scholarly journals Thrombin generation reveals high procoagulant potential in the plasma of sickle cell disease children

2011 ◽  
Vol 87 (2) ◽  
pp. 145-149 ◽  
Author(s):  
Denis F. Noubouossie ◽  
Phu Quoc Lê ◽  
Francis Corazza ◽  
France Debaugnies ◽  
Laurence Rozen ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Thrombin Generation ◽  
Cell Disease

Fetal hemoglobin in sickle cell disease: relationship to erythrocyte phosphatidylserine exposure and coagulation activation

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1119-1124 ◽  
Author(s):  
B. N. Yamaja Setty ◽  
Surekha Kulkarni ◽  
A. Koneti Rao ◽  
Marie J. Stuart
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Thrombin Generation ◽  
Fetal Hemoglobin ◽  
Strong Relationship ◽  
Cell Disease ◽  
Red Cell Membrane ◽  
Prothrombin Fragment ◽  
F Cells

In sickle cell disease (SCD), loss of erythrocyte membrane phospholipid asymmetry occurs with the exposure of phosphatidylserine (PS), which provides a docking site for coagulation proteins. In vivo sickling/desickling, with resulting red cell membrane changes and microvesicle formation, appears to be one of the factors responsible for PS exposure. We evaluated children with SCD homozygous for sickle hemoglobin (SS disease) and controls (n = 65) and demonstrate that high levels of fetal hemoglobin (assessed as F cells) are associated with decreased microvesicle formation, PS exposure, and thrombin generation. F cells correlated inversely with both microvesicles and PS positivity (P < .000001) in SS disease. Multiple regression analyses using various hematologic parameters as independent variables, and either microvesicles or PS positivity as the dependent variable, showed a strong relationship only with F cells. Additionally, plasma prothrombin fragment F1.2 levels (a marker for thrombin generation) correlated with both PS positivity (P < .001) and F cells (P < .01). An F-cell level of approximately 70% was associated with normal levels of prothrombin fragment F1.2 and with microvesicle formation indistinguishable from control values. We suggest that the use of such surrogate biologic markers in conjunction with F-cell numbers may provide valuable insights into the biology and consequences of in vivo sickling.

The acceleration of the propagation phase of thrombin generation in patients with steady-state sickle cell disease is associated with circulating erythrocyte-derived microparticles

2012 ◽  
Vol 107 (06) ◽  
pp. 1044-1052 ◽  
Author(s):  
Grigoris Gerotziafas ◽  
Patrick Van Dreden ◽  
Mourad Chaari ◽  
Vassiliki Galea ◽  
Amir Khaterchi ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Thrombin Generation ◽  
Generation Process ◽  
Cell Disease ◽  
Significant Acceleration ◽  
High Concentrations ◽  
The Impact ◽  
Functional Alteration

SummarySickle cell disease (SCD) is linked to hypercoagulability and is characterised by high concentrations of erythrocyte-derived microparticles (Ed-MPs). However, the impact of procoagulant cell-derived microparticles on the thrombin generation process remains unclear. We analysed the alterations of each phase of thrombin generation (TG) in relation to the concentration of erythrocyte- or platelet-derived microparticles (Ed-MPs and Pd-MPs) in a cohort of patients with steady-state SCD. We studied 92 steady-state SCD patients, 19 of which were under treatment with hydroxyurea, and 30 healthy age- and sex-matched individuals. TG was assessed by calibrated automated thrombogram. Ed-MP and Pd-MP expressing or not phosphatidylserine (PS) were determined by means of flow cytometry. Procoagulant phospholipid-dependent activity in the plasma was evaluated by the Procoag-PPL assay. Levels of thrombomodulin and haemoglobin in the plasma as well as red blood cell and reticulocyte counts were measured. SCD patients, independently of the administration of hydroxyurea, were marked by a significant acceleration in the propagation phase of TG which correlated with the Ed-MP/PS+ concentration. TG was significantly attenuated in hydroxyurea-treated patients. In conclusion, the acceleration of the propagation phase of TG, driven by Ed-MP/PS+, is a major functional alteration in blood coagulation in patients with steady-state SCD. Treatment with hydroxyurea, in addition to the regulation of haemolysis, lowers Ed-MPs and attenuates thrombin generation. The thrombogram could be a useful tool for the diagnosis of hypercoagulability and optimisation of the treatment in patients with SCD.

scholarly journals The contribution of red blood cells to thrombin generation in sickle cell disease: meizothrombin generation on sickled red blood cells

2013 ◽  
Vol 11 (12) ◽  
pp. 2187-2189 ◽  
Author(s):  
M. F. Whelihan ◽  
M. J. Mooberry ◽  
V. Zachary ◽  
R. L. Bradford ◽  
K. I. Ataga ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
Thrombin Generation ◽  
Cell Disease

The utility of thromboelastography and thrombin generation in assessing the prothrombotic state of adults with sickle cell disease

2017 ◽  
Vol 158 ◽  
pp. 113-120 ◽  
Author(s):  
Marije Wijnberge ◽  
Kiran Parmar ◽  
Rachel Kesse-Adu ◽  
Jo Howard ◽  
Alexander T. Cohen ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Thrombin Generation ◽  
Cell Disease ◽  
Prothrombotic State

Thrombin generation and cell-dependent hypercoagulability in sickle cell disease

2016 ◽  
Vol 14 (10) ◽  
pp. 1941-1952 ◽  
Author(s):  
M. F. Whelihan ◽  
M. Y. Lim ◽  
M. J. Mooberry ◽  
M. G. Piegore ◽  
A. Ilich ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Thrombin Generation ◽  
Cell Disease

Abstract 607: Kininogen Regulates Thrombin Generation in a Mouse Model of Sickle Cell Disease

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Erica M Sparkenbaugh ◽  
Kasemsiri Chandarajoti ◽  
Nigel S Key ◽  
Andras Gruber ◽  
Nigel Mackman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Thrombin Generation ◽  
Vascular Inflammation ◽  
Factor Xa ◽  
Cell Disease ◽  
Intrinsic Pathway ◽  
Coagulation Pathway

Sickle cell disease (SCD) is associated with activation of coagulation and vascular inflammation. We previously demonstrated that, in mouse models of SCD, tissue factor (TF) expressed on leukocytes activates coagulation and contributes to inflammation via microvascular thrombosis, whereas non-coagulant form of TF expressed by endothelial cells mediates factor Xa (FXa)-PAR2 signalling and contributes to inflammation via IL-6 expression. We also showed that both rivaroxaban and dabigatran, oral inhibitors of FXa and thrombin, attenuated the hypercoagulable state in sickle mice. It has been proposed that anticoagulants that target the intrinsic coagulation pathway may be associated with a lower risk of bleeding compared to targeting the extrinsic or common coagulation pathways. Therefore, we tested if the intrinsic pathway contributes to the activation of coagulation in sickle cell mice. Bone marrow from sickle (SS) and non-sickle (AA) Townes mice was transplanted into wild-type (WT) (n=18 AA, 15 SS), FXII-/- (n=14 AA, 22 SS), or FXI-/- (n=21 AA, 23 SS) recipients (all on C57Bl/6 genetic background). In addition, bone marrow from AA or SS mice was transplanted into high molecular weight kininogen (HK)+/+ (n=17 AA, 16 SS) or HK-/- (n=10 AA, 19 SS) mice. All mice were used for experiments 5 months after BMT. Thrombin generation, measured by plasma thrombin anti-thrombin (TAT) levels, was increased in WT mice injected with SS bone marrow (WT/BMSS) compared to WT/BMAA mice (4.4±0.7 vs 2.6±0.3 ng/mL, p<0.05, mean ± S.E.M), however neither FXII nor FXI deficiency affected this parameter. Consistent with these data, inhibition of FXIIa-dependent activation of FXI with 14E11 antibody also did not reduce plasma TAT levels in SS Townes mice. Interestingly, elevated plasma TAT levels observed in HK+/+/BMSS mice was significantly reduced in HK-/-/BMSS mice (4.8±0.5 versus 3.48±0.2 ng/mL, p<0.05). These data indicate that HK, but not FXII and FXI, contributes to thrombin generation in SCD at steady state of disease. In vitro, HK fragments induce TF expression on monocytes via activation of CD11b/18. We are now investigating if inhibition of HK fragments-induced TF expression on monocytes may attenuate the hypercoagulabIe state in SCD mice without impacting hemostasis.

Fetal hemoglobin in sickle cell disease: relationship to erythrocyte phosphatidylserine exposure and coagulation activation

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 1119-1124 ◽  
Author(s):  
B. N. Yamaja Setty ◽  
Surekha Kulkarni ◽  
A. Koneti Rao ◽  
Marie J. Stuart
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Thrombin Generation ◽  
Fetal Hemoglobin ◽  
Strong Relationship ◽  
Cell Disease ◽  
Red Cell Membrane ◽  
Prothrombin Fragment ◽  
F Cells

Abstract In sickle cell disease (SCD), loss of erythrocyte membrane phospholipid asymmetry occurs with the exposure of phosphatidylserine (PS), which provides a docking site for coagulation proteins. In vivo sickling/desickling, with resulting red cell membrane changes and microvesicle formation, appears to be one of the factors responsible for PS exposure. We evaluated children with SCD homozygous for sickle hemoglobin (SS disease) and controls (n = 65) and demonstrate that high levels of fetal hemoglobin (assessed as F cells) are associated with decreased microvesicle formation, PS exposure, and thrombin generation. F cells correlated inversely with both microvesicles and PS positivity (P &lt; .000001) in SS disease. Multiple regression analyses using various hematologic parameters as independent variables, and either microvesicles or PS positivity as the dependent variable, showed a strong relationship only with F cells. Additionally, plasma prothrombin fragment F1.2 levels (a marker for thrombin generation) correlated with both PS positivity (P &lt; .001) and F cells (P &lt; .01). An F-cell level of approximately 70% was associated with normal levels of prothrombin fragment F1.2 and with microvesicle formation indistinguishable from control values. We suggest that the use of such surrogate biologic markers in conjunction with F-cell numbers may provide valuable insights into the biology and consequences of in vivo sickling.

Thrombin generation in vivo and ex vivo in sickle cell disease patients

2021 ◽  
Vol 197 ◽  
pp. 165-171
Author(s):  
Valéria Sutana Ladeira ◽  
Sílvia Letícia de Oliveira Toledo ◽  
Letícia Gonçalves Resende Ferreira ◽  
Marina Mendes Oliveira ◽  
Ana Paula Ferreira Silva ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Thrombin Generation ◽  
Ex Vivo ◽  
Cell Disease

Thrombin generation in children with sickle cell disease: relationship with age, hemolysis, transcranial doppler velocity, and hydroxyurea treatment

2013 ◽  
Vol 91 (1) ◽  
pp. 46-54 ◽  
Author(s):  
Denis C. F. Noubouossie ◽  
Phu Q. Lê ◽  
Laurence Rozen ◽  
France Ziereisen ◽  
Dominique Willems ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Transcranial Doppler ◽  
Thrombin Generation ◽  
Doppler Velocity ◽  
Cell Disease ◽  
Hydroxyurea Treatment
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