Changes in coagulation and fibrinolysis in patients with sickle cell disease compared with healthy Black controls

Increased von Willebrand factor antigen and high molecular weight multimers in sickle cell disease associated with nocturnal hypoxemia

“…To our knowledge there is only one other published study [20] that performed extended vWF testing in a heterogeneous, adult group of SCD patients (n=14, mean age =29 years). This study also confirmed the observation (Hagger et al [9]) of increased vWF:Ag levels at baseline with further elevations during VOC. The need for investigation of children and adolescents with sleep hypoxemia as a vulnerable sub-population at potentially greater risk for SCD vasoocclusion is supported by our pilot findings of increased vWF:Ag levels and higher proportion of HMW-vWF multimers -suggestive of an increase in total functional vWF present -that are inversely correlated with SaO2 (Fig 1).…”

“…Wick et al first demonstrated that ULvWF multimers increased sickle RBCs adhesion to endothelial cells under flow conditions in vitro [9].Using ex vivo rat mesocecum preparations, Kaul et al showed that Desmopressin (an inducer of endothelial vWF release) increased sickle erythrocyte-endothelial adhesion [10]. Heterogenous adhesive complexes (including RBCadhesive ligand-endothelial cell) contribute to sickle RBC adhesion.…”

“…In recent years, SCD pathophysiology has been recognized to extend beyond the direct effects of polymerization of sickle hemoglobin, with vaso-occlusion resulting from complex interactions between sickle erythrocyte-endothelial adhesion, platelet activation, and the participation of adhesinogenic ligands, including vWF in the adhesive process [8]. Elevated vWF:Ag levels have been previously noted in steady state SCD and during vasoocclusive crises (VOC) [9] and several lines of experimental evidence suggest a pro-adhesive role for ULvWF multimers in sickle RBC-endothelial interactions [10,11]. We therefore sought to evaluate, in a pilot study, whether children and adolescents with documented nocturnal hypoxemia demonstrated differences in their vWF profiles that could potentially modulate the occurrence of vaso-occlusive events.…”

Sickle blood contains tissue factor–positive microparticles derived from endothelial cells and monocytes

“…11 Activation of the coagulation system is evidenced by platelet activation, thrombin generation, and fibrinolysis in patients with sickle cell disease [11][12][13][14][15][16] and may play a role in thrombotic complications of sickle cell disease such as stroke. 17 Consistent with these findings, in sickle cell disease tissue factor (TF) is abnormally expressed on circulating endothelial cells (CECs), 8 and whole blood TF procoagulant activity, believed to be associated with monocytes, is elevated.…”

Pulmonary Hypertension in Hemolytic Disorders

“…29 Hemolysis and decreased NO bioavailability also induce platelet activation, 33 thrombin generation, and tissue factor activation. 34 Further, there is a correlation between the rate of hemolysis and the levels of procoagulant factors in the blood of patients with SCD. [35][36][37] Hemolysis also is associated with the formation of RBC microvesicles expressing phosphatidyl serine, which activate tissue factor.…”