Platelet hyperactivity in sickle-cell disease: a consequence of hyposplenism.

Kenny, M. W.; George, A J; Stuart, J.

doi:10.1136/jcp.33.7.622

Cited by 75 publications

(52 citation statements)

References 25 publications

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“…Another major cause of thrombocytosis in SCD seems to be hyposplenism [7,9], Enhanced platelet activation was also found in 10 pa tients during asymptomatic periods with plasma PF4 and pTG levels significantly higher than in normal controls. These findings arc similar to those reported by others [9,12,13,21], indicating increased platelet activity in SCD during steady state.…”

Section: Discussionmentioning

confidence: 94%

“…These findings arc similar to those reported by others [9,12,13,21], indicating increased platelet activity in SCD during steady state. The mechanism of excess platelet acti vation in steady state has not been clarified yet, although observations attribute the process to anatomical or func tional splenectomy [7,9], Elevated platelet count in asymptomatic periods seems to be responsible for some of the increased plasma levels of the platelet-specific pro teins (particularly of (ITG) because of platelet activation in vitro during and after blood collection.…”

Section: Discussionmentioning

confidence: 99%

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

Papadimitriou¹,

Travlou²,

Kalos³

et al. 1993

Acta Haematol

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Although there are many reports providing evidence for platelet hyperactivity during acute infarctive crisis in sickle cell disease, little attention has been paid to the study of platelet release reaction in steady state. Plasma levels of the α-granule constituents β-thromboglobulin and platelet factor 4 were measured in patients with sickle cell anemia during steady state and vaso-occlusive crisis in order to determine in vivo platelet activity. Significantly higher plasma levels of both proteins were found in steady state and in crisis when compared with those of normal controls. Platelet hyperactivity was also found to be more vigorous in painful crisis, suggesting a possible therapeutic role for drugs that inhibit platelet function.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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

Papadimitriou¹,

Travlou²,

Kalos³

et al. 1993

Acta Haematol

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“…4,5 These data imply that activation of endothelium with its associated inflammatory response is necessary for leukocyte adherence and subsequent vaso-occlusion. Patients in sickle cell crisis have multiple indicators of an inflammatory response, including elevated white counts, [6][7][8][9] C-reactive protein (CRP) levels, [10][11][12][13] and cytokines, [14][15][16][17] as well as activated monocytes, 13,18 neutrophils, [19][20][21] platelets, 18,[22][23][24][25][26][27][28] and endothelial cells 29,30 in circulation. In vitro, monocytes from sickle patients activate human endothelial cell nuclear factor B (NF-B) that governs the expression of a wide variety of genes associated with inflammation, including adhesion molecules, tissue factor, cytokines, and acute-phase proteins.…”

Section: Introductionmentioning

confidence: 99%

Transgenic sickle mice have vascular inflammation

Belcher

Bryant

Nguyen

et al. 2003

Blood

210

187

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Inflammation may play an essential role in vaso-occlusion in sickle cell disease. Sickle patients have high white counts and elevated levels of serum C-reactive protein (CRP), cytokines, and adhesion molecules. In addition, circulating endothelial cells, leukocytes, and platelets are activated. We examined 4 transgenic mouse models expressing human ␣-and sickle ␤-globin genes to determine if they mimic the inflammatory response seen in patients. These mouse models are designated NY-S, Berk-S Antilles , NY-S/S Antilles (NY-S ؋ Berk-S Antilles ), and Berk-S. The mean white counts were elevated 1.4-to 2.1-fold (P < .01) in the Berk-S Antilles , NY-S/S Antilles , and Berk-S mice, but not in the NY-S mice compared with controls. Serum amyloid P-component (SAP), an acute-phase response protein with 60% to 70% sequence homology to CRP, was elevated 8.5-to 12.1-fold (P < .001) in transgenic sickle mice. Similarly, serum interleukin-6 (IL-6) was elevated 1.6-to 1.9-fold (P < .05). Western blots, confirming immunohistochemical staining, showed vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), and platelet-endothelial cell adhesion molecule (PECAM) were up-regulated 3-to 5-fold (P < .05) in the lungs of sickle mice. Ribonuclease protection assays (RPAs) demonstrated VCAM mRNA also was elevated in sickle mice 1.2-to 1.4-fold (P < .01). Nuclear factor B (NF-B), a transcription factor critical for the inflammatory response, was elevated 1.9-fold (P < .006) in NY-S sickle mouse lungs. We conclude that transgenic sickle mice are good models to study vascular inflammation and the potential benefit of anti-inflammatory therapies to prevent vasoocclusion in sickle cell disease. (Blood. 2003; 101:3953-3959)

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“…The repetitive vaso-occlusive episodes cause tissue ischemia and reperfusion injury, resulting in endothelial cell activation and inflammation [4,5]. Sickle patients have multiple indicators of an inflammatory response including elevated white counts [6][7][8][9], C-reactive protein levels [10][11][12][13], cytokines [14][15][16][17], as well as activated monocytes [13,18], neutrophils [19][20][21], platelets [18,[22][23][24][25][26][27][28], and endothelial cells [29,30] in circulation.…”

Section: Introductionmentioning

confidence: 99%

Microvascular blood flow and stasis in transgenic sickle mice: Utility of a dorsal skin fold chamber for intravital microscopy

et al. 2004

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Vascular inflammation, secondary to ischemia-reperfusion injury, may play an essential role in vaso-occlusion in sickle cell disease (SCD). To investigate this hypothesis, dorsal skin fold chambers (DSFCs) were implanted on normal and transgenic sickle mice expressing human a and b s /b s-Antilles globin chains. Microvessels in the DSFC were visualized by intravital microscopy at baseline in ambient air and after exposure to hypoxia-reoxygenation. The mean venule diameter decreased 9% (P < 0.01) in sickle mice after hypoxia-reoxygenation but remained constant in normal mice. The mean RBC velocity and wall shear rate decreased 55% (P < 0.001) in sickle but not normal mice after hypoxia-reoxygenation. None of the venules in normal mice became static at any time during hypoxia-reoxygenation; however, after 1 hr of hypoxia and 1 hr of reoxygenation, 11.9% of the venules in sickle mice became static (P < 0.001). After 1 hr of hypoxia and 4 hr of reoxygenation, most of the stasis had resolved; only 3.6% of the subcutaneous venules in sickle mice remained static (P = 0.01). All of the venules were flowing again after 24 hr of reoxygenation. Vascular stasis could not be induced in the subcutaneous venules of sickle mice by tumor necrosis factor alpha (TNF-a). Leukocyte rolling flux and firm adhesion, manifestations of vascular inflammation, were significantly higher at baseline in sickle mice compared to normal (P < 0.01) and increased 3-fold in sickle (P < 0.01), but not in normal mice, after hypoxia-reoxygenation. Plugs of adherent leukocytes were seen at bifurcations at the beginning of static venules. Misshapen RBCs were also seen in subcutaneous venules. Am.

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Platelet hyperactivity in sickle-cell disease: a consequence of hyposplenism.

Cited by 75 publications

References 25 publications

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

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

Transgenic sickle mice have vascular inflammation

Microvascular blood flow and stasis in transgenic sickle mice: Utility of a dorsal skin fold chamber for intravital microscopy

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