Comparison of plasma prothrombin and factor VII and urine prothrombin F1 concentrations in patients on long-term warfarin therapy and those in the initial phase

Abstract

Control of warfarin anticoagulation during the initial phase of therapy is difficult and empirically based. Plasma and urine samples were obtained from normal controls, patients under stable anticoagulation, and patients in the initial phase of anticoagulation. Total plasma prothrombin, des-carboxy (non-adsorbable with barium chloride) prothrom-bin, and native (total minus non-adsorbable) prothrombin were quantitated using Echis carinatus venom activation. Functional plasma factor VII (VII) was measured using a one-stage clotting assay. Total and des-carboxy urine prothrombin F1 (F1) were measured by ELISA. All urine F1 in normals and both anticoagulated groups was adsorbed by barium chloride. Plasma des-carboxy prothrombin concentration was similar for the two anticoagulated groups and did not correlate with 1/INR. Native prothrombin correlated with 1/INR in both the stable (r = 0.76) and initial phase (r = 0.74) groups. For any given INR, the subjects on stable anticoagulation had lower native prothrombin concentrations than the initial phase patients. Functional factor VII concentration also correlated significantly with 1/INR in both the stable (r = 0.64) and initial phase (r = 0.76) patients. Unlike native prothrombin, VII concentrations did not vary between the two cohorts for any given INR. Previous studies indicate that native prothrombin is a superior predictor of both hemorrhagic and thromboembolic complications during warfarin therapy. Our findings indicate that VII, and not prothrombin, may be the predominant factor monitored by the INR. This further supports the need to reevaluate the usefulness of the INR in the monitoring of warfarin therapy during the initial phase. Am.

Phospholipid composition controls thromboplastin sensitivity to individual clotting factors

“…Coumarins depress the plasma levels of FVII, FX, and prothrombin to differing degrees, ranging from about 10–40% of normal in therapeutically anticoagulated patients [12,13,25–29]. To better compare thromboplastin properties using clotting factor deficiencies spanning the therapeutic range, we replotted PT ratio data from Fig.…”

“…Even in stably anticoagulated patients, the plasma levels of FVII, FX, and prothrombin may be depressed to different degrees [25–28]. Some studies have attempted to correlate the plasma activities of single coagulation factors with INR values from individual patients, variously concluding that INR correlates best with deficiency in FVII [12,25], a combination of FVII and prothrombin deficiency [29], or native prothrombin [35]. Our results suggest that differences in the apparent contributions of individual clotting factors to INR may result from using thromboplastins with differing relative sensitivities to FVII, FX, and prothrombin.…”

“…Recombinant thromboplastins have also been criticized for being overly sensitive to plasma FVII levels [7–9]. FVII has a short plasma half‐life so its levels may fluctuate, especially during the onset of oral anticoagulant therapy [12–15].…”

Factor VII R353Q genetic polymorphism is associated with altered warfarin sensitivity among CYP2C9 *1/*1 carriers

“…Thus, even when identical INR values are measured, the plasma concentration of these coagulation factors may greatly vary between induction and stable anticoagulation within the same patient. In the study by Weinstock et al [35], plasma levels of factors II and VII were compared in the initial phase of warfarin treatment and during long-term anticoagulation therapy. Both factors significantly correlated with INR in both phases.…”

Native prothrombin as an alternative to prothrombin time determination for monitoring oral anticoagulant therapy

“…Technically, they developed an antibody versus fully carboxylated native prothrombin which was applied in a radioimmunoassay. Weinstock et al (10) used barium ion absorption for isolating and differentiation of native vs. non-carboxylated prothrombin. They compared stably vs. initially anticoagulated patients and found that native prothrombin correlates with 1/INR in both groups, but for any given INR, the concentration among stably anticoagulated patients is significantly lower than among patients in the initial phase.…”