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

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.

The risk of arterial thrombosis in carriers of natural coagulation inhibitors: a prospective family cohort study

“…These findings are consistent with those obtained in investigations that addressed the risk of subsequent VTE in the same settings [2,3]. In our recent prospective observation, the incidence of spontaneous thrombosis and that related to risk periods these incidences were 1.2% (0.9-1.7) and 21.2%(13.1-32.4), respectively [13]. These results provide further compelling evidence in support of the association between venous and arterial thrombotic complications [6].…”

“…Our study results add to the growing evidence that inherited thrombophilia is likely to increase not only the risk of VTE [13], but also of that of atherothrombosis and its complications. They are consistent with those found in the EPCOT study (0.18% in deficient subjects vs 0.03% in the control group) [10] and with those found by Mahmoodi et al (0.32% in deficient subjects vs 0.19% in non-deficient subjects) in two retrospective family cohort studies on the risk of ATE in carriers of hereditary deficiencies of protein C, protein S, or antithrombin [11].…”

“…After a follow-up of 4240 patient-years in the carriers group and 3810 in the non-carriers, the mean observation time in each group was 12 years (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). ATE occurred in 19 and 7 subjects, respectively, accounting for an annual incidence of 0.45% (95% CI 0.3-0.7) and 0.18% (95%, CI 0.07-0.4) patient-years, respectively; as shown in Table 2, among carriers ATE developed in 1 (1.3%) of the family members with AT deficiency, in 8 (6%) of those with PC defects, and in 10 (8%) of those with PS defects.…”

“…The rate of events occurring in carriers was compared with that occurring in non-carriers. In the same cohort, we have previously reported the data on the risk of venous thromboembolism (VTE) [13]. This article is not currently available.…”

Protein C or Protein S deficiency associates with paradoxically impaired platelet‐dependent thrombus and fibrin formation under flow

“…The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Padova University Hospital (protocol code 4303/AO/17; July 28, 2017). Patients with known deficiency of plasma protein C ( n = 12) or protein S ( n = 11) were enrolled among the cohort of patients previously referred to the Thrombotic Unit of Padova University Hospital for thrombophilia screening and identified as thrombophilia carriers 5 . Inclusion criteria were age >18 years, documented protein C or protein S deficiency, availability to come to our center the day of the study.…”