Synopsis of the SapFire Registry


Sepsis-Associated Purpura Fulminans International Registry – Europe

Short title (Acronym)


Rationale and background

Purpura fulminans is the clinical manifestation of disseminated thrombosis in dermal and systemic microcirculation. This rare disease is frequently associated with multiple organ failure and represents a life-threatening condition with mortality exceeding 50 %. Apart from isolated idiopathic cases, deficiency of Protein C, a major intrinsic anti-coagulant, is considered the leading cause of Purpura fulminans. In the vast proportion of cases, the condition has been shown to emerge secondary to acquired Protein C deficiency associated with severe sepsis, mostly of meningococcal or pneumococcal origin.
A consistent therapeutic approach to sepsis-associated Purpura fulminans (SAPF) has not been established yet. With exaggerated pro-coagulant activity being confirmed as the key pathogenic aspect, several treatment modalities aiming at the balance restoration in the coagulation cascade have been considered. Based on the experience gathered in patients with inherited Protein C deficiency, supplementation with Protein C formulations has been used as adjuvant therapy in SAPF.

Most of the information on SAPF incidence and therapy has been obtained before 2004. Meanwhile, lack of comprehensive data poses considerable difficulties with regard to its diagnosis and treatment. SAPF causality might have been substantially altered in the wake of widespread meningococcal vaccination. There are neither evidence-based treatment guidelines nor comparative evaluation of the efficacy of different therapeutic approaches. Therefore there is a pronounced need of systematic data collection and evaluation covering several aspects of SAPF, such as epidemiology, causality, morbidity and therapy.

Research question and objectives

  • Systematic acquisition, analysis and dissemination of information on incidence and prehospital/inhospital course of Purpura fulminans, (possible long-term follow up) and its relation to infectious agents (e.g. meningococcemia, streptococcus etc.)
  • Systematic acquisition, analysis and dissemination of information on current management of PF (sepsis bundles and replacement strategies – protein C, AT, etc.)
  • Systematic acquisition, analysis and dissemination of information on outcomes (morbidity, mortality) of PF with current management strategies, stratified for use or non-use of protein C


Prospective multicenter registry derived from systematic data collection on the incidence and treatment of sepsis-associated Purpura fulminans


Patients diagnosed with Purpura fulminans associated with severe sepsis


  • All-cause in-hospital mortality
  • Morbidity at defined post-diagnosis intervals and over 7 consecutive days
  • – Mean total SOFA score (age > 16)
    – PELOD score (age < 16)
    - ∆SOFA or dPELOD score for day-to-day comparisons

  • Extent and severity of Purpura lesions
  • Need for reconstructive surgery (amputations, skin grafts)
  • Length of ICU stay (days)
  • Length of hospital stay (days)
  • Changes in hematological parameters
  • – WBC count
    – Thrombocyte count
    – Hemoglobin

  • Changes in coagulation parameters
  • – Prothrombin time (PT)
    – Activated partial thromboplastin time (aPTT)
    – Fibrinogen
    – D-dimers
    – Thrombin-antithrombin complex (TATc)
    – Protein C activity
    – Antithrombin III activity

  • Changes in inflammatory parameters
  • – C-reactive protein (CRP)
    – Procalcitonin (PCT)
    – Interleukin 6 (IL-6)

  • Changes in organ dysfunction parameters
  • – Glucose
    – Lactate
    – Creatine kinase (CK)

  • Duration of mechanical ventilation (days)
  • Duration of renal replacement therapy (days)
  • Vasopressor use (days/doses)
  • Sepsis-inducing pathogen
  • Adverse event related to PF treatment (reporting as per decision of the
  • – Bleeding
    – Thrombotic events

Inclusion criteria

– Diagnosis of severe sepsis and Purpura fulminans
– Signed informed consent (according to local legal regulations)

Exclusion criteria

– premature neonates (< 36 gestational week)


Approx. 30 participating centers in Germany, Austria, Ireland, UK, Italy, Spain, Netherlands (selected centers)


First patient in Q1 2015
Registry duration 3 years, with an option of prolongation
Estimated enrolment Approx. 50 patients/year
Interim Analysis Biannually