Table 1.
Pharmacodynamic studies on the use of low-molecular-weight heparin and fondaparinux for venous thromboembolism prophylaxis in obese patients.
| Study, year (n) |
Study design | Population | Obese (%) | Maximum weight (kg) |
Agent and dose |
Target anti-FXa prophylactic range (units/ml) |
Peak (4-h) anti-FXa levels (units/ml) |
Comments | Ref. |
|---|---|---|---|---|---|---|---|---|---|
| Frederiksen et al., 2003 (19) | PC | Surgical | NR | ~150 | Enoxaparin 40 mg single dose | NR | NR | Negative correlation with increasing body weight | [43] |
| Hainer et al., 2002 (37) | Prospective open label† | Healthy, heavyweight subjects (vs historical controls <100 kg) | 97 | 165 | Tinzaparin 75 IU/kg | NR | Nonobese: 0.30 (range: 0.28–0.32); obese: 0.34 (range: 0.303–0.375) | Predictable response maximum anti-FXa activity regardless of body weight | [46] |
| Simone et al., 2008 (40) | PC | Bariatric surgery | 100 | NR | Enoxaparin 40 mg b.i.d. vs 60 mg b.i.d. | 0.18–0.44 | Nonobese: 0.21 vs obese: 0.43 (p < 0.001) | Subtherapeutic (<0.18 u/ml) 44 vs 0%; supratherapeutic (>0.44 u/ml) 0 vs 57% | [49] |
| Borkgren- Onkonek et al., 2008 (223) | Prospective open label | Bariatric surgery | 100 | NR | Enoxaparin 40 mg b.i.d. if BMI <50 and 60 mg b.i.d. if BMI >50 | 0.18–0.44 | Nonobese: 0.32 vs obese: 0.26 | 1 nonfatal VTE (0.45%) Major bleeding: 1.79% | [52] |
| Rowan et al., 2008 (52) | PC | Bariatric surgery | 100 | NR | Enoxaparin 30 mg b.i.d. vs 40 mg b.i.d. | NR | Nonobese: 0.008 vs obese: 0.15 (p < 0.05) for third dose | [48] | |
| Imberti et al., 2009 (66) | Multicenter open label, pilot study of RCT | Bariatric surgery | 100 | Maximum BMI 64.1 kg/m2 | Parnaparin 4250 IU/day vs 6400 IU/day | 0.1–0.4 | Nonobese: 4150 U dose 98% in range; obese: 62.3% 6400 IU/day out of range | Anti-FXa level did not correlate with BMI when compared above and below BMI 45 (BMI range: 36.1–64.1) | [24] |
| Mayr et al., 2002 (89) | PC | General and surgical ICU | NR | ~150 | Enoxaparin 40 mg/day | 0.1–0.3 | High body weight significantly correlated with low anti-Fxa | [44] | |
| Jimenez et al., 2008 (112) | PC | Medically ill, respiratory illness | 21 | NR | Enoxaparin 40 mg/day | 0.2–0.6 | BMI <23: 0.28; BMI 23–26: 0.23; BMI 26–29: 0.15; BMI >30: 0.13 (p < 0.002) |
[45] | |
| Rondina et al., 2010 (28) | PC | Medically ill, respiratory illness | 100 | 210 | Enoxaparin 0.5 mg/kg once daily | 0.2–0.6 | 0.25 u/ml (SD: 0.11) | Anti-FXa levels did not correlate with BMI using weight-based dosing | [47] |
| Raftopoulos et al., 2008 (10) | Prospective randomized crossover study | Morbidly obese volunteers | 100 | 248 | Fondaparinux 2.5 mg daily vs 5 mg daily | Maximum concentration 0.34‡ | 2.5-mg dose: 0.21 (SD: 0.08); 5-mg dose: 0.41 (SD: 0.16) | Lower dose did not reach target levels for maximum concentration | [55] |
†
Cohort compared with normal historical controls.
‡
Reported as maximum fondaparinux plasma concentration mean (range).
b.i.d.: Twice per day; FXa: Factor Xa; ICU: Intensive care unit; LMWH: Low-molecular-weight heparin; NR: Not reported; PC: Prospective cohort; RCT: Randomized controlled trial; SD: Standard deviation; VTE: Venous thromboembolism.
Data taken from [64].