thromboprophylaxisinorthopedicsurgery-171212082736.pptx

Miltefosine

o Miltefosine, an oral drug, is effective in treating visceral leishmaniasis, especially in India, with a 28-day course.
o It can also be used in combination with liposomal amphotericin.
o Miltefosine is effective against New World cutaneous leishmaniasis as well.

o Common side effects include vomiting and diarrhea, while liver enzyme elevations and nephrotoxicity may occur transiently.
o Pregnancy should be avoided during treatment due to teratogenic effects.

Paromomycin

o Paromomycin sulfate, an aminoglycoside antibiotic, has been developed for treating visceral leishmaniasis.
o It is less expensive than other treatments and showed excellent efficacy in a trial in India.
o However, a trial in Africa showed poorer efficacy compared to sodium stibogluconate.
o Initial studies reported good tolerability, with mild injection pain, uncommon ototoxicity, reversible liver enzyme elevations, and no nephrotoxicity.
o Paromomycin has also shown effectiveness when applied topically for cutaneous leishmaniasis.

Miltefosine

o Miltefosine, an oral drug, is effective in treating visceral leishmaniasis, especially in India, with a 28-day course.
o It can also be used in combination with liposomal amphotericin.
o Miltefosine is effective against New World cutaneous leishmaniasis as well.

o Common side effects include vomiting and diarrhea, while liver enzyme elevations and nephrotoxicity may occur transiently.
o Pregnancy should be avoided during treatment due to teratogenic effects.

Paromomycin

o Paromomycin sulfate, an aminoglycoside antibiotic, has been developed for treating visceral leishmaniasis.
o It is less expensive than other treatments and showed excellent efficacy in a trial in India.
o However, a trial in Africa showed poorer efficacy compared to sodium stibogluconate.
o Initial studies reported good tolerability, with mild injection pain, uncommon ototoxicity, reversible liver enzyme elevations, and no nephrotoxicity.
o Paromomycin has also shown effectiveness when applied topically for cutaneous leishmaniasis.

Miltefosine

o Miltefosine, an oral drug, is effective in treating visceral leishmaniasis, especially in India, with a 28-day course.
o It can also be used in combination with liposomal amphotericin.
o Miltefosine is effective against New World cutaneous leishmaniasis as well.

o Common side effects include vomiting and diarrhea, while liver enzyme elevations and nephrotoxicity may occur transiently.
o Pregnancy should be avoided during treatment due to teratogenic effects.

Paromomycin

o Paromomycin sulfate, an aminoglycoside antibiotic, has been developed for treating visceral leishmaniasis.
o It is less expensive than other treatments and showed excellent efficacy in a trial in India.
o However, a trial in Africa showed poorer efficacy compared to sodium stibogluconate.
o Initial studies reported good tolerability, with mild injection pain, uncommon ototoxicity, re
Miltefosine

o Miltefosine, an oral drug, is
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1. Supervision by: Ghazi Ariki RESEARCH Of deep veen thrombosis and pulmonary embolism Done by : basheer mohammed alkamali بشير محمد دبوان الكمالي Level 4 Group B

2. PRESENTATION OBJECTIVES Provide a brief background regarding VTE Identify the risk factors for developing VTE Review general principles for Thromboprophylaxis Review CHEST Guideline VTE prophylaxis recommendations for Medical Conditions Orthopedic Surgery Review old and new suggested medications to be used for VTE prevention Describe potential drug-interactions

3. VENOUS THROMBOEMBOLISM Result of clot formation in venous circulation Manifests as Deep vein thrombosis (DVT) or Pulmonary embolism (PE) Develops as a result of three primary components known as Virchow’s triad

4. VIRCHOW’S TRIAD

5. 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: Symptomatic DVT or PE Fatal PE Increased spending for investigation symptomatic patients Increased risk of recurrence Chronic post-thrombotic syndrome DVT prophylaxis, has a desirable benefit-to-risk ratio

6. RISK FACTORS

7. GENERAL THROMBOPROPHYLAXIS RECOMMENDATIONS Level of Risk Estimated DVT Risk Suggested Thromboprophylaxis Low Minor surgery in mobile patients Medical patients who are fully mobile < 10% Early and aggressive ambulation Moderate Medical pts, bed rest or sick Most general, open gynecologic or urologic surgery patients Moderate VTE + High bleeding risk 10%-40% LMWH, LDUH BID/TID or Fondaparinux Mechanical Thromboprophylaxis High Risk Hip or knee arthroplasty, Major Trauma, SCI High VTE + High Bleeding risk 40% - 80% LMWH Mechanical Thromboprophylaxis

8. Additional risk factors for VTE in medical patients

9. Thromboprophylaxis in orthopedic surgery

10. Why thromboprophylaxis in orthopedic surgery? Incidence of venous thromboembolism (VTE) complications such as deep vein thrombosis (DVT) pulmonary embolism (PE) Most of these thrombi resolve spontaneously; 1–4% - develop into symptomatic VTE. Fatal pulmonary embolisms – 0.3–1% following total joint arthroplasty (TJA) and 3.6% after hip fracture surgery (HFS). A proactive approach to reduce the incidence of VTE is therefore of paramount importance. 40–60% within 7 to 14 days

11. 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.

12. History of thromboprophylaxis 1937 -Relationship between surgery and venous thromboembolism (VTE) 1954 - Vit K antagonist for thromboprophylaxis 1980 s-LMWH -superior to UFH 2002 - Fondaparinux introduced. 2008 -Dabigatran and Rivaroxaban 2011 -Apixaban

13. Thromboprophylaxis Options Mechanical Pharmacological

14. 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

15. 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

16. Graduated Compression Stockings

17. VENOUS FOOT PUMP

18. ACTIVE EXTERNAL COMPRESSION DEVICES INTERMITTENT

19. ACTIVE EXTERNAL COMPRESSION DEVICES CONTINOUS

20. PHAMACOLOGICAL THERAPY FOR VTE PROPHYLAXIS 23

21. 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 (0.4 0 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

22. 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 pharmacological 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

23. Warfarin (Coumadin ® ) INR target of 2.5 (Range between 2 – 3) Dose adjust based on INR Results Reversal with Vitamin K Many drug and food interactions Metabolized primarily by CYP2c9 and CYP3A4 Works by inhibiting the formation of Vitamin-K dependent clotting factors Adverse Effects: Alopecia, hemorrhage, tissue necrosis (rare) 26

24. Warfarin - MOA

25. Unfractionated Heparin VTE Prophylaxis Dosing 5000 Units subcutaneously every 8 – 12 hours Knee or hip replacement: give 2 hours before surgery, resume at full dose after surgery for at least 7 days Renal adjustment not required 28

26. Mechanism of UFH

27. Unfractionated Heparin Adverse Effects Thrombocytopenia (up to 30%) – monitor platelets Hemorrhage (5-10%) Increased ALT/AST

28. Low molecular weight Heparin Generic name Brand name Dalteparin Fragmin Enoxaparin Lovenox Tinzaparin Innohep

29. Mechanism of LMWH

30. Enoxaparin (Lovenox ® ) DVT Prophylaxis Dosing Knee or Hip Replacement: 30 mg subcutaneous every 12 hours Medical Patients: 40mg subcutaneously every 24 hours Dose Reduction is required in patients with CrCl less than 30 mL/min Knee or Hip replacement: 30 mg every 24 hours Medical patients: 30mg every 24 hours 33

31. LMWH Adverse Effects Hemorrhage (7%), AST/ALT elevation (6%), Fever (5%), Local Site reactions (2-5%)

32. FACTOR Xa INHIBITORS

33. FACTOR Xa INHIBITORS FACTOR Xa INHIBITORS DIRECT INHIBITORS INDIRECT INHIBITORS RIVAROXABAN FONDAPARINUX Synthetic indirect inhibitor of Factor Xa APIXABAN EDOXABAN

34. DIRECT FACTOR Xa INHIBITORS Rivaroxaban Apixaban Edoxaban Prevention of VTE in patients undergoing elective hip or knee replacement surgery ✓ ✓ ✓ (Japan only) Treatment of DVT and PE and prevention of recurrent DVT and PE ✓a ✓a ✓ Prevention of stroke and systemic embolism in patients with NVAF with ≥1 risk factors ✓ ✓ ✓ Secondary prevention of ACS ✓ b x x a Can be used without pre-treatment with parenteral anticoagulant; b In patients with elevated cardiac biomarkers and no prior stroke or TIA, and co-administered with ASA or ASA plus clopidogrel or ticlopidine

35. 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 BIOAVAILABILITY 80% 66% 62% HALF LIFE 7-11 13 10-14 ONSET 2-4 1-3 1-2

36. 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 (Arixtra ® )

37. Fondaparinux (Arixtra ® ) VTE Prophylaxis Dosing (Patients >50kg) 2.5mg subcutaneously every 24 hours Knee or Hip Replacement: Give 6-8 hours AFTER surgery No official dose adjustment recommendations CrCl 20 – 50 mL/min: 1.5 mg every 24 hours has been used Clearance is reduced 25-40% in patients with CrCl between 30 and 80 mL/min CONTRAINDICATED if CrCl is less than 30mL/min Adverse Effects Anemia (20%), Fever (14%), Nausea (11%), Rash (7.5%) 40

38. 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.

39. Dabigatran (Pradaxa ® ) FDA Approved for VTE prophylaxis 150mg by mouth twice daily 75mg by mouth if CrCl is less than 30 mL/min Surgical considerations 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 Reinitiate ASAP after procedures Not reversible Adverse Effects GI effects (6.1%), Bleeding (16.6%) 42

40. Rivaroxaban (Xarelto ® ) VTE Prophylaxis Dosing Knee or hip replacement surgery: 10mg by mouth daily Begin 6 – 10 hours after surgery Continue for 12 days after knee, 35 days after hip Secondary DVT/PE Prophylaxis: 2omg by mouth daily DISCONTINUE at least 24 hours prior to procedure Avoid if CrCl is less than 30 mL/min Adverse Effects Bleeding (5.8%), Epidural hematoma Carries same Black box Warning as LMWHs 43

41. Apixaban (Eliquis ® ) New reversible and selective active site inhibitor of factor Xa Dosing (European Medicines Agency-Approved dosing) Knee replacement surgery: 2.5mg by mouth daily Begin 12 – 24 hours after surgery Continue 10 – 14 days Hip replacement surgery: 2.5mg by mouth twice daily Begin 12 – 24 hours after surgery Continue 32 – 38 days DISCONTINUE 24 - 48 hours prior to elective or invasive surgery procedures Dose adjusted for body weight, age, renal impairment, and CYP3A4 inhibitors 44

42. IMPORTANT DRUG INTERACTIONS Medications that increase bleeding risk SSRI’s and SNRIs Medications for pain (NSAIDs, Willow Bark) Kava Kava may impair blood clotting due to effects on the liver Medications that alter metabolism Barbiturates, such as phenobarbital, may induce metabolism of heparins, decreasing effect Carbamazepine/oxcarbamezapine and St. John’s Wort induce metabolism of warfarin and apixaban by inducing 3A4 and 2C9 Bad habits Smoking induces metabolism Alcohol increasing bleeding risk 45

43. DVT Prevention in Knee Replacement (Total DVT by venography )

44. Prolonged (≥28 Days) Versus Standard (7 – 10 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

45. 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 Goal is to achieve 18h daily compliance

46. 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 Goal is to achieve 18h daily compliance Hip Fracture Surgery Low-Molecular Weight Heparin Fondaparinux Low-Dose Unfractionated Heparin Warfarin (INR 2-3) Aspirin

47. Additional Considerations L ow-Molecular Weight Heparins (Enoxaparin) 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

48. BLACK BOX WARNING!!! “Epidural 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 puncture” 51

49. Choice of Long-Term (First 3 Months) and Extended (No Scheduled Stop Date) Anticoagulant In patients with proximal DVT or pulmonary embolism (PE), long-term (3 months) anticoagulant therapy over no such therapy (Grade1B). 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).

50. Choice of Long-Term (First 3 Months) and Extended (No Scheduled Stop Date) Anticoagulant 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). 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).

51. 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).

52. 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 treatment of a shorter period (Grade 1B) and treatment of a longer time-limited period ( eg , 6, 12, or 24 months) (Grade 1B). 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).

53. 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. 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). Adequate levels of II, VII, IX, and X may not be present until the INR is within reference limits. T he 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).

54. 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 NSAIDs , Ticlopidine and Clopidogrel , UFH , and LMWH

55. 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).

56. 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).

57. 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).

58. 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).

59. Anesthetic Management of the Patient Receiving Low-molecular-Weight Heparin 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 ). 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 ).

60. 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 )

61. • 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 ).

62. 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.

63. 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.

64. Venous Thromboprophylaxis in Adult Hip Fracture Surgery, Elective Peri-Acetabular Osteotomy and Surgical Hip Dislocation Key: AES – anti-embolic stockings CrCL - creatinine clearance HIT – Heparin-induced thrombocytopenia VTE – venous thromboembolism

65. 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 / m 2 ) 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.

66. Contra-indications to AES Gross oedema Leg deformity/condition Peripheral vascular disease If peripheral arterial disease present, seek expert opinion before fitting Peripheral neuropathy

67. Contra-indications to pharmacological thromboprophylaxis On oral anticoagulant with INR > 2. 0 Thrombocytopenia (platelets < 50 x 10 9 / L) Known bleeding disorder Evidence of active bleeding Uncontrolled hypertension (BP > 230 / 120 mm Hg) Lumbar puncture/ epidural/ spinal analgesia expected within next 12 hours or performed within last 4 hours (24 hours if traumatic) New stroke ( ischaemic or haemorrhagic )

68. 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.

69. Time course of DVT ( untreated THR patients)

70. In patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) Recommendation: minimum of 10 to 14 days rather than no antithrombotic prophylaxis: low-molecular-weight heparin (LMWH), fondaparinux , apixaban , dabigatran , rivaroxaban , low-dose unfractionated heparin (LDUH), adjusted-dose vitamin K antagonist (VKA), aspirin (all Grade 1B) , or an intermittent pneumatic compression device (IPCD)(Grade 1C)

71. 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: LMWH, fondaparinux , LDUH, adjusted-dose VKA, Aspirin (all Grade 1B) , or an IPCD (Grade 1C) .

72. 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) .

73. 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): fondaparinux , apixaban , dabigatran , rivaroxaban , LDUH (all Grade 2B) , adjusted-dose VKA, or aspirin (all Grade 2C) .

74. 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) .

75. In patients undergoing major orthopedic surgery and who decline or are uncooperative with injections or an IPCD Recommendation: Using Apixaban Dabigatran Rivaroxaban adjusted-dose VKA (if apixaban or dabigatran are unavailable) rather than alternative forms of prophylaxis (all Grade 1B) .

76. 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) .

77. 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) .