scholarly journals Evaluation of thromboelastometry, thrombin generation and plasma clot lysis time in patients with bleeding of unknown cause: A prospective cohort study

Haemophilia ◽  
2020 ◽  
Vol 26 (3) ◽  
Author(s):  
Caroline S. B. Veen ◽  
Elise J. Huisman ◽  
Marjon H. Cnossen ◽  
Regina Kom‐Gortat ◽  
Dingeman C. Rijken ◽  
...  
PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e51447 ◽  
Author(s):  
Ludwig Traby ◽  
Marietta Kollars ◽  
Lisbeth Eischer ◽  
Sabine Eichinger ◽  
Paul A. Kyrle

2018 ◽  
Vol 170 ◽  
pp. 69-74 ◽  
Author(s):  
Amihai Rottenstreich ◽  
Gabriel Levin ◽  
Uriel Elchalal ◽  
Geffen Kleinstern ◽  
Galia Spectre ◽  
...  

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2336-2336
Author(s):  
Brett L. Houston ◽  
Dhruva J. Dwivedi ◽  
Peter Grin ◽  
Michelle Kwong ◽  
Enrico Rullo ◽  
...  

Abstract BACKGROUND: Sepsis is a leading cause of mortality among critically ill patients and is associated with both systemic inflammation and up-regulation of coagulation. In the translational sub-study of the HALO (Heparin AnticoaguLation to improve Outcomes in septic shock) pilot trial, we evaluated the mechanisms by which unfractionated heparin (UFH) may reduce inflammation and coagulation in patients with septic shock. METHODS: In this multicenter pilot randomized trial of 69 patients diagnosed with septic shock, we evaluated the feasibility of administering therapeutic dose intravenous UFH (18 IU/kg/hr) compared to thromboprophylactic subcutaneous dalteparin (5000 IU daily). Blood samples were collected on days 1 (baseline prior to study infusion), 2, 3, 5, and 7. We evaluated coagulation using assays for protein C, activated protein C, thrombin-antithrombin (TAT), thrombin generation, clot lysis, plasminogen activator inhibitor-1 (PAI-1) and cell-free DNA (cf-DNA). Systematic inflammation was evaluated by measuring inflammatory cytokines (interleukin (IL)-6, IL-8, IL-10, and IL-17). RESULTS: The mean age of the study population was 61 years, of whom 43% were male. Thirty two patients (46%) were randomized to receive unfractionated heparin while 37 (54%) received dalteparin. The baseline mean aggregate Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 25 ± 7.8, and Multiple Organ Dysfunction Score (MODS) 5.6 ± 2.38. Baseline laboratory testing (coagulation assays and inflammatory cytokines) was not statistically different between UFH vs. LMWH treated patients. On day 2, the median clot lysis time in UFH-treated patients compared to those receiving dalteparin was significantly decreased [6630 (IQR 0 - 14156) seconds vs. 9615 (IQR 8209 - 11018) seconds; p = 0.008] (Figure 1). UFH administration was associated with increased protein C levels [66.4% of normal (IQR 9.9 - 122.9) vs. 41.1% of normal (IQR 4.8 - 77.4); p = 0.02], and reduced thrombin generation of 0 (IQR 0 - 1725) units/min vs. 3393 (IQR 0 - 8519) units/min; p<0.001]. On day 2, we observed no differences between thrombin-antithrombin complex (TAT), activated protein C, plasminogen activator inhibitor-1 (PAI-1) or cell-free DNA (cf-DNA). Similarly, there were no differences between treatment groups in inflammatory markers, including IL-6, IL-8, IL-10 or IL-17. Analysis thus far is limited to samples collected on days 1 and 2; day 3-7 analyses are ongoing. CONCLUSION: In patients diagnosed with septic shock, IV UFH reduces thrombin generation, shortens clot lysis time and improves endogenous protein C levels compared to dalteparin administered for thromboprophylaxis. Analyses for samples obtained on days 3, 5 and 7 are ongoing. These preliminary data provide a biologic rational for the use of heparin in sepsis. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Disclosures No relevant conflicts of interest to declare.


2017 ◽  
Vol 117 (02) ◽  
pp. 295-302 ◽  
Author(s):  
Katie A. Greenhalgh ◽  
Mark W. Strachan ◽  
Saad Alzahrani ◽  
Paul D. Baxter ◽  
Kristina F. Standeven ◽  
...  

SummaryBoth type 2 diabetes (T2DM) and Bß448Lys variant of fibrinogen are associated with dense fibrin clots, impaired fibrinolysis and increased cardiovascular risk. It was our objective to investigate whether BßArg448Lys adds to vascular risk by modulating fibrin network structure and/or fibrinolysis in diabetes. The primary aim was to study effects of BßArg448Lys on fibrin network characteristics in T2DM. Secondary aims investigated interactions between gender and BßArg448Lys substitution in relation to fibrin clot properties and vascular disease. Genotyping for BßArg448Lys and dynamic clot studies were carried out on 822 T2DM patients enrolled in the Edinburgh Type 2 Diabetes Study. Turbidimetric assays of individual plasma samples analysed fibrin clot characteristics with additional experiments conducted on clots made from purified fibrinogen, further examined by confocal and electron microscopy. Plasma clot lysis time in Bß448Lys was longer than Bß448Arg variant (mean ± SD; 763 ± 322 and 719 ± 351 seconds [s], respectively; p<0.05). Clots made from plasma-purified fibrinogen of individuals with Arg/Arg, Arg/Lys and Lys/Lys genotypes showed differences in fibre thickness (46.75 ± 8.07, 38.40 ± 6.04 and 25 ± 4.99 nm, respectively; p<0.001) and clot lysis time (419 ± 64, 442 ± 87 and 517 ± 65 s, respectively; p=0.02), directly implicating the polymorphism in the observed changes. Women with Bß448Lys genotype had increased risk of cerebrovascular events and were younger compared with Bß448Arg variant (67.2 ± 4.0 and 68.2 ± 4.4 years, respectively; p=0.035). In conclusion, fibrinogen Bβ448Lys variant is associated with thrombotic fibrin clots in diabetes independently of traditional risk factors. Prospective studies are warranted to fully understand the role of BβArg448Lys in predisposition to vascular ischaemia in T2DM with the potential to develop individualised antithrombotic management strategies.


2019 ◽  
Vol 8 (11) ◽  
pp. 1447-1454 ◽  
Author(s):  
Marc Blondon ◽  
Emmanuel Biver ◽  
Olivia Braillard ◽  
Marc Righini ◽  
Pierre Fontana ◽  
...  

Objective Vitamin D deficiency is associated with increased risks of arterial and venous cardiovascular events. Hypothetically, supplementation with vitamin D may lead to a less prothrombotic phenotype, as measured by global coagulation assays and fibrin clot structure. Methods In this prospective cohort study, we enrolled adult outpatients attending the Primary Care Division of the Geneva University Hospitals with a severe vitamin D deficiency (25-hydroxyvitamin-D3 (25-OHD) <25 nmol/L), excluding obese patients or with a recent acute medical event. We evaluated changes in coagulation times, thrombin generation assay, clot formation and clot lysis time, 25-OHD and parathormone before and 1–3 months after cholecalciferol oral supplementation with one-time 300,000 IU then 800 IU daily. Paired t-tests with a two-sided alpha of 0.05 compared absolute mean differences. Results The 48 participants had a mean age of 43.8 ± 13.8 years. After supplementation, 25-OHD levels increased from 17.9 ± 4.6 nmol/L to 62.5 ± 20.7 nmol/L 6.4 ± 3.0 weeks after inclusion. Endogenous thrombin potential and thrombin generation peak values both decreased significantly (−95.4 nM × min (95%CI −127.9 to −62.8), P < 0.001; −15.1 nM (−23.3 to −6.8), P < 0.001). The maximum absorbance by turbidimetry decreased significantly (P = 0.001) after supplementation. There was no change in clot lysis time, coagulation times or plasminogen activator inhibitor-1 and homocysteine levels. Conclusions In severe vitamin D deficiency, a high-dose cholecalciferol supplementation was associated with a reduction in thrombin generation and an average decreased number of fibrin protofibrils per fibers and fibrin fiber size measured by turbidimetry. This suggests that severe vitamin D deficiency may be associated with a potentially reversible prothrombotic profile.


PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e48881 ◽  
Author(s):  
Zelda de Lange ◽  
Marlien Pieters ◽  
Johann C. Jerling ◽  
Annamarie Kruger ◽  
Dingeman C. Rijken

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e83151 ◽  
Author(s):  
Zelda de Lange ◽  
Dingeman C. Rijken ◽  
Tiny Hoekstra ◽  
Karin R. Conradie ◽  
Johann C. Jerling ◽  
...  

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