Thrombin Generation Profile Using ST-Genesia after PEG-asparaginase in Pediatric Patients with Acute Lymphoblastic Leukemia

Anna Ruiz-Llobet; Susanna Gassiot; Edurne Sarrate; Josune Zubicaray; Susana Rives; Warda Suleman; Rubén Berrueco

doi:10.1055/a-2316-4547

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2024; 124(10): 973-985
DOI: 10.1055/a-2316-4547

Stroke, Systemic or Venous Thromboembolism

Thrombin Generation Profile Using ST-Genesia after PEG-asparaginase in Pediatric Patients with Acute Lymphoblastic Leukemia

Anna Ruiz-Llobet

¹Pediatric Hematology Department, Hospital Sant Joan de Déu Barcelona, Institut de Recerca Pediàtrica, Hospital San Joan de Déu de Barcelona (IRP-HSJD), Esplugues de Llobregat, Universitat de Barcelona, Barcelona, Spain

²Instituto Nacional de Investigación Biomédica en Enfermedades Raras (CIBER ER), Instituto de Salud Carlos III, Madrid, Spain

,

Susanna Gassiot

³Laboratory of Hematology, Hospital Sant Joan de Déu Barcelona, Institut de Recerca Pediàtrica, Hospital San Joan de Déu de Barcelona (IRP-HSJD), Esplugues de Llobregat, Universitat de Barcelona, Barcelona, Spain

,

Edurne Sarrate

³Laboratory of Hematology, Hospital Sant Joan de Déu Barcelona, Institut de Recerca Pediàtrica, Hospital San Joan de Déu de Barcelona (IRP-HSJD), Esplugues de Llobregat, Universitat de Barcelona, Barcelona, Spain

,

Josune Zubicaray

⁴Servicio de Hematología y Hemoterapia, Hematología y Oncología Pediátricas, Hospital Infantil Universitario Niño Jesús, Fundación para la Investigación Biomédica del Hospital Infantil Universitario Niño Jesús, Madrid, Spain

,

Susana Rives

²Instituto Nacional de Investigación Biomédica en Enfermedades Raras (CIBER ER), Instituto de Salud Carlos III, Madrid, Spain

⁵Hematology and Oncology, Leukemia and Lymphoma Department, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Déu de Barcelona, Esplugues de Llobregat, Institut de Recerca Pediàtrica, Hospital San Joan de Déu de Barcelona (IRP-HSJD), Esplugues de Llobregat, Barcelona, Spain

,

Warda Suleman

³Laboratory of Hematology, Hospital Sant Joan de Déu Barcelona, Institut de Recerca Pediàtrica, Hospital San Joan de Déu de Barcelona (IRP-HSJD), Esplugues de Llobregat, Universitat de Barcelona, Barcelona, Spain

,

Rubén Berrueco

¹Pediatric Hematology Department, Hospital Sant Joan de Déu Barcelona, Institut de Recerca Pediàtrica, Hospital San Joan de Déu de Barcelona (IRP-HSJD), Esplugues de Llobregat, Universitat de Barcelona, Barcelona, Spain

²Instituto Nacional de Investigación Biomédica en Enfermedades Raras (CIBER ER), Instituto de Salud Carlos III, Madrid, Spain

› Author Affiliations

Abstract

Background Venous thromboembolism (VTE) etiology in children with acute lymphoblastic leukemia (ALL) is multifactorial. The use of global assays of hemostasis as a thrombin generation test (TGT) is useful to individualize VTE risk in adult patients. This prospective cohort study aimed to evaluate the usefulness of an automated TGT to evaluate VTE risk during ALL treatment in children.

Methods TGT (automated analyzer ST Genesia; ThromboScreen) and pro- and anticoagulant plasma proteins were analyzed during ALL treatment in pediatric patients following LAL-SEHOP-PETHEMA-2013 guidelines. Results were compared with a series of pediatric normal controls and evaluated according to pegylated asparaginase PEG-ASP administration and to VTE risk factors.

Results The study included 67 patients: males n = 35, B-ALL (n = 60). None had a VTE during the evaluated period. Compared to healthy controls, the normalized endogenous thrombin potential (N-ETP) ratio in patients was higher and ETP inhibition (ETP-inh) was lower, especially after PEG-ASP administration. Plasmatic protein C and protein S levels decreased after PEG-ASP administration, but antithrombin mean level did not. A bivariant analysis showed that ETP-inh was lower in patients >10 years old (p = 0.05) and in those with non-O blood type (p = 0.005). A linear mixed model also showed a higher TGT prothrombotic profile in patients with inherited thrombophilia.

Conclusion TGT could be a biomarker of a high VTE risk in ALL pediatric patients. Non-O blood group and inherited thrombophilia were associated with a significantly higher thrombotic profile, and an increased profile was also observed after administration of PEG-ASP.

Keywords

acute lymphoblastic leukemia - children - thrombosis - thrombin generation - physiological anticoagulants

Full Text

References

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Supplementary Material

Supplementary Material