CME/CE

JUNE 2008

Venous Thromboembolism in Gynecologic Surgery

Rebecca Byler Dann, MD, MPH; Thomas C. Krivak, MD; Kristin Zorn, MD

Although venous thromboembolism remains a significant complication of gynecologic surgery, mechanical and pharmacologic prophylaxis—together with advanced diagnostic imaging—can help to mitigate the consequences.

Continuing Medical Education

GOAL To discuss the diagnosis and management of venous thromboembolism (VTE) in the setting of gynecologic surgery. OBJECTIVES To look at the risk factors associated with surgery-related VTE. To consider prophylactic measures for VTE. To examine management strategies for patients with VTE, pulmonary embolism, and those receiving long-term anticoagulation therapy. ACCREDITATION This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Albert Einstein College of Medicine and Quadrant HealthCom Inc. Albert Einstein College of Medicine is accredited by the ACCME to provide continuing medical education for physicians. This activity has been peer reviewed and approved by Brian Cohen, MD, Professor of Clinical ObGyn, Albert Einstein College of Medicine. Review date: May 2008. It is designed for -ObGyns, primary care physicians, and nurse practitioners. Albert Einstein College of Medicine designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Participants who answer 70% or more of the questions correctly will obtain credit. To earn credit, see the instructions on page 55 and mail your answers according to the instructions on page 56. CONFLICT OF INTEREST STATEMENT The “Conflict of Interest Disclosure Policy” of Albert Einstein College of Medicine requires that authors participating in any CME activity disclose to the audience any relationship(s) with a pharmaceutical or equipment company. Any author whose disclosed relationships prove to create a conflict of interest, with regard to their contribution to the activity, will not be permitted to present. The Albert Einstein College of Medicine also requires that faculty participating in any CME activity disclose to the audience when discussing any unlabeled or investigational use of any commercial product, or device, not yet approved for use in the United States. Drs Dann and Krivak report no conflict of interest. Dr Zorn reports that she is on the Speakers Bureau for Merck & Co., Inc. The disclosure reported by the author presents no conflict of interest to this article. The authors report no discussion of off-label use. Dr Cohen reports no conflict of interest. The staff of CCME of Albert Einstein College of Medicine have no conflicts of interest with commercial interest related directly or indirectly to this educational activity.

Venous thromboembolism (VTE), comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a significant source of morbidity and mortality in the United States, with 500,000 cases and 200,000 attributable deaths annually.1 The triad of venous stasis, intimal damage, and hypercoagulability predisposes to VTE in many gynecologic cases; as DVT occurs in up to 40% of gynecologic surgery patients receiving no prophylaxis, routine prophylaxis is indicated for most gynecologic procedures.2 However, even when prophylaxis is used, VTE will continue to occur in some high-risk patients.

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PROPHYLAXIS

Table 1 lists risk factors for the development of VTE.3 Current VTE prevention strategies include early ambulation, graduated compression stockings (GCS), pneumatic compression devices (PCD), and anticoagulants such as warfarin, subcutaneous unfractionated heparin (SUFH), and low-molecular–weight heparin (LMWH).1,2 The choice of prophylactic regimen should be based on the clinician’s assessment of individual patient risk.

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TABLE 1. Risk factors for Deep Vein Thrombosis

Placed on the lower extremity, GCS exert pressure throughout the stocking to decrease pooling of venous blood—an effective intervention for preventing VTE in surgery with few side effects. Pneumatic (or sequential) compression devices extend to either the knee or thigh and also prevent venous pooling, together with stimulating release of fibrinolytic factors. Studies suggest that PCD may decrease the risk of VTE—particularly in patients with no history of VTE—with few complications.4

Pharmacologic agents utilized in DVT prevention include vitamin K antagonists (warfarin), SUFH, and LMWH. Studies of SUFH have demonstrated a decrease in VTE rates with doses of 5,000 U twice daily in gynecologic surgery patients, and 5,000 U 3 times daily in gynecologic oncology patients.4 Theoretical advantages have been attributed to LMWH, including decreased risk of bleeding complications and once-daily dosing. Studies comparing moderate-dose LMWH with either postoperative PCD or twice-daily SUFH have shown similar rates of DVT prevention and patient compliance, with no increase in bleeding complications when utilizing LMWH.4

Heparin anticoagulation therapy confers risks that include bleeding, osteoporosis with prolonged SUFH use, and heparin-induced thrombocytopenia (HIT) (which is potentially life-threatening). The risks of bleeding with SUFH appear to be higher due to UFH-binding proteins and a less predictable patient response. Patients treated with any form of heparin have a risk of developing HIT, although this risk appears lower with LMWH. Currently, LMWH is generally preferred over UFH because of easier dosing, equivalent efficacy, and equivalent or decreased complication rates.5

Contraindications to heparin use include active bleeding; history of HIT, bleeding ulcer, or heparin allergy; and a recent surgical procedure. In these patients, inferior vena cava filter (IVCF) placement may be an option. Other common indications for IVCF placement include perioperative protection in patients at high risk for bleeding with anticoagulation and active DVT in a patient requiring surgery. Placement of an IVCF appears to be safe and effective for preventing life-threatening VTE, but randomized trials are lacking. Possible complications from IVCF placement include filter migration, incomplete protection from PE, perforation, worsening of lower-extremity edema, and the need for anticoagulation (if possible) to protect against heightened DVT risk below the IVCF.6

Some patients still develop VTE despite prophylaxis, leading to the development of “dual prophylaxis” (usually combining heparin and PCD) for those at high risk (Table 2). Studies have yielded mixed results for this approach.7

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TABLE 2. Risk-Based Prophylaxis of Deep Vein Thrombosis

Fifty percent of DVTs form during surgery, while 25% occur within 72 hours postoperatively.1 It is therefore important to initiate prophylaxis prior to induction of anesthesia in moderate- to high-risk patients. Placement of GCS or a PCD can be done prior to entering the operating room. Preoperative administration of LMWH and UFH in high-risk patients has been shown to reduce DVT formation with an acceptable complication rate. Although some studies of preoperative heparin administration suggest a risk of operative bleeding and blood transfusion, this has not been demonstrated consistently.5 Therefore, decisions regarding preoperative heparin must be individualized.

The duration of prophylaxis depends on the degree of thrombotic risk. Discontinuation of prophylaxis at the time of discharge is acceptable in most ambulatory patients. In patients with known gynecologic malignancies, however, 4 weeks of LMWH, 40 mg, was shown to significantly decrease the rate of VTE without increasing complications.8

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DIAGNOSIS

Clinical assessment of patients with suspected DVT can be misleading, as symptoms are often nonspecific or absent. Tests include D-dimer testing, duplex Doppler ultrasonography, impedance plethysmography, and venography.1 D-dimer testing has a high sensitivity (85%) and an excellent negative predictive value for DVT; however, levels are altered postoperatively in patients with malignancy, even in the absence of VTE. Thus, D-dimer testing may be considered a screening tool, but elevated levels are not diagnostic of VTE.9

Duplex Doppler ultrasonography can be used either alone or in combination with D-dimer screening to evaluate for the presence of DVT. Venography has been the “gold standard” for the diagnosis of VTE, but the high sensitivity and ease of use of compression and duplex Doppler ultrasonography have largely replaced it. Venography should be reserved for patients with consistent symptoms, a high risk for VTE, or contraindications to anticoagulation. Figure 1 provides a diagnostic algorithm.10

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Figure 1. Diagnostic algorithm for venous thromboembolism.10

The diagnosis of pelvic thrombotic disease represents a distinct challenge. Although patients undergoing gynecologic surgery are at risk for pelvic vein thromboses, most cases are largely asymptomatic. Ultrasonography is not sensitive for detecting iliac-vein DVT, with contrast venography (CV) and magnetic resonance imaging (MRI) showing increased reliability. For detection of noniliac venous thrombosis, MRI offers good sensitivity while retaining excellent specificity. Clots extending into or involving the inferior vena cava are particularly difficult to detect radiographically. New techniques incorporating abdominopelvic computed tomography (CT)/venography following CT chest imaging may resolve this problem, but expose the patient to significantly more radiation. The use of MRI may be beneficial, but duplex ultrasonography has limited use in this setting.11

Clinical diagnosis of PE is problematic in that, as with DVT, patients may have few symptoms. Decreased oxygen saturation is not a common presenting sign of PE in the absence of a massive saddle embolus. Ultimately, untreated PE may lead to clot propagation, right-sided heart failure, and pulmonary hypertension. Diagnostic tests may include arterial blood gas levels, complete blood cell counts, chest radiography, ventilation-perfusion scan (VQS), helical CT (HCT), compression ultrasonography of the lower extremities, and pulmonary angiography.12 Chest radiography may not be diagnostic, but assists in excluding pleural effusions, pneumonia, pneumothorax, and pulmonary edema. The sensitivity and specificity of HCT are high, largely eclipsing pulmonary angiography. Indeed, it has now been suggested that HCT should be used early in the evaluation of suspected PE (Figure 2).13

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Figure 2. Helical computed tomography evaluation.10

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TREATMENT

Patients with untreated symptomatic proximal DVT have a 50% chance of developing acute PE, emphasizing the need for prompt attention. Management strategies include SUFH, intravenous UFH (IUFH), LMWH, warfarin, IVCF placement, and/or thrombolytic therapy. Classic treatment for stable postoperative patients with newly diagnosed DVT consists of IUFH followed by warfarin. However, the associated cost, need for frequent blood tests, and complication rate have led to an increased interest in LMWH. It is easy to administer LMWH as a subcutaneous injection without need for initial bolus, and it requires less laboratory follow-up, improves predictability of therapeutic anticoagulation, and is as effective as IUFH.14

Regarding the duration of anticoagulation to prevent recurrent thrombosis, patients with risk factors for DVT should receive at least 6 months of oral therapy. However, patients receiving long-term anticoagulation may experience increased bleeding complications.

In patients with known DVT for whom pharmacologic anticoagulation is inadequate, preoperative IVCF placement is recommended to prevent PE. Other candidates for IVCF placement include patients who have clot propagation while on anticoagulation therapy, or those who cannot tolerate anticoagulation due to side effects. Potential side effects and complications from IVCF placement are significant, however, and recommendations are variable.6 Consultation with an interventional radiologist prior to IVCF placement is thus critical.

Thrombolytic therapy has limited use in patients with massive PE, as recent surgery is a contraindication. Given the complication rate, thrombolytics should be reserved for life-threatening PE, and used only in consultation with a critical care specialist in an intensive care setting. Thrombectomy may be utilized in patients with massive PE or DVT that has progressed to significant arterial insufficiency. Consultation with a vascular surgeon and an interventional radiologist is mandatory.14

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CHRONIC ANTICOAGULATION

Some patients undergoing gynecologic surgery are receiving long term (chronic) anticoagulation therapy, perhaps as prophylaxis against a new clot or treatment for an existing thrombus. Challenges in this setting include the length of time (several days) required for both the resolution and reestablishment of oral anticoagulation perioperatively, as well as the risk of rebound hypercoagulability. The latter effect may be potentiated by the prothrombotic effect of surgery itself, which is magnified by malignancy. In patients treated with warfarin, therapy should be discontinued 3 to 4 days prior to surgery, instituting UFH or LMWH if the preoperative international normalized ratio (INR) falls to less than 2. Heparin should be continued until 6 hours prior to surgery, with monitoring of activated partial thromboplastin time (aPTT) with UFH use.

Chronic anticoagulation therapy should be resumed 12 hours postoperatively, and continued until drug levels are stable in the therapeutic range (or indefinitely for long-term LMWH administration). If possible, elective surgery should be avoided in patients with a recent history (1 to 2 months) of thromboembolism; if such surgery is necessary or there is a high risk of bleeding with heparin, preoperative IVCF placement should be considered.15

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CONCLUSION

Astute prophylaxis of VTE can do much to reduce the risk of this devastating complication of “routine” surgery. If VTE occurs despite appropriate measures, treatment can inhibit further clot propagation and avert PE and recurrent VTE, preventing long-term sequelae such as postthrombotic syndrome, venous insufficiency, pulmonary hypertension, and right-sided heart failure.

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Rebecca Byler Dann, MD, MPH, is Fellow Physician; Thomas C. Krivak, MD, is Assistant Professor; and Kristin Zorn, MD, is Assistant Professor; all in the Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Magee Womens Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA.

References

1. American College of Obstetricians and Gynecologists. Prevention of deep vein thrombosis and pulmonary embolism. ACOG Practice Bulletin No. 21. Obstet Gynecol. 2000;96(4):1-10.
2. Bonnar J. Can more be done in obstetrics and gynecologic practice to reduce morbidity and mortality associated with venous thromboembolism? Am J Obstet Gynecol. 1999:180(4):784-791.
3. Cook D, Crowther M, Meade M, et al. Deep vein thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors. Crit Care Med. 2005; 33(7):1565-1571.
4. Maxwell GL, Synan I, Dodge R, Carroll B, Clarke-Pearson DL. Pneumatic compression versus low molecular weight heparin in gynecologic oncology surgery: a randomized trial. Obstet Gynecol. 2001,98(6):989-995.
5. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Antithrombolytic Therapy. Chest. 2004;126(3 Suppl): 338S-400S.
6. Rutherford RB. Prophylactic indications for vena cava filters: critical appraisal. Semin Vasc Surg. 2005;18(3):158-165.
7. Dainty L, Maxwell GL, Clarke-Pearson DL, Myers ER. Cost-effectiveness of combination thromboembolism prophylaxis in gynecologic oncology surgery. Gynecol Oncol. 2004;93(2):366-373.
8. Bergqvist D, Agnelli G, Cohen AT, et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med. 2002,346(13):975-980.
9. Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med. 2003; 349(13):1227-1235.
10. Krivak TC, Zorn KK. Venous Thromboembolism in Obstetrics and Gynecology. Obstet Gynecol. 2007;109(3):761-777.
11. Cuevas C, Raske M, Bush WH, et al. Imaging primary and secondary tumor thrombus of the inferior vena cava: multi-detector computed tomography and magnetic resonance imaging. Curr Probl Diagn Radiol. 2006;35(3):90-101.
12. Roy PM, Colombet I, Durieux P, Chatellier G, Sors H, Meyer G. Systematic review and meta-analysis of strategies for the diagnosis of suspected pulmonary embolism. BMJ. 2005:331(7511):1-9.
13. Doyle NM, Ramirez MM, Mastrobattista JM, Monga M, Wagner LK, Gardner MO. Diagnosis of pulmonary embolism: a cost effective analysis. Am J Obstet Gynecol. 2004:191(3):1019-1023.
14. Büller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest. 2004:126(3 Suppl): 401S-428S.
15. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):188S-203S.

DISCLAIMER
The opinions expressed herein are those of the author and do not necessarily represent the views of the sponsor or the publisher. Please review complete prescribing information of specific drugs or combination of drugs, including indications, contraindications, warnings and adverse effects before administering pharmacologic therapy to patients.

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