Further Inpatient Care
- In general, inpatient care requires the administration and continuation of IV or SC anticoagulants, with an oral anticoagulant (warfarin sodium) started within 72 hours of SC or, when using IV heparin, once the aPTT is therapeutic (1.5-2 times baseline). An oral coumarin derivative (ie, warfarin sodium) is started after anticoagulation with SC or IV anticoagulants has been achieved because warfarin can have an initial procoagulant effect, particularly in patients with protein C or protein S deficiencies, potentially causing fat necrosis. For patients who required thrombolysis for acute massive PE causing hemodynamic instability, heparin infusion should be started once the thrombin time or aPTT is less than 2 times baseline. Treatment with an oral coumarin derivative should begin after 24-48 hours of consistent anticoagulation.
- Appropriate anticoagulation with the oral medication has been accomplished when the INR is between 2.0 and 3.0.
- Once the INR is consistently within the desired range, treatment can continue in the outpatient setting as long as no other concomitant conditions are present that require continued inpatient treatment.
Further Outpatient Care
- Prolongation of the prothrombin time should be monitored in the outpatient setting by the routine measurement of the INR and its adjustment to maintain its level between 2.0 and 3.0. Oral anticoagulant treatment should be continued for at least 3 months.
- In those with recurrent venous thrombosis or with a continuing risk factor, such as a hematologic factor or a malignancy, prolonged and even indefinite anticoagulant treatment should be considered.
- One study evaluated data from 344 patients with a low risk of death at 19 emergency departments internationally. Patients in the inpatient group experienced no recurrent venous thromboembolism events within 90 days and no major bleeding within 14 days or at 90 days. While the outpatient group developed recurrent venous thromboembolism within 90 days (1 of 171) and major bleeding within 14 days or at 90 days (2 of 171 and 3 of 171, respectively), patients in the outpatient group experienced less mean length of stay than the inpatient group (0-5 d vs 3-9 d, respectively). These results suggest that outpatient care may be a safe and effective alternative to inpatient care in selected, hemodynamically stable patients with pulmonary embolism.[24]
Inpatient & Outpatient Medications
- Inpatient medications should include heparin or a LMWH followed by the initiation of an oral coumarin derivative. The predominant coumarin derivative in clinical use in North America is warfarin sodium. Patients with acute massive PE causing hemodynamic instability may be treated initially with a thrombolytic agent (ie, streptokinase, TPA, urokinase).
- Unfractionated heparin, LMWH, and warfarin sodium each are ordered for their anticoagulant properties through their effects on the factors and cofactors of the coagulation cascade as described earlier in the article.
- Tissue plasminogen activator has been used increasingly as the first choice thrombolytic agent. Antibodies to streptokinase may be developed, limiting the use of streptokinase, and urokinase is of limited availability.
- In the outpatient setting, the oral anticoagulant, warfarin sodium, is continued.
Deterrence/Prevention
- Thromboprophylaxis has been reported to reduce the incidence of deep venous thrombosis and fatal pulmonary embolism. Prophylaxis may be achieved with medication or with mechanical devices. Medical prophylaxis should begin either 12 hours before surgery or immediately after surgery and should be continued for 7-10 days.[25, 26, 27, 28, 29, 30, 31, 32] Unfractionated heparin, given SC, can reduce the incidence of thromboembolism. It must be administered 2 or 3 times daily, and bleeding can be a complication. LMWHs have a longer half-life and greater bioavailability than does unfractionated heparin. The requirement for monitoring is less.
- Data from a double-blind, double-dummy, placebo-controlled trial found that a short-term course of thromboprophylaxis with enoxaparin was more effective than an extended course of apixaban, with significantly less major bleeding events.[33]
- Danaparoid, a low molecular weight glycosaminoglycan, has been shown to be effective in preventing DVT and PE. It also has been used in patients whose treatment course has been complicated by heparin-induced thrombocytopenia (HIT).
- Warfarin is effective for thromboprophylaxis. It causes the depletion of vitamin K–dependent elements in the coagulation cascade. Warfarin requires close monitoring, and bleeding can be a complication. Dose-adjusted therapy should be monitored, keeping the INR in the range of 2.0-3.0.
- External pneumatic compression has been shown to temporarily prevent the reduction in fibrinolytic activity that normally follows surgical operations. Studies have found compression devices to be effective only in patients with head trauma or spinal fracture. In total hip replacement, studies have shown them to be efficacious in preventing distal DVT but not in preventing proximal DVT.
- Another method of nonpharmacologic prophylaxis is early ambulation, unless the patient has an absolute contraindication. Studies have demonstrated that both symptomatic and ultrasound-diagnosed DVT are significantly less common with early ambulation following hip arthroplasty.
- One study evaluated the risk of postdischarge venous thromboembolism after cancer surgery. Using data from 44,656 patients undergoing surgery for 9 cancers, the results showed that venous thromboembolisms occurred postdischarge at an overall rate of 33.4%. Venous thromboembolism was significantly more likely after GI, lung, prostate, and ovarian/uterine operations. These results suggest that routine postdischarge prophylaxis should be considered for high-risk patients.[34]
- A prospective cohort study including 69,950 female nurses found an association between physical inactivity and the incidence of pulmonary embolism in women. The data found that the risk of pulmonary embolism was more than 2-fold in women who spent more time sitting compared with those who spent less time sitting. Activities that decrease the amount of time sitting may lower the risk of pulmonary embolism in women.[35]
Complications
- Fifty percent of patients treated with full anticoagulation for deep venous thrombosis still can have complications of postphlebitic syndrome characterized by chronic deep venous insufficiency, chronic pain, venous stasis, recurrent cellulitis, and lower extremity ulceration.
- The most feared complication of the treatment of pulmonary embolism is severe and fatal bleeding. Major risk factors for bleeding include intensity and duration of therapy, increased age, and significant hepatic or renal dysfunction. Comparison studies of the incidence of severe and fatal bleeding complications between heparin and rt-PA demonstrate no significant differences.
- Heparin-induced thrombocytopenia (HIT) and thrombosis may develop in 3-4% of patients receiving heparin. It is an immune-mediated process that typically presents within 5-10 days of therapy. It can result in bleeding or thrombosis and should be suspected when the platelet count falls precipitously to less than 50% below its baseline or to less than 100,000/µL. Heparin therapy should be stopped immediately. LMWH cross-reacts with the antibody in vitro in 90% of cases. Therefore, it should not be substituted in the acute setting. Danaparoid, a heparinoid, has less than 10% cross-reactivity with the antibody. Recombinant hirudin recently has been approved for HIT and thrombosis. Plasmapheresis and immunoglobulin G (IgG) infusion may be effective in cases with thrombosis.
- Heparin-induced osteopenia has been reported following treatment with unfractionated heparin of more than 1-month duration.
- Coumarin derivatives can cause skin necrosis, which is due to widespread subcutaneous microthrombosis. This can occur in individuals who are protein C-deficient, either genetically or owing to large loading doses of a coumarin derivative. Areas usually affected include the breasts, the abdominal wall, and the lower extremities.
- Recurrence of thromboembolism had been documented following discontinuation of therapy. After a 3- to 6-month course of anticoagulant therapy, the risk of recurrent thromboembolism is lower in patients who have reversible risk factors. The recurrence rate is greater in patients with previous proximal vein thrombosis compared to calf vein thrombosis.
- Following a 3-month course of anticoagulant therapy, secondary thrombosis risk is 2-4% in the first year. In subsequent years, the risk falls to less than 2%. In idiopathic proximal vein thrombosis, the risk of recurrence is 9-27%. It is lower in the second and subsequent years. However, there is an increased risk for at least 6 years.
Prognosis
- Studies demonstrate a 95% risk reduction with treatment of thromboembolic disease. There is a risk of recurrence following the discontinuation of treatment that is related to the type and number of risk factors and whether they persist following completion of treatment. Five to seven percent of all recurrences are fatal recurrences.
- Sequelae of treated deep venous thrombosis includes a postthrombotic syndrome, which is a chronic complication of venous thromboembolism characterized by pain and swelling. Chronic deep venous insufficiency, recurrent cellulitis, venous stasis, and ulceration of the skin can develop in up to 50% of patients treated with full anticoagulation. The results from an open-label, randomized controlled trial suggest that additional treatment with catheter-directed thrombolysis using alteplase reduced the development of postthrombotic syndrome, prompting the authors to suggest it should be considered for patients at low risk of bleeding who have high proximal DVT.[36]
Patient Education
- For the success and ease of outpatient treatment, patients on oral warfarin anticoagulation should be educated on the impact of dietary choices on treatment goals and the need for frequent monitoring.
- Education on the avoidance of reversible risk factors would be helpful in preventing disease recurrence.
- For patient education resources, visit the Lung and Airway Center and Circulatory Problems Center, as well as Pulmonary Embolism and Blood Clot in the Legs.
Merli GJ. Prevention of thrombosis with warfarin, aspirin, and mechanical methods. Clin Cornerstone. 2005;7(4):49-56. [Medline].
Agnelli G, Sonaglia F, Becattini C. Direct thrombin inhibitors for the prevention of venous thromboembolism after major orthopaedic surgery. Curr Pharm Des. 2005;11(30):3885-91. [Medline].
Agudelo JF, Morgan SJ, Smith WR. Venous thromboembolism in orthopedic trauma patients. Orthopedics. Oct 2005;28(10):1164-71; quiz 1172-3. [Medline].
Mismetti P, Zufferey P, Pernod G, Baylot, Estebe JP, Barrelier MT, et al. [Thromboprohylaxis in orthopedic surgery and traumatology]. Ann Fr Anesth Reanim. Aug 2005;24(8):871-89. [Medline].
Jaffer AK, Barsoum WK, Krebs V, Hurbanek JG, Morra N, Brotman DJ. Duration of anesthesia and venous thromboembolism after hip and knee arthroplasty. Mayo Clin Proc. Jun 2005;80(6):732-8. [Medline].
Eikelboom JW, Karthikeyan G, Fagel N, Hirsh J. American Association of Orthopedic Surgeons and American College of Chest Physicians guidelines for venous thromboembolism prevention in hip and knee arthroplasty differ: what are the implications for clinicians and patients?. Chest. Feb 2009;135(2):513-20. [Medline].
Prevention of Symptomatic Pulmonary Embolism in Patients Undergoing Total Hip or Knee Arthroplasty. AAOS Clinical Practice Guideline Summary:. American Academy of Orthopaedic Surgeons. Available at http://www5.aaos.org/dvt/physician/ADU013/suppPDFs/OKO_ADU013_S10.pdf. Accessed December 9, 2009.
Lachiewicz PF. Prevention of symptomatic pulmonary embolism in patients undergoing total hip and knee arthroplasty: clinical guideline of the American Academy of Orthopaedic Surgeons. Instr Course Lect. 2009;58:795-804. [Medline].
Johanson NA, Lachiewicz PF, Lieberman JR, Lotke PA, Parvizi J, Pellegrini V, et al. Prevention of symptomatic pulmonary embolism in patients undergoing total hip or knee arthroplasty. J Am Acad Orthop Surg. Mar 2009;17(3):183-96. [Medline].
Markel DC, York S, Liston MJ Jr, Flynn JC, Barnes CL, Davis CM 3rd. Venous Thromboembolism Management by American Association of Hip and Knee Surgeons. J Arthroplasty. Oct 16 2009;[Medline].
Merli G, Spyropoulos AC, Caprini JA. Use of emerging oral anticoagulants in clinical practice: translating results from clinical trials to orthopedic and general surgical patient populations. Ann Surg. Aug 2009;250(2):219-28. [Medline].
Hippisley-Cox J, Coupland C. Development and validation of risk prediction algorithm (QThrombosis) to estimate future risk of venous thromboembolism: prospective cohort study. BMJ. Aug 16 2011;343:d4656. [Medline]. [Full Text].
Qaseem A, Chou R, Humphrey LL, Starkey M, Shekelle P. Venous Thromboembolism Prophylaxis in Hospitalized Patients: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. Nov 1 2011;155(9):625-632. [Medline].
Woller SC, Stevens SM, Jones JP, et al. Derivation and validation of a simple model to identify venous thromboembolism risk in medical patients. Am J Med. Oct 2011;124(10):947-954.e2. [Medline].
Pabinger I, Ay C. Biomarkers and venous thromboembolism. Arterioscler Thromb Vasc Biol. Mar 2009;29(3):332-6. [Medline].
Bauer KA. New anticoagulants. Curr Opin Hematol. Sep 2008;15(5):509-15. [Medline].
Akl EA, Gunukula S, Barba M, et al. Parenteral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database Syst Rev. Apr 13 2011;4:CD006652. [Medline].
Akl EA, Vasireddi SR, Gunukula S, et al. Oral anticoagulation in patients with cancer who have no therapeutic or prophylactic indication for anticoagulation. Cochrane Database Syst Rev. Jun 15 2011;6:CD006466. [Medline].
Boutitie F, Pinede L, Schulman S, et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants' data from seven trials. BMJ. May 24 2011;342:d3036. [Medline]. [Full Text].
Akl EA, Labedi N, Barba M, et al. Anticoagulation for the long-term treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev. Jun 15 2011;6:CD006650. [Medline].
Goldhaber SZ, Haire WD, Feldstein ML, et al. Alteplase versus heparin in acute pulmonary embolism: randomised trial assessing right-ventricular function and pulmonary perfusion. Lancet. Feb 27 1993;341(8844):507-11. [Medline].
Hirsh J, Dalen J, Guyatt G. The sixth (2000) ACCP guidelines for antithrombotic therapy for prevention and treatment of thrombosis. American College of Chest Physicians. Chest. Jan 2001;119(1 Suppl):[Medline].
The EINSTEIN Investigators. Oral Rivaroxaban for Symptomatic Venous Thromboembolism. N Engl J Med. Dec 3 2010;[Medline]. [Full Text].
Aujesky D, Roy PM, Verschuren F, et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, non-inferiority trial. Lancet. Jul 2 2011;378(9785):41-8. [Medline].
Schulman S. Current strategies in prophylaxis and treatment of venous thromboembolism. Ann Med. 2008;40(5):352-9. [Medline].
Prevention of venous thromboembolism in orthopedic surgery. Med Lett Drugs Ther. Nov 3 2008;50(1298):86-8. [Medline].
Jaffer AK, Brotman DJ. Prevention of venous thromboembolism after surgery. Clin Geriatr Med. Nov 2008;24(4):625-39, viii. [Medline].
Piazza G, Goldhaber SZ. Physician alerts to prevent venous thromboembolism. J Thromb Thrombolysis. Nov 4 2009;[Medline].
Wittkowsky AK. New oral anticoagulants: a practical guide for clinicians. J Thromb Thrombolysis. Nov 4 2009;[Medline].
Lu JP, Knudson MM, Bir N, Kallet R, Atkinson K. Fondaparinux for prevention of venous thromboembolism in high-risk trauma patients: a pilot study. J Am Coll Surg. Nov 2009;209(5):589-94. [Medline].
Muntz J. Thromboprophylaxis in orthopedic surgery: how long is long enough?. Am J Orthop. Aug 2009;38(8):394-401. [Medline].
Huo MH, Muntz J. Extended thromboprophylaxis with low-molecular-weight heparins after hospital discharge in high-risk surgical and medical patients: a review. Clin Ther. Jun 2009;31(6):1129-41. [Medline].
Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. Dec 8 2011;365(23):2167-77. [Medline].
Merkow RP, Bilimoria KY, McCarter MD, et al. Post-Discharge Venous Thromboembolism After Cancer Surgery: Extending the Case for Extended Prophylaxis. Ann Surg. Jul 2011;254(1):131-137. [Medline].
Kabrhel C, Varraso R, Goldhaber SZ, Rimm E, Camargo CA Jr. Physical inactivity and idiopathic pulmonary embolism in women: prospective study. BMJ. Jul 4 2011;343:d3867. [Medline].
Enden T, Haig Y, Kløw NE, et al. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet. Jan 7 2012;379(9810):31-8. [Medline].
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