Clinical, laboratory, and genetic risk factors for thrombosis in sickle cell disease

Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediat...

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Published inBlood advances Vol. 4; no. 9; pp. 1978 - 1986
Main Authors Srisuwananukorn, Andrew, Raslan, Rasha, Zhang, Xu, Shah, Binal N., Han, Jin, Gowhari, Michel, Molokie, Robert E., Gordeuk, Victor R., Saraf, Santosh L.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 12.05.2020
American Society of Hematology
Subjects
Adult
Aged
Anemia, Sickle Cell - complications
Anemia, Sickle Cell - epidemiology
Anemia, Sickle Cell - genetics
Child
Humans
Laboratories
Red Cells, Iron, and Erythropoiesis
Retrospective Studies
Risk Factors
Thrombosis - etiology
Thrombosis - genetics
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Abstract Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ0-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ0-genotype patients (P < .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ0 genotype, and higher white blood cell (WBC) counts and Hb (P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD. •Traditional (kidney disease) and SCD-specific (SS/Sβ0-thal, HU, low Hb F%, high WBC count, and Hb) risk factors are associated with thrombosis.•Stroke recurrence was 24% despite being at transfusion goal and VTE recurrence was lower with direct oral anticoagulant vs other therapies. [Display omitted]
AbstractList Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ0-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ0-genotype patients (P < .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ0 genotype, and higher white blood cell (WBC) counts and Hb (P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD.
Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ0-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ0-genotype patients (P < .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ0 genotype, and higher white blood cell (WBC) counts and Hb (P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD. •Traditional (kidney disease) and SCD-specific (SS/Sβ0-thal, HU, low Hb F%, high WBC count, and Hb) risk factors are associated with thrombosis.•Stroke recurrence was 24% despite being at transfusion goal and VTE recurrence was lower with direct oral anticoagulant vs other therapies. [Display omitted]
Traditional (kidney disease) and SCD-specific (SS/Sβ0-thal, HU, low Hb F%, high WBC count, and Hb) risk factors are associated with thrombosis. Stroke recurrence was 24% despite being at transfusion goal and VTE recurrence was lower with direct oral anticoagulant vs other therapies. Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ 0 -genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ 0 -genotype patients ( P < .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ 0 genotype, and higher white blood cell (WBC) counts and Hb ( P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD.
Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ0-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ0-genotype patients (P < .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ0 genotype, and higher white blood cell (WBC) counts and Hb (P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD.Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and risk factors are not clear. We investigated the incidence and predictors for thrombosis in a retrospective, longitudinal cohort of 1193 pediatric and adult SCD patients treated at our institution between January 2008 and December 2017. SCD diagnosis and thrombotic complications were identified using International Classification of Diseases coding and verified through medical chart review. Clinical and laboratory data were extracted from the medical records. With a median follow-up of 6.4 years, 208 (17.4%) SCD patients experienced 352 thrombotic events (64 strokes, 288 venous thromboembolisms [VTE]). Risk factors for stroke included older age and HbSS/Sβ0-genotype and a lower hemoglobin (Hb) F% in the subset of HbSS/Sβ0-genotype patients (P < .05). VTE risk was independently associated with lower estimated glomerular filtration rate, hydroxyurea (HU) use, HbSS/Sβ0 genotype, and higher white blood cell (WBC) counts and Hb (P ≤ .03). Two thrombomodulin gene variants previously associated with thrombosis in the general African American population, THBD rs2567617 (minor allele frequency [MAF] 0.25; odds ratio [OR], 1.5; P = .049) and THBD rs1998081 (MAF, 0.24; OR, 1.5; P = .059), were associated with thrombosis in this cohort. In summary, thrombotic complications are common, and several traditional and SCD-specific risk factors are associated with thrombotic risk. Future studies integrating clinical, laboratory, and genetic risk factors may improve our understanding of thrombosis and guide intervention practices in SCD.
Author Srisuwananukorn, Andrew
Saraf, Santosh L.
Zhang, Xu
Han, Jin
Gowhari, Michel
Raslan, Rasha
Gordeuk, Victor R.
Shah, Binal N.
Molokie, Robert E.
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  surname: Srisuwananukorn
  fullname: Srisuwananukorn, Andrew
  organization: Sickle Cell Center, Department of Medicine, University of Illinois at Chicago, Chicago, IL
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  givenname: Rasha
  surname: Raslan
  fullname: Raslan, Rasha
  organization: Sickle Cell Center, Department of Medicine, University of Illinois at Chicago, Chicago, IL
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  givenname: Xu
  surname: Zhang
  fullname: Zhang, Xu
  organization: Sickle Cell Center, Department of Medicine, University of Illinois at Chicago, Chicago, IL
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  givenname: Binal N.
  surname: Shah
  fullname: Shah, Binal N.
  organization: Sickle Cell Center, Department of Medicine, University of Illinois at Chicago, Chicago, IL
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  surname: Han
  fullname: Han, Jin
  organization: Sickle Cell Center, Department of Medicine, University of Illinois at Chicago, Chicago, IL
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  surname: Gowhari
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  organization: Sickle Cell Center, Department of Medicine, University of Illinois at Chicago, Chicago, IL
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  givenname: Robert E.
  surname: Molokie
  fullname: Molokie, Robert E.
  organization: Sickle Cell Center, Department of Medicine, University of Illinois at Chicago, Chicago, IL
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  givenname: Victor R.
  surname: Gordeuk
  fullname: Gordeuk, Victor R.
  organization: Sickle Cell Center, Department of Medicine, University of Illinois at Chicago, Chicago, IL
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  givenname: Santosh L.
  surname: Saraf
  fullname: Saraf, Santosh L.
  email: ssaraf@uic.edu
  organization: Sickle Cell Center, Department of Medicine, University of Illinois at Chicago, Chicago, IL
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Snippet Sickle cell disease (SCD) patients are at a four- to 100-fold increased risk for thrombosis compared with the general population, although the mechanisms and...
Traditional (kidney disease) and SCD-specific (SS/Sβ0-thal, HU, low Hb F%, high WBC count, and Hb) risk factors are associated with thrombosis. Stroke...
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StartPage 1978
SubjectTerms Adult
Aged
Anemia, Sickle Cell - complications
Anemia, Sickle Cell - epidemiology
Anemia, Sickle Cell - genetics
Child
Humans
Laboratories
Red Cells, Iron, and Erythropoiesis
Retrospective Studies
Risk Factors
Thrombosis - etiology
Thrombosis - genetics
Title Clinical, laboratory, and genetic risk factors for thrombosis in sickle cell disease
URI https://www.clinicalkey.com/#!/content/1-s2.0-S2473952920313306
https://dx.doi.org/10.1182/bloodadvances.2019001384
https://www.ncbi.nlm.nih.gov/pubmed/32384541
https://www.proquest.com/docview/2400546589
https://pubmed.ncbi.nlm.nih.gov/PMC7218424
Volume 4
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