Venous thromboembolism - prevention after orthopaedic surgery

1
Venous thromboembolism Primary prevention after
major orthopaedic surgery
2
Effect of prophylaxis on total DVT rates after
total hip replacement
No of n Prevalence trials
(95Cl) RRR
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 Warfari
n 13 1828 22 (20-24) 59 IPC 7 423 20 (17-24) 63 LM
WH 30 6216 16 (15-17) 70 R-hirudin 3 1172 16 (14-1
9) 70
Geerts WH et al. Chest 2001119132S175S
3
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 23)
• For TKR, intermittent pneumatic compression is
  an alternative Grade 2B

Geerts WH et al. Chest 2004126338S400S
4
7th ACCP recommendations Total hip, knee
replacement or hip fracture surgery

• Prophylaxis should be extended until 2835 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 126338S400S
5
Timing of anticoagulant therapy in orthopaedic
surgery
In Europe, the first dose of LMWH is commonly
administered the evening (10-12 hours) before
surgery
6
Timing of anticoagulant therapy in orthopaedic
surgery
In North America the initial dose of warfarin,or
less common, LMWH is not administereduntil 12-24
hours after surgery
7
Prophylaxis most effective when initiated in
close relation to surgery
Odds ratio
1.4
Quadratic fit for study odds ratio for DVT vs.
the number of hours from surgery for the first
dose of LMWH
1.0
0.6
0.2
-10
10
0
20
Hours from surgery
Upper and lower dashed lines indicate the 95
confidence interval for the estimated odds ratio
Hull R et al. Arch Intern Med 20011602208-15
8
Thrombin activation at bone traumatisation
during THR surgery
Thrombin-antithrombin (TAT) (ng/mL)
Prothrombin F1 2 (nmol/L)
5

4
p0.0001
Bone trauma
Bone trauma
3

2


1
0
0.5
1.0
1.5
2.0
2.5
0
0.5
1.0
1.5
2.0
2.5
Time (h)
Time (h) (h)
Saline
UFH 10 units/kg
UFH 20 units/kg
Sharrock NE et al. Clin Orthop 199531916-27
9
Increasing thrombin generation and thrombus
growth after one week
F12
20
Arterial blood
15
10
5
Mixed venous blood
0
8
7
6
5
4
1
3
2
Intraoperatively (h)
Dahl OE et al. Thromb Res 199370451-8 Dahl OE
et al. Blood Coagul Fibrinolysis 19956709-17
Thrombin generation factors
10
Onset of VTE after THR / TKR - cumulated risk
within 3 months
All VTE
PE
Thromboembolic events ()
Pulmonary embolism ()
3.5
1.3
Primary hip
Primary hip
Primary knee
Primary knee
3.0
1.0
2.5
0.8
2.0
1.5
0.5
1.0
0.3
0.5
0.0
0.0
0
14
28
42
56
70
84
0
14
28
42
56
70
84
Days
Days
White RH et al. Arch Intern Med.
19981581525-1531
11
Duration of thrombin generation in THR
Thrombin activity (TAT ng/mL)
D-dimer (ng/mL)
6000
30
TAT complexes
25
D-dimer LMWH
4000
20
15
10
2000
5
0
0
0
1
6
14
20
35
Days after surgery
32
DVT at venography
16
Dahl OE et al. Thromb Res 199580299-306 Dahl
OE et al. Thromb Haemost 19977726-31
12
Effect of continuing prophylaxis on asymptomatic
DVT
DVT
7 days
30
Proximal DVT
35 days
25
20
15
10
5
0
Total DVT
40
30
20
10
0
Lassen 1998
Bergqvist 1996
Planes 1996
Dahl 1997
Spiro 1997
Hull 2000
13
Extended LMWH reduces symptomatic VTE
Extended Control OR (95 CI)
n (N) n (N)
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)
Cohen A et al. Thromb Haemost 200185940-1
14
Relative risk for DVT out-of-hospital
No. patients with events
Relative risk
Study Year LMWH group Control
group Weight (95 CI fixed) p value n/n
() () Bergqvist et al 1996 21/117 (17.9) 45/11
6 (38.8) 28.6 0.46 (0.300.73) 0.001 Planes
et al 1996 6/85 (7.1) 17/88 (19.3) 10.6 0.
37 (0.150.88) 0.025 Dahl et al 1997
11/93 (11.8) 23/89 (25.8) 14.9 0.46
(0.240.88) 0.020 Lassen et al 1998 5/113
(4.4) 12/102 (11.8) 8.0 0.38 (0.141.03)
0.057 Hull et al 2000 14/291 (4.8) 14/133 (10.5)
12.2 0.46 (0.220.93) 0.031 Comp et
al 2001 15/152 (9.9) 39/138 (28.2) 25.9 0.35
(0.200.60) lt0.001 Total 72/911 (7.9) 150/666
(22.5) 100.0 0.41 (0.320.54) lt0.001
Hull RD et al. Ann Intern Med 2001135858-69
15
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 value n/n () () Bergqvist et
al 1996 2/131 (1.5) 10/131 (7.6) 26.3 0.20
(0.040.90) 0.035 Planes et al 1996
3/90 (3.3) 7/89 (7.9) 18.5 0.42
(0.111.59) 0.2 Dahl et al 1997 4/117 (3.4)
6/110 (5.5) 16.3 0.63 (0.182.16) gt0.2 Lassen
et al 1998 2/140 (1.4) 3/141 (2.1) 7.9 0.67
(0.113.96) gt0.2 Hull et al 2000 4/389 (1.0)
3/180 (1.7) 10.8 0.62 (0.142.73) gt0.2 Comp et
al 2001 0/224 (0.0) 7/211 (3.3) 20.3 0.06
(0.001.09) 0.058 Total 15/1,091 (1.4)
36/862 (4.2) 100.0
0.36 (0.020.67) lt0.001
Hull RD et al. Ann Intern Med 2001135858-69