Clinical Pearls & Morning Reports
Published March 10, 2021
Purpura fulminans is a medical emergency. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: What types of bacterial infection are most commonly associated with acute infectious purpura fulminans?
A: Acute infectious purpura fulminans is an extremely thrombotic type of disseminated intravascular coagulation that is most commonly associated with invasive infection with Neisseria meningitidis, Streptococcus pneumoniae, or Capnocytophaga canimorsus.
Q: What are some of the clinical and laboratory features of purpura fulminans?
A: Purpura fulminans results from uncontrolled systemic thrombosis triggered by a maladaptive inflammatory response in the host, leading to the triad of severe consumptive coagulopathy, systemic inflammatory response syndrome (SIRS), and purpuric rash. The onset of illness is extremely rapid, with a reticular rash and skin mottling often occurring in the early stages and life-threatening SIRS and coagulopathy usually developing within 24 hours or less. Patients with purpura fulminans typically have a low or pseudonormal fibrinogen level in the presence of overwhelming inflammatory stimuli. In some patients, profound hypofibrinogenemia results in decoupling of the C-reactive protein level and the erythrocyte sedimentation rate, with an isolated increase in the C-reactive protein level and a disproportionately low erythrocyte sedimentation rate. Low levels of the endogenous anticoagulants proteins C and S and antithrombin are features of purpura fulminans.
A: The management of acute infectious purpura fulminans is based on our understanding of the mechanisms underlying the disease process, which remains incomplete. However, we know that purpura fulminans is associated with a severe inflammatory reaction that results in diffuse activation of coagulation and failure of endogenous anticoagulant mechanisms, in particular the protein C system. Thrombomodulin, a crucial cofactor for the activation of protein C, is lost from the endothelium. Therefore, rapid repletion of protein C and antithrombin is needed to reverse these processes. It is important to note that immediate therapy is key. Protein C repletion may have a benefit only within 48 to 72 hours after the first symptoms of purpura fulminans develop, owing to the diminishing retention of thrombomodulin on the vascular endothelium. Protein C repletion has been associated with an increase in survival among patients with purpura fulminans, as well as with a reduction in tissue loss and in amputation procedures among survivors.
A: Fresh-frozen plasma provides balanced repletion of coagulation factors. Once target levels of protein C and antithrombin (>70% for each) are sustainably achieved through the administration of fresh-frozen plasma and factor concentrates, maintenance therapy can consist of fresh-frozen plasma alone, with a slow taper in the volume of plasma administered each day. Despite the underlying coagulopathy, patients with purpura fulminans benefit from the use of therapeutic heparin. Intravenous unfractionated heparin should be administered aggressively in patients with purpura fulminans, regardless of any derangements on laboratory coagulation testing.