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. 2020 Nov 10;4(21):5442-5448.
doi: 10.1182/bloodadvances.2020002781.

Incidence of VTE in asymptomatic children with deficiencies of antithrombin, protein C, and protein S: a prospective cohort study

Daniela Tormene  1 , Elena Campello  1 , Chiara Simion  1 , Giacomo Turatti  1 , Michelangelo Marobin  1 , Claudia Maria Radu  1 , Anna Pontarin  1 , Paolo Prandoni  2 , Paolo Simioni  1
Affiliations

Incidence of VTE in asymptomatic children with deficiencies of antithrombin, protein C, and protein S: a prospective cohort study

Daniela Tormene et al. Blood Adv. .

Abstract

Although antithrombin, protein C, and protein S defects are well-recognized inherited risk factors for venous thromboembolism (VTE) in adults, whether they predispose children to these vascular disorders as well is undefined. In a prospective cohort study, we assessed the incidence of spontaneous and risk period-related VTE in children who were family members of adults who, after an episode of symptomatic VTE, had then been identified as carriers of these abnormalities. A total of 134 children from 87 families were enrolled. Seventy (51.5%) of these children were carriers of an inherited defect, and the remaining 64 were not; the mean observation period was 4 years (range, 1-16 years) and 3.9 years (range, 1-13), respectively. Sixteen risk periods were experienced by carriers, and 9 by noncarriers. Six VTE occurred in the 70 carriers during 287 observation-years, accounting for an annual incidence of 2.09% patient-years (95% confidence interval, 0.8-4.5), compared with none in the 64 noncarriers during 248 observation-years. Of the 14 children with thrombophilia who experienced a risk period for thrombosis, 4 (28.6%) developed a VTE episode. The overall incidence of risk-related VTE was 25% per risk period (95% confidence interval, 6.8-64). In conclusion, the thrombotic risk in otherwise healthy children with severe inherited thrombophilia does not seem to differ from that reported for adults with the same defects. Screening for thrombophilia in children who belong to families with these defects seems justified to identify those who may benefit from thromboprophylaxis during risk periods for thrombosis.

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Conflict of interest statement

Conflicts-of-interest disclosure: The authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Family cohorts with hereditary antithrombin, protein C, or protein S deficiencies. *Deep vein thrombosis at 14 years of age after a posttraumatic fracture of the lower limbs (antithrombotic prophylaxis was not used in this circumstance). †Idiopathic VTE event at 8 years of age. ‡Thrombosis of the cerebral venous sinuses after birth.
Figure 2.
Figure 2.
The cumulative incidence of VTE between carriers and noncarriers.
Figure 3.
Figure 3.
The incidence of thrombosis according to years of life.
Figure 4.
Figure 4.
The cumulative incidence of VTE, according to years of age, between carriers and noncarriers.
See this image and copyright information in PMC

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