The effect of spicules obtained from sickle red cells on clotting activity

Westerman, Maxwell P.; Cole, Edmond R.; Ke-gui, WU

doi:10.1111/j.1365-2141.1984.tb02180.x

Cited by 48 publications

(22 citation statements)

References 12 publications

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“…Both protein S and protein C can exert their anticoagulant effects on phosphatidylserine expressing sickle red blood cell membranes [7,8,10]. In patients with lower hemoglobin levels, there are more dense cells and membrane-shed vesicles, as well as reticulocytes (which all have high phosphatidylserine exposure) [44][45][46][47][48]. As total, but not free, protein S correlates positively to hemoglobin levels, it does not seem likely that this association reflects protein S consumption on phosphatidylserine-expressing red cells and vesicles.…”

Section: Discussionmentioning

confidence: 99%

Protein C and S and inflammation in sickle cell disease

et al. 2004

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Reduced activity of naturally occurring anticoagulants (NOAC) protein C and protein S may contribute to vaso-occlusion in sickle cell disease (SCD). We studied whether protein C and S are related to clinical vaso-occlusion, hematological markers of disease severity (hemoglobin levels, leukocyte counts, and percentage of fetal hemoglobin), and inflammation in SCD. Protein C activity, protein S (free and total) antigen, endothelial activation markers (soluble vascular cell adhesion molecule-1 [sVCAM-1], von Willebrand antigen [vWF]), and high sensitive C-reactive protein (hsCRP) levels were measured in 30 HbSS and 20 HbSC patients and in race-matched HbAA controls. NOAC levels were reduced in patients, and endothelial activation markers and hsCRP were elevated (except vWF in HbSC patients). Protein C activity and vWF levels were lower in HbSC patients who experienced painful crises compared to HbSC patients who were clinically asymptomatic. No other differences were observed between patients who did and did not experience vaso-occlusive events (painful crises, stroke, acute chest syndromes) or leg ulcers. A significant positive correlation between total protein S with hemoglobin levels and a significant negative correlation between total and free protein S and sVCAM-1 were detected in HbSS patients. Except perhaps for protein C in relation to painful crises in HbSC patients, these markers were not associated with the occurrence of clinical events. The protein S, hemoglobin, and sVCAM-1 associations may suggest decreased endothelial protein S production due to the more severe endothelial perturbation in HbSS patients with lower hemoglobin levels. Am.

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Section: Discussionmentioning

confidence: 99%

Protein C and S and inflammation in sickle cell disease

et al. 2004

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“…6,8,12 Our recent observation also shows that the ULVWF multimers are prevalent in 60-70 % of SCD patients who are in stable conditions of their health. As in SCD, activation of the vascular endothelium is primarily triggered by the inflammatory cytokines tumor necrosis factor alpha (TNFα), interleukin (IL)-1β/6/8/10, 13 and mediators such as superoxide 14 and cell-free Hb.…”

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confidence: 85%

“…6 An ex vivo experiment has shown that VWF secreted from desmopressin-stimulated endothelium in wild-type mice agglutinated infused sickled-RBCs in microvessels; the agglutination was significantly inhibited by an anti-VWF antibody. 8 VWF binds potently to aggregate platelets spontaneously by forming high-strength bonds with its platelet-receptor glycoprotein Ib (GPIb).…”

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confidence: 99%

Extracellular Hemoglobin Regulation of von Willebrand Factor Activity in Plasma of Patients with Sickle Cell Disease

Zhou¹,

Guchhait²

2011

Oncology &Amp; Hematology Review (US)

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Sickle cell disease (SCD) is a common hemolytic anemia caused by a single gene mutation in the β-subunit of hemoglobin (Hb), 1 affects millions of people worldwide, and is associated with significant morbidity and mortality. An estimated 83,000 US citizens have been diagnosed with the disease and more than two million carry the genes for related disorders, including sickle cell anemia and sickle-beta AbstractElevated levels of ultralarge (UL) von Willebrand factor (VWF) multimers in plasma play an important role in cell adhesion and vascular occlusion in sickle cell disease (SCD). Recently, we have shown that the binding of extracellular hemoglobin (ECHb) to the A2 domain of VWF significantly blocks VWF cleavage by the metalloprotease ADAMTS13 in vitro. We speculated that on release from the inflamed endothelium, the VWF multimers maintain the UL structure in plasma if ECHb prevents their cleavage. We observed that a subpopulation of VWF multimers that are bound to ECHb (HbVWF), which accounted for about 14 % of the total VWF in the plasma of SCD patients. The plasma HbVWF level is parallely correlated with the ECHb and VWF-antigen levels. The HbVWF multimers are resistant to the metalloprotease ADAMTS13 in vitro and are more adhesive to platelets and collagen compared with their Hb-free counterpart. Therefore, we speculate that the HbVWF, which are probably UL multimers, play an important role in tethering and stably adhering blood cells to the vascular endothelium and culminate in vascular occlusion/thrombosis/strokes in SCD patients. Thus, this article provides a new insight into the molecular pathophysiology of SCD.

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“…5 Previous observations also suggested a possible contribution of circulating cell-derived microparticles to the hypercoagulable state in SCD. 6 Microparticles are small membrane vesicles released from cells by budding upon activation or during apoptosis; microparticles in the blood can originate from platelets, erythrocytes, leukocytes and endothelial cells. 7 Elevated numbers of circulating microparticles have been reported in patients suffering from a variety of diseases with vascular involvement and hypercoagulability, including SCD.…”

Section: Introductionmentioning

confidence: 99%

Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease

Beers¹,

Schaap²,

Berckmans³

et al. 2009

Haematologica

241

221

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BackgroundSickle cell disease is characterized by a hypercoagulable state as a result of multiple factors, including chronic hemolysis and circulating cell-derived microparticles. There is still no consensus on the cellular origin of such microparticles and the exact mechanism by which they may enhance coagulation activation in sickle cell disease. Design and MethodsIn the present study, we analyzed the origin of circulating microparticles and their procoagulant phenotype during painful crises and steady state in 25 consecutive patients with sickle cell disease. ResultsThe majority of microparticles originated from platelets (GPIIIa,CD61) and erythrocytes (glycophorin A,CD235), and their numbers did not differ significantly between crisis and steady state. Erythrocyte-derived microparticles strongly correlated with plasma levels of markers of hemolysis, i.e. hemoglobin (r=-0.58, p<0.001) and lactate dehydrogenase (r=0.59, p<0.001), von Willebrand factor as a marker of platelet/endothelial activation (r=0.44, p<0.001), and D-dimer and prothrombin fragment F1+2 (r=0.52, p<0.001 and r=0.59, p<0.001, respectively) as markers of fibrinolysis and coagulation activation. Thrombin generation depended on the total number of microparticles (r=0.63, p<0.001). Anti-human factor XI inhibited thrombin generation by about 50% (p<0.001), whereas anti-human factor VII was ineffective (p>0.05). The extent of factor XI inhibition was associated with erythrocyte-derived microparticles (r=0.50, p=0.023). ConclusionsWe conclude that the procoagulant state in sickle cell disease is partially explained by the factor XI-dependent procoagulant properties of circulating erythrocyte-derived microparticles.Key words: microparticles, sickle cell disease, coagulation activation, hemolysis. Citation

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The effect of spicules obtained from sickle red cells on clotting activity

Cited by 48 publications

References 12 publications

Protein C and S and inflammation in sickle cell disease

Protein C and S and inflammation in sickle cell disease

Extracellular Hemoglobin Regulation of von Willebrand Factor Activity in Plasma of Patients with Sickle Cell Disease

Circulating erythrocyte-derived microparticles are associated with coagulation activation in sickle cell disease

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