The significance of high molecular weight kininogen for contact activation of rat blood coagulation,in vitro.

1990 ◽  
Vol 98 (1) ◽  
pp. 67-73 ◽  
Author(s):  
J. Damas ◽  
V. Bourdon
Keyword(s):  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
High Molecular Weight Kininogen ◽  
Contact Activation ◽  
Rat Blood

Surface Independent Factor XI Activation by Thrombin in the Presence of High Molecular Weight Kininogen

1994 ◽  
Vol 72 (03) ◽  
pp. 397-402 ◽  
Author(s):  
Peter A Kr von dem Borne ◽  
Stefan J Koppelman ◽  
Bonno N Bouma ◽  
Joost C M Meijers
Keyword(s):  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Dextran Sulfate ◽  
Factor Xa ◽  
Factor X ◽  
High Molecular Weight Kininogen ◽  
Factor Xi ◽  
Factor Xia

SummaryA deficiency of one of the proteins of the contact system of blood coagulation does not result in a bleeding disorder. For this reason activation of blood coagulation via this system is believed to be an in vitro artefact. However, patients deficient in factor XI do suffer from variable bleeding abnormalities. Recently, an alternative pathway for factor XI activation has been described. Factor XI was found to be activated by thrombin in the presence of dextran sulfate as a surface. However, high molecular weight kininogen (HK), to which factor XI is bound in plasma, and fibrinogen were shown to block this activation suggesting it to be an in vitro phenomenon. We investigated the thrombin-mediated factor XI activation using an amplified detection system consisting of factors IX, VIII and X, which was shown to be very sensitive for factor XIa activity. This assay is approximately 4 to 5 orders of magnitude more sensitive than the normal factor XIa activity assay using a chromogenic substrate. With this assay we found that factor XI activation by thrombin could take place in the absence of dextran sulfate. The initial activation rate was approximately 0.3 pM/min (using 25 nM factor XI and 10 nM thrombin). The presence of dextran sulfate enhanced this rate about 8500-fold. A very rapid and complete factor X activation was observed in the presence of dextran sulfate. Although only minute amounts of factor XIa were formed in the absence of dextran sulfate, significant activation of factor X was detected in the amplification assay within a few minutes. HK inhibited the activation of factor XI by thrombin strongly in the presence, yet only slightly in the absence of dextran sulfate (26 and 1.2 times, respectively). Despite the strong inhibition of HK on the activation of factor XI by thrombin in the presence of dextran sulfate, HK had only a minor effect on the factor Xa generation.We conclude that activation of factor XI by thrombin can take place regardless of the presence of a surface or HK. This activation might therefore be physiologically relevant. The inhibitory effect of HK on the thrombin-mediated factor XI activation is largely dextran sulfate dependent. Due to the amplification in the intrinsic system, trace amounts of factor XIa might generate physiological sufficient amounts of factor Xa for an adequate haemostatic response.

The Contact Phase of Blood Coagulation in Diabetes Mellitus and in Patients with Vasculopathy

1984 ◽  
Vol 52 (03) ◽  
pp. 221-223 ◽  
Author(s):  
M Christe ◽  
P Gattlen ◽  
J Fritschi ◽  
B Lämmle ◽  
W Berger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Negative Correlation ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
High Molecular Weight Kininogen ◽  
Contact Phase ◽  
Α2 Macroglobulin

SummaryThe contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also α2-macroglobulin are significantly elevated in diabetics with complications, for α1-macroglobulin especially in patients with nephropathy, 137.5% ± 36.0 (p <0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 ± 22.1 (p <0.01).Prekallikrein (PK) is increased in all patients’ groups (Table 2) as compared to normals. PK is particularly high (134% ± 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.

Pro-angiogenic effect of human kallikrein-related peptidase 12 (KLK12) in lung endothelial cells does not depend on kinin-mediated activation of B2 receptor

2013 ◽  
Vol 394 (3) ◽  
pp. 385-391 ◽  
Author(s):  
Thomas Kryza ◽  
Gilles Lalmanach ◽  
Marion Lavergne ◽  
Fabien Lecaille ◽  
Pascale Reverdiau ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Endothelial Cells ◽  
High Molecular Weight ◽  
High Molecular Weight Kininogen ◽  
Kinin Receptor ◽  
Angiogenic Effect ◽  
Lung Endothelial Cells ◽  
Carboxy Terminal

Abstract Kallikrein-12 (KLK12) may play an important role in angiogenesis modulating proangiogenic factor bioavailability and activating the kinin receptor B2 pathway. We studied whether KLK12 had an impact on angiogenesis and the activation of kinin receptor B2 results from the KLK12-dependent generation of kinins. KLK12 efficiently hydrolyzed high molecular weight kininogen, liberating a fragment containing the carboxy-terminal end of kinins. The kininogenase activity of KLK12 was poor, however, due to the cleavage resistance of the N-terminal side of the kinin sequence. A very low amount of kinins was accordingly released after in vitro incubation of high molecular weight kininogen with KLK12 and thus the proangiogenic activity of KLK12 in lung endothelial cells was not related to a kinin release.

scholarly journals Interaction of high molecular weight kininogen, factor XII, and fibrinogen in plasma at interfaces

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 156-159 ◽  
Author(s):  
L Vroman ◽  
AL Adams ◽  
GC Fischer ◽  
PC Munoz
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Marked Change ◽  
Human Platelets ◽  
Blue Staining ◽  
Factor Xii ◽  
High Molecular Weight Kininogen ◽  
Contact Activation ◽  
Coomassie Blue Staining ◽  
Coated Surfaces

Abstract Using ellipsometry, anodized tantalum interference color, and Coomassie blue staining in conjunction with immunologic identification of proteins adsorbed at interfaces, we have previously found that fibrinogen is the main constituent deposited by plasma onto many man- made surfaces. However, the fibrinogen deposited from normal plasma onto glass and similar wettable materials is rapidly modified during contact activation until it can no longer be identified antigenically. In earlier publications, we have called this modification of the fibrinogen layer “conversion,” to indicate a process of unknown nature. Conversion of adsorbed fibrinogen by the plasma was not accompanied by marked change in film thickness, so that we presumed that this fibrinogen was not covered but replaced by other protein. Conversion is now showen to be markedly delayed in plasma lacking high molecular weight kininogen, slightly delayed in plasma lacking factor XII, and normal in plasma that lack factor XI or prekallikrein. We conclude that intact plasma will quickly replace the fibrinogen it has deposited on glass-like surfaces by high molecular weight kininogen and, to a smaller extent, by factor XII. Platelets adhere preferentially to fibrinogen-coated surfaces; human platelets adhere to hydrophobic nonactivating surfaces, since on these, adsorbed firbinogen is not exchanged by the plasma. The adsorbed fibrinogen will be replaced on glass-like surfaces during surface activation of clotting, and platelets failing to find fibrinogen will not adhere.

Hypoxia alters blood coagulation during acute decompression in humans

1984 ◽  
Vol 56 (3) ◽  
pp. 666-670 ◽  
Author(s):  
H. M. O'Brodovich ◽  
M. Andrew ◽  
G. W. Gray ◽  
G. Coates
Keyword(s):  
Molecular Weight ◽  
Platelet Count ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Plasma Protein ◽  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Total Plasma ◽  
High Molecular Weight Kininogen ◽  
Total Plasma Protein

Acute decompression is associated with a shortening of the activated partial thromboplastin time (aPTT). This study was performed to examine whether this change in aPTT results from hypoxia or hypobaria. We exposed healthy adults on three separate occasions to 2 h of 1) hypoxic hypobaria (410 Torr, n = 5), 2) hypoxic normobaria (fractional inspired O2 tension = 0.11, n = 4), or 3) normoxic hypobaria (410 Torr breathing supplemental O2, n = 5). The aPTT shortened during hypoxic hypobaria and hypoxic normobaria (P less than 0.05) but was unchanged during normoxic hypobaria. The prothrombin and thrombin times, hematocrit, and concentrations of fibrinogen, total plasma protein, and fibrinogen-fibrin fragment E were unchanged. During hypoxic hypobaria biologic levels of prekallikrein, high-molecular-weight kininogen, and factors XII, XI, X, VII, V, and II were unchanged, but procoagulant VIII (VIII:C) increased 50% without an increase in VIII-related antigen levels (VIIIR:Ag). Fibrin monomer was not detected in any group. In one subject who became ill after 1.5 h of hypoxic normobaria aPTT shortened by 10 s; the platelet count decreased by 93,000/mm3; VIII:C increased fivefold, but VIIIR:Ag only increased three-fold. We conclude that it is the hypoxia which shortens aPTT during acute decompression to 410 Torr and speculate that it results from an increase in plasma VIII:C-like activity.

Mechanisms of Human Blood VII Activation in Plasma During Contact Activation, Clotting and Exposure to Cold

1979 ◽  
Author(s):  
U. Seligsohn ◽  
B. østerud ◽  
S.F. Brown ◽  
J.H. Griffin ◽  
S.I. Rapaport
Keyword(s):  
Molecular Weight ◽  
Tissue Factor ◽  
High Molecular Weight ◽  
Human Blood ◽  
Factor Vii ◽  
High Molecular Weight Kininogen ◽  
Contact Activation ◽  
Partial Activation ◽  
No Activation ◽  
Fold Activation

Factor VII(VII) is activated, giving shorter clotting times with tissue factor, when plasma is exposed to kaolin, is clotted or exposed to cold. The mechanisms involved were studied. Incubation of plasma with kaolin resulted in: No activation in XII deficiency plasma (dp), partial activation (2.5 fold) in Prekallikrein (PK) dp and High Molecular Weight Kininogen (HMWK) dp, and 4.5-9 fold activation in normal or other dp. Clotting plasma by recalcification resulted in: No activation with XII dp, HMWK dp, XI dp and IX dp, and 4-5 fold activation with VIII dp, X dp and V dp. The mechanism of cold promoted activation of VII in plasma was studied by adding purified 125-XII or 125I-IX to plasma before storage at 4° and observing the extent of their proteolysis (a measure of activation) from their radioactivity profiles on reduced Polyacrylamide gels following electrophoresis in the presence of SDS. Significantly greater 125I-IX and 125I-XII proteolysis was observed in plasma from 4 subjects whose VII activated in the cold, than in plasma from 5 subjects whose VII was not activated in the cold. Addition of anti-IX antiserum inhibited 50% of the observed cold activation of VII. Thus, with kaolin XIIa was the principal activator of VII; after clotting IXa was the principal activator and in cold activation both XIIa and IXa played roles.

Sign in / Sign up

Export Citation Format

Share Document