Pathogenesis of venous thromboembolism.
ABSTRACT Three factors are related with the pathogenesis of venous thrombosis: (1) blood stasis, (2) hypercoagulability, and (3) vessel damage. Local and systemic factors are implicated in blood stasis. Remarkable advances have been recently achieved regarding the understanding of the concept of hypercoagulability, with special emphasis to thrombophilic molecular abnormalities. Increased thromboembolic risk has been described in patients with antithrombin III, protein C, or protein S deficiencies as well as factor V Leiden, prothrombin mutation G20210A, or hyperhomocystinemia. Vessel wall has a remarkable role in protecting against and in promoting thrombosis. The role of inflammation on venous thrombosis is under investigation.
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ABSTRACT: The intent of the study was to determine whether ultrasonic tissue characterization (UTC) could indicate acuteness and stability of deep venous thrombosis (DVT) of the lower extremities. Thrombi presenting as filling defects on color Doppler imaging in the common or superficial femoral or popliteal veins in 50 extremities in 45 patients with DVT were studied. Acute DVT was less than 4 days duration, and chronic DVT was greater than 21 days duration. UTC analysis of parameters from the normalized power spectrum of backscattered ultrasound signals from venous filling defects was performed. This spectrum approaches a straight line, and its basic parameters, slope, and Y-intercept are related to scatterer size, concentration, and the square of the scatterer-to-medium acoustic impedances. Ten of the DVT extremities were reexamined at 1 week to assess UTC changes that would indicate thrombus instability. Acute DVT (19 of the 50 extremities) could be distinguished from chronic DVT, mainly on the basis of significantly higher intercept values for the acute group, which were 11.6 relative decibels (dBr) higher than those of the chronic DVT group. Discriminant linear analysis of the two parameters indicated a sensitivity of 94.7% and specificity of 90.3% in correctly diagnosing acute DVT. In a small sample of 10 extremities reexamined at 1 week, acute DVT extremities showed a mean 9.4 dBr decrease in intercept values with no significant change in slope. UTC distinguished clinically defined acute from chronic DVT. In a small series of extremities, UTC revealed significant instability of acute thrombi in a selected patient population.Journal of Vascular Surgery 07/1995; 21(6):976-84. DOI:10.1016/S0741-5214(95)70226-1 · 2.98 Impact Factor
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ABSTRACT: Recent report, particularly the Women's Health Initiative, demonstrated that hormone therapy with combined estrogen plus progestin increased the incidence of heart attacks, stroke, blood clots, breast cancer and dementia in women over 65 years old. We investigated the role of synthetic progestins in initiating the adverse events associated with estrogen therapy. We used a fluorescence imaging technique, which allows video microscopic recordings of blood flow, blood vessel morphology and activities of various blood cells in a live animal. The acute peripheral and cerebrovascular responses were measured following intraperitoneal (5 or 10 mg) or intravenous (10 or 100 microg) administration of progesterone, synthetic progestins (medroxyprogesterone acetate and norethindrone) or estrogens (conjugated equine estrogens and 17 beta-estradiol). In both peripheral and cerebral vasculature, synthetic progestins caused endothelial disruption, accumulation of monocytes in the vessel wall, platelet activation and clot formation, which are early events in atherosclerosis, inflammation and thrombosis. Natural progesterone or estrogens did not show such toxicity. The risk associate with combined estrogen plus progestin therapy may be a consequence of vascular actions of progestins. Using progestins with minimal vascular toxicity may lead to safer estrogen preparations for menopausal women.Climacteric 01/2004; 6(4):293-301. DOI:10.1080/cmt.6.4.293.301 · 2.24 Impact Factor
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ABSTRACT: Deaths resulting from pulmonary emboli are common. The autopsy dissection, documentation, and ancillary studies pertaining to pulmonary emboli are important components of evaluating such fatalities. The detection of a saddle embolism at autopsy does not signify the end of the investigation because the underlying risk factors still may need to be determined. The gross, microscopical, and genetic findings can distinguish various thrombotic risk factors and etiologies. Because deaths caused by pulmonary emboli may involve medicolegal issues, a dependable protocol is needed for their investigation. In particular, the timing of a pulmonary embolism may have important medicolegal consequences. Because of the pathophysiology and propagation of a thrombus, one may see a broad histological range of thrombosis and organization. Histological examination of residual deep vein thrombus provides the best opportunity to properly age the thrombus. Understanding the pathogenesis and pitfalls of venous thromboembolism allows the pathologist to properly certify the proximate cause of death. Currently, there are DNA techniques that allow for the postmortem diagnosis of some hereditary thrombophilias. These include factor V, prothrombin, and methylenetetrahydrofolate reductase mutations. Decedents who are candidates for these tests include those who are younger than 45 years of age; those whose deaths were related to pregnancy; those with a history of recurrent or unexplained stillbirths, oral contraceptive pill use, hormone replacement, or treatment with chemotherapy; those with weak risk factors (long car ride, flights, obesity); or those with deep venous thrombosis of undetermined etiology. These tests benefit the investigator, who is attempting to discern the proximate cause, and potentially the surviving family members.12/2004: pages 285-302;