학술논문
Constitutive hypercoagulability in pediatric sickle cell disease patients with hemoglobin SS genotype.
Document Type
Academic Journal
Author
Sussman RG; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.; Mburu J; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.; Steele M; Department of Pediatrics, Section of Pediatric Hematology, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada.; Bang A; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, Ontario, Canada.; Friedman J; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.; Goldman R; Division of Clinical Pharmacology and Pediatric Emergency Medicine, Department of Pediatrics, British Columbia Children's Hospital, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada.; Kirby M; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.; Rand ML; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.; Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.; Blanchette VS; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.; Pluthero FG; Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.; Williams S; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.; Kahr WHA; Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.; Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.; Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada.; Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Source
Publisher: Elsevier Country of Publication: United States NLM ID: 101703775 Publication Model: eCollection Cited Medium: Internet ISSN: 2475-0379 (Electronic) Linking ISSN: 24750379 NLM ISO Abbreviation: Res Pract Thromb Haemost Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
Background: Constitutive inflammation and hemostatic activation have been identified as key contributors to the pathophysiology of sickle cell disease (SCD), leading to clinical consequences such as vaso-occlusive crises and stroke. Patients with hemoglobin SS (HbSS) and hemoglobin SC (HbSC) genotypes are reported to have different symptoms, as do patients in steady-state and crisis situations. Differences among these groups remain unclear in pediatric patients.
Objectives: To compare hemostatic activity in HbSS and HbSC pediatric patients during steady state, in crisis, and in clinical follow-up and compare HbSS and HbSC patients with normal healthy children.
Methods: Whole-blood coagulation assay thromboelastography (TEG) was used to assess hemostatic activity. In parallel, flow cytometry was used to assess procoagulant surface expression of platelets and red blood cells.
Results: TEG results indicated no significant differences in clotting onset (R time), clot maximum amplitude, or maximum rate of thrombus generation among steady-state, crisis, and follow-up subgroups of HbSS and HbSC patients. TEG parameters did not differ significantly between HbSC patients and healthy children, while HbSS patients showed significantly shorter R time and greater maximum amplitude and maximum rate of thrombus generation, all indicative of a constitutive hypercoagulable state. Flow cytometry results did not detect increased platelet integrin αIIb β 3 activation or red blood cell procoagulant surface expression in SCD patients compared with unaffected children.
Conclusion: Our results indicate that pediatric SCD patients with the HbSS genotype have constitutively activated hemostasis relative to HbSC patients and healthy children. It remains to be determined how treatments that improve clinical outcomes in SCD patients affect this constitutively hypercoagulable state.
(© 2024 The Author(s).)
Objectives: To compare hemostatic activity in HbSS and HbSC pediatric patients during steady state, in crisis, and in clinical follow-up and compare HbSS and HbSC patients with normal healthy children.
Methods: Whole-blood coagulation assay thromboelastography (TEG) was used to assess hemostatic activity. In parallel, flow cytometry was used to assess procoagulant surface expression of platelets and red blood cells.
Results: TEG results indicated no significant differences in clotting onset (R time), clot maximum amplitude, or maximum rate of thrombus generation among steady-state, crisis, and follow-up subgroups of HbSS and HbSC patients. TEG parameters did not differ significantly between HbSC patients and healthy children, while HbSS patients showed significantly shorter R time and greater maximum amplitude and maximum rate of thrombus generation, all indicative of a constitutive hypercoagulable state. Flow cytometry results did not detect increased platelet integrin α
Conclusion: Our results indicate that pediatric SCD patients with the HbSS genotype have constitutively activated hemostasis relative to HbSC patients and healthy children. It remains to be determined how treatments that improve clinical outcomes in SCD patients affect this constitutively hypercoagulable state.
(© 2024 The Author(s).)