Influence Of High Molecular Weight Factor VIII On The Expression Of Factor VIII Procoagulant Activity

1981 ◽  
Author(s):  
W Muntean ◽  
W E Hathaway ◽  
R R Montgomery
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
High Molecular Weight ◽  
Procoagulant Activity ◽  
Two Stage ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
The One ◽  
Relationship Of ◽  
The Relationship

The relationship of the high molecular weight (HMW) moiety and low molecular weight (LMW) moiety of factor VIII in expressing procoagulant activity (VIII C) was studied. LMW VIII C was prepared by immunoadsorbent chromatography; HMW VIII was prepared by chromatographing hemophilic cryo- precipitate in 4% agarose. The LMW VIII C obtained by immunoadsorbent chromatography gave higher VIII C values when tested in the one stage partial thromboplastin time (PTT) system using von Willebrand’s disease plasma as substrate than using hemophilic plasma as substrate. This finding was shown to be due to the VIII related antigen (VIIIR:Ag) in the substrate plasmas. When the VIIIR:Ag was removed from the hemophilic substrate plasma by immuno-adsorption, the VIII C values obtained for the LMW VIII C were higher. Also, adding purified HMW VIII to the von Willebrand’s disease substrate plasma resulted in lower VIII C values for the LMW VIII C in the PTT system.When the LMW VIII C was tested in the two stage assay, all VIII C was adsorbed to A1(0H)3. The adsorption of the LMW VIII C was prevented by mixing it with hemophilic plasma. From normal undiluted plasma only 5-21% of VIII C and no VIII related antigen were adsorbed to A1(OH)3, but after activation of the factor VIII of normal plasma by small amounts of thrombin, most of the VIII C was adsorbed. No VIII related antigen was adsorbed after activation.Nevertheless, when unadsorbed LMW VIII C was assayed by the two stage method both with and without HMW VIII or VIIIR:Ag, the results were the same.Our studies suggest that VIIIR:Ag prevents to some extent the activation of LMW VIII C. LMW VIII C that is not bound or protected by VIIIRiAg is adsorbed from plasma by A1(0H)3. These findings may help explain the differences for VIII C found in some patients and certain clinical circumstances with the one and two stage assays.

scholarly journals Relationship of contact activation cofactor (CAC) procoagulant activity to kininogen

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 935-945 ◽  
Author(s):  
S Schiffman ◽  
P Lee ◽  
DI Feinstein ◽  
R Pecci
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Procoagulant Activity ◽  
Antigenic Determinants ◽  
High Molecular Weight Kininogen ◽  
Contact Activation ◽  
Precipitin Line ◽  
A Site ◽  
Relationship Of ◽  
The Relationship

Abstract Contact activation cofactor (CAC) facilitates the interaction of factors XI and XII. Patients lacking CAC have a coagulation defect and are deficient in high molecular weight kininogen. The coincidence of these two defects suggests that a single protein may be responsible for both physiologic functions. Immunologic and activity studies have been made on isolated CAC to clarify the relationship between CAC and kininogen. CAC forms a single precipitin line with anti-human kininogen, and antikininogen neutralizes CAC activity. CAC and high molecular weight kininogen show a reaction of identity on immunodiffusion against rabbit anti-CAC. Anti-CAC forms two precipitin lines with normal plasma which can be identified as high and low molecular weight kininogen. Monospecific immunoabsorbed anti-CAC forms a single precipitin line with plasma high molecular weight kininogen and neutralizes CAC activity. Cleavage of kinin fragment from CAC by insoluble trypsin or kalikrein does not proportionally reduce procoagulant activity. CAC neutralized by anti-CAC can release kinins on exposure to trypsin or kallikrein. The results support the conclusions that CAC procoagulant activity is a function of high molecular weight kininogen, that antigenic determinants unique to high molecular weight kininogen are shared by the CAC portion of the molecule, and that the clotting reactions may occur at a site removed from the kinin peptide.

HEAT-TREATED FACTOR VIII CONCENTRATES IN VON WILLEBRAND'S DISEASE AND RELATED DISORDERS: STUDIES IN PLATELET-TYPE VON WILLEBRAND'S DISEASE

1987 ◽  
Author(s):  
Hoyu Takahashi ◽  
Wataru Tatewaki ◽  
Reizo Nagayama ◽  
Masaharu Hanano ◽  
Shin-ichiro Takizawa ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
High Molecular Weight ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Heat Treated ◽  
Factor Viii Concentrates ◽  
Spontaneous Platelet Aggregation

Cryoprecipitate has proved to correct the hemostatic defects in von Willebrand1s disease (vWd). However, recent studies have revealed that transmission of the AIDS retrovirus (HIV) occurs through exposure to blood products including cryoprecipitate. Treatment with heat-treated factor VIII concentrates may have certain advantages over treatment with non-heated products, if these preparations are efficacious in vWd and related disorders. We investigated the multimeric compositoin of von Willebrand factor (vWf), contents of vWf antigen (vWf:Ag) and ristocetin cofactor activity (RCof) in the heat-treated factor VIII concentrates and cryoprecipitate, and their capacity to directly induce aggregation of platelet-type (or pseudo-) vWd platelets in vitro. The vWf multimers were visualized by a newly developed, immuno-enzymatic staining of the gel, following a discontinuous SDS-agarose gel electrophoresis. The RCof/vWf:Ag ratio was around 1.0 in cryoprecipitate, and ranged from 0.19 to 0.96 in factor VIII concentrates. Among four commercially available concentrates studied, Haemate P contained the most high-molecular-weight multimers of vWf and the highest RCof relative to vWf:Ag, and induced the aggregation of platelet-type vWd platelets at the lowest concentration. When infused into a patient with platelet-type vWd, Haemate P (144 units vWf:Ag/kg body weight) shortened the prolonged bleeding time and caused spontaneous platelet aggregation in vitro with a mild diminution of platelet count (from the preinfusion value of 183,000μl to 139,000μl at 5 minutes). These results indicate that some of the heat-treated factor VIII concentrates contain the high-molecular-weight vWf multimers and may provide a safer, yet still effective, treatment for platelet-type vWd, and possibly for various types of vWd as well.

scholarly journals Relationship of contact activation cofactor (CAC) procoagulant activity to kininogen

Blood ◽  
1977 ◽  
Vol 49 (6) ◽  
pp. 935-945
Author(s):  
S Schiffman ◽  
P Lee ◽  
DI Feinstein ◽  
R Pecci
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Procoagulant Activity ◽  
Antigenic Determinants ◽  
High Molecular Weight Kininogen ◽  
Contact Activation ◽  
Precipitin Line ◽  
A Site ◽  
Relationship Of ◽  
The Relationship

Contact activation cofactor (CAC) facilitates the interaction of factors XI and XII. Patients lacking CAC have a coagulation defect and are deficient in high molecular weight kininogen. The coincidence of these two defects suggests that a single protein may be responsible for both physiologic functions. Immunologic and activity studies have been made on isolated CAC to clarify the relationship between CAC and kininogen. CAC forms a single precipitin line with anti-human kininogen, and antikininogen neutralizes CAC activity. CAC and high molecular weight kininogen show a reaction of identity on immunodiffusion against rabbit anti-CAC. Anti-CAC forms two precipitin lines with normal plasma which can be identified as high and low molecular weight kininogen. Monospecific immunoabsorbed anti-CAC forms a single precipitin line with plasma high molecular weight kininogen and neutralizes CAC activity. Cleavage of kinin fragment from CAC by insoluble trypsin or kalikrein does not proportionally reduce procoagulant activity. CAC neutralized by anti-CAC can release kinins on exposure to trypsin or kallikrein. The results support the conclusions that CAC procoagulant activity is a function of high molecular weight kininogen, that antigenic determinants unique to high molecular weight kininogen are shared by the CAC portion of the molecule, and that the clotting reactions may occur at a site removed from the kinin peptide.

Studies on the Characterization of Factor VIII and a Co-factor VIII

1974 ◽  
Vol 31 (02) ◽  
pp. 328-338
Author(s):  
M. M. P Paulssen ◽  
H. L. M. A Vandenbussche-Scheffers ◽  
P. B Spaan ◽  
T de Jong ◽  
M. C Planje
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
The Body ◽  
Haemophilia A ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Polysaccharide Content ◽  
Plasma Factor ◽  
Two Factors

SummaryFactor VIII occurs in the body in two different forms. In lymph factor VIII is bound to chylomicra. In plasma, factor VIII is bound to a protein.After delipidation of chylomicra we obtained a glycoprotein with a high polysaccharide content and a molecular weight of approx. 160,000.In plasma, factor VIII is attached to a protein which is present in normal concentrations in plasma of patients with haemophilia A and in serum (co-factor VIII).This factor is deficient in both the plasma and the serum of patients with von Willebrand’s disease.The binding between factor VIII and co-factor VIII is reversible.Some properties of these two factors are described.

Comparison of Factor VIII Levels after Adrenalin in Classic Hemophilia and von Willebrand’s Disease (vWd)

1978 ◽  
Vol 39 (03) ◽  
pp. 657-662 ◽  
Author(s):  
M Elaine Eyster ◽  
James O Ballard ◽  
David Prager
Keyword(s):  
Factor Viii ◽  
Subcutaneous Injection ◽  
Stimulation Test ◽  
Procoagulant Activity ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Significant Change ◽  
Baseline Factor

SummaryThe factor VIII response to adrenalin was compared in 5 patients with von Willebrand’s disease (vWd) and 10 hemophiliacs with baseline factor VIII procoagulant activity (VIIIAHF) of 0.01 u/ml or greater. Patients with vWd showed a two-fold VIII AHF increase, while those with hemophilia showed no significant change 1 hr following the subcutaneous injection of adrenalin. These results suggest that the adrenalin stimulation test may be of value in distinguishing certain patients with mild hemophilia from those with vWd.

HYPOTHYROIDISM AND ACQUIRED VON WILLEBRAND'S DISEASE

1987 ◽  
Author(s):  
F E Preston ◽  
M Greaves ◽  
B Sampson ◽  
P B A Kernoff ◽  
G Savidge ◽  
...  
Keyword(s):  
Factor Viii ◽  
Inverse Correlation ◽  
Factor Ix ◽  
Bleeding Tendency ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Thyroxine Therapy ◽  
Type Ia ◽  
The Relationship ◽  
Normal Controls

A diagnosis of type IA von Willebrand's disease was made in three patients presenting with a mild bleeding tendency. Previously unrecognised hypothyroidism was also confirmed in two patients. In the third, hypothyroidism was diagnosed four years after initial presentation. In all three patients, thyroxine therapy was associated with correction of the haemostatic defect and resolution of the bleeding tendency.The association of von Willebrand's disease and hypothyrodism prompted us to examine the relationship between thyrotrophin (TSH), T3, T4 and components of the factor VIII complex in 12 patients with clinical and biochemical hypothyroidism. Factor IX was also studied. Mean VIII:C (measured by 2 stage assay) was 0.90 u/ul (range 0.55 - 1.14); mean vWF:Ag 0-83 u/ul (range 0.44 - 1.64); mean VIII:Rcof 0.75 (range 0.45 - 1.55); mean factor IX 0.72 (range 0.39 - 1.19). Multimeric analysis of vWF:Ag performed in samples from 8 patients was normal. VIII:Rcof levels were significantly lower than those of normal controls. A significant inverse correlation was obtained between TSH and factor IX and T4 and vWF:Ag. Although there is a definite inverse relationship between TSH and factor IX, this is not evident with respect to factor VIII and a different mechanism is probably responsible for the modest reduction of vWF:Ag and the occurrence of clinically-evident von Willebrand's disease which we have demonstrated in a small proportion of hypothyroid patients.

scholarly journals A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity

Blood ◽  
1982 ◽  
Vol 60 (1) ◽  
pp. 201-207 ◽  
Author(s):  
RR Montgomery ◽  
WE Hathaway ◽  
J Johnson ◽  
L Jacobson ◽  
W Muntean
Keyword(s):  
Factor Viii ◽  
Functional Activity ◽  
Type I ◽  
Two Stage ◽  
Functional Abnormality ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
New Variant ◽  
Von Willebrand

Reports on variants of von Willebrand's disease are numerous, but many of these are based on tests that will show marked fluctuations with time and tests that might not be similar in affected family members. This report describes 8 patients with a new variant of von Willebrand';s disease in which there is a normal APTT, slightly reduced one-stage factor VIII:C assay (VIII:C-1), and a drastically reduced two- stage factor VIII:C assay (VIII:C-2). The VIII:C in this variant is more readily adsorbed to AI(OH)3. This variability in VIII:C assays and excessive adsorption to AI(OH)3 are corrected by the addition of either hemophilic plasma or hemophilic factor-VIII-related antigen. This variant is stable with restudy on multiple occasions and is inherited in a stable fashion in three generations of one family. The multimeric structure of the VIIIR:Ag appears normal, although the concentration is moderately reduced. The differences in functional activity, the adsorption to AI(OH)3, and the differences between functional and antigenic (VIII:C Ag) assays of VIII:C support that this is a functional abnormality of type I von Willebrand's disease.

scholarly journals Intrinsic Viscosity-molecular Weight Relationship of Poly (Hexanediol Adipate)

2019 ◽  
pp. 1-8
Author(s):  
Jiankun Li ◽  
Zegang Zong ◽  
Dehua Hou ◽  
Bojun Tu ◽  
Weilan Xue ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Intrinsic Viscosity ◽  
Average Molecular Weight ◽  
Group Analysis ◽  
Gel Permeation Chromatography ◽  
Molecular Weights ◽  
The One ◽  
Relationship Of ◽  
The Relationship ◽  
End Group

In this work, a series of poly(Hexanediol adipate)(PHA) samples (103＜Mn＜104) with narrow molecular weight distribution were prepared by the polymerization between adilic acid and 1,6-hexandiol. End-group analysis was applied to determine the number average molecular weight (Mn) of PHA. Gel permeation chromatography (GPC) was employed to obtain the average molecular weights (Mn, Mv, Mw).The intrinsic viscosity of the samples in the tetrahydrofuran (THF) solution was determined at 298 K by the dilution extrapolation method and the one-point method. The relationship between the intrinsic viscosity and the molecular weight for PHA was studied by the Mark-Houwink-Sakurada (MHS) equation, and the parameters of equation were determined.

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