Plasma anti Xa-levels in obese patients undergoing bariatric surgery and receiving low molecular weight heparins for thromboprophylaxis.

Venous thromboembolism (VTE) is a significant risk factor in patients
undergoing bariatric surgery for morbid obesity and may be associated with
significant morbidity and mortality. In patients undergoing bariatric surgery,
the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE)
varies from 1.2 to 1.6% and from 0.8 to 3.2%, respectively. Several
thromboprophylactic measures have been proposed to reduce the high incidence of
VTE complications in postoperative bariatric surgical patients. Low molecular
weight heparins (LMWH) have been demonstrated to be both effective and safe for
the prevention of VTE. However, there are no clear guidelines regarding the
optimal dosage of LMWHs to prevent or to treat VTE in morbid obese patients.
For VTE prophylaxis, fixed doses of enoxaparin, dalteparin, and tinzaparin are
typically used, regardless of total body weight. Studies have reported that
fixed doses are safe and well-tolerated and it is as effective in prophylaxis
of VTE as the higher dose. However, in these studies, no patients with a body
weight over 150 kg were included, and the number of patients with a body weight
between 120 kg and 150 kg was underrepresented. Previous recommendations have
suggested increasing prophylactic doses of LMWH in obese patients, but studies
evaluating the weight-based dosage of LMWH are limited and criteria for dose
adjustment in obese (BMI/30 kg/m2) and severely obese (BMI/50 kg/m2) patients
remain controversial. The commonly used LMWH for thromboprohylaxis at the
Slotervaart Hospital in Amsterdam in the Netherlands is enoxaparin (Clexane)
with a dosing regimen of 40 mg twice daily subcutaneously. Dosing adjustments
are made only in patients with high risk for VTE. Currently, there is limited
evidence to guide the use of prophylactic enoxaparin, especially in morbidly
obese patients. Some manufacturers recommend a maximum daily dose for obese
patients, whereas others recommend a linear increase in dosage for patients>100
kg. Since all patients at the Slotervaart Hospital receive the same amount oF
LMWH after bariatric surgery, the situation enables us to investigate the
relationship between body weight and ant-Xa concentration in the morbid obese
range.

The purpose of the proposed study is to investigate the anti-Xa levels of
enoxaparin in patients after bariatric surgery and to correlate these with
actual body weight.

We will conduct a prospective, observational, study in patients who have
undergone bariatric surgery at the Slotervaart Hospital, Amsterdam, the
Netherlands. To examine the correlation between body weight and anti-Xa levels
on a continous scale, different weight categories will be defined, for example
weight < 110 kg, weight between 100 and 150 kg, and all other patients
weighing > 150 kg. In each category 15 patients will be included. A sample size
calculation with the present literature is difficult. In the study of
Frederiksen et al (2003) a strong negative correlation was shown between
body-weight and anti-Xa activity in 19 patients in total. Assuming that the
difference in anti-Xa levels will be 30% between the lowest en highest body
weight categories, a sample size of 15 patients in each weight category will
be sufficient to be able to detect a significant difference between the groups.
Anti-Xa levels will be measured 4 hours after administration on day 10 of
thromboprophylaxis, with a maximum range of 14 (last day of use of enoxaparin).
To correlate for the kidney function, creatinine will also be measured on the
same day. In obese patients, the preferred sampling time for the steady-state
anti-Xa assay is 4 hours after the third dose or a late dose according to the
enoxaparin pharmacokinetics and pharmacodynamics.

There are no risks expected for patients participating in this study.
Patients will be asked to come once to the hospital for a venapuncture.