title: Protein C and S and inflammation in sickle cell disease.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands. jschnog@hotmail.com
authors.forename: J B
authors.initials: JB
authors.lastname: Schnog
authors.forename: M R
authors.initials: MR
authors.lastname: Mac Gillavry
authors.forename: A P
authors.initials: AP
authors.lastname: van Zanten
authors.forename: J C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: R A
authors.initials: RA
authors.lastname: Rojer
authors.forename: A J
authors.initials: AJ
authors.lastname: Duits
authors.forename: H
authors.initials: H
authors.lastname: ten Cate
authors.forename: D P M
authors.initials: DP
authors.lastname: Brandjes
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000378:metabolism; D001777:Blood Coagulation; D002637:Chest Pain / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism*; D017293:Protein S / Q000378:metabolism*; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D011486:Protein C; D017293:Protein S