Critically Appraised Topic:
Does the use of protein-C, heparin, and hemodiafiltration improve the outcome of patients with meningococcus-induced purpura fulminans?
Appraised by: Deb Bynum, MD
Date: December 8, 1997
Clinical Bottom Lines:
1. It is felt that an acquired severe protein C deficiency in meningococcemia contributes to the pathogenesis of the thrombotic necrotic lesions in the skin and other organs and probably has an important role in the inflammatory response contributing to the overall mortality rate of over 50%.
2. In this series of 12 patients with confirmed meningococcemia and septic shock, widespread purpura, skin necrosis and DIC, the treatment with protein-C concentrate in all 12 patients, intravenous heparin in 11 patients, and hemodiafiltration in 9 patients was associated with a 0% mortality.
3. Two patients had lower-limb amputations, one of whom had a thrombotic CVA. It was noted that both of these patients had received the protein-C concentrate and heparin later than the rest of the group (60 hrs vs 12 hrs).
4. One patient developed chronic renal failure (despite receiving protein C infusion within the first 16 hrs of admission).
5. No adverse reactions to the treatment were seen.
6. The 12 patients included all had low protein-C concentrations documented prior to treatment.
7. Antithrombin concentrations were below the normal range in 11 of the 12 patients, but antithrombin III concentrate was only used in one patient who had a level of 29 IU/mL because of the observation that heparin is only effective if the antithrombin concentrations are above 35 IU/mL.
1. Nonrandomized, noncontrolled study of 12 patients who had a definitive microbiological diagnosis of meningococcemia with septic shock, purpura fulminans, skin necrosis, DIC, and low protein C concentrations. All patients received received protein-C concentrate; patients received heparin to achieve a PTT INR of 1.5-2.0, antithrombin III concentrate if level less than 35, and hemodiafiltration if clinically needed. Protein-C was given to keep the level within a normal range and platelet and cryoprecipitate was given to keep platelets and fibrinogen levels up. The main outcomes were as above.
1. Although these 12 patients had a better than expected outcome given their severity of presentation, there is no control group and no randomization to make a conclusion about the degree of benefit of treatment.
2. It is not possible to determine whether treatment with protein-C, heparin, hemodiafiltration, cryoprecipitate, or platelets or some combination of these are responsible for the results seen.
3. This approach would be difficult in practice and would require consultation and much expense with following levels of all factors, protein-c, antithrombin III, and fibrinogen -- however, these patients are young, usually otherwise healthy, and in this study had the opportunity to make full recoveries.
Smith OP, White B, Vaughan D, Rafferty M, Claffey L, Lyons B, Casey W. Use of protein-C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans. Lancet. 1997: 350: 1590-93.