Next-line protocol

Severe Protein C Deficiency with Disseminated Intravascular Coagulation or Purpura Fulminans: Next Step When Protein C Concentrate Fails to Reach Target Levels

This protocol addresses severe protein C deficiency presenting with disseminated intravascular coagulation (DIC), purpura fulminans, or acute venous thromboembolism, in the specific situation where first-line therapy has not achieved the required targets.

Clinical scenario

Severe protein C deficiency — defined by protein C activity below 1 IU/dL — presenting with disseminated intravascular coagulation, purpura fulminans, or acute venous thromboembolism. This rare autosomal recessive disorder typically manifests in the neonatal period with purpura fulminans and severe DIC, often with concomitant venous thromboembolism.

First-line treatment — escalation trigger

The preceding line used protein C concentrate (initial bolus followed by repeat dosing every 6–12 h) with therapeutic anticoagulation; where concentrate was unavailable, fresh frozen plasma was given as a bridge with the same anticoagulation. Escalation to this protocol is indicated when the following goals are not met: a protein C activity trough of 50 IU/dL (or greater than 10 IU/dL trough while on fresh frozen plasma), decreasing or normalisation of D-dimer, and target anti-Xa activity on the anticoagulation regimen in use.

Next-line approach — partial overview

When protein C concentrate has not achieved required activity levels, a recombinant alternative has been used in this setting to control purpura fulminans and support protein C activity. The complete structured regimen — including agent, dosing, monitoring parameters, and escalation criteria — is available in the full protocol below.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1111/j.1365-2516.2008.01838.x
Severe protein C deficiency (i.e. protein C activity <1 IU dL⁻¹) is a rare autosomal recessive disorder that usually presents in the neonatal period with purpura fulminans (PF) and severe disseminated intravascular coagulation (DIC), often with concomitant venous thromboembolism (VTE).
Severe protein C deficiency who have DIC or acute thrombosis can be treated acutely with an initial bolus of 100 IU kg⁻¹ followed by 50 IU kg⁻¹ every 6 h.
Recombinant APC (Xigris; Eli Lilly, Indianapolis, IN, USA) has been used by the authors to treat PF in a child with severe protein C deficiency.
Recombinant APC, administered at a dose of 24 μg kg⁻¹ h⁻¹ (the regimen recommended for sepsis), resulted in a plasma protein C activity of 5 IU dL⁻¹ and has been variably effective in controlling PF.

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