1. IN THE NAME OF GOD

2. Prevention of Venous Thromboembolism Dr.Shirali

3. The prevention of VTE is the number one strategy to improve patient safety in hospitals according to the Agency for Health Care Research and Quality. Effective and safe prophylactic measures are now available for most high risk patients and numerous evidence-based guidelines have been published for the prevention of VTE.

4. In spite of the availability of these guidelines and the availability of safe and effective prophylactic agents, numerous audits have demonstrated that appropriate thromboprophylaxis is not being offered to large numbers of surgical patients:examples

5. Prophylaxis against DVT therefore should be used in an effort to decrease the incidence of PE. Each patient should be assessed for thromboembolic risk. Every hospital should develop a formal active strategy for the prevention of VTE in medical and surgical patients.This should be in the form of a written institution-wide thromboprophylaxis policy endorsed by department heads.

6. There are two approaches to the prevention of fatal PE : Primary prophylaxis : Primary prophylaxis is carried out using either drugs or physical methods that are effective for preventing DVT. Secondary prevention : Secondary prevention involves the early detection and treatment of subclinical venous thrombosis by screening postoperative patients with objective tests that are sensitive for the presence of DVT.

7. However, no single screening method (eg, contrast venography, ultrasonography, MRI venography) has found universal acceptance for secondary prevention. Accordingly, primary prophylaxis is preferred in most clinical circumstances; it is more cost effective than treatment of complications once they occur. Secondary prevention with screening is reserved for patients in whom primary prophylaxis is either contraindicated or shown to be ineffective.

8. Surgical risk groups : The risk of post- operative VTE depends upon a number of factors related to the surgical procedure itself (degree of invasiveness, type and duration of anaesthesia, requirement for immobilization), as well as a number of patient-related adverse risk factors.

9. Stasis Immobility Congestive heart failure Injury Surgery (especially major orthopedic and pelvic) Trauma Thrombophilia Cancer Oral contraceptives Hereditary states

10. RISK FACTORS FOR VTE — There are numerous risk factors for the development of VTE in surgical patients, including the type and extent of surgery or trauma duration of hospital stay, immobility recent sepsis presence of a central venous access device pregnancy or the postpartum period

11. Increasing age Prior VTE in patient or family members Presence of malignancy or obesity Presence of an inherited or acquired hypercoagulable state One or more significant medical comorbidities (eg, heart disease, infection, inflammatory conditions, recent stroke)

12. 2008 ACCP Guidelines have divided patients undergoing surgical procedures into : 1.low risk 2. moderate risk 3. high risk groups.

13. Low risk patients : 1.under the age of 40 + 2.no adverse patient-related or surgery- related risk factors + 3.general anaesthesia for less than 30 minutes. Without prophylaxis their risk of DVTis less than 1 percent and the risk of fatal PE is less than 0.01 percent.

14. Moderate risk patients : 1- Include those undergoing minor surgery who have additional risk factors. or 2- those age 40 to 60 who will require general anaesthesia for more than 30 minutes and have no additional adverse patient- or surgery-related risk factors. Without prophylaxis their risk of DVT is 2 to 4 percent and their risk of fatal PEis 0.1 to 0.4 percen.

15. High risk patients : The high risk surgical group includes those >60 years of age undergoing major surgical procedures as well as those ages 40 to 60 with additional patient- or surgery- related risk factors. Without prophylaxis the risk of DVTand fatal PE in this group has been estimated to be 4 to 8 percent and 0.4 to 1.0 percent, respectively.

17. 50-year-old woman scheduled to undergo elective laparoscopic cholecystectomy PMH notable for moderate COPD No personal or family history of VTE Medications: Spiriva®, albuterol Stopped smoking 1 year ago What should we recommend for perioperative VTE prophylaxis in this patient?

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21. Reflects system adopted for all ACCP guidelines The strength of any recommendation depends on two factors: The trade-off between benefits, risks, costs, and level of confidence in estimates of those benefits and risks The quality of the evidence upon which the recommendations are based If benefits do outweigh risks, and costs, a strong (Grade 1) recommendation is used. If there is less certainty about magnitude of benefits and risks, burdens, and costs, a weak (Grade 2) recommendation is used. Support for recommendations may come from high- quality, moderate-quality, or low-quality evidence, labeled, respectively, A, B, and C. The phrase “we recommend” is used for strong recommendations (Grade 1A, 1B, 1C) and “we suggest” for weak recommendations (Grade 2A, 2B, 2C).

25. Targets one or two legs of Virchow’s triad: Mechanical prophylaxis (stasis) Elastic compression stockings Intermittent pneumatic compression devices Pharmacological prophylaxis (hypercoagulability) Unfractionated heparin Low-molecular-weight heparins Fondaparinux. Aspirin (?)

26. Targets one or two legs of Virchow’s triad: Mechanical prophylaxis (stasis) Elastic compression stockings Intermittent pneumatic compression devices

27. Perioperative Management of Antithrombotic Therapy in Nonorthopedic Surgical Patients ----- Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Copyright: American College of Chest Physicians 2012 ©

28. 1- For general and abdominal-pelvic surgery patients at very low risk for VTE (0.5%;Rogers score,7; Caprini score, 0), we recommend that no specific pharmacologic (Grade 1B) or mechanical (Grade 2C) prophylaxis be used other than early ambulation.

29. 2. For general and abdominal-pelvic sur- gery patients at low risk for VTE ( 1.5%; Rogers score, 7-10; Caprini score, 1-2), we suggest mechanical prophylaxis, preferably with inter- mittent pneumatic compression (IPC), over no prophylaxis (Grade 2C).

30. 3. For general and abdominal-pelvic sur-gery patients at moderate risk for VTE ( 3.0%; Rogers score,. 10; Caprini score, 3-4) who are not at high risk for major bleeding complica- tions, we suggest LMWH (Grade 2B ), LDUH (Grade 2B), or mechanical prophylaxis, prefer- ably with IPC (Grade 2C), over no prophylaxis.

31. 4. For general and abdominal-pelvic sur- gery patients at moderate risk for VTE (3.0%;Rogers score, 10; Caprini score, 3-4) who are at high risk for major bleeding complications or those in whom the consequences of bleeding are thought to be particularly severe, we suggest mechanical prophylaxis, preferably with IPC, over no prophylaxis (Grade 2C).

32. 5. For general and abdominal-pelvic surgery patients at high risk for VTE ( 6.0%;Caprini score, 5) who are not at high risk for major bleeding complications, we recommend pharmacologic prophylaxis with LMWH (Grade 1B) or LDUH (Grade 1B) over no prophylaxis. We suggest that mechanical prophylaxis with elastic stockings or IPC should be added to pharmacologic prophylaxis (Grade 2C).

33. 6. For high-VTE-risk patients undergoing abdominal or pelvic surgery for cancer who are not otherwise at high risk for major bleed- ing complications, we recommend extended- duration pharmacologic prophylaxis (4 weeks) with LMWH over limited-duration prophylaxis (Grade 1B)

34. 7. For high-VTE-risk general and abdominal- pelvic surgery patients who are at high risk for major bleeding complications or those in whom the consequences of bleeding are thought to be particularly severe, we suggest use of mechanical prophylaxis, preferably with IPC, over no prophylaxis until the risk of bleeding diminishes and pharmacologic prophylaxis may be initiated (Grade 2C).

35. 8. For general and abdominal-pelvic surgery patients at high risk for VTE (6%; Caprini score, 5) in whom both LMWH and unfrac- tionated heparin are contraindicated or unavailable and who are not at high risk for major bleeding complications, we suggest low- dose aspirin (Grade 2C), fondaparinux (Grade 2C), or mechanical prophylaxis, preferably with IPC (Grade 2C), over no prophylaxis.

36. 9. For general and abdominal-pelvic surgery patients, we suggest that an inferior vena cava (IVC) filter should not be used for primary VTE prevention (Grade 2C). 10. For general and abdominal-pelvic surgery patients, we suggest that periodic surveillance with venous compression ultrasound (VCU) should not be performed (Grade 2C).

37. Timing of commencement of prophylaxis : Prophylaxis is ideally started either before or shortly after surgery and continued at least until the patient is fully ambulatory. The administration of thromboprophylaxis in close proximity to surgery has been shown to enhance its efficacy in a systematic review that compared prophylaxis with LMW heparin versus warfarin.

38. In general, LMW heparin has been shown to be superior to UFH or warfarin but inferior to fondaparinux in terms of efficacy, with similar bleeding rates in patients undergoing total hip or total knee replacement surgery. The use of the enoxaparin differs between regions : In North America, enoxaparin is commonly used in the dose of 30 mg twice daily starting 12 to 24 hours postoperatively. In Europe, enoxaparin at a dose of 40 mg is started 12 hours preoperatively and is then given once daily. Other LMW Heparin preparations have usually been given in a once daily dosage, starting postoperatively.

39. Extended prophylaxis : As the result of shortened hospital length of stay, many patients will require out-of-hospital prophylaxis. This is particularly true after total hip replacement, where the evidence is that patients require 28 to 35 days of prophylaxis with LMW heparin, rather than 7 to 10 days. Although warfarin is effective in extended prophylaxis, the incidence of major bleeding was higher than that seen with LMW heparin.

40. Patients undergoing cancer surgery or major abdominal surgery also benefit from extended prophylaxis.

41. A meta-analysis in patients undergoing cancer surgery concluded that there was no difference between LMW heparin and UFH in terms of efficacy, DVT location, or bleeding complications.

42. Low dose unfractionated heparin : Low dose subcutaneous unfractionated heparin (UFH) for prophylaxis of VTE is usually given in a dose of 5000 units two hours preoperatively and then every 8 to 12 hours postoperatively (ie, either twice or three times daily).

43. In addition to its relatively low side effect profile, low dose UFH has the advantage that it is relatively inexpensive, easily administered, and anticoagulant monitoring is not required. However, the platelet count should be monitored regularly in all patients receiving low dose UFH to detect the development of heparin-induced thrombocytopenia.

44. Low molecular weight heparin : A number of low molecular weight heparin (LMW Heparin) preparations are available. These drugs have the advantage that they can be given subcutaneously once or twice daily at a constant dose without laboratory monitoring. In addition, there is a lower incidence of heparin-induced thrombocytopenia than with UFH.

45. Fondaparinux has been evaluated in the prevention of VTE in patients undergoing orthopedic surgery, general surgery, and in hospitalized medical patients. Fondaparinux 2.5 mg once/day by subcutaneous injection has been compared with the enoxaparin 40 mg once daily starting 12 hours preoperatively in patients undergoing total hip or total knee replacement, with enoxaparin 30 mg twice daily in patients undergoing total hip replacement, and with enoxaparin 40 mg daily in patients suffering hip fracture.In a 2002 meta-analysis of four available trials, it was concluded that the efficacy of fondaparinux was superior to that of enoxaparin.

46. In these studies, major bleeding occurred more frequently in fondaparinux-treated subjects, but there was not an increase in bleeding leading to death or re- operation or bleeding into a critical organ with fondaparinux compared with enoxaparin. Most of the patients who bled had their initial fondaparinux injection less than eight hours postoperatively.

47. Oral anticoagulation : Oral anticoagulation with vitamin K antagonists (VKA) such as warfarin can be commenced preoperatively, at the time of surgery, or postoperatively for the prevention of VTE. However, therapy started at the time of surgery or in the early postoperative period may not prevent small venous thrombi from forming because the anticoagulant effect of the VKAs is not achieved until the third or fourth day of treatment.

48. Nonetheless, warfarin appears to effectively inhibit extension of such thrombi if present, thereby preventing clinically important VTE. Because of its delayed onset of action along with bleeding rates similar to those seen with LMW heparin, warfarin has been favored as a thromboprophylactic agent by orthopedic surgeons in the United States.

49. Venous Thromboembolism (VTE) in Patients with Cancer

50. The risk of VTE including (DVT) and (PE) is increased several-fold in patients with cancer. Hospitalized patients with cancer and those receiving active therapy seem to be at the greatest risk for development of VTE. In a population-based study, cancer was associated with a 4.1- fold greater risk of thrombosis, whereas the use of chemotherapy increased the risk 6.5-fold.

51. Risk Factors for VTE in Patients With Malignant Disease

52. Patient-related factors Older age Race (higher in African Americans; lower in Asian-Pacific Islanders) Comorbid conditions (obesity, infection, renal disease, pulmonary disease, arterial thromboembolism) Prior history of VTE Elevated prechemotherapy platelet count Heritable prothrombotic mutations

53. Cancer-related factors Primary site of cancer (GI, brain, lung, gynecologic, renal, hematologic) Initial 3-6 months after diagnosis Current metastatic disease Treatment-related factors Recent major surgery Current hospitalization Active chemotherapy Active hormonal therapy Current or recent antiangiogenic therapy (thalidomide, lenalidomide, bevacizumab) Current erythropoiesis-stimulating agents Presence of central venous catheters

54. SHOULD HOSPITALIZED PATIENTS WITH CANCER RECEIVE ANTICOAGULATION FOR VTE PROPHYLAXIS ?

55. 1. Hospitalized patients who have active malignancy with acute medical illness or reduced mobility should receive pharmacologic thromboprophylaxis in the absence of bleeding or other contraindications. 2. Hospitalized patients who have active malignancy without additional risk factors may be considered for pharmacologic thromboprophylaxis in the absence of bleeding or other contraindications. 3. Data are inadequate to support routine thromboprophylaxis in patients admitted for minor procedures or short chemotherapy infusion, or in patients undergoing stem cell/ bone marrow transplantation.

56. Pharmacologic Prophylaxis in Hospitalized medical patients Unfractionated heparin 5,000 U q8h Dalteparin 5,000 U qd Enoxaparin40 mg qd Fondaparinux 2.5 mg qd Duration for medical patients is for the length of hospital stay or is fully ambulatory. Unfractionated heparin 5,000 U every 12 hours has also been used but appears to be less effective;

57. SHOULD AMBULATORY PATIENTS WITH CANCER RECEIVE ANTICOAGULATION FOR VTE PROPHYLAXIS DURING SYSTEMIC CHEMOTHERAPY ?

58. 1. Routine pharmacologic prophylaxis is not recommended in cancer outpatients. 2. Based on limited RCT data, clinicians may consider LMWH prophylaxis on a case-by-case basis in highly selected outpatients with solid tumors receiving chemotherapy. Consideration of such therapy should be accompanied by a discussion with the patient about the uncertainty concerning benefits and harms, as well as dose and duration of prophylaxis in this setting. 3. Patients with multiple myeloma receiving thalidomide- or lenalidomide-based regimens with chemotherapy and/or dexamethasone should receive pharmacologic thromboprophylaxis with either aspirin or LMWH for lower-risk patients and LMWH for higher-risk patients

59. SHOULD PATIENTS WITH CANCER UNDERGOING SURGERY RECEIVE PERIOPERATIVE VTE PROPHYLAXIS?

60. 1. All patients with malignant disease undergoing major surgical intervention should be considered for pharmacologic thromboprophylaxis with either UFH or LMWH unless contraindicated because of active bleeding or a high bleeding risk. 2. Prophylaxis should be commenced preoperatively. 3. Mechanical methods may be added to pharmacologic thromboprophylaxis, but should not be used as monotherapy for VTE prevention unless pharmacologic methods are contraindicated because of active bleeding or high bleeding risk.

61. 4. A combined regimen of pharmacologic and mechanical prophylaxis may improve efficacy, especially in the highest-risk patients. 5. Pharmacologic thromboprophylaxis for patients undergoing major surgery for cancer should be continued for at least 7-10 days. Extended prophylaxis with LMWH for up to 4 weeks postoperatively should be considered for patients undergoing major abdominal or pelvic surgery for cancer who have high-risk features such as restricted mobility, obesity, history of VTE, or with additional risk factors.In lower risk surgical settings, the decision on appropriate duration of thromboprophylaxis should be made on a case-by-case basis considering the individual patient.

62. Surgical patients Unfractionated heparin 5,000 U 2-4 h pre-op and q8h thereafter or 5,000 U 10-12 h preop and 5,000 U qd thereafter Dalteparin 2,500 U 2-4 h pre-op and 5,000 U qd thereafter or 5,000 U 10-12 h pre-op and 5,000 U qd thereafter Enoxaparin 20 mg 2-4h pre-op and 40 mg qd thereafter or 40 mg 10-12 hr pre-op and 40 mg qd thereafter Fondaparinux 2.5 mg qd beginning 6-8h post-op

63. All doses are given as subcutaneous injections except as indicated, When neuraxial anesthesia or analgesia is planned, prophylactic doses of once-daily LMWH should NOT be given within 10 – 12 h prior to the procedure/instrumentation (including epidural catheter removal). After the surgery, the first dose of LMWH can be given 6 – 8 h postoperatively. After catheter removal, the first dose of LMWH can be given no earlier than 2 h afterwards. Clinicians should refer to their institutional and the American Society of Regional Anesthesia Guidelines for more information.

64. for surgical patients, prophylaxis should be continued for at least 7-10 days. Extended prophylaxis for up to 4 weeks should be considered for high- risk patients.