Clot retraction, inhibition

Tephorine and Diparcol, both synthetic antihistamines known to inhibit clot retraction (Bounameaux, 1957 Hugues, 1959), only partially inhibit ATPase activity and superprecipitation of thrombosthenin. Finally, monoiodoacetate, a powerful inhibitor of clot retraction, inhibits neither phenomenon. 

Cytochalasins, drugs that inhibit cellular processes that require actin polymerization and depolymerization (e.g., phagocytosis, cytokinesis, clot retraction, etc.), also act by severing and capping actin filaments. Actin filaments can be stabilized by phalloidin, derived from the poisonous mushroom Amanita phalloides. Assembly of actin filaments into bundles (as in microvilli) and three-dimensional networks is accomplished by two groups of cross-linking proteins (Table 21-6). 

Ticlopidine and clopidogrel are thienopyridines, which through inhibition of platelet aggregation prolong bleeding time and delay clot retraction. The thienopyridines are prescribed for reduction of myocardial infarction and stroke, for treatment of peripheral arterial disease, and in combination with aspirin for acute coronary syndromes. This latter utility appears to result from the fact that both aspirin and the thienopyridines block major amplification pathways, leading to platelet aggregation... 

K8. Kunitada, S., Fitzgerald, G. A., and Fitzgerald, D. J., Inhibition of clot lysis and decreased binding of tissue-type plasminogen activator as a consequence of clot retraction. Blood 19, 1420-1427 (1992). 

Inhibition of platelet aggregation induced by arachidonic acid, U46619, collagen, and ADP (with IC50 values of 51, 84, 191, and 640 pg/ml, respectively) was observed in guinea pig platelet-rich plasma treated with lavandin essential oil. Lavandin oil also destabilized clot retraction (IC50 of 149 pg/ml) induced by thrombin on rat platelet-rich plasma (Ballabeni et al. 2004). 

With very simple equipment, it is possible to observe the inhibition of clot retraction in the presence of the offending drug. However there are limiting factors to the routine application of this procedure. Clot retraction requires the presence of platelets in sufficient numbers. Frequently, the recovery of a normal platelet level after a reaction takes 5-15 days, a time which might be sufficient to allow the antibodies to disappear. 

The inhibition of clot retraction (Ackroyd 1964) should probably be the first test in any program of investigation of suspected allergic platelet destruction. Other procedures used are documented clearly by Ackroyd (1964), who employed them in a classic investigation of thrombocytopenia following Sedormid therapy. 

Fennel oil has antiplatelet activity and ability to inhibit clot retraction in experimental animals. The activity has been correlated with the phenylpropanoid content of the oil. ... 

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