Increased Factor VIII/von Willebrand Factor Antigen and von Willebrand Factor Activity in Scleroderma and in Raynaud's Phenomenon

Kahaleh, M. Bashar

doi:10.7326/0003-4819-94-4-482

Cited by 215 publications

(63 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…During this period, observations ofthe pathogenesis of scleroderma have focused on vascular and microvascular lesions; on evidence of endothelial damage; on platelet adhesion, aggregation, and release; and on the subsequent activation both of smooth muscle cells to produce the intimal proliferation and of interstitial fibroblasts to produce fibrosis (7)(8)(9)(10). A unifying hypothesis would propose the presence offactors released from plasma or platelets which act as stimuli to fibrosis; among such factors, the potent mitogen, plateletderived growth factor (PDGF), is released during endothelial injury and platelet adhesion to the subendothelium (11).…”

mentioning

confidence: 99%

Replication and phenotypic expression of control and scleroderma human fibroblasts: responses to growth factors.

LeRoy¹,

Mercurio²,

Sherer³

1982

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

To explore the mechanism of increased collagen synthesis by scleroderma skin fibroblasts in vitro, control and scleroderma fibroblasts were compared in confluent monolayer cultures growth-arrested by serum deprivation; responses to optimal mitogenic doses of platelet-derived growth factor, fibroblast growth factor, epidermal growth factor and nerve growth factor were compared. Plateletderived growth factor had a selective mitogenic effect on control skdn fibroblasts not observed with scleroderma skin fibroblasts. None of the factors studied had a selective effect on collagen synthesis independent of cell replication; scleroderma and control fibroblasts responded similarly. Therefore, the growth factors studied may not be involved in generating the activated scleroderma fibroblast directly; platelet-derived growth factor may play an indirect role in fibroblast replication in human fibrotic disorders.More than a decade ago, it was observed that fibroblasts from involved skin of patients with scleroderma synthesized increased levels of collagen in vitro (1, 2); today the mechanism remains unknown (3-6). During this period, observations ofthe pathogenesis of scleroderma have focused on vascular and microvascular lesions; on evidence of endothelial damage; on platelet adhesion, aggregation, and release; and on the subsequent activation both of smooth muscle cells to produce the intimal proliferation and of interstitial fibroblasts to produce fibrosis (7-10). A unifying hypothesis would propose the presence offactors released from plasma or platelets which act as stimuli to fibrosis; among such factors, the potent mitogen, plateletderived growth factor (PDGF), is released during endothelial injury and platelet adhesion to the subendothelium (11). Therefore, the influence of PDGF on skin fibroblast collagen synthesis was studied.Endothelial damage and platelet interaction with the exposed subendothelium, resulting in release of platelet-derived mitogenic factors (including PDGF), have been proposed, at least indirectly, to play a role in the evolution of the scleroderma vascular lesion. Events preceding endothelial injury are poorly understood; altered immunity leading to humoral or lymphocyte/monocyte mediators ofinjury has been proposed with supporting evidence (12). If PDGF is the direct mediator of fibroblast activation in scleroderma, the enhanced collagen synthesis of scleroderma fibroblasts should be accompanied by increased cell replication at some stage in the process. Thus, a PDGF mechanism in scleroderma would imply replication offibroblast populations instead of, or in addition to, the selective stimulation ofcollagen synthesis per cell; in earlier studies, increased collagen synthesis per cell was observed in vitro without evidence of increased cell replication (1, 2). If PDGF is the mediator of fibroblast activation in scleroderma, its action should account for the initial observations of increased collagen synthesis per cell.A second characteristic of scleroderma fibroblasts in culture has been ...

show abstract

mentioning

confidence: 99%

Replication and phenotypic expression of control and scleroderma human fibroblasts: responses to growth factors.

LeRoy¹,

Mercurio²,

Sherer³

1982

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Endothelial damage resulting from vasculitis in SLE may predispose to thrombus formation. In scleroderma and Raynaud's phenomenon (21), marked elevations of factor VIII von Willebrand factor have also been reported. In Kawasaki disease, a childhood arteritis, evidence of activation of coagulation and increased factor VIII activity has been reported (22).…”

Section: Discussionmentioning

confidence: 99%

Evidence for intravascular coagulation in systemic onset, but not polyarticular, juvenile rheumatoid arthritis

Scott

Gerber

Maryjowski

et al. 1985

Arthritis & Rheumatism

View full text Add to dashboard Cite

After observing a child with systemic onset juvenile rheumatoid arthritis (S-JRA) who developed purpura fulminans in association with disseminated intravascular coagulation, with subsequent gangrene and autoamputation, we undertook a prospective study of coagulation parameters in children with JRA. Ten consecutive children with S-JRA, 10 children with rheumatoid factor-negative, polyarticular juvenile rheumatoid arthritis (P-JRA), and 10 age-and sex-matched controls were studied. Routine coagulation screening tests were performed, as were tests for plasma fibrinopeptide A (a sensitive measure of intravascular thrombin generation), factor VIII-related antigen (an endothelial cell protein), and platelet factor 4 (a plateletsecreted protein). Our studies suggest that activation of intravascular coagulation is common in systemic onset JRA, but not in rheumatoid factor-negative, polyarticular disease. The coagulopathy may cause severe morbidity. In addition, marked elevations of plasma factor VIII-related antigen suggest perturbation of endothelial cells and vascular involvement in S-JRA, but not in P-JRA. Normal ranges of platelet factor 4 indicate that

show abstract

“…The first study in which high vWF:Ag levels in vasculitis were determined was conducted by Kahaleh et al [4]. High vWF:Ag levels had been found in scleroderma patients with Raynaud phenomenon, and it was suggested that this may be related to release from injured endothelial cells.…”

Section: Discussionmentioning

confidence: 99%

Von Willebrand factor antigen levels in Behçet disease

et al. 2005

View full text Add to dashboard Cite

High von Willebrand factor antigen (vWF:Ag) levels can be found due to vascular endothelial injury in Behç et disease. The aim of this study is to evaluate whether there is any relationship between vWF:Ag levels and vascular or other organ involvements and acute-phase reactants in Behç et disease. Fifteen controls and 17 Behç et's patients were included; 10 had oral ulcers, 5 had genital ulcers, 3 had skin lesions, 6 had ocular involvement, 5 had arthritis, and 6 had vascular involvement. VWF:Ag levels were higher in Behç et's patients than controls. VWF:Ag levels in Behç et's patients with oral ulcers, genital ulcers, and ocular and vascular involvement were statistically higher than in the control group. Differences between vWF:Ag levels in Behç et's patients with and without organ involvement were not statistically significant. A linear correlation between serum ferritin levels and vWF:Ag levels was observed. These results demonstrate that elevated levels of plasma vWF:Ag are related to Behç et disease exacerbation rather than vascular involvement. Am.

show abstract

Increased Factor VIII/von Willebrand Factor Antigen and von Willebrand Factor Activity in Scleroderma and in Raynaud's Phenomenon

Cited by 215 publications

References 11 publications

Replication and phenotypic expression of control and scleroderma human fibroblasts: responses to growth factors.

Replication and phenotypic expression of control and scleroderma human fibroblasts: responses to growth factors.

Evidence for intravascular coagulation in systemic onset, but not polyarticular, juvenile rheumatoid arthritis

Von Willebrand factor antigen levels in Behçet disease

Contact Info

Product

Resources

About