Idiopathic purpura fulminans (IPF) is a rare but severe pro-thrombotic coagulation disorder that can occur after chickenpox or HHV6 infection. IPF leads to an autoantibody-mediated decrease in the protein S plasma concentration. We conducted a retrospective multicenter study involving IPF patients from 13 French pediatric centers and a systematic review of literature-published cases. Eighteen patients were included in our case series, and thirty-four as literature review cases. The median age was 4.9 years and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 (94%) patients with typical lesions. A recent history of VZV or HHV6 infection was present in 41 (78%) and 7 (14%) of cases, respectively. Most of the patients received heparin (n=51, 98%) and fresh frozen plasma transfusions (n=41, 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis appeared to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.

IntroductionIdiopathic purpura fulminans (IPF) is a rare and severe coagulation disorder, associated with transient anti-protein S (anti-PS) antibodies in the context of post-viral infection such as varicella. Anti-protein S antibodies are frequently found in the context of varicella, in contrast with the rarity of IPF. Other factors such as anti-phospholipid antibodies (APL) and inherited thrombophilia may be associated with severe vascular complication.MethodThis is an ancillary study of a French multicenter retrospective series and systematic review of literature. We analyzed patients who were tested for inherited thrombophilia, namely antithrombin, protein C, protein S deficiency; prothrombin gene G20210A polymorphism (FII:G20210A),Factor V R506Q polymorphism (FV:R506Q); and/or for APL (lupus anticoagulant (LA), anti-cardiolipin antibodies (ACL), or anti-beta 2-GPI antibodies (Aβ2GP1).ResultsAmong the 25 patients tested for inherited thrombophilia, 7 (28%) had positive results. Three had FV R506Q, two FII:G20210A, one compound heterozygote FV:R506Q associated to FII:G20210A, and one protein C deficiency. APL testing was performed in 32 patients. It was positive in 19 patients (59%): 17 ACL (53%), 5 LA (16%), 4 Aβ2GP1 (13%). The risk of severe complications was not associated with presence of inherited thrombophilia or APL presence, with RR: 0.8 [95% CI: 0.37–1.71], p = 1 and RR: 0.7 [95% CI: 0.33–1.51], p = 0.39, respectively. We found a high prevalence of inherited thrombophilia or APL in a population of patients with IPF. However, we do not find an association with the occurrence of severe vascular complications or venous thromboembolism.