Biomedical subjects

Grace Gilmore

Publications and source records attributed to Grace Gilmore.

3 recordsLinked to original sources

PubMed2006

The tissue factor pathway in ischemic stroke.

To explore the role of the the tissue factor (TF) pathway in ischemic stroke. We measured blood concentrations of markers of the TF pathway [TF antigen, free tissue factor pathway inhibitor antigen (TFPIf) and activity (TFPIac), and activated factor VII (FVIIa)] within 7 days (acute phase) and after 3-6 months (convalescence) in 150 patients with first-ever ischemic stroke and 150 community controls. During the acute phase, TF antigen and TFPIf were not significantly altered but TFPIac was increased (mean 1.27 versus 1.13 U/ml, P = 0.04) and FVIIa was decreased in cases compared with controls (mean 43.3 versus 57.9 mU/ml, P = 0.0004). After adjusting for baseline differences between cases and controls, increasing quartiles of TFPIf were independently associated with reduced odds of stroke, and reducing quartiles of FVIIa and increasing quartiles of TFPIac with increased odds of stroke. During the convalescent phase, FVIIa and TFPIac returned to normal but TF antigen and TFPIf were significantly decreased compared with controls [median TF antigen, 110 (follow-up) versus 155 pg/ml (controls), P = 0.0008; median TFPIf, 15.5 (follow-up) versus 23.3 ng/ml (controls), P = 0.002]. Alterations of blood concentrations of TF pathway markers are common in patients with acute ischemic stroke. The mechanisms are unclear but may relate to enhanced formation of TF-FVIIa complexes and upregulation and release of TFPI during the acute phase, and ongoing consumption of TF antigen and TFPIf during the chronic phase as the atherosclerotic plaque heals.

Aged↗

PubMed2004

Evaluation of the phospholipid-rich dilute Russell's viper venom assay to monitor oral anticoagulation in patients with lupus anticoagulant.

The International Normalized Ratio (INR) is generally recommended to monitor anticoagulant therapy in patients treated with warfarin. However, there has been concern about the validity of the INR to monitor warfarin therapy in patients with lupus anticoagulant, particularly when there is prolongation of the baseline INR. An alternative approach is to use a chromogenic factor X assay that is not sensitive to lupus anticoagulant. However, this assay is expensive, not widely available, and does not have an established therapeutic range. We hypothesized that the phospholipid-rich dilute Russell viper venom time (prdRVVT), a simple, rapid and inexpensive assay, might be suitable to monitor warfarin therapy in this situation since Russell's viper venom directly activates coagulation factor X while the phospholipid in the reagent reduces or negates any effect of lupus anticoagulant on the assay. We measured the INR, chromogenic factor X, and prdRVVT in 50 patients stabilized on warfarin for at least 6 weeks, 12 of whom had lupus anticoagulant, and 37 patients not taking warfarin, 17 of whom had lupus anticoagulant. Factor X was negatively correlated with INR in anticoagulated patients both in the absence (r = -0.45, P = 0.01) and presence (r = -0.43, P = 0.17) of lupus anticoagulant. The prdRVVT was also strongly correlated with INR in anticoagulated patients without lupus anticoagulant (r = 0.60, P < 0.0001) but there was no correlation in the presence of lupus anticoagulant (r = -0.13, P = 0.68). Our results suggest that the prdRVVT is not suitable for monitoring warfarin therapy in patients with lupus anticoagulant.

Anticoagulants↗

PubMed2002

A comparative multi-laboratory assessment of three factor VIII/von Willebrand factor concentrates.

Five expert laboratories have participated in a cross-laboratory study to co-evaluate and compare three commercial Factor VIII/von Willebrand factor (VWF) concentrates. A total of nine factor concentrate lots were evaluated, comprising AHF (High Purity) (AHF HP; x3), Biostate (x3) and Humate/Haemate (x3). All laboratories blind tested for FVIII: C, VWF: Ag and VWF: CB, four tested for VWF: RCo, and one performed VWF: Multimers. The study yielded inter-laboratory CVs for VWF: Ag and FVIII:C around 10-15%, and for VWF:CB and VWF:RCo around 20%, significantly lower than those of previous multi-laboratory surveys. All three lots of AHF HP contained in the vicinity of 25 U/ml FVIII:C, around 60-75 U/ml of VWF:Ag, but only 30-45 U/ml of VWF:CB and 40-50 U/ml of VWF:RCo (thus, CB/Ag ratio around 0.5-0.6 and RCo/Ag ratio around 0.6-0.7). Study determined that FVIII: C and VWF: RCo levels were similar to manufacturer assigned levels. Some loss of the high molecular weight (HMW) multimers was observed, together with an intense low molecular weight (LMW) VWF band consistent with some reduction or proteolysis of HMW VWF. All three lots of Humate/Haemate contained in the vicinity of 23-32 U/ml of FVIII:C, 70-105 U/ml of VWF: Ag, 50-90 U/ml of VWF: CB and VWF: RCo (i.e. CB/Ag ratio around 0.6-0.9 and RCo/Ag ratio around 0.6-1.1). Study-determined FVIII: C and VWF: RCo levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was also observed with Humate/Haemate. All three lots of Biostate contained in the vicinity of 40-55 U/ml of FVIII:C, 105-170 U/ml of VWF:Ag, 90-150 U/ml of VWF:CB, and 90-135 U/ml of VWF:RCo (i.e. CB/Ag and RCo/Ag ratios around 0.7-1.0). Study-determined FVIII:C levels were similar to manufacturer-assigned levels. The LMW multimer band seen with AHF HP was not observed with Biostate. The defined pattern of increasing CB/ Ag from AHF HP to Humate/Haemate and Biostate was consistently observed in study data from each of the five laboratories. In conclusion, study findings indicate some differences in the retention of functional/ HMW VWF between factor concentrates, and this is expected to have significant implications in terms of clinical efficacy for therapy in VWD.

Dimerization↗