A study of β-thromboglobulin and platelet factor-4 plasma levels in steady state sickle cell patients

Adamides, S.; Konstantopoulos, K.; Toumbis, Michael; Douratsos, D.; Travlou, Αnthi; Kasfiki, A.

doi:10.1007/bf01744139

Cited by 17 publications

(7 citation statements)

References 7 publications

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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: 98%

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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Section: Discussionmentioning

confidence: 98%

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

View full text Add to dashboard Cite

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“…Other investigators also have provided evidence for platelet activation, including elevated plasma β‐thromboglobulin levels ( Mehta, 1980; Adamides et al , 1990 ), decreased platelet ADP/ATP ratios ( Buerling‐Harbury & Schade, 1989), increased urinary thromboxane metabolites ( Kuranstin‐Mills et al , 1994 ), and increased platelet procoagulant activity ( Tomer et al , 1992 ). Browne et al (1996 ) demonstrated increased plasma and decreased platelet thrombospondin‐1 levels in sickle cell anaemia patients, which most probably reflects ongoing platelet activation.…”

Section: Discussionmentioning

confidence: 99%

“…There is evidence that platelets are activated in SCD ( Mehta & Mehta, 1980; Buchanan & Holtkamp, 1981; Mehta, 1980; Adamides et al , 1990 ; Buerling‐Harbury & Schade, 1989; Kuranstin‐Mills et al , 1994 ; Tomer et al , 1992 , 1994; Hebbel et al , 1993 ; Browne et al , 1996 ). The precise mechanism for the apparent platelet activation in these patients has not been established, nor have the circumstances of its occurrence.…”

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confidence: 99%

Platelet activation in patients with sickle cell disease

et al. 1998

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Vascular occlusion and vasculopathy underlie much of the morbidity in patients with sickle cell anaemia. Platelets may play a role in this vasculopathy. Samples from 43 patients with sickle cell disease (SCD) were examined for evidence of platelet activation using fluorescent‐labelled monoclonal antibodies and flow cytometry. There was increased expression of activation‐dependent antigens on the platelets from patients with SCD compared to those from both Caucasian and African‐American controls. In addition, SCD patients had increased levels of platelet microparticles. Platelets are activated in patients with sickle cell disease. The contribution of platelet activation to sickle cell pathophysiology is under active investigation in our laboratories.

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“…Thrombocytosis and several qualitative platelet abnormalities, including defects in platelet aggregation and evidence for in vivo platelet activation, have been described in patients with SCD (6)(7)(8)(9)(10)(11)(12)(13)(14). While some studies have suggested that platelets contribute to vasoocclusive crisis (15)(16)(17)(18), there is considerable doubt about their role (19) because antiplatelet agents have not significantly altered the frequency or severity of pain crisis (20-22;22-24).…”

Section: Introductionmentioning

confidence: 99%

Morphological and functional platelet abnormalities in Berkeley sickle cell mice

Shet

Hoffmann

Jiroušková

et al. 2008

Blood Cells, Molecules, and Diseases

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Berkeley sickle cell mice are used as an animal model of human sickle cell disease but there are no reports of platelet studies in this model. Since humans with sickle cell disease have platelet abnormalities, we studied platelet morphology and function in Berkeley mice (SS). We observed elevated mean platelet forward angle light scatter (FSC) values (an indirect measure of platelet volume) in SS compared to wild type (WT) (37 ± 3.2 vs. 27 ± 1.4, mean ± SD; p <0.001), in association with moderate thrombocytopenia (505 ± 49 × 10 3 /μl vs. 1151 ± 162 × 10 3 /μl; p <0.001). Despite having marked splenomegaly, SS mice had elevated levels of Howell-Jolly bodies and "pocked" erythrocytes (p <0.001 for both) suggesting splenic dysfunction. SS mice also had elevated numbers of thiazole orange positive platelets (5 ± 1 % vs. 1 ± 1%; p <0.001), normal to low plasma thrombopoietin levels, normal plasma glycocalicin levels, normal levels of platelet recovery, and near normal platelet life spans. Platelets from SS mice bound more fibrinogen and antibody to Pselectin following activation with a threshold concentration of a protease activated receptor (PAR)-4 peptide compared to WT mice. Enlarged platelets are associated with a predisposition to arterial thrombosis in humans and some humans with SCD have been reported to have large platelets. Thus, additional studies are needed to assess whether large platelets contribute either to pulmonary hypertension or the large vessel arterial occlusion that produces stroke in some children with sickle cell disease.

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A study of β-thromboglobulin and platelet factor-4 plasma levels in steady state sickle cell patients

Cited by 17 publications

References 7 publications

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

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

Platelet activation in patients with sickle cell disease

Morphological and functional platelet abnormalities in Berkeley sickle cell mice

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