Prevention Of Thromboembolic Disease Research Articles

A Novel Thrombomodulin Gene Mutation in a Patient Suffering from Sagittal Sinus Thrombosis

Thrombomodulin is an endothelial cell membrane glycoprotein that promotes protein C activation. It has been clearly demonstrated that the anticoagulant functions of the protein C system are important in the prevention of thromboembolic disease. Patients with protein C or protein S deficiency and/or resistance to activated protein C (APC resistance) are at higher risk for developing thromboembolic disease. The first mutation in the thrombomodulin gene was discovered in an American patient suffering from pulmonary embolism at the age of 45 (Ohlin and Marlar 1995). Here we report a case of sagittal sinus thrombosis in a 42-year-old Swedish woman. She was found to carry a heterozygous point mutation changing G127 to A, predicting an Ala25 to a Thr change in the mature thrombomodulin protein. This mutation was also found in her 16-year-old daughter, who so far has not suffered from any thrombotic events. The patient had no other detectable prothrombotic genetic defects associated with the coagulation system. This case supports the hypothesis of an association between mutations in the thrombomodulin gene and venous thrombosis.

Soluble thrombomodulin antigen in plasma is increased in patients with acute myocardial infarction treated with thrombolytic therapy

Thrombomodulin (TM) is an integral endothelial cell membrane protein that functions as a cofactor for thrombin mediated activation of protein C. The anticoagulant functions of the protein C system are important in contributing to a hemostatic balance and prevention of thromboembolic disease. It has been suggested that impaired TM cofactor function could also constitute a prothrombotic abnormality leading to thromboembolic diseases. TM exists not only on the surface of endothelial cells but also as soluble fragment(s) circulating in plasma. The concept of a thrombotic occlusion as the critical event in acute myocardial infarction (AMI) forms the rationale for thrombolytic therapy. After successful reperfusion, patients remain at substantial risk for recurrent infarctions due to rethrombosis. The balance between procoagulant and anticoagulant mechanisms in the postthrombolytic phase have not been studied in detail. We have studied whether the plasma levels of soluble TM are influenced by thrombolytic therapy with streptokinase in patients suffering from AMI. Soluble TM concentrations increased significantly by 24 to 48h after thrombolytic treatment, simultaneously with an increase in C-reactive protein (CRP, a marker of the inflammatory component of the cell damage) and in thio-barbituric acid reactive substances (TBARS, an indirect marker of lipid peroxidation).

Enoxaparin

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.

Elevated total plasma homocysteine, a risk factor for thrombosis. Relation to coagulation and fibrinolytic parameters

Homocystinuria is a rare inherited metabolic disease. Arterial and venous thromboembolic events represent frequent and life-threatening complications in homocystinuric patients. It has been suggested that mild homocysteinemia could be a risk factor for vascular disease. We have therefore measured total plasma homocysteine (HCy) concentrations by radioisotopic assay in 50 subjects with venous or arterial thrombosis and studied the relationship between HCy, coagulation and fibrinolytic parameters. Values were considered abnormal if they were higher than 2.7 standard deviations (SD) above the mean. i.e., 14.1 mmol/1. Thus, eighteen of the 50 patients with thrombosis were classified in the hyperhomocysteinemia group. Nine of these subjects had only this isolated risk factor. No correlations were found between HCy and antithrombin III, protein C, protein S and plasminogen levels, or plasma plasminogen activator inhibitor activity. Nevertheless, the correlation between tissue-plasminogen activator antigen and total plasma HCy was significant (r= 0.61, p< 0.001). Increased homocysteinemia seems to be a risk factor for thrombotic events especially knowing that HCy presents a direct cytotoxic effect. Vitamin therapy, already used in homozygote homocystinuric patients, might be beneficial in the prevention of thromboembolic disease in heterozygous patients.

Prevention of Thromboembolic Disease Following Total Knee Arthroplasty

Seventy-two patients were randomized into a prospective clinical trial to evaluate the effects of epidural (EA) versus general anesthesia (GA) on the incidence of thromboembolic disease (TED) following total knee arthroplasty (TKA). Males received aspirin 650 mg po bid and females low-dose warfarin daily to maintain the prothrombin time at 15 to 16 seconds for pharmacologic prophylaxis against TED. Thirty-four patients had EA and 38 GA for their primary TKA. Contrast venography and ventilation-perfusion scanning were performed on the sixth, seventh, and eighth postoperative days, and these were interpreted in a blinded fashion. The mean age of the 45 males and 27 females was 64 years (range, 42-84 years). There were no significant differences between the two groups with respect to hematocrit, operative time, blood loss, number of units transfused, or hospital stay. Twelve of the 34 patients (35%) receiving an EA and 10 of the 38 patients (26%) receiving GA developed TED, an overall incidence of 31% (p greater than 0.05) Fifty-three percent of the clots were located in the popliteal vein above the trifurcation or more proximal. However, the incidence of proximal vein thrombosis was significantly less in patients receiving an EA (46%) rather than a GA (64%). The incidence and distribution of clots was not affected by the type of pharmacologic prophylaxis, gender, or use of methylmethacrylate. Ten percent of the patients had a positive scan by strict criteria and were thought to have a pulmonary embolism (PE). In patients with a femoral vein clot, the incidence of PE was 67%. One bleeding complication occurred in a patient who took double the appropriate warfarin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Etiology and prevention of thromboembolic disease. Taming a complex circulatory malfunction.

Deep venous thrombosis is a complex process involving many factors in the circulatory system, an important one apparently being the intrinsic fibrinolytic system. Specific activators of the process include venous trauma and hypercoagulability states. In spite of efforts at prophylaxis, venous thrombosis will occur, a dangerous condition in itself and also a precursor of pulmonary embolism. Several schemes for prophylaxis, including drug regimens and mechanical means, have been tried, and future research will surely identify others. A patient's best protection against thrombosis at present, however, is a vigilant physician with a high index of suspicion who will expedite diagnosis and treatment if necessary.

Doubts about dipyridamole as an antithrombotic drug

Dipyridamole (Persantin-Boehringer Ingelheim) was introduced in 1959 as a vasodilator for the treatment of angina, but it is now little used for this purpose. The discovery of its effects on platelets has led to its widespread use in a variety of thrombotic conditions, both alone and in combination with other drugs. The manufacturer claims that dipyridamole “offers a real opportunity in the prevention of thromboembolic disease” and the NHS spends well over £5 million a year on the drug. What is the evidence for its clinical efficacy?

Low-dose heparin for prevention of thromboembolic disease in pregnancy

Low-dose heparin for prevention of thromboembolic disease in pregnancy

Prevention of Thromboembolic Disease by External Pneumatic Compression in Patients Undergoing Total Hip Arthroplasty

A prospective study was undertaken in order to test the efficacy of intermittent calf compression for prevention of thromboembolism in patients undergoing total hip arthroplasty. The patients were studied pre- and postoperatively by routine Doppler ultrasound examinations in addition to clinical assessment. Statistically significant evidence substantiates the view that intermittent calf compression decreased the incidence of thr thromboembolic problem.

Prevention of Thromboembolic Disease after Elective Surgery of the Hip

1. A high incidence (53.6 per cent) of venous thrombosis occurs after elective surgery of the hip. 2. The diagnosis of venous thrombosis by clinical signs and symptoms is far less sensitive than by venography. 3. Low molecular weight dextran has a marked protective effect against the occurrence of thromboembolism as demonstrated in a controlled study of 106 elective hip operations. 4. Low molecular weight dextran has been shown to be safe as well as effective. 5. The prophylactic administration of low molecular weight dextran is recommended for patients undergoing elective surgery of the hip.

The Prevention of Thromboembolic Disease By Prophylactic Anticoagulation

A statistically significant protective effect against the occurrence of thromboembolic disease has been demonstrated in a controlled series of 169 elective hip operations in 137 consecutive patients by the use of prophylactic anticoagulation with warfarin.No case of pulmonary embolism and only five