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PubMed1995

Enoxaparin. A reappraisal of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disease.

Enoxaparin (enoxaparin sodium) is a low molecular weight derivative of unfractionated heparin which has been evaluated for the treatment and prevention of thromboembolic disease. Since a previous review in Drugs, well controlled clinical trials have confirmed the effectiveness of enoxaparin as prophylaxis in patients with a high risk for deep venous thrombosis (DVT), i.e. those undergoing hip or knee replacement surgery. Enoxaparin 30mg twice daily, initiated postoperatively, offers an overall balance of prophylactic efficacy and haemorrhagic tolerability which is superior to that of unfractionated heparin. In comparative clinical trials, this dosage demonstrated either improved efficacy and a similar haemorrhagic profile, or a similar degree of efficacy with a lower rate of haemorrhagic events, compared with unfractionated heparin 5000IU 3 times daily. Limited data indicate that an enoxaparin regimen of 40mg once daily, starting preoperatively, is more effective than unfractionated heparin in patients undergoing hip replacement and has a comparable haemorrhagic profile. In patients with a moderate risk for DVT, enoxaparin is similar to unfractionated heparin in both efficacy and haemorrhagic profile, while preliminary investigations have demonstrated the utility of enoxaparin in the prevention of DVT in elderly, nonsurgical patients. Enoxaparin may also be useful for the treatment of existing DVT and as an anticoagulant in haemodialysis. Thus, enoxaparin is an effective form of prophylaxis for thromboembolic disease in moderate to high risk surgical situations. Recent evidence for improved efficacy, together with a similar incidence of haemorrhagic complications in most situations, may lead to enoxaparin being preferred to unfractionated heparin for the routine prevention of DVT after high risk surgery. Although detailed comparisons with other low molecular weight heparins and antithrombotic agents are required before its relative clinical utility can be fully assessed, enoxaparin is likely to play a significant role in the prophylaxis of thromboembolic disorders.

Biological Availability↗
PubMed2002

Antipsychotic-induced venous thromboembolism: a review of the evidence.

Psychiatric disorders themselves and treatment with conventional antipsychotic medications have in a number of early studies been associated with venous thromboembolism. In general, information on the relationship between antipsychotics and this possible adverse effect is in the form of case reports and open cross-sectional studies. However, recently the association between conventional antipsychotics and venous thrombosis has been strengthened as a result of the publication of a large, nested, case-control study. In this study, low-potency antipsychotic drugs were more strongly associated with venous thrombosis than high-potency drugs. In addition, recent epidemiological data support an association between the atypical antipsychotic agent clozapine and venous thromboembolism. The risk for venous thromboembolism seems to be highest during the initial months of treatment with antipsychotics. The biological mechanisms responsible for this possible adverse drug reaction are unknown, but a number of hypotheses have been suggested. The increased risk may be the result of drug-induced sedation, obesity, hyperleptinaemia, antiphospholipid antibodies and increased activity in the coagulation system. The association could also be related to underlying risk factors present in patients with psychosis such as smoking. Despite the limitations of present knowledge, clinicians should be aware of this possible adverse drug reaction and should consider interrupting or changing the antipsychotic regimen in patients in whom this reaction is suspected. More studies are needed in order to further elucidate this adverse effect, particularly to determine the incidence rate, possible predisposing factors and the biological mechanisms involved.

Antipsychotic Agents↗
PubMed1985

Perfusion lung scanning: differentiation of primary from thromboembolic pulmonary hypertension.

Of eight patients with pulmonary arterial hypertension, final diagnosis established by autopsy or angiography, four had primary hypertension and four hypertension from thromboembolism. The perfusion lung scan was distinctly different in the two groups. The lung scan in primary pulmonary hypertension was associated with nonsegmental, patchy defects of perfusion, while in thromboembolic hypertensives it was characterized by segmental and/or lobar defects of perfusion with or without subsegmental defects. The perfusion lung scan is a valuable, noninvasive study in the evaluation of the patient with pulmonary hypertension of undetermined cause and in the exclusion of occult large-vessel pulmonary thromboembolism.

Adult↗
PubMed1977

Nitroblue tetrazolium test in pulmonary thromboembolism and pneumonia.

The histochemical nitroblue tetrazolium (NBT) test was performed in 88 patients with acute pulmonary thromboembolism or lobar pneumonia and in 88 healthy control subjects. In the control group, the mean NBT score was 5.4%. In the group of 55 patients with pulmonary thromboembolism the mean NBT score was 6.5% which is insignificantly different from the control mean. Only 3 of these patients had scores above normal. 35 embolism patients were followed by repeated examinations for 1 week after admission. The NBT scores remained within normal limits. 29 of the 33 patients with lobar pneumonia had elevated scores, and the mean NBT score was 33.5%. Endotoxin stimulated NBT test disclosed normal enhancement of NBT reduction by neutrophils from patients in either group as well as controls. The NBT test is of value in the differential diagnosis of pulmonary infection and thromboembolic disease. However, the results should be interpreted in the light of other pertinent laboratory and clinical findings.

Acute Disease↗
PubMed2003

Improvements in the prevention of postoperative venous thromboembolism in hip fracture patients.

Hip fracture surgery carries a high risk of venous thromboembolism and, until recently, was poorly investigated. The efficacy and safety of fondaparinux, a new synthetic antithrombotic, were investigated in two large, thromboprophylaxis studies. Results of the Penthifra study, which was a randomized, double-blind phase III trial, showed that 1 week of fondaparinux, compared with enoxaparin, significantly reduced venous thromboembolic events from 19.1% to 8.3% (relative risk reduction: 56.4%; P<.001) without increasing bleeding risk. Penthifra Plus results showed that extending fondaparinux prophylaxis from 1 to 4 weeks was well tolerated and, compared to placebo, significantly reduced delayed venous thromboembolism events from 35% to 1.4% (relative risk reduction: 95.9%; P<.001). Based on these findings, 4-week fondaparinux treatment may become the standard thromboprophylaxis after hip fracture surgery.

Adolescent↗
PubMed2006

Surgical treatment of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension is a commonly overlooked cause of physical incapacity and dyspnoea, with a higher incidence than is generally appreciated and a poor prognosis. The diagnosis can be suspected based on echocardiographic examinations and ventilation perfusion scanning of the lung. Pulmonary angiography still remains the gold standard for the diagnosis of thromboembolic pulmonary hypertension and the assessment of operability. Pulmonary endarterectomy is a complex surgical procedure, which provides permanent relief of thromboembolic pulmonary hypertension and cure for most of the patients. The operation resembles a true endarterectomy of the pulmonary artery branches using extracorporeal circulation and periods of hypothermic circulatory arrest. In experienced centres, the operative risk has been decreased to an acceptable level. Following successful surgery, long-term survival and quality of life are excellent. Earlier referral to surgery might avoid the occurrence of a secondary vasculopathy in the unaffected areas of the pulmonary vascular tree, and therefore further improve early and late results. A multidisciplinary approach and surgical experience are the prerequisites for success of this demanding procedure.

Animals↗
PubMedDate not supplied

Paraneoplastic thrombocytosis-induced systemic thromboembolism in a cat.

A six-year-old cat presented with clinical signs consistent with distal aortic thromboembolism while clinical signs of cardiovascular disease were absent. Diagnostics, including thoracic radiographs, electrocardiography, and echocardiography revealed no cardiovascular anomalies. Thoracic radiographs revealed multifocal pulmonary lesions consistent with neoplasia. Complete blood cell count demonstrated a marked thrombocytosis, leukopenia, and neutropenia. Histopathology of the pulmonary lesions confirmed multiple bronchoalveolar carcinomas. Myelodysplasia with megakaryocytic hyperplasia and ineffective myelopoiesis was noted on bone-marrow histopathology from multiple sites. The absence of other causes suggested a paraneoplastic thrombocytosis. The diagnosis of paraneoplastic thrombocytosis-induced thromboembolism was made due to the lack of underlying cardiac disease and the presence of a marked thrombocytosis. The presence of thrombocytosis and thromboembolism associated with neoplasia is discussed.

Animals↗
PubMedDate not supplied

Thromboembolism after hip and knee arthroplasty: diagnosis and treatment.

Postoperative thromboembolism is a potentially lethal complication. Its diagnosis may be difficult, as the classic clinical signs and symptoms are often absent, making a high index of suspicion imperative for diagnosis. Anticoagulant therapy is effective in reducing morbidity and mortality due to thromboembolism, but is associated with a substantial rate of bleeding complications in the immediate postoperative period. Inferior vena cava filters constitute an alternative to anticoagulant therapy, but are also associated with a substantial complication rate. The appropriate use of diagnostic tests combined with clinical suspicion can guide the orthopaedic surgeon in deciding which patients require treatment for thromboembolism.

Algorithms↗
PubMed1993

D-dimer in the early diagnosis of thromboembolic disease in acute spinal injuries.

The role of monitoring plasma levels of D-dimer (XDP) as a diagnostic aid for thromboembolic disease was investigated in 267 patients admitted for acute care to the Prince Henry Hospital Spinal Unit. Elevated plasma XDP levels were found in 103 patients (39%) and a diagnosis of thromboembolic disease was made in 33. Thromboembolic disease was not found in patients whose XDP levels remained normal.

Acute Disease↗
PubMed2001

Combined factor V Leiden and prothrombin genotyping in patients presenting with thromboembolic episodes.

BACKGROUND: Several genetic defects are associated with increased risk of venous thrombosis. The factor V Leiden (FVL) and prothrombin G20210A mutations are the most frequent causes of inherited thrombophilia. OBJECTIVES: To evaluate combined genotyping for these 2 mutations in patients presenting with thromboembolic episodes and to correlate genotypic findings with clinical characteristics. RESULTS: Blood specimens were collected from 401 patients presenting with thromboembolic disease between January 1998 and September 1998, and genotyping for both FVL and prothrombin mutations was performed. Thirty-two patients (8%) were heterozygous for FVL, 4 (1%) were homozygous for FVL, and 20 (5%) were heterozygous for the prothrombin mutation. Two cases (0.5%) were identified with combined FVL and prothrombin mutations. The most common clinical presentation was lower-extremity deep vein thrombosis with or without pulmonary embolism. Arterial events were rare. The thromboembolic episodes were often precipitated by additional risk factors. Recurrent disease was found in 73.9% of FVL carriers and 52.9% of prothrombin mutation carriers; 52% of the patients with FVL and 50% of prothrombin mutation carriers had a first thrombotic episode before age 45 years. The 2 cases with combined genetic defects demonstrate amplified thrombotic risk. In the first case this was effected in thrombosis at a young age, and recurrence of thrombotic events even in the absence of precipitating factors. A complex interplay between genetic and additional risk factors was seen in the second case. CONCLUSIONS: Identification of both FVL and prothrombin mutations is important in the overall assessment and management of patients with thrombophilia. Detection of these mutations can identify patients at high risk and help evaluate the interaction of genetic and acquired risk factors.

Adult↗
PubMed2002

Factor XIII polymorphisms and venous thromboembolism.

OBJECTIVE: To review the relationship between factor XIII polymorphisms and venous thromboembolism. METHODS: Review of the medical literature using computerized databases and secondary sources identified through reviews of bibliographies. DATA SYNTHESIS: Plasma factor XIII is the precursor of a transglutaminase that cross-links fibrin, thereby altering its properties, including resistance to fibrinolysis. It is, therefore, biologically plausible that alterations in factor XIII activity could affect thrombosis risk. There are 4 common polymorphic forms of factor XIII that differ among ethnic groups. The Val34Leu polymorphism results in an amino acid change near the thrombin cleavage site that may alter the rate of activation. Several case-control studies have investigated the relation of the Val34Leu polymorphism to venous thromboembolism. Some have shown a potentially protective effect of this polymorphism, but the association is not consistent. CONCLUSION: Evidence is conflicting regarding the association of the factor XIII Val34Leu polymorphism with risk of venous thromboembolism, and further studies are needed before screening for this polymorphism can be recommended for evaluation of thrombophilia.

Blood Coagulation Tests↗
PubMed1998

Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography.

BACKGROUND: Transesophageal echocardiography (TEE) visualizes potential sources of embolism in patients with atrial fibrillation, but the clinical significance of TEE findings has not been prospectively established. OBJECTIVE: To define TEE predictors of stroke in patients with atrial fibrillation and to examine response to antithrombotic therapy. DESIGN: Prospective correlation of TEE findings at study entry with subsequent ischemic stroke during 1.1-year mean follow-up of participants in a randomized trial. SETTING: 18 echocardiography laboratories. PATIENTS: 382 patients with atrial fibrillation at high risk for thromboembolism. INTERVENTION: Adjusted-dose warfarin (international normalized ratio, 2 to 3) or low-intensity warfarin (international normalized ratio, 1.2 to 1.5) plus aspirin (325 mg/d). MEASUREMENTS: Size of left atrium and left atrial appendage, flow velocity, spontaneous echocardiographic contrast, thrombus, and plaque on the aortic arch. RESULTS: 23 ischemic strokes occurred. In patients with dense spontaneous echocardiographic contrast (20%), the rate of stroke was 18.2% per year with combination therapy (2.9 times the rate in patients without this finding; P = 0.06) and 4.5% per year with adjusted-dose warfarin (P = 0.09 for rate reduction). Appendage thrombus, detected in 10% of patients, was associated with dense spontaneous echocardiographic contrast (P < 0.001), was seen more frequently after 2 weeks of combination therapy (15%) than after 2 weeks of adjusted-dose warfarin (4%) (P = 0.004), and tripled the overall rate of stroke (P = 0.04). Patients with complex aortic plaque (35%) had a fourfold increased rate of stroke compared with plaque-free patients (P = 0.005); adjusted-dose warfarin decreased risk by 75% (P = 0.02). Dense spontaneous echocardiographic contrast and complex aortic plaque were independent of each other as predictors of thromboembolism. CONCLUSIONS: In high-risk patients with atrial fibrillation, subsequent rates of thromboembolism are correlated with dense spontaneous echocardiographic contrast, thrombus of the atrial appendage, and aortic plaque. Adjusted-dose warfarin reduces the rate of stroke among patients with dense contrast and complex plaque. In patients with atrial fibrillation, the pathogenesis of stroke is multifactorial, and warfarin seems effective for the diverse mechanisms.

Aged↗
PubMedDate not supplied

[Prophylaxis of venous thromboembolism in medical patients: from medical decision tools to the use of low molecular weight heparin].

In France, low molecular weight heparins are largely used for prophylaxis of venous thromboembolic disease in medical patients. Although clinical trials show their efficacy in some particular clinical situations, there is no consensus about their use in non-surgical patients. A consequence is a wide disparity of prophylaxis of venous thromboembolic disease regimens: such a situation was observed during a practice survey in two medical units of the general hospital of Lunéville. So, prior assessment for pharmacists and physicians was carried out to determine tools which guide decision-making. These comprise clinical practice guidelines, a record card which allows the scoring of risk for venous thromboembolic disease and a clinical algorithm leading to the appropriate prescription according to the risk and the haematological results. A second concomitant practice survey was organized in the same two units in order to measure the appropriateness of the decision-making tools in medical practice. The four-month study included 108 medical patients. The process was successful because: (1) validated practices are improved, particularly in respect of biological monitoring during treatment, and (2) the disparity of therapeutic strategies is highly reduced, the clinical practice guidelines being followed in 81 per cent of all cases. Despite the lack of consensus, heightened awareness of the attendant risk in many medical conditions allows appropriate prophylactic measures to be taken. These measures need decision-making tools that are easy to use and that improve heparin prescribing and thus healthcare quality.

Aged↗
PubMed1999

Bileaflet mechanical prostheses for aortic valve replacement in patients younger than 65 years and 65 years of age or older: major thromboembolic and hemorrhagic complications.

OBJECTIVE: To determine major thromboembolic and hemorrhagic complications and predictive risk factors associated with aortic valve replacement (AVR), using bileaflet mechanical prostheses (CarboMedics and St. Jude Medical). DESIGN: A case series. SETTING: Cardiac surgical services at the teaching institutions of the University of British Columbia. PATIENTS AND METHODS: Patients 2 age groups who had undergone AVR between 1989 and 1994 were studied. Group 1 comprised 384 patients younger than 65 years. Group 2 comprised 215 patients 65 years of age and older. RESULTS: The linearized rates of major thromboembolism (TE) occurring after AVR were 1.54%/patient-year for group 1 and 3.32%/patient-year for group 2; the rates for major TE occurring more than 30 days after AVR were 1.13%/patient-year for group 1 and 1.55%/patient-year for group 2. The crude rates for major TE occurring within 30 days of AVR were 1.04% for group 1 and 3.72% for group 2. The death rate from major TE in group 1 was 0.31%/patient-year and in group 2 was 0.88%/patient-year. Of the major TE events occurring within 30 days, 100% of patients in both age groups were inadequately anticoagulated at the time of the event, and for events occurring more than 30 days after AVR, 45% in group 1 and 57% in group 2 were inadequately anticoagulated (INR less than 2.0). The overall linearized rates of major hemorrhage were 1.54%/patient-year for group 1 and 2.21%/patient-year for group 2. There were no cases of prosthesis thrombosis in either group. The mean (and standard error) overall freedom from major TE for group 1 patients at 5 years was 95.6% (1.4%) and with exclusion of early events was 96.7% (1.3%); for group 2 patients the rates were 90.0% (3.2%) and 93.7% (3.0%), respectively. The mean (and SE) overall freedom from major and fatal TE and hemorrhage for group 1 patients was 90.1% (2.3%) and with exclusion of early events was 91.2% (2.3%); for group 2 patients the rates were 87.9% (3.1%) and 92.5% (2.9%), respectively. The 5-year rate for freedom from valve-related death for group 1 patients was 96.3% (2.1%) and for group 2 patients was 97.2% (1.2%). CONCLUSION: The thromboembolic and hemorrhagic complications after AVR with bileaflet mechanical prostheses occur more frequently and result in more deaths in patients 65 years of age and older than in patients years younger than 65 years.

Adult↗
PubMedDate not supplied

[Long term prevention of thromboembolic accidents with acetylsalicylic acid in auricular fibrillation patients].

For the past few years various authors have reported the antiplatelet action and prolongation of bleeding time with the use of acetyl-salicilic acid. In the present work, we review the frequency of thromboembolism in a group of patients with rheumatic or sclerotic heart disease with atrial fibrillation, in which the treatment with coumarins was suspended and substituted for 1 gram of aspirin P.O. daily. The results were compared with a similar group studied by Cárdenas and col. During the time of the observation 10 patients had 14 thromboembolic accidents, slightly predominated by the emboli in the inferior members and in the cerebral vascular territory. The mortality was 2.5% and in 9 patients hemorrhages of little importance appeared, which could have been caused by the ASA, although it can not be proven. In comparing the results of this work with the above mentioned of Cárdenas, it appeared that the number of thromboemboli, of deaths, and secondary accidents in the group treated with ASA was less than in the group which received coumarin or which were maintained without treatment. Based on the results, it can be concluded that it is possible to substitute the coumarins with acetyl-salicilic acid in the prevention of thromboembolism, in patient with rheumatic or sclerotic heart disease with atrial fibrillation.

Adult↗
PubMed1999

Cancer and venous thromboembolism: an overview.

BACKGROUND AND OBJECTIVE: Although the relationship between malignant diseases and venous thromboembolism has been convincingly demonstrated, the clinical implications of this association still have to be thoroughly elucidated. The aim of this study was to review briefly the mechanisms by which cancer may induce the development of thrombosis and to analyze critically the most recent clinical advances in this field. EVIDENCE AND INFORMATION SOURCES: The material examined in the present review includes articles published in journals covered by the Science Citation Index and Medline . STATE OF THE ART: Neoplastic cells can activate the clotting system directly, thereby generating thrombin, or indirectly, by stimulating mononuclear cells to synthesize and express various procoagulants. Cancer cells and chemotherapeutic agents can injure endothelial cells, thereby intensifying hypercoagulability. Currently, primary prevention of venous thrombosis should be considered for cancer patients during and immediately after chemotherapy, when long-term indwelling central venous catheters are placed, during prolonged immobilization from any cause, and following surgical interventions. Secondary prevention of recurrent venous thromboses usually necessitates long-term anticoagulation. In some patients with cancer the condition is resistant to warfarin, and long-term adjusted high-dose heparin is required. The diagnosis of venous thromboembolism may help to uncover previously occult carcinoma by prompting a complete physical examination and a few routine tests. PERSPECTIVES: Further investigations are required to evaluate the cost-benefit ratio of extensive diagnostic screening for occult malignancy in all patients presenting with idiopathic venous thromboembolism, and to explore the potential of low molecular weight heparins for improving survival in patients with cancer.

Humans↗
PubMed1999

[Thromboembolic diseases in children].

The incidence of thromboembolic diseases in children is increasing, probably as a consequence of medical progress and modern intensive care. Due to lack of scientific evidence, clinical recommendations for treatment of children are mainly based on opinions and extrapolations from adult medicine. This article presents current concepts of thromboembolic diseases in children, based on a review of the literature. Characteristic features are presented and differences between the disease in adults and children are outlined. Guidelines for antithrombotic treatment are provided. We suggest that screening for thrombophilic disorders should be performed on wide indications, and that modern principles of treatment in adult medicine should also be applied for children with thromboembolic diseases.

Adult↗
PubMed1999

Thrombophilic factors and their relation to thromboembolic and other clinical manifestations in Behçet's disease.

OBJECTIVE: To evaluate the prevalence of thrombophilic factors known to induce intravascular clotting and to assess their relationship with thromboembolic complications and the other clinical manifestations in Behçet's disease (BD). METHODS: Twenty-five patients with established BD were studied. Twenty patients with rheumatic conditions not known to be associated with venous or arterial thromboembolic phenomena served as controls. Eight of the patients with BD (32%) had either deep vein thrombosis (6 patients), arterial thromboembolic phenomena (2), or both (2). All participants were tested for IgG and IgM anticardiolipin antibody (aCL) levels, the presence of circulating lupus anticoagulant (LAC), protein C, protein S, and antithrombin III activity, activated protein C resistance, and where appropriate factor V Leiden mutation. RESULTS: Elevated levels of IgG aCL were detected in 10 (40%) patients with BD compared to one (5%) in the control group (p = 0.012). No significant differences were noted in the other variables studied between the 2 groups. No statistically significant correlation was found between any variable and the clinical manifestations. CONCLUSION: Patients with BD do not have decreased protein C, protein S, or antithrombin III activity, activated protein C resistance, circulating LAC, or elevated levels of IgM aCL. A significant number of patients have elevated levels of IgG aCL but they are not associated with venous or arterial thrombosis. No correlation was found between any variable and other clinical manifestations of the disease.

Adult↗