Upper extremity deep vein thrombosis associated with indwelling peripheral venous catheters in gynecology oncology patients

Available online at www.sciencedirect.com R

Gynecologic Oncology 89 (2003) 301–305

www.elsevier.com/locate/ygyno

Upper extremity deep vein thrombosis associated with indwelling peripheral venous catheters in gynecology oncology patients Veronica L. Schimp, D.O.,* Adnan R. Munkarah, M.D., Robert T. Morris, M.D., Gunter Deppe, M.D., and John Malone, Jr., M.D. Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Wayne State University/Harper Hospital, Detroit, MI 48201, USA Received 21 August 2002

Abstract Objective. The goal of this study was to review the clinical presentation, management, and outcome of upper extremity deep vein thrombosis (UEDVT) in women with gynecologic malignancies who had indwelling peripheral venous access catheters. Methods. From a retrospective review of medical records, we identified 13 patients with various gynecologic malignancies who were diagnosed with UEDVT during their disease course. We obtained tumor data, detailed information regarding the indwelling catheters used, and the diagnosis and management of UEDVT. Results. Two hundred sixty-four women with gynecologic malignancies underwent insertion of an indwelling peripheral catheter by interventional radiology over a 5-year period. A total of 325 catheters were placed in these patients. Thirteen patients developed UEDVTs, and all had a catheter in situ at the time of DVT diagnosis. Eleven of thirteen patients had Peripheral Access System (PAS) Ports and two had peripheral indwelling central catheters (PICCs). The mean age of the patients was 53 years (range, 32–70). At the time of UEDVT diagnosis patients had the following: progressive cancer (n ⫽ 8), stable disease (n ⫽ 1), no evaluable disease (n ⫽ 4), and actively receiving chemotherapy (n ⫽ 7). Clinical signs/symptoms at the time of diagnosis included: catheter occlusion (n ⫽ 2), arm swelling and pain (n ⫽ 10), and superior vena cava syndrome (n ⫽ 1). Diagnosis of thrombosis was confirmed using Doppler ultrasound (n ⫽ 4), venography (n ⫽ 5), and both modalities (n ⫽ 4). Management of UEDVT consisted of anticoagulation with warfarin (2– 6 months) (n ⫽ 9), urokinase infusion (n ⫽ 2), intravenous antibiotics for 21 days and heparin for 10 days (n ⫽ 1), arm elevation only (n ⫽ 1), Lovenox for 60 days (n ⫽ 1), and no therapy (n ⫽ 1). There were no complications associated with anticoagulation. No patient had a pulmonary embolism. The incidence of UEDVT among our patients with indwelling venous catheters was 5.7%. Conclusion. Symptomatic UEDVT is an uncommon complication of indwelling peripheral venous catheters in women with gynecologic malignancies. The risk of pulmonary embolism is low in this patient population. © 2003 Elsevier Science (USA). All rights reserved. Keywords: Upper extremity deep vein thrombosis; Subclavian vein thrombosis; Indwelling catheters; Gynecologic malignancies

Introduction Indwelling vascular access devices are commonly used during the treatment of patients with gynecologic malignancies. They are used for chemotherapy infusion and parenteral nutrition. They have proven useful in improving qual-

* Corresponding author: Department of Gynecologic Oncology, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 440, Houston, TX 77030, USA. Fax: ⫹1-713-745-7586. E-mail address: [email protected] (V.L. Schimp).

ity of life by decreasing patient discomfort secondary to multiple needle sticks and probing for veins. Complications of indwelling catheters include pneumothorax, bacteremia, port occlusion, superior vena cava syndrome, and deep vein thrombosis. These complications have potentially serious consequences to the patient such as pulmonary embolism and death. Upper extremity deep vein thrombosis (UEDVT) is a rarely diagnosed entity, representing only 1 to 3% of all deep vein thromboses. Approximately 30% of UEDVTs are secondary to indwelling peripheral catheters. The risk of pulmonary embolism in

0090-8258/03/$ – see front matter © 2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S0090-8258(03)00074-X

302

V.L. Schimp et al. / Gynecologic Oncology 89 (2003) 301–305

patients with UEDVT ranges from 0 to 36% [1–3]. versus an approximate risk of 50% in patients with proximal lower extremity deep vein thromboses (LEDVTs) [4]. The management of patients with associated UEDVT is not well established. Our objective was to review the incidence, clinical presentation, management, and outcome of UEDVT in gynecologic cancer patients with indwelling peripheral venous catheters.

blood return. The skin incision was closed with a subcuticular stitch using 4-O vicryl. The port was then accessed with a 20- or 22- gauge Huber needle and flushed with 100 units of heparin. The PICC lines are placed in a similar fashion; however, these do not have a portal inserted into the subcutaneous tissue of the arm.

Results Material and methods The study population consisted of patients, with gynecologic malignancies, who developed an UEDVT with an indwelling peripheral venous catheter in the period 1994 – 1998. From a retrospective review of our medical records, we retrieved detailed information regarding patient age, tumor data, number of peripheral catheters placed and duration of catheter placement, and the diagnosis and management of UEDVTs. For the purpose of this study, we included patients with clinical diagnosis of axillary, subclavian, brachial, basilic, or superior vena cava thromboses confirmed by either color flow doppler, compression ultrasound, or venography. Surgical technique for indwelling catheters The Peripheral Access System (PAS) Port (Sims-Deltec, St. Paul, MN, USA) consists of a titanium portal measuring 26.7 ⫻ 16.5 ⫻ 10.0 mm and a polyurethane catheter with an outer diameter of 1.9 mm (5.8 French) and an inner diameter of 1.0 mm. The peripheral indwelling central catheter (PICC) line system (Cook, Inc., Bloomington, IN, USA) includes a Cook 5-French single-lumen or 6-French doublelumen silicone catheter. The radiologists in the Interventional Radiology Department at Harper Hospital inserted these catheters. Prior to the insertion of either a PICC or PAS Port system, a venogram was performed of the upper extremity to verify the patency of the venous system. Intravenous contrast was injected and the location of the brachial and basilic veins was marked approximately 3 in. above the antecubital fossa. Under fluoroscopic guidance the brachial, basilic, or cephalic vein was entered with a 21-gauge needle. By use of the Seldinger technique, a guidewire was advanced through the sheath into the superior vena cava and a tapered 4-French catheter was inserted. A 0.035-mm guidewire was inserted with subsequent placement of a 6-French vascular sheath over this guidewire. The PAS Port catheter was advanced through the sheath to the level of the superior vena cava. A subcutaneous pocket 2 ⫻ 2.5 cm was established adjacent to the puncture site. The catheter was then trimmed to the appropriate length and connected to the port, after removal of the vascular sheath. The wire was removed, and the port was secured in the pocket by suturing it to the underlying fascia, after confirmation of satisfactory

Two hundred sixty-four women with gynecologic malignancies underwent insertion of an indwelling peripheral catheter by interventional radiology at Wayne State University/Hutzel Hospital during the study period. A total of 324 catheters were placed. Of 264 patients, 13 (5.7%) were diagnosed with UEDVT; 11 had a PAS Port and 2 had PICCs. In comparison, 83 of these patients had a LEDVT (31.4%). The mean age of the patients was 53 years (range, 32–70). Patients’ characteristics and tumor data at the time of UEDVT diagnosis are summarized in Table 1. Patients presented with various symptoms and signs. One patient presented with pain only; one with swelling only; two with pain, swelling, and erythema; one with septic thrombophlebitis (diagnosed by the presenting signs and symptoms of fever, chills, pain, swelling, and erythema of the upper extremity and Staphylococcus aureus bacteremia); two with nonfunctioning catheters only; one with superior vena cava syndrome; and five with pain and swelling only. The patient with superior vena cava syndrome presented with acute left shoulder pain, and swelling and was diagnosed with thrombosis of the left brachial vein and partial thrombosis of the right innominate vein. This patient had removal of the catheter and 60 days of Lovenox therapy after 4 days of intravenous heparin. Doppler compression ultrasound and venography confirmed the diagnosis of UEDVT in four patients, venography only in five patients, and ultrasound only in four patients. Ten patients had leftsided UEDVTs, four had right-sided UEDVTs, and one had bilateral UEDVTs. A total of 24 catheters were placed in these 13 patients (median ⫽ 1). The average life span of the catheters was 156 days (range, 12–730 days). Two patients had recurrent UEDVT and two had a history of LEDVT. One patient had a recurrence 180 days after a Groshong catheter was placed and the other recurred 425 days after a second PAS Port was inserted. No patient developed a pulmonary embolus. In three patients, the thrombus was extensive and involved the basilic, brachial, axillary, and subclavian veins. Five patients had a thrombus affecting their subclavian, axillary, and brachial veins, two had only subclavian vein thrombosis, one had both brachial and basilic vein occlusion, one had subclavian and brachial vein involvement, and two patients had brachial and basilic vein occlusions only. Six of the thirteen patients in this study were dead of cancer progression at the time of review. The management of UEDVT varied per patient and ac-

V.L. Schimp et al. / Gynecologic Oncology 89 (2003) 301–305

303

Table 1 Demographics of patient cancer diagnosis, status, and treatment Patient

Age

Cancer diagnosis, cell type

Stage

Disease status

Current treatment

Alive

1 2 3 4 5 6 7 8 9

51 32 70 48 49 53 60 57 57

IIIC IIIC IIIC IIIC IIIC IIIC IIIC IVA IIIA

Primary Progressive Primary Progressive Recurrent Progressive Primary Progressive NED NED NED Primary Progressive Recurrent Progressive

Ifosfamide Docetaxel/VP-16 Paclitaxel/carboplatin Paclitaxel/cisplatin Observation Observation Observation Tamoxifen Doxyrubicin/cisplatin

Yes Yes No No Yes Yes No No No

10 11 12 13

64 41 67 49

Ovarian, PS adenocarcinoma Ovarian PS adenocarcinoma Ovarian, PS adenocarcinoma Ovarian, PS adenocarcinoma Ovarian, PS adenocarcinoma Ovarian, PS adenocarcinoma Ovarian, PS adenocarcinoma Ovarian, PS adenocarcinoma Endometrial, endometrioid adenocarcinoma Endometrial, leiomyosarcoma Endometrial, MMMT Cervical squamous cell Cervical squamous cell

IVB IIB IIIA IIIB

Primary Progressive NED Stable Primary Progressive

Doxyrubicin Observation Radiation/TPE Carboplatin

No Yes Yes No

PS, papillary serous; MMMT, mixed malignant mullerian tumor; NED, no evaluable disease; TPE, total pelvic exenteration.

cording to individual physician preference (Table 2). Twelve catheters were removed on diagnosis of UEDVT. One of the patients with catheter occlusions was treated successfully with 5000 U of urokinase injected into the catheters and no further anticoagulation. The other patient with catheter occlusion had the catheter removed along with elevation of the upper extremity per consultation with the

vascular surgery service. One patient had an extensive UEDVT with a functioning catheter and received no therapy. One patient who presented with septic thrombophlebitis had the catheter removed and received 10 days of intravenous heparin and 21 days of intravenous antibiotics. One patient received 60 days of Lovenox therapy. The remaining patients were treated with short-course intravenous heparin

Table 2 Description of catheters and treatment of upper extremity deep vein thrombosis (UEDVT)a Patient 1 2 3 4 5

6 7 8c 9c 10d 11

12 13d

Type of catheter

No. of catheters placed

Catheter life span (days)

Treatment of UEDVT (days)

PICCb PAS Port Groshong PAS Portb PICC PASport PAS Portb PICC

2

Removal, warfarin (60)

PAS Port PICCb PAS Port PAS Port PAS Port PAS Portb Groshong PICCb PAS Port

1 2 1 1 2

PAS Port PAS Port

1 2

201 63 135 180 30 90 120 6 16 Unknown 14 120 41 90 730 12 180 75 28 64 120 90 210 32

1 2 1 4

4

Removal, warfarin (40) Removal Removal, warfarin (60) Removal, warfarin (60)

Warfarin (180) Removal, warfarin (90) Removal, warfarin (60) Removal, warfarin (45) Removal/LT Removal, warfarin (90) Removal IV antibiotics (21) Heparin (10) Urokinase Removal, Lovenox (60) Urokinase

a PAS Port, peripheral access system Port; PICC, peripheral intravenous central catheter; US, ultrasound (doppler and compression); IV, intravenous; LT, local therapy; Lovenox, 30 ␮g subcutaneous twice daily; warfarin, dosage adjusted to international ratio (INR) 1.5 to 2.0 times control value. b Patient with recurrent UEDVTs. c Patient with LEDVTs. d Catheter in place at the time of the diagnosis of UEDVT.

304

V.L. Schimp et al. / Gynecologic Oncology 89 (2003) 301–305

(4 –7 days) followed by oral warfarin. The range of warfarin therapy was 10 to 180 days with a mean of 69.5 days (median, 60 days).

Discussion Catheter-associated thrombosis is an increasingly major cause of secondary UEDVTs. The reported incidence of all catheter-induced thrombosis varies widely from one study to the next and is dependent on the type of study (prospective, retrospective, or autopsy study) and method of diagnosis used. Prospective studies and autopsy reports identified more cases of axillary and subclavian venous thrombosis [2,3,5]. The reported risk of catheter-related UEDVT is in the range 0 –35%. It is estimated that approximately 30% of symptomatic UEDVTs are catheter-related [6,7]. Pulmonary embolism is a life-threatening complication associated with DVT. A number of publications have reported a 12% incidence (range, 0 –37%) of pulmonary embolization in patients with UEDVT [1,3,6 –9]. In a study done by Monreal and colleagues, a ventilation–perfusion lung scan was performed on 30 patients within 48 h of diagnosis of a catheter-related (peripheral or central catheter) UEDVT. Two patients had suspicious clinical symptoms but no patient had a radiologically confirmed pulmonary embolus. On the other hand, Harley and others found a 35.7% incidence of pulmonary embolus in 14 patients diagnosed with UEDVT. Two of the 14 UEDVTs were catheter-related (14.2%), and of the five patients diagnosed with a pulmonary embolus, one was catheter-related (20%). All five of these patients had symptoms consistent with a pulmonary embolus and either ventilation–perfusion scans or angiography confirmed the diagnoses. Peripheral venous access catheters are commonly used for long-term venous access in women with gynecologic malignancy [9]. Compared with indwelling central venous catheters, the peripheral devices have many potential advantages such as lower cost, improved cosmetic results, and a decrease in major surgical complications including subclavian artery laceration and pneumothorax [7]. Other infrequent but serious complications have been associated with the peripheral indwelling catheters including superior vena cava syndrome, migration of the catheter into the right heart or pulmonary vasculature, venous gangrene, pulmonary embolization, and even death. A review of the English literature fails to provide a general consensus on the treatment of catheter-associated UEDVT with either central or peripheral catheters. In addition to symptomatic therapy, which includes rest and elevation, recommended treatments have varied from simple removal of the catheter to full anticoagulation [2,3,5,10,11]. Hill and Berry advocate removal of the catheter after the diagnosis of UEDVT and then either treating with a short course of heparin followed by warfarin or

letting the body’s own fibrinolytic system dissolve the thrombus [11]. The benefit of early initiation of heparinization (within 7 days of onset) is to prevent thrombus propagation and maintain the venous collaterals for adequate venous drainage. Other authors recommend the use of warfarin therapy for several months after diagnosis [12]. In the present study, we found that for most patients immediate initiation of heparin followed by warfarin use for 5– 8 weeks was associated with minimal toxicity and prevented pulmonary embolism. Streptokinases indirectly convert plasminogen to plasmin via a proactivator and can lyse thrombi directly. Urokinase (Abbokinase Open Catheter; Abbott Laboratories, North Chicago, IL, USA) directly acts on plasminogen to form plasmin. Both have been used for the management of the occluded catheter as well as for the acute treatment of UEDVT. In a study by Whigham et al., the use of urokinase in doses of 5000 to 15,000 U by direct catheter infusion resulted in the resolution of occlusion in 98.7% of the 76 patients treated [11]. Similarly, Cassidy et al. reported dissolution of catheter thrombi in 87% of their patients treated with low-dose streptokinase (3000 U/h) [13]. Streptokinase is associated with a 5% incidence of severe complications including intracranial hemorrhage, anaphylactic shock, and death. Another theoretical problem with streptokinase is the formation of inhibitory antibodies to streptokinase, which could render streptokinase useless from Day 7 to approximately 6 months after a course of therapy with streptokinase [14]. Urokinase has advantages of direct action, no antigenicity, and greater affinity for fibrin-bound plasminogen [6,15–17]. These agents are used to manage acute (within 72 h) LEDVT when confined to the common femoral and/or iliac venous systems and the patient is not posttraumatic or postoperative [18]. The question remains: What can be done to prevent deep vein thrombosis development in the patient who has an indwelling catheter? Bern et al. conducted a randomized prospective trial of very low doses of warfarin in patients with indwelling central venous catheters [19]. They started with a pilot study to establish a dose of warfarin that would not prolong the prothrombin time. Comparing 1.0 mg daily doses of warfarin of 2.5, 2.0, and 1.0 mg, they found the 1-mg dose was the only one that did not prolong the prothrombin time. They then randomized patients receiving infusion chemotherapy via a chronic indwelling central venous catheter to receive either 1 mg warfarin daily or no therapy. Subclavian venograms were done after 90 days in the study or if signs and symptoms suggesting deep vein thrombosis occurred. They concluded that 1 mg of warfarin per day can protect against thrombosis without inducing a hemorrhagic state in the patient with an indwelling catheter and an underlying malignant diagnosis [10]. In 1992, the American College of Chest Physicians advocated prophylactic anticoagulation for patients with indwelling catheters. This group recommended that cancer patients with indwell-

V.L. Schimp et al. / Gynecologic Oncology 89 (2003) 301–305

ing central catheters receive 1 mg of warfarin daily for the duration of the life of the catheter [17]. Treatment of UEDVT continues to be a controversial subject. We found that short-term anticoagulation was successful in relieving the acute signs of swelling and pain as well as preventing pulmonary embolism. Based on the data for DVT prophylaxis in patients with thrombosis associated with central catheters, the use of low-dose warfarin should be considered in gynecologic oncology patients with peripheral indwelling catheters, especially because the benefits of such treatment seem to outweigh the risks. References [1] Harley DP, White RA, Nelson RJ, Mehringer CM. Pulmonary embolism secondary to venous thrombosis of the arm. Am J Surg 1984;47:221– 4. [2] Prandoni P, Polistena P, Bernardi E, Cogo A, Casara D, Verlato F, et al. Upper-extremity deep vein thrombosis: risk factors, diagnosis and complications. Arch Intern Med 1997;157:57– 62. [3] Monreal M, Lafoz E, Ruiz J, Valls R, Alastrue A. Upper-extremity deep venous thrombosis and pulmonary embolism. Chest 1991;99:280–3. [4] Becker D, Philbrick J, Walker F. Axillary and subclavian venous thrombosis. Arch Intern Med 1991;151:1934 – 43. [5] Whigham C, Greenbaum M, Fisher R, Goodman C, Thornby J, Thomas J. Incidence and management of catheter occlusion in implantable arm ports: results in 391 patients. J Vasc Intern Radiol 1999;10:767–74. [6] Horattas MC, Wright D, Fenton A, Evans D, Oddi M, Kamienski R, Shields E. Changing concepts of deep venous thrombosis of the upper extremity: report of a series and review of the literature. Surgery 1988;104:561–7. [7] Cunningham MJ, Collins M, Kredentser D, Malfetano J. Peripheral infusion ports for central venous access in patients with gynecologic malignancies. Gynecol Oncol 1996;60:397–9.

305

[8] Malviya VK, Deppe G, Gove N, Malone JM. Vascular access in gynecologic cancer using the Groshong right atrial catheter. Gynecol Oncol 1989;33:313– 6. [9] Deppe G, Kahn ML, Malviya VK, Malone JM, Christensen CW. Experience with the P.A.S.-PORT venous access device in patients with gynecologic malignancies. Gynecol Oncol 1996;62:340 –3. [10] Bern M, Lokich J, Wallach S, Bothe Jr A, Benotti P, Arkin C, et al. Very low doses of warfarin can prevent thrombosis in central venous catheters. Ann Intern Med 1990;112:423– 8. [11] Hill S, Berry R. Subclavian vein thrombosis: a continuing challenge. Surgery 1990;108:1–9. [12] Roos DB. Axillary–subclavian vein occlusion. In: Rutherford RB, editor. Vascular surgery. Philadelphia: WB Saunders; 1984, p. 1385– 93. [13] Cassidy FP, Zajko AB, Bron KM, Reilly JJ, Peitzman AB, Steed DI. Noninfectious complications of long-term central venous catheters: radiologic evaluation and management. AJR Am J Roentgenol 1987; 149:671–5. [14] Rubin RN. Local installation of small doses of streptokinase for treatment of thrombotic occlusions of long-term access catheters. J Clin Oncol 1983;1:572–3. [15] Taberner DA, Poller L, Burslem RW, Jones J. Oral anticoagulants controlled by the British comparative thromboplastin versus low-dose heparin in prophylaxis of deep vein thrombosis. Br Med J 1978;1: 272– 4. [16] Silver DF, Hempling RE, Recio F, Piver MS, Eltabbakh GH. Complications related to indwelling caval catheters on a gynecologic oncology service. Gynecol Oncol 1998;70:329 –33. [17] Clagett GP, Anderson FA, Levine MN. Prevention of venous thromboembolism. Chest 1992;102:391S– 407S. [18] Schwartz, S. I., Shines, T. G., Spencer, F. C., Husser, W. C., Greenfield, L. J.Venous and lymphatic disease In: Principles of surgery, 7th ed. Vol. 1. New York: McGraw–Hill; 1997, Ch. 21, p. 989 –1014. [19] Gleeson NC, Fiorica JV, Mark JE, Pinelli DM, Hoffman MS, Roberts WS, Cavanagh D. Externalized Groshong catheters and Hickman ports for central venous access in gynecologic oncology patients. Gynecol Oncol 1993;51:372– 6.