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PubMed2004

Current options in the prevention of thromboembolic disease.

Significant advances in the pharmacological prophylaxis of venous thromboembolism have occurred since warfarin and unfractionated heparin were introduced for this indication nearly 60 years ago. Despite these advances, coumarin derivatives such as warfarin remain the only orally active anticoagulants available for prophylaxis in venous thromboembolism. Although administered orally, coumarin derivatives are not convenient to use, because they have narrow therapeutic indexes and require routine coagulation monitoring and dose adjustment. This is inconvenient for patients and physicians and costly for the healthcare system. Low-molecular-weight heparins, which are administered in fixed or weight-adjusted doses and do not require monitoring, are widely used for the prevention of venous thromboembolism in patients in both the hospital and the outpatient setting. However, these drugs must be given subcutaneously, which can be difficult for outpatients and resource-intensive for in-hospital use. Likewise, fondaparinux, the synthetic pentasaccharide, must be administered subcutaneously. Consequently, there remains a need for new orally active anticoagulants that can be given in fixed doses and do not have a narrow therapeutic index, so that coagulation monitoring is unnecessary. Because such agents would be more convenient for patients and physicians, they would probably expand the use of prophylaxis in venous thromboembolism in those at risk, and would simplify treatment of patients with established venous thromboembolism.

Administration, Oral↗
PubMed2005

Direct thrombin inhibitors for the prevention of venous thromboembolism after major orthopaedic surgery.

Unfractionated heparin, low-molecular-weight heparins and vitamin K antagonists are established antithrombotic agents, but all have a number of limitations. Unfractionated heparin requires parenteral administration, has a short half-life and variable dose-response relationship. Low molecular weight heparins are more effective than low-fixed-dose unfractionated heparin in the prevention of postoperative venous thromboembolism in high-risk surgical patients but they still require subcutaneous administration. Vitamin K antagonists have a narrow therapeutic window and require a careful laboratory monitoring to minimize the risk of bleeding or thrombosis. Direct thrombin inhibitors are selective inhibitors of this key enzyme. Direct thrombin inhibitors inactivate thrombin without requiring any plasma cofactor, inhibit both free and fibrin-bound thrombin, and do not appreciably bind to plasma proteins. Ximelagatran, the first oral direct thrombin inhibitor, is rapidly absorbed and converted to its active form melagatran, which can itself be administered subcutaneously. Ximelagatran has been evaluated in the prevention of venous thromboembolism after major orthopaedic surgery, in the treatment of venous thromboembolism, in the prevention of stroke in patients with atrial fibrillation and in the prevention of recurrence after acute coronary syndromes. In the European studies in major orthopaedic surgery ximelagatran was administered orally after one or two days of melagatran, given subcutaneously. This review will report on the mechanism of action and clinical pharmacology of direct antithrombin agents and on the results of the clinical trials performed with direct thrombin inhibitors in the prevention of venous thromboembolism after major orthopaedic surgery. Taken together, these results indicate that direct thrombin inhibitors, ximelagatran in particular, have the potential to be a valid alternative to low molecular weight heparins and oral anticoagulants in the prevention of venous thromboembolism after major orthopaedic surgery.

Animals↗
PubMed2003

Antiphospholipid antibodies and the risk of thromboembolic events in valvular heart disease.

OBJECTIVE: To investigate the role of antiphospholipid antibodies (aPLs) in subsequent thromboembolic events and mortality in a prospective follow-up of 89 patients with severe, nonspecific valvular heart disease. PATIENTS AND METHODS: Between November 1, 1993, and March 31, 1994, 89 patients with valvular heart disease were assessed for the presence of anticardiolipin antibodies and lupus anticoagulant. The primary end point was thromboembolic events, and the secondary end points were cardiovascular mortality and overall mortality. RESULTS: All patients were followed up for a mean of 59 months; 1 patient (without aPLs) was lost to follow-up. Nineteen patients had increased titers of aPLs. Thromboembolic events were significantly more frequent in the aPL-positive group than in the aPL-negative group (7/19 [37%] vs 8/70 [11%]; P=.01). Cardiovascular mortality tended to be higher in the aPL-positive group than in the aPL-negative group (3 [16%] vs 6 [9%]; P = .40). However, in multivariate Cox analysis, presence of aPLs was not an independent risk factor for thromboembolic events. CONCLUSION: Our results suggest that patients with severe valvular heart disease and aPLs have an increased risk for developing thromboembolic events.

Antibodies, Anticardiolipin↗
PubMed2003

The use of the rapid D-dimer test for the exclusion of acute venous thromboembolism in a regional hospital.

BACKGROUND: The performance of rapid D-dimer ELISA assay has been validated as a part of various diagnostic work-ups in tertiary care hospitals for the exclusion of acute thromboembolism in the medical emergency department. In order to measure the performance of this test outside of predetermined protocols and in a different medical setting, we retrospectively analysed a cohort of adult patients admitted to the emergency department of a regional hospital with a suspicion of acute venous thromboembolism. METHODS: All D-dimer assays performed during an 18-month period were retrieved. The patients' data were collected from hospital charts. Six-month follow-up was determined either by a written or telephone questionnaire or after contact with the patient's physician. The patients for whom this process was completed were included in the study and a retrospective diagnostic assessment was performed using a combination of clinical probability and objective testing. The diagnosis was then compared to the result of the initial D-dimer assay. RESULTS: During the study period 494 patients were included with 110 venous thromboembolic episodes. The sensitivity and negative predictive value of the D-dimer assay were respectively 94.5% (95% CI 88.4 to 97.7%) and 96.8% (95% CI 93.2 to 98.7%). CONCLUSIONS: The yield of the rapid D-dimer assay in this study is comparable to the results of management studies performed in tertiary centres. D-dimer ELISA assay can be used to exclude venous thromboembolism, particularly in cases with a low clinical probability, in the emergency department and for larger populations in various clinical settings, even in the absence of a formal diagnostic work-up. False negative results can occur, particularly in the presence of a high clinical probability of acute thromboembolism.

Acute Disease↗
PubMed1998

Incidence of idiopathic deep venous thrombosis and secondary thromboembolism among ethnic groups in California.

BACKGROUND: Few studies have compared the incidence of deep venous thrombosis among ethnic groups. OBJECTIVE: To determine the incidence of deep venous thrombosis among ethnic groups. DESIGN: Analysis of the linked California Patient Discharge Data Set from 1991 to 1994. SETTING: California. PATIENTS: 17991 patients with idiopathic deep venous thrombosis (thrombosis without cancer or hospitalization within preceding 6 months) and 5573 patients with secondary thromboembolism (thromboembolism occurring within 3 months of seven different events). MEASUREMENTS: Ethnicity was determined by using race as documented in the data set. For idiopathic deep venous thrombosis, standardized age- and sex-adjusted incidences were calculated. For secondary thromboembolism, proportional hazards modeling was done. RESULTS: The annual incidence of idiopathic deep venous thrombosis per 1000000 persons older than 18 years of age was 230 for white persons, 293 for African Americans (rate ratio, 1.27 [95% CI, 1.07 to 1.51]), 139 for Hispanic persons (rate ratio, 0.60 [CI, 0.54 to 0.67]), and 60 for Asians and Pacific Islanders (rate ratio, 0.26 [CI, 0.22 to 0.30]). Compared with white persons, Asians and Pacific Islanders who developed secondary thromboembolism had a significantly lower relative risk (range, 0.22 to 0.61) for all seven conditions analyzed. CONCLUSIONS: Compared with white persons, Asians and Pacific Islanders have a very low incidence of idiopathic deep venous thrombosis and a very low relative risk for secondary venous thromboembolism.

Adult↗
PubMed2002

Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the U.S. Preventive Services Task Force.

BACKGROUND: Postmenopausal estrogen replacement is widely used in the United States but poses important health risks. PURPOSE: To assess the risk for venous thromboembolism with postmenopausal estrogen replacement by using literature review and meta-analysis. DATA SOURCES: All relevant English-language studies identified in searches of the MEDLINE (1966 to December 2000), HealthSTAR (1975 to December 2000), and Cochrane Library databases, and references lists of key articles. STUDY SELECTION: All published studies of postmenopausal estrogen replacement reporting venous thromboembolism as an outcome or adverse event. DATA EXTRACTION: 12 studies of estrogen were identified (3 randomized, controlled trials; 8 case-control studies; and 1 cohort study). Data were extracted on participants, interventions, event rates, and confounders. Two reviewers independently rated study quality on the basis of established criteria. DATA SYNTHESIS: A Bayesian meta-analysis was conducted. When data from all studies were pooled, current estrogen use was associated with an increased risk for venous thromboembolism (relative risk, 2.14 [95% credible interval, 1.64 to 2.81]). Estimates did not significantly change when studies were pooled according to study design, quality score, or whether participants had preexisting coronary artery disease. The absolute rate increase was 1.5 venous thromboembolic events per 10 000 women in 1 year. Six case-control studies that reported risk according to duration of use found that risk was highest in the first year of use (relative risk, 3.49 [credible interval, 2.33 to 5.59]). CONCLUSION: Postmenopausal estrogen replacement is associated with an increased risk for venous thromboembolism, and this risk may be highest in the first year of use.

Bayes Theorem↗
PubMed1999

Anti-cardiolipin, anti-endothelial-cell and anti-malondialdehyde-LDL antibodies in uremic patients undergoing hemodialysis: relationship with vascular access thrombosis and thromboembolic events.

Patients with chronic renal failure requiring regular hemodialysis are known to be prone to thromboembolic events due to a hypercoagulable state. Vascular access thrombosis (VAT; including thrombosis of the vascular shunt or graft) represents a serious complication and jeopardizes life in these patients. In the current study, conducted on 81 consecutive patients from the Hemodialysis Unit, we have employed ELISA for the estimation of various autoantibody levels (anti-endothelial cell antibodies, anti-cardiolipin, anti-beta 2GPI and anti-modified LDL antibodies) and correlated them with the occurrence of thromboembolic events in general, and VAT in particular. We have found that the levels of antibodies reactive with human umbilical vein endothelial cells (HUVEC) but not with other EC lines (microvascular or EaHy 929) were significantly higher in hemodialysed patients with VAT in comparison with patients with no VAT (p = 0.001). A weaker but yet positive correlation was observed between the levels of anti-HUVEC and anti-cardiolipin antibodies and the occurrence of thromboembolic events including deep vein thrombosis, pulmonary infarction, cerbrovascular events and VAT (both p-values equal 0.02). Anticardiolipin antibodies (aCL) were not cross reactive with beta 2GPI or with HUVEC. Antibodies to modified LDL, although higher in hemodialyzed patients, did not correlate with thromboembolic events. The results of this study suggest that antibodies to HUVEC may prove as a fairly good marker of VAT in hemodialysis. High levels of aCL are weakly associated with thromboembolic events and antibodies to modified LDL do not correlate with a prothrombotic state.

Adult↗
PubMed1999

[Incidence of thromboembolic complications in cesarean sections and heparin prophylaxis].

BACKGROUND AND AIM: Venous thromboembolism is a rare but severe complication of pregnancy and puerperium: it is the most frequent cause of death and maternal morbidity. Pregnancy leads to hemodynamic, hormonal and hematological changes which make hypercoagulability a secondary condition. In particular, surgical birth via an abdominal route is burdened with a higher risk of thromboembolic disease compared to spontaneous birth. The aim of this study was to highlight the increased incidence of deep venous thrombosis and pulmonary embolism after caesarean section. METHODS: All the pregnant women (no = 879) admitted to the institute from January 1997 to May 1998 were monitored: their clinical conditions were followed both during the last period of pregnancy and after birth in order to identify the onset of pre- and post-partum thromboembolic episodes. RESULTS: Among the women examined, 9 cases (1.02%) of lung embolism were observed, one of which was fatal. All 9 women had undergone caesarean section and in all cases the thromboembolic episode occurred between the second and fourth day after birth. Prophylactic therapy was not administered in any of the above cases. CONCLUSIONS: It is important that anti-thrombotic prophylaxis with heparin should be administered. Although this presents a number of collateral effects (hemorrhage, platelet deficiency, osteoporosis), it protects the woman from the risk of thromboembolic episodes, above all if a caesarean section is performed or if the personal and/or family medical history is positive for this pathology.

Blood Coagulation Disorders↗
PubMed1999

Perioperative bleeding and thromboembolic risk during non-cardiac surgery in patients with mechanical prosthetic heart valves: an institutional review.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to determine the risk of thromboembolic and bleeding complications in patients with mechanical heart valve prostheses who underwent non-cardiac surgery under different regimens of perioperative anticoagulation. Data were analyzed on the basis of surgery type and underlying disease. METHODS: A series of 235 patients (mean age 63 +/- 4.5 years) with one or two mechanical heart valves underwent subsequent non-cardiac surgery comprising abdominal, vascular and thoracic, orthopedic, urologic, neurosurgery, ENT, plastic and reconstructive, and gynecologic operations. Mean interval between heart valve replacement and non-cardiac surgery was 3.9 +/- 3.3 years. Perioperative oral anticoagulation was managed by discontinuation of oral anticoagulation and intravenous heparin administration; or by discontinuation and early postoperative re-institution of oral anticoagulation without intravenous heparin; or by no withdrawal of oral anticoagulation. Patients with bioprostheses were excluded. RESULTS: Overall hospital mortality during non-cardiac surgery was 2.9%. Thromboembolic events included cerebral embolism with transient deficit (n = 3), residual defect (n = 1) and irreversible defect (n = 1), as well as peripheral embolism (n = 11). Hemorrhagic complications included wound hematoma (n = 10) and increased postoperative bleeding (n = 8) with re-exploration in five patients. Thromboembolic complications occurred most often in patients with prosthetic mitral valve and atrial fibrillation; the lowest risk was in patients with sinus rhythm after aortic valve replacement. Most complications occurred after discharge and in patients with surgery for malignancy, within 10 days of instituting oral anticoagulation, and despite a therapeutic INR value. CONCLUSIONS: Minor surgical procedures can be performed safely without discontinuing anticoagulation. When major non-cardiac surgery is planned, discontinuing oral anticoagulation and starting perioperative intravenous heparin minimizes bleeding and thromboembolic risks. Thromboembolic complications may occur within one month of surgery, despite adequate oral anticoagulation, though permanent morbidity is low.

Anticoagulants↗
PubMed2000

[Rationalization of risk factors for venous thromboembolism in medical inpatients. A prospective study].

BACKGROUND: In terms of preventive management of venous thromboembolism in medical inpatients, very large differences may be observed. Rationalization of behaviour requires the evaluation of simple and logical parameters, which takes into account both patient safety and economic considerations. AIM: The aim of this study was to evaluate a preventive scheme including the rationalization of the indications and the use of low molecular weight heparin. METHODS EXPERIMENTAL DESIGN: Epidemiologic investigation. SETTING AND PATIENTS: Patients hospitalized in five medical departments in the Hospital Center of Nantes, France. INTERVENTION: The risk of venous thromboembolism was rated as high, intermediate and low. Patients with high or intermediate risk were eligible for prevention therapy (table I). MEASURES: The main criterion was the occurrence during hospital stay of deep or superficial venous thrombosis of the lower limbs, pulmonary embolism, or unexplained sudden death. The screening was based on clinical features double-checked by venous doppler ultrasonography of the lower limbs and/or ventilation-perfusion lung scanning. RESULTS: 24,497 patients were eligible (table II), 15% were considered at risk and treated with Nadroparin, 6% had the same risk profile but were not treated and 14. 7% had low risk and no prevention. No bleeding event was reported. The incidence of venous thromboembolism was 0.75%, 1.7% and 0.14% respectively (p <0.01) (table III). This efficacy does not appear to depend on body weight or the existence of multiple risk factors observed (table IV and V). CONCLUSIONS: This analysis of risk factors separates two populations with rates of incidence dramatically and significantly different. The prevention of venous thromboembolism by fixed dose of low molecular weight heparin remains justified since it reduces the risk of venous thromboembolism by a factor of 2.5.

Adult↗
PubMed2000

[Thromboembolism in plastic surgery: review of the literature and proposal of a prophylaxis algorithm].

There is still less incidence of venous thromboembolic accidents in plastic surgery (% of unknown deep vein thrombosis and pulmonary embolism unknown) than in general surgery (6 to 12% of deep vein thrombosis and 0.3 to 1.1% of pulmonary embolism). However, these accidents present a dangerous and dreaded complication. Based on the recommendations of the Assistance Publique--Hôpitaux de Paris and on a recently published medical study, an algorithm of preventive measures is proposed. The combination of the type of surgical procedure (liposuction, dermolipectomy and abdominoplasty) and the predisposing individual patient risk factors (age, obesity, varicose veins, estrogens, venous thromboembolism history, inherited disorders of coagulation) defines the level of thromboembolic risk which can be mild, moderate or high. Prevention is based on general guidelines (early mobilization, leg elevation, etc.); in addition, at every level of potential risk, the use of low molecular weight heparin (LMWH) and/or wearing anti-thrombosis stockings, as well as surveillance of detection of venous thromboembolism, notably the duplex venous scanning of lower limbs, will be adapted to each patient. This algorithm is a means to elaborate a rational, but unfixed strategy or protocol of prevention to reduce the risk of venous thromboembolic complications, and if they occur, to detect them at an early stage and to treat them in order to avoid evolution towards pulmonary embolism, notably mortal pulmonary embolism.

Algorithms↗
PubMed2000

[Thromboembolic risk factors in atrial flutter. Transesophageal echocardiographic study].

BACKGROUND: The thromboembolic risk of atrial flutter (AFL) is not well defined. On the other hand, in atrial fibrillation (AF), the echocardiographic demonstration of thrombus or spontaneous echo contrast in the left atria or its appendage, a lower flow velocity in the left atrial appendage, and its reduced mobility, are well known risk factors of thromboembolism. AIM: To study the incidence of these echocardiographic risk factors in patients with AFL. MATERIAL AND METHODS: We prospectively studied 50 consecutive patients with AFL comparing them with two groups of patients with a well known increased risk of thromboembolism: 54 patients with AF and 24 patients with sinus rhythm and severe mitral stenosis (RSEMS). The group of patients with AFL was also compared with a control group of 27 patients with sinus rhythm and no increased risk of thromboembolism. In each group, we studied the presence of thrombi and spontaneous echo contrast in the left atria and left atrial appendage, emptying velocity (Vel A), filling flow (Vel B) and motility of the left atrial appendage and left atrial dimensions. RESULTS: When compared with control patients, AFL subjects had a higher incidence of spontaneous echo contrast in the left atria and left atrial appendage (11 and 42% respectively, p < 0.05); slower flow velocity in the left atrial appendage (Vel A 69.25 +/- 25 and 41 +/- 19 cm/s respectively, Vel B 55 +/- 16 and 46 +/- 20 cm/s respectively, p < 0.05); lower atrial appendage wall motility (4 and 84% respectively, p < 0.001) and a larger left atrium (40 +/- 10 and 45 +/- 0.6 mm respectively, p < 0.05). Patients with AFL had a lower incidence of echocardiographic abnormalities than subjects with AF or RSEMS. Thrombi were found in 2 patients with AFL, 12 patients with AF, 4 patients with RSEMS and in no control patient. CONCLUSIONS: In AFL, there are echocardiographic markers of increased thromboembolic risk in comparison with a control group. Nevertheless, the incidence of these factors is lower than in patients with AF or with RSEMS.

Adolescent↗
PubMedDate not supplied

[Study of combined anticoagulant (fluindione)-aspirin therapy in patients with atrial fibrillation at high risk for thromboembolic complications. A randomized trial (FFAACS)].

BACKGROUND: A combination of low-dose aspirin (A) and anticoagulation (AC) may provide better protection against thromboembolic events compared with AC alone in high-risk patients with atrial fibrillation (AF). METHODS: We performed a multicentric placebo-controlled double blind-trial to test the preventive efficacy against thromboembolic events of the addition of aspirin (A) (100 mg) or placebo (P) to anticoagulant treatment in patients with high-risk atrial fibrillation. A total of 157 patients were included, with atrial fibrillation and previous thromboembolic event or older than 65 years with either a history of hypertension, a recent episode of heart failure or a left ventricular dysfunction. All patients received fluindione (F) and P or F and A, with an INR target between 2 and 2.6. The primary endpoint was a combined endpoint of stroke (ischaemic or haemorrhagic), myocardial infarction, systemic arterial emboli or vascular death. RESULTS: The study had to be stopped prematurely owing to a too low recruitment rate. During follow-up (0.84 years) 3 non-fatal thromboembolic events were recorded (1P, 2A) and 6 patients died (3P, 3A), none of them from a thromboembolic complication. However, 3 deaths were secondary to severe haemorrhagic complications (1P, 2A). Non-fatal haemorrhagic complications occurred more often in group A (n = 10, 13.1 pour cent) compared with group P (n = 1, 1.2 pour cent), p = 0.003. CONCLUSION: The FFAACS study was not able to show any therapeutic benefit from the addition of aspirin to anticoagulant in patients with high-risk AF. Such a combination increased the incidence rate of bleeding complications, which therefore greatly reduces its potential overall benefit.

Aged↗
PubMed2001

[No indication for thrombophilia screening in patients with idiopathic venous thromboembolism and their relatives].

In 70% to 80% of patients with venous thromboembolism, a thrombophilic defect can be identified. The most important defects are: antibodies to phospholipids or lupus anticoagulants, mutation of factor V Leiden, prothrombin mutation, mild hyperhomocysteinaemia, and increased factor VIII levels. Deficiencies of antithrombin, protein C or protein S are rare. Whether or not screening for thrombophilia in patients with idiopathic venous thromboembolism is justified, depends on the potential benefits for the patients, or their relatives. At present, patients with a thrombophilic defect do not appear to have a much higher risk for recurrent venous thromboembolism, than patients with thrombosis but without a defect. The absolute risks of venous thromboembolism in asymptomatic relatives with a thrombophilic defect are too low to justify initiating a general policy of family screening. In conclusion, a conservative approach towards thrombophilia screening in idiopathic venous thromboembolism is warranted.

Diagnosis, Differential↗
PubMed2001

Risk factors in venous thromboembolism.

Venous thromboembolism is a serious disorder because of its potential complications, such as pulmonary embolism and the post-thrombotic syndrome. Inherited determinants of venous thromboembolism are only in part known, but in the past decades considerable progress has been made in the understanding of risk factors for the disease and their clinical impact. In particular, the development of molecular biology techniques and the increasing interest in their application, allowed an identification of two causes of inherited thrombophilia, i.e., factor V Leiden and the prothrombin G20210A mutation. Their recent discovery provided a new approach for improving the knowledge of inherited thrombophilia. In contrast to deficiencies of the naturally occurring anticoagulant proteins antithrombin, protein C and protein S, these two mutations cannot be considered true genetic defects, since they are nucleotide substitutions resulting in a more efficient coagulation process. Since they are rather common in the general populations of Caucasian descent and are associated with a moderate increased risk of venous thromboembolism, the effect of the interaction between inherited and environmental risk factors for venous thromboembolism has become an even greater field of interest. Prevention of first events and recurrences of venous thromboembolism can be optimized only through a knowledge of the main risk factors, their effect, and their interaction with environmental factors.

Female↗
PubMed2001

The epidemiology of venous thromboembolism in the community.

The incidence of venous thromboembolism exceeds 1 per 1000; over 200,000 new cases occur in the United States annually. Of these, 30% die within 30 days; one-fifth suffer sudden death due to pulmonary embolism. Despite improved prophylaxis, the incidence of venous thromboembolism has been constant since 1980. Independent risk factors for venous thromboembolism include increasing age, male gender, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, central venous catheter/transvenous pacemaker, prior superficial vein thrombosis, and varicose veins; among women, risk factors include pregnancy, oral contraceptives, and hormone replacement therapy. About 30% of surviving cases develop recurrent venous thromboembolism within ten years. Independent predictors for recurrence include increasing age, obesity, malignant neoplasm, and extremity paresis. About 28% of cases develop venous stasis syndrome within 20 years. To reduce venous thromboembolism incidence, improve survival, and prevent recurrence and complications, patients with these characteristics should receive appropriate prophylaxis.

Adolescent↗
PubMed2001

Thromboembolic complications in Thai pediatric patients.

Sixty patients with thromboembolic complications from 1987 to 1997 at the Department of Pediatrics, Ramathibodi Hospital were retrospectively studied. Twenty patients were infants and 40 patients were children and adolescents with a mean age of 18 days and 8 years, respectively. The sites of thromboembolic complications were in the central nervous system, 27.5 per cent; skin as purpura fulminans or necrotic lesions, 24.5 per cent; gangrene of the toe, finger or colon, 19 per cent; deep vein thrombosis, 16 per cent; and other sites such as heart and lungs, 13 per cent. Most of them had triggering conditions (80%) and underlying diseases (76.7%) causing thromboembolism. The low levels of either antithrombin III, protein C or protein S were found in 42 per cent (15/36). The management included administration of standard or low molecular weight heparin if not contraindicated, replacement of fresh frozen plasma 10 ml/kg twice a day and treatment of underlying and triggering conditions. The fatality rate was 15 per cent (9/60). Subsequent episodes of thromboembolism occurred in 6 patients including: pulmonary emboli in one patient with protein C deficiency who refused warfarin administration, deep vein thrombosis in 2 patients with unidentified etiology, and necrotic skin lesions in 3 patients with vasculitis who did not respond to treatment. In conclusion, a comprehensive investigation and specific treatment for patients with thromboembolic complications are emphasized in order to prevent recurring episodes.

Adolescent↗
PubMed2002

Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism.

BACKGROUND: Preliminary evidence suggests that use of antipsychotic drugs is associated with an increased risk of venous thromboembolism. OBJECTIVE: To evaluate the relationship between antipsychotic or antidepressant drug use and venous thromboembolism among adults aged 65 years and older. DESIGN: Retrospective cohort study using linked health care administrative databases over a nine year period. SETTING: The entire province of Ontario, Canada. PARTICIPANTS: Individuals aged 65 years and over exclusively prescribed either antipsychotic drugs (n = 22,514), antidepressant drugs (n = 75,649) or thyroid replacement hormones (33,033), the referent control group. We excluded those with an antecedent history of cardiovascular disease, venous thromboembolism or cancer, as well as those dispensed warfarin before study entry. MEASUREMENTS: Diagnosis of deep vein thrombosis or pulmonary embolism. RESULTS: Relative to those prescribed thyroid hormones, neither antidepressant (adjusted hazard ratio 1.02, 95% CI 0.91-1.14) nor antipsychotic (adjusted hazard ratio 1.13, 95% CI 0.96-1.32) drug use was associated with an increased risk for deep vein thrombosis. Similar risk estimates were found for deep vein thrombosis or pulmonary embolism. In a sub-group analysis, only butyrophenone use was found to be associated with a slightly increased risk of deep vein thrombosis (adjusted HR 1.51, 95% CI 1.23-1.86) as well as deep vein thrombosis or pulmonary embolism (adjusted HR 1.43, 95% CI 1.18-1.74). CONCLUSIONS: In a large cohort of adults aged 65 years and older, neither antipsychotic or antidepressant drug use was associated with an increased risk of venous thromboembolism, with the exception of a slightly increased risk among those prescribed butyrophenones. Further data are required before use of these psychoactive drugs can be considered a risk factor for venous thromboembolism.

Aged↗