THROMBIN FORMATION. I. THE ROLE OF CALCIUM, SERUM AC-GLOBULIN AND TISSUE THROMBOPLASTIN 1

SummaryThrombin generation has been studied in the plasma of severely factor XI deficient patients under conditions in which contact activation did not play a role. In platelet-rich as well as platelet-poor plasma, thrombin generation was dependent upon the presence of factor XI at tissue factor concentrations of between 1 and 20 pg/ml i.e. ~ 0.01 to 0.20% of the concentration normally present in the thromboplastin time determination. The requirement for factor XI is low; significant thrombin generation was seen at 1% factor XI; at 10%, thrombin formation was nearly normalised. A suspension of normal platelets in severely factor XI deficient plasma did not increase thrombin generation. This implies that there is no significant factor XI activity carried by normal platelets, although the presence of factor XI and factor XI inhibitors in platelets cannot be ruled out.

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THROMBIN FORMATION. II. EFFECTS OF LYSIN (FIBRINOLYSIN, PLASMIN) ON PROTHROMBIN, AC-GLOBULIN AND TISSUE THROMBOPLASTIN. 1

Journal of Clinical Investigation ◽

10.1172/jci102216 ◽

1949 ◽

Vol 28 (6 Pt 2) ◽

pp. 1507-1510 ◽

Cited By ~ 13

Author(s):

Jessica H. Lewis ◽

Ann C. Howe ◽

J. H. Ferguson

Keyword(s):

Tissue Thromboplastin ◽

Thrombin Formation

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The Role of Vitamins in Hemostasis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647871 ◽

1975 ◽

Vol 33 (02) ◽

pp. 191-198

Author(s):

Armand J Quick

Keyword(s):

Vitamin K ◽

Physiological Mechanism ◽

Factor Vii ◽

Clotting Factors ◽

The Third ◽

Abnormal Bleeding ◽

Vitamin Q ◽

Tissue Thromboplastin ◽

And Control

SummaryThe physiological mechanism to prevent and control abnormal bleeding is dependent on three vitamins (C, K, and Q). Two of these are unequivocally established as essential for hemostasis while the existence of the third (Q) is supported by experimental evidence and by clinical and therapeutic observations (Quick 1972; Quick 1974). The interrelationship of these three vitamins has remained moot except for clue observations. Both vitamins C and K have a key structure in their molecules which supplies a redox mechanism, ascorbic acid and 2-methyl, 1,4-naphthoquinone, respectively. Both vitamins are concerned with growth. Lack of vitamin C, which clinically is the basic defect in scurvy, does not appear to cause a defect in blood coagulation while vitamin K affects the clotting mechanism by being essential for the production of four distinct clotting factors: prothrombin, factors VII, IX and X.In this presentation an attempt is made to correlate the action of the vitamin K-dependent clotting factors grouping them in a diagram to show how two systems of thrombin formation exist, one being essentially intrinsic, the second extrinsic requiring tissue thromboplastin and factor VII. The possible interlocking of vitamin Q in this mechanism is presented.

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The Role of Factor IX in Tissue Thromboplastin Induced Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657215 ◽

1982 ◽

Vol 48 (01) ◽

pp. 054-058 ◽

Cited By ~ 9

Author(s):

A M H P van den Besselaar ◽

I E Ram ◽

G H J Alderkamp ◽

R M Bertina

Keyword(s):

Human Factor ◽

Factor Ix ◽

Factor Vii ◽

Factor Xii ◽

Factor Xi ◽

Proteolytic Activation ◽

Human Factor Ix ◽

Tissue Thromboplastin ◽

The Difference

SummaryTissue thromboplastin apoprotein was partially purified from human brain. The apoprotein was recombined with mixed phospholipids to yield active thromboplastin. The recombined thromboplastin induced proteolytic activation of isolated human factor IX in the presence of factor VII and Ca2+. The clotting times of various deficient plasmas were determined as a function of apoprotein concentration, keeping the phospholipid concentration constant. The clotting times of a factor XII-deficient plasma were the same as those of a factor XII/factor IX-deficient plasma, except at very low apoprotein concentrations. However, under those conditions the difference in clotting times was independent of the presence of anti-factor VII serum. Similar observations were made for factor XI-deficient plasma in comparison with factor XI/factor IX-deficient plasma. These results indicate that activation of factor IX by factor VII/tissue thromboplastin does not significantly contribute to plasma coagulation.

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Experimental Studies on Factor VIII Inhibitor Bypassing Activity

10.1055/s-0039-1682503 ◽

1977 ◽

Author(s):

H. Vinazzer

Keyword(s):

Factor Viii ◽

Calcium Chloride ◽

Experimental Studies ◽

Factor Xa ◽

Factor Viii Inhibitor ◽

Factor V ◽

Factor X ◽

Tissue Thromboplastin ◽

Viii Inhibitor ◽

Thrombin Formation

The exact action of factor VIII inhibitor bypassing activity (FEIBA) is still unclear. For this reason, a series of experimental studies was carried out. Procoagulant activities were examined by standard one-stage methods while factor Xa and thrombin were measured by chromogenic substrates. Activities of factors II, VII, IX, and X were similar to PPSB fractions. In addition, low factor V activity and a phospholipid were detected. No activated factor X was present in FEIBA but there was a trace amount of 2.1 NIH units of thrombin per 100 FEIBA units. On addition of calcium chloride slow thrombin formation could be observed which however, reached 1100 NIH units of thrombin per 100 FEIBA units within an incubation time of 10 min. The velocity of thrombin formation was greatly enhanced by addition of a PTT reagent and of thromboplastin respectively. Factor Xa on the other hand, was neither formed after addition of calcium chloride nor by a PTT reagent. Tissue thromboplastin however, activated Xa from FEIBA in the same manner as a PTT reagent plus barium sulfate plasma. From these results, the conclusion could be drawn that thrombin could readily be made available from FEIBA while activation of Xa either needed the complete endogenous pathway or the presence of tissue thromboplastin. The procoagulant activity of FEIBA therefore, could be attributed to direct thrombin formation. By this process, an activation of the clotting mechanism in plasmas deficient in endogenous coagulation factors, and a complete independence from the presence or absence of a specific antibody could be explained.

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Role of Plasma Accelerator-Globulin and Serum Accelerator-Globulin in Conversion of Prothrombin

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1958.194.1.1 ◽

1958 ◽

Vol 194 (1) ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Betty R. Johnston ◽

H. Jensen

Keyword(s):

Calcium Ions ◽

Maximum Rate ◽

Conversion Factor ◽

Plasma Accelerator ◽

Complete Conversion ◽

Platelet Factor ◽

Antihemophilic Factor ◽

Thrombin Formation

Either plasma accelerator-globulin or serum accelerator-globulin must be present in order to obtain complete conversion of prothrombin in the presence of serum-eluate factor(s) [proconvertin or plasma thromboplastin component or both], antihemophilic factor, platelet factor 3, and calcium ions. If plasma accelerator-globulin is present, it must first be converted to serum accelerator-globulin by the action of thrombin before the maximum rate of prothrombin conversion is reached. Serum accelerator-globulin does neither affect the degree nor the rate of interaction of serum-eluate factor(s), antihemophilic factor, platelet factor 3, and calcium ions forming a prothrombin-conversion factor but affects thrombin formation at a point just prior to or during the conversion of prothrombin.

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