with atrial fibrillation lasting less than 48 hours is associated with a low risk for thromboembolism. However, no clinical data support this assumption. OBJECTIVE: To determine the incidence of cardioversion-related clinical thromboembolism among patients presenting with atrial fibrillation lasting less than 48 hours. DESIGN: Patients were prospectively identified on admission, and clinical data on the duration of atrial fibrillation were recorded. Data on cardioversion and thromboembolism were obtained retrospectively from hospital and outpatient records. SETTING: Academic medical center. PATIENTS: 1822 consecutive patients admitted to the hospital for atrial fibrillation were screened. Three hundred seventy-five adults (mean age +/- SD, 68 +/- 16 years) with atrial fibrillation that had lasted less than 48 hours were identified. One hundred eighty-one patients (48.3%) had a history of atrial fibrillation; 23 (6.1%) had a history of thromboembolism. RESULTS: 357 patients (95.2%) converted to sinus rhythm during the index admission; spontaneous conversion occurred in 250 patients (66.7%) and active pharmacologic or electrical conversion was done in 107 patients (28.5%). Three patients (0.8% [95% CI, 0.2% to 2.4%]), all of whom had converted spontaneously after ventricular rate control was begun, had a clinical thromboembolic event: One had a stroke, 1 had a transient ischemic attack, and 1 had a peripheral embolus. None of these 3 patients had a history of atrial fibrillation or thromboembolism, and all had normal left ventricular systolic function. CONCLUSION: Among patients presenting with atrial fibrillation that was clinically estimated to have lasted less than 48 hours, the likelihood of cardioversion-related clinical thromboembolism is low. These data support the current recommendation for early cardioversion in these patients.

Adult↗
PubMed1998

The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis.

BACKGROUND: The factor V Leiden mutation is a genetic defect associated with an increased incidence of venous thromboembolism. When the incidence of venous thromboembolism in relatives of patients known to have the mutation outweighs the disadvantages of prophylactic strategies, family screening may be necessary. OBJECTIVE: To determine the incidence of venous thromboembolism in first-degree relatives of symptomatic carriers of the factor V Leiden mutation. DESIGN: Retrospective blinded study. SETTING: University hospitals. PARTICIPANTS: 437 first-degree relatives of 112 heterozygous propositi and 30 relatives of 6 homozygous propositi. MEASUREMENTS: Before DNA testing, information on previous venous thromboembolism and concomitant risk factors was obtained. Relatives with and without the FV: Q506 mutation were compared. RESULTS: The annual incidence of thromboembolism in relatives of heterozygous propositi was 0.45% (95% CI, 0.28% to 0.61%) in those with the mutation and 0.10% (CI, 0.02% to 0.19%) in those without the mutation (relative risk, 4.2 [CI, 1.8 to 9.9]). Among carriers, the incidence increased from 0.25% (CI, 0.12% to 0.49%) in the 15- to 30-year-old age group to 1.1% (CI, 0.24% to 3.33%) in persons older than 60 years of age. Half of the episodes of venous thromboembolism occurred spontaneously, 20% were related to surgery, and 30% were associated with pregnancy or use of oral contraceptives. CONCLUSIONS: The observed low annual risk for venous thromboembolism in persons carrying the factor V Leiden mutation does not seem to outweigh the risks for bleeding associated with coumarin prophylaxis or justify discouragement of the use of oral contraceptives. A general policy of screening the families of all patients with the factor V Leiden mutation does not seem to be indicated. The observations in this moderate-size, retrospective study need to be confirmed by prospective follow-up studies.

Adolescent↗
PubMed1999

Activated protein C resistance and factor V Leiden mutation are independent risk factors for venous thromboembolism.

BACKGROUND: Resistance to activated protein C due to the factor V R506Q (Leiden) mutation is the most common clotting abnormality in patients with venous thromboembolism. OBJECTIVE: To evaluate the risk for venous thromboembolism associated with the factor V Leiden mutation or with resistance to activated protein C in the general population. DESIGN: Cross-sectional survey. SETTING: General community of Vicenza, Italy. PATIENTS: A population-based sample of 15,109 white persons 18 to 65 years of age who were randomly selected from the census list. MEASUREMENTS: Sequential validated approach based on participants' reports and Doppler ultrasonography. Resistance to activated protein C was investigated in all participants; 2134 participants with resistance to activated protein C were screened for the factor V Leiden mutation. RESULTS: Carriers of the factor V Leiden mutation had a relative risk of 3.3 (95% CI, 1.7 to 6.1) for venous thromboembolism before 65 years of age. The fraction of cases attributable to the factor V Leiden mutation was 6.6%. By 65 years of age, 5.7% of carriers of the mutation had had venous thromboembolism, mostly after surgery. Participants with a reduced response to activated protein C were at higher risk even if they did not carry the mutation (odds ratio, 1.7 [CI, 1.0 to 2.7]); the attributable risk for venous thromboembolism was 5.1%. CONCLUSIONS: The factor V Leiden mutation and resistance to activated protein C are important, independent risk factors for venous thromboembolism. Screening strategies for the factor V Leiden mutation in patients undergoing surgery or experiencing major trauma cannot be recommended, but phenotypic evaluation of resistance to activated protein C should be encouraged in patients with venous thromboembolism.

Activated Protein C Resistance↗
PubMed2001

A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism.

BACKGROUND: The factor V Leiden mutation is a common genetic defect associated with an increased risk for venous thromboembolism. The clinical implications for asymptomatic carriers of this mutation and, consequently, the usefulness of screening families in which a proband has both the mutation and venous thromboembolism are unclear. OBJECTIVE: To determine the incidence of venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation. DESIGN: Prospective cohort study. SETTING: University hospitals in the Netherlands. PARTICIPANTS: 470 asymptomatic carriers of the factor V Leiden mutation (234 men, 236 women; mean age, 43 years [range, 15 to 88 years]), 12 of whom were homozygous. Carriers were identified by screening the first-degree relatives (>15 years of age) of 247 symptomatic probands. MEASUREMENTS: Objectively diagnosed episodes of venous thromboembolism and the relationship between incidence and exposure to high-risk situations. RESULTS: Nine venous thromboembolic events were observed in 1564 observation-years, resulting in an annual incidence of 0.58% (95% CI, 0.26% to 1.10%). The incidence of spontaneous venous thromboembolism was 0.26% (CI, 0.07% to 0.65%) per year; 3.5% (CI, 0.1% to 17.8%) per episode of surgery, trauma, or immobilization; 0.0% (CI, 0.0% to 19.5%) per pregnancy; 1.8% (CI, 0.4% to 5.2%) per year of oral contraceptive use; and 2.9% (CI, 0.8% to 15.3%) per year of use of hormone replacement therapy. CONCLUSIONS: The absolute annual incidence of spontaneous venous thromboembolism in asymptomatic carriers of the factor V Leiden mutation is low and does not justify routine screening of the families of symptomatic patients.

Adolescent↗
PubMed2000

Cardioversion of persistent atrial flutter in non-anticoagulated patients at low risk for thromboembolism.

BACKGROUND: The true risk of thromboembolic events after cardioversion of atrial flutter was not addressed carefully. Nevertheless, thromboembolic events were thought to be rare and less likely to occur after cardioversion of atrial fibrillation. The aim of this study was to prospectively evaluate if the interruption of persistent typical atrial flutter could be safely performed without anticoagulation in a group of patients at low risk for thromboembolic events. METHODS: We studied 64 subjects selected among 138 consecutive patients with persistent typical atrial flutter (minimal duration 72 hours) in whom a transesophageal atrial pacing was performed in our electrophysiology laboratory from October 1994 to May 1999. Exclusion criteria included: anticoagulation therapy during the previous 4 weeks; previous history of atrial fibrillation; recent (< 1 month) myocardial infarction; history of thromboembolic events; left ventricular ejection fraction < 40%; presence of moderate or severe mitral regurgitation or stenosis; induction of sustained (> 6 hours) atrial fibrillation during transesophageal atrial pacing. Patients in whom atrial flutter persisted in spite of transesophageal atrial pacing underwent external direct current cardioversion or right atrial overdrive pacing within 24 hours. Thromboembolic events were checked for 4 weeks after the restoration of sinus rhythm. RESULTS: Sinus rhythm was restored in 54 patients by transesophageal atrial pacing, in 8 patients by electrical cardioversion, and in 2 by right atrial pacing. The mean duration of atrial flutter was 18 +/- 19 days, the mean left atrial size 41.3 +/- 6.2 mm, and the mean left ventricular ejection fraction 54.8 +/- 7.3%. During the study period no episodes of thromboembolism were recorded. CONCLUSIONS: Cardioversion of persistent typical atrial flutter in non-anticoagulated patients at low risk for thromboembolic events appears safe.

Aged↗
PubMed2000

[Risk factors for thromboembolism in patients with atrial fibrillation during treatment with aspirin: a multicenter, cooperative retrospective study. Research Group for Antiarrhythmic Drug Therapy].

Warfarin is effective in preventing thromboembolism in patients with atrial fibrillation, but aspirin is frequently used as an alternative treatment. A multicenter, retrospective study was undertaken to identify patients at risk for thromboembolism during treatment with aspirin. The study group consisted of 470 patients (318 males, 152 females, mean age 59.9 +/- 11.8 years at initial examination) with atrial fibrillation who were treated with aspirin. Thirty-seven percent of patients had paroxysmal atrial fibrillation and 65% of patients received aspirin at a daily dose of 81 mg. Thromboembolism occurred in 31 patients (6.6%) during the follow-up period, resulting in cerebral infarction in 19 patients, transient ischemic attack in 7, and embolism of peripheral arteries in 5. Patients with thromboembolism had lower prevalence of New York Heart Association (NYHA) functional class I (52% vs 72%, p < 0.02) and paroxysmal atrial fibrillation (23% vs 38%, p = 0.085) compared with patients without thromboembolism. Multivariate analysis with the Cox proportional hazard model determined age (> or = 65 years, relative risk 2.29, p = 0.032) as an independent risk factor. NYHA functional class (> or = class II) tended to indicate an increased risk of thromboembolic events (relative risk 1.90, p = 0.076). These results suggest that aspirin has limited efficacy for prevention of thromboembolism in patients with atrial fibrillation who are old (> or = 65 years) or have symptomatic heart failure.

Age Factors↗
PubMed2000

Risk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis.

Carriers of a mutation in the prothrombin (clotting factor II) or factor V gene have a 2- to 4-fold greater risk for venous thromboembolism than subjects without the mutations. Whether both mutations also predispose to recurrent venous thromboembolism is unclear. Outpatients who had a first episode of proven symptomatic deep-vein thrombosis and a long-term follow-up were studied. The outcome measure was the cumulative incidence of confirmed venous thromboembolic complications. Two hundred fifty-one patients were enrolled in the study. Mean duration of follow-up was 8.3 years. The prothrombin gene mutation was demonstrated in 27 patients (prevalence, 10.8%; 95% CI, 6.9 to 14.6), and the factor V gene mutation was demonstrated in 41 patients (prevalence, 16.3%; 95% CI, 11.8 to 20.9). The cumulative incidence of venous thromboembolic complications after 10 years was 61.3% (95% CI, 35.7 to 87.9), and the hazard ratio was 2.4 (95% CI, 1.3 to 4.7; P =.004) in patients with the prothrombin gene mutation); the cumulative incidence of venous thromboembolic complications after 10 years was 55.2% (95% CI, 36.4 to 74.0), and the hazard ratio was 2.4 (95% CI, 1.4 to 4.1; P =.001) in patients with the factor V gene mutation. In comparison, the cumulative incidence of venous thromboembolic complications after 10 years was 23.1% (95% CI, 16.2 to 30.1) in patients without the mutations. Prothrombin and factor V gene mutations occur frequently in patients with venous thrombosis and are associated with an increased risk for recurrent venous thromboembolic complications.

Adult↗
PubMed2004

[Predictive value of coagulative molecular markers for thromboembolism in patients with nonvalvular atrial fibrillation: prospective five-year follow-up study].

OBJECTIVES: Nonvalvular atrial fibrillation is a known risk factor for thromboembolism. This study investigated the use of coagulation markers to predict thromboembolism in nonvalvular atrial fibrillation patients. METHODS: One hundred thirty nonvalvular atrial fibrillation patients (104 males, 26 females, mean age 63.7 +/- 10.7 years) treated at the Sendai Cardiovascular Center from April 1996 to August 1997 were enrolled in this study. Coagulation markers such as prothrombin fragment 1 + 2, thrombin-antithrombin III complex and D-dimer were measured, and the patients were followed up prospectively to October 2001. RESULTS: One hundred and twenty-six patents (100 males, 26 females, chase rate 96.9%) were included in this investigation based on the medical chart and telephone interview. During five-year follow-up, 16 patients had thromboembolism accidents (3.25%/year) and two were suspected to die of thromboembolism. Three patients died of malignant disease, four of heart disease, and five of other diseases. Eight (25.8%) of the 31 patients with high levels of thrombin-antithrombin III complex and 6 (33.3%) of 18 patients with high levels of D-dimer suffered thromboembolism accidents. High thrombin-antithrombin III complex and D-dimer were statistically positive predictive markers for thromboembolism in patients with nonvalvular atrial fibrillation (p < 0.05). CONCLUSIONS: Coagulation markers such as thrombin-antithrombin III complex and D-dimer can predict thromboembolism accidents in nonvalvular atrial fibrillation patients.

Aged↗
PubMed2006

Cancer and thromboembolism: from biology to clinics.

The association between cancer and thromboembolic disease is a well-known phenomenon and can contribute significantly to the morbidity and mortality of cancer patients. Recent studies evidenced that malignant growth has also been linked to activity of heparin-like glycosoaminoglycans, to neoangiogenesis, to protease activity, to immune function and gene expression in addition with activation of coagulation and fibrinolysis. These evidences suggest that antithrombotic drugs may play an additional role in tumour cell growth and in cancer dissemination. The spectrum of thromboembolic manifestations in cancer patients includes deep vein thrombosis, pulmonary embolism, but also intravascular disseminated coagulation and abnormalities in the clotting system in the absence of clinical manifestations. Antithrombotic drugs such as unfractioned heparin (UFH) and, particularly, low molecular weight heparins (LMWH) in addition with dicumaroids, are widely used for the prevention and treatment of thromboembolic manifestations that commonly accompanies malignancies. The aims of the study are to review the pathogenetic mechanisms of thromboembolic disease in cancer patients, the efficiency of antithrombotic drugs in preventing and treating of cancer related thromboembolic complications and review the thromboprophylaxis strategies to prevent thromboembolic complications of cancer patients. Meta-analyses comparing UFH and LMWH for the treatment of deep vein thrombosis have shown better outcome with reduction of major bleeding complications in patients treated with LMWH. Many studies have demonstrated the efficiency and the safeness of antithrombotic agents in the prophylaxis and in the treatment of thromboembolic complication that accompanies malignancies. Many experimental studies, reviewed in this paper, support the hypothesis that antithrombotic agents, but especially heparins can affect cancer progression in many of the different steps of cancer biology. First of all, due to their anticoagulant effect, antithrombotic agents may interfere with thrombin generation and with fibrin formation induced by cancer cells, thus inhibiting the mechanism of metastasis.

Anticoagulants↗
PubMed1991

Audit of attitudes to and use of postoperative thromboembolic prophylaxis in a regional health authority.

A survey of usage and attitudes to thromboembolic prophylaxis among 46 general surgeons in the Mersey Region found that 87% use either low-dose heparin, graduated compression stockings or both on a regular basis for their major cases. However, there was a wide variation of usage: 9 (19.6%) always used heparin in combination with thromboembolic stockings, 4 (8.7%) always used heparin alone, no surgeon used thromboembolic stockings alone. A total of 18 (39%) used thromboembolic stockings in combination with heparin, one-half of them selectively. A further 24% of surgeons used either low-dose heparin or thromboembolic stockings or both on selected patients. Current literature beliefs concerning the efficacy of low-dose heparin and thromboembolic stockings showed a similar variation, with 13% of surgeons believing that the efficacy of low-dose heparin against postoperative deep vein thrombosis has not been shown, 22% believing that thromboembolic stockings were ineffective against postoperative deep vein thrombosis, and 24% believing that low-dose heparin was of no value as a prophylactic agent against postoperative pulmonary embolism. Published meta-analysis has shown these beliefs to be wrong.

Attitude of Health Personnel↗