Elevated plasma factor VIII enhances venous thrombus formation in rabbits: Contribution of factor XI, von Willebrand factor and tissue factor

The present studies were undertaken to determine whether factor VIII/von Willebrand factor (vWF) present in the vessel wall (in addition to that in plasma) may mediate the attachment of platelets to subendothelium. Subendothelium from everted rabbit aorta was exposed to human citrated blood flowing through an annular perfusion chamber at 40 mL/min (wall shear rate of 2,600 s-1 for five minutes). The vessel segments were incubated at 37 degrees C for one hour with various dilutions of either goat-anti-rabbit factor VIII/vWF serum or an IgG fraction prepared from the serum. Control segments were incubated with serum or IgG from a nonimmunized goat. Values of platelet contact (C), platelet adhesion (C + S), and thrombus formation (T) on the subendothelium were evaluated by a morphometric technique. Compared with vessels incubated with fractions prepared from a normal goat, a significant decrease in platelet adhesion (C + S), ranging from 45% to 65%, was observed on vessels incubated with various dilutions (1:5 to 1:50) of either serum or IgG fractions of goat-anti-rabbit factor VIII/vWF. A similar decrease in platelet adhesion was observed with vessels incubated with an F(ab')2 fragment against rabbit factor VIII/vWF prepared in the goat. When goat-anti-rabbit factor VIII/vWF IgG was added to rabbit blood (1:75 dilution), platelet adhesion was reduced to the same extent (65%) on normal rabbit vessels and on vessels pre-incubated with goat-anti-rabbit factor VIII/vWF. Immunofluorescence studies revealed the presence of rabbit factor VIII/vWF in the subendothelium of rabbit aorta and the continued binding of the goat-anti-factor VIII/vWF antibodies on subendothelium during the perfusion studies. No uptake of human factor VIII/vWF on the rabbit subendothelium was observed by this immunologic technique; human factor VIII/vWF was found to be entirely associated with the attached human platelets. Thus, factor VIII/vWF in the vessel wall may mediate platelet attachment to subendothelium in a manner similar to that of plasma factor VIII/vWF.

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Growth hormone (GH) therapy in GH-deficient patients, the plasma Factor VIII-von Willebrand factor complex, and capillary fragility. A double-blind, placebo-controlled crossover study

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.3109/00365519009091600 ◽

1990 ◽

Vol 50 (4) ◽

pp. 417-420 ◽

Cited By ~ 13

Author(s):

J. O. L. Jørgensen ◽

S. A. Pedersen ◽

J. Ingerslev ◽

F J. Møller ◽

J. S. Christiansen

Keyword(s):

Growth Hormone ◽

Factor Viii ◽

Crossover Study ◽

Von Willebrand Factor ◽

Gh Therapy ◽

Double Blind ◽

Double Blind Placebo ◽

Plasma Factor ◽

Von Willebrand ◽

Willebrand Factor

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Multimeric composition of factor VIII/von Willebrand factor following administration of DDAVP: implications for pathophysiology and therapy of von Willebrand's disease subtypes

Blood ◽

10.1182/blood.v59.6.1272.1272 ◽

1982 ◽

Vol 59 (6) ◽

pp. 1272-1278 ◽

Cited By ~ 241

Author(s):

ZM Ruggeri ◽

PM Mannucci ◽

R Lombardi ◽

AB Federici ◽

TS Zimmerman

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

Resting State ◽

Bleeding Time ◽

Type I ◽

Von Willebrand's Disease ◽

Von Willebrand’S Disease ◽

Plasma Factor ◽

Von Willebrand ◽

Willebrand Factor

Abstract We have studied the modifications in the multimeric composition of plasma factor VIII/von Willebrand factor and the bleeding time response following administration of 1-Deamino-[8-D-arginine]-Vasopressin (DDAVP) to patients with different subtypes of von Willebrand's disease. In type I, all multimers were present in plasma in the resting state, though they were decreased in concentration. Administration of DDAVP resulted in an increased concentration of these forms as well as the appearance of larger forms than were previously present. There was concomitant correction of the bleeding time. In type IIA, large multimers were absent in the resting state, and although DDAVP induced an average threefold increase in the plasma concentration of factor VIII/von Willebrand factor, the larger multimers did not appear and the bleeding time, although shortened, was not corrected. In contrast, the larger multimers that were also absent from type IIB plasma in the resting state rapidly appeared following DDAVP administration. However, their appearance was transitory and the bleeding time, as in IIA patients, was shortened but not corrected. The characteristic multimeric composition of platelet factor VIII/von Willebrand factor in given subtypes predicted the alteration in plasma factor VIII/von Willebrand factor induced by DDAVP. These studies provide evidence that the different subtypes of von Willebrand's disease represent distinct abnormalities of factor VIII/von Willebrand factor. They also suggest that complete hemostatic correction following DDAVP can be routinely expected only in type I von Willebrand's disease, and only if factor VIII/von Willebrand factor can be raised to normal levels.

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Presence Of Receptor For Activated Factor VIII On The Surface Of Released Platelets

10.1055/s-0038-1652900 ◽

1981 ◽

Author(s):

K Brodén ◽

L-O Andersson

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

Factor X ◽

Factor Viii Activity ◽

Platelet Receptor ◽

Plasma Factor ◽

Centrifuge Tube ◽

Dilute Suspension ◽

Von Willebrand ◽

Willebrand Factor

In normal plasma Factor VIII activity is associated with a series of high molecular weight glycoprotein complexes also containing von Willebrand Factor related activities. To study the possible binding of various forms of Factor VIII to released platelets, a solution containing Factor VIII was mixed with a dilute suspension of platelets, which were released by addition of collagen. After 10 minutes of incubation the mixture was layered over 1.5 ml of 30% human serum albumin solution in a centrifuge tube and subjected to centrifugation at 7,000xg. Fractions were collected and analyzed for Factor VIII activity and phospholipid-related procoagulant activity. When purified Factor VUI/von Willebrand Factor complex was studied no significant association between the Factor VIII activity and the platelets were found. When purified Factor VUI/von Willebrand Factor complex was activated with 10-3 units/ml of thrombin and then tested, the main part of the Factor VIII activity became associated with the platelets. Even at very low platelet counts this binding was clearly detectable. The binding occurred both in the presence and in the absence of Ca2+. Thus released platelets bind thrombin-activated Factor VIII but not the Factor VUI/von Willebrand Factor complex. It is known that activation of Factor VIII by thrombin causes dissociation of the Factor VIII from the von Willebrand Factor part of the complex. The data obtained indicate that this dissociation is necessary in order to get the Factor VIII to bind to the platelet receptor. It may work as an amplification mechanism where the first traces of Thrombin formed upon initiation of coagulation dissociates Factor VIII from von Willebrand Factor, followed by binding to receptor on released platelets and formation of Factor X activator complex on the surface of the platelets.

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J.L. Moake, C.K. Rudy and J.H. Troll et al., Unusually large plasma factor VIII : von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura, New Engl. J. of Med. 307 (1982), pp. 1432–1435.

Revue Fran&#xE7 aise de Transfusion et Immuno-h&#xE9 matologie ◽

10.1016/s0338-4535(83)80059-2 ◽

1983 ◽

Vol 26 (1) ◽

pp. 105-106 ◽

Cited By ~ 1

Author(s):

E RACADOT

Keyword(s):

Factor Viii ◽

Thrombotic Thrombocytopenic Purpura ◽

Von Willebrand Factor ◽

Thrombocytopenic Purpura ◽

Plasma Factor ◽

Von Willebrand ◽

Willebrand Factor

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COVID-19 and Acute Coronary Syndromes: From Pathophysiology to Clinical Perspectives

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/4936571 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Luca Esposito ◽

Francesco Paolo Cancro ◽

Angelo Silverio ◽

Marco Di Maio ◽

Patrizia Iannece ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Tissue Factor ◽

Von Willebrand Factor ◽

Acute Coronary Syndromes ◽

Oxygen Supply ◽

Thrombus Formation ◽

Cellular Damage ◽

Coronary Syndromes ◽

Von Willebrand ◽

Willebrand Factor

Acute coronary syndromes (ACS) are frequently reported in patients with coronavirus disease 2019 (COVID-19) and may impact patient clinical course and mortality. Although the underlying pathogenesis remains unclear, several potential mechanisms have been hypothesized, including oxygen supply/demand imbalance, direct viral cellular damage, systemic inflammatory response with cytokine-mediated injury, microvascular thrombosis, and endothelial dysfunction. The severe hypoxic state, combined with other conditions frequently reported in COVID-19, namely sepsis, tachyarrhythmias, anemia, hypotension, and shock, can induce a myocardial damage due to the mismatch between oxygen supply and demand and results in type 2 myocardial infarction (MI). In addition, COVID-19 promotes atherosclerotic plaque instability and thrombus formation and may precipitate type 1 MI. Patients with severe disease often show decrease in platelets count, higher levels of d-dimer, ultralarge von Willebrand factor multimers, tissue factor, and prolongation of prothrombin time, which reflects a prothrombotic state. An endothelial dysfunction has been described as a consequence of the direct viral effects and of the hyperinflammatory environment. The expression of tissue factor, von Willebrand factor, thromboxane, and plasminogen activator inhibitor-1 promotes the prothrombotic status. In addition, endothelial cells generate superoxide anions, with enhanced local oxidative stress, and endothelin-1, which affects the vasodilator/vasoconstrictor balance and platelet aggregation. The optimal management of COVID-19 patients is a challenge both for logistic and clinical reasons. A deeper understanding of ACS pathophysiology may yield novel research insights and therapeutic perspectives in higher cardiovascular risk subjects with COVID-19.

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Effect of multimeric structure of the factor VIII/von Willebrand factor protein on binding to platelets

Blood ◽

10.1182/blood.v58.2.387.bloodjournal582387 ◽

1981 ◽

Vol 58 (2) ◽

pp. 387-397 ◽

Cited By ~ 2

Author(s):

HR Gralnick ◽

SB Williams ◽

DK Morisato

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

Competitive Inhibition ◽

Human Platelets ◽

Factor Vii ◽

Variant Form ◽

Factor Binding ◽

Plasma Factor ◽

Von Willebrand ◽

Willebrand Factor

The characteristics of the intact factor VIII/von Willebrand factor protein binding to human platelets was compared to 2-mercaptoethanol- treated factor VIII/von Willebrand factor protein and to fractions of plasma factor VIII/von Willebrand factor protein that elute after the void volume. These studies indicate that the factor VIII/von Willebrand factor protein larger size oligomers bind preferentially with high affinity to low capacity sites on human platelets. The intermediate and smaller size oligomers bind with intermediate or low affinity to sites with a much greater capacity. The results from binding analysis are also paralleled by the competitive inhibition of the intact factor VIII/von Willebrand factor protein by the various 2-mercaptoethanol- treated materials. These studies indicate that the two classes of binding sites seen in previous reports of factor VII/von Willebrand factor binding reflect heterogeneity in the oligomer size of the factor VIII/von Willebrand factor protein used in these assays. This study provides a model for understanding some of the normal structure- function relationships of the normal factor VIII/von Willebrand factor protein and the defect(s) in a variant form of von Willebrand's disease. In this form of the disease, decreased factor VIII/von Willebrand factor binding to platelets is reflected in decreased von Willebrand factor activity but coagulant and/or antigen levels are normal or only slightly decreased.

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Effect of multimeric structure of the factor VIII/von Willebrand factor protein on binding to platelets

Blood ◽

10.1182/blood.v58.2.387.387 ◽

1981 ◽

Vol 58 (2) ◽

pp. 387-397 ◽

Cited By ~ 65

Author(s):

HR Gralnick ◽

SB Williams ◽

DK Morisato

Keyword(s):

Factor Viii ◽

Von Willebrand Factor ◽

Competitive Inhibition ◽

Human Platelets ◽

Factor Vii ◽

Variant Form ◽

Factor Binding ◽

Plasma Factor ◽

Von Willebrand ◽

Willebrand Factor

Abstract The characteristics of the intact factor VIII/von Willebrand factor protein binding to human platelets was compared to 2-mercaptoethanol- treated factor VIII/von Willebrand factor protein and to fractions of plasma factor VIII/von Willebrand factor protein that elute after the void volume. These studies indicate that the factor VIII/von Willebrand factor protein larger size oligomers bind preferentially with high affinity to low capacity sites on human platelets. The intermediate and smaller size oligomers bind with intermediate or low affinity to sites with a much greater capacity. The results from binding analysis are also paralleled by the competitive inhibition of the intact factor VIII/von Willebrand factor protein by the various 2-mercaptoethanol- treated materials. These studies indicate that the two classes of binding sites seen in previous reports of factor VII/von Willebrand factor binding reflect heterogeneity in the oligomer size of the factor VIII/von Willebrand factor protein used in these assays. This study provides a model for understanding some of the normal structure- function relationships of the normal factor VIII/von Willebrand factor protein and the defect(s) in a variant form of von Willebrand's disease. In this form of the disease, decreased factor VIII/von Willebrand factor binding to platelets is reflected in decreased von Willebrand factor activity but coagulant and/or antigen levels are normal or only slightly decreased.

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