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

Ladeira, Valéria Sutana; Toledo, Sílvia Letícia de Oliveira; Ferreira, Letícia Gonçalves Resende; Oliveira, Marina Mendes; Silva, Ana Paula Ferreira da; Júnior, Wander Valadares de Oliveira; Duarte, Rita Carolina Figueiredo; Renó, Cristiane de Oliveira; Dusse, Luci Maria Sant’Ana; Santos, Herica L.; Carvalho, Maria das Graças; Pinheiro, Melina de Barros; Rios, Danyelle Romana Alves

doi:10.1016/j.thromres.2020.10.040

Cited by 5 publications

(5 citation statements)

References 50 publications

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“…Gerotziafas et al demonstrated no difference in ETP and lagtime associated with a higher peak and velocity and a lower TTP in 92 SCD patients at steady state treated or not with hydroxyurea using 5 pM of TF and 4 µM of PL concentrations (22). Moreover, previous studies demonstrated a lower ETP compared to healthy controls, in SCD patients treated with hydroxyurea and exchange blood transfusion (23,30). A lack of standardization in performing the assays contributed largely to a poor correlation between assays and study results with TGA (31).…”

Section: Discussionmentioning

confidence: 89%

“…Several studies have demonstrated thrombin generation modification in SCD treated with hydroxyurea ( 22 , 23 ). Hydroxyurea reduced hypercoagulability in treated patients with a higher lagtime and TTP, a lower peak and velocity and no difference in ETP compared to untreated patients.…”

Section: Discussionmentioning

confidence: 99%

“…TGA is a global assay which allows to differentiate hypo- or hyper-coagulable profiles ( 19 , 20 ). Several studies have been published on TGA ex vivo in patients with SCD in steady state but the results are inconsistent requiring further studies ( 21 – 23 ).…”

Section: Introductionmentioning

confidence: 99%

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Investigation of thrombin generation assay to predict vaso-occlusive crisis in adulthood with sickle cell disease

Feugray

Kasonga

Grall

et al. 2022

Front. Cardiovasc. Med.

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IntroductionSickle cell disease (SCD) is an inherited hemoglobinopathy disorder. The main consequence is synthesis of hemoglobin S leading to chronic hemolysis associated with morbidity. The aim of this study was to investigate Thrombin Generation Assay (TGA) to assess hypercoagulability in SCD and TGA parameters as biomarkers of vaso-occlusive crisis (VOC) risk and hospitalization within 1 year.Materials and methodsWe performed TGA in platelet poor plasma (PPP) with 1 pM of tissue factor and 4 μM of phospholipid-standardized concentration, in duplicate for patients and controls. We measured thrombomodulin (TM), soluble endothelial Protein C Receptor and Tissue Factor Pathway Inhibitor (TFPI).ResultsA total of 113 adult patients with SCD, 83 at steady state and 30 during VOC, and 25 healthy controls matched on age and gender were included. Among the 83 patients at steady state, (36 S/S-1 S/β0, 20 S/Sα3.7, and 19 S/C-7 S/β+) 28 developed a VOC within 1 year (median: 4 months [2.25–6]). We observed an increase of peak and velocity associated with a shortening of lagtime and time to peak (TTP) and no difference of endogenous thrombin potential (ETP) in patients compared to controls. TFPI (p < 0.001) and TM (p = 0.006) were significantly decreased. TGA confirmed hypercoagulability in all SCD genotypes and clinical status. The association of ETP > 1,207 nM.min and peak >228.5 nM presented a sensitivity of 73.5% and a specificity of 93.9% to predict VOC development within 1 year.ConclusionWe have demonstrated a hypercoagulable state in SCD associated with chronic hemolysis. These preliminary findings suggest that TGA parameters, as ETP and peak, could be used to predict VOC development within 1 year.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Investigation of thrombin generation assay to predict vaso-occlusive crisis in adulthood with sickle cell disease

Feugray

Kasonga

Grall

et al. 2022

Front. Cardiovasc. Med.

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“…2 Thrombin can be used as a biomarker for the diagnosis and treatment of certain diseases, 5 such as cancer cell metastases, 6 tumor growth, 7 inflammation, 8 and other diseases related to blood coagulation. 9 Thrombin is produced in the early stage of coagulation and then quickly neutralized by the anticoagulant substances in the body, 10 so it is highly difficult to be directly measured. Indeed, rapid, specific, and sensitive detection of thrombin is significantly required during surgery or treatment of cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

“…Thrombin, a multifunctional serine proteinase, plays a key role in the maintenance of normal hemostatic function and participates in several key bioregulatory processes, such as blood coagulation, angiogenesis, and blood circulation . Thrombin can be used as a biomarker for the diagnosis and treatment of certain diseases, such as cancer cell metastases, tumor growth, inflammation, and other diseases related to blood coagulation . Thrombin is produced in the early stage of coagulation and then quickly neutralized by the anticoagulant substances in the body, so it is highly difficult to be directly measured.…”

Section: Introductionmentioning

confidence: 99%

Aptamer-Based Solution-Gated Graphene Transistors for Highly Sensitive and Real-Time Detection of Thrombin Molecules

Zhao

Xiao

et al. 2021

Anal. Chem.

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Thrombin is an important biomarker for various diseases and biochemical reactions. Rapid and real-time detection of thrombin that quickly neutralizes in early coagulation in the body has gained significant attention for its practical applications. Solution-gated graphene transistors (SGGTs) have been widely studied due to their higher sensitivity and low-cost fabrication for chemical and biological sensing applications. In this paper, the ssDNA aptamer with 29 bases was immobilized on the surface of the gate electrode to specifically recognize thrombin. The SGGT sensor achieved high sensitivity with a limit of detection (LOD) up to fM. The LOD was attributed to the amplification function of SGGTs and the suitable aptamer choice. The ssDNA configuration folding induced by thrombin molecules and the electropositivity of thrombin molecules could arouse the same electrical response of SGGTs, helping the device obtain a high sensitivity. The channel current variation of sensors had a good linear relationship with the logarithm of thrombin concentration in the range of 1 fM to 10 nM. The fabricated device also demonstrated a short response time to thrombin molecules, and the response time to the 1 fM thrombin molecules was about 150 s. In summary, the sensing strategy of aptamer-based SGGTs with high sensitivity and high selectivity has a good prospect in medical diagnosis.

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Thrombin generation and all-cause mortality in The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Gonçalves Resende Ferreira,

Maria Barreto,

Bicalho Maluf

et al. 2024

Clinica Chimica Acta

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

Cited by 5 publications

References 50 publications

Investigation of thrombin generation assay to predict vaso-occlusive crisis in adulthood with sickle cell disease

Investigation of thrombin generation assay to predict vaso-occlusive crisis in adulthood with sickle cell disease

Aptamer-Based Solution-Gated Graphene Transistors for Highly Sensitive and Real-Time Detection of Thrombin Molecules

Thrombin generation and all-cause mortality in The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

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