Coagulation activation in sickle cell trait: an exploratory study.
Recent epidemiologic data suggest that sickle cell trait (HbAS; AS) is a risk factor for venous thromboembolism. We conducted an exploratory study of healthy subjects with AS under baseline conditions to determine whether a chronic basal hyperactivation of coagulation exists, and if so, what mechanism(s) contribute to this state. Eighteen healthy AS individuals were compared to 22 African-American controls with a normal haemoglobin profile (HbAA; AA) and 17 patients with sickle cell disease (HbSS; SS). Plasma thrombin-antithrombin complexes and D-dimer levels were elevated in AS relative to AA patients (P = 0·0385 and P = 0·017, respectively), and as expected, were much higher in SSversusAA (P < 0·0001 for both). Thrombin generation in platelet poor plasma was indistinguishable between AA and AS subjects, whereas a paradoxical decrease in endogenous thrombin potential was observed in SS (P ≤ 0·0001). Whole blood tissue factor was elevated in SS compared to AA (P = 0·005), but did not differ between AA and AS. Plasma microparticle tissue factor activity was non-significantly elevated in AS (P = 0·051), but was clearly elevated in SS patients (P = 0·004) when compared to AA controls. Further studies in larger cohorts of subjects with sickle cell trait are needed to confirm the results of this preliminary investigation.
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Chirag
C
Amin
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Soheir
S
Adam
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Micah J
MJ
Mooberry
Department of Medicine, Georgia Regents University, Augusta, GA, USA.
Abdullah
A
Kutlar
Department of Medicine, Georgia Regents University, Augusta, GA, USA.
Ferdane
F
Kutlar
Department of Biostatistics, School of Public Health, Yale University, New Haven, CT, USA.
Denise
D
Esserman
Department of Cell Biology and Anatomy, Georgia Regents University, Augusta, GA, USA.
Julia E
JE
Brittain
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Kenneth I
KI
Ataga
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Jen-Yea
JY
Chang
Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Alisa S
AS
Wolberg
Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.|Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Nigel S
NS
Key
D000328:Adult; D001741:Black or African American; D000755:Anemia, Sickle Cell / Q000097:blood; D000990:Antithrombin III / Q000032:analysis; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000737:chemistry; D016207:Cytokines / Q000097:blood; D005260:Female; D005337:Fibrin / Q000096:biosynthesis; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis; D010949:Plasma; D012805:Sickle Cell Trait / Q000097:blood* / Q000150:complications; D013917:Thrombin / Q000096:biosynthesis; D019851:Thrombophilia / Q000097:blood / Q000209:etiology*; D013925:Thromboplastin / Q000032:analysis; D054556:Venous Thromboembolism / Q000209:etiology
D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D005337:Fibrin; D013925:Thromboplastin; D010447:Peptide Hydrolases; D013917:Thrombin
coagulation; sickle; thrombin; tissue factor; venous thrombosis