Related Experiment Videos
Effect of the Factor V Leiden mutation on the severity of meningococcal disease
S Kondaveeti1, M L Hibberd, R Booy
1Department of Paediatrics, Imperial College School of Medicine at St. Mary's, London, UK.
Background:
One of the most serious complications of meningococcal disease is the syndrome of purpura fulminans, which is characterized by intravascular thrombosis and hemorrhagic infarction of skin, limbs and digits. The reasons why some patients with meningococcal disease develop purpura fulminans while others have minimal thrombotic and skin involvement despite having profound septic shock are not yet understood. The Factor V Leiden mutation (FV(L)) is associated with thrombotic events, and we hypothesized that children carrying FV(L) who develop meningococcal disease may be at increased risk of purpura fulminans.
Methods:
We determined the FV(L) genotype by PCR and restriction enzyme digestion (Mnl1) in 259 children with meningococcal disease and 80 healthy controls. In addition 79 parents of children with fatal meningococcal disease were studied.
Results:
There was no significant increase in the frequency of FV(L) in patients with meningococcal disease (10%) as compared with healthy controls (9%) or with the parents of children who died of meningococcal disease (12%). Although the mortality was not increased in patients heterozygous for FV(L), they had increased complications of purpura fulminans, as assessed by requirement for skin grafting, referral to plastic surgeon and/or amputation. Among survivors 5 of 24 (21%) of those heterozygous for FV(L) had complications, compared with 14 of 233 (7%) who were wild type [P < 0.03; relative risk, 3.1 (95% confidence intervals, 1.2 to 7.9)].
Conclusions:
FV(L) exacerbates purpura fulminans in meningococcal disease but does not have a significant effect on mortality.
Insights
Factor V Leiden mutation (FV(L)) increases the risk of purpura fulminans complications in children with meningococcal disease. However, FV(L) does not significantly impact mortality rates in these patients.
Area of Science:
- Genetics
- Pediatrics
- Infectious Diseases
Background:
- Meningococcal disease can lead to purpura fulminans, a severe complication involving thrombosis and skin necrosis.
- The underlying reasons for developing purpura fulminans in some patients remain unclear.
- The Factor V Leiden mutation (FV(L)) is a known risk factor for thrombotic events.
Purpose of the Study:
- To investigate if the Factor V Leiden mutation (FV(L)) increases the risk of purpura fulminans in children with meningococcal disease.
- To determine the association between FV(L) and mortality in pediatric meningococcal disease.
Main Methods:
- Genotyping for the Factor V Leiden mutation (FV(L)) using PCR and restriction enzyme digestion.
- Study included 259 children with meningococcal disease, 80 healthy controls, and 79 parents of children deceased from meningococcal disease.
Main Results:
- FV(L) frequency was similar in patients (10%), controls (9%), and parents (12%).
- Patients heterozygous for FV(L) showed a significantly higher incidence of purpura fulminans complications (21% vs. 7%; P < 0.03).
- FV(L) heterozygosity was associated with a 3.1-fold increased risk of purpura fulminans complications.
Conclusions:
- Factor V Leiden mutation exacerbates purpura fulminans in meningococcal disease.
- FV(L) does not significantly affect mortality in children with meningococcal disease.