What are the available treatment options and supporting evidence to treat Purpura Fulminans in critical ill patients?

Comment by InpharmD Researcher

The available treatment options for purpura fulminans (PF) include supportive care and comprehensive treatments to curb the underlying cause and manage complex coagulopathy. The most common type of PF is acute infectious PF, occurring with sepsis and requiring appropriate antimicrobials, consideration for IVIG, and management of the underlying coagulopathy. Additional treatments for PF include anticoagulants and replacement of depleted blood and/or factors including protein C concentrate (available as Ceptrotin), blood products, or therapeutic plasma exchange. A multidisciplinary approach to mitigate the severe thrombotic and inflammatory manifestations including thrombosis, disseminated intravascular coagulation (DIC), and circulatory collapse may include a combination of medications, wound care, and surgeries. The supporting evidence to guide the treatment decisions for PF is limited to small observational studies and case reports lacking robust methodology.

Background

Several review articles aimed to discuss the etiology, diagnosis, and management of purpura fulminans (PF) to help guide clinical practice. Purpura fulminans is multifaceted, necessitating prompt diagnosis and comprehensive treatment strategies to curb the underlying cause and manage complex coagulopathy. Initial treatment includes supportive care and adequate hydration. Anticoagulation and replacement of blood, factors, and platelets may be required. Proposed treatments include Protein C (PC) concentrate, heparin, and therapeutic plasma exchange (TPE), all aimed at addressing the underlying coagulopathy. Ceprotin is available as the only PC concentrate in the United States. Cases of infectious PF require broad-spectrum antibiotics and consideration for intravenous immunoglobulin (IVIG) therapy. Medical management emphasizes the importance of timely intervention, leveraging a combination of anticoagulants and supportive therapies to mitigate the severe thrombotic and inflammatory manifestations of PF while data supporting the treatment options for PF are limited to small studies lacking robust methodology. [1], [2]

Children presenting with PF are initially assumed to have a septic cause and managed with full supportive care, urgent broad-spectrum antimicrobials, and adjunctive therapy. Fresh frozen plasma (FFP) is required in those with DIC, a potentially lethal complication of PF, at doses of 10–20 mL/kg every 8–12 hours. This intervention aims to replenish pro-coagulant and anticoagulant plasma proteins consumed during the DIC process. The treatment protocol may also include transfusions of platelet concentrates (10–15 mL/kg) or cryoprecipitate (5 mL/kg) for significant thrombocytopenia or hypofibrinogenemia, respectively. Empiric FFP is appropriate for other scenarios such as postinfectious PF and suspected severe heritable protein C (PC) or Protein S (PS) deficiency prior to definitive diagnosis. In scenarios where PF arises post-infection, the increased autoimmune clearance of PS might render FFP ineffective in achieving therapeutic plasma levels of protein S, prompting consideration for plasma exchange and immunosuppressive therapy. The role of Ceprotin in children with PF and severe sepsis remains unknown. Ceprotin has demonstrated safety and efficacy in the prevention of PF in severe heritable PC deficiency and may minimize FFP exposure. Anticoagulation should be used with caution but is usually necessary with acute PF with large vessel thrombosis and severe heritable PC deficiency. [3]

The challenge in treating PF underscores the urgency of its recognition and the rapid initiation of a comprehensive management strategy, balancing the aggressive replacement of depleted factors with meticulous attention to the potential for fluid overload and allergenic or immunologic responses to transfusions. The overarching goal in acute PF management is to prevent the progression of thrombotic injury while stabilizing or correcting DIC and preventing new lesions, adjusting the intensity of therapy based on the evolving clinical scenario and laboratory markers. The complexity of PF treatment, especially in children, stresses the necessity for careful consideration of the risks and benefits associated with specific therapeutic interventions, including the controversial use of recombinant PC concentrates in septic pediatric patients. Given the lack of large, well-designed clinical trials, future robust evidence is warranted to provide definitive guidance for the management of PF. [2], [3]

References:

[1] Perera TB, Murphy-Lavoie HM. Purpura Fulminans. In: StatPearls. Treasure Island (FL): StatPearls Publishing; July 17, 2023.
[2] Colling ME, Bendapudi PK. Purpura Fulminans: Mechanism and Management of Dysregulated Hemostasis. Transfus Med Rev. 2018;32(2):69-76. doi:10.1016/j.tmrv.2017.10.001
[3] Chalmers E, Cooper P, Forman K, et al. Purpura fulminans: recognition, diagnosis and management. Arch Dis Child. 2011;96(11):1066-1071. doi:10.1136/adc.2010.199919

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

What are the available treatment options and supporting evidence to treat Purpura Fulminans in critical ill patients?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→



Please see Tables 1-2 for your response.


 

Enter title in bold, with all first words capitalized, and without a reference number

Design

Objective terms describing the type of study (randomized, uncontrolled, retrospective, placebo-controlled, cross-over, etc.); N= (total subjects)

Objective

State the objective (purpose) of the study using the author’s language(usually beginning with “To” and without a period, assuming a non-complete sentence)

Study Groups

Only the separate groups and their cohort number (n) should be listed. You can describe more details of the cohorts in the methods section so this section can stay very succinct.

Inclusion Criteria

Include relevant inclusion criteria (not a comprehensive list).

Exclusion Criteria

Include relevant exclusion criteria (not a comprehensive list).

Methods

This is our most important section. Data collection and any other information needed to understand the results is presented. Any loose ends from all other sections are tied up here, as concisely as possible.

Duration

Include the duration of the trial as a whole, as well as the duration of the interventions.

Outcome Measures

If the primary outcome measure isn’t explicit from the study, all outcome measures applicable to the inquiry can be listed in this section. If the primary outcome measure is explicit, then make separate sections for ‘Primary’ and ‘Secondary’ Outcome Measures.  


All outcome measures listed should correlate directly/exactly with the results presented later.

Baseline Characteristics

 

A

B

 

Age, years

     

Female

     

White

     

---

     

Include relevant baseline characteristics that will provide a general (big picture) view of the patients in the study.

Results

Endpoint

A

B

p-Value

----

     

----

     

All results listed should correlate directly/exactly with the outcome measures presented previously.Results that do not have to do with the inquiry should not be included; just the stated outcomes need corresponding results.


Tables are encouraged to display the most info using the least space/words.

Adverse Events

Common Adverse Events: (or those deemed frequent; if not listed in study, use N/A or “Not disclosed”)

Serious Adverse Events: (or those deemed high risk; if not listed in study, use N/A or “Not disclosed”)

Percentage that Discontinued due to Adverse Events: (if not listed in study, use N/A or “Not disclosed”)

Study Author Conclusions

Copy and paste the author’s conclusions on the question at hand, using full sentences. Don’t include any conclusions that don’t correspond to results we list.

InpharmD Researcher Critique

As the expert, add 1-2 sentences on strengths, weaknesses, and takeaways from this study. Focus on insight as “more research is needed” is obvious.



References:

Manco-Johnson MJ, Bomgaars L, Palascak J, et al. Efficacy and safety of protein C concentrate to treat purpura fulminans and thromboembolic events in severe congenital protein C deficiency. Thromb Haemost. 2016;116(1):58-68. doi:10.1160/TH15-10-0786

 

Enter title in bold, with all first words capitalized, and without a reference number

Design

Objective terms describing the type of study (randomized, uncontrolled, retrospective, placebo-controlled, cross-over, etc.); N= (total subjects)

Objective

State the objective (purpose) of the study using the author’s language(usually beginning with “To” and without a period, assuming a non-complete sentence)

Study Groups

Only the separate groups and their cohort number (n) should be listed. You can describe more details of the cohorts in the methods section so this section can stay very succinct.

Inclusion Criteria

Include relevant inclusion criteria (not a comprehensive list).

Exclusion Criteria

Include relevant exclusion criteria (not a comprehensive list).

Methods

This is our most important section. Data collection and any other information needed to understand the results is presented. Any loose ends from all other sections are tied up here, as concisely as possible.

Duration

Include the duration of the trial as a whole, as well as the duration of the interventions.

Outcome Measures

If the primary outcome measure isn’t explicit from the study, all outcome measures applicable to the inquiry can be listed in this section. If the primary outcome measure is explicit, then make separate sections for ‘Primary’ and ‘Secondary’ Outcome Measures.  


All outcome measures listed should correlate directly/exactly with the results presented later.

Baseline Characteristics

 

A

B

 

Age, years

     

Female

     

White

 Veldman A, Fischer D, Wong FY, et al. Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients. Crit Care. 2010;14(4):R156. doi:10.1186/cc9226  Veldman A, Fischer D, Wong FY, et al. Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients. Crit Care. 2010;14(4):R156. doi:10.1186/cc9226  

---

     

Include relevant baseline characteristics that will provide a general (big picture) view of the patients in the study.

Results

Endpoint

A

B

p-Value

----

     

----

     

All results listed should correlate directly/exactly with the outcome measures presented previously.Results that do not have to do with the inquiry should not be included; just the stated outcomes need corresponding results.


Tables are encouraged to display the most info using the least space/words.

Adverse Events

Common Adverse Events: (or those deemed frequent; if not listed in study, use N/A or “Not disclosed”)

Serious Adverse Events: (or those deemed high risk; if not listed in study, use N/A or “Not disclosed”)

Percentage that Discontinued due to Adverse Events: (if not listed in study, use N/A or “Not disclosed”)

Study Author Conclusions

Copy and paste the author’s conclusions on the question at hand, using full sentences. Don’t include any conclusions that don’t correspond to results we list.

InpharmD Researcher Critique

As the expert, add 1-2 sentences on strengths, weaknesses, and takeaways from this study. Focus on insight as “more research is needed” is obvious.



References:

Veldman A, Fischer D, Wong FY, et al. Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients. Crit Care. 2010;14(4):R156. doi:10.1186/cc9226