Study of Platelet Function in Patients with Sickle Cell Anemia during Steady State and Vaso-Occlusive Crisis

Papadimitriou, Christos; Travlou, Αnthi; Kalos, A.; Douratsos, D.; Lalï, Polyxene

doi:10.1159/000204519

Cited by 20 publications

(11 citation statements)

References 10 publications

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“…Our results support this finding. Similar to others [35,36], we found ( Table 2) increased procoagulant activity with the platelet release products PF4 and b-TG which were highly elevated in patients with sickle cell disease during acute pain episodes. We also confirm previous findings [37][38][39]] of a reduced protein S level.…”

Section: Discussionsupporting

confidence: 90%

Clinical evaluation of a new functional test for detection of plasma procoagulant phospholipids

Dreden

Rousseau

Fontaine

et al. 2009

Blood Coagulation &Amp; Fibrinolysis

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The objective of this study was to validate a simple factor Xa-based clotting test developed to monitor procoagulant phospholipids (PPLs) and platelet-derived microparticles (PMPs). This assay is easily automated, giving it a major advantage over the more laborious and expensive flow cytometry, electron microscopy and ELISA techniques in general usage at present. The intra-assay and inter-assay variation coefficients were less than 5% at both low and high levels of PPLs. The test is not affected by other clotting factors is assured by the use of a phospholipid-free animal plasma, which provides excess factor V, fibrinogen and prothrombin. This test was evaluated in apparently healthy volunteers and in selected patient groups associated with increased levels of PMPs in the circulation (diabetes mellitus, sickle cell disease, thyroid cancer and patients with multiple trauma). The study showed that XaCT has a high discriminating power for PPLs and that the patient groups have significantly highly increased PPLs activities when compared with healthy volunteers. Although of a preliminary nature, the test has shown that it has the sensitivity for discriminating severity of disease, as it could detect patients in sickle cell crisis and differentiate between type 1 and 2 diabetes. In conclusion, the combination of reliability, reproducibility and easy performance makes the XaCT assay a simple test to screen for PPLs in plasma samples.

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Section: Discussionsupporting

confidence: 90%

Clinical evaluation of a new functional test for detection of plasma procoagulant phospholipids

Dreden

Rousseau

Fontaine

et al. 2009

Blood Coagulation &Amp; Fibrinolysis

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“…Not only do vasoocclusive crises occur during inflammatory insults such as infections or surgery, but the steady-state patient has elevated leukocyte counts (3,55), activated leukocytes (7,21,25,33,59) and platelets (1,39,56), elevated cytokines (14,23,34), and circulating endothelial cell adhesion molecules (13). Vasoocclusion in sickle cell disease is transient and episodic (18,29), which would promote tissue ischemia and reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Critical role of endothelial cell activation in hypoxia-induced vasoocclusion in transgenic sickle mice

Belcher¹,

Mahaseth²,

Welch³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

149

142

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Activation of vascular endothelium plays an essential role in vasoocclusion in sickle cell disease. The anti-inflammatory agents dexamethasone and adhesion molecule-blocking antibodies were used to inhibit endothelial cell activation and hypoxia-induced vasoocclusion. Transgenic sickle mice, expressing human alpha-, beta(S)-, and beta(S-Antilles)-globins, had an activated vascular endothelium in their liver, lungs, and skin, as exhibited by increased activation of NF-kappaB compared with normal mice. NF-kappaB activation increased further in the liver and skin after sickle mice were exposed to hypoxia. Sickle mice had decreases in red blood cell (RBC) velocities and developed vasoocclusions in subcutaneous venules in response to hypoxia. Dexamethasone pretreatment prevented decreases in RBC velocities and inhibited vasoocclusions and leukocyte-endothelium interactions in venules after hypoxia. Dexamethasone treatment inhibited NF-kappaB, VCAM-1, and ICAM-1 expression in the liver, lungs, and skin of sickle mice after hypoxia-reoxygenation. VCAM-1 or ICAM-1 blockade with monoclonal antibodies mimicked dexamethasone by inhibiting vasoocclusion and leukocyte adhesion in sickle mice, demonstrating that endothelial cell activation and VCAM-1 and ICAM-1 expression are necessary for hypoxia-induced vasoocclusion in sickle mice. VCAM-1, ICAM-1, and vasoocclusion increased significantly 3 days after dexamethasone discontinuation, possibly explaining rebounds in vasoocclusive crises observed after withdrawal of glucocorticosteroids in sickle patients. We conclude that anti-inflammatory treatments that inhibit endothelial cell activation and adhesion molecule expression can inhibit vasoocclusion in sickle cell disease. Rebounds in vasoocclusive crises after dexamethasone withdrawal are caused by rebounds in endothelial cell activation.

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“…The relocation of CD40L from platelets to plasma in HbSS patients is consistent with reports that other plateletreleased proteins are also elevated in SCA. 28,29 Indeed, HbSS patients average 5.7 ng of CD40L per 3ϫ10 8 platelets compared with 13.3 ng of CD40L found in HbAA platelets (Figure 2). Assuming a platelet count of 3ϫ10 8 platelets/mL of plasma, 7.6 ng of CD40L relocated from platelets to the plasma would correspond to a nearly 200-fold increase over circulating levels of 0.04 ng CD40L/mL in HbAA plasma, suggesting that the amount depleted from HbSS platelets could more than account for the 30-fold elevation found in HbSS plasma (Figure 1).…”

Section: Lee Et Al Cd40l In Sickle Cell Anemia 1629mentioning

confidence: 96%

Biologically Active CD40 Ligand Is Elevated in Sickle Cell Anemia

Lee

Ataga

Orringer

et al. 2006

ATVB

141

112

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Objective-After activation, platelets expose CD40 ligand (CD40L) on their surface, then subsequently release the inflammatory mediator as a soluble fragment (sCD40L). Because sickle cell anemia (SCA) is noted for both platelet activation and chronic inflammation, we asked whether platelet-released CD40L potentially plays a role in SCA. Methods and Results-ELISAs demonstrate that SCA patient plasma contains 30-fold more sCD40L than control plasma. Correspondingly, platelets from these patients contain less than half the CD40L found in control platelets. Platelets from patients in painful crises are further depleted of CD40L, with even higher plasma levels, suggesting a correlation to the patient's clinical state. In addition, elevated sCD40L correlates with increased tissue factor in SCA plasma. Blockage of the CD40L receptor CD40 reduces SCA plasma-induced production of tissue factor and endothelial intercellular adhesion molecule-1 (ICAM-1). Finally, sCD40L activity in SCA plasma is confirmed by its induction of B-cell proliferation. Conclusions-Platelet-derived sCD40L is elevated in SCA, further elevated in crises, and biologically active. The participation of sCD40L in SCA plasma-induced production of B cells, tissue factor, and ICAM-1 suggests that CD40L may contribute to the chronic inflammation and increased thrombotic activity known to occur in SCA.

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Study of Platelet Function in Patients with Sickle Cell Anemia during Steady State and Vaso-Occlusive Crisis

Cited by 20 publications

References 10 publications

Clinical evaluation of a new functional test for detection of plasma procoagulant phospholipids

Clinical evaluation of a new functional test for detection of plasma procoagulant phospholipids

Critical role of endothelial cell activation in hypoxia-induced vasoocclusion in transgenic sickle mice

Biologically Active CD40 Ligand Is Elevated in Sickle Cell Anemia

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