Different effects of heparin in males and females.
OBJECTIVE
To determine whether women have a Pharmacological predisposition to bleeding and a worse outcome than men during heparin therapy, in light of recent studies showing that women have a higher risk of bleeding complications following anticoagulant therapy for thrombotic disorders than men.


METHODS
Prospectively planned subgroup analysis of a double-blind randomized study.


METHODS
Academic tertiary care hospitals in Hamilton, Ont.


METHODS
A total of 199 consecutive patients (105 women, 93 men) presenting with proximal deep vein thrombosis. (One patient was not included due to incomplete data).


METHODS
Activated partial thromboplastin time (APTT) values and heparin levels were assessed every 4 to 6 hours after a standard heparin bolus and infusion. The effect of sex on heparin doses and levels was also assessed after stable therapeutic heparin infusions were achieved.


RESULTS
The women had higher heparin levels than the men (0.560 [standard error of the mean, SEM 0.056] units/mL v. 0.347 [SEM 0.062] units/mL, p < 0.0001) and higher APTT values (94.9 [SEM 0.50] seconds v. 81.2 [SEM 0.53] seconds, p = 0.0002) 4 to 6 hours after being given the same heparin bolus and infusion doses. After achieving therapeutic APTT values, the women received lower heparin doses than the men (27.9 [SEM 0.24] 1000 units/24 hours v. 34.5 [SEM 0.24] 1000 units/24 hours, p < 0.0001) but had higher heparin levels (0.349 [SEM 0.035] units/mL v. 0.292 [SEM 0.036] units/mL, p = 0.034). The effect of sex was also determined after correcting for the known effects of weight and age on heparin therapy. After adjusting for patient weight, among the women, older women had higher heparin levels but, among the men, there was little effect of age. There were no sex differences with respect to bleeding complications or recurrent thromboembolic disease.


CONCLUSIONS
Women showed alterations in the pharmacokinetics of heparin, which could explain a predisposition to bleeding complications. Under the heparin protocol used in this study, heparin doses were rapidly adjusted, which may explain why rates of bleeding complications and recurrent thromboembolism were similar in men and women. We do not recommend changes in heparin therapy based on these results, but suggest the use of protocols that assess coagulation parameters frequently and then adjust heparin doses rapidly, in order to individualize therapy. Further study is required to determine whether there are sex differences in bleeding complications associated with anticoagulant therapy, and to confirm the altered pharmacokinetics of heparin in women.
Campbell
N R
NR
Division of General Internal Medicine, Faculty of Medicine, University of Calgary, Alta.
Hull
R D
RD
Brant
R
R
Hogan
D B
DB
Pineo
G F
GF
Raskob
G E
GE
D000375:Aging; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006493:Heparin / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D011446:Prospective Studies; D012727:Sex Characteristics; D013924:Thrombophlebitis / Q000188:drug therapy
D006493:Heparin