Post on 17-Dec-2015
LIFEBLOODTHE
ThrombosisCHARITY
Venous thromboembolism –Primary prevention after major orthopaedic surgery
LIFEBLOODTHE
ThrombosisCHARITY
No of n Prevalence trials % (95%Cl) RRR %
Effect of prophylaxis on total DVT rates after total hip replacement
Placebo/control 12 626 54 (50-58) -
Elastic stockings 4 290 42 (36-48) 23
Aspirin 6 473 40 (35-45) 26
Low-dose UFH 11 1016 30 (27-33) 45
Warfarin 13 1828 22 (20-24) 59
IPC 7 423 20 (17-24) 63
LMWH 30 6216 16 (15-17) 70
R-hirudin 3 1172 16 (14-19) 70
Geerts WH et al. Chest 2001;119:132S–175S
LIFEBLOODTHE
ThrombosisCHARITY 7th ACCP recommendations
Total hip, knee replacement or hip fracture surgery
• Thromboprophylaxis for at least 10 days [Grade 1A] with:
– LMWH (high-risk dose)
– Fondaparinux (2.5 mg daily)
– Vitamin K antagonist (VKA, target INR 2.5 [INR range 2–3])
– For TKR, intermittent pneumatic compression is an alternative [Grade 2B]
Geerts WH et al. Chest 2004;126:338S–400S
LIFEBLOODTHE
ThrombosisCHARITY
• Prophylaxis should be extended until 28–35 days after surgery
– THR: LMWH, VKA or fondaparinux [all Grade 1A)]
– HFS: Fondaparinux (Grade 1A), LMWH or VKA [both Grade 1C+]
– TKR: Benefits remain unclear
Geerts WH et al. Chest 2004; 126:338S–400S
7th ACCP recommendations Total hip, knee replacement or hip fracture surgery
LIFEBLOODTHE
ThrombosisCHARITY
Timing of anticoagulant therapy in orthopaedic surgery
In Europe, the first dose of LMWH is commonly administered the evening
(10-12 hours) before surgery
LIFEBLOODTHE
ThrombosisCHARITY
In North America the initial dose of warfarin,or less common, LMWH is not administered
until 12-24 hours after surgery
Timing of anticoagulant therapy in orthopaedic surgery
LIFEBLOODTHE
ThrombosisCHARITY
Prophylaxis most effective when initiated in close relation to surgery
Upper and lower dashed lines indicate the 95% confidence interval for the estimated odds ratio
Quadratic fit for study odds ratio for DVT vs. the number of hours from surgery for the
first dose of LMWH
10Hours from surgery
Odds ratio
-10
1.4
1.0
0.6
0.2
0 20
Hull R et al. Arch Intern Med 2001;160:2208-15
LIFEBLOODTHE
ThrombosisCHARITY
Thrombin activation at bone traumatisation during THR surgery
Prothrombin F1 + 2 (nmol/L)
0 0.5 1.0 1.5 2.0 2.5
4
3
5
1
2
Time (h)
Bone trauma
Thrombin-antithrombin (TAT) (ng/mL)
*p=0.0001
0 0.5 1.0 1.5 2.0 2.5
Time (h) (h)
100
0
80
60
40
20
*
*
**
Bone trauma
Sharrock NE et al. Clin Orthop 1995;319:16-27
Saline
UFH 10 units/kg
UFH 20 units/kg
LIFEBLOODTHE
ThrombosisCHARITY
Increasing thrombin generation and thrombus growth after one week
Mixed venous blood
876543210
20
15
10
5
Intraoperatively (h)
Arterial blood
Venography shows DVT ~1 week after surgery
F1+2*
* Thrombin generation factors
631
Days after Surgery
Scanning electron microscopy shows DVT ~1 hour after
THR surgery
Dahl OE et al. Thromb Res 1993;70:451-8 Dahl OE et al. Blood Coagul Fibrinolysis 1995;6:709-17
LIFEBLOODTHE
ThrombosisCHARITY
Onset of VTE after THR / TKR- cumulated risk within 3 months
White RH et al. Arch Intern Med. 1998;158:1525-1531
Thromboembolic events (%)
0.00 14 28 42 56 70 84
Days
0.5
1.0
1.5
2.0
2.5
3.0
3.5 Primary hipPrimary knee
Pulmonary embolism (%)
0.00 14 28 42 56 70 84
Days
0.3
0.5
0.8
1.0
1.3 Primary hipPrimary knee
All VTE PE
LIFEBLOODTHE
ThrombosisCHARITY
0
5
10
15
20
25
30
0 1 6 14 20 35
Thrombin activity(TAT; ng/mL)
Days after surgery
D-dimer (ng/mL)
0
2000
4000
6000
16%
32%
TAT complexes
D-dimer – LMWH
DVT at venography
Duration of thrombin generation in THR
Dahl OE et al. Thromb Res 1995;80:299-306 Dahl OE et al. Thromb Haemost 1997;77:26-31
LIFEBLOODTHE
ThrombosisCHARITY
0
10
20
30
40
Effect of continuing prophylaxis on asymptomatic DVT
Bergqvist 1996
Planes1996
Dahl1997
Spiro1997
Lassen1998
Hull2000
Total DVT
DVT %
Proximal DVT
0
5
10
15
20
25
30 7 days35 days
LIFEBLOODTHE
ThrombosisCHARITY
Extended Control OR (95% CI) n (N) n (N)
Cohen A et al. Thromb Haemost 2001;85:940-1
Extended LMWH reduces symptomatic VTE
Bergqvist 2 (131) 10 (131) 0.25 (0.08, 0.79)
Dahl 4 (117) 6 (110) 0.62 (0.17, 2.19)
Heit 7 (607) 10 (588) 0.68 (0.26, 1.76)
Hull 4 (291) 3 (133) 0.58 (0.12, 2.91)
Lassen 2 (140) 3 (141) 0.67 (0.11, 3.92)
Planes 3 (90) 7 (89) 0.43 (0.12, 1.52)
Total 22 (1376) 39 (1192) 0.50 (0.30, 0.83)
LIFEBLOODTHE
ThrombosisCHARITY
Relative risk for DVT out-of-hospital
No. patients with events Relative risk
Study Year LMWH group Control group Weight (95% CI fixed) p valuen/n (%) (%)
Bergqvist et al 1996 21/117 (17.9) 45/116 (38.8) 28.6 0.46 (0.30–0.73) 0.001
Planes et al 1996 6/85 (7.1) 17/88 (19.3) 10.6 0.37 (0.15–0.88) 0.025
Dahl et al 1997 11/93 (11.8) 23/89 (25.8) 14.9 0.46 (0.24–0.88) 0.020
Lassen et al 1998 5/113 (4.4) 12/102 (11.8) 8.0 0.38 (0.14–1.03) 0.057
Hull et al 2000 14/291 (4.8) 14/133 (10.5) 12.2 0.46 (0.22–0.93) 0.031
Comp et al 2001 15/152 (9.9) 39/138 (28.2) 25.9 0.35 (0.20–0.60) <0.001
Total 72/911 (7.9) 150/666 (22.5) 100.0 0.41 (0.32–0.54) <0.001
Hull RD et al. Ann Intern Med 2001;135:858-69
LIFEBLOODTHE
ThrombosisCHARITY
Relative risk for symptomatic VTE out-of-hospital
No. patients with events Relative risk
Study Year LMWH group Control group Weight (95% CI fixed) p valuen/n (%) (%)
Bergqvist et al 1996 2/131 (1.5)10/131 (7.6) 26.3 0.20 (0.04–0.90) 0.035
Planes et al 1996 3/90 (3.3) 7/89 (7.9) 18.5 0.42 (0.11–1.59) 0.2
Dahl et al 1997 4/117 (3.4) 6/110 (5.5) 16.3 0.63 (0.18–2.16) >0.2
Lassen et al 1998 2/140 (1.4) 3/141 (2.1) 7.9 0.67 (0.11–3.96) >0.2
Hull et al 2000 4/389 (1.0) 3/180 (1.7) 10.8 0.62 (0.14–2.73) >0.2
Comp et al 2001 0/224 (0.0) 7/211 (3.3) 20.3 0.06 (0.00–1.09) 0.058
Total 15/1,091 (1.4) 36/862 (4.2) 100.0 0.36 (0.02–0.67) <0.001
Hull RD et al. Ann Intern Med 2001;135:858-69