| 1. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
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Effects of fibrinogen and platelet transfusion on coagulation and platelet function in bleeding cardiac surgery patients.
- 2019
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 63:4, s. 475-482
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Tidskriftsartikel (refereegranskat)abstract
- Excessive bleeding is a significant problem in cardiac surgery. Fibrinogen and platelet concentrate transfusion are used clinically to improve haemostasis and reduce bleeding but little is known about their functional effects on coagulation and platelet function in patients with ongoing bleeding.Forty-two patients with ongoing bleeding after cardiac surgery were included in an observational study. Patients received either fibrinogen concentrate (n=16), platelet concentrate (n=12), or both fibrinogen and platelets (n=14), median doses 2g fibrinogen and 2 units platelets given at one occasion. Blood samples were collected before and after transfusion. Coagulation (clotting time and clot stability) was analysed with rotational thromboelastometry, and platelet function with impedance aggregometry. In addition, platelet count and fibrinogen concentration was measured. Chest drain output was measured before and after the transfusion.Fibrinogen infusion resulted in an increase in fibrinogen concentration and clot stability (P=0.001), but had no effect on platelet aggregation. Platelet transfusion did not significantly affect coagulation, but improved arachidonic acid- and TRAP-induced platelet aggregation (P=0.017 and 0.034 respectively) and increased platelet count. Combined fibrinogen and platelet transfusion shortened clotting time (P=0.005) and increased clot stability (P=0.001), and improved arachidonic acid- and TRAP-induced platelet aggregation (P=0.004 and 0.016 respectively), and increased fibrinogen concentration and platelet count. The median bleeding volume was 150 (25th-75th percentile 70-240)mL/h before, and 60 (40-110)mL/h after transfusion of fibrinogen and/or platelet concentrate (P<0.001).The results demonstrate improved coagulation and platelet function following fibrinogen and platelet transfusion in patients bleeding after cardiac surgery.
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| 2. |
- Singh, Sukhi, 1990, et al.
(författare)
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Adrenaline enhances in vitro platelet activation and aggregation in blood samples from ticagrelor-treated patients
- 2018
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Ingår i: Research and Practice in Thrombosis and Haemostasis. - : John Wiley & Sons. - 2475-0379. ; 2:4, s. 718-725
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Tidskriftsartikel (refereegranskat)abstract
- Background: Temporarily improved platelet reactivity may reduce the bleeding in patients on antiplatelet therapy who have ongoing bleeding or who are in need of acute surgery. Adrenaline can bind to adrenergic alpha(2A)-receptors on platelets and potentially enhance platelet reactivity.Objective: To assess if adrenaline can improve adenosine diphosphate (ADP)-induced platelet aggregation and activation in blood samples from patients on dual antiplatelet therapy with acetylsalicylic acid (ASA) and the ADP-receptor antagonist ticagrelor.Methods: Blood samples were collected from a total of forty acute coronary syndrome patients on dual antiplatelet therapy with ASA and ticagrelor. ADP-induced platelet aggregation (by impedance aggregometry) and activation (by flow cytometry) were assessed before and after supplementation with adrenaline and/or platelet concentrate.Results: Adrenaline supplementation (770 nmol L-1) increased median ADP-induced aggregation from 15 (25-75th percentiles: 10-20) to 26 (18-38) aggregation units. The effect was independent of concomitant platelet supplementation. Adrenaline also increased ADP-induced platelet activation: from 40% (36-54%) to 83% (74-88%) platelets with active fibrinogen receptor (binding PAC-1) and from 13% (7-21%) to 35% (18-50%) P-selectin-expressing platelets.Conclusions: Adrenaline potentiated ADP-induced platelet aggregation and activation in blood samples from ticagrelor-treated patients. Adrenaline infusion may be a new method to enhance platelet function in ticagrelor-treated patients who are in need of acute surgery or have ongoing bleeding. In vivo studies are needed to confirm the present results.
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| 3. |
- Singh, Sukhi, 1990, et al.
(författare)
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Adrenaline Improves Platelet Reactivity in Ticagrelor-Treated Healthy Volunteers
- 2019
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Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 119:5, s. 735-743
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Administration of agents that enhance platelet reactivity may reduce the perioperative bleeding risk in patients treated with the adenosine diphosphate (ADP)-receptor antagonist ticagrelor. Adrenaline potentiates ADP-induced aggregation and activation in blood samples from ticagrelor-treated patients, but it has not previously been evaluated in vivo.METHODS: Ten healthy male subjects were included in an interventional study. A loading dose of ticagrelor (180 mg) was administered, followed 2 hours later by a gradually increased intravenous adrenaline infusion (0.01, 0.05, 0.10 and 0.15 µg/kg/min; 15 minutes at each step). Blood pressure, heart rate, platelet aggregation (impedance aggregometry), platelet activation (flow cytometry), clot formation (rotational thromboelastometry) and adrenaline plasma concentration were determined before and after ticagrelor administration and at the end of each adrenaline step.RESULTS: = 0.007).CONCLUSION: Infusion of adrenaline at clinically relevant doses improves in vivo platelet reactivity and clot formation in ticagrelor-treated subjects. Adrenaline could thus potentially be used to prevent perioperative bleeding complications in ticagrelor-treated patients. Studies in patients are necessary to determine the clinical importance of our observations.TRIAL REGISTRY NUMBER: ClinicalTrials.gov NCT03441412.
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| 4. |
- 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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| 5. |
- Singh, Sukhi, 1990
(författare)
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Platelet activation and aggregation: Clinical and experimental studies
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Dual antiplatelet therapy with acetylsalicylic acid (ASA) and the adenosine diphosphate (ADP)-receptor antagonist ticagrelor increases the risk of bleeding complications during cardiac surgery. The overall aim of this thesis was to identify and evaluate current and potential methods to reduce and prevent bleeding complications in patients with ongoing antiplatelet therapy. Methods: In Study I, three types of platelet concentrates were sampled on day 1, 4 and 7 after donation. In Study II, adrenaline and platelet concentrate were added to blood samples from acute coronary syndrome patients on ASA and ticagrelor. In Study III, blood samples from healthy volunteers were collected after ticagrelor, adrenaline and metoprolol administration. In Study IV, blood samples were collected before and after anesthesia induction from cardiac surgery patients randomized to standard treatment or maintenance of preoperative mean arterial pressure using noradrenaline. Platelet aggregation was assessed with impedance aggregometry (Studies I‒IV) while platelet activation was assessed with flow cytometry (Studies I‒III). Clot formation was assessed with thromboelastometry (Studies III and IV). Results: Platelets in interim platelet unit (IPU) concentrates maintained a lower activation state and better aggregation response to the end of storage compared to buffy-coat concentrates (I). More platelets in IPU concentrates were activated and had a lower aggregation response throughout storage compared to apheresis concentrates (I). Adrenaline, but not platelet concentrate, improved ADP-induced platelet aggregation and activation in the presence of ticagrelor in vitro (II). Adrenaline infusion improved ADP-induced platelet aggregation, activation and clot formation in healthy volunteers treated with ticagrelor (III). Intraoperative noradrenaline infusion improved ADP-induced platelet aggregation and clot formation in cardiac surgery patients (IV). Conclusions: The quality of IPU concentrates is at least comparable to buffy-coat concentrates. Adrenergic agents improve platelet reactivity and may thus potentially be used to prevent excessive bleeding during surgery in patients with ongoing antiplatelet therapy.
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| 6. |
- Singh, Sukhi, 1990, et al.
(författare)
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Platelet storage lesion in interim platelet unit concentrates: A comparison with buffy-coat and apheresis concentrates.
- 2017
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Ingår i: Transfusion and Apheresis Science. - : Elsevier BV. - 1473-0502. ; 56:6, s. 870-874
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Tidskriftsartikel (refereegranskat)abstract
- Platelet storage lesion is characterized by morphological changes and impaired platelet function. The collection method and storage medium may influence the magnitude of the storage lesion. The aim of this study was to compare the newly introduced interim platelet unit (IPU) platelet concentrates (PCs) (additive solution SSP+, 40% residual plasma content) with the more established buffy-coat PCs (SSP, 20% residual plasma content) and apheresis PCs (autologous plasma) in terms of platelet storage lesions. Thirty PCs (n=10 for each type) were assessed by measuring metabolic parameters (lactate, glucose, and pH), platelet activation markers, and in vitro platelet aggregability on days 1, 4, and 7 after donation. The expression of platelet activation markers CD62p (P-selectin), CD63 (LAMP-3), and phosphatidylserine was measured using flow cytometry and in vitro aggregability was measured with multiple electrode aggregometry. Higher platelet activation and lower in vitro aggregability was observed in IPU than in buffy-coat PCs on day 1 after donation. In contrast, metabolic parameters, expression of platelet activation markers, and in vitro aggregability were better maintained in IPU than in buffy-coat PCs at the end of the storage period. Compared to apheresis PCs, IPU PCs had higher expression of activation markers and lower in vitro aggregability throughout storage. In conclusion, the results indicate that there are significant differences in platelet storage lesions between IPU, buffy-coat, and apheresis PCs. The quality of IPU PCs appears to be at least comparable to buffy-coat preparations. Further studies are required to distinguish the effect of the preparation methods from storage conditions.
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| 7. |
- Stolt, Henrik, et al.
(författare)
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A comparison of the in vitro effects of three fibrinogen concentrates on clot strength in blood samples from cardiac surgery patients
- 2021
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 65:10, s. 1439-1446
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Tidskriftsartikel (refereegranskat)abstract
- Background Fibrinogen concentrate is used clinically to improve hemostasis in bleeding patients. We investigated and compared the efficacy of three commercially available fibrinogen concentrates to improve clot strength in blood samples from cardiac surgery patients. Objectives Postoperative blood samples were collected from 23 cardiac surgery patients. Samples were each divided into four vials, each supplemented with 1.125 mg of fibrinogen of one of three fibrinogen concentrates (RiaSTAP(R), Fibryga(R), FibCLOT(R)), or placebo. The fibrinogen dose corresponded to 2.5 g per 70 kg of body weight. Clot strength after supplementation was assessed in duplicate with rotational thromboelastometry (ROTEM(R)) using FIBTEM maximum clot firmness, EXTEM clot formation time, and maximum clot firmness assays. Results In vitro fibrinogen concentrate supplementation of the samples resulted in higher plasma fibrinogen concentrations and improved clot strength with all three concentrates. Supplementation with FibCLOT increased FIBTEM maximum clot firmness (+46% [25th-75th percentile 35-55] compared to placebo) significantly more than did supplementation with Fibryga (+26% [21-35]) and RiaSTAP (+29% [22-47], p < .001). FibCLOT supplementation also shortened EXTEM clot formation time and increased EXTEM maximum clot firmness to a greater extent than did the other concentrates (both p < .001). Conclusions At the selected dose, FibCLOT was more effective than Fibryga and RiaSTAP in restoring clot strength in postoperative blood samples from cardiac surgery patients. These results may have implications for the choice of fibrinogen concentrate and dosing.
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