preventing vte in gynaecological surgery · 2017. 5. 25. · disclosures for ajay kakkar research...
TRANSCRIPT
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Preventing VTE in gynaecological surgery
Rt Hon. Professor the Lord Kakkar PC Thrombosis Research Institute and
University College London UK
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Disclosures for Ajay Kakkar
Research support/principal investigator: Bayer
Consultant/Advisory Board/Honoraria: Bayer HealthCare, sanofi-aventis, Boehringer Ingelheim, Daiichi Sankyo, Janssen
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My talk today
Burden of disease
Rationale for thromboprophylaxis
Mechanical methods
Extended thromboprophylaxis
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Adaptation of the Caprini model by ACCP 2012
Gould MK, et al. Chest 2012; 141 (Suppl):e227s–77s.
Patient population
Patients undergoing major general thoracic or vascular
surgery
Patients undergoing general surgery, including GI, urological, vascular, breast
and thyroid procedures Patients undergoing plastic and
reconstructive surgery
Other surgical populations in risk category
AT9 VTE risk category
Rogers score
Observed risk of symptomatic VTE, %
Caprini score
Observed risk of symptomatic VTE, %
Caprini score
Observed risk of VTE, %
Very low < 7 0.1 0 0 0–2 NA Most outpatient or same-day surgery
Low 7–10 0.4 1–2 0.7 3–4 0.6 Spinal surgery for non-malignant disease
Moderate > 10 1.5 3–4 1.0 5–6 1.3 Gynaecological non-cancer surgery Cardiac surgery
Most thoracic surgery Spinal surgery for malignant disease
High NA NA ≥ 5 1.9 7–8 2.7 Bariatric surgery Gynaecological cancer surgery
Pneumonectomy Craniotomy
Traumatic brain injury Spinal cord injury
Other major trauma
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VTE risk assessment scores: gynaecological oncology
17,713 National Surgical Quality Improvement Program cervical, ovarian, uterine, vaginal, vulvar cancers between 2008 and
2013 Caprini and Rogers scores were calculated for each patient 30 day VTE rate 1.8%
Barber EL et al. Am J Obstet Gynecol 2016;215:445.e1‒9
Caprini Rogers Low risk 0% Low risk 0.2% Moderate 0.1% Medium 36.9% High 3.0% High (>10) 63.0% Highest (≥5) 96.9%
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VTE: type of gynaecologic malignancy
National Surgical Quality Improvement Program database 104,368 gynaecologic surgeries: 11,427 for malignancy
Ovarian: 2.7% (n=2800); uterine: 6.8% (n=7114); cervical: 1.0% (n=1026); vulvar: 0.5% (n=487)
VTE rate: 1.8% (202/11,427)
Ovarian cancer :OR 1.5 (95% CI, 1.10‒2.16) VTE 64% lower: MIS vs open surgery VTE higher disseminated vs early cancer (OR, 5.96; p=0.027)
Graul A et al. Int J Gynecol Cancer 2017;27:581‒587
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VTE: abdominal vs minimally invasive hysterectomy
Hysterectomy for benign conditions between 2010 and 2012
National Surgical Quality Improvement
44,167 patients included
2,733 (28.8%) open
22,559 (51.1%) laparoscopic
8875 (20.1%) vaginal
Barber EL et al. Am J Obstet Gynecol 2015;212:609.e1‒7
Open Minimally invasive 0.6% 81 / 12,733 0.2% 73 / 31,434
p
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VTE: laparoscopic surgery for malignancy
2219 NSQIP patients: uterine, ovarian or cervical cancer
VTE rate: 0.7% (15/2219) median time 6 days
No difference in rate of VTE between cancer types
VTE predictive of higher 30-day mortality OR, 26.0; 95% CI, 2.2‒306.9; p=0.01
Mahdi H et al. J Minim Invasive Gynecol 2016;23:1057‒1062
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Impact of VTE on mortality after surgery for different malignant tumours
Trinh VQ, et al. JAMA Surgery 2014; 149:43–9. OR = odds ratio; VTE = venous thromboembolism.
Mortality
Cancer type Overall, % Without VTE, % With VTE, % OR (95%) P-value
Overall 2.0 1.9 12.0 5.30 (4.88–5.76) < 0.001
Colectomy 3.1 2.9 11.3 3.74 (3.34–4.19) < 0.001
Cystectomy 2.5 2.3 9.6 4.58 (3.22–6.51) < 0.001
Oesophagectomy 7.2 6.9 13.6 2.01 (1.13–3.56) 0.02
Gastrectomy 5.7 5.5 14.7 2.81 (2.12–3.73) < 0.001
Hysterectomy 0.4 0.3 5.2 10.93 (6.85–17.45) < 0.001
Lung resection 2.9 2.6 19.8 8.73 (7.39–10.31) < 0.001
Pancreatectomy 4.9 4.7 13.2 3.08 (2.05–4.61) < 0.001
Prostatectomy 0.1 0.1 3.9 56.42 (30.54–104.25) < 0.001
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Venous thromboembolism: Long-term complications and burden
• Post-thrombotic syndrome • Frequency of PTS 20–50% • Severe PTS in 5–10%
• Incidence of sympto-
matic pulmonary hypertension after PE • 1.0% at 6 months • 3.1% at 1 year • 3.8% at 2 years
Pengo V., Lensing A.W.A., Prins M.H., et al. N Engl J Med 2004; 350:2257 - 2264
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4
9
26 132 postoperative patients
40
92 normal
Natural history of postoperative DVT
Kakkar VV, et al. Lancet. 1969;2:230-232.
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Efficacy of low-dose unfractionated heparin (UFH) in prevention of DVT after major surgery
42
8
05
1015202530354045
Control Low-dose UFH
– s.c. low-dose UFH: pre-operative and b.i.d. post-operative
– 78 ‘high-risk’ patients
s.c., subcutaneous; b.i.d., twice a day Kakkar et al. Lancet 1972;2:101–6
Pharmacological Prevention of Thrombosis
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Num
ber o
f pat
ient
s w
ith fa
tal P
E
P < 0.005
Prophylaxis of fatal, postoperative PE with low-dose UFH (2)
16
2
0 2 4 6 8
10 12 14 16 18
Control UFH
Low-dose UFH saves 7 lives for every 1000 operated patients. Kakkar VV et al, Lancet. 1975;2:45-51.
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Bleeding complications
Control Heparin P
Excessive blood loss 126 182 NS
Wound hematoma 117 158 < 0.01
Mean transfusion requirements (mL) 1285 1316 0.34
Mean Hb fall (g/100 mL) 0.7 1.0 0.23
NS = not significant. Kakkar vv et al, Lancet. 1975;2:45-51.
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Thromboprophylaxis in cancer surgery: dose of LMWH
Prospective, randomized, double-blind multicentre trial
LMWH once daily
dalteparin 2,500 IU versus 5,000 IU daily
total duration 7 days
Therapy commenced pre-operatively
2,070 patients randomized
67% malignancy (1,303/1,957)
p = 0.001
Bergqvist D, et al. Br J Surg. 1995;82:496-501.
Bleeding complications in patients operated on for malignant disease occurred in 3.6% of those receiving dalteparin 2,500 IU and 4.6% of those receiving dalteparin 5,000 IU (p = NS).
DV
T in
pat
ient
s w
ith m
alig
nanc
y (%
)
Chart1
Dalteparin 2,500 IU
Dalteparin 5,000 IU
% DVT
14.9
8.5
Sheet1
Dalteparin 2,500 IUDalteparin 5,000 IU
% DVT14.98.5
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LMWH for thromboprophylaxis in benign gynaecologic surgery
Bemiparin 3500 IU n=387 vs. or no intervention n=387
Clinical DVT, PE and fatal PE within 30 days
Immobility OR 7.1; 95% CI, 1.3‒36.2
Varicose veins OR 16.8; 95% CI, 3.1‒76.2
Thrombophilia OR 39.3; 95% CI, 1.5‒1006.7
No major bleeding events or side effects related to bemiparin Alalaf SK et al. J Thromb Haemost 2015;13:2161‒2167
Bemiparin Control 0% 0 / 377 3.2% 12 / 380
95% CI, 0.002-0.6
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(a) Compression (monotherapy) Graduated 9 57/665 133/627 –39.7 37.2 66% (10) compression stockings (8.6%) (21.2%) Intermittent 19 112/1108 268/1147 –76.3 71.0 66% (7) pneumatic compression (10.1%) (23.4%) Footpump 2 11/61 34/65 –10.7 7.3 77% (19) (18.0%) (52.3%)
30 180/1834 435/1839 –126.7 115.5 67% (6)
(9.8%) (23.7%) 2p < 0.00001
No. of Deep venous Stratified Odds ratio and % odds trials thrombosis statistics confidence interval reduction Category with data Compression Control O–E Variance (compression : control) (SE)
Effects of compression methods of thromboprophylaxis on DVT
99% or 95% confidence intervals 0.0 0.5 1.0 1.5 2.0
Compression Compression better worse Treatment effect 2p < 0.00001
Roderick P, et al. Health Technology Assessment 2005; Vol. 9: No. 49.
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(a) Compression (monotherapy) (a) Orthopaedic 8 66/460 172/502 –49.3 38.9 72% (9)
(14.3%) (34.3%) (b) General surgery 11 60/654 150/673 –44.7 40.7 67% (10)
(9.2%) (22.3%) (c) Neurosurgery/spinal 6 27/357 69/354 –21.1 20.8 64% (14)
(7.6%) (19.5%) (d) Gynaecological 3 19/267 32/254 –6.8 11.0 46% (22)
(7.1%) (12.6%) (e) Mixed surgery 1 1/31 5/24 –2.4 1.3 84% (40)
(3.2%) (20.8%) (f) Medical/unknown 1 7/65 7/32 –2.4 2.7 (10.8%) (21.9%) 30 180/1834 435/1839 –126.7 115.4 67% (6)
(9.8%) (23.7%) 2p < 0.00001
No. of Deep venous Stratified Odds ratio and % odds trials thrombosis statistics confidence interval reduction Category with data Compression Control O–E Variance (compression : control) (SE)
Effects of compression methods on DVT among different types of patients
99% or 95% confidence intervals 0.0 0.5 1.0 1.5 2.0
Compression Compression better worse Treatment effect 2p < 0.00001
Roderick P, et al. Health Technology Assessment 2005; Vol. 9: No. 49.
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(a) Compression (monotherapy) Graduated 3 0/123 4/90 –1.8 0.9 compression stockings (0.0%) (4.4%) Intermittent 8 14/590 18/618 –1.6 7.6 pneumatic compression (2.4%) (2.9%) Footpump 1 0/28 0/32 (0.0%) (0.0%) 12 14/741 22/740 –3.4 8.5 33% (28) (1.9%) (3.0%) 2p > 0.1; NS
No. of Deep venous Stratified Odds ratio and % odds trials thrombosis statistics confidence interval reduction Category with data Compression Control O–E Variance (compression : control) (SE)
Effects of compression methods of thromboprophylaxis on PE
99% or 95% confidence intervals 0.0 0.5 1.0 1.5 2.0
Compression Compression better worse Treatment effect 2p = 0.006
Roderick P, et al. Health Technology Assessment 2005; Vol. 9: No. 49.
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VTE: mechanical vs pharmacological prophylaxis
Robotic (n=739) or laparoscopic hysterectomy (n=674) for endometrial carcinoma or
complex hyperplasia with atypia
All patients received mechanical prophylaxis; 61% received additional pharmacologic prophylaxis
Incidence of VTE was 0.35% (5/1413)
Freeman AH et al. Gynecol Oncol 2016;142:267‒272
Pharmacologic Mechanical 0.23% 2 / 865 0.55% 3 / 548
p=0.38
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@RISTOS: VTE risk persists in cancer surgery patients
Agnelli G, et al. Ann Surg. 2006;243:89-95.
Days post-surgery
0
2
4
6
8
10
12
14
1–5 6–10 11–15 16–20 21–25 26–30 > 30
Num
ber o
f VTE
eve
nts
40% of VTEs were observed more than 21 days after cancer surgery
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RIETE: Time course and clinical presentation of post-operative VTE
Arcelus, et al. Thromb Haemost 2008;99:546–51
19%
55% of VTEs were diagnosed after prophylaxis was discontinued
77%
PE Proximal DVT Distal DVT
1 2 7 15 30 60
Clinically overt PE 22 (2.8%) 41 (5.2%) 149 (19%) 376 (48%) 608 (77%) 787 (100%)
Proximal DVT 9 (1.4%) 21 (3.3%) 91 (14%) 248 (39%) 432 (68%) 633 (100%)
Distal DVT 2 (1.1%) 5 (2.7%) 34 (19%) 98 (54%) 145 (80%) 182 (100%)
Days
Cum
ulat
ive
inci
denc
e
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Extended thromboprophylaxis after cancer surgery
All VTE
Proximal DVT
Rasmussen MS, et al. Cochrane Database. 2009:CD004318.
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9th ACCP recommendations on prophylaxis after non-orthopedic surgery
VTE risk categories: very low, low, moderate, and high
For general and abdomino-pelvic surgery at very low risk (Caprini score 0): no specific pharmacologic prophylaxis (1B) or mechanical (2C) other than early ambulation
For general surgery patients at low risk (Caprini score 1-2) suggest mechanical prophylaxis (IPC) over no prophylaxis (2C)
For general surgery patients at moderate risk (Caprini score 3-4) who are not at high risk for major bleeding: suggest LMWH (2B), LDUH (2B), or mechanical prophylaxis with IPC (2C) over no prophylaxis Remark: 3 of 7 authors favored a strong recommendation in favor of LMWH or LDU over no prophylaxis
Gould MK , et al. Chest. 2012; 141 (2) (Suppl): e227s-e277s
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9th ACCP recommendations on prophylaxis after non-orthopedic surgery (II)
For moderate-risk patients undergoing general surgery who are at high risk for major bleeding suggest mecanical prophylaxis, preferably with IPC over no prophylaxis (2C)
For general surgery patients at high-risk for VTE (Caprini score >4) who are not at high risk for bleeding recommend LMWH (1B) or LDUH (1B) over no prophylaxis. We suggest that mechanical prophylaxis with stockings or IPC should be added (2C)
For patients at high risk for VTE undergoing abdominal or pelvic surgery for cancer without high risk for bleeding, we recommend extending pharmacological prophylaxis with LMWH four weeks over limited-duration prophylaxis (1B)
Gould MK , et al. Chest. 2012; 141 (2) (Suppl): e227s-e277s
Preventing VTE in gynaecological surgeryDisclosures for Ajay KakkarMy talk todayAdaptation of the Caprini model by�ACCP 2012VTE risk assessment scores: gynaecological oncology VTE: type of gynaecologic �malignancyVTE: abdominal vs minimally invasive hysterectomy VTE: laparoscopic surgery �for malignancyImpact of VTE on mortality after surgery for different malignant tumoursVenous thromboembolism: �Long-term complications and burdenNatural history of postoperative DVT Pharmacological Prevention of ThrombosisProphylaxis of fatal, postoperative �PE with low-dose UFH (2)Bleeding complicationsThromboprophylaxis in cancer surgery: dose of LMWH LMWH for thromboprophylaxis �in benign gynaecologic surgeryEffects of compression methods of thromboprophylaxis on DVTEffects of compression methods on DVT �among different types of patientsEffects of compression methods of thromboprophylaxis on PE VTE: mechanical vs pharmacological prophylaxis@RISTOS: VTE risk persists in cancer surgery patientsRIETE: Time course and clinical presentation of post-operative VTESlide Number 309th ACCP recommendations on prophylaxis after non-orthopedic surgery9th ACCP recommendations on prophylaxis after non-orthopedic surgery (II)