THROMB-HEM study: detection of venous thrombosis depending on the type of underlying disease

Backgrond. Venous thrombotic episodes (VTE), both symptomatic (sVTE) and asymptomatic (aVTE), are not uncommon complications of the course and therapy of malignant diseases in children. While the largest number of studies in children is devoted to the problem of VTE in acute lymphoblastic leukemia (ALL), the incidence of thrombotic events in other types of blood diseases remains poorly studied.

The aim of the study – to evaluate the incidence of VTE in children with hemoblastosis and bone marrow aplasia depending on the underlying disease by event-based survival analysis.

Materials and methods. The current study was prospective monocenter observational in nature. We analyzed the cumulative probability of detection (CPD) of VTE, aVTE and cVTE in 1623 pediatric patients hospitalized at the Dmitry Rogachev Center from 01.01.2013 to 31.12.2017.

Results. The 3-year incidence of VTE was 34.8 % (95 % confidence interval (CI) 31.3–38.7). The majority of VTE presented as aVTE: 3-year CPD 28.9 %; 95 % CI 25.7–32.5, and the 3-year CPD with aVTE was more than 3-fold lower: 3-year CPD 8.2 %; 95 % CI 5.8–11.5. While the highest incidence of aVTE was found in children with ALL and lymphomas, followed by myeloleukemia, histiocytosis and bone marrow aplasia. The majority of sVTE episodes were diagnosed in lymphomas followed by ALL, myeloleukemia and histiocytosis.

More than half of sVTE episodes were diagnosed in the first 6 months of treatment, with most episodes in children with lymphomas and myeloleukemia diagnosed in the first 3 months.

Conclusion. The highest incidence of VTE episodes was found in patients with ALL and lymphomas, with most episodes diagnosed in the first 3 months of treatment. The CPD for detecting sVTE in the first 3 months after hospitalization in patients with histiocytosis is comparable to that in ALL. Further prospective studies with the formation of risk-adapted models of primary antithrombotic prophylaxis in children with blood diseases are needed.

1. Zharkov P.A., Voronin K.A., Evstratov D.A., Fedorova D.V., Pshonkin A.V., Rumyantsev A.G., Novichkova G.A. The THROMBHEM study: fi rst results and future prospects. Voprosy gematologii/ onkologii i immunopatologii v pediatrii = Pediatric Hematology/ Oncology and Immunopathology. 2022;21(2):61–5. (In Russ.).

2. Zharkov P.A., Morozova D.S., Gobadze D.A., Evstratov D.A., Fedorova D.V., Zharikova L.I., Pshonkin A.V., Novichkova G.A. Deep veins thrombosis in children with blood diseases. Onkogematologiya = Oncohematology 2019;14(1):20–30. (In Russ.).

3. Athale U.H., Nagel K., Khan A.A., Chan A.K.C. Thromboembolism in children with lymphoma. Thromb Res Thromb Res. 2008;122(4):459–65. doi: 10.1016/j.thromres.2007.12.006.

4. Gartrell J., Kaste S.C., Sandlund J.T., Flerlage J., Zhou Y., Cheng C., Estepp J., Metzger M.L. The association of mediastinal mass in the formation of thrombi in pediatric patients with non-lymphoblastic lymphomas. Pediatr Blood Cancer. 2020;67(2):e28057. doi: 10.1002/pbc.28057.

5. Zharikova L.I., Rumyantseva Yu.V., Karachunsky A.I. Thromboses in children with acute lymphoblastic leukemia (review of literature). Voprosy gematologii/ onkologii i immunopatologii v pediatrii = Pediatric Hematology/ Oncology and Immunopathology. 2015;14(3):39–47. (In Russ.).

6. Athale U., Siciliano S., Thabane L., Pai N., Cox S., Lathia A., Khan A., Armstrong A., Chan A.K.C. Epidemiology and clinical risk factors predisposing to thromboembolism in children with cancer. Pediatr Blood Cancer. 2008;51:792–7.

7. Pelland-Marcotte M.C., Pole J.D., Kulkarni K., Athale U., Stammers D., Sabapathy C., Halparin J., Brandão L.R., Sung L. Thromboembolism incidence and risk factors in children with cancer: a population-based cohort study. Thromb Haemost. 2018;118:1646–55.

8. Fedorova D.V., Zharkov P.A., Pshonkin A.V. Thrombotic occlusions on central venous catheters as a risk factor of development of deep vein catheter-associated thrombosis. Voprosy gematologii/ onkologii i immunopatologii v pediatrii = Pediatric Hematology/ Oncology and Immunopathology. 2016;15(2):20–6. (In Russ.).