scholarly journals INR and Vitamin K Dependent Coagulation Factor Fluctuation during Warfarin Initiation and Stable Therapy in Patients Dosed with the Fiix-Prothrombin Time or the Quick Prothrombin Time. the Fiix Trial

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4278-4278 ◽  
Author(s):  
Brynja R. Gudmundsdottir ◽  
Petur I. Jonsson ◽  
Pall T. Onundarson
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Target Range ◽  
Startup Company ◽  
Warfarin Treatment ◽  
Monitoring Group ◽  
Equity Ownership ◽  
Patent Applications

Abstract Introduction: The Quick prothrombin time (PT) is equally sensitive to the influence of factors (F) II, VII and X but experiments suggest that it is mainly the influence of warfarin on factors (F) II and X that cause its anticoagulant effect. The new Fiix prothrombin time (Fiix-PT) differs from the PT in it being sensitive only to factors (F) II and X and not being sensitive at all to FVII activity in the test plasma. The Fiix-trial has demonstrated increased stability of warfarin anticoagulation and possibly improved efficacy when monitored with Fiix-PT compared to PT monitoring (unpublished data). However, as very low levels of vitamin K dependent (VKD) factors not measured with the Fiix-PT could possibly have deleterious effect on anticoagulation (AC) outcome, we measured the VKD coagulation factors in plasma obtained from patients on stable warfarin anticoagulation and during the first 30 days of warfarin treatment monitored either with the Fiix-PT or the PT. Methods: In order to define stable anticoagulation in terms of coagulation factor activity, samples from patients enrolled in the Fiix trial and monitored either with Fiix-PT or PT were used. Frozen samples from 20 patients were obtained from each monitoring group. All the samples had been drawn from patients during very stable warfarin treatment (INR within range 2-3 for over 10 months by serial monitoring). Serial samples were also obtained from 10 patients in each group during days 1-30 of warfarin initiation. PT, Fiix-PT and VKD coagulation factors were measured. An INR was calculated for both PT and Fiix-PT. Results: During stable AC, the median INR (range) was 2.5 (2.1-3.0) in the Fiix-group vs 2.4 (2.0-3.0) in the PT group (p=ns). The median (95% range) VKD factor percent coagulant activity was as follows in the stable Fiix-group vs the stable PT-group: FII 28 (19-40) vs 25 (18-40), FVII 48 (30-88) vs 42 (23-85), FIX 66 (41-85) vs 61 (36-79), and FX 15 (11-17) vs 15 (10-22). Although the medians tended to be higher in the Fiix group except for FX, p was n.s. for all. In patients starting on warfarin a stable Fiix-INR (defined as two INRs within target range) was reached on day 14 (median) in the Fiix group vs a stable PT-INR on day 11 in the PT controls. Following this, however, the PT-INR fluctuates more out of the INR target range than the Fiix-INR does. As shown in the figures, the earlier rise in INR in the PT group is mainly a reflection of a rapid fall in FVII activity. The FVII level decreases to a nadir of 20% in the Fiix group compared to a nadir of 30% in the PT monitoring group. Subsequently FII, FVII and FX fluctuate less in the Fiix-PT group than in the PT group. During the first 30 days 46% of Fiix-INRs in the Fiix-group were within target range vs 29% of INRs in the controls (p=0.06). Also during the initiation period FII was 47% vs. 30% within the 95% stable range established for the PT method (p=0.06), FVII 60% vs. 73% (p=0.13), FIX 41% vs 36% (p=0.69), and FX 51% vs 38% (p=0.20), respectively. The more fluctuating INR in the PT group is also reflected by a rollercoaster like pattern of warfarin dosing as opposed to the more cascade like pattern that is observed in the Fiix group. Figure 1 Figure 1. Figure 2 Figure 2. Conclusion: During stable warfarin AC VKD factors are similarly reduced with Fiix-PT or PT monitoring.During initiation of warfarin monitored with the Fiix-PT, FVII decreases initially more than with PT monitoring but subsequently stabilizes and fluctuates less. Fiix-PT leads to smoother reduction in FII and X which stabilize faster than during PT monitoring. The smoother anticoagulant effect is also reflected by the warfarin dose pattern during initiation. The results may suggest that the Quick-PT confounds warfarin management during initiation and dose changes. Disclosures Gudmundsdottir: Fiix Diagnostics Ltd: Equity Ownership, I am a co-inventor of the Fiix prothrombin time and have stocks in Fiix Diagnostics, a startup company with the two inventors of the test as majority shareholders. The company is responsible for patent applications in process. Patents & Royalties. Onundarson:Fiix Diagnostics Ltd: Equity Ownership, I am a co-inventor of the Fiix prothrombin time and have stocks in Fiix Diagnostics, a startup company with the two inventors of the test as majority shareholders. The company is responsible for patent applications in process. Patents & Royalties.

Coagulation Induced by Dilute Tissue Factor Depends More Critically on Factor II and X Concentration Than on FVII or FIX

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4084-4084
Author(s):  
Brynja R. Gudmundsdottir ◽  
Alexia M Bjornsdottir ◽  
Pall T. Onundarson
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Platelet Rich Plasma ◽  
Coagulation Factor ◽  
Maximum Velocity ◽  
Coagulation Factors ◽  
Factor X ◽  
Platelet Poor Plasma ◽  
Stabilization Phase ◽  
Maximum Clot Firmness

Abstract Prothrombin time based tests used to monitor coumarin anticoagulation measure the initiation phase of fibrin formation (clotting time, CT) in platelet poor plasma. Additional information can be obtained using computerized rotational thromboelastometry (ROTEM) which also measures the consequent propagation phase (measured as maximum velocity, Vmax), and the stabilization phase (maximum clot firmness, MCF). We used ROTEM to study the effect of individual vitamin K dependent (VK) coagulation factor (F) concentration on clotting induced by dilute thromboplastin in platelet poor and platelet rich plasma (PPP and PRP). As expected, FII, FVII and FX in PPP equally affected the prothrombin time whereas FIX did not. In PPP the ROTEM CT, however, was affected more by the concentration of FII and FX than by FVII (data not shown). To imitate physiological clotting better, factor deficient platelet poor plasma was repleted by adding frozen platelets in an optimal concentration corresponding to 100 × 109/L.. In the PRP the ROTEM CT was more dependent on the concentration of FII than of FVII, more dependent on FX than on FII and not dependent on FIX at all (left figure). The Vmax (reflecting the propagation phase) was also more dependent on FII and factor X than on the concentration of FVII or FIX which both may demonstrate a threshold effect (right figure). The stabilization phase or maximum clot firmness (MCF, not shown) was influenced similarly by FII and FX but was not influenced by FVII or FIX. Figure Figure Conclusion: During deficiency of vitamin K dependent coagulation factors the concentration of FII and FX may be more critical for hemostasis than FVII or FIX concentration. This may have practical implications for the appropriate choice of monitoring assays during coumarin administration.

scholarly journals Differential Impact of Dietary Vitamin K (phylloquinone) on Coagulation Factor Activities and Clotting Times in Warfarin-Treated Rats

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1310-1310
Author(s):  
Guylaine Ferland ◽  
Cylia Djennadi ◽  
Bouchra Ouliass
Keyword(s):  
Vitamin K ◽  
Clinical Laboratory ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Diet Group ◽  
Dietary Vitamin ◽  
Plain Water ◽  
Coagulation Activity ◽  
Warfarin Treatment ◽  
The Impact

Abstract Objectives Investigate the impact of variable vitamin K (VK) intakes on the coagulation activities of four VK-dependent factors and clotting times, in warfarin-treated rats. Methods Male Wistar rats were randomly allocated to a AIN-93 based diet containing low (L: 80 mcg/kg/d), adequate (A: 750 mcg/kg/d) or enriched (E: 2000 mcg/kg/d) phylloquinone (K1) containing diet (n = 24/diet group). After one week, half the animals from each diet group were randomly allocated to receive 0.2 mg warfarin/kg/d through drinking water (W gp) or plain water (C gp), for 10 weeks. Coagulation activity (%) was assessed for factors II, VII, IX and X, and clotting times were based on prothrombin [PT (sec)] and activated thromboplastin times [APTT (sec)]. Measures were obtained at the end of the study and were conducted in the hospital clinical laboratory using standard procedures. Diet effects within C and W groups were investigated using one-way ANOVA and uncorrected Fisher post-hoc tests. Results Warfarin treatment resulted in significantly higher clotting times (PT and APTT) in all diet groups when compared to corresponding C groups (p < 0.05), the highest increase being observed in the L, followed by A and E groups, each diet being statistically different from each other (p < 0.01). Warfarin treatment also resulted in statistically significant decreases in activities of all coagulation factors although the impact of the diets varied according to factors: FVII and FX, between L and E groups only; FIX, between L and A, and L and E groups; FII, between all diet groups; (p < 0.05 in all cases). Conclusions Results from this study confirm the impact of dietary VK on coagulation factor activities and resulting clotting times, and suggest that for a given dose of W, this impact will depend on VK intake levels. Currently, individuals undergoing warfarin treatment are advised to aim for stable daily VK intakes. Results from this study provide data supporting this recommendation. Funding Sources This study was funded by CIHR and MHI Foundation.

Critical Role of Factors II and X During Coumarin Anticoagulation and Their Combined Measurement with a New Prothrombin Time Variant (Fiix-PT),

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3354-3354
Author(s):  
Pall T. Onundarson ◽  
Brynja R. Gudmundsdottir ◽  
Charles W. Francis
Keyword(s):  
Prothrombin Time ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Critical Role ◽  
Patent Application ◽  
Maximum Velocity ◽  
Coagulation Factors ◽  
Clot Formation ◽  
Normal Platelet ◽  
Anticoagulated Patients

Abstract Abstract 3354 Introduction: Vitamin K antagonists (VKA) are monitored with prothrombin time (PT) based assays that are equally sensitive to reductions in factors II, VII or X. However, previous studies suggest that the anticoagulant effect of VKA depends primarily on reductions in factors II and X and not VII. Aim and methods: We compared the effect of vitamin K dependent (VKD) coagulation factors on PT (Quick and Owren methods) and also on rotational thromboelastometric (ROTEM) parameters. The experiments used normal platelet poor plasma (PPP) and PPP selectively immunodepleted of individual VKD factors, with and without added platelet phospholipid or washed platelets. Results: The PT was equally sensitive to reductions in factors II, VII or X. However, ROTEM parameters correlated poorly with the PT in anticoagulated patients` plasmas. ROTEM experiments showed that the clotting time, maximum velocity of clot formation and the maximum clot firmness were more affected by reductions in FII or FX than by FVII or FIX concentrations which had little influence except at very low concentrations. We developed a modified PT that was sensitive only to reductions in factors II and X by using factor II and X (Fiix) depleted plasma in the PT system. The Fiix-PT (Fiix-INR) correlated well with PT (INR) but the Fiix-INR fluctuated less than the INR in anticoagulated patients reflecting its insensitivity to FVII. Conclusion: The ROTEM results suggest that mild to moderate reductions in factors II or X are more important in clot formation than factors VII or IX at therapeutically relevant factor concentrations. Reductions in FII and X may therefore better reflect anticoagulation with VKA than FVII or IX. FVII may be a confounding source of unwanted variation in PT-INR. The new Fiix-PT that is sensitive only to FII and FX may more accurately reflect the degree of therapeutic anticoagulation in patients treated with VKA than do the current PT assays which may overestimate the fluctuation in anticoagulation. Disclosures: Onundarson: See i. other: Patent application for Fiix method in process. Gudmundsdottir:Other, see i: patent applicaiton filed for Fiix method.

Immunoaffinity purification of factor IX from commercial concentrates and infusion studies in animals

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1269-1277
Author(s):  
KJ Smith
Keyword(s):  
Replacement Therapy ◽  
Vitamin K ◽  
Disease Transmission ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor Ix ◽  
Heat Treated ◽  
Coagulation Factor Concentrates ◽  
Risk Of Disease ◽  
Factor Ix Deficiency

Thrombosis and transmission of viral diseases are the principal adverse effects of current replacement therapy for factor IX deficiency when using heat-treated concentrates of vitamin K-dependent coagulation factors. More highly purified factor IX preparations could decrease the risk of disease transmission, reduce patient exposure to allogeneic proteins, and reduce the risk of thrombosis. In this study, two immunoaffinity-purified factor IX preparations from commercial vitamin K-dependent coagulation factor concentrates had specific activities of 134 and 155 U/mg. Crude concentrates and purified factor IX preparations were tested for thrombogenicity in rabbits. One of two crude concentrates tested in the stasis-thrombosis assay caused large thrombi at doses of 50 U/kg. Purified factor IX from this concentrate was not thrombogenic at 106 to 234 U/kg. A heparin-treated concentrate that was not active in the stasis model at 100 U/kg caused significant (P less than .05) delayed consumption of rabbit fibrinogen, platelets, antithrombin III antigen, and factor VIII activity at the same dose. Factor IX prepared from this concentrate caused no consumption of coagulation factors at 214 to 243 U/kg despite the presence of trace amounts of activated factor IX. These results indicate that more highly purified preparations could reduce the risk of thrombosis in replacement therapy for hemophilia B. Also, at least for the preparations tested, factor IX and factor IXa were not the thrombogenic components of the crude concentrates.

Coagulation factor levels in neurosurgical patients with mild prolongation of prothrombin time: effect on plasma transfusion therapy

2011 ◽  
Vol 114 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Karén Matevosyan ◽  
Christopher Madden ◽  
Samuel L. Barnett ◽  
Joseph E. Beshay ◽  
Cynthia Rutherford ◽  
...  
Keyword(s):  
Prothrombin Time ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Scientific Data ◽  
Factor Vii ◽  
Plasma Transfusion ◽  
Transfusion Therapy ◽  
Study Results ◽  
Neurosurgical Patients ◽  
Transfusion Guidelines

Object Neurosurgical patients often have mildly prolonged prothrombin time (PT) or international normalized ratio (INR). In the absence of liver disease this mild prolongation appears to be due to the use of very sensitive PT reagents. Therefore, the authors performed relevant coagulation factor assays to assess coagulopathy in such patients. They also compared plasma transfusion practices in their hospital before and after the study. Methods The authors tested 30 plasma specimens from 25 patients with an INR of 1.3–1.7 for coagulation factors II, VII, and VIII. They also evaluated plasma orders during the 5-month study period and compared them with similar poststudy periods following changes in plasma transfusion guidelines based on the study results. Results At the time of plasma orders the median INR was 1.35 (range 1.3–1.7, normal reference range 0.9–1.2) with a corresponding median PT of 13.6 seconds (range 12.8–17.6 seconds). All partial thromboplastin times were normal (median 29.0 seconds, range 19.3–33.7 seconds). The median factor VII level was 57% (range 25%–124%), whereas the hemostatic levels recommended for major surgery are 15%–25%. Factors II and VIII levels were also within the hemostatic range (median 72% and 118%, respectively). Based on these scientific data, plasma transfusion guidelines were modified and resulted in a 75%–85% reduction in plasma orders for mildly prolonged INR over the next 2 years. Conclusions Neurosurgical patients with a mild prolongation of INR (up to 1.7) have hemostatically normal levels of important coagulation factors, and the authors recommend that plasma not be transfused to simply correct this abnormal laboratory value.

International Normalized Ratio Versus Plasma Levels of Coagulation Factors in Patients on Vitamin K Antagonist Therapy

2011 ◽  
Vol 135 (4) ◽  
pp. 490-494 ◽  
Author(s):  
Gene Gulati ◽  
Megan Hevelow ◽  
Melissa George ◽  
Eric Behling ◽  
Jamie Siegel
Keyword(s):  
Vitamin K ◽  
Warfarin Therapy ◽  
Clinical Laboratory ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
International Normalized Ratio ◽  
Activity Levels ◽  
Factor X ◽  
Life Threatening ◽  
Average Factor

Abstract Context.—The key question when managing patients on warfarin therapy who present with life-threatening bleeding is how to use the international normalized ratio (INR) to best direct corrective therapy. The corollary question for the clinical laboratory is at what level will the INR reflect a critical value that requires notifying the clinician. Objective.—To determine the levels of vitamin K–dependent factors over a range of INR values. Design.—Evaluation of the vitamin K–dependent coagulation factor levels on plasma remnants from patients in whom a prothrombin time and INR was ordered to monitor warfarin therapy. There were a total of 83 specimens evaluated with an INR range from 1.0 to 8.26. Results.—The mean activity levels of all 4 factors remained near or above 50% when the INR was less than 1.5. The average factor X level was 23% when the INR range was 1.6 to 2.5, but levels of factors II, VII, and IX did not drop below the hemostatic range until the INR was greater than 2.5. At an INR of 3.6 or more, the activity levels of all 4 factors were less than 30% in more than 90% of the specimens. Conclusion.—Levels of factors II, VII, IX, and X declined with increasing INR but not at the same rate and not to the same level at a given INR. However, most of the values were below the hemostatic value once the INR was 3.6 or more, the level that was also considered critical for physician notification.

scholarly journals Immunoaffinity purification of factor IX from commercial concentrates and infusion studies in animals

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1269-1277 ◽  
Author(s):  
KJ Smith
Keyword(s):  
Replacement Therapy ◽  
Vitamin K ◽  
Disease Transmission ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor Ix ◽  
Heat Treated ◽  
Coagulation Factor Concentrates ◽  
Risk Of Disease ◽  
Factor Ix Deficiency

Abstract Thrombosis and transmission of viral diseases are the principal adverse effects of current replacement therapy for factor IX deficiency when using heat-treated concentrates of vitamin K-dependent coagulation factors. More highly purified factor IX preparations could decrease the risk of disease transmission, reduce patient exposure to allogeneic proteins, and reduce the risk of thrombosis. In this study, two immunoaffinity-purified factor IX preparations from commercial vitamin K-dependent coagulation factor concentrates had specific activities of 134 and 155 U/mg. Crude concentrates and purified factor IX preparations were tested for thrombogenicity in rabbits. One of two crude concentrates tested in the stasis-thrombosis assay caused large thrombi at doses of 50 U/kg. Purified factor IX from this concentrate was not thrombogenic at 106 to 234 U/kg. A heparin-treated concentrate that was not active in the stasis model at 100 U/kg caused significant (P less than .05) delayed consumption of rabbit fibrinogen, platelets, antithrombin III antigen, and factor VIII activity at the same dose. Factor IX prepared from this concentrate caused no consumption of coagulation factors at 214 to 243 U/kg despite the presence of trace amounts of activated factor IX. These results indicate that more highly purified preparations could reduce the risk of thrombosis in replacement therapy for hemophilia B. Also, at least for the preparations tested, factor IX and factor IXa were not the thrombogenic components of the crude concentrates.

Compound Heterozygosity in the Novel Mutations W157R and T591K in the γ-Glutamyl Carboxylase Gene Causes Hereditary Combined Vitamin K-Dependent Coagulation Factor Deficiency in a Tunisian Family.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2147-2147
Author(s):  
Dhouha Darghouth ◽  
Kevin W. Hallgren ◽  
Rebecca L. Hain ◽  
Amel Mrad ◽  
Youssef Gharbi ◽  
...  
Keyword(s):  
Vitamin K ◽  
Protein Function ◽  
Mutational Analysis ◽  
Coagulation Factor ◽  
Normal Subjects ◽  
Coagulation Factors ◽  
Compound Heterozygosity ◽  
Wild Type ◽  
Family Analysis ◽  
Coagulation Factor Deficiency

Abstract Combined deficiency in vitamin K-dependent (VKD) coagulation factors is an autosomal recessive bleeding disorder associated with defects in either the VKD carboxylase which converts Glus to Glas in VKD proteins to render them active or the vitamin K epoxide reductase (VKORC1) which supplies the reduced vitamin K cofactor required for carboxylation. Such defects are rare, and we now report the fourth case of deficiency caused by mutations in the carboxylase gene. The mutations were identified in a two year old Tunisian girl who exhibited impaired function in several VKD procoagulant and anticoagulant factors that was not restored by vitamin K administration. Sequence analysis of the propositus did not identify any mutations in the VKORC1 gene but, remarkably, revealed three heterozygous mutations in the carboxylase gene, D31N, W157R and T591K within exons 2, 4 and 13, respectively. None of these mutations have previously been reported. Family analysis showed that D31N and T591K were coallelic and transmitted by the mother while W157R was transmitted by the father. The mutations were not found in the genomes of 200 normal subjects, ruling out frequent polymorphisms. Mutational analysis indicated wild type activity for the D31N carboxylase. In contrast, the W157R and T591K enzymes had activities that were, respectively, 7% and 0% that of wild type carboxylase, and their compound heterozygosity can therefore account for defective carboxylation. Residues 157 and 591 are both highly evolutionarily conserved, and residue 157 lies within a region previously suggested to be important for carboxylase binding to VKD Glus or propeptide. However, the hydrophobic nature of this region and inability of vitamin K administration to restore VKD protein function alternatively suggests that residue 157 may be important for vitamin K binding.

Anticoagulation beyond direct thrombin and factor Xa inhibitors: indications for targeting the intrinsic pathway?

2013 ◽  
Vol 110 (08) ◽  
pp. 223-232 ◽  
Author(s):  
Maurits van Montfoort ◽  
Joost Meijers
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor Xa Inhibitors ◽  
Therapeutic Window ◽  
Intrinsic Pathway ◽  
Antithrombotic Drugs

SummaryAntithrombotic drugs like vitamin K antagonists and heparin have been the gold standard for the treatment and prevention of thromboembolic disease for many years. Unfortunately, there are several disadvantages of these antithrombotic drugs: they are accompanied by serious bleeding problems, it is necessary to monitor the therapeutic window, and there are various interactions with food and other drugs. This has led to the development of new oral anticoagulants, specifically inhibiting either thrombin or factor Xa. In terms of effectiveness, these drugs are comparable to the currently available anticoagulants; however, they are still associated with issues such as bleeding, reversal of the drug and complicated laboratory monitoring. Vitamin K antagonists, heparin, direct thrombin and factor Xa inhibitors have in common that they target key proteins of the haemostatic system. In an attempt to overcome these difficulties we investigated whether the intrinsic coagulation factors (VIII, IX, XI, XII, prekallikrein and high-molecular-weight kininogen) are superior targets for anticoagulation. We analysed epidemiological data concerning thrombosis and bleeding in patients deficient in one of the intrinsic pathway proteins. Furthermore, we discuss several thrombotic models in intrinsic coagulation factor-deficient animals. The combined results suggest that intrinsic coagulation factors could be suitable targets for anticoagulant drugs.

A Plasma Factor Enhances Activity of Vitamin K-Dependent Coagulation Proteins

1983 ◽  
Vol 50 (03) ◽  
pp. 749-752 ◽  
Author(s):  
Michael R Owens ◽  
Catherine D Cimino
Keyword(s):  
Rat Liver ◽  
Vitamin K ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Rat Plasma ◽  
Factor Vii ◽  
Coagulation Activity ◽  
Factor Ii ◽  
Plasma Factor ◽  
Coagulation Proteins

SummaryA plasma factor, “coagulopoietin”, present in animals with depleted vitamin K-dependent coagulation factors, appears to enhance activity of these factors in normal animals. We have investigated the effects of “coagulopoietin” on synthesis of certain coagulation proteins by the isolated rat liver perfused for eight hours. Liver donor rats received plasma injections from vitamin K-deficient rats or from normal rats 24 hr before sacrifice. Coagulation activity of Factor VII and Factor II in liver perfusate samples was measured with a coagulation assay; Factor II synthesis was also measured by rocket immunoelectrophoresis and by activation with E. carinatus venom. Cumulative hepatic synthesis of. Factor VII coagulation activity was increased by 43% when rat liver donors received vitamin K-deficient rat plasma compared to normal rat plasma. Cumulative synthesis of Factor II coagulation activity was increased by 51%, but synthesis of the protein measured immunologically or by activation with venom was not affected. The “coagulopoietin” factor in these studies appears to increase measurable coagulation factor activity without increasing total protein synthesis.

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