Effect of levothyroxine replacement therapy on coagulation and fibrinolysis in severe hypothyroidism.
OBJECTIVE
We previously demonstrated that patients suffering from moderate hypothyroidism were at increased risk of thrombosis contrasting with the bleeding tendency of those presenting severe hypothyroidism. The latter state is associated with hemostatic anomalies including von Willebrand type 1 disease and increased fibrinolytic capacity. With the exception of von Willebrand type 1 disease, reversibility of hemostatic changes is not established after levothyroxine replacement therapy. Therefore our objective was to analyze the reversibility of these anomalies.


METHODS
We analyzed the impact of levothyroxine treatment on lipid parameters, fibrinogen, platelet count, D-dimers, alpha2 antiplasmin activity, plasminogen activity, tissue plasminogen activator antigen (t-PA Ag), plasminogen activator inhibitor type 1 antigen (PAI-1 Ag) and coagulation factors (factor VIII coagulant, von Willebrand factor antigen, von Willebrand factor and factor IX) in 23 patients with severe hypothyroidism (TSH level > 50 mU/ I).


RESULTS
Mean fibrinogen levels increased by 14.2% while t-PA Ag and PAI-1 Ag increased by 42.6 and 69%, respectively, after correction of hypothyroidism. Interestingly, post-treatment PAI-1 Ag levels tended to be higher in patients with normal-high final TSH levels than in patients with normal-low final TSH levels. Our results suggest that normalization of fibrinolysis is obtained after a transient decrease of fibrinolytic activity. We also confirmed the correction of coagulation factor abnormalities upon levothyroxine replacement therapy.


CONCLUSIONS
We demonstrated that the coagulation disorders and the hyperfibrinolytic status of severe hypothyroid patients were corrected upon levothyroxine therapy. However, the clinical consequences of the transient decrease of the fibrinolytic activity during the course of TSH normalization need further studies.
Chadarevian
R
R
Service d'Endocrinologie-Métabolisme, Hôpital Pitié Salpétrière, Paris, France.
Jublanc
C
C
Bruckert
E
E
Giral
P
P
Ankri
A
A
Leenhardt
L
L
Chapman
J
J
Turpin
G
G
D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000209:etiology*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007037:Hypothyroidism / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013974:Thyroxine / Q000627:therapeutic use*
D013974:Thyroxine