Thrombophilia Testing in Patients with Venous Thrombosis

Background. Routine thrombophilia testing is controversial because of the low yield of positive tests, costs involved, and debate about the clinical usefulness of the data obtained from testing. Laboratory investigations are rarely done for those with superficial venous thrombosis (SVT) or isolated calf vein thrombosis (CVT) which are often not treated with anticoagulants. Objective. To identify the incidence of markers of thrombophilia in patients with deep vein thrombosis (DVT), SVT, isolated CVT or a history of thrombosis in a referral practice. Methods. One hundred and sixty-six patients were referred to our thrombosis unit for consultation, including patients with SVT, DVT, and preoperative patients with a previous history of SVT or DVT. Patients underwent thrombophilia screening and patients with a diagnosis of SVT or DVT were confirmed by bilateral duplex ultrasonography of all lower limb veins. Thrombophilia testing included factor V Leiden (FVL), prothrombin 20210A mutation (P2), methylene tetrahydrofolate reductase deficiency (MTHFR), fasting serum homocysteine (HC), lupus anticoagulant (LA), anticardiolipin antibodies (ACA), antithrombin deficiency (AT), protein S deficiency (PS), and protein C deficiency (PC). Results. The incidence of any significant abnormality in patients with DVT was 27/44 (61%; 95% Confidence interval [CI], 47-76%) and 10 of these patients were positive for FVL (23%; 95% CI, 10-35%). Twelve patients with isolated CVT were seen and five had at least one abnormality (42%; 95% CI, 14-70%) including one with FVL (8%; 95% CI, 0-24%). Thirtynine patients with isolated SVT were seen including 14 with at least one abnormality (36%; 95% CI, 21-51%) and five of these patients with SVT had FVL (13%; 95% CI, 2-23%). Nine patients with recurrent DVT were seen and five of these had at least one abnormal test (56%; 95% CI, 23-88%). Finally, 18 of the 166 patients had more than one abnormality (11%; 95% CI, 6-16%). Conclusion. The presence of one or more markers of thrombophilia was significantly higher in this patient population compared to reports from other centres. This study identified 18/166 (10.8%; 95% CI, 6-16%) with more than one defect where life-long anticoagulation might be considered. The results in this subset of patients as well as the serious defects found in some patients with provoked DVT, isolated CVT or isolated SVT demonstrate the value of this screening program to both these patients and their blood relatives. On the other hand, this is a small series from a referral practice where the incidence of these defects is greater than one would expect in the general population. These studies are preliminary and it is not recommended that all VTE patients should be screened on the basis of the current report

GRID/GOLPE 3D quantitative structure-activity relationship study on a set of benzamides and naphthamides, with affinity for the dopamine D3 receptor subtype

In the search for drugs against schizophrenia and depression without extrapyramidal side effects, compounds that selectively antagonize the dopamine D3 receptor subtype are thought to be a solution. In order to create a model with which the D3 activity can be predicted and that can generate new ideas for future synthesis, we performed a comparative molecular field analysis (CoMFA). In our model 30 ligands were described quantitatively in the GRID program, and the model was optimized by selecting only the most informative variables in the GOLPE program. We found the predictive ability of the model to increase significantly when the number of variables was reduced from 25110 to 784. A Q2 of 0.65 was obtained with the final model, confirming the predictive ability of the model. By studying the PLS coefficients in informative 3D contour plots, ideas for the synthesis of new compounds can be generate