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- Dahlbäck, Björn, et al.
(författare)
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New functional test for the TFPIα cofactor activity of Protein S working in synergy with FV-Short
- 2019
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 17:4, s. 585-595
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Tidskriftsartikel (refereegranskat)abstract
- Essentials Protein S and FV-Short are synergistic cofactors to Tissue Factor Pathway Inhibitor α (TFPIα). An assay for the TFPIα synergistic cofactor activity of protein S with FV-Short was developed. The assay was specific for the synergistic TFPIα-cofactor activity of free protein S. Protein S deficient individuals with known mutations were correctly distinguished from controls. Summary: Background Protein S is an anticoagulant cofactor to both activated protein C and tissue factor pathway inhibitor (TFPIα). The TFPIα-cofactor activity of protein S is stimulated by a short isoform of factor V (FV-Short), the two proteins functioning in synergy. Objective Using the synergistic TFPIα-cofactor activity between protein S and FV-Short to develop a functional test for plasma protein S. Patients/Methods TFPIα-mediated inhibition of FXa in the presence of FV-Short, protein S and negatively charged phospholipid vesicles was monitored in time by synthetic substrate S2765. TFPIα, FXa and FV-Short were purified proteins, whereas diluted plasma from protein S deficient patients or controls were used as source for protein S. Results The assay was specific for free protein S demonstrating good correlation to free protein S plasma levels (r = 0.92) with a Y-axis intercept of −5%. Correlation to concentrations of total protein S (free and C4BPβ+-bound) was lower (r = 0.88) and the Y-axis intercept was +46%, which is consistent with the specificity for free protein S. The test distinguished protein S-deficient individuals from 6 families with known ProS1 mutations from family members having no mutation. Protein S levels of warfarin-treated protein S deficient cases were lower than protein S in cases treated with warfarin for other causes. Conclusions We describe a new assay measuring the TFPIα-cofactor activity of plasma protein S. The test identifies type I/III protein S deficiencies and will be a useful tool to detect type II protein S deficiency having defective TFPIα-cofactor activity.
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| 2. |
- Singh, Sukhi, 1990, et al.
(författare)
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Intraoperative infusion of noradrenaline improves platelet aggregation in patients undergoing coronary artery bypass grafting: a randomized controlled trial
- 2019
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 17:4, s. 657-665
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Tidskriftsartikel (refereegranskat)abstract
- Background New approaches to prevent bleeding complications during cardiac surgery are needed. Objective To investigate if noradrenaline (NA) enhances platelet aggregation in patients undergoing coronary artery bypass grafting (CABG). Patients/Methods Twenty-four patients undergoing coronary artery bypass grafting (CABG) were included in a prospective parallel-group randomized study. All patients but one were treated with acetylsalicylic acid (ASA). In the treatment group (n = 12), mean arterial blood pressure (MAP) was maintained at pre-induction levels by NA infusion. In the control group (n = 12), NA was administered only if MAP decreased below 60 mmHg. Platelet aggregation (impedance aggregometry with ADP, arachidonic acid [AA] and thrombin-receptor activating peptide [TRAP] as initiators) and clot formation (clotting time, clot formation time and maximum clot firmness by EXTEM, INTEM and FIBTEM tests with thromboelastometry) were assessed before and 50 min after anesthesia induction (before cardiopulmonary bypass was initiated). Results All patients in the treatment group received NA (median dose after 50 min 0.09 (range 0-0.26) mu g kg(-1) min(-1)). Four patients in the control group also received NA (0.03-0.12 mu g kg(-1) min(-1)). There were differences between the treatment group and the control group in ADP- and AA-induced aggregation changes (ADP, +16 [25th-75th percentiles, 5-26] vs. -7 [-19 to -1] U; AA, +12 [-4 to 16] vs. -9 [-13 to 1] U). INTEM maximum clot firmness increased in the treatment group but not in the control group. Conclusion Infusion of clinically relevant doses of NA enhanced platelet aggregation and clot firmness in ASA-treated CABG patients. NA infusion is hence a potential new method to acutely improve platelet reactivity in patients on antiplatelet therapy undergoing surgery.
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