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Differences between purpura fulminans due to Severe Congenital Protein C Deficiency or due to acquired protein C deficiency

Protein C Deficiency: Is It Acquired or Congenital ?

Determining the root cause of purpura fulminans

Ruling out ACQUIRED Protein C (PC) DEFICIENCY as a cause of purpura fulminans (PF)

Diagnosing Severe Congenital Protein C Deficiency (SCPCD) as a root cause of neonatal PF can be difficult. This is a result of the correlation between Disseminated Intravascular Coagulation (DIC) and severe acute infections, sepsis, and SCPCD.1

For proper diagnosis of SCPCD, determining the underlying cause of PF is crucial.1,2

 

acquired VS. congenital protein C (PC) deficiency: Differences in clinical and laboratory findings

PF due to
ACQUIRED PC DEFICIENCY

SKIN LESIONS THAT:1

  • Develop in distal extremities and progress proximally
  • Appear as a generalized or diffuse rash affecting entire body surface

UNDETECTABLE PROTEIN C LEVELS1,**

ISOLATION OF CAUSATIVE AGENT1

e.g., Neisseria meningitides, streptococcus pneumoniae, Group A and B streptococci, etc.1

LABORATORY EVIDENCE OF A SEVERE ACUTE PHASE REACTION1

RESPONSE TO ANTIMICROBIAL THERAPY1

 

 

PF due to
SCPCD

SKINS LESIONS THAT:1

  • Develop on the lower limbs and male genitalia*
  • Form at pressure points, such as the heels and buttocks

UNDETECTABLE PROTEIN C LEVELS2,3,**

  • In carriers of a protein C mutation, protein S levels are higher than non-carriers4

CEREBRAL VENOUS THROMBOSIS1

Blindness arising from vitreal bleeding, retinal vein, artery or vitreal vein thrombosis with retinal detachment in the form of leukocoria or ischemic optic atrophy1

FREQUENTLY DUE TO CONSANGUINEOUS PARENTS and a POTENTIAL HISTORY of miscarriages1

*This may also occur in an identical way to postinfectious PF.1
**However, DIC, which can also indirectly result from sepsis, is associated with reduced Protein C and S levels because of consumption.1

Differential diagnosis can be PERFORMED by:#

PC activity ASSAY1,3,##

Protein S assay1,## (low PC levels but normal Protein S levels are suggestive of SCPCD)4

PC antigen5

Full blood count (Hemoglobin, White blood cells, Platelets)5,6

Fibrinogen2,5

D-dimer5

Prothrombin time (PT)2,5

Activated partial prothrombin time2,5

Genetic analysis2

To rule out acquired PC deficiency:

Blood culture, procalcitonin levels8 (to test for bacterial infections including Meningococcal, Streptococcus, Haemophilus and Staphylococcus sepsis) and liver function tests1,5,7,8,###

PC level testing in parents1

PC activity assay and PC antigen

MRI (to check for cerebral venous thrombosis)1

#All the tests mentioned above may not necessarily be done independently but in conjunction to help provide a complete diagnostic picture.
##Interpretation of PC and PS levels may be hindered if emergency treatment like fresh frozen plasma was already given.
###This list does not include all tests to test for the different causes of acquired PC deficiency.

References:

  1. Chalmers E, et al. Purpura fulminans: recognition, diagnosis and management. Archives of Disease in Childhood. 2011;96(11):1066-1071.

  2. Price VE, et al. Diagnosis and management of neonatal purpura fulminans. Semin Fetal Neonatal Med. 2011;16(6):318-22.

  3. Goldenberg N, Manco-Johnson M. Protein C deficiency. Haemophilia. 2008;14(6):1214–1221.

  4. Libourel EJ, et al. Protein C/S ratio, an accurate and simple tool to identify carriers of a protein C gene mutation. British Journal of Haematology. 2002;118:615–618.

  5. Khor B, et al. Laboratory tests for protein C deficiency. Am. J. Hematol. 2010;85:440–442.

  6. Tairaku S, et al. Prenatal genetic testing for falmilial severe congenital protein C deficiency. Hum Genome Var. 2015;2.15017

  7. Rhodes A, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.
    Intensive Care Med. 2017;43(3):304-377.

  8. Wacker C, et al. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis.
    Lancet Infect Dis. 2013;13(5):426-435.

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