Levels of Blood-coagulation Factors During Anticoagulant Therapy with Phenindione

Abstract

The complex mechanism of the factors concerned in blood coagulation has been investigated in many ways, not least among these being a study of such factors during anticoagulant therapy, and by the use of plasma from patients treated with anticoagulant drugs in crossmixture experiments with plasma from patients having congenital coagulation defects. Earlier results from such investigations indicated a simple deficiency of prothrombin and "factor VII." It is now known, however, that Christmas factor (Douglas, 1955;Biggs, 1956;Naeye, 1957), plasma thromboplastin antecedent (Naeye, 1957), and Prower-Stuart factor (Telfer, Denson, and Wright, 1956;Hougie, Barrow, and Graham, 1957;Denson, 1958) are all reduced. Factor X* (Duckert, Fliickiger, Matter, and Koller, 1955) is also reduced early in therapy. The existence of the latter factor as a separate entity, however, has not been established, and it is probably an intermediate product of thromboplastin formation. Horder (1958) studied levels of factor VII, ProwerStuart factor, and prothrombin, together with the partial thromboplastin time, and thromboplastin generation in one case receiving anticoagulant therapy with the coumarin derivative phenprocoumon (" marcoumar"; 4-hydroxy-3-(1-phenylpropyl)coumarin).Hicks and Bonnin (1959) compared the reduction in plasma thromboplastic factors, the one-stage prothrombin time, and the two-stage prothrombin levels in several cases receiving anticoagulant therapy with different drugs, and concluded that the one-stage assay provided an adequate measure of the reduction in thromboplastic factors.The present study was undertaken in order to provide a clearer insight into the fate of specific bloodcoagulation factors during anticoagulant therapy with the drug phenindione (" dindevan "; 2-phenyl-1,3-indanedione), and to endeavour to discover by means of specific assays the contribution of individual factors to the overall effect of anticoagulant therapy. Materials and MethodsCollection and Storage of Plasma and Serum Samples.-Blood was collected simultaneously into a clean sterile tube for the production of serum, and into 1/10 volume of 3.8% sodium citrate for citrated plasma. The clotted specimen was centrifuged after four to six hours and the serum separated and stored at 0°C. for periods of up to 10 days for the assay of thromboplastic factors; these assays were carried out in batches. Plasma was obtained by centrifuging the citrated blood at 2,500 r.p.m. for five minutes. Prower-Stuart factor assays and factor VII assays were performed within two to three hours of collection, and the remaining plasma was stored at 00 C. for periods of up to two weeks for the two-stage prothrombin determinations, which were carried out in batches.*Prower-Stuart factor has now been designated Factor X by international convention.Prower-Stuart Factor Assay and Specific Factor VII Assay.-These were performed as previously described (Denson, 1961).Assay of Serum Thromboplastic Factors.-This was carried out using the thromboplastin generation method of...

Coagulation factors in chronic liver disease

“…On the other hand we have found Thrombotest to be a good indicator of deficiency of factor IX ( Fig. 1) in this group of patients, although Thrombotest has been reported as relatively insensitive in detecting deficiency of factor IX in the plasma of patients with Christmas disease or in patients who are receiving therapy with phenindione (Denson, 1961). We do not have an explanation for this (unexpected) finding, although we note that the occasional patient with congenital factor IX deficiency may have a prolonged Thrombotest (Kidd, Denson, and Biggs, 1963).…”

The Levels of Factors II, VII, IX and X by Antibody Neutralization Techniques in the Plasma of Patients Receiving Phenindione Therapy

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The levels of factors I1 (prothrombin), VII, IX and X in the plasma of patients on anticoagulant therapy with phenindione have been shown to be higher by antibody neutralization tests than by specific assays.It has now been established by many authors that the plasma concentrations of prothrombin, factor VII, factor IX and factor X are reduced by anticoagulant therapy with phenindione (Dindevan) (Horder, 1958;Denson, 1961; etc.). Recently it has been shown that structurally defective forms of factors VIII, IX and X can be demonstrated in the plasma of patients with haemophilia, Christmas disease and the factor-X defect (Denson et al, 1968(Denson et al, , 1969(Denson et al, , 1970 Hoyer & Breckenridge, 1969; Hougie& Twomey, 1967).

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Comparison of two laboratory tests in the control of anticoagulant therapy

“…This supports our clinical impression that the British corrected ratio is a more reliable guide to safe and effective anticoagulation. Denson (1961) showed that when an oral anticoagulant is administered the levels of the various blood clotting factors fall at different rates. Factor VII is the first to fall and this is reflected in a rapidly lengthening prothrombin time.…”

“…The test most widely used to control anticoagulant therapy is the one-stage prothrombin time based on Quick's technique (Poller, 1969). This test is sensitive to deficiency of factors II, V, VII, and X but is insensitive to a deficiency of factor IX (Denson, 1961).Haemorrhagic complications may occur when the prothrombin time is within the desired therapeutic range (Pollard et al, 1962), and this is a common clinical observation. Eastham (1968) suggested that the activated partial thromboplastin time was a more valuable test for the control of anticoagulant therapy.…”

“…The test most widely used to control anticoagulant therapy is the one-stage prothrombin time based on Quick's technique (Poller, 1969). This test is sensitive to deficiency of factors II, V, VII, and X but is insensitive to a deficiency of factor IX (Denson, 1961).…”