Influence of Increasing Levels of High Purity Factor VIII on Thrombin Generation In-Vitro

Ibbotson, S H; Tate, G. M.; Hampton, K.K.; Davies, J. A.

doi:10.1042/cs079015pa

Cited by 6 publications

(7 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The method used in this study to measure thrombin generation is sensitive, precise and reproducible [16]. We have shown Ts0, to be sensitive to the addition of increasing concentrations of FVIII:C in vitro [9] and to be reduced progressively with increasing age of the subject and plasma FVIII:C concentration in vivo [22]. It is more sensitive to reduced coagulation times than standard laboratory tests such as the APTT [22].…”

Section: Discussionmentioning

confidence: 88%

“…Similarly, FVIII:C concentrations rise in humans after administration of adrenaline [8]. Increasing concentrations of FVIII:C reduce plasma coagulation times in vitro [9] and clinical studies have demonstrated acute increases in circulating FVIII:C concentrations in response to various physical stresses such as hypoglycaemia, diabetic ketoacidosis and surgery [10][11][12]. However, it is not clear whether these sudden increases in FVIII:C lead to a corresponding enhancement of coagulation in vivo.…”

mentioning

confidence: 99%

“…Plasma A (--) with factor VIII:C concentration of 1.62 IU/ml has a shorter lag time (lag) and time to generation of 50% maximal thrombin activity (Ts0) than plasma B (---), with factor VIII:C concentration of 0.44 IU/ml Relationships between plasma factor VIII:C level (IU/ml) and HBAm concentration (%) and time taken to reach 50% maximal thrombin activity (Ts0/s). Results from diabetic patients( 9 ) and control subjects (O) combined, n = 70. Factor VIII:C correlated with HbAlc (r = 0.315, p = 0.008) and inversely with Ts0 (r = -0.395, p < 0.01)…”

mentioning

confidence: 99%

See 2 more Smart Citations

Generation of thrombin activity in relation to factor VIII: C concentrations and vascular complications in Type 1 (insulin-dependent) diabetes mellitus

et al. 1992

View full text Add to dashboard Cite

A possible association between plasma coagulant activity and the presence of vascular complications in patients with diabetes mellitus was studied by measuring the generation of thrombin in plasma of 20 control subjects and 50 diabetic patients classified according to the presence or absence of microvascular complications. Thrombin production was determined in defibrinated plasma using a semi-automated technique with measurement of thrombin activity using chromogenic peptide S2238. Values determined were the lag time to appearance of thrombin activity and time taken to generate 50% maximal thrombin activity. Thrombin activity was related to concentrations of coagulant factor VIII activity and fibrinopeptide A and these were correlated with HbA1C levels. The median time to generate 50% maximal thrombin activity was not significantly reduced in diabetic patients compared with control subjects (53 vs 54 s, p = 0.076) and there were no significant differences between patients with and without microvascular complications. There were no differences in median fibrinopeptide A concentrations between the diabetic and control subjects (1.5 vs 2.2 nmol/l, p = 0.169). Time to 50% maximal thrombin activity correlated inversely with factor VIII:C concentrations in diabetic patients (r = -0.344, p = 0.015, n = 50) and both this and lag time correlated with factor VIII:C in diabetic patients and control subjects combined (r = -0.395, p less than 0.01; r = -0.327, p = 0.006, n = 70). Factor VIII:C concentrations increased with age of the subject and with HbA1C concentrations. The results failed to show enhancement of coagulation in contact-activated diabetic plasma compared with control plasma and suggest that a relationship between high levels of factor VIII:C in diabetes and the development of mcirovascular complications is unlikely to be mediated through procoagulant activity in plasma.

show abstract

Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Generation of thrombin activity in relation to factor VIII: C concentrations and vascular complications in Type 1 (insulin-dependent) diabetes mellitus

et al. 1992

View full text Add to dashboard Cite

show abstract

“…Current opinion favours the role of increased vWF concentra tion as an early marker of existing endothelial damage (25). There is also some evidence that high plasma levels of FVIII :C may contribute to a procoagulant milieu (26,27).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Insulin-Induced Hypoglycaemia on Factor VIII: C Concentrations and Thrombin Activity in Subjects with Type 1 (Insulin-Dependent) Diabetes

et al. 1995

View full text Add to dashboard Cite

SummaryThe effect of insulin-induced hypoglycaemia on plasma coagulant activity was studied in 11 subjects with well-controlled, uncomplicated type 1 diabetes. Thrombin generation was determined in plasma by a computer ex-vivo assisted chromogenic method and by the activated partial thromboplastin time (APTT). In addition, factor VIII :C, thrombin-antithrombin III (TAT) complex and fibrindpeptide A (FPA) levels were measured. Hypoglycaemia induced a rise in mean (SD) factor VIII: C concentrations from a baseline level of 1.13 (0.32) IU/ml to a peak 15 min after onset of symptoms and they remained increased at 90 min [1.54 (0.57) and 1.5 (0.54) IU/ml, p <;0.001 respectively]. A corresponding reduction in time to generate 50% maximal thrombin activity occurred from a pre-insulin value of 56 (6) s to a minimum reading of 46 (7) s at 15 min (p <;0.001) and remained low at 90 min [48 (6) s, p <;0.001]. APTT shortened from 43.3 (4.8) s to 40.1 (4.6) s at 30 min (p <;0.001) but did not fall below the normal range (37.6-42.7 s) and no significant changes in TAT or FPA levels were noted. Factor VIII: C correlated inversely with time to generate 50% maximal thrombin activity and APTT (r = -0.580, p <;0.001; r = -0.673, p <;0.001, n = 66, respectively). The results show that the rise in plasma factor VIII: C levels induced by hypoglycaemia is accompanied by accelerated rates of generation of thrombin in contact-activated plasma, though concentrations of FPA and TAT remain unchanged, although TAT complexes are not a sensitive marker of in vivo thrombin generation.

show abstract

“…FVIILC is co-factor in the intrinsic pathway of coagulation, accelerating the activation of factor X by factor IXa but not having enzymatic activity itself. Invitro work has shown that an increased level of FVIILC directly accelerates blood coagulation and is rate-limiting in its action (5). FVIILC has been reported to be elevated in patients with diabetes mellitus, a chronic condition complicated by micro-and macro-vascular disease, but whether the association between high FVIILC concentrations and the vascular complications of diabetes is cause or effect is unclear (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

The Influence of Infusions of 1-Desamino-8-D-Arginine Vasopressin (DDAVP) In Vivo on Thrombin Generation In Vitro

1992

View full text Add to dashboard Cite

SummaryTo investigate the effect of increasing FVIII:C in-vivo on coagulation ex-vivo, DDAVP was infused over 15 min in 10 volunteers and in-vitro thrombin generation measured. FVIII:C rose from 0.42 and 0.43 IU/ml before DDAVP to 1.38, 1.73 and 1.78 IU/ml at 15, 30 and 60 min respectively (p <0.001).A computer-assisted thrombin generation test was performed in defibrinated plasma using chromogenic substrate, S2238. Time to reach 50% maximal thrombin activity (T50/s) and lag phase of thrombin generation (lag/s) were measured. Lag shortened from 75 and 60 s before to 45 s during and after infusion (p <0.001). T50 shortened from 78.5 and 76.0 to 62.5, 60.0 and 58.5 s at times 15 (p <0.01), 30 (p <0.001) and 60 (p <0.001) min. FVIII:C correlated inversely with lag and T50 (r = –0.847, p <0.001, r = –0.826, p <0.001, n = 10) respectively.These findings show that acute elevations of FVIII:C in-vivo accelerate in-vitro thrombin production. This work suggests that elevated FVIII:C levels in-vivo may be important in thrombo-occlusive disease.

show abstract

Influence of Increasing Levels of High Purity Factor VIII on Thrombin Generation In-Vitro

Cited by 6 publications

References 0 publications

Generation of thrombin activity in relation to factor VIII: C concentrations and vascular complications in Type 1 (insulin-dependent) diabetes mellitus

Generation of thrombin activity in relation to factor VIII: C concentrations and vascular complications in Type 1 (insulin-dependent) diabetes mellitus

The Effect of Insulin-Induced Hypoglycaemia on Factor VIII: C Concentrations and Thrombin Activity in Subjects with Type 1 (Insulin-Dependent) Diabetes

The Influence of Infusions of 1-Desamino-8-D-Arginine Vasopressin (DDAVP) In Vivo on Thrombin Generation In Vitro

Contact Info

Product

Resources

About