Hypercoagulable state as demonstrated by thromboelastometry in hemoglobin E/beta-thalassemia patients: Association with clinical severity and splenectomy status

Natesirinilkul, Rungrote; Charoenkwan, Pimlak; Nawarawong, Weerasak; Boonsri, Settapong; Tantivate, Pakinee; Wongjaikum, Suwakon; Manowong, Suphara; Sanguansermsri, Torpong

doi:10.1016/j.thromres.2016.02.014

Cited by 14 publications

(14 citation statements)

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“…In contrast to our results, Hassan et al reported significantly decreased PC and PS levels in splenectomized β-TM patients compared with controls [15] and Musumeci et al reported that the lowest PC and AT III levels were observed in older splenectomized patients [43]. Natesirinilkul et al found no significant differences in PC and PS levels in splenectomized and nonsplenectomized Hb E/β-thal patients [1]. Splenectomy had been performed a median of 2 (range 0.5-22) years in our patients.…”

Section: Tablecontrasting

confidence: 99%

“…Comparison of the anticoagulant proteins, thrombotic and endothelial injury markers between TDT and NTDT patients. unlike previous studies the PS antigen level was increased in β-TM patients compared with the control group, but the differences in PS level in the β-TI, α-TI, and α + β-thal and in the control group were not significant [1,21]. Approximately 40% of PS circulates as a free protein; the remaining 60% is bound to C4b-binding protein.…”

Section: Tablecontrasting

confidence: 63%

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Alterations of anticoagulant proteins and soluble endothelial protein C receptor in thalassemia patients of Chinese origin

Huang¹,

Yuan²,

Deng

et al. 2018

Thrombosis Research

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Background: Thalassemia is characterized by a hypercoagulable state in which the protein C (PC) pathway controls thrombosis. We investigated changes in PC, protein S (PS), antithrombin III (AT III) and soluble endothelial protein C receptor (sEPCR) in thalassemia. Methods: A group of 129 patients with β-thalassemia major (β-TM), β-thalassemia intermedia (β-TI), α-thalassemia intermedia (α-TI) and combined α-/β-thalassemia (α + β-thal) were compared with 32 gender-and age-matched controls. PC, PS, AT III, sEPCR, thrombin-antithrombin complex (TAT), and intercellular adhesion molecule1 (ICAM-1) antigens were measured by enzyme-linked immunosorbent assay. PC, AT III, and PS activity were assayed by substrate chromatography and a prothrombin time (PT)-based free protein S assay. Results: PC deficiency was seen in 95.3% of the patients and PS deficiency was seen in 77.5%. Concomitant reductions in PC and AT III antigen and activity were observed in β-TM, β-TI, and α-TI than in controls (p < 0.005). PC activity was lower in β-TM than in α-TI (p = 0.004). PS antigen was elevated in β-TM (p = 0.011) and sEPCR was elevated in α-TI (p = 0.018). Nonsplenectomized patients had lower PC (p = 0.001) and PS (p = 0.006) and higher sEPCR (p = 0.021) than postsplenectomy patients. Transfusion dependent thalassemia (TDT) patients had lower PC levels (p < 0.005) than those with nontransfusion dependent thalassemia (NTDT). ICAM-1 was increased in patient subgroups (p < 0.001), especially those with splenectomies (p = 0.009), and TAT was increased in all patient subgroups compared with controls (p < 0.001) except for α + β-thal. Conclusions: Deficiencies of anticoagulant proteins and elevated sEPCR contributed to chronic hypercoagulability in these thalassemia patients of Chinese origin. Splenectomy alleviated these alterations in this patient cohort with the median duration since splenectomy of two years. Blood transfusion was not ideal for avoiding thrombosis. 1. Introduction Mutations or deletions of globin genes in thalassemia result in an imbalance of globin synthesis, decreased erythropoiesis, and extravascular hemolysis. Hypercoagulability states are common occurrences in thalassemia patients in southeast Asia, the Mediterranean, and the Middle East regions [1-3]. The prevalence of β-thalassemia is approximately 4.91% and that of α-thalassemia is about 14.13% in the Guangxi province of China, and the various causes of coagulation disorders deserve investigation [4]. Accumulation of unmatched globin chains results in premature destruction of erythrocyte precursors in bone marrow, hemolysis of erythrocytes in the peripheral blood, and the appearance of abnormal red blood cells (RBCs). Loss of deformability impairs passage of RBCs through capillaries [5], and the resulting hemostasis may elicit a procoagulant condition [6]. Other reasons may include endothelial injury, platelet activation, increased plasma microparticles, impaired nitric oxide bioavailability, increased blood oxidants, and phosphatidylserine exposure on the outer ...

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Section: Tablecontrasting

confidence: 99%

Section: Tablecontrasting

confidence: 63%

Alterations of anticoagulant proteins and soluble endothelial protein C receptor in thalassemia patients of Chinese origin

Huang¹,

Yuan²,

Deng

et al. 2018

Thrombosis Research

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“…Higher amounts of platelets in the HbE/b-thalassemic patients, particularly the splenectomized patients, were also reported by Natesirinilkul and colleagues. 12 Previous studies of the proteomics profile in EVs in the plasma released from the platelets and RBCs of b-thalassemic patients reported a higher level of proteins involved in the oxidative stress response, for example, catalase, peroxiredoxin 2 (PRDX2), and heat shock proteins 70 (Hsp70) when compared with healthy individuals. 13,14 In addition, evidence of increased RBC generation in b-thalassemia was identified, such as detection of m hemoglobin, which is transcribed from the a gene (HBM) and usually expressed in cord blood reticulocytes.…”

Section: Introductionmentioning

confidence: 99%

Quantitative proteomics of plasma vesicles identify novel biomarkers for hemoglobin E/β-thalassemic patients

et al. 2018

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Key Points• Chaperones, antioxidants, ironsequestering proteins, and cathepsin S exhibited increased abundance in thalassemic EVs.• Haptoglobin and hemopexin are reduced in thalassemic patients' EVs, reflecting hemolysis. These could be used as clinical biomarkers.Hemoglobin E (HbE)/b-thalassemia has a wide spectrum of clinical manifestations that cannot be explained purely by its genetic background. Circulating extracellular vesicles (EVs) are one factor that likely contributes to disease severity. This study has explored the differences in protein composition and quantity between EVs from HbE/b-thalassemic patients and healthy individuals. We used tandem mass tag labeling mass spectrometry to analyze the EV proteins isolated from the plasma of 15 patients compared with the controls.To reduce biological variation between individuals, the EV proteins isolated from randomly assigned groups of 5 HbE/b-thalassemic patients were pooled and compared with 5 pooled age-and sex-matched controls in 3 separate experiments. Alpha hemoglobin-stabilizing protein had the highest fold increase. Catalase, superoxide dismutase, T-complex proteins, heat shock proteins, transferrin receptor, ferritin, and cathepsin S were also upregulated in thalassemic circulating EVs. Importantly, haptoglobin and hemopexin were consistently reduced in patients' EVs across all data sets, in keeping with the existing hemolysis that occurs in thalassemia. The proteomic data analysis of EV samples isolated from 6 individual HbE/b-thalassemic patients and western blotting results corroborated these findings. In conclusion, we have successfully identified consistent alterations of protein quantity between EVs from HbE/b-thalassemic and healthy individuals. This work highlights haptoglobin, hemopexin, and cathepsin S as potential clinically relevant biomarkers for levels of hemolysis and inflammation. Monitoring of these plasma proteins could help in the clinical management of thalassemia.

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“…After operation, compared with the control group, the number of platelets and haemoglobin in the rivaroxaban group was significantly smaller and the PT and APPT obviously decreased. Natesirinilkul et al investigated that a higher platelet count may lead to hypercoagulable state [27]. Coagulation tests are mostly conducted with PT and APPT [28].…”

Section: Discussionmentioning

confidence: 99%

Effect of rivaroxaban on preventing deep vein thrombosis in aged diabetics with femoral neck fractures after hip replacement

2017

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The present study estimates the effect of rivaroxaban on preventing deep vein thrombosis (DVT) in aged diabetics with femoral neck fractures after hip replacement. Our study consisted of 236 aged diabetics with femoral neck fractures, which were divided into the rivaroxaban and control groups. Reaction time (R time), clot formation time (K time), α angle (α), maximum amplitude (MA), clot elasticity (G) and coagulation index (CI), prothrombin time (PT) and activated partial thromboplastin time (APTT) were measured. DVT was diagnosed by color duplex Doppler ultrasound (CDDU). The risk factors of DVT were analysed by logistic regression analysis. Compared with the control group, in the rivaroxaban group, R time and K time were extended and α, MA and G decreased 1 day before operation. One day after operation, the rivaroxaban group had less PT and APPT and lower incidence of DVT than the control group. In the two groups, preoperative and postoperative PT and APPT significantly differed. Body mass index (BMI) ≥25, abnormal coagulation indicators, use of cemented femoral hip prosthesis, high haemoglobin content and non-ankle pump exercise after operation were the risk factors for DVT. Rivaroxaban could prevent DVT in aged diabetics with femoral neck fractures after hip replacement.

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Hypercoagulable state as demonstrated by thromboelastometry in hemoglobin E/beta-thalassemia patients: Association with clinical severity and splenectomy status

Cited by 14 publications

References 44 publications

Alterations of anticoagulant proteins and soluble endothelial protein C receptor in thalassemia patients of Chinese origin

Alterations of anticoagulant proteins and soluble endothelial protein C receptor in thalassemia patients of Chinese origin

Quantitative proteomics of plasma vesicles identify novel biomarkers for hemoglobin E/β-thalassemic patients

Effect of rivaroxaban on preventing deep vein thrombosis in aged diabetics with femoral neck fractures after hip replacement

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