Abstract 568: Biomarkers of Hemostasis and Thrombosis in Hemophilia A and B Patients

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Zhu Chen ◽  
Weizhen Wu ◽  
Lan Ge ◽  
Marina Ichetovkin ◽  
Kunal Desai ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Hemophilia A ◽  
Platelet Reactivity ◽  
Statistical Significance ◽  
Vascular Inflammation ◽  
Bleeding Risk ◽  
Strong Positive Correlation ◽  
Pai 1

The defective hemostatic process in hemophiliacs overlaps with the underlying physiology contributing to bleeding risk in anticoagulated patients. Hemophiliacs may also develop compensatory changes in fibrinolysis, platelet reactivity, vascular inflammation, and remodeling secondarily. We therefore explored markers for these processes in hemophilia A and B as part of our larger effort to develop translational biomarkers to guide antithrombotic therapy and minimize bleeding risk. Plasmas from hemophilia A patients (11 severe; 1 moderate) and hemophilia B patients (3 severe; 3 mild or moderate), sampled after a treatment washout period, and 7 normal subjects were procured. Markers/assays pursued include: coagulation (F1+2, FPA, TAT, D-dimer), fibrinolysis (PAP, PAI-1, tPA), platelet activation (soluble P-selectin (sP-sel)), vascular inflammation (MCP-1), angiogenesis (VEGF), PT, aPTT, and thrombin generation assay (TGA). Consistent with aPTT prolongation and changes in TGA, both hemophilia groups displayed numerically lower than normal levels of all 4 coagulation markers, with hemophilia A reaching statistical significance for F1+2 and TAT. Hemophilia A also exhibited a significant decrease in PAP and a numerical increase in PAI-1 compared to normal. VEGF and MCP-1 exhibited no appreciable difference. In the combined analysis for hemophilia A and B (“A+B”), PAP displayed a strong positive correlation with F1+2 and a strong negative correlation with PAI-1; A+B exhibited a statistically significant reduction in F1+2, FPA, and TAT, and a non-significant increase in sP-sel and non-significant decrease in PAP, compared to normal. In conclusion, hemophilia A and B plasma samples had significantly reduced markers of in vivo thrombin generation, thrombin activity, and coagulation, and trends evidencing increased platelet activation and decreased fibrinolysis, possibly as compensation. Lack of signal in vascular inflammation or angiogenesis could be due to the (near optimal) hemostatic therapies. Our results illustrate the potential value of biomarkers of in vivo coagulation, fibrinolysis, and platelet activation in translational research on antithrombotic therapies for both their efficacy and bleeding risk.

Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin

1987 ◽  
Vol 57 (01) ◽  
pp. 062-066 ◽  
Author(s):  
P A Kyrle ◽  
J Westwick ◽  
M F Scully ◽  
V V Kakkar ◽  
G P Lewis
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Low Dose ◽  
Bleeding Time ◽  
Blood Platelets ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Plug Formation ◽  
Granule Release

SummaryIn 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.

tPA Point Mutation at Autolysis Loop Enhances Resistance to PAI-1 Inhibition and Catalytic Activity

2018 ◽  
Vol 119 (01) ◽  
pp. 077-086 ◽  
Author(s):  
Shuangzhou Peng ◽  
Guangpu Xue ◽  
Shanli Chen ◽  
Zhuo Chen ◽  
Cai Yuan ◽  
...  
Keyword(s):  
Thrombolytic Therapy ◽  
Catalytic Efficiency ◽  
Bleeding Risk ◽  
Tissue Type ◽  
Clot Lysis ◽  
High Dose ◽  
Thrombolytic Activity ◽  
Serine Protease Domain ◽  
Pai 1

AbstractRecombinant tissue-type plasminogen activator (r-tPA) was approved by U.S. Food and Drug Administration as a thrombolytic drug. However, a high dose of r-tPA (up to 100 mg/person) is typically used in clinical applications. Such high dosage leads to severe side effects including haemorrhage and neurotoxicity, which can be fatal. To improve the proteolytic properties of tPA to enhance thrombolytic therapy, we designed a series of mutants in tPA serine protease domain (tPA-SPD) based on the crystal structure of tPA-SPD:plasminogen activators inhibitor-1 (PAI-1) complex that we determined recently. We found that the A146Y substitution in tPA-SPD(A146Y) enhanced resistance to PAI-1 inactivation by 30-fold compared with original tPA-SPD. Interestingly, the tPA-SPD(A146Y) variant showed fivefold higher activation for plasminogen compared with tPA-SPD. The variant also demonstrated thrombolytic activity stronger than tPA-SPD in a clot lysis assay. In vivo, we showed tPA-SPD(A146Y) possessed higher thrombolytic efficacy in a pulmonary embolism model compared with original tPA-SPD. Furthermore, a mouse tail bleeding assay showed that tPA-SPD(A146Y) did not increase bleeding risk compared with clinical drug r-tPA. Together, our findings reveal novel functions of A146Y variant, which not only increases the catalytic efficiency of the enzyme, but also enhances resistance to PAI-1 inhibition, and demonstrating that tPA-SPD (A146Y) variant is a much improved agent for thrombolytic therapy.

Multi-Cellular Activation In Vivo by Endotoxin in Humans – Limited Protection by Adenosine Infusion

2000 ◽  
Vol 84 (09) ◽  
pp. 381-387 ◽  
Author(s):  
Nailin Li ◽  
Anne Soop ◽  
Alf Sollevi ◽  
Paul Hjemdahl
Keyword(s):  
Von Willebrand Factor ◽  
Thrombin Generation ◽  
Platelet Reactivity ◽  
Adenosine Infusion ◽  
Cellular Activation ◽  
Soluble P ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Secretion

SummaryThe influence of adenosine infusion (40 µg/kg/min for 4 h) on inflammatory and hemostatic parameters was investigated in healthy males without (n = 10) or with (n = 11) intravenous endotoxin injection (4 ng/kg). Without endotoxin, adenosine elevated circulating leukocytes and circulating platelet-leukocyte aggregates. Endotoxin activated platelets and leukocytes in vivo. Platelet activation was seen as slightly increased platelet P-selectin expression, decreased platelet counts, and elevated plasma soluble P-selectin (from 39.6 ± 3.4 to 68.9 ± 6.6 ng/ml; P <0.01). Leukocyte activation was evidenced by increased CD11b expression (from MFI of 0.54 ± 0.02 to 2.21 ± 0.17; P <0.01) and plasma elastase levels (from 25.3 ± 2.5 to 169.3 ± 22.5 ng/ml; P <0.01). Endotoxin also enhanced platelet and leukocyte responsiveness to in vitro stimulation. Endotoxin induced von Willebrand factor secretion (from 92 ± 8 units to 265 ± 19 units at 4 h; P <0.001) and enhanced thrombin generation in vivo. Endotoxin induced leukocytosis and thus increased circulating platelet-leukocyte, mainly platelet-neutrophil, aggregates. Adenosine caused slight attenuation of platelet reactivity to agonist stimulation, enhanced the endotoxin-induced leukocytosis, and detained more platelet-leukocyte aggregates in circulation, but did not attenuate endotoxin-induced neutrophil elastase secretion, von Willebrand factor secretion, or thrombin generation. Thus, endotoxemia induces multi-cellular activation in vivo. Adenosine inhibits leukocyte adhesion and extravasation, and mildly attenuates platelet responsiveness and soluble P-selectin release. Adenosine has the potential of becoming a therapeutic antiinflammatory drug, but an optimal treatment strategy needs to be developed.

Injection of recombinant activated factor VII can induce transient increase in circulating procoagulant microparticles

2004 ◽  
Vol 91 (05) ◽  
pp. 873-878 ◽  
Author(s):  
Bénédicte Hugel ◽  
Benoit Guillet ◽  
Catherine Trichet ◽  
Anne Rafowicz ◽  
Thierry Lambert ◽  
...  
Keyword(s):  
Short Duration ◽  
Platelet Activation ◽  
Thrombin Generation ◽  
Transient Increase ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Activated Factor Vii ◽  
Therapeutic Doses

SummaryRecombinant activated factor VII (rFVIIa) is an effective haemostatic treatment in haemophiliacs with inhibitors. In vitro, FVIIa concentrations corresponding to those obtained with therapeutic doses of rFVIIa have been shown to induce normal thrombin generation and platelet activation in the absence of factors VIII or IX. To further study the in vivo haemostatic changes induced by rFVIIa, circulating procoagulant microparticles (MP) were measured in patients treated with discontinuous injections of Novoseven®. In 6 out of 15 patients, a transient peak of procoagulant MP was observed after injection, occurring 15 min to 2 h after infusion. It was composed primarily of platelet-derived MP and was of very short duration. This peak was not observed in haemophiliacs without inhibitor, who were treated with conventional replacement therapies. Our results provide further in vivo evidence that rFVIIa specifically activates platelets, either directly or as a consequence of a burst of thrombin generation that could account for its haemostatic efficacy.

scholarly journals RGS10 and RGS18 differentially limit platelet activation, promote platelet production, and prolong platelet survival

Blood ◽  
2020 ◽  
Vol 136 (15) ◽  
pp. 1773-1782 ◽  
Author(s):  
Daniel DeHelian ◽  
Shuchi Gupta ◽  
Jie Wu ◽  
Chelsea Thorsheim ◽  
Brian Estevez ◽  
...  
Keyword(s):  
Platelet Count ◽  
G Protein ◽  
Platelet Activation ◽  
Platelet Reactivity ◽  
Rgs Proteins ◽  
Platelet Recovery ◽  
Platelet Production ◽  
Platelet Survival

Abstract G protein–coupled receptors are critical mediators of platelet activation whose signaling can be modulated by members of the regulator of G protein signaling (RGS) family. The 2 most abundant RGS proteins in human and mouse platelets are RGS10 and RGS18. While each has been studied individually, critical questions remain about the overall impact of this mode of regulation in platelets. Here, we report that mice missing both proteins show reduced platelet survival and a 40% decrease in platelet count that can be partially reversed with aspirin and a P2Y12 antagonist. Their platelets have increased basal (TREM)-like transcript-1 expression, a leftward shift in the dose/response for a thrombin receptor–activating peptide, an increased maximum response to adenosine 5′-diphosphate and TxA2, and a greatly exaggerated response to penetrating injuries in vivo. Neither of the individual knockouts displays this constellation of findings. RGS10−/− platelets have an enhanced response to agonists in vitro, but platelet count and survival are normal. RGS18−/− mice have a 15% reduction in platelet count that is not affected by antiplatelet agents, nearly normal responses to platelet agonists, and normal platelet survival. Megakaryocyte number and ploidy are normal in all 3 mouse lines, but platelet recovery from severe acute thrombocytopenia is slower in RGS18−/− and RGS10−/−18−/− mice. Collectively, these results show that RGS10 and RGS18 have complementary roles in platelets. Removing both at the same time discloses the extent to which this regulatory mechanism normally controls platelet reactivity in vivo, modulates the hemostatic response to injury, promotes platelet production, and prolongs platelet survival.

TFPI Antagonist Aptamer ARC19499 Is a Procoagulant In Vitro and In Vivo.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1134-1134 ◽  
Author(s):  
Kathleen E. McGinness ◽  
Emily K. Waters ◽  
Ryan M. Genga ◽  
Karen A. Olson ◽  
Jennifer A. Nelson ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Hemophilia A ◽  
Specific Interaction ◽  
Hemophilia B ◽  
Model Systems ◽  
Primary Role ◽  
Procoagulant Effect ◽  
Coagulation Pathway

Abstract Abstract 1134 Hemophilia is a bleeding disorder that results from deficiencies in coagulation factor VIII (FVIII; hemophilia A) or factor IX (FIX; hemophilia B), primarily impacting the intrinsic coagulation pathway. The extrinsic coagulation pathway remains intact in hemophiliacs and is negatively regulated by tissue factor pathway inhibitor (TFPI). The primary role of TFPI is regulation of the FVIIa:tissue factor complex through inhibition of FVIIa and FXa. Inhibition of TFPI may provide an effective treatment for hemophilia by allowing sufficient thrombin generation via the extrinsic coagulation pathway to bypass the defect in clot propagation caused by deficiency of FVIII or FIX. ARC19499 is an aptamer that is a potent, specific inhibitor of TFPI. We have employed a variety of in vitro and in vivo methods to demonstrate that ARC19499 mediates a procoagulant effect in hemophilic plasma and in a model of hemophilia A in non-human primates (NHP). Plasma-based experiments that measure thrombin generation over time demonstrate that ARC19499 mediates a procoagulant response in both hemophilia A and hemophilia B plasma, restoring thrombin generation to near normal levels at 10 – 100 nM aptamer. Experiments in TFPI-depleted plasma and in vitro binding experiments demonstrate that this procoagulant effect is dependent on the specific interaction between ARC19499 and TFPI. ARC19499 restores thrombin generation to a level that is equivalent to or better than 14% FVIII replacement at a concentration of 30 nM in hemophilia A plasma and has an additive effect on thrombin generation when used in combination with FVIII. In a NHP model of hemophilia, cynomolgus monkeys acquire a hemophilia A-like state following administration of an anti-FVIII antibody as measured by ex vivo thromboelastography (TEG). TEG coagulation parameters are corrected following administration of ARC19499. In addition, antibody-mediated FVIII depletion moderately prolongs saphenous-vein bleeding time. ARC19499 corrects bleeding times to normal. These experiments demonstrate that the anti-TFPI aptamer ARC19499 mediates a procoagulant hemostatic effect both in vitro and in vivo in hemophilia model systems that is dependent on specific interaction between the aptamer and TFPI. ARC19499 may provide an effective alternative to replacement factors and bypassing agents for the treatment of hemophilia. Additionally, aptamer therapeutics have the advantage of subcutaneous bioavailability which provides an opportunity for improved treatment regimens in hemophilia. Disclosures: McGinness: Archemix Corporation: Employment. Waters:Archemix Corporation: Employment. Genga:Archemix Corporation: Employment. Olson:Archemix Corporation: Employment. Nelson:Archemix Corporation: Employment. Kurz:Archemix Corporation: Employment. Schaub:Archemix Corporation: Employment.

scholarly journals In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation

Blood ◽  
2012 ◽  
Vol 119 (17) ◽  
pp. 4066-4072 ◽  
Author(s):  
Bethan Psaila ◽  
James B. Bussel ◽  
Matthew D. Linden ◽  
Bracken Babula ◽  
Youfu Li ◽  
...  
Keyword(s):  
Platelet Activation ◽  
Platelet Function ◽  
Whole Blood ◽  
Immune Thrombocytopenia ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
High Dose ◽  
Platelet Surface

Abstract The effects of eltrombopag, a thrombopoietin-receptor agonist, on platelet function in immune thrombocytopenia (ITP) are not fully characterized. This study used whole blood flow cytometry to examine platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28. Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and without low and high adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) concentrations. Before eltrombopag treatment with no ex vivo agonist, platelet activation was higher in ITP patients than controls. Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-selectin was observed. Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during eltrombopag treatment than at baseline. Eltrombopag led to a slight increase in platelet reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; whole blood experiments demonstrated that this increase was probably because of higher platelet counts rather than higher platelet reactivity. In conclusion, although thrombocytopenic ITP patients have higher baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-reactivity, irrespective of whether the platelet count increased.

Mechanisms of platelet activation: Need for new strategies to protect against platelet-mediated atherothrombosis

2009 ◽  
Vol 102 (08) ◽  
pp. 248-257 ◽  
Author(s):  
Lisa Jennings
Keyword(s):  
Antiplatelet Therapy ◽  
Platelet Activation ◽  
Platelet Reactivity ◽  
Thrombus Formation ◽  
Antiplatelet Agents ◽  
Bleeding Risk ◽  
Adenosine Diphosphate ◽  
Adp Receptor ◽  
Activation Pathways ◽  
New Strategies

SummaryPlatelets are central mediators of haemostasis at sites of vascular injury, but they also mediate pathologic thrombosis. Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease. They also interact with endothelial cells and leukocytes to promote inflammation, which contributes to atherosclerosis. Multiple pathways contribute to platelet activation, and current oral antiplatelet therapy with aspirin and a P2Y12 adenosine diphosphate (ADP) receptor antagonist target the thromboxane A2 and ADP pathways, respectively. Both can diminish activation by other factors, but the extent of their effects depends upon the agonist, agonist strength, and platelet reactivity status. Although these agents have demonstrated significant clinical benefit, residual morbidity and mortality remain high. Neither agent is effective in inhibiting thrombin, the most potent platelet activator. This lack of comprehensive inhibition of platelet function allows continued thrombus formation and exposes patients to risk for recurrent thrombotic events. Moreover, bleeding risk is a substantial limitation of antiplatelet therapy, because these agents target platelet activation pathways critical for both protective haemostasis and pathologic thrombosis. Novel antiplatelet therapies that provide more complete inhibition of platelet activation without increasing bleeding risk could considerably decrease residual risk for ischemic events. Inhibition of the protease-activated receptor (PAR)-1 platelet activation pathway stimulated by thrombin is a novel, emerging approach to achieve more comprehensive inhibition of platelet activation when used in combination with current oral antiplatelet agents. PAR-1 inhibition is not expected to increase bleeding risk, as this pathway does not interfere with haemostasis.

scholarly journals Thrombomodulin-modified thrombin generation after in vivo recombinant factor VIII treatment in severe hemophilia A

Haematologica ◽  
2008 ◽  
Vol 93 (9) ◽  
pp. 1351-1357 ◽  
Author(s):  
A. W.J.H. Dielis ◽  
W. M.R. Balliel ◽  
R. van Oerle ◽  
W. T. Hermens ◽  
H. M.H. Spronk ◽  
...  
Keyword(s):  
Factor Viii ◽  
Thrombin Generation ◽  
Hemophilia A ◽  
Recombinant Factor Viii ◽  
Severe Hemophilia

scholarly journals Procoagulant Profile in Patients with Immune Thrombocytopaenia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1062-1062
Author(s):  
Nora Butta ◽  
Ihosvany Fernandez Bello ◽  
María Teresa Álvarez Román ◽  
María Isabel Rivas Pollmar ◽  
Miguel Canales ◽  
...  
Keyword(s):  
Platelet Count ◽  
Plasma Concentration ◽  
Thrombin Generation ◽  
Alpha Angle ◽  
Bleeding Risk ◽  
Endothelial Damage ◽  
Healthy Controls ◽  
Platelet Counts ◽  
Spearman Test ◽  
Pai 1

Abstract Background: Patients with platelet counts less than 20 or 30 x 109/L have an increased risk of bleeding. Nevertheless, some patients with immune thrombocytopenia (ITP) have fewer bleeding symptoms than expected. In a previous communication (ASH 2014) we reported that these patients presented high microparticles (MP)-associated procoagulant activity to compensate bleeding risk and that cellular origin of these MPs were platelets and red cells. However, other mechanisms might be involved. Objective: The aim of this work was to analyse the involvement of other factors to compensate bleeding risk in thrombocytopenic ITP patients. Moreover, the feasibility of using the coagulation global assays thromboelastrometry (ROTEM) and Calibrated Automated Thrombogram (CAT) to test haemostasis in these patients was evaluated. Methods: Fifty patients with chronic ITP with platelet count less than 50 x 109/L and twenty-five healthy controls were included. Platelet counts were determined with a Coulter Ac. T Diff cell counter (Beckman Coulter, Madrid, Spain). Citrated blood was centrifuged at 152 g 10 min at 23°C for obtaining platelet rich plasma (PRP) and at 1,500 g for 15 min at 23°C for platelet-poor plasma (PPP) and aliquots were stored at -70ºC until analysis. To assess the kinetics of clot formation, non-activated ROTEM was performed on PRP adjusted to a platelet count of 25 x 109/L. Clotting time (CT, time from start of measurement until initiation of clotting [in seconds], alpha angle, which reflects the rate of fibrin polymerisation (tangent to the curve at 2-mm amplitude [in degrees]), maximum clot firmness,which reflects the maximum tensile strength of the thrombus (MCF, [in mm]) and LI60, which describes the percentage of maximum clot strength present at 60 min (in %), were recorded. Plasma thrombin generation was measured in PPP using the Calibrated Automated Thrombogram (CAT) test at a final concentration of 1 pM tissue factor and 4 mM phospholipids (PPP-Reagent LOW, Thrombinoscope BV, Maastricht, The Netherlands). We evaluated the endogenous thrombin potential (ETP, the total amount of thrombin generated over time); the lag time (the time to the beginning of the explosive burst of thrombin generation); the peak height of the curve (the maximum thrombin concentration produced); and the time to the peak. Fibrinolytic proteins and E-selectin was tested in PPP using commercialized kits. Results were expressed as mean±SD. Comparisons of quantitative variables were made with Mann-Whitney test and correlations with Spearman test. Values of p≤0.05 were considered statistically significant. Results: PRP from ITP patients showed a prolonged CT (control: 550+ 95 sec, ITP: 890+165 sec, p<0.01), diminished alpha angle (control: 62.8+4.3, ITP: 53.5+7.5, p<0.05), and increased MCF (control: 46.7+3.1mm, ITP: 52.4+6.1 mm, p<0.05) and LI60 (control: 90.6+3.0% , ITP: 95.5+3.4, p<0.05) when compared with controls. In order to evaluate whether increased LI60 values were due to an imbalance in fibrinolysis related proteins, tPA, uPA, TAFI and PAI-1 plasma levels were measured. No differences were observed between patients and healthy controls except for PAI-1 which level was increased in ITP patients (control: 14.7 ng/ml+11.7 ng/ml, ITP: 30.4+17.5, p<0.05). Since plasma PAI-1 might be increased as consequence of endothelial damage, plasma concentration of E-selectin, marker of endothelial injury, was determined. E-selectin was increased in samples from ITP patients (control: 10.5 ng/ml+3.9 ng/ml, ITP: 31.6+14.0, p<0.05). Moreover, MCF and LI60 ROTEM parameters correlated to E-selectin plasma concentration (Spearman r values 0.6643, p<0.001 for MCF; 0.6053, p<0.001 for LI60). Thrombin generation in PPP was also measured and a shorter time to peak (control: 9.3+1.2 sec, ITP: 8.3+1.7 sec,p<0.05) and increased ETP (control: 1223.8+257.7 nMxmin, ITP: 1696.4+524 nMxmin,p<0.05) and peak (control: 225.7+82.8.1 nM, ITP: 330.4+106.1 nM,p<0.05) were observed in ITP patients. Conclusions: We demonstrated that ITP patients presented a hypercoagulable profile that might be related, at least in part, to a reduced fibrinolysis mainly caused by an increase in PAI-1 level that seemed to be related to endothelial damage. Moreover ROTEM and CAT appeared to be useful tools for evaluating coagulant profile in ITP patients. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document