Heparin

Additional information

Pharmacokinetics and dosing

When given the same dose of heparin (93 men, 103 women), women had higher concentrations and APTT values (activated partial thromboplastin time) 4-6 hours after bolus and infusion. After adjusting for weight the difference remained in older women [1].

Effects

Clinical trials have shown that female sex is associated with increased APTT. After administration of standardized doses of unfractionated heparin, women had higher heparin levels and greater prolongation of the APTT than men. Therefore, women might require a lower dose of heparin to achieve therapeutic APTT value [1, 2]. Similarly, low-molecular-weight heparin given in the same dose resulted in higher anti-factor Xa levels in women, even after compensating for age, body weight and smoking [3].

Adverse effects

In general, female sex is associated with an increased bleeding risk with thrombolytics, unfractionated heparin and low-molecular-weight heparin [4, 5].  The original manufacturer reports that a higher incidence of bleeding has been reported in patients over 60 years of age, especially women. Therefore, it has been suggested that lower doses of heparin may be indicated in these patients [6].

A randomized clinical trial (93 men, 105 women) found that women compared to men had different pharmacokinetics of unfractionated heparin, but the rates of bleedings were similar in men and women [1]. Similarly, a subgroup analysis from a randomized trial comparing unfractionated heparin with bivalirudin found no sex difference in bleeding (411 men, 391 women) [7].

An analysis of register data, a clinical trial and systematic reviews showed that women more than men are at higher risk for heparin-induced thrombocytopenia (HIT). The overall increased risk for HIT in women was 2.37 (95%CI, 1.37-4.09). The increased risk was observed mostly in patients treated with unfractionated heparin [8].

A large international cohort study (in total 24 401 patients) observed that treatment of venous thromboembolism (VTE) with unfractionated heparin increased the risk of thrombocytopenia in women but not in men, when compared to treatment with low molecular weight heparin (HR 4.90 (95%CI 2.58-9.31) in women vs. 1.60 (0.64-3.97) in men) [9].

Heparin resistance occurs early in the heparin therapy and may put patients at risk of progression of the underlying thrombotic process. Close monitoring of the APTT (activated partial thromboplastin time) and heparin dose adjustment is recommended to reduce the risk. A prospective observation study (99 men, 47 women) found that women were more resistant to heparin than men. The higher rate of resistance to heparin in women extended for up to 48 h. A possible explanation may be the higher level of endogenous factor VIII in women probably because of higher levels of estrogen [10].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).