Thromboembolism (Proceedings) - Veterinary Healthcare
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Thromboembolism (Proceedings)


CVC IN SAN DIEGO PROCEEDINGS


Nephrotic syndrome

The etiology of thrombosis in nephrotic syndrome is multifactorial. The association of increased risk has been found in both human and veterinary patients. Factors contributing include decreased anticoagulant activity, increased platelet aggregability , reduced fibrinolysis and increased amounts of clotting factors. Incidence varies in studies from 10-40% of nephrotics, although severity of disease may not be predictive of risk. Other factors to consider include hyperviscosity , hypovolemia and dyslipidemia. The changes noted may be the result of coagulation activation (thrombin generation and tissue factor production) in the damaged glomeruli.

Platelet activity

Evidence includes thrombocytosis, in vitro aggregation studies showing enhanced reactivity to a variety of agonists (ADP, epinephrine, collagen, arachnidonic acid), spontaneous aggregation and elevated β-thromboglobulin levels.

Studies using in vitro models of blood flow have also cast doubt on the significance of the aggregation studies. Although the platelets are more likely to aggregate in suspension, they do not aggregate under flow conditions. Instead fibrin was formed that blocked endothelial cell/platelet interaction. Addition of excess fibrinogen to normal platelets mimicked the findings in nephrotic patients.

Anticoagulant proteins

Reduced levels of AT III have been found and are related somewhat to degree of proteinuria. This often has been linked to increased risk of thrombosis. Other studies have shown increased levels of Protein C, α2-macroglobulin, and heparin cofactor which may partially counterbalance the low ATIII. Total plasma antithrombin activity is in fact enhanced. Tissue factor pathway inhibitor levels are normal.

Fibrinolysis

Generally it has been shown that fibrinolysis is decreased. Clot lysis times are increased. Elevated levels of PAI, lipoprotein (a) and 2-macroglobulin would interfere with fibrinolysis. In addition high levels of fibrinogen and low albumin interfere with plasminogen binding to fibrin.

Elevated clotting factors

Levels of fibrinogen, vWf, factor V, factor VIII and factor XIII are increased in nephrotic syndrome. This is felt to be a result of increased hepatic synthesis or vascular injury.

Pharmacologic manipulations

Aspirin has been shown to be beneficial in slowing the progress of membranous glomerulonephritis in people (950mg/day). Heparin may be very beneficial as it has been able to normalize fibrinopeptide A levels in nephrotics. Fibrinopeptide A is a sensitive indicator of thrombin activity on fibrinogen. Additionally heparin is known to inhibit mesangial cell growth in vitro. The effects of EFA on glomerulonephritis has been investigated in humans and has proven to be beneficial. In those instances where emboli have occurred warfarin may be indicated.

Feline cardiomyopathy

Aortic thromboembolism is a serious complication of feline cardiomyopathy and often predates evidence of heart disease. A retrospective study identified 58% of cats having hypertrophic cardiomyopathy, 27% having intermediate-form, 6.3% having restrictive and 3.2 % having dilated cardiomyopathy. Left atrial enlargement was common with 56.9% having a LA:Ao of 2.0 or greater. Only 5.2% had a normal ratio. Radiographically 88.8% had cardiomegaly and 66.3% had evidence of congestive heart failure. Survival rate was determined as follows: died during hospitalization 28%, euthanized 35%, survived 37%. Warfarin was started in 18 of 22 survivors that were followed. Average survival time of those that died was 9.7 months. Four cases are still alive with an average survival time of 24.3 months. Reembolization occurred in 50% of cases.

Etiology of thrombi

Perturbations of blood flow in the dilated left atrium are felt to be an important factor in pathogenesis of emboli in cardiomyopathy. In addition endomyocardial lesions may be sites for thrombus formation. Platelet aggregation studies have shown a potential hyperaggregable state.


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Source: CVC IN SAN DIEGO PROCEEDINGS,
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