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Catheter-Related Thrombosis: Risks, Diagnosis, and Management JN049_Jrnl_40910Linen.qxd 9/26/06 10:03 PM Page 889 889 Original Article Catheter-Related Thrombosis: Risks, Diagnosis, and Management Michael L. Linenberger, MD, Seattle, Washington Key Words are needed to identify the safest and most effective anticoagulant Thrombosis, central venous catheter, deep vein thrombosis, pul- agents, treatment durations, and alternative venous access strate- monary embolism, anticoagulation gies for cancer patients who develop catheter-associated thrombo- sis. (JNCCN 2006;4:889–901) Abstract Symptomatic thromboembolic complications of central venous Implanted and external semipermanent central venous catheters (CVCs) occur in 5% or less of general oncology patients. catheters (CVCs) are essential for optimal management Asymptomatic CVC-related thrombi are more common, but their clinical significance is unclear. Thrombotic risk may be increased by of complicated patients with solid tumors and hematologic primary thrombophilic disorders, especially the factor V G1691A malignancies. Their usefulness for blood sampling, infu- (Leiden) mutation, thrombogenic catheter material, larger catheter sions, and, in some cases, apheresis procedures is coun- diameter and greater number of lumens, catheter tip malposition, terbalanced by the fact that these devices are nonbiologic left-sided placement, percutaneous or multiple insertion attempts, foreign bodies that can activate coagulation locally and a previous CVC or preexisting venous obstruction, prothrombotic therapeutic agents, catheter-associated infections, and fibrinous interact physiologically with hereditary and acquired hy- catheter lumen occlusion. Three recent randomized, prospective, percoagulable conditions to induce thrombosis. placebo-controlled trials observed no benefit of routine low-dose Among the general population, roughly 9% of first ve- warfarin or low-molecular-weight heparin in preventing catheter- nous thromboembolic events are causally associated with associated thrombosis. Nevertheless, thromboprophylaxis may be a CVC or transvenous pacemaker, and recent CVC place- appropriate and safe for selected high-risk patients. Duplex ultra- sound can accurately detect CVC-related thrombi involving the jugu- ment increases the risk for upper-extremity deep vein 1,2 lar, axillary, distal subclavian, and arm veins. Contrast venographic thrombosis (DVT) by 5- to 7-fold. Spontaneous upper- imaging is required for indeterminate duplex findings and to eval- extremity DVT is 2.6- to 8-fold more likely among patients uate the deep central veins and pulmonary arteries. Therapeutic with active cancer,3,4 and a CVC significantly augments anticoagulation, with or without catheter removal, is indicated for that risk.4,5 The managing oncologist must be cognizant patients with acute deep vein thrombosis (DVT) or pulmonary em- bolism who have no contraindications. Catheter removal alone, with of this risk and that additional circumstances that fur- close follow-up, may be sufficient when bleeding risk precludes safe ther predispose to thrombosis may justify the use of pro- anticoagulation. Approaches to managing catheter-associated phylactic anticoagulation for selected patients. Moreover, thrombosis, including the use of thrombolytic agents, are guided by because catheter-associated thromboembolic events are limited published experience and extrapolation from practices used still relatively common among high-risk subgroups, the for lower-extremity DVT. Prospective, randomized, controlled trials optimal approaches for diagnosis and management are important to understand. From the Division of Hematology and Department of Medicine, University of Washington, and Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, Washington. Submitted July 17, 2006; accepted for publication July 28, 2006. Device-Related Incidence and Risk Factors The author has no financial interest, arrangement, or affiliation with the manufacturers of any products discussed in the article or Central venous access devices that are designed for their competitors. long-term use include surgically tunneled, externalized Correspondence: Michael L. Linenberger, MD, Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance (G6-800), single or multiple lumen catheters, and fully implanted 825 Eastlake Avenue E, P.O. Box 19023, Seattle, WA 98109-1023. catheters that are connected to resealable diaphragm ports E-mail: [email protected] that are positioned under the skin of the chest or arm. © Journal of the National Comprehensive Cancer Network | Volume 4 Number 9 | October 2006 JN049_Jrnl_40910Linen.qxd 9/26/06 10:03 PM Page 890 890 Original Article Linenberger Peripherally inserted central catheters (PICCs) are External Tunneled Catheters also commonly used for patients who require only tem- Long-term, tunneled, external CVCs induce throm- porary access (e.g., weeks as opposed to many months). bosis at rates similar to implanted chest port catheters; Different models of each of these catheter types are however, the reported incidence varies based on the manufactured with intraluminal pressure-sensitive study population and diagnostic criteria. In the early valves that prevent passive blood reflux. Temporary or 1990s, approximately 9% of patients with hemato- tunneled CVCs are also available with larger lumen di- logic malignancies undergoing HSCT developed symp- ameters that accommodate the high flow rates neces- tomatic CVC-related thrombosis and up to 63% were sary for leukapheresis (e.g., to collect peripheral blood found to have asymptomatic subclavian vein thrombi stem cells) or other apheresis procedures. These on venographic surveillence.16–19 More recent prospec- double- or triple-lumen external devices are inserted tive and retrospective studies that included only can- into the internal jugular, subclavian, or femoral vein. cer patients observed symptomatic thrombosis in 4.7% 20–22 Tunneled apheresis catheters that are used for stem to 10% of adults and 2% to 2.5% of children with 23,24 cell collection are commonly retained throughout the tunneled external CVCs. Incidence rates of asymp- 25,26 course of hematopoietic stem cell transplant (HSCT), tomatic clots ranged from 30% to 74%. As with unless a complication necessitates removal. implanted ports, tunneled catheters with closed (valved) lumens offer no added protection from throm- PICCs botic complications when compared with open-lumen Thrombotic complications specifically associated with catheters.17 One patient subgroup that appears to be PICCs and implanted port systems have been charac- at greater risk with external catheters than with im- terized in retrospective and prospective cohort studies. planted ports is children with acute lymphoblastic Based on recent observations, occult PICC-related ve- leukemia (ALL). A 3.9-fold higher rate of thrombo- nous thrombosis is detected in 23% to 39% of cancer sis was observed among 49 children with ALL and ex- patients undergoing surveillance venography,6,7 whereas ternal CVCs compared with 236 children with symptomatic thromboembolism (manifested by pain, implanted ports.27 swelling, or erythema) or thrombotic occlusion requir- General Incidence and Technical Risk Factors ing catheter removal occurs in only 3.4% to 3.9% of Recent prospective thromboprophylaxis trials that in- patients.8,9 Most symptomatic events with PICCs oc- cluded patients with all types of catheters showed gen- cur within the first 2 weeks of placement and involve erally lower incidence rates of CVC-related thrombosis the cephalic or basilic arm veins rather than the cen- compared with earlier studies (see later discussion). tral vessels. Higher thrombotic risk is associated with This trend contradicts the higher annual percentages larger lumen diameter and infusion of chemotherapy.8 of venous or arterial thrombotic complications diag- nosed among cancer patients in 2002 compared with Central Port Catheters 1995.28 The reason for this discrepancy is not clear but Clinically overt upper-extremity thrombosis occurs in may relate to avoidance or minimization of technical 0% to 9% of cancer patients with port catheters that risk factors that predispose to CVC-associated throm- are implanted in the chest.10–16 By comparison, throm- bosis, including thrombogenic catheter material (e.g., botic complications are more common in arm ports, polyethylene compared with polyurethane or sili- with incidence rates ranging from 2% to 30%.10,11,14 As cone),29 larger catheter diameter or greater number with PICCs, many of the events with arm ports in- of catheter lumens,8,17,20,22,24 catheter tip malposi- volve the proximal arm veins rather than the central tion,12–14,20,21,30 percutaneous insertion techniques (com- veins.Port-related DVT is predisposed by catheter tip pared with cut-down),31 left-sided placement,14,15,31,32 malposition.12–14 Left-sided placement (compared with or two or more insertion attempts (compared with right) has been identified as a risk factor in some stud- one; see Table 1).33 A potential additional risk, at least ies14,15 but not in others.13,16 One prospective random- in some adults with malignancies22 and children with ized clinical trial found no differences in the rates of ALL who receive asparaginase,31 but not in general overall thrombosis with central (chest) ports con- medical or surgical patients,34 is the insertion of the nected to valved lumens compared with port catheters CVC in the subclavian vein compared with the in- with open lumens (4% vs. 7.3%).16
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