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document
A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease . Abnormal blood flow accounts for most of the clinical morbidity of sickle cell disease ( SCD ) [ 1,2 ] . Most notably , occlusion of flow in the microvasculature causes the acute pain crises [ 3 ] that are the commonest cause for patients with SCD to seek medical attention [ 4 ] and major determinants of their quality of life [ 5 ] . Based on evidence that endothelial P-selectin is central to the abnormal blood flow in SCD we provide results from four of our studies that are germane to microvascular blood flow in SCD . A proof-of-principle study established that doses of heparin lower than what are used for anticoagulation but sufficient to block P-selectin improved microvascular blood flow inpatients with SCD . An in vitro study showed that Pentosan Polysulfate Sodium ( PPS ) had greater P-selectin blocking activity than heparin . A Phase I clinical study demonstrated that a single oral dose of PPS increased microvascular blood flow in patients with SCD . A Phase II clinical study that was not completed documented that daily oral doses of PPS administered for 8 weeks lowered plasma levels of sVCAM-1 and tended to improve microvascular blood flow in patients with SCD . These data support the concept that P-selectin on the microvascular endothelium is critical to both acute vascular occlusion and chronically impaired microvascular blood flow in SCD . They also demonstrate that oral PPS is beneficial to microvascular sickle cell blood flow and has potential as an efficacious agent for long-term prophylactic therapy of SCD .
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Intervention_Pharmacological
P-selectin blocking agent
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Intervention_Pharmacological
heparin
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Intervention_Pharmacological
Pentosan Polysulfate Sodium ( PPS )
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Intervention_Pharmacological
PPS
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Intervention_Pharmacological
PPS
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Outcome_Mental
marker of endothelial cell injury
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Outcome_Physical
Abnormal blood flow
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Outcome_Physical
abnormal blood flow in SCD
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Outcome_Physical
microvascular blood flow
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Outcome_Other
microvascular blood flow
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Outcome_Other
acute vascular occlusion and chronically impaired microvascular blood flow in SCD .
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Participant_Condition
sickle cell disease
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Participant_Condition
SCD
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Participant_Condition
SCD