Background: Multiple investigators have described an increased incidence of thromboembolic events in SARS-CoV-2-infected individuals. Data concerning hemostatic complications in children hospitalized for COVID-19/multisystem inflammatory syndrome in children (MIS-C) are scant. Objectives: To share our experience in managing SARS-CoV-2-associated pro-coagulant state in hospitalized children. Methods: D-dimer values were recorded at diagnosis in children hospitalized for SARS-CoV-2-related manifestations. In moderately to critically ill patients and MIS-C cases, coagulation and inflammatory markers were checked at multiple time points and median results were compared. Pro-thrombotic risk factors were appraised for each child and thromboprophylaxis was started in selected cases. Results: Thirty-five patients were prospectively enrolled. D-dimer values did not discriminate COVID-19 of differing severity, whereas were markedly different between the COVID-19 and the MIS-C cohorts. In both cohorts, D-dimer and C-reactive protein levels increased upon clinical worsening but were not accompanied by decreased fibrinogen or platelet values, with all parameters returning to normal upon disease resolution. Six patients had multiple thrombotic risk factors and were started on pharmacological thromboprophylaxis. No deaths or thrombotic or bleeding complications occurred. Conclusions: COVID-19 pediatric patients show mildly altered coagulation and inflammatory parameters; on the other hand, MIS-C cases showed laboratory signs of an inflammatory driven pro-coagulant status. Universal anticoagulant prophylaxis in hospitalized children with SARS-CoV-2-related manifestations is not warranted, but may be offered to patients with other pro-thrombotic risk factors in the context of a multi-modal therapeutic approach.

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Sepsis related coagulopathy ranges from mild laboratory alterations up to severe disseminated intravascular coagulation (DIC). There is evidence that DIC is involved in the pathogenesis of microvascular dysfunction contributing to organ failure. Additionally, the systemic activation of coagulation, by consuming platelets and coagulation factors, may cause bleeding. Thrombin generation via the tissue factor/factor VIIa route, contemporary depression of antithrombin and protein C anticoagulant systems, as well as impaired fibrin degradation, due to high circulating levels of PAI-1, contribute to enhanced intravascular fibrin deposition. This deranged coagulopathy is an independent predictor of clinical outcome in patients with severe sepsis. Innovative supportive strategies aiming at the inhibition of coagulation activation should comprise inhibition of tissue factor-mediated activation or restoration of physiological anticoagulant pathways, as the administration of recombinant human activated protein C or concentrate. In spite of some promising initial studies, additional trials are needed to define their clinical effectiveness in adults and children with severe sepsis.

Functional evaluation identified changes in gait pattern in patients with severe and moderate haemophilia, compared with normal values. Gait analysis may be a useful tool to facilitate early diagnosis of joint damage, prevent haemophilic arthropathy, design a personalized rehabilitative treatment and monitor functional status over time.

Introduction FVIII inhibitor development is the most serious contemporary treatment complication in haemophilia A, particularly in previously untreated patients (PUPs). No inhibitors developed in clinical trials in previously treated patients treated with simoctocog alfa (Nuwiq), a fourth-generation recombinant FVIII produced in a human cell line. Methods The NuProtect study investigated the immunogenicity of simoctocog alfa in PUPs. NuProtect was a prospective, multinational, open-label, non-controlled, phase III study. PUPs with severe haemophilia A (FVIII:C <1%) of any age and ethnicity were treated with simoctocog alfa for 100 exposure days or a maximum of 5 years. Patients were true PUPs without prior exposure to FVIII concentrates or blood components. Inhibitor titres were measured with the Nijmegen-modified Bethesda assay; cut-off for positivity was 0.6 BU mL−1 (≥0.6 to <5 low-titre, ≥5 high titre). Results A total of 108 PUPs with a median age at first treatment of 12.0 months (interquartile range: 8.0–23.5) were treated with simoctocog alfa. F8 mutation type was known for 102 patients (94.4%) of whom 90 (88.2%) had null F8 mutations and 12 (11.8%) had non-null mutations. Of 105 PUPs evaluable for inhibitor development, 28 (26.7%) developed inhibitors; 17 high titre (16.2%) and 11 low titre (10.5%). No PUPs with non-null F8 mutations developed inhibitors. Conclusion In the NuProtect study, the rate of inhibitor development in PUPs with severe haemophilia A treated with simoctocog alfa was lower than the rate reported for hamster-cell-derived recombinant factor VIII products in other recent clinical trials. No inhibitors were reported in PUPs with non-null F8 mutations.