Chapter 95
Deep Venous Thrombosis in Gynecologic Surgery
Daniel L. Clarke-Pearson and Larry Maxwell
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Daniel L. Clarke-Pearson, MD
James M. Ingram Professor of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina (Vol 1, Chap 95)

Larry Maxwell, MD
Fellow, Division of Gynecologic Oncology, Duke University Medical Center, Durham, North Carolina (Vol 1, Chap 95)

INTRODUCTION
PATHOPHYSIOLOGY
RISK FACTORS
PREVENTION
DIAGNOSIS
TREATMENT
CONCLUSION
REFERENCES

INTRODUCTION

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are two major complications after gynecologic surgery that can result in significant morbidity and mortality. Each year, about 260,000 cases of clinically diagnosed DVT occur,1 resulting in 100,000 recognized deaths attributed directly to PE.2 The incidence of DVT is suspected to be higher because of undiagnosed and asymptomatic cases as well as nationally low rates of autopsy detecting fatal PE in nursing home and rehabilitation hospital settings.1,2

The incidence of DVT in gynecologic surgery varies widely depending on the risk factors of the individual patient. About 14% of patients undergoing gynecologic surgery for benign indications develop thromboembolism.3 DVT has been observed in 38% of gynecologic oncology patients postoperatively.4 Pulmonary embolism accounts for 3% of all deaths after gynecologic surgery5 and is a leading cause of postoperative death in the highest-risk patients with uterine, ovarian, or cervical carcinoma.6 Strategies to lower the rate of fatal PE must be directed at preventing the occurrence of DVT in patients at risk.

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PATHOPHYSIOLOGY

In 1858, Virchow7 reported that the development of thromboembolism is dependent on three factors: hypercoagulability, venous stasis, and vessel wall injury. Gynecologic surgery patients are predisposed to thromboembolism because of alteration in one or more of these factors. Perioperative immobility can adversely affect the drainage of blood from the lower extremity, promoting the development of a DVT.8 Surgically induced hematomas or lymphocysts also can lead to postoperative venous stasis.9 Additionally, vessel wall injury can result from surgical dissection or malignant growth of a tumor into vascular tissues. Coagulation can result from decreased fibrinolytic activity associated with an operative procedure.10 Elevated coagulation factors (i.e., factors I, V, VIII, IX, X, and XI), activated intermediates (thrombin-antithrombin III complexes), and platelet abnormalities contribute to a hypercoagulable state in the gynecologic oncology patient.11 Cancer cells also secrete procoagulants (e.g., tissue factor and cancer procoagulant) as well as factors that affect endothelial permeability (e.g., vascular endothelial growth factor) and promote fibrin deposition.12

Once a thrombus is formed, the risk of PE depends on the location of the clot. In a prospective study of 382 gynecologic oncology patients, 17% of subjects developed DVT. Eighty-five percent of these thrombi were located in the calf veins.13 Nearly one third of these calf thrombi lysed spontaneously, and 65% did not propagate during postoperative surveillance. Only 4% propagated to the proximal leg veins, and an additional 4% became symptomatic pulmonary emboli. These findings emphasize that calf vein thrombosis, although a frequent event, is of minimal clinical significance. Moreover, 40% of the gynecologic oncology patients, who developed postoperative symptomatic PE, had no evidence of DVT in the legs, emphasizing that pelvic vein thrombi pose a high risk of PE.13 Prevention of PE secondary to proximal vein thrombosis also may prove difficult because half of these thrombi are clinically silent.14

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RISK FACTORS

Identification of risk factors that predispose patients to postoperative DVT and PE is important in the detection of high-risk patients and in the appropriate use of prophylactic therapies. Three prospective studies have evaluated clinical factors associated with the postoperative occurrence of DVT in patients undergoing major gynecologic surgery.15,16,17 Clayton and colleagues15 prospectively evaluated 124 surgical patients, none of whom received DVT prophylaxis. Using linear regression analysis, the investigators identified several risk factors for postoperative DVT: age, varicose veins, percentage overweight, euglobulin lysis time, and serum fibrin-related antigen. A prognostic index score, using these five risk factors, identified 95% of the patients who developed postoperative DVT in the study.15 Crandon and associates16 subsequently evaluated 105 patients and found that unnecessary prophylaxis could be avoided by using this prognostic index score.

A prospective investigation of 411 consecutive patients undergoing major abdominal and pelvic gynecologic surgery was undertaken at Duke University Medical Center.17 Demographic risk factors identified in this study included age, nonwhite patients, increasing stage of malignancy, past history of radiation therapy, previous DVT, lower extremity edema or venous stasis changes, varicose veins, and obesity. Intraoperative risk factors associated with postoperative DVT included increased blood loss, increased anesthesia time, and transfusion requirements in the operating room. When all of these factors were evaluated in a stepwise logistic regression model, age, type of surgical procedure, ankle edema, nonwhite race, varicose veins, past history of radiation therapy, previous DVT, and duration of surgery were found to be the most important variables associated with thromboembolic complications. Table 1 shows the frequency of DVT associated with these variables. Beginning at age 40 years, the risk increases enough that thrombosis prophylaxis should be offered to all oncology patients. This risk was increased nearly twofold in women 60 years of age compared with those who were 40 years of age.

TABLE 1. Variables Associated with Postoperative Deep Venous Thrombosis (DVT)


Diagnosis

DVT (%)

Pvalue

Benign

6

 

Cancer

17.7

 

Recurrent cancer

39

<0.001

Past history of DVT

56

<0.001*

Prior radiation therapy

36

<0.001*

Nonwhite races

25

0.03*

Ankle edema

40

0.005*

Leg stasis changes

45

0.022

Severe varicose veins

86

0.001*

Radical vulvectomy

32

0.001*

Pelvic exenteration

88

0.001*

Duration of surgery (min)

 

 

 <120

5

0.001*

 <120–300

14

 

 >300

32

 

Estimated blood loss (mL)

 

 

 <200

17.7

0.01

 200–600

12

 

 >600

23.5

 

Weight

 

0.02

Age

 

<0.001*


*Factors significant in logistic regression model.

Hormonal therapy may increase the risk of postoperative DVT.18 A review of the Michigan Medicaid data revealed that oral contraceptive formulations containing 50 μg of estrogen were associated with an increased risk of DVT.19 The risk associated with preparations containing lower doses of estrogen used is not known. A metaanalysis by Koster and colleagues20 indicated that the risk of DVT for nonoral contraceptive users was 1.1 per 10,000 and that the risk for oral contraceptive users was 3.3 per 10,000. This analysis included patients predominantly using preparations containing higher estrogen content.

Preoperative screening for an inherited defect in coagulation should be considered in low-risk patients who have a history of DVT while taking oral contraceptives. Activated protein C resistance results from a point mutation in factor V Leiden. Vandenbroucke and associates21 noted that patients with this mutation who take oral contraceptives have a 30-fold increased risk of DVT when compared with women without the mutation who do not use oral contraceptives. Other studies have confirmed an increased risk of DVT among carriers of this mutation who use oral contraceptives.22,23

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PREVENTION

Pulmonary embolism occurs in 1.6% of patients who undergo abdominal surgery without prophylaxis, resulting in death in 0.9% of patients.24 About 70% of patients with fatal PE are diagnosed at autopsy because the diagnosis of PE is not suspected clinically.25,26 Most patients experiencing fatal PE die within 30 minutes of the onset of symptoms,27 preventing timely administration of thrombolytic therapy or surgical intervention. Improved methods of DVT prevention (in contrast to surveillance or intervention) must therefore be devised to decrease the mortality associated with PE. The ideal prophylactic method should be effective, free of significant side effects, well accepted by the patient and nursing staff, applicable to most patient groups, and inexpensive.28

Pharmacologic

UNFRACTIONATED LOW-DOSE HEPARIN.

Unfractionated low-dose heparin (LDH) is a polymer of glycosaminoglycan units with an approximate molecular weight of 15,000 daltons. The heparin molecule mediates anticoagulant activity by binding antithrombin III, primarily resulting in thrombin (factor IIa) and factor Xa inhibition. The half-life of heparin can vary from 60 minutes for intravenous infusion to 3 hours for subcutaneous administration.29

The efficacy of LDH has been demonstrated in benign gynecologic surgery patients. A regimen of LDH, 5000 U given subcutaneously 2 hours preoperatively and then every 12 hours postoperatively, has reduced the incidence of DVT. In an evaluation of 110 patients, predominantly with benign gynecologic disease, the incidence of postoperative DVT was 29% among controls and 3.6% among the patients treated with the LDH regimen (p < 0.001).30 A reduction of 22% (p < 0.05) in the rate of thromboembolism was also noted in a separate trial by Taberner et al.31

At Duke University Medical Center, LDH regimens also have been evaluated as prophylaxis for gynecologic oncology patients undergoing major pelvic and abdominal surgery.32 A regimen of LDH, 5000 U given subcutaneously 2 hours preoperatively and every 12 hours postoperatively, was found to be ineffective in lowering the incidence of DVT in these high-risk patients. In this randomized controlled trial of 185 patients, the overall incidence of DVT was 12.4% among controls and 14.8% among LDH patients. When the analysis was limited to the first 7 days after surgery (during the time of prophylaxis), the incidence was 12.4% for the control group and 6.8% for the LDH group. Although this trend suggests prophylactic efficacy, the difference was not statistically significant (p = 0.2).

In a subsequent controlled trial, 304 patients were randomly assigned to receive no prophylaxis (control); 5000 U administered subcutaneously 2 hours preoperatively and every 8 hours postoperatively for 7 days (regimen I); or 5000 U administered subcutaneously every 8 hours preoperatively (three to nine doses) and every 8 hours postoperatively for 7 days (regimen II). Regimen II significantly lowered the rate of postoperative thromboembolic events when compared with controls (p = 0.008), even after logistic regression analysis adjusting for confounding variables (p = 0.005). No significant complications of bleeding were associated with any of these regimens.33

The beneficial effects of prophylactic LDH in gynecologic surgery patients are similarly seen in general surgery patients. In a metaanalysis of more than 8000 patients from 29 studies, LDH (5000 U given subcutaneously 2 hours preoperatively and every 12 hours postoperatively for 7 days) was shown to reduce the incidence of postoperative DVT from 25% to 8%.24 Additional trials have demonstrated a significant prophylactic effect of LDH on decreasing postoperative PE.34,35 A risk reduction in nonfatal and fatal pulmonary embolism of 40% and 64%, respectively, was reported by Collins and colleagues36 in an analysis of more than 70 randomized trials using heparin in general, orthopedic, and urologic surgery.

In gynecologic surgery, the complications of bleeding or lymphocele that may be associated with LDH are of particular concern. In most series, excessive bleeding is associated with LDH prophylaxis, although the absolute excess in bleeding is only about 2%.37 More intense LDH regimens (e.g., 5000 U given every 8 hours for three doses preoperatively and 7 days postoperatively) have been associated with an increased requirement for postoperative blood transfusion.38 Thrombocytopenia also may occur as a result of heparin-induced antiplatelet antibodies, although it is more common with the therapeutic doses of heparin used to treat DVT and PE.

In oncology patients undergoing pelvic and paraaortic lymphadenectomy, LDH may increase the incidence of postoperative lymphatic fluid drainage. A prospective study of 182 oncology patients given LDH, 5000 U 2 hours preoperatively and every 12 hours for 7 days, revealed significantly increased daily retroperitoneal Hemovac drainage.37 Lymphatic fluid drainage was increased nearly twofold in a subsequent prospective trial involving the use of LDH in gynecologic oncology patients.38 A prospective trial in which 48 prostatic cancer patients undergoing prostatectomy were randomized to LDH or no thromboprophylaxis revealed a significantly increased incidence of postoperative lymphocele in the LDH group.39

LOW-MOLECULAR-WEIGHT HEPARIN.

Low molecular-weight heparin (LMWH) is fragmented, unfractionated heparin that varies in size from 4500 to 6500 daltons. When compared with unfractionated heparin, LMWH has more anti-factor Xa and less antithrombin activity, leading to less effect on activated partial thromboplastin time (aPTT). Decreased platelet inhibition and microvascular bleeding has been noted with LMWH, which also may lead to fewer complications with bleeding.40 An increased half-life of 4 hours (in both intravenous and subcutaneous administrations) leads to increased bioavailability when compared with unfractionated heparin; this may allow once- or twice-daily dosing. Several LMWH preparations are available internationally, but only two (enoxaparin and dalteparin) have been approved by the US Food and Drug Administration for DVT prophylaxis.29,40

The investigation of perioperative LMWH prophylaxis is limited in gynecologic surgery. Four randomized controlled trials have compared LMWH to unfractionated LDH, revealing similar rates of bleeding complications.41,42,43,44 The rate of thromboembolism was about 2% in this collective group of 521 operative patients, with DVT diagnosed in 7 patients receiving LDH and in 3 patients receiving LMWH prophylaxis. A metaanalysis of general and gynecologic surgery patients from 32 trials likewise indicated that daily LMWH administration is as effective as unfractionated LDH in DVT prophylaxis without any difference in hemorrhagic complications.45 Caution should be maintained in interpretation of assimilated data involving LMWH because different anti-factor Xa activities are associated with the different preparations.46 In a comparison of prophylactic methods of DVT treatment, LMWH has been suggested by some investigators to be more cost-effective than LDH in general and orthopedic surgery patients, owing to the convenience of once-daily dosing.47,48

Mechanical

GRADED COMPRESSION STOCKINGS.

The grade compression stockings (GCS) are designed so that the gradient of pressure is highest at the ankle and diminishes toward the thigh. The use of GCS can increase the lower extremity blood flow velocity by about 20% over baseline,49 which can have a beneficial effect on the stasis associated with the postoperative patient at risk of developing DVT.

The use of GCS in benign gynecologic surgery patients has not been studied extensively. The single study performed included 196 benign gynecology surgery patients; 4 of 92 control patients and none of the 104 GCS patients developed postoperative DVT (p = 0.048).50

Ensuring proper fit of the GCS is important, and clinicians should understand that variations in body habitus prohibit the safe use of stockings in 15% to 20% of cases.24 In a retrospective study of 281 gynecologic oncology patients at Duke University Medical Center,6 a fourfold increased risk of postoperative DVT or PE was noted in patients who weighed more than 90 kg and who wore GCS postoperatively. Tourniquet-like leg compression by poorly fitting GCS in these obese patients may have led to increased venous stasis.

In general surgery, the use of GCS has been demonstrated in metaanalysis to reduce the risk of postoperative DVT by 64%.24 Another metaanalysis evaluating 1752 patients involving moderate-risk surgery (i.e., abdominal, gynecologic, and neurosurgical) revealed a similar risk reduction of 68%.51 In high-risk patients undergoing total hip replacement, GCS results in a risk reduction of only 25%24; therefore, in gynecologic oncology patients with several risk factors, the use of GCS alone may not be adequate prophylaxis against postoperative DVT.

INTERMITTENT PNEUMATIC COMPRESSION.

Cyclic compression of the lower extremity venous system by pneumatically inflated sleeves (intermittent pneumatic compression [IPC]) has been used in an attempt to improve the venous stasis that often occurs perioperatively. IPC stockings can augment lower extremity blood flow 180% to 240% over baseline.52 Application of IPC should be performed before surgery because venous stasis begins with the induction of anesthesia.8 Prostaglandin-mediated stimulation of the endogenous fibrinolytic system has been suggested as an additional mechanism by which IPC decreases the incidence of thromboembolism.53 Knight and Dawson's54 findings of decreased DVT among patients receiving intermittent compression of the arm support this theory.

Different methods of IPC have been evaluated in an effort to optimize prophylactic effects. Salzman and associates,55 in a randomized trial involving 136 patients, demonstrated that the incidence of postoperative DVT does not appear to be influenced by whether uniform or sequential methods of calf compression are used. The use of sequential thigh and calf IPC when compared with uniform calf IPC leads to a significantly higher rate of blood velocity and a lower incidence of proximal postoperative DVT.52 It is possible that the use of IPC that includes both the thigh and calf may improve postoperative rates of DVT when compared with devices that include only the calf. No studies are available that compare sequential and uniform IPC devices. The surgical nursing staff should be instructed in the proper use of the particular IPC device; improper functioning of the device has been observed in 52% of patients on routine nursing U and in 22% of patients in the intensive care setting.56

IPC has not been evaluated in benign gynecologic surgery patients. In a metaanalysis of general surgery patients, however, Clagett and colleagues24 found a risk reduction of 60% with the use of IPC in moderate- and high-risk patients. In gynecologic oncology patients, the use of IPC has been shown to decrease the incidence of postoperative DVT from 34.6% to 12.7% (p < 0.005).57 In this prospective trial, calf compression was applied intraoperatively and for the first 5 days after surgery. The maximal effect was noted during the 5 days of compression and diminished after IPC was stopped. A subsequent trial evaluated whether IPC would have similar a prophylactic effect if used only intraoperatively and for the first 24 hours after surgery; no reduction of DVT was seen.58 It appears that patients with gynecologic malignancies may constitute a high-risk group of patients who require at least 5 days of IPC to demonstrate reduction in the risk of DVT.

Subsequent trials involving gynecologic surgery patients have compared IPC to various LDH regimens in DVT prophylaxis. In a prospective trial, 107 patients received LDH, 5000 U given subcutaneously every 8 hours for three doses preoperatively and for 7 days postoperatively, and 101 patients received calf IPC for 5 days postoperatively. The incidence of postoperative DVT was similar in both groups; however, the frequency of transfusion requirements and the volume of retroperitoneal lymphatic drainage were significantly increased in patients receiving LDH.38 Borow and Goldson59 also revealed no difference in postoperative DVT among gynecologic surgery patients receiving LDH or IPC.

Combination Therapy (Pharmacologic and Mechanical)

Combination therapy using heparin and a compression device has been used in an attempt to diminish both the hypercoaguability and venous stasis that can be found in many postoperative patients. The prophylactic use of LDH has been compared with LDH combined with GCS for DVT prophylaxis among general surgery patients. Willie-Jorgensen and associates,60 in an investigation involving 245 patients undergoing acute extensive abdominal operations, demonstrated that the rate of postoperative DVT was significantly lower among 79 patients receiving a combination regimen of GSC and LDH (5000 U given subcutaneously 1 hour preoperatively and every 12 hours postoperatively) when compared with patients receiving only the LDH regimen (p = 0.013). A statistically significant improvement (p < 0.05) in postoperative DVT was similarly noted by the same investigators in the evaluation of 176 patients undergoing elective abdominal surgery.61 A metaanalysis of six studies involving 898 general surgery patients subsequently revealed that combination therapy with LDH and GCS provides significantly better DVT prophylaxis postoperatively than either single modality (odds ratio, 0.40; 95% confidence interval, 0.27 to 0.59).62 Although the prophylactic efficacy of combination therapy has not been specifically evaluated in gynecologic surgery, this method often is recommended for the high-risk gynecologic surgery patient.

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DIAGNOSIS

Clinical Signs and Symptoms

The classic signs and symptoms of DVT include the acute onset of lower extremity edema, pain, and erythema. About 70% of patients with DVT who develop PE do not have symptoms.25,26 Additionally, only half of patients who have signs and symptoms of DVT have proven thrombosis on venography.63 Because of the low sensitivity and specificity associated with the clinical diagnosis, all clinical events suggestive of DVT should undergo more accurate diagnostic testing.

Venography

The most accurate diagnostic test for detecting DVT is ascending contrast venography, and other, less invasive methods must be assessed against this diagnostic gold standard. The invasive nature of the procedure and the requirements for significant radiographic technical support can make venography less appealing as a diagnostic test. The procedure can result in discomfort in 18% to 44% of patients and may lead to postvenography thrombosis in 8% to 9% of patients.64 Venography should be performed to confirm the clinical suspicion of DVT; it should not be used as a method of surveillance for DVT in the asymptomatic patient. Patients with signs and symptoms suggestive of DVT who have a negative venogram do not need anticoagulant therapy. Hull and co-workers65 followed 160 patients who had negative venograms and found that 2 (1.3%) subsequently developed DVT and none developed a pulmonary embolism. Recent economic analysis indicates that venography, even when performed on an outpatient basis, is less cost-effective than serial noninvasive methods (e.g., Doppler ultrasonography and impedance plethysmography) in the diagnosis of postoperative DVT.66

Impedance Plethysmography

Impedance plethysmography is a noninvasive diagnostic test that measures venous capacitance and outflow as reflected in changes of electrical impedance within the calf. In gynecologic surgery patients with clinical symptoms of DVT, impedance plethysmography testing has a positive predictive value of 96%, sensitivity of 88%, and specificity of 94% in the detection of proximal DVT.67 Impedance plethysmography is less accurate in detecting thrombi confined to the calf veins because venous flow is not significantly altered by calf vein thrombi. False-positive results may be encountered in patients with vascular disease and cardiac failure, as may abnormal venous drainage secondary to extrinsic compression by a pelvic mass or lymphocyst. If a patient who maintains persistent symptoms of DVT has negative test results initially, the test should be repeated serially or a venogram obtained to rule out nonocclusive or proximally extending thrombi. Impedance plethysmography is neither sensitive nor specific enough to be used for surveillance of high-risk patients who do not have symptoms.

Ultrasound

B-mode ultrasonography provides a two-dimensional image of the lower extremity vessels and, using compression techniques, results in a sensitivity of 88% to 89% and specificity of 96% to 100% in the detection of DVT.68,69 Duplex ultrasonography combines B-mode with Doppler flow, which provides information regarding flow velocity. Color Doppler flow has been used with compression B-mode ultrasonography (color duplex ultrasonography) to provide information regarding flow direction in addition to velocity. Color flow may be helpful when compression B-mode ultrasonography results are indeterminate or in situations in which a patient's body habitus or clinical status prevents an optimal ultrasonographic study.70 Patients suspected of having DVT should undergo serial noninvasive testing (ultrasonography or impedance plethysmography), and anticoagulant therapy should not be administered if test results are normal.

Magnetic Resonance Venography

Magnetic resonance venography (MRV) is an imaging technique that uses magnetic resonance imaging to provide venograms without the use of intravenous contrast. Additionally, MRV provides an infinite number of views reconstructed from a single imaging session. The predictive value, sensitivity, and specificity of MRV are similar to those of duplex scanning, but the cost can be 2.5 times more in some institutions.71 The more costly nature and the lack of improvement in detection over ultrasonographic methods may hinder the widespread application of MRV in the diagnosis of DVT.

Scintigraphy

The use of radiopharmaceuticals followed by scintigraphy has been investigated in the diagnosis of DVT. Labeled substances that bind directly to the clot are more specific than contrast venography because they exclude vascular obstruction secondary to extrinsic sources. Radiopharmaceuticals have been designed to bind to mature thrombi in patients with symptoms and to bind to thrombi as they form in high-risk patients as part of postoperative screening. Fibrin-directed radiopharmaceuticals, such as labeled fibrin fragment E1, tissue plasminogen activator, or antifibrin monoclonal antibodies, bind to fibrin monomers or cross-linked fibrin within the thrombus.72 Antiplatelet monoclonal antibodies and indium-111-labeled platelets alternatively bind platelets as they organize to form the DVT.72,73 Data regarding the clinical efficacy of various scintigraphic methods is limited and has not yet demonstrated improvements over standard methods.

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TREATMENT

Deep Venous Thrombosis and Pulmonary Embolism

STANDARD REGIMENS.

Patients with documented DVT or PE should undergo anticoagulation to prevent propagation of the thrombus and to allow physiologic thrombolytic pathways to dissolve the clot. A bolus of intravenous heparin followed by continuous infusion is administered with a goal of maintaining the aPTT at 1.5 to 2.5 times control. Patients should be managed aggressively to achieve prompt anticoagulation. Wheeler and colleagues,74 in a report on physician practices in three university-affiliated hospitals, revealed that 60% of patients failed to achieve an adequate anticoagulant response (i.e., threshold of aPTT more than 1.5) during the first 24 hours of heparin infusion. Over the next 3 to 4 days, more than 30% of patients maintained suboptimal aPTT values.74

Traditionally, heparin has been given for 10 days, with the initiation of anticoagulant therapy on the 5th day of heparin administration. Alternatively, Hull and co-workers75 demonstrated that the risks of DVT recurrence and bleeding complications were similar when anticoagulants were initiated with heparin on the first day of a 5-day treatment regimen. To shorten the duration of hospitalization, most clinicians use the 5-day regimen. The change in the international normalized ratio (INR) resulting from warfarin administration often precedes the anticoagulant effects by about 2 days, during which time low protein C levels are associated with a transient hypercoagulable state.76 Therefore, heparin should administered until the INR has been maintained in a therapeutic range for at least 2 days, confirming proper warfarin dose.77 Patients who experience a thromboembolic event for the first time should take warfarin for about 3 to 6 months to prevent recurrence of thrombus.78 Longer periods of anticoagulation should be considered in patients who experience a second recurrence. Indefinite anticoagulation has not been proved to decrease the risk of DVT recurrence, and the risk of bleeding is increased in patients who maintain prolonged therapy.79

LOW-MOLECULAR-WEIGHT HEPARIN.

The efficacy and safety of treatment with LMWH have been compared with those of unfractionated heparin in numerous studies. A metaanalysis concluded that weight-adjusted LMWH was more effective and safer than weight-adjusted unfractionated heparin in the treatment of patients with DVT.80 Because the different LMWH preparations are not interchangeable in terms of anti-factor Xa activity, the conclusions of the study should be interpreted with caution. For the individual LMWH preparations, however, relative risk reduction was significant for Fraxiparine (p < 0.04) in this analysis.80

In an effort to improve the cost-effectiveness of DVT treatment, the use of LMWH on an outpatient basis has been compared with that of standard inpatient regimens using intravenous unfractionated heparin. Because patients who take LMWH do not have an associated change in aPTT, laboratory monitoring is not required, and daily or twice-daily administration is convenient in the home setting. Two prospective randomized trials collectively involving 900 patients have both concluded that home administration of LMWH is a safe and effective alternative to inpatient heparin infusion.81,82 These regimens have not yet been evaluated in postoperative patients, but findings in the surgical population would be expected to be similar.

INFERIOR VENA CAVA INTERRUPTION.

Inferior vena cava interruption is considered to be an alternative method of PE prophylaxis in patients with DVT and an absolute contraindication to heparin use (e.g., recent hemorrhagic cerebrovascular accident, neurosurgery, ocular or spinal surgery), embolization despite adequate anticoagulation, or severe complications resulting from heparin use (e.g., thrombocytopenia, bleeding requiring ongoing transfusions).83 Methods of interruption have included clipping, suture ligation, and intravascular filters. Heaps and Lagasse84 reported the successful clipping of the vena cavae of 16 patients during laparotomy for gynecologic cancer. All patients had a history of DVT at the time of surgery; none developed PE postoperatively.

Intravenous insertion of vena caval filters avoids the use of general anesthesia and is associated with a lower mortality rate (0.7%) than is surgical ligation (15%).85 No controlled trials have evaluated the efficacy and safety of vena caval filters in the treatment or prophylaxis of DVT or PE. Numerous case series have reported on the risk of complications and DVT recurrence associated with intravascular filters.

Cohen and colleagues85 have advocated the use of the Greenfield filter instead of heparin as primary treatment for DVT or PE in patients. In this series of 41 patients, 1 patient was noted to have chronic prong penetration of the vena cava, and another was diagnosed with PE recurrence. The investigators concluded that filter insertion was safe and effective and eliminated the patient's burden of heparin administration.85 Anticoagulants may be used after filter placement to prevent insertion-site DVT, inferior vena cava thrombosis, and cephalad propagation from an occluded filter. Anticoagulation after filter insertion would eliminate the advantages associated with this procedure as primary treatment in patients with no contraindications to anticoagulant therapy.

Septic Pelvic Thrombophlebitis

In a pathologic analysis of 500 consecutive hysterectomy specimens, Hayden86 noted the presence of asymptomatic pelvic thrombophlebitis in 12 gynecologic patients. Symptomatic pelvic thrombophlebitis resulting in hectic postpartum fevers has been reported in 0.05 to 0.18 of routine obstetric patients and in about 1% to 2% of patients undergoing cesarean delivery. Pelvic surgery may predispose patients not only to postoperative pelvic thrombosis but also to infection as a result of iatrogenic inoculation of bacteria. Bacteria also may enter the pelvis through the ovarian venous plexus, which communicates with both the uterine and vaginal vasculature. The incidence of symptomatic pelvic thrombophlebitis in nonpregnant gynecologic surgery patients has not been reported and presumably occurs rarely.87

Diagnosis of septic pelvic thrombophlebitis often is made presumptively in postpartum or postoperative patents with nonfocal fevers despite antibiotics. A thorough evaluation of possible sources of infection must be performed before initiation of anticoagulant therapy. Intravenous heparin is continued for 7 to 10 days, and defervescence usually occurs by day 5 of treatment.88 Surgical intervention is reserved for patients who fail to respond to medical management. Ligation of the thrombosed vein is performed, but resection of the infected vessel is not required. Interruption of the inferior vena cava is performed concurrently in patients with perioperative PE or in patients in whom the thrombus extends to this large vessel.87

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CONCLUSION

DVT and subsequent PE are a significant source of morbidity and mortality in gynecologic surgery. Most patients experiencing fatal thromboembolism are diagnosed at autopsy. Prophylaxis against DVT therefore should be used in an effort to decrease the incidence of PE. Each patient should be assessed for thromboembolic risk. Women at low risk benefit from GCS. Moderate-risk patients should be treated with either LDH, LMWH, GCS, or IPC. High-risk patients (i.e., older than 60 years, history of DVT or PE, presence of neoplasm) should be treated with more intense techniques; those at very high-risk may benefit from combined prophylaxis (Table 2).

TABLE 2. Prophylactic Techniques Appropriate for the Obstetric and Gynecologic Surgery Patient


Risks

Risk Category

Prophylactic Techniques

-

 Low

Graduated compression

 

 

 stockings (GCS)

Age <40 years and other

 Moderate

Intermittent pneumatic compression

 risk factors*

 

 (IPC) (24 h)

 

 

Low-dose heparin (LDH)

 

 

Low-molecular-weight heparin

 

 

GCS

Age >40 and no other

Moderate

 

 risk factors

 

 

Age >60 y

High

IPC (5 d)

 

 

LDH (q8h)

Cancer

High

 

Pelvic exenteration

Very high

Combination of methods (e.g.,

 

 

 IPC and GCS or IPC and LDH)

 

 

Inferior vena cava interruption

Radical vulvectomy

Very high

 

Prior history of deep venous

Very high

 

 thrombosis or pulmonary

 

 

 embolism

 

 


*See
Table 1.
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REFERENCES

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