Use of Different Tissue Thromboplastins in the Control of Anticoagulant Therapy

Abstract

As anticoagulant therapy has become more widespread and a greater knowledge has been accumulated regarding the mode of action of coumarin derivatives, problems arising from the use of different thromboplastin preparations have been subjected to greater scrutiny. This paper presents an evaluation of the dependability and significance of different types of tissue thromboplastin in the determination of effects of coumarin derivatives. The main difference between thromboplastin extracts seems to be that brain preparations have a factor VII-like activity. As the exact evaluation of factor VII activity appears to be of primary importance in patients treated with coumarin derivatives, a thromboplastin preparation that does not contain factor VII activity is recommended.A THE indications for anticoagulant therapy become more extended, some problems in the management of anticoagulant therapy with coumarin derivatives and their laboratory control become increasingly important.Until recently very little was known about the mode of action of coumarin derivatives. It has been shown that the activity of factor VII and subsequently of prothrombin decreases during coumarin therapy. This diminution is usually directly related to the antithrombotic activity of coumarin derivatives. Douglas' has recently shown that the prothrombin level of the blood does not fall below 50 per cent of normal during adequate therapy with 3,3'-carboxymethylenebis (4 -hydroxycoumarin) ethyl ester (Tromexan). The prolongation of the prothrombin time by the 1-stage method is partly due to the deficiency of factor VII and the moderate depression of prothrombin is insufficient to decrease blood coagulability. Recent studies have also demonstrated that the activity of other clotting factors, such as plasma thromboplastin component (PTC, factor IX, Christmas factor)2' 3 and factor X4 5 decreases during coumarin therapy. The influence of coumarin derivatives on the latter 2 factors is not detected by the 1-stage prothrombin determination because potent tissue thromFrom the Vascular

Studies on the Differences in Activity of Lung and Brain Thromboplastin

“…When different tissue Tpl's are used to perform prothrombin times on the plasma of a patient receiving coumarin derivatives, widely varying results may be obtained (1,2,6,(17)(18)(19)(20)(21). In particular, it has been noted that lung Tpl's give longer prothrombin times than do brain Tpl's.…”

“…As evidence for this, it has been observed that as factor VII concentration decreases in the plasma of Dicumarol '-treated patients, the prothrombin time obtained with lung Tpl becomes disproportionately longer than that obtained with brain Tpl (1). The inference from this observation has been that brain Tpl contains a factor VII-like activity, not possessed by lung Tpl.…”

“…If the factor VII-like activity of tissue Tpl was due to contamination by blood and not to intrinsic properties of Tpl itself, one would expect brain Tpl to show less such activity than lung Tpl, inasmuch as lung preparations are more heavily contaminated by blood during their preparation. In addition, Verstraete and associates (1) found that when Tpl solutions were adsorbed with BaSO4, lung Tpl showed a pronounced decrease 1 Bishydroxycoumarin.…”

“…Recent reports have suggested that thromboplastin (Tpl) prepared from lung may reflect more accurately than does brain Tpl the changes produced in the prothrombin complex by coumarin derivatives (1,2). As evidence for this, it has been observed that as factor VII concentration decreases in the plasma of Dicumarol '-treated patients, the prothrombin time obtained with lung Tpl becomes disproportionately longer than that obtained with brain Tpl (1).…”

“…This activity would mask a lowered plasma concentration of factor VII and would result in spuriously short prothrombin times. Verstraete, Clark and Wright (1,2) concluded that brain thromboplastins possess, although to a lesser degree, the disadvantage previously observed for Russell's viper venom (3,4). The latter, by virtue of its intrinsic convertin-like activity, is insensitive to changes in factor VII concentration and is, therefore, no longer used in following anticoagulated patients.…”