Platelet Aggregation and Activation in Thalassemia Major Patients in Indonesia

Setiabudy, Rahajuningsih Dharma; Wahidiyat, Pustika Amalia; Setiawan, Lyana

doi:10.1177/1076029607306397

Cited by 10 publications

(7 citation statements)

References 18 publications

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“…Additionally, a previous study revealed that PLT activation, induced by ADP, is higher in splenectomized than in nonsplenectomized thalassemia patients, 69 aligning with our findings where both β-TDT groups exhibited higher ADPinduced PLT aggregation compared to the normal control. However, our study showed that PLT activation induced by collagen in splenectomized patients had lower maximum 70 This discrepancy might be attributed to iron overload conditions, as our splenectomy group displayed higher plasma ferritin levels, potentially affecting the PLT function via collagen induction.…”

Section: ■ Discussionsupporting

confidence: 93%

“…A chronic hypercoagulable state is related with PLT activation. , Therefore, to examine PLT activities, we performed PLT aggregation tests induced by adenosine diphosphate (ADP) or collagen and measured the percentage of maximum PLT aggregation. As shown in Figure A,B, the maximum ADP-induced PLT aggregation in the splenectomy group was significantly higher ( p -value < 0.01), while the nonsplenectomy group showed a slightly higher but not significant ( p -value = 0.93) compared to the control group.…”

Section: Resultsmentioning

confidence: 99%

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A Compact Differential Dynamic Microscopy-based Device (cDDM): An Approach Tool for Early Detection of Hypercoagulable State in Transfusion-Dependent-β-Thalassemia Patients

Petiwathayakorn,

Paradee,

Hantrakool

et al. 2024

ACS Appl. Bio Mater.

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β-Thalassemia especially transfusion-dependent thalassemia (TDT) associates with a hypercoagulable state, which is the main cause of thromboembolic events (TEE). Plasma viscosity and rheological parameters could be essential markers for determining hypercoagulable state in β-thalassemia patients. The traditional methods for measuring viscosity are often limited by large sample volumes and are impractical for routine clinical monitoring. The compact differential dynamic microscopy-based device (cDDM), an optical microscopy for quantitative rheological assessment, was developed and applied for prognosis of the hypercoagulable state in β-TDT with and without splenectomy. The device was performed plasma viscosity measurement using low plasma volume (8 μL) and revealed a value as modulus of complex viscosity |η(ω)| in 7 min. We also parallelly demonstrated the correlation of the viscosity and related-coagulable parameters: complete blood count, prothrombin time (PT), activated partial thromboplastin time (APTT), protein C (PC), protein S (PS), CD62P and CD63 expression, and platelet aggregation test. The thalassemia plasma exhibited a higher value of |η(ω)| than healthy plasma, which can represent a different viscoelastic property among the groups. Even all related-coagulable parameters indicated hypercoagulable state in both nonsplenectomies and splenectomies β-TDT patients when compared to control, only high platelet numbers significantly correlated to high plasma viscosity in the splenectomy group. However, the other coagulable parameters have shown a trend of positive relationship with high plasma viscosity in all β-1thalassemia TDT patients. The relative results suggested that our device would be an approach tool for early detection of hypercoagulable state in transfusion-dependent-β-thalassemia patients, which can help to prevent TEE and the critical consequent-complications.

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Section: ■ Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

A Compact Differential Dynamic Microscopy-based Device (cDDM): An Approach Tool for Early Detection of Hypercoagulable State in Transfusion-Dependent-β-Thalassemia Patients

Petiwathayakorn,

Paradee,

Hantrakool

et al. 2024

ACS Appl. Bio Mater.

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“…Tissue hypoxia due to chronic anemia may damage the endothelium causing interaction of platelets with the vessel wall. This results in the formation of circulating aggregates by the more active platelets while the less active ones are detected in vitro as poorly aggregable [ 16 , 19 ]. Orudzhev et al observed increased levels of circulating antiplatelet antibodies, immunoglobulins, and variable-sized immune complexes in their β-thalassemia patients and suggested their role in causing increased platelet disaggregation with resultant in vitro hypoaggregation of platelets [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Bleeding Versus Thrombotic Tendency in Young Children With Beta-Thalassemia Major

Singh

Yadav

Kushwaha

et al. 2021

Cureus

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Introduction Bleeding and thrombotic events are known to occur in beta-thalassemia major (BTM) patients and have been attributed to hepatic iron overload associated with multiple blood transfusions. We evaluated hemostatic parameters in children with BTM who had no previous history of bleeding or thrombotic episodes. Materials and Methods Hemostatic parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), platelet aggregation, protein C and S, iron profile, and liver function tests were evaluated in 54 children (median age = 12 months, age range = 4-144 months) with BTM and 15 age and sex-matched controls. Results The mean PT and APTT of patients were significantly higher ( P =0.016 and P <.001) than that of controls. Mean protein C, protein S activity and platelet aggregability with adenosine 5-diphosphate (ADP) as an agonist in patients were significantly lower ( P <.001, P <.001 and P =0.007, respectively) than that in controls. Mean serum ferritin in BTM children was not significantly elevated to be associated with hepatic dysfunction. Conclusion Deranged hemostatic parameters indicative of bleeding and thrombotic tendencies are observed in BTM children from an early age and may not be solely due to hyperferritinemia-associated hepatic dysfunction. Despite the presence of deranged hemostatic parameters, a state of balance exists between bleeding and thrombosis, and an imbalance may lead to bleeding or thrombotic events at a later age.

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“…ADP secreted from granules is important in mediating the next steps of activation and aggregation, causing platelets to adhere to one another. Thalassemia patients have increased P-selectin expression on platelets and soluble P-selectin in plasma [ 17 , 24 , 27 ]. Herein, we provide additional data on the association of nitrite reductase activity of HbE with P-selectin expression on platelets.…”

Section: Discussionmentioning

confidence: 99%

Decreased nitrite reductase activity of deoxyhemoglobin correlates with platelet activation in hemoglobin E/ß-thalassemia subjects

et al. 2018

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Nitric oxide (NO) can be generated from nitrite by reductase activity of deoxygenated hemoglobin (deoxyHb) apparently to facilitate tissue perfusion under hypoxic condition. Although hemoglobin E (HbE) solutions have been shown to exhibit decreased rate of nitrite reduction to NO, this observation has never been reported in erythrocytes from subjects with hemoglobin E/ß-thalassemia (HbE/ß-thal). In this study, we investigated the nitrite reductase activity of deoxyHb dialysates from 58 non-splenectomized and 23 splenectomized HbE/ß-thal subjects compared to 47 age- and sex-matched normal subjects, and examined its correlation with platelet activity. Iron-nitrosyl-hemoglobin (HbNO) was measured by tri-iodide reductive chemiluminescence as a marker of NO generation. HbNO produced from the reaction of nitrite with deoxyHb dialysate from both non-splenectomized and splenectomized HbE/ß-thal subjects was lower than that of normal (AA) hemoglobin subjects. P-selectin expression, a marker of platelet activation, at baseline and in reactivity to stimulation by adenosine diphosphate (ADP), were higher in HbE/ß-thal subjects than normal subjects. HbNO formation from the reactions of nitrite and deoxyHb inversely correlated with baseline platelet P-selectin expression, HbE levels, and tricuspid regurgitant velocity (TRV). Nitrite plus deoxygenated erythrocytes from HbE/ß-thal subjects had a lower ability to inhibit ADP-induced P-selectin expression on platelets than erythrocytes from normal subjects. We conclude that deoxyHb in erythrocytes from HbE/ß-thal subjects has a decreased ability to reduce nitrite to NO, which is correlated with increased platelet activity in these individuals.

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Platelet Aggregation and Activation in Thalassemia Major Patients in Indonesia

Cited by 10 publications

References 18 publications

A Compact Differential Dynamic Microscopy-based Device (cDDM): An Approach Tool for Early Detection of Hypercoagulable State in Transfusion-Dependent-β-Thalassemia Patients

A Compact Differential Dynamic Microscopy-based Device (cDDM): An Approach Tool for Early Detection of Hypercoagulable State in Transfusion-Dependent-β-Thalassemia Patients

Bleeding Versus Thrombotic Tendency in Young Children With Beta-Thalassemia Major

Decreased nitrite reductase activity of deoxyhemoglobin correlates with platelet activation in hemoglobin E/ß-thalassemia subjects

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