scholarly journals Mechanism of transient adsorption of fibrinogen from plasma to solid surfaces: role of the contact and fibrinolytic systems

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 932-939 ◽  
Author(s):  
JL Brash ◽  
CF Scott ◽  
P ten Hove ◽  
P Wojciechowski ◽  
RW Colman
Keyword(s):  
Solid Surfaces ◽  
Factor Xii ◽  
Contact Activation ◽  
Transient Detection ◽  
Normal Plasma ◽  
Plasma Factor ◽  
Factor Xiia ◽  
Factor Xia ◽  
Specific Proteins

Abstract The transient detection of fibrinogen on surfaces has been described (Vroman effect) and high-mol-wt kininogen (HK) has been shown to play a role in this reaction. In this study, we attempted to identify the form of HK responsible for preventing detection of the fibrinogen initially adsorbed from plasma to various artificial surfaces and to determine if other plasma components were involved. We compared 125I-fibrinogen adsorption in the presence of normal plasma to plasma deficient in specific proteins. On all surfaces tested, we found that fibrinogen was displaced from the surface. The extent of displacement was greatly reduced, however, but not eliminated in HK-deficient plasma. Factor XII- deficient plasma also showed reduced fibrinogen displacement. These data indicate that HK can actually displace fibrinogen; however, factor XII, or a factor XII-mediated reaction also appears to be necessary for this displacement to occur. Furthermore, when normal plasma was first subjected to extensive contact activation by dextran sulfate, during which the HK was extensively degraded to components smaller than the light chain (as assessed by Western blotting), we observed greatly reduced displacement of fibrinogen. Extensive contact activation of Factor XI-deficient plasma failed to show low-mol-wt derivatives, however, and displacement of fibrinogen was similar to normal plasma that had not undergone extensive activation. These data indicate that HKa (active cofactor produced during contact activation by factor XIIa or kallikrein) is primarily responsible for displacing fibrinogen, and that HKi (inactive cofactor generated by factor XIa) cannot displace fibrinogen. The fibrinogen from all plasma samples looked similar by Western blot analysis, suggesting that fibrinogenolysis was not a component of the Vroman effect. In addition, experiments performed with plasma prechromatographed on lysine agarose showed that a lysine- agarose adsorbable protein may be minimally involved in fibrinogen desorption and a synergism may exist between HK and that protein.

scholarly journals Mechanism of transient adsorption of fibrinogen from plasma to solid surfaces: role of the contact and fibrinolytic systems

Blood ◽  
1988 ◽  
Vol 71 (4) ◽  
pp. 932-939 ◽  
Author(s):  
JL Brash ◽  
CF Scott ◽  
P ten Hove ◽  
P Wojciechowski ◽  
RW Colman
Keyword(s):  
Solid Surfaces ◽  
Factor Xii ◽  
Contact Activation ◽  
Transient Detection ◽  
Normal Plasma ◽  
Plasma Factor ◽  
Factor Xiia ◽  
Factor Xia ◽  
Specific Proteins

The transient detection of fibrinogen on surfaces has been described (Vroman effect) and high-mol-wt kininogen (HK) has been shown to play a role in this reaction. In this study, we attempted to identify the form of HK responsible for preventing detection of the fibrinogen initially adsorbed from plasma to various artificial surfaces and to determine if other plasma components were involved. We compared 125I-fibrinogen adsorption in the presence of normal plasma to plasma deficient in specific proteins. On all surfaces tested, we found that fibrinogen was displaced from the surface. The extent of displacement was greatly reduced, however, but not eliminated in HK-deficient plasma. Factor XII- deficient plasma also showed reduced fibrinogen displacement. These data indicate that HK can actually displace fibrinogen; however, factor XII, or a factor XII-mediated reaction also appears to be necessary for this displacement to occur. Furthermore, when normal plasma was first subjected to extensive contact activation by dextran sulfate, during which the HK was extensively degraded to components smaller than the light chain (as assessed by Western blotting), we observed greatly reduced displacement of fibrinogen. Extensive contact activation of Factor XI-deficient plasma failed to show low-mol-wt derivatives, however, and displacement of fibrinogen was similar to normal plasma that had not undergone extensive activation. These data indicate that HKa (active cofactor produced during contact activation by factor XIIa or kallikrein) is primarily responsible for displacing fibrinogen, and that HKi (inactive cofactor generated by factor XIa) cannot displace fibrinogen. The fibrinogen from all plasma samples looked similar by Western blot analysis, suggesting that fibrinogenolysis was not a component of the Vroman effect. In addition, experiments performed with plasma prechromatographed on lysine agarose showed that a lysine- agarose adsorbable protein may be minimally involved in fibrinogen desorption and a synergism may exist between HK and that protein.

scholarly journals Demonstration and mode of action of an inhibitor for activated Hageman factor (factor XIIa) of the intrinsic blood coagulation pathway from Schistosoma mansoni

Blood ◽  
1977 ◽  
Vol 49 (4) ◽  
pp. 619-633
Author(s):  
VC Tsang ◽  
RT Damian
Keyword(s):  
Schistosoma Mansoni ◽  
Anticoagulant Activity ◽  
Factor Xii ◽  
Contact Activation ◽  
Factor Xi ◽  
Heat Stable ◽  
Normal Plasma ◽  
Factor Xiia ◽  
Factor Xia ◽  
Coagulation Pathway

An anticoagulant activity from adult Schistosoma mansoni whole worm homogenate is described. The inhibitor appears to be specific for the contact activation step of the intrinsic pathway. Experiments with both human and mouse plasmas have defined the specificity of the inhibitor as follows: (1) It lengthens the partial thromboplastin time of normal plasma. (2) It has no effect on the prothombin time and Russell's viper venom time of normal plasma. (3) Preactivation of normal plasma by a contact activator such as Celite eliminates essentially all inhibitory activity. (4) The inhibitor appears to be heat stable and can be precipitated by centrifugation above 27,000 g. (5) The inhibitor has no effect on the activation of factor XII by Celite. (6) The activation of factor XI by factor XIIa, however, is inhibited by the schistosomal inhibitor. The above data are consistent with the view that S. mansoni adults possess an anticoagulant that is capable of specifically inhibiting the conversion of factor XI to factor XIa by factor XIIa.

scholarly journals Demonstration and mode of action of an inhibitor for activated Hageman factor (factor XIIa) of the intrinsic blood coagulation pathway from Schistosoma mansoni

Blood ◽  
1977 ◽  
Vol 49 (4) ◽  
pp. 619-633 ◽  
Author(s):  
VC Tsang ◽  
RT Damian
Keyword(s):  
Schistosoma Mansoni ◽  
Anticoagulant Activity ◽  
Factor Xii ◽  
Contact Activation ◽  
Factor Xi ◽  
Heat Stable ◽  
Normal Plasma ◽  
Factor Xiia ◽  
Factor Xia ◽  
Coagulation Pathway

Abstract An anticoagulant activity from adult Schistosoma mansoni whole worm homogenate is described. The inhibitor appears to be specific for the contact activation step of the intrinsic pathway. Experiments with both human and mouse plasmas have defined the specificity of the inhibitor as follows: (1) It lengthens the partial thromboplastin time of normal plasma. (2) It has no effect on the prothombin time and Russell's viper venom time of normal plasma. (3) Preactivation of normal plasma by a contact activator such as Celite eliminates essentially all inhibitory activity. (4) The inhibitor appears to be heat stable and can be precipitated by centrifugation above 27,000 g. (5) The inhibitor has no effect on the activation of factor XII by Celite. (6) The activation of factor XI by factor XIIa, however, is inhibited by the schistosomal inhibitor. The above data are consistent with the view that S. mansoni adults possess an anticoagulant that is capable of specifically inhibiting the conversion of factor XI to factor XIa by factor XIIa.

PLASMA-ARTIFICIAL SURFACE INTERACTIONS; ROLE OF CONTACT AND FIBRINOLYTIC SYSTEMS

1987 ◽  
Author(s):  
Cheryl F Scott ◽  
John L Brash ◽  
Pauline ten Hove ◽  
Peter Wojciechowaki ◽  
Robert W Colman
Keyword(s):  
Dextran Sulfate ◽  
Plasma Concentrations ◽  
Contact Activation ◽  
Normal Plasma ◽  
Single Protein ◽  
Factor Xia ◽  
Artificial Surface ◽  
Displacement Pattern ◽  
Specific Proteins

The transient adsorption of fibrinogen (Fg) to artificial surfaces (Vroman Effect) is modulated principally by the procofactor, high molecular weight kininogen (HK). We investigated which form of HK was responsible for Fg displacement and also whether other proteins participated in the Vroman Effect. Experiments were performed at 23°C with a 5 min surface exposure to various concentrations of either normal plasma or plasma deficient in specific proteins to which 125I Fg had been added. Typically, Fg adsorption reached a maximum at 1% plasma and decreased at higher plasma concentrations. On all surfaces tested, Fg displacement was greatly reduced in HK-deficient plasma. Normal plasma,when exposed to the contact system activator, dextran sulfate, prior to its interaction with glass, displayed Fg displacement similar to untreated HK-deficient plasma.However, if Factor Xl-deficient plasma was incubated with dextran sulfate prior to exposure to glass, the Fg displacement pattern resembled normal, untreated plasma. These results suggest that the inactive cofactor form of HK (HMWKi) generated by Factor XIa (formed during extensive contact activation) does not displace Fg. Furthermore, Fg displacement was also reduced in untreated Factor Xll-deficient plasma exposed to glass, suggesting that the active cofactor form of HK (HMWKa) generated by exposure to kallikrein (during Factor Xll-dependent contact activation) may be the active participant in the Vroman Effect. The cofactor function of HK and its ability to displace Fg, therefore, appear to parallel. We also found that plasminogen or plasminogen activators were minimally involved in the Vroman Effect. Fg adsorption to glass in plasminogen-depleted HK-deficent plasma resembled Fg adsorption in a single protein system since more Fg was adsorbed and desorption failed to occur. A synergism may therefore exist between plasminogen and HK in the Vroman Effect. A better understanding of the mechanism of blood-artificial surface interaction is essential for the design of less thrombogenic biomaterials.

scholarly journals A monoclonal anti-human plasma prekallikrein antibody that inhibits activation of prekallikrein by factor XIIa on a surface

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1053-1062
Author(s):  
D Veloso ◽  
LD Silver ◽  
S Hahn ◽  
RW Colman
Keyword(s):  
Heavy Chain ◽  
Sodium Dodecyl ◽  
Factor Xii ◽  
Contact Activation ◽  
Fab Fragments ◽  
Microtiter Plates ◽  
Normal Plasma ◽  
Reducing Conditions ◽  
Factor Xiia ◽  
Kallikrein Activity

Of five IgGI/k murine monoclonal anti-human prekallikrein antibodies produced (MAbs), MAb 13G11 was selected for studying interaction of prekallikrein with factor XII and high-mol-wt kininogen (HMWK) during activation on a surface. Immunoblots from sodium dodecyl sulfate (SDS) gels showed that this MAb recognizes two variants (88 kd and 85 kd) of prekallikrein and kallikrein both in purified proteins and normal plasma. Under reducing conditions, kallikrein exhibits the epitope on the heavy chain but not on the light chains. Preincubation of MAb 13G11 with prekallikrein (added to prekallikrein-deficient plasma) or with normal plasma inhibited surface activation of prekallikrein 60% to 80%, as judged by amidolytic and coagulant assays. In normal plasma, inhibition by the Fab fragments was 87% of that with the entire MAb. Inhibition was not by competition between the MAb and HMWK, since neither binding of 13G11 to prekallikrein (coated on microtiter plates) was inhibited by an excess of HMWK, nor was hydrolysis of HMWK by kallikrein inhibited by 13G11. Using purified proteins in a system mimicking contact activation, inhibition by 13G11 of prekallikrein activation by factor XIIa, HMWK, and kaolin present was approximately 80%. Decreased inhibition (55% to 25%) occurred without HMWK or when kallikrein was used instead of prekallikrein. Kallikrein activity was not inhibited by 13G11 Fab fragments. These results indicate that the effect of 13G11 in plasma was neither dissociation of prekallikrein- HMWK complex nor a direct effect on kallikrein activity. Similar to the results in plasma, activation of prekallikrein, HMWK present, by factor XIIa bound to kaolin, was inhibited approximately 70% by 13G11. The results suggest a previously unrecognized site on the prekallikrein (heavy chain) required for its interaction with factor XIIa, either shared with the 13G11 epitope or located in very close proximity. The inhibition of kallikrein by intact 13G11 indicates that its binding site on the heavy chain is sterically related to the active site (light chain).

scholarly journals A monoclonal anti-human plasma prekallikrein antibody that inhibits activation of prekallikrein by factor XIIa on a surface

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1053-1062 ◽  
Author(s):  
D Veloso ◽  
LD Silver ◽  
S Hahn ◽  
RW Colman
Keyword(s):  
Heavy Chain ◽  
Sodium Dodecyl ◽  
Factor Xii ◽  
Contact Activation ◽  
Fab Fragments ◽  
Microtiter Plates ◽  
Normal Plasma ◽  
Reducing Conditions ◽  
Factor Xiia ◽  
Kallikrein Activity

Abstract Of five IgGI/k murine monoclonal anti-human prekallikrein antibodies produced (MAbs), MAb 13G11 was selected for studying interaction of prekallikrein with factor XII and high-mol-wt kininogen (HMWK) during activation on a surface. Immunoblots from sodium dodecyl sulfate (SDS) gels showed that this MAb recognizes two variants (88 kd and 85 kd) of prekallikrein and kallikrein both in purified proteins and normal plasma. Under reducing conditions, kallikrein exhibits the epitope on the heavy chain but not on the light chains. Preincubation of MAb 13G11 with prekallikrein (added to prekallikrein-deficient plasma) or with normal plasma inhibited surface activation of prekallikrein 60% to 80%, as judged by amidolytic and coagulant assays. In normal plasma, inhibition by the Fab fragments was 87% of that with the entire MAb. Inhibition was not by competition between the MAb and HMWK, since neither binding of 13G11 to prekallikrein (coated on microtiter plates) was inhibited by an excess of HMWK, nor was hydrolysis of HMWK by kallikrein inhibited by 13G11. Using purified proteins in a system mimicking contact activation, inhibition by 13G11 of prekallikrein activation by factor XIIa, HMWK, and kaolin present was approximately 80%. Decreased inhibition (55% to 25%) occurred without HMWK or when kallikrein was used instead of prekallikrein. Kallikrein activity was not inhibited by 13G11 Fab fragments. These results indicate that the effect of 13G11 in plasma was neither dissociation of prekallikrein- HMWK complex nor a direct effect on kallikrein activity. Similar to the results in plasma, activation of prekallikrein, HMWK present, by factor XIIa bound to kaolin, was inhibited approximately 70% by 13G11. The results suggest a previously unrecognized site on the prekallikrein (heavy chain) required for its interaction with factor XIIa, either shared with the 13G11 epitope or located in very close proximity. The inhibition of kallikrein by intact 13G11 indicates that its binding site on the heavy chain is sterically related to the active site (light chain).

scholarly journals Rapid Loss of Factor XII- and XI-Activity in Ellagic Acid Activated Normal Plasma: Role of Plasma Inhibitors and Implications for Automated Aptt-Recording

1977 ◽  
Author(s):  
J. H. Joist ◽  
J. F. Cowan ◽  
M. Khan
Keyword(s):  
Ellagic Acid ◽  
Clinical Laboratory ◽  
Coagulation Factors ◽  
Activation Process ◽  
Factor Xii ◽  
Naturally Occurring ◽  
Normal Plasma ◽  
Factor Xiia ◽  
Loss Of Contact

Rapid prolongation of the activated partial thromboplastin time (aPTT) of normal plasma upon incubation with ellagic acid containing aPTT reagents was observed. The aPTT prolongation was not due to time dependent changes in pH in the incubation mixtures or loss of activity of the labile coagulation factors VIII and V, but occurred as a result of rapid progressive inactivation of ellagic acid activated factors XII and XI. Prolongation of the aPTT and loss of contact factor activities was not observed in plasma incubated with particulate activator reagents. This finding seemed to indicate that adsorption of factors XII and XI to larger particles during the activation process may protect these factors from inactivation by naturally occurring plasma inhibitors. Evidence is presented which supports previous observations that Ci-inhibitor, α1-antitrypsin and antithrombin III (in the presence of heparin contribute to factor XIIa- and XIa-inactivation in ellagic acid activated plasma and that plasma albumin may compete with factor XII for ellagic acid binding. The findings indicate that ellagic acid containing aPTT reagents have unfavorable properties which seriously limit their usefulness in the clinical laboratory, particularly in respect to recording of the aPTT with certain fully automated clot timers.

scholarly journals The contact activation mechanism in human plasma: activation induced by dextran sulfate

Blood ◽  
1982 ◽  
Vol 59 (6) ◽  
pp. 1225-1233 ◽  
Author(s):  
F van der Graaf ◽  
FJ Keus ◽  
RA Vlooswijk ◽  
BN Bouma
Keyword(s):  
Human Plasma ◽  
Dextran Sulfate ◽  
Activation Mechanism ◽  
Factor Xii ◽  
Contact Activation ◽  
Prolonged Incubation ◽  
Normal Plasma ◽  
Essential Components ◽  
Factor Xiia ◽  
Kallikrein Activity

Abstract Incubation of normal human plasma with dextran sulfate for 7 min at 4 degrees C generates kallikrein amidolytic activity. No kallikrein activity is generated in factor XII or prekallikrein-deficient plasma and only small amounts (8%) in high molecular weight (HMW) kininogen- deficient plasma. Addition of specific antisera directed against prekallikrein or HMW kininogen to normal plasma blocked the generation of kallikrein activity by dextran sulfate. Thus, factor XII, prekallikrein, and HMW kininogen are essential components for optimal activation of prekallikrein. The role of limited proteolysis in the activation of prekallikrein induced by dextran sulfate was studied by adding 125I-prekallikrein to plasma. The generation of kallikrein activity paralleled the proteolytic cleavage of prekallikrein as judged on SDS gels in the presence of reducing agents. The same cleavage fragments were observed as obtained by activation of purified prekallikrein by beta-factor-XIIa. Addition of 131I-HMW kininogen and 125I-factor XII or 131I-HMW kininogen and 125I-prekallikrein to normal plasma followed by activation with dextran sulfate and analysis on SDS gels indicated that the observed cleavage of prekallikrein and HMW kininogen is fast compared to the observed cleavage of factor XII, which is much slower and less extensive. During the first minutes of incubation of normal plasma with dextran sulfate, mainly alpha-factor- XIIa is formed. During prolonged incubation, beta-factor-XIIa is also formed.

scholarly journals Quantification of plasma factor XIIa-Cl(-)-inhibitor and kallikrein-Cl(- )-inhibitor complexes in sepsis

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 1841-1848 ◽  
Author(s):  
JH Nuijens ◽  
CC Huijbregts ◽  
AJ Eerenberg-Belmer ◽  
JJ Abbink ◽  
RJ Strack van Schijndel ◽  
...  
Keyword(s):  
Septic Shock ◽  
Molar Ratio ◽  
Plasma Kallikrein ◽  
Factor Xii ◽  
Plasma Samples ◽  
Contact Activation ◽  
Highly Sensitive ◽  
Plasma Factor ◽  
Factor Xiia ◽  
Serial Samples

Abstract Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(- )-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)-Inh complexes using a monoclonal antibody (MoAb Kok 12) that binds to a neodeterminant exposed on both complexed and cleaved Cl(-)-Inh. Plasma samples were serially collected from 48 patients admitted to the intensive care unit because of severe sepsis. Forty percent of patients on at least one occasion had increased levels of plasma factor XIIa-Cl(-)-Inh (greater than 5 x 10(-4) U/mL) and kallikrein-Cl(-)-Inh (greater than 25 x 10(- 4) U/mL), that correlated at a molar ratio of approximately 1:3. Levels of factor XII antigen in plasma and both the highest as well as the levels on admission of plasma factor XIIa-Cl(-)-Inh in 23 patients with septic shock were lower than in 25 normotensive patients (P = .015: factor XII on admission; P = .04: highest factor XIIa-Cl(-)-Inh; P = .01: factor XIIa-Cl(-)-Inh on admission). No significant differences in plasma kallikrein-Cl(-)-Inh or prekallikrein antigen were found between these patients' groups. Elevated Cl(-)-Inh complex levels were measured less frequently in serial samples from patients with septic shock than in those from patients without shock (P less than .0001). Based on these results, we conclude that plasma Cl(-)-Inh complex levels during sepsis may not properly reflect the extent of contact activation.

scholarly journals Quantification of plasma factor XIIa-Cl(-)-inhibitor and kallikrein-Cl(- )-inhibitor complexes in sepsis

Blood ◽  
1988 ◽  
Vol 72 (6) ◽  
pp. 1841-1848 ◽  
Author(s):  
JH Nuijens ◽  
CC Huijbregts ◽  
AJ Eerenberg-Belmer ◽  
JJ Abbink ◽  
RJ Strack van Schijndel ◽  
...  
Keyword(s):  
Septic Shock ◽  
Molar Ratio ◽  
Plasma Kallikrein ◽  
Factor Xii ◽  
Plasma Samples ◽  
Contact Activation ◽  
Highly Sensitive ◽  
Plasma Factor ◽  
Factor Xiia ◽  
Serial Samples

Considerable evidence indicates that activation of the contact system of intrinsic coagulation plays a role in the pathogenesis of septic shock. To monitor contact activation in patients with sepsis, we developed highly sensitive radioimmunoassays (RIAs) for factor XIIa-Cl(- )-inhibitor (Cl(-)-Inh) and kallikrein-Cl(-)-Inh complexes using a monoclonal antibody (MoAb Kok 12) that binds to a neodeterminant exposed on both complexed and cleaved Cl(-)-Inh. Plasma samples were serially collected from 48 patients admitted to the intensive care unit because of severe sepsis. Forty percent of patients on at least one occasion had increased levels of plasma factor XIIa-Cl(-)-Inh (greater than 5 x 10(-4) U/mL) and kallikrein-Cl(-)-Inh (greater than 25 x 10(- 4) U/mL), that correlated at a molar ratio of approximately 1:3. Levels of factor XII antigen in plasma and both the highest as well as the levels on admission of plasma factor XIIa-Cl(-)-Inh in 23 patients with septic shock were lower than in 25 normotensive patients (P = .015: factor XII on admission; P = .04: highest factor XIIa-Cl(-)-Inh; P = .01: factor XIIa-Cl(-)-Inh on admission). No significant differences in plasma kallikrein-Cl(-)-Inh or prekallikrein antigen were found between these patients' groups. Elevated Cl(-)-Inh complex levels were measured less frequently in serial samples from patients with septic shock than in those from patients without shock (P less than .0001). Based on these results, we conclude that plasma Cl(-)-Inh complex levels during sepsis may not properly reflect the extent of contact activation.

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