[Diagnosis of thrombophilia based on coagulation and genetic studies]

Venous thromboembolism and associated complications often leading to permanent disability or death are an important problem in modern medicine. Congenital or acquired disorders of the hemostatic system, such as hypercoagulation or thrombophilia, predispose to thrombosis. The aims of the study were as follows: 1. To assess the prevalence of thrombophilia in venous thromboembolism and in healthy subjects by testing resistance to activated protein C and other markers of hemostasis; 2. To screen for factor V Leiden with a PCR-based assay; 3. To evaluate the usefulness of the adopted analytical approach for the detection of thrombophilia in clinical practice. 29 patients (17 females and 12 males) with venous thromboembolism and a history of thrombotic episodes before the age of 40, either idiopathic or associated with protracted immobilization, pregnancy or puerperium, were enrolled in the study. The control group consisted of 25 age-matched healthy subjects (14 females and 11 males) without any history of thrombosis. The following hemostatic parameters were measured: 1. Activated protein C resistance (APC-R); 2. Protein C (PC) and antithrombin III (AT III) activities; 3. Protein S (PS) activity; 4. Fibrinogen (FB) concentration; 5. Euglobin lysis time (ELT); 6. Prothrombin time (PT); 7. Activated partial thromboplastin time (APTT). The presence of Leiden mutation was detected by PCR amplification and digestion of products with Mnl 1 restrictase. The results were tested statistically using: 1. Kolmogorov-Smirnov D test; 2. Student's t-test; 3. linear regression analysis; 4. chi 2 test. The following conclusions were drawn: 1. Prevalence of thrombophilia in patients with venous thromboembolism is 31%, a figure consistent with literature data (no signs of thrombophilia were found in the control group); 2. Resistance to activated protein C is sufficient proof of Leiden mutation provided that APCR index (r) is less than 0.9 (borderline r values (0.9-1.1) require further genetic testing). 3. Methods of diagnosis of thrombophilia used in this study could be applied in routine clinical practice, the most useful ones being resistance to activated protein C, fibrinogen concentration and protein S activity. With this approach the detection of higher risk of thrombotic-embolic episodes, either acquired or inborn, is possible in most cases.