2. PRESENTATION OBJECTIVES
â˘Provide a brief background regarding VTE
â˘Identify the risk factors for developing VTE
â˘Review general principles for Thromboprophylaxis
â˘Review CHEST Guideline VTE prophylaxis
recommendations for
â˘Medical Conditions
â˘Orthopedic Surgery
â˘Review old and new suggested medications to be used
for VTE prevention
â˘Describe potential drug-interactions
3. VENOUS THROMBOEMBOLISM
Result of clot formation in venous circulation
Manifests as
â˘Deep vein thrombosis (DVT) or
â˘Pulmonary embolism (PE)
Develops as a result of three primary components
known as Virchowâs triad
7. DVT prophylaxis
Incidence of DVT in the hospital is 10-40% per month
for medical or general surgical patients and 40-60%
following major orthopedic surgeries
Consequences of unprevented VTE:
â˘Symptomatic DVT or PE
â˘Fatal PE
â˘Increased spending for investigation symptomatic
patients
â˘Increased risk of recurrence
â˘Chronic post-thrombotic syndrome
DVT prophylaxis, has a desirable benefit-to-risk ratio
8. RISK FACTORS
Strong Risk Factors
Odds Ratio > 10
â˘Hip or Leg Fracture
â˘Hip or Knee Replacement
â˘Major General Surgery
â˘Major Trauma
â˘Spinal Cord Injury
Moderate Risk Factors
Odds Ratio 2-9
â˘Athroscopic Knee Surgery
â˘Central Venous Lines
â˘Chemotherapy
â˘CHF or Respiratory Failure
â˘Hormone Replacement
Therapy
â˘Malignancy
â˘Oral Contraceptive Therapy
â˘Paralytic Stroke
â˘Pregnancy/ Postpartum
â˘Previous VTE
â˘Thrombophilia
Weak Risk Factors
Odds Ration <2
â˘Bed rest>3 days
â˘Immobility due to sitting
â˘Increasing Age
â˘Laparoscopic Surgery
â˘Obesity
â˘Pregnancy/ Antepartum
â˘Varicose Veins
9. GENERAL THROMBOPROPHYLAXIS
RECOMMENDATIONS
Level of Risk Estimated DVT Risk Suggested Thromboprophylaxis
Low
ď Minor surgery in mobile patients
ď Medical patients who are fully
mobile
<10% Early and aggressive ambulation
Moderate
ď Medical pts, bed rest or sick
ď Most general, open gynecologic or
urologic surgery patients
ď Moderate VTE + High bleeding risk
10%-40%
LMWH, LDUH BID/TID or
Fondaparinux
Mechanical
Thromboprophylaxis
High Risk
ď Hip or knee arthroplasty, Major
Trauma, SCI
ď High VTE + High Bleeding risk 40% - 80%
LMWH
Mechanical Thromboprophylaxis
10. Additional risk factors for VTE in
medical patients
Advanced age Previous VTE Cancer
Stroke with
lower extremity
weakness
Congestive
Heart Failure
COPD
Exacerbation
Sepsis Bed Rest
12. Why thromboprophylaxis in orthopedic
surgery?
Incidence of venous thromboembolism (VTE)
complications such as
ď§ deep vein thrombosis (DVT)
ď§ pulmonary embolism (PE)
Most of these thrombi resolve spontaneously;
â 1â4% - develop into symptomatic VTE.
Fatal pulmonary embolisms â
ď§ 0.3â1% following total joint arthroplasty (TJA) and
ď§ 3.6% after hip fracture surgery (HFS).
A proactive approach to reduce the incidence of VTE
is therefore of paramount importance.
40â60% within 7 to 14 days
13. Baseline Postoperative Risks of VTE Outcomes
in the Absence of Pharmacological Prophylaxis
Outcome Total Hip
Replacement
Strength of
Evidence
(THR)
Total Knee
Replacement
Strength of
Evidence
(TKR)
Pulmonary
embolism
6% Low 1% Low
Deep vein
thrombosis
39% Low 46% Low
Major
bleeding
1% Moderate 3% Low
Minor
bleeding
5% Low 5% Moderate
Sobieraj DM, Coleman CI, Tongbram V, et al. Comparative Effectiveness Review No. 49. Available at
www.effectivehealthcare.ahrq.gov/thrombo.cfm.
14. History of thromboprophylaxis
⢠1937-Relationship between surgery and venous
thromboembolism (VTE)
⢠1954- Vit K antagonist for thromboprophylaxis
⢠1980s-LMWH -superior to UFH
⢠2002- Fondaparinux introduced.
⢠2008-Dabigatran and Rivaroxaban
⢠2011-Apixaban
16. Thromboprophylaxis Options
Mechanical Pharmacological
Graduated Compression Stockings
ASPIRIN and other antiplatelet agents
HEPARIN UFH
LMWH
Venous Foot Pumps
Vit K antagonist WARFARIN
Active External Compression Devices
Factor Xa
Inhibitors
FONDAPARINUX
APIXABAN
Continuous Intermittent RIVAROXABAN
DABIGATRAN
17. Comparative Effectiveness of Mechanical
Prophylaxis Versus No Thromboprophylaxis
⢠Mechanical prophylaxis significantly
decreased deep vein thrombosis (DVT; results from
one randomized controlled trial; strength of evidence not rated).
⢠The risk for proximal or distal DVT was
not significantly different (results from one randomized
controlled trial; strength of evidence not rated).
⢠Data are not available to evaluate the
comparative effect of mechanical
prophylaxis versus no prophylaxis on
other outcomes
23. Comparative Effectiveness of Pharmacological
Prophylaxis Versus No Pharmacological Prophylaxis
Outcome Magnitude of
Effect
RR/OR (95% CI),
NNT/NNH
Strength
of Evidence
DVT Decreases risk by
44%
RR 0.56 (0.47 to 0.68),
NNT 3 to 33
Moderate
Proximal DVT Decreased risk by
47%
RR 0.53 (0.39 to 0.74),
NNT 4 to 213
High
Distal DVT Decreased risk by
41%
RR 0.59 (0.42 to 0.82),
NNT 8 to 35
High
Asymptomatic
DVT
Decreased risk by
48%
RR 0.52 (0.40 to 0.69),
NNT 4 to 6
Moderate
Abbreviations: 95% CI = 95-percent confidence interval; NNH = number needed to harm (the calculated range); NNT = number
needed to treat (the calculated range; NR = not reported or insufficient evidence to permit conclusions; OR = odds ratio; RR =
relative risk
24. Comparative Effectiveness of Pharmacological
Prophylaxis Versus No Pharmacological Prophylaxis
Outcome Magnitude of
Effect
RR/OR (95% CI),
NNT/NNH
Strength
of Evidence
Symptomatic VTE NR
Major VTE Decreased risk by
79%
RR 0.21 (0.05 to 0.95),
NNT 19 to 22
Low
PE No difference OR 0.38 (0.13 to 1.07) Low
Major Bleeding No difference RR 0.74 (0.36 to 1.51) Moderate
Minor Bleeding Relative risk is
higher for
pharmacologica
l prophylaxis by
67%
RR 1.67 (1.18 to
2.38),
NNH 30 to 75
High
Abbreviations: 95% CI = 95-percent confidence interval; NNH = number needed to harm (the calculated range); NNT = number
needed to treat (the calculated range; NR = not reported or insufficient evidence to permit conclusions; OR = odds ratio; RR =
relative risk
25. Warfarin (CoumadinÂŽ)
⢠INR target of 2.5 (Range between 2 â 3)
â Dose adjust based on INR Results
â Reversal with Vitamin K
⢠Many drug and food interactions
â Metabolized primarily by CYP2c9 and CYP3A4
â Works by inhibiting the formation of Vitamin-K
dependent clotting factors
⢠Adverse Effects:
â Alopecia, hemorrhage, tissue necrosis (rare)
25
27. Unfractionated Heparin
⢠VTE Prophylaxis Dosing
â 5000 Units subcutaneously every 8 â 12
hours
â Knee or hip replacement: give 2 hours
before surgery, resume at full dose after
surgery for at least 7 days
⢠Renal adjustment not required
27
32. Enoxaparin (LovenoxÂŽ)
⢠DVT Prophylaxis Dosing
â Knee or Hip Replacement: 30 mg subcutaneous
every 12 hours
â Medical Patients: 40mg subcutaneously every
24 hours
⢠Dose Reduction is required in patients with
CrCl less than 30 mL/min
â Knee or Hip replacement: 30 mg every 24 hours
â Medical patients: 30mg every 24 hours
32
33. LMWH
⢠Adverse Effects
â Hemorrhage (7%),
â AST/ALT elevation (6%),
â Fever (5%),
â Local Site reactions (2-5%)
35. FACTOR Xa INHIBITORS
FACTOR Xa INHIBITORS
DIRECT INHIBITORS INDIRECT INHIBITORS
RIVAROXABAN FONDAPARINUX
Synthetic
indirect inhibitor of Factor Xa
APIXABAN
EDOXABAN
36. DIRECT FACTOR Xa INHIBITORS
Rivaroxaban Apixaban Edoxaban
Prevention of VTE in patients
undergoing elective hip or knee
replacement surgery
â â
â
(Japan only)
Treatment of DVT and PE and
prevention of recurrent DVT and PE
âa âa â
Prevention of stroke and systemic
embolism in patients with NVAF
with âĽ1 risk factors
â â â
Secondary prevention of ACS âb x x
aCan be used without pre-treatment with parenteral anticoagulant;
bIn patients with elevated cardiac biomarkers and no prior stroke or TIA, and co-
administered with ASA or ASA plus clopidogrel or ticlopidine
37. DIRECT FACTOR Xa INHIBITORS
Rivaroxaban Apixaban Edoxaban
BRAND NAME XARELTO ELIQUIS SAVAYSA
MECHANISM DIRECT Xa
INHIBITORS
DIRECT Xa
INHIBITORS
DIRECT Xa
INHIBITORS
INDICATION ATRIAL
FIBRILLATION
T/T OF VTE
PROPHYLAXIS OF
VTE
ATRIAL
FIBRILLATION
T/T OF VTE
PROPHYLAXIS OF
VTE
ATRIAL
FIBRILLATION
T/T OF VTE
BIOAVAILABIL
ITY
80% 66% 62%
HALF LIFE 7-11 13 10-14
ONSET 2-4 1-3 1-2
38. ⢠Fondaparinux -synthetic pentasaccharide
fac- Xa inhibitor.
⢠O-methyl group + five monomeric sugar
units
⢠Binding of heparin/HS to ATIII has been shown to increase the anti-
coagulant activity of antithrombin III 1000 fold.
⢠In contrast to heparin, fondaparinux does
not inhibit thrombin.
Fondaparinux (ArixtraÂŽ)
39. Fondaparinux (ArixtraÂŽ)
⢠VTE Prophylaxis Dosing (Patients >50kg)
â 2.5mg subcutaneously every 24 hours
â Knee or Hip Replacement: Give 6-8 hours AFTER surgery
⢠No official dose adjustment recommendations
â CrCl 20 â 50 mL/min: 1.5 mg every 24 hours has been used
â Clearance is reduced 25-40% in patients with CrCl between
30 and 80 mL/min
â CONTRAINDICATED if CrCl is less than 30mL/min
⢠Adverse Effects
â Anemia (20%), Fever (14%), Nausea (11%), Rash (7.5%)
39
40. Fondaparinux vs Enoxaparin for the Prevention of Venous
Thromboembolism in Major Orthopedic Surgery: A Meta-analysis of 4
Randomized Double-blind Studies. Arch Intern Med. 2002;162(16):1833-1840
⢠Methods : A meta-analysis of 4 multicenter, randomized, double-blind trials in patients undergoing
elective hip replacement, elective major knee surgery, and surgery for hip fracture (N = 7344) was
performed to determine whether a subcutaneous 2.5-mg, once-daily regimen of fondaparinux sodium
starting 6 hours after surgery was more effective and as safe as approved enoxaparin regimens in
preventing VTE. The primary efficacy outcome was VTE up to day 11, defined as deep vein thrombosis
detected by mandatory bilateral venography or documented symptomatic deep vein thrombosis or
pulmonary embolism. The primary safety outcome was major bleeding.
⢠Results: Fondaparinux significantly reduced the incidence of VTE by day 11 (182 [6.8%] of 2682
patients) compared with Enoxaparin (371 [13.7%] of 2703 patients), with a common odds reduction of
55.2% (95% confidence interval, 45.8% to 63.1%; P<.001); this beneficial effect was consistent across
all types of surgery and all subgroups. Although major bleeding occurred more frequently in the
fondaparinux-treated group (P = .008), the incidence of clinically relevant bleeding (leading to death or
reoperation or occurring in a critical organ) did not differ between groups.
⢠Conclusion: In patients undergoing orthopedic surgery, 2.5 mg of fondaparinux sodium once daily,
starting 6 hours postoperatively, showed a major benefit over enoxaparin, achieving an overall risk
reduction of VTE greater than 50% without increasing the risk of clinically relevant bleeding.
41. Dabigatran (PradaxaÂŽ)
⢠FDA Approved for VTE prophylaxis
â 150mg by mouth twice daily
â 75mg by mouth if CrCl is less than 30 mL/min
⢠Surgical considerations
â Discontinue 1-2 days prior to an invasive or elective surgical
procedure
⢠Discontinue 3-5 days prior to procedure if CrCl is less than 50
â Reinitiate ASAP after procedures
â Not reversible
⢠Adverse Effects
â GI effects (6.1%), Bleeding (16.6%)
41
42. Rivaroxaban (XareltoÂŽ)
⢠VTE Prophylaxis Dosing
â Knee or hip replacement surgery: 10mg by mouth daily
⢠Begin 6 â 10 hours after surgery
⢠Continue for 12 days after knee, 35 days after hip
â Secondary DVT/PE Prophylaxis: 2omg by mouth daily
â DISCONTINUE at least 24 hours prior to procedure
⢠Avoid if CrCl is less than 30 mL/min
⢠Adverse Effects
â Bleeding (5.8%), Epidural hematoma
⢠Carries same Black box Warning as LMWHs
42
43. Apixaban (EliquisÂŽ)
⢠New reversible and selective active site inhibitor of factor Xa
⢠Dosing (European Medicines Agency-Approved dosing)
â Knee replacement surgery: 2.5mg by mouth daily
⢠Begin 12 â 24 hours after surgery
⢠Continue 10 â 14 days
â Hip replacement surgery: 2.5mg by mouth twice daily
⢠Begin 12 â 24 hours after surgery
⢠Continue 32 â 38 days
â DISCONTINUE 24 - 48 hours prior to elective or invasive surgery
procedures
⢠Dose adjusted for body weight, age, renal impairment, and
CYP3A4 inhibitors
43
44. IMPORTANT DRUG INTERACTIONS
⢠Medications that increase bleeding risk
â SSRIâs and SNRIs
â Medications for pain (NSAIDs, Willow Bark)
â Kava Kava may impair blood clotting due to effects on the liver
⢠Medications that alter metabolism
â Barbiturates, such as phenobarbital, may induce metabolism of
heparins, decreasing effect
â Carbamazepine/oxcarbamezapine and St. Johnâs Wort induce
metabolism of warfarin and apixaban by inducing 3A4 and 2C9
⢠Bad habits
â Smoking induces metabolism
â Alcohol increasing bleeding risk
44
46. Prolonged (âĽ28 Days) Versus Standard (7â10 Days)
Pharmacological Prophylaxis: Clinical Outcomes
Prolonged Versus
Standard-Duration
Prophylaxis
Magnitude of
Effect
Risk/Odds (95% CI) NNT/NNH Strength of
Evidence
Symptomatic VTE Decreased
risk by 62%
RR 0.38
(0.19 to 0.77)
NNT 8 to 54 Moderate
PE Decreased
odds by 87%
OR 0.13
(0.04 to 0.47)
NNT 24 to 232 High
Nonfatal PE Decreased odds by
87%
OR 0.13 (0.03 to
0.54)
NNT 58 Moderate
DVT Decreased risk by
63%
RR 0.37 (0.21 to
0.64)
NNT 5 to 32 Moderate
Asymptomatic DVT Decreased risk by
52%
RR 0.48 (0.31 to
0.75)
NNT 8 to 65 High
Symptomatic DVT Decreased odds by
64%
OR 0.36 (0.16 to
0.81)
NNT 27 to 79 High
Proximal DVT Decreased
risk by 71%
RR 0.29
(0.16 to 0.52)
NNT 9 to 71 High
47. Total Hip or Knee Arthroplasty
Pharmacological Options
⢠Low-Molecular Weight
Heparin
⢠Fondaparinux
⢠Apixaban
⢠Dabigatran
⢠Rivaroxaban
⢠Low-Dose Unfractionated
Heparin
⢠Warfarin (INR 2-3)
⢠Aspirin
Additional Remarks
⢠LMWH Preferred
⢠Pharmacological therapy
should be continued for a
minimum of 10-14 days
⢠Intermittent pneumatic
compression devices should be
used with patients with high
bleeding risk
â Goal is to achieve 18h daily
compliance
48. Pharmacological Options Additional Remarks
⢠LMWH Preferred
⢠Pharmacological therapy should
be continued for a minimum of
10-14 days
⢠Intermittent pneumatic
compression devices should be
used with patients with high
bleeding risk
â Goal is to achieve 18h daily
compliance
Hip Fracture Surgery
⢠Low-Molecular Weight
Heparin
⢠Fondaparinux
⢠Low-Dose
Unfractionated Heparin
⢠Warfarin (INR 2-3)
⢠Aspirin
49. Additional Considerations
⢠Low-Molecular Weight Heparins (Enoxaparin)
â Start 12 or more hours preoperatively OR 12 hours or more
postoperatively
⢠Guidelines suggest to extend prophylaxis in the outpatient period
for up to 35 days from the date of surgery
⢠Guidelines Suggest using dual prophylaxis with an
antithrombotic agent AND an IPCD during hospital stay
⢠Therapy is not recommended in patients undergoing knee
arthroscopy
50. BLACK BOX WARNING!!!
âEpidural or spinal
hematomas, which may
result in long-term paralysis,
may occur in patients who
are anticoagulated with
LMWHs or heparinoids and
are receiving neuroaxial
anesthesia or undergoing
spinal punctureâ
50
51. Choice of Long-Term (First 3 Months) and Extended
(No Scheduled Stop Date) Anticoagulant
1. In patients with proximal DVT or pulmonary embolism (PE),
long-term (3 months) anticoagulant therapy over no such
therapy (Grade1B).
2. In patients with DVT of the leg or PE and no cancer, as long-
term (first 3 months) anticoagulant therapy,
dabigatran, rivaroxaban, apixaban,or edoxaban over
vitamin K antagonist (VKA)therapy (all Grade 2B).
⢠For patients with DVT of the leg or PE and no cancer who are
not treated with dabigatran, rivaroxaban,apixaban, or
edoxaban, VKA therapy over low-molecular
weight heparin (LMWH) (Grade 2C).
52. Choice of Long-Term (First 3 Months) and Extended
(No Scheduled Stop Date) Anticoagulant
3. In patients with DVT of the leg or PE and cancer
(cancer-associated thrombosis), as long-term (first3
months) anticoagulant therapy, we suggest LMWH
over VKA therapy (Grade 2B), dabigatran (Grade 2C),
rivaroxaban (Grade 2C), apixaban (Grade 2C), or
edoxaban (Grade 2C).
4. In patients with DVT of the leg or PE who receive
extended therapy, we suggest that there is no need to
change the choice of anticoagulant after the first 3
months (Grade 2C).
53. Duration of Anticoagulant Therapy
⢠In patients with a proximal DVT of the leg or PE
provoked by surgery, we recommend treatment with
anticoagulation for 3 months over
⢠(i) treatment of a shorter period (Grade 1B),
⢠(ii) treatment of a longer time-limited period
(eg, 6, 12, or 24 months)(Grade 1B), or
⢠(iii) extended therapy (no scheduled stop date)
(Grade 1B).
54. Duration of Anticoagulant Therapy
6. In patients with a proximal DVT of the leg or PE
provoked by a nonsurgical transient risk factor,
Anticoagulation For 3 Months over
(i) treatment of a shorter period (Grade 1B) and
(ii) treatment of a longer time-limited period (eg, 6,
12, or 24 months) (Grade 1B).
(iii) anticoagulation for 3 months over extended
therapy if there is a low or moderate bleeding
risk (Grade 2B), and recommend treatment for 3
months over extended therapy if there is a high
risk of bleeding (Grade 1B).
55. Regional Anesthetic Management of
the Patient on Oral Anticoagulants
1. Caution should be used when performing neuraxial techniques
in patients recently discontinued from long-term warfarin
therapy.
â˘In the first 1 to 3 days after discontinuation of warfarin therapy, the
coagulation status (reflected primarily by factor II and X levels) may
not be adequate for hemostasis despite a decrease in the INR
(indicating a return of factor VII activity).
â˘Adequate levels of II, VII, IX, and X may not be present until the
INR is within reference limits.
â˘The anticoagulant therapy must be stopped (ideally 4 to 5 days
before the planned procedure) and the INR must be normalized before
initiation of neuraxial block (grade 1B).
56. Regional Anesthetic Management of the Patient on Oral
Anticoagulants
2. Avoid concurrent use of medications that affect other
components of the clotting mechanisms and may increase the risk
for bleeding complications for patients receiving oral
anticoagulants and do so without influencing the INR. (grade 1A).
These medications include aspirin and other
â˘NSAIDs,
â˘Ticlopidine and Clopidogrel,
â˘UFH, and
â˘LMWH
57. Regional Anesthetic Management of the Patient on Oral
Anticoagulants
3. In patients who are likely to have an enhanced response to the
drug, a reduced dose be administered.
Algorithms have been developed to guide physicians in the
appropriate dosing of warfarin based on desired indication, patient
factors, and surgical factors.
These algorithms may be extremely useful in patients at risk for an
enhanced response to warfarin (grade 1B).
4. In patients receiving an initial dose of warfarin before surgery, the
INR should be checked before neuraxial block if the first dose was
given more than 24 hours earlier or if a second dose of oral
anticoagulant has been administered (grade 2C).
58. Regional Anesthetic Management of the Patient on Oral
Anticoagulants
5. In patients receiving low-dose warfarin therapy during epidural
analgesia, we suggest that their INR be monitored on a daily
basis (grade 2C).
6. Neurologic testing of sensory and motor function should be
performed routinely during epidural analgesia for patients on
warfarin therapy.
To facilitate neurologic evaluation the type of analgesic solution be
tailored to minimize the degree of sensory and motor blockade
(grade 1C).
59. Regional Anesthetic Management of the Patient on Oral
Anticoagulants
7. As thromboprophylaxis with warfarin is initiated, neuraxial
catheters should be removed when the INR is less than 1.5.
Neurologic assessment be continued for at least 24 hours after
catheter removal for these patients (grade 2C).
8. In patients with INR greater than 1.5 but less than 3, removal of
indwelling catheters should be done with caution and the
medication record reviewed for other medications that may
influence hemostasis that may not affect the INR (e.g., NSAIDs,
ASA, clopidogrel, ticlopidine, UFH, LMWH)(grade 2C).
Neurologic status be assessed before catheter removal and
continued until the INR has stabilized at the desired prophylaxis
level (grade 1C).
60. Regional Anesthetic Management of the Patient on Oral
Anticoagulants
9. In patients with an INR greater than 3, the warfarin dose be
held or reduced in patients with indwelling neuraxial catheters
(grade 1A).
There is no definitive recommendation regarding the management
to facilitate removal of neuraxial catheters in patients with
therapeutic levels of anticoagulation during neuraxial catheter
infusion (grade 2C).
61. Anesthetic Management of the Patient Receiving Low-
molecular-Weight Heparin
1. The anti-Xa level is not predictive of the risk for bleeding. We
recommend against the routine use of monitoring of the anti-Xa
level (grade 1A).
2. Antiplatelet or oral anticoagulant medications administered in
combination with LMWH increase the risk for spinal hematoma.
Education of the entire patient care team is necessary to avoid
potentiation of the anticoagulant effects. We recommend against
concomitant administration of medications affecting hemostasis,
such as antiplatelet drugs, standard heparin, or dextran, regardless
of LMWH dosing regimen (grade 1A).
62. 3. The presence of blood during needle and catheter
placement does not necessitate postponement of surgery.
We suggest that initiation of LMWH therapy in this
setting should be delayed for 24 hours postoperatively and
that this consideration be discussed with the surgeon
(grade 2C).
4. Preoperative LMWH.
⢠Patients on preoperative LMWH thromboprophylaxis
can be assumed to have altered coagulation. In these
patients,we recommend that needle placement should
occur at least 10 to 12 hours after the LMWH dose (grade
1C)
63. ⢠In patients receiving (treatment) doses of LMWH, such as
enoxaparin 1 mg/kg every 12 hours, enoxaparin 1.5 mg/kg daily,
dalteparin 120 units/kg every 12 hours, dalteparin 200 units/kg daily,
or tinzaparin 175 units/kg daily, delay of at least 24 hours to ensure
normal hemostasis at the time of needle insertion (grade 1C).
⢠In patients administered a dose of LMWH 2 hours preoperatively
(general surgery patients), AVOID neuraxial techniques because
needle placement would occur during peak anticoagulant activity
(grade 1A).
64. 5. Postoperative LMWH. Patients with postoperative LMWH
thromboprophylaxis may safely undergo single-injection and
continuous catheter techniques. Management is based on total daily
dose, timing of the first postoperative dose and dosing schedule
(grade 1C).
⢠Twice-daily dosing. This dosage regimen is associated with an
increased risk for spinal hematoma. The first dose of LMWH should
be administered no earlier than 24 hours postoperatively, regardless of
anesthetic technique, and only in the presence of adequate (surgical)
hemostasis. Indwelling catheters should be removed before initiation
of LMWH thromboprophylaxis. If a continuous technique is selected,
the epidural catheter may be left indwelling overnight, but must be
removed before the first dose of LMWH. Administration of LMWH
should be delayed for 2 hours after catheter removal.
65. ⢠Single-daily dosing.
⢠The first postoperative LMWH dose should be administered 6 to 8
hours postoperatively. The second postoperative dose should occur
no sooner than 24 hours after the first dose. Indwelling neuraxial
catheters may be safely maintained. However, the catheter should
be removed a minimum of 10 to 12 hours after the last dose of
LMWH. Subsequent LMWH dosing should occur a minimum of 2
hours after catheter removal. No additional hemostasis-altering
medications should be administered because of the additive
effects.
66. Venous Thromboprophylaxis in Adult Hip Fracture Surgery,
Elective Peri-Acetabular Osteotomy and Surgical Hip Dislocation
Key:
AES â anti-embolic stockings
CrCL- creatinine clearance
HIT â Heparin-induced thrombocytopenia
VTE â venous thromboembolism
67. The risk of VTE is further increased in the
presence of:
⢠Active cancer/ cancer treatment
⢠Age > 60 years
⢠Critical care admission
⢠Dehydration
⢠Known thrombophilias
⢠Obesity (BMI > 30 kg / m2)
⢠One or more significant medical co-morbidities e.g. heart disease;
metabolic, endocrine or respiratory pathologies; acute infectious diseases;
inflammatory conditions
⢠Personal or first-degree family history of VTE
⢠Hormone therapy - combined oral contraceptives, HRT, high dose
progestogens, selective oestrogen receptor modulators
⢠Varicose veins with associated phlebitis
⢠Pregnancy or < 6 weeks post partum.
68. Contra-indications to AES
⢠Gross oedema
⢠Leg deformity/condition
⢠Peripheral vascular disease
⢠If peripheral arterial disease present, seek
expert opinion before fitting
⢠Peripheral neuropathy
69. Contra-indications to pharmacological
thromboprophylaxis
I. On oral anticoagulant with INR > 2. 0
II. Thrombocytopenia (platelets < 50 x 109 / L)
III. Known bleeding disorder
IV. Evidence of active bleeding
V. Uncontrolled hypertension (BP > 230 / 120 mm Hg)
VI. Lumbar puncture/ epidural/ spinal analgesia expected
within next 12 hours or performed within last 4 hours
(24 hours if traumatic)
VII. New stroke (ischaemic or haemorrhagic)
70. Aspirin for the Prophylaxis of Venous Thromboembolic Events in Orthopedic Surgery Patients: A
Comparison of the AAOS and ACCP Guidelines With Review of the Evidence.
David W Stewart, Jessica E Freshour. The Annals of Pharmacotherapy. 2013;47(1):63-74.
Objective: To evaluate the appropriateness of aspirin to prevent VTE in high-risk orthopedic
surgery patients.
Data sources: Guidelines published by the AAOS in 2011 and the ACCP in 2012 were
compared regarding their recommendations on the use of aspirin for the prevention of
VTE. A literature search was also conducted to identify clinical trials that evaluated the
use of aspirin for the prevention of VTE in this patient population.
Study selection and data extraction: Any study that evaluated aspirin, even in combination
with another method of prophylaxis (such as pneumatic compression devices), and had
been published during or after 1985 was included.
Conclusions: Recent changes to both the ACCP and AAOS guidelines are in agreement for
those who choose to use aspirin for chemoprophylaxis of VTE. Current surgical care
improvement project measures do not include aspirin as an appropriate sole option for
the prevention of VTE, but in patients undergoing elective TKA or who have a
contraindication to pharmacologic prophylaxis and undergo a THA or HFS, aspirin in
conjunction with compression devices as part of a multimodal approach would meet
these measures. Data do not support the hypothesis that aspirin is less likely to cause
adverse bleeding events than more potent anticoagulants.
72. In patients undergoing total hip arthroplasty (THA)
or total knee arthroplasty (TKA)
⢠Recommendation: minimum of 10 to 14 days
rather than no antithrombotic prophylaxis:
â low-molecular-weight heparin (LMWH),
â fondaparinux,
â apixaban,
â dabigatran,
â rivaroxaban,
â low-dose unfractionated heparin (LDUH),
â adjusted-dose vitamin K antagonist (VKA),
â aspirin (all Grade 1B) , or
⢠an intermittent pneumatic compression device
(IPCD)(Grade 1C)
73. In patients undergoing hip fracture
surgery (HFS)
⢠Recommendation:
⢠one of the following rather than no
antithrombotic prophylaxis for a minimum of
10 to 14 days:
â LMWH,
â fondaparinux,
â LDUH,
â adjusted-dose VKA,
â Aspirin (all Grade 1B) ,
⢠or an IPCD (Grade 1C) .
74. For patients undergoing major orthopedic surgery (THA,
TKA, HFS) and receiving LMWH as thromboprophylaxis
⢠Starting either 12 h or more
preoperatively or
⢠12 h or more postoperatively rather
than within 4 h or less preoperatively
or 4 h or less postoperatively
⢠(Grade 1B) .
75. In patients undergoing THA or TKA
⢠Irrespective of the concomitant use of an IPCD or length
of treatment,
⢠Recommendation:
⢠use of LMWH in preference to the other agents
(alternatives):
â fondaparinux,
â apixaban,
â dabigatran,
â rivaroxaban,
â LDUH (all Grade 2B) ,
â adjusted-dose VKA, or
â aspirin (all Grade 2C) .
76. For patients undergoing major orthopedic
surgery
⢠Recommendation:
⢠extending thromboprophylaxis in the outpatient
period for up to 35 days from the day of surgery
rather than for only 10 to 14 days (Grade 2B) .
⢠using dual prophylaxis with an antithrombotic agent
and an IPCD during the hospital stay (Grade 2C) .
⢠With increased risk of bleeding using an IPCD or no
prophylaxis rather than pharmacologic treatment
(Grade 2C) .
77. In patients undergoing major orthopedic surgery and who decline
or are uncooperative with injections or an IPCD
⢠Recommendation: Using
â Apixaban
â Dabigatran
â Rivaroxaban
⢠adjusted-dose VKA (if apixaban or
dabigatran are unavailable) rather than
alternative forms of prophylaxis (all Grade
1B) .
78. In patients undergoing major orthopedic
surgery
⢠Suggestion against
⢠using inferior vena cava (IVC) filter
placement for primary prevention over no
thromboprophylaxis
⢠in patients with an increased bleeding risk
⢠contraindications to both pharmacologic
and mechanical thromboprophylaxis
(Grade 2C) .
79. No prophylaxis rather than
pharmacologic
thromboprophylaxis⢠In patients with isolated lower-leg injuries
requiring leg immobilization
(Grade 2C) .
⢠For patients undergoing knee arthroscopy
without a history of prior VTE
⢠For asymptomatic patients following major
Orthopedic surgery, we recommend against
doppler (or duplex) ultrasound (DUS)
screening before hospital discharge (grade 1B)
.
Editor's Notes
following orthopaedic lower limb surgery without thromboprophylaxis (1,2).
Heparin potentiates the activities of antithrombin III. This inactivates Factor X and inhibits to conversion of thrombin to thrombin and prevents fibrin conversion to fibrinogen during active thrombosis.
O-methyl group at the reducing end of the molecule, the identitWithin heparin and heparin sulfate this monomeric sequence is thought to form the high-affinity binding site for the anti-coagulant factor antithrombin III (ATIII). y and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units of the polymeric
Fondaparinux is an agent that selectively binds to antithrombin III and potentiates the neutralization of Factor Xa, inhibiting thrombin formation
Directly inhibits thrombin (Factor IIa). This prevents free and clot-bound thrombin and thrombin-induced platelet aggregation
Rivaroxaban selectively inhibits factor Xa without the need of a cofactor. In other words, it works like heparin, but does not need antithrombin III
Phenobarbital may be used for patients with sedation. It has a very long half life, and effects on medications may not be stabilized for 3 â 4 weeks.
Adapted from the NICE Clinical Guideline 92 Venous Thromboembolism: Reducing the Risk Evidence - Review by October 2016