Influence of inherited and acquired thrombophilic defects on the clinical manifestations of mixed cryoglobulinaemia.
OBJECTIVE
To investigate the contribution of inherited and acquired thrombophilic defects to the clinical manifestations of mixed cryoglobulinaemia vasculitis.


METHODS
The following thrombophilic defects were investigated in 64 consecutive patients with HCV-associated mixed cryoglobulinaemia: aPLs, lupus anti-coagulant, homocysteinaemia, protein C and protein S concentrations, activated protein C resistance, plasminogen activator inhibitor-1 4G4G and 5G5G genotypes, and the presence of mutations of factor V (Leiden and H1299R), of prothrombin (G20210A) and of methyl tetrahydrofolate reductase (C677T and A1298C). Additional variables were demographic data, duration of the disease, cryocrit level and vascular risk factors (diabetes, hypertension, hypercholesterolaemia and smoking habit). The following clinical manifestations of mixed cryoglobulinaemia were analysed as dependent covariates: severity of purpura, presence of necrotic skin ulcers, presence of peripheral neuropathy and presence of kidney disease.


RESULTS
Logistic regression analysis identified hyperhomocysteinaemia as a risk factor for severe purpura (P < 0.0001) and for the presence of skin ulcers (P < 0.0001), whereas none of the other thrombophilic defects influenced the clinical presentation of mixed cryoglobulinaemia. Purpura improved in two patients after lowering homocysteine with vitamin supplementation.


CONCLUSIONS
Hyperhomocysteinaemia may be a risk factor for severe cutaneous manifestations in mixed cryoglobulinaemia.
Casato
M
M
Department of Clinical Immunology, Sapienza University of Rome, Rome 00185, Italy.
Carlesimo
M
M
Francia
A
A
Timarco
C
C
Antenucci
A
A
Bove
M
M
Martini
H
H
Visentini
M
M
Fiorilli
M
M
Conti
L
L
D020016:Activated Protein C Resistance; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003449:Cryoglobulinemia / Q000150:complications* / Q000235:genetics; D005165:Factor V / Q000235:genetics; D005260:Female; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications* / Q000235:genetics; D016015:Logistic Models; D016682:Lupus Coagulation Inhibitor / Q000235:genetics; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D011516:Prothrombin / Q000235:genetics; D012307:Risk Factors; D012867:Skin / Q000098:blood supply; D012883:Skin Ulcer / Q000209:etiology* / Q000235:genetics; D014657:Vasculitis / Q000209:etiology* / Q000235:genetics
D016682:Lupus Coagulation Inhibitor; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)