Purpura fulminans : Is it acquired or congenital?
Ruling out acquired PC deficiency as a cause of purpura fulminans (PF)
One of the difficulties in diagnosing the cause of PF in neonates is that disseminated intravascular coagulation (DIC) is associated with severe acute infections, sepsis and Severe Congenital Protein C Deficiency.1
For proper management of PF, diagnosing the underlying cause is crucial.1,2
acquired VS. congenital protein C (PC) deficiency: Differences in clinical and laboratory findings
ACQUIRED PC DEFICIENCY
SKIN LESIONS THAT:1
- Develop in distal extremities and progress proximally
- Appear as a generalised or diffuse rash affecting entire body surface
UNDETECTABLE PROTEIN C LEVELS1*
ISOLATION OF CAUSATIVE AGENT
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
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-carriers5
CEREBRAL VENOUS THROMBOSIS1
Blindness arising from vitreal bleeding, retinal vein, artery or vitreal vein thrombosis with retinal detachment in the form of leukocoria or ischaemic optic atrophy1
CONSANGUINEOUS PARENTS AND A POTENTIAL HISTORY OF MISCARRIAGES1
Differential diagnosis can be PERFORMED by:
PROTEIN C (PC) ACTIVITY ASSAY1,3
Protein S assay1 (low PC levels but normal Protein S levels are suggestive of SCPCD)4
Full blood count (Haemoglobin, White blood cells, Platelets)5,6
Prothrombin Time (PT)2,5
Activated partial prothrombin time2,5
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 tests.5,7,8**
PC level testing in parents1
PC activity assay and PC antigen
MRI (to check for cerebral venous thrombosis)1
**This list does include all tests to test for the different causes of acquired protein C deficiency.
Chalmers E, et al. Purpura fulminans: recognition, diagnosis and management. Archives of Disease in Childhood. 2011;96(11):1066-1071.
Price VE, et al. Diagnosis and management of neonatal purpura fulminans. Semin Fetal Neonatal Med. 2011;16(6):318-22.
Goldenberg N, Manco-Johnson M. Protein C deficiency. Haemophilia. 2008;14(6):1214–1221.
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.
Khor, B, et al. Laboratory tests for protein C deficiency. Am. J. Hematol. 2010;85:440–442.
Tairaku S, et al. Prenatal genetic testing for falmilial severe congenital protein C deficiency. Hum Genome Var. 2015;2.15017
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.
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.