Long-Term Investigation on Age-Dependent Variations of Coagulation Factors in Patients with Von Willebrand Disease and Hemophilia,

Age dependent variations of coagulation factors are well known in the general population. This investigation studies the long/term, age-dependent variations of coagulation factors in patients with hemophilia A (HA) and von Willebrand disease (VWD) in correlation to the co-morbidity.

In this retrospective, single center cohort study, the median observation time was 14 years (5–43). Technical equipment did not change during the observation time. We compared FVIII:C, vWF:Ag and vWF:RCo levels of 65 pt with HA (mild n=48, moderate n=10, severe n=7; median age 28 years at first blood withdrawal, 47 years at last withdrawal), 84 pt with VWD (54w, 30m; type 1 n=57, type 2 n=15, type 3 n=10, type not specified n=2; median age 30,5 years at first blood withdrawal, 47,5 years at last withdrawal) and 23 conductors of HA (median age 36 years at first blood withdrawal, 42 years at last withdrawal).

FVIII:C levels collected from pt with mild HA displayed a significant median increase of 6,5% (−15 – 31%) with proceeding age from 14,5% (5,3 – 47%) to 19% (4,8 – 76%) (p=0,001335). For pt with moderate HA a non significant median increase of 1,05% (−3,6 – 16%) from 4,95% (2,8 – 11%) to (3 – 20%) was found. Eight pt showed FVIII:C levels during the last blood withdrawal, that indicated a change of severity from moderate to mild HA. Conductors of HA showed a non significant median increase of 8% (−52 – 95%) from 59% (21 – 118%) to 55% (33 – 145%). The course of FVIII:C levels in pt with severe HA did not vary. FVIII:C levels of pt with mild HA and conductors of HA showed a non significant tendency to higher increase at higher age. Also, a stronger increase at higher initial FVIII:C levels (assessed at first blood withdrawal) was found. Neither cardiovascular diseases nor hepatitis status correlated significantly to the age dependant increase of FVIII:C.

FVIII:C levels of patients with VWD displayed an age-dependant significant median increase of 7,5% (−39 – 54%) from 62% (1 – 98%) to 68% (1 – 138%) (p = 0.010038). Additionally, a significant median increase of vWF:Ag of 7% (−61 – 67%) from 49% (0 – 112%) to 57% (3 – 105%) (p = 0.000072) and a non significant median increase of VWF:RCo of 2,5% (−42 – 82%) from 50% (0 – 90%) to 49,5% (0 – 143%) (p = 0.867876) were observed. The type of VWD (1, 2, 3), BMI, smoking status, treatment preparation, and co-morbidity (CHD, thrombosis, hypertonus, malignant disease and smoking) did not correlate to the observed increases.

Pt with mild HA/VWD showed a significant increase of FVIII:C levels parallel to the ageing process. This increase was not significant in pt with moderate HA and conductors of HA. The course of FVIII:C levels in pt with severe HA did not vary. Pt with VWD additionally showed a significant increase of VWF:Ag and a non significant increase of VWF:RCo at proceeding age. No correlation to lifestyle factors or co-morbidity could be found.

No relevant conflicts of interest to declare.