Possible Evidence for an Increased Factor VIII Antigen Synthesis in Vascular Endothelium of Diabetic Subjects

Giustolisi, Rosario; Musso, R; Russo, Mario Salvatore; Catania, N; Lombardo, Turiddu; Cacciola, Elio Gentilini

doi:10.1055/s-0038-1657188

Cited by 9 publications

(5 citation statements)

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“…1); this is consistent with a response to endothelial cell injury, as VIII: C is not synthesised or stored by vascular endothelium. It is also in accord with the observation that the ability of endothelial cells to synthesise VIII: Ag is enhanced in diabetic patients [27]. However, the possibility also exists that the smaller increase and more rapid fall of plasma VIII: C is due to the presence of a consumptive coagulopathy, VIII: C being a procoagulant protein which is consumed during fibrin generation; intravascular coagulation is a feature of some cases of diabetic ketoacidosis [25,28].…”

Section: Discussionsupporting

confidence: 82%

Changes in the factor VIII complex in diabetic ketoacidosis: evidence of endothelial cell damage?

et al. 1987

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Factor VIII-related antigen and von Willebrand factor are synthesised by and released from vascular endothelium. Acute increases in the plasma concentration of these proteins may reflect endothelial cell damage. We have thus measured the plasma concentration of factor VIII-related antigen and von Willebrand factor, together with procoagulant factor VIII, during the course of acute diabetic ketoacidosis in seven patients. In addition, evidence for qualitative changes in the factor VIII complex was sought. Plasma factor VIII-related antigen and von Willebrand factor were markedly increased (plasma factor VIII-related antigen at presentation, median 2.75 U/ml; von Willebrand factor 2.95 U/ml) and returned toward normal with clinical and biochemical resolution (plasma factor VIII-related antigen at clinical recovery, median 1.80 U/ml; von Willebrand factor 2.05 U/ml). Plasma procoagulant factor VIII followed a similar pattern, but levels were less elevated (plasma procoagulant factor VIII, at presentation, median 1.6 U/ml; at clinical recovery, 1.2 U/ml). Crossed immunoelectrophoresis and sodium dodecyl sulphate-acrylamide electrophoresis with autoradiographic identification of multimeric structure revealed no evidence of structurally abnormal factor VIII-related antigen in diabetic ketoacidosis. However, an extra peak on crossed immunoelectrophoresis ("pre-peak") was a feature in the acute phase ketoacidotic plasma in six subjects, and may represent aggregated factor VIII. Changes in plasma factor VIII are a feature of diabetic ketoacidosis and, whilst not specific to this condition, may be the result of endothelial cell damage.

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Section: Discussionsupporting

confidence: 82%

Changes in the factor VIII complex in diabetic ketoacidosis: evidence of endothelial cell damage?

et al. 1987

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“…The studies of Giustolisi and co-workers postulate that the increase in plasma Factor VIIIR:Ag levels in diabetic patients after several hours of venostasis occurs' through the mechanism of increased synthesis and release of stored Factor VIIIR:Ag. 12 Our preliminary studies showing an increase in cellular Factor VIIIR:Ag levels with increasing glucose concentration are in agreement with either increased storage and/or synthesis. To elucidate which of the above mechanisms are responsible for the increased levels of Factor VIIIR:Ag found in our preliminary studies will require isotopic labeling and pulse-chase experiments.…”

Section: Discussionsupporting

confidence: 76%

Elevated Glucose Concentrations Increase Factor VIIIR:Ag Levels in Human Umbilical Vein Endothelial Cells

Mordes¹,

Lazarchick

Colwell

et al. 1983

Diabetes

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To determine if endothelial cell metabolism is affected by the elevated glucose concentrations known to occur in diabetes mellitus, we measured cellular Factor VIIIR:Ag in endothelial cells grown under conditions of increased glucose concentration. The results of this study illustrate that, under cell culture conditions, an increase in glucose concentration results in increased cellular levels of Factor VIIIR:Ag. Specifically, a glucose concentration of 300 mg/dl resulted in a 23% increase in Factor VIIIR:Ag levels while a glucose concentration of 600 mg/dl resulted in a 54% increase in Factor VIIIR:Ag levels. These in vitro findings may relate to the increase in plasma Factor VIIIR:Ag levels known to occur in diabetic patients.

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“…There is general agreement in the literature that plasma levels of FVIII RAg and FVIII Rcof are increased in patients with diabetes mellitus (1,2,3,(16)(17)(18)(19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 81%

“…In a later study of FVIII measured after repeated venostasis, they found evidence of increased synthesis, too, in patients with diabetes (19).…”

Section: Discussionmentioning

confidence: 94%

The Effect of Diabetes Regulation on Platelet Release, Fibrinolysis and Coagulation Tests, Before and After Stimulation with DDAVP

Jh¹,

Ac²,

Ma³

et al. 1985

Thromb Haemost

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SummaryIn this longitudinal study we measured β-TG, PF4, fibrinolytic activity (extrinsic and euglobulin fraction), fibrinogen, FVIII RAg and FVIII Rcof before and after i.v. DDAVP (FPA was only measured before DDAVP) in 20 patients with diabetes mellitus. These parameters were measured on three occasions: phase I: during disregulation, phase II: after three weeks of strict control, phase III: after nine weeks of good control. Twenty-two healthy volunteers served as normal controls.No significant differences related to metabolic control were found for β-TG, PF4, FPA and fibrinogen. There was no change after i.v. DDAVP administration. Fibrinolytic activity showed a significant increase after i.v. DDAVP. Baseline values and post-DDAVP increase were not significantly different from our normal controls.FVIII RAg and FVIII Rcof were both significantly elevated in diabetes mellitus. Both increased significantly after DDAVP. The FVIII RAg release (ΔFVIII RAg) was significantly less in the diabetics. Fibrinolytic activity, FVIII RAg and FVIII Rcof are independent of the degree of metabolic control in patients with diabetes.

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Possible Evidence for an Increased Factor VIII Antigen Synthesis in Vascular Endothelium of Diabetic Subjects

Cited by 9 publications

References 0 publications

Changes in the factor VIII complex in diabetic ketoacidosis: evidence of endothelial cell damage?

Changes in the factor VIII complex in diabetic ketoacidosis: evidence of endothelial cell damage?

Elevated Glucose Concentrations Increase Factor VIIIR:Ag Levels in Human Umbilical Vein Endothelial Cells

The Effect of Diabetes Regulation on Platelet Release, Fibrinolysis and Coagulation Tests, Before and After Stimulation with DDAVP

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