The risk of thromboembolism in asymptomatic patients with protein C and protein S deficiency: a prospective cohort study.
BACKGROUND
Prospective studies on the incidence of thrombosis in asymptomatic individuals with hereditary protein C- or protein S deficiency have not been performed so far.


OBJECTIVE
We have carried out a prospective cohort study in 44 asymptomatic protein C- and protein S deficient subjects and in 49 asymptomatic non-deficient relatives (age at study entry > 14 years) of symptomatic deficient patients.


METHODS
20 asymptomatic protein C deficient (median age 20 years) and 24 asymptomatic protein S deficient patients (median age 21.5 years) were prospectively followed and compared with 20 asymptomatic non-deficient relatives (median age 25 years) of protein C- and 29 (median age 27 years) of protein S deficient patients. The total observation period was 118.8 patient years for protein C deficient and 92.8 for protein S deficient patients. Patients were not on anticoagulants except for short duration in case of high risk situations.


RESULTS
Eight thromboembolic events (1 pulmonary embolism, 1 deep vein thrombosis + pulmonary embolism, 3 deep vein thrombosis, 1 caval vein thrombosis and 2 superficial vein thrombosis) occurred in 6 deficient patients. The incidence of thromboembolism was 2.5% per patient year for protein C deficient and 3.5% per patient year for protein S deficient patients. 4 events occurred spontaneously, in 2 patients thromboembolic events were triggered by high risk situations (caesarean section, minor trauma). In the controls no thromboembolic events occurred. The probability for thromboembolism was significantly higher in protein C and protein S deficient patients compared to the control group (Wilcoxon test, p = 0.002, log rank test, p = 0.001). One major and 5 minor uneventful surgeries were carried out in the deficient patients using heparin prophylaxis. 1/8 pregnancies was complicated by superficial vein thrombosis during the second trimester despite prophylactic heparin administration. The same pregnancy was complicated by pulmonary embolism 5 weeks after delivery after discontinuation of heparin.


CONCLUSIONS
Asymptomatic deficient relatives of symptomatic patients with protein C or protein S deficiency are at an increased risk of thrombosis compared to nondeficient individuals. Prophylactic treatment seems to be highly effective in high risk situations.
Pabinger
I
I
Department of Hematology and Blood Coagulation, University Hospital Vienna, Austria.
Kyrle
P A
PA
Heistinger
M
M
Eichinger
S
S
Wittmann
E
E
Lechner
K
K
D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D011183:Postoperative Complications / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D011446:Prospective Studies; D020151:Protein C Deficiency; D018455:Protein S Deficiency; D011644:Puerperal Disorders / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D012306:Risk; D013923:Thromboembolism / Q000453:epidemiology* / Q000209:etiology; D013924:Thrombophlebitis / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control