title: Association of coagulation activation with clinical complications in sickle cell disease.
abstract: BACKGROUND
  The contribution of hypercoagulability to the pathophysiology of sickle cell disease (SCD) remains poorly defined. We sought to evaluate the association of markers of coagulation and platelet activation with specific clinical complications and laboratory variables in patients with SCD.
  
  
  METHODS
  Plasma markers of coagulation activation (D-dimer and TAT), platelet activation (soluble CD40 ligand), microparticle-associated tissue factor (MPTF) procoagulant activity and other laboratory variables were obtained in a cohort of patients with SCD. Tricuspid regurgitant jet velocity was determined by Doppler echocardiography and the presence/history of clinical complications was ascertained at the time of evaluation, combined with a detailed review of the medical records.
  
  
  RESULTS
  No significant differences in the levels of D-dimer, TAT, soluble CD40 ligand, and MPTF procoagulant activity were observed between patients in the SS/SD/Sβ⁰ thalassemia and SC/Sβ+ thalassemia groups. Both TAT and D-dimer were significantly correlated with measures of hemolysis (lactate dehydrogenase, indirect bilirubin and hemoglobin) and soluble vascular cell adhesion molecule-1. In patients in the SS/SD/Sβ⁰ thalassemia group, D-dimer was associated with a history of stroke (p = 0.049), TAT was associated with a history of retinopathy (p = 0.0176), and CD40 ligand was associated with the frequency of pain episodes (p = 0.039). In multivariate analyses, D-dimer was associated with reticulocyte count, lactate dehydrogenase, NT-proBNP and history of stroke; soluble CD40 ligand was associated with WBC count and platelet count; and MPTF procoagulant activity was associated with hemoglobin and history of acute chest syndrome.
  
  
  CONCLUSIONS
  This study supports the association of coagulation activation with hemolysis in SCD. The association of D-dimer with a history of stroke suggests that coagulation activation may contribute to the pathophysiology of stroke in clinically severe forms of SCD. More research is needed to evaluate the contribution of coagulation and platelet activation to clinical complications in SCD.
authors.affiliation: Division of Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina, United States of America. kataga@med.unc.edu
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Ataga
authors.forename: Julia E
authors.initials: JE
authors.lastname: Brittain
authors.forename: Payal
authors.initials: P
authors.lastname: Desai
authors.forename: Ryan
authors.initials: R
authors.lastname: May
authors.forename: Susan
authors.initials: S
authors.lastname: Jones
authors.forename: John
authors.initials: J
authors.lastname: Delaney
authors.forename: Dell
authors.initials: D
authors.lastname: Strayhorn
authors.forename: Alan
authors.initials: A
authors.lastname: Hinderliter
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Key
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000150:complications* / Q000201:enzymology; D000991:Antithrombins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology*; D055252:Cell-Derived Microparticles; D003710:Demography; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D015539:Platelet Activation / Q000502:physiology; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000991:Antithrombins; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D019010:Vascular Cell Adhesion Molecule-1; C036309:fibrin fragment D; D013925:Thromboplastin; D007770:L-Lactate Dehydrogenase; D013917:Thrombin