Is antithrombotic prophylaxis required in cancer patients with central venous catheters? Yes for special patient groups.

Abstract

Venous thromboembolism (VTE) occurs frequently in patients with hemato‐oncological diseases and is one of the leading causes of death [1Geerts W.H. Pineo G.F. Heit J.A. Bergqvist D. Lassen M.R. Colwell C.W. Ray J.G. Prevention of venous thromboembolism.Chest. 2004; 126: 338S-400SAbstract Full Text Full Text PDF PubMed Scopus (2828) Google Scholar]. The risk for developing VTE may be significantly increased high during the chemotherapy, after cancer surgery and as a result of long‐term indwelling central vein catheter (CVC) placement. Many patients with hemato‐oncological diseases get CVCs for different reasons, including chemotherapy, stem cell infusions, and parenteral nutrition. Although its role in facilitating high quality patient care is evident, the use of long‐term CVC may be associated with complications. Early complications, including catheter misplacement or breakage, injury into adjacent anatomical structures, pneumothorax or hematothorax, are thought to occur in 0.3% to 12% [2Mansfield P.F. Hohn D.C. Fornage B.D. Gregurich M.A. Ota D.M. Complication and failure of subclavian‐vein catheterization.N Engl J Med. 1994; 331: 1735-8Crossref PubMed Scopus (721) Google Scholar]. Late complications include catheter occlusion by catheter sleeve, local or systemic infection and CVC‐related deep vein thrombosis (DVT), the latter of which may be followed by pulmonary embolism (PE). The thrombosis associated with a CVC can be limited to the catheter tip, the length of the catheter (fibrin sheath), or the catheterized vein in the arm, with or without the more proximally located veins of the neck or mediastinum [3Bona R.D. Thrombotic complications of central venous catheters in cancer patients.Semin Thromb Hemost. 1999; 25: 147-55Crossref PubMed Scopus (117) Google Scholar]. The incidence of CVC‐related VTE has been studied in several studies. Inconsistencies, including study design, population, catheter insertion techniques, definition of VTE events, and accuracy of diagnostic tests to diagnose thrombosis (i.e. the use of compression ultrasonography, echo‐Doppler, or venography), have hampered an accurate estimation. In a recently performed systematic review [4Verso M. Agnelli G. Venous thromboembolism associated with long‐term use of central venous catheters in cancer patients.J Clin Oncol. 2003; 21: 3665-75Crossref PubMed Scopus (464) Google Scholar], the reported incidence of symptomatic CVC‐related DVT in adult patients varied between 0.3% and 28.3%. Of note, in 50% of the prospectively performed studies reviewed the reported incidence of symptomatic CVC‐related DVT was 5% or less. Further, if the review is limited to the studies reported after 2000, the reported incidence of symptomatic CVC‐related thrombosis, assessed in prospective studies, ranged between 1.5% and 7.3%. This is in line with a study, in which 6% of patients with venography proven CVC‐related DVT were symptomatic [5De Cicco M. Matovic M. Balestreri L. Panarello G. Fantin D. Morassut S. Testa V. Central venous thrombosis: an early and frequent complication in cancer patients bearing long term silastic catheter – a prospective study.Thromb Res. 1997; 86: 101-13Abstract Full Text Full Text PDF PubMed Scopus (184) Google Scholar]. The incidence of CVC‐related DVT – of which most thrombi were asymptomatic – assessed by venography ranged from 27% to 66%. Pulmonary embolism has been shown to occur in 15% to 25% of patients, although it is unclear what exact percentage of patients had symptomatic PE. In two of the studies analyzed, PE was called symptomatic in 25% and 30% of patients, this translates into 5% of patients in both studies – but few patients were included and therefore confidence limits are therefore wide [6Monreal M. Lafoz E. Ruiz J. Valls R. Alastrue A. Upper extremity deep venous thrombosis and pulmonary embolism: a prospective study.Chest. 1991; 99: 280-3Abstract Full Text Full Text PDF PubMed Scopus (219) Google Scholar, 7Monreal M. Raventos A. Lerma R. Ruiz J. Lafoz E. Alastrue A. Llamazares J.F. Pulmonary embolism in patients with upper extremity DVT associated to venous central lines: a prospective study.Thromb Haemost. 1994; 72: 548-50Crossref PubMed Scopus (197) Google Scholar]. In another review article [9Bern M.M. Lokich J.J. Wallach S.R. Bothe A, J.r. Benotti P.N. Arkin C.F. Greco F.A. Huberman M. Moore C. Very low doses of warfarin can prevent thrombosis in central venous catheters: a randomized prospective trial.Ann Intern Med. 1990; 112: 423-8Crossref PubMed Scopus (796) Google Scholar], the incidences of catheter‐related thrombosis ranged between 27% and 90%, with symptomatic thrombosis ranging between 0% and 20%. Several randomized studies have been performed to evaluate the efficacy and safety of antithrombotic prophylaxis in patients with cancer and a CVC [4Verso M. Agnelli G. Venous thromboembolism associated with long‐term use of central venous catheters in cancer patients.J Clin Oncol. 2003; 21: 3665-75Crossref PubMed Scopus (464) Google Scholar, 8Klerk C.P.W. Smorenburg S.M. Buller H.R. Thrombosis prophylaxis in patient populations with a central venous catheter.Arch Int Med. 2003; 163: 1913-21Crossref PubMed Scopus (103) Google Scholar]. Low‐dose warfarin and low doses of unfractionated heparin (UFH) or LMW heparin have been evaluated. A number of older studies were open‐labeled and had relatively small sample sizes. Very recently, larger studies, including two using a double‐blind design, have been reported. In a clinical trial, a fixed low dose of warfarin (1 mg d−1) was given for 3 months in 82 patients with a malignancy (hematological or solid tumors) who had a CVC (Port‐a‐Cath) [9Bern M.M. Lokich J.J. Wallach S.R. Bothe A, J.r. Benotti P.N. Arkin C.F. Greco F.A. Huberman M. Moore C. Very low doses of warfarin can prevent thrombosis in central venous catheters: a randomized prospective trial.Ann Intern Med. 1990; 112: 423-8Crossref PubMed Scopus (796) Google Scholar]. This dose regimen was based on a demonstrated effect in the prophylaxis in patients undergoing gynecologic surgery [10Poller L. McKernan A. Thomson J.M. Elstein M. Hirsch P.J. Jones J.B. Fixed mini‐dose warfarin: a new approach to prophylaxis against venous thrombosis after major surgery.BMJ. 1987; 295: 1309-12Crossref PubMed Scopus (147) Google Scholar]. Venography was performed at 90 days. Fourteen (37.5%) of 40 control patients developed a DVT vs. four (9.5%) of 42 patients on warfarin (P < 0.001). Seventeen events were symptomatic, in most patients the prothrombin time did not prolong and there was no increase in bleeding in the warfarin‐treated patients. Two subsequent trials, however, did not show any effect with minidoses of warfarin vs. no prophylaxis [11Heaton D.C. Han D.Y. Inder A. Minidose (1 mg) warfarin as prophylaxis for central vein catheter thrombosis.Intern Med. 2002; 32: 84-8Crossref Scopus (141) Google Scholar, 12Couban S. Goodyear M. Burnell M. Dolan S. Wasi P. Barnes D. Macleod D. Burton E. Andreou P. Anderson D.R. Randomized placebo‐controlled study of low‐dose warfarin for the prevention of central venous catheter‐associated thrombosis in patients with cancer.J Clin Oncol. 2005; 23: 4063-9Crossref PubMed Scopus (284) Google Scholar]. In the latter study, with a double‐blind design, a clinically overt thromboembolic event occurred in six of 130 (4.6%) patients in the group treated with warfarin 1 mg day−1 and in five of the 125 (4%) in the placebo group (hazard ratio 1.20, 95% CI 0.37–3.94) [11Heaton D.C. Han D.Y. Inder A. Minidose (1 mg) warfarin as prophylaxis for central vein catheter thrombosis.Intern Med. 2002; 32: 84-8Crossref Scopus (141) Google Scholar]. There was no difference in major or minor bleeding in the two groups. Of note, in more than half of patients the warfarin treatment had to be interrupted for more than 7 days because of thrombocytopenia. In another study among 95 patients with central lines given warfarin 1 mg, 33% had an INR > 2.0, 27% had an INR of >3.0 and 7% had an INR of >7.0. Bleeding was observed in eight patients, seven of whom had an INR > 7.0. [13Masci G. Magagnoli M. Zucali P.A. Castagna L. Carnaghi C. Sarina B. Pedicini V. Fallini M. Santoro A. Minidose warfarin prophylaxis for catheter‐associated thrombosis in cancer patients: can it be safely associated with fluorouracil‐based chemotherapy.J Clin Oncol. 2003; 21: 736-9Crossref PubMed Scopus (101) Google Scholar]. The 2004 ACCP consensus guidelines on antithrombotic therapy recommend against the use of fixed‐dose warfarin for this indication [1Geerts W.H. Pineo G.F. Heit J.A. Bergqvist D. Lassen M.R. Colwell C.W. Ray J.G. Prevention of venous thromboembolism.Chest. 2004; 126: 338S-400SAbstract Full Text Full Text PDF PubMed Scopus (2828) Google Scholar] (LMW) heparin. In an open study of 29 patients with cancer and CVC, dalteparin or placebo was randomly given in a dose of 2.500 IU subcutaneously per day for a period of 90 days. Upper extremity venography was carried out at 90 days, or earlier if symptoms appeared. The study was prematurely stopped after eight of 13 patients in the control group had developed thrombosis vs. one of 16 patients assigned to LWMH (62 vs. 6%P = 0.002) [14Monreal M. Alastrue A. Rull M. Mira X. Muxart J. Rosell R. Abad A. Upper extremity deep venous thrombosis in cancer patients with venous access devices: prophylaxis with a low molecular weight heparin (Fragmin)..Thromb Haemost. 1996; 75: 251-3Crossref PubMed Scopus (386) Google Scholar]. Six of the 29 thrombotic episodes were symptomatic; there was no increased risk of bleeding associated with the use of LMWH. Different results were seen in a more recent double‐blind study in which 425 patients with cancer receiving chemotherapy through a CVC were randomized to receive dalteparin 5.000 IU subcutaneously once daily or placebo for a period of 16 weeks. Clinically apparent VTE occurred in 3.7% and 3.4% respectively in the dalteparin and the placebo‐treated patients [15Reichardt P. Kretzschmar A. Biakhov M. A phase III, randomized, double‐blind, placebo‐controlled study evaluating the efficacy and safety of daily low‐molecular‐weight‐heparin (dalteparin sodium) in preventing catheter‐related complications (CRCs) in cancer patients with central venous catheters (CVCs).Proc Am Soc Clin Oncol. 2002; 21: 369aGoogle Scholar]. Very recently, two studies evaluating prophylactic (LMW) heparin have been published [16Abdelkefi A. Ben Othman T. Kammoun L. Chelli M. Romdhane N.B. Kriaa A. Ladeb S. Torjman L. Lakhal A. Achour W. Ben Hassen A. Hsairi M. Ladeb F. Ben Abdeladhim A. Prevention of central venous line related thrombosis by continuous infusion of low dose unfractionated heparin in patients with hemato‐oncological disease.Thromb Haemost. 2004; 92: 654-61Crossref PubMed Scopus (79) Google Scholar, 17Verso M. Agnelli G. Bertoglio S. Di Somma F.C. Paoletti F. Ageno W. Bazzan M. Parise P. Quintavalla R. Naglieri E. Santoro A. Imberti D. Soraru M. Mosca S. Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double‐blind, placebo‐controlled, randomized study in cancer patients.J Clin Oncol. 2005; 23: 4057-62Crossref PubMed Scopus (272) Google Scholar]. In the first study, which had an open‐randomized design, patients with hematological malignancies, coming from one hospital, were randomized to receive 100 U kg−1 UFH daily (maximum 10.000 IU) per continuous infusion or saline, both during their treatment. [16Abdelkefi A. Ben Othman T. Kammoun L. Chelli M. Romdhane N.B. Kriaa A. Ladeb S. Torjman L. Lakhal A. Achour W. Ben Hassen A. Hsairi M. Ladeb F. Ben Abdeladhim A. Prevention of central venous line related thrombosis by continuous infusion of low dose unfractionated heparin in patients with hemato‐oncological disease.Thromb Haemost. 2004; 92: 654-61Crossref PubMed Scopus (79) Google Scholar] Catheter thrombosis was assessed by ultrasound. CVC‐related thrombosis occurred in 1 of 65 (1.5%) CVC's in the UFH group vs. 8 of 63 (12.5%) in the control group (P = 0.03). Symptomatic thrombosis occurred in one patient in the UFH group vs. five patients in the control group. Catheter dysfunction occurred in 11(17%) and 33 (52%) in the UFH and control group, respectively (P = 0.001). Two and three patients got severe bleeding in the UFH and control group, respectively (P = 0.18), one patient in the control died of severe bleeding. In the second multicenter study with a double‐blind design, patients with hemato‐oncological tumors (91% of patients had solid tumors, 9% had a hematological malignancy) were randomly assigned to receive either enoxaparin 40 mg d−1 subcutaneously or matching placebo injections for a period of 6 weeks. All patients underwent routine CVC limb venography at the end of the treatment period [17Verso M. Agnelli G. Bertoglio S. Di Somma F.C. Paoletti F. Ageno W. Bazzan M. Parise P. Quintavalla R. Naglieri E. Santoro A. Imberti D. Soraru M. Mosca S. Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double‐blind, placebo‐controlled, randomized study in cancer patients.J Clin Oncol. 2005; 23: 4057-62Crossref PubMed Scopus (272) Google Scholar]. Three independent radiologists assessed the presence of thrombosis. In the enoxaparin group, the incidence of DVT was 14.1% (22 of 155 patients), in the placebo group the thrombosis rate was 18.0% (28 of 155 patients), for a relative risk of 0.78 (95% CI 0.47–1.31). DVT was occlusive in 14 patients and 36 were non‐occlusive. Eight patients (2% of all patients) developed symptomatic DVT (two in the enoxaparin group and six in the placebo group). No major bleeding occurred during the treatment period. The authors give several explanations to their results. Firstly, the 18% rate of thrombosis in the placebo group was substantially lower than rates in earlier mentioned studies (37.5% and 62%, respectively). This could be because of the improved biocompatibility of the CVC's used as well as the less invasive insertion procedures applied. A second point was the lower relative reduction exerted by enoxaparin than provided by the study hypothesis, which predicted a relative reduction of 50% based on a 30% DVT rate in the placebo group vs. 15% DVT rate in the enoxaparin group. Given the absence of major bleeding in the treated group, the dose of 40 mg enoxaparin per day may have been too low and higher doses could be justified based on the absence of major bleeding in the enoxaparin group. Although it has been observed that most episodes of thrombosis have occurred during the first 6 weeks after insertion, a second option is to prolong the period of prophylaxis beyond 6 weeks. The challenge for the clinician involved in cancer patient care is how to weigh the outcome in the different studies, in order to make a decision for the next patient who gets a CVC catheter in daily clinical practice. There are several points that deserve attention. Firstly, a different approach in the choice of endpoints was used in the studies. In some studies, venography, in the presence or absence of symptoms, of the upper limb at the end of the treatment period was used, while in other studies clinically manifest thromboembolism, as assessed by objective tests, was used. The use of the screening venography approach was derived from the prophylactic studies in the post‐operative setting in general and orthopedic surgery, with lower leg venography after 7–10 days [1Geerts W.H. Pineo G.F. Heit J.A. Bergqvist D. Lassen M.R. Colwell C.W. Ray J.G. Prevention of venous thromboembolism.Chest. 2004; 126: 338S-400SAbstract Full Text Full Text PDF PubMed Scopus (2828) Google Scholar]. Asymptomatic thrombosis in the deep veins of the lower leg is considered as a valid surrogate endpoint as 20% of calf vein thrombi extend in to the more proximally located veins and 50% of the proximal thrombi will embolize to the lungs. There is a caveat, however, when this is extrapolated to the CVC‐related thrombosis risk, as the natural history of CVC‐related thrombosis is not as well defined as post‐operative thrombosis. In addition, there is a substantial variation among studies in the reported rates of PE. [3Bona R.D. Thrombotic complications of central venous catheters in cancer patients.Semin Thromb Hemost. 1999; 25: 147-55Crossref PubMed Scopus (117) Google Scholar, 4Verso M. Agnelli G. Venous thromboembolism associated with long‐term use of central venous catheters in cancer patients.J Clin Oncol. 2003; 21: 3665-75Crossref PubMed Scopus (464) Google Scholar] Importantly, among the studies using clinical endpoints a considerably lower event rate (2–4.6%) was observed than in studies using asymptomatic routine venography‐proven thrombosis. As nicely pointed out in an accompanying editorial on the Verso study [18Levine M. Kakkar A.K. Catheter‐associated thrombosis: thromboprophylaxis or not.J Clin Oncol. 2005; 23: 4006-8Crossref PubMed Scopus (29) Google Scholar], the choice of two different outcomes is very similar to a debate on endpoints used in prophylaxis trials in the orthopedic surgery setting [1Geerts W.H. Pineo G.F. Heit J.A. Bergqvist D. Lassen M.R. Colwell C.W. Ray J.G. Prevention of venous thromboembolism.Chest. 2004; 126: 338S-400SAbstract Full Text Full Text PDF PubMed Scopus (2828) Google Scholar, 19Hull R.D. Pineo G.F. Stein P.D. Extended out of hospital low molecular weight heparin prophylaxis against deep vein thrombosis in patients after hip arthroplasty.Ann Int Med. 2001; 135: 858-69Crossref PubMed Scopus (300) Google Scholar]. Although the standard in orthopedic surgery has been mandatory venography, the alternative argument is that the only appropriate endpoint is symptomatic VTE. In view of the uncertain natural history of asymptomatic thrombi, it may be that in trials evaluating antithrombotic prophylaxis in cancer patients with CVC the better endpoint symptomatic thrombosis is a better outcome. In spite of the endpoint taken, it is obvious that given the fact that the event rates in recently performed trials are much lower than anticipated, any future trial would require a much large sample size to detect a clinically relevant (50%) reduction. Secondly, although on the basis of contemporary trials a reasonable general recommendation is not to give on a routine basis any antithrombotic prophylaxis to cancer patients with CVC catheter, some patients may be at particular high risk for developing CVC‐related thrombosis. Several studies have reported an association between the presence of a factor V Leiden (FV Leiden) mutation and increased risk of CVC‐related thrombosis [20Mandala M. Curigliano G. Bucciarelli P. Ferretti G. Mannucci P.M. Colleoni M. Ventura A. Peruzzotti G. Severi G. Pelicci P.G. Biffi R. Orsi F. Cinieri S. Goldhirsch A. Factor V. Leiden and G20210A prothrombin mutation and the risk of subclavian vein thrombosis in patients with breast cancer and a central venous catheter.Ann Oncol. 2004; 15: 590-3Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar, 21Van Rooden C.J. Rosendaal F.R. Meinders A.E. Van Oostayen J.A. Van Der Meer F.J. Huisman M.V. The contribution of factor V Leiden and prothrombin G20210A mutation to the risk of central venous catheter‐related thrombosis.Haematologica. 2004; 89: 201-6PubMed Google Scholar, 22Jansen F.H. Van Der Straaten H.M. Roest M. Haas F. De Groot P.G. Fijnheer R. Elevated levels of D‐dimer and fragment 1&2 upon central venous catheter insertion and factor V Leiden predict subclavian vein thrombosis.Haematologica. 2005; 90: 499-504PubMed Google Scholar, 23Abdelkefi A. Ben Romdhane N. Kriaa A. Prevalence of inherited prothrombotic abnormalities and central venous catheter‐related thrombosis in haematopoietic stem cell transplants recipients.Bone Marrow Transplant. 2005; 36: 885-9Crossref PubMed Scopus (27) Google Scholar], although in one study this association was not observed [24Tesselaar M.E. Ouwerkerk J. Nooy M.A. Rosendaal F.R. Osanto S. Risk factors for thrombosis in cancer patients.Eur J Cancer. 2004; 40: 2253-9Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar]. In view of the reluctance of physicians to prescribe antithrombotic agents to patients at high risk for bleeding, it has been argued to offer hereditary screening for thrombophilia as a basis for prophylactic treatment [25Van Rooden C.J. Monraats P.S. Kettenis I.M. Low physician compliance of prescribing anticoagulant prophylaxis in patients with solid tumor or hematological malignancies and central vein catheters.J Thromb Haemost. 2003; 1: 1842-3Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar]. Whether this approach is cost‐effective has not been demonstrated. A more practical way could be to consider antithrombotic prophylaxis in all cancer patients with a CVC who have a prior history of unprovoked (idiopathic) VTE irrespective of the presence or absence of FV Leiden mutation. Thirdly, the selection of patients included in the intervention studies might be debated. In most studies, a mixed population of patients with hematological malignancies and with solid malignant tumors have been included. In the studies, no subgroup analysis has been carried out. The intensity of treatment including bone marrow transplantation and related neutropenia and thrombocytopenia makes patients with hematological malignancies a very vulnerable group with respect to risk for infection and bleeding. Of note, in two recent cohort studies of patients with hematological malignancies undergoing intensive chemotherapy, the incidence of symptomatic CVC‐related thrombosis was nine percent and 13%, respectively [26Van Rooden C.J. Rosendaal F.R. Barge R.M. Van Oostayen J.A. Van Der Meer F.J. Meinders A.E. Huisman M.V. Central venous catheter related thrombosis in haematology patients and prediction of risk by screening with Doppler‐ultrasound.Br J Haematol. 2003; 123: 507-12Crossref PubMed Scopus (64) Google Scholar, 27Jansen F.H. Van Der Straaten H.M. Roest M. Haas F. De Groot P.G. Fijnheer R. Elevated levels of D‐dimer and fragment 1 + 2 upon central venous catheter insertion and factor V Leiden predict subclavian vein thrombosis.Haematologica. 2005; 90: 499-504PubMed Google Scholar], which is more than 2–4‐fold the incidence of symptomatic VTE in the mixed population that the recent studies described above. There may be a need to perform studies in separate patient groups focussing on patients with hematological malignancies and intensive chemotherapy. Finally, besides exerting antithrombotic prophylaxis, (LWM) heparin may well interfere with the risk for CVC‐related infection. The catheter sleeve, being an adherent coating of fibrin and collagen, that envelopes the CVC can facilitate the development of local infection and sepsis and may lead to thrombosis [28Hoch J.R. Management of the complications of long‐term venous access.Semin Vasc Surg. 1997; 10: 135-43PubMed Google Scholar]. Otherwise, a relationship between thrombus formation and catheter‐related septicemia, pulmonary emboli and septic thrombi have been observed [29Raad I.I. Luna M. Khalil S.A. Costerton J.W. Lam C. Bodey G.P. The relationship between the thrombotic and infectious complications of central venous catheters.JAMA. 1994; 271: 1014-6Crossref PubMed Scopus (440) Google Scholar]. Catheter‐related infection is observed in 2–43% of patients [2Mansfield P.F. Hohn D.C. Fornage B.D. Gregurich M.A. Ota D.M. Complication and failure of subclavian‐vein catheterization.N Engl J Med. 1994; 331: 1735-8Crossref PubMed Scopus (721) Google Scholar]. In a meta‐analysis of studies evaluating prophylactic doses of heparin (up to 5000 IU four times daily) or heparin bonding to the CVC catheter, a reduced risk of bacterial colonization (RR 0.18; 95% CI 0.06–0.60) [30Randolph A.G. Cook D.J. Gonzales C.A. Andrew M. Benefit of heparin in central venous and pulmonary artery catheters; a meta‐analysis of randomised controlled trials.Chest. 1998; 113: 165-71Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar] was observed [24Tesselaar M.E. Ouwerkerk J. Nooy M.A. Rosendaal F.R. Osanto S. Risk factors for thrombosis in cancer patients.Eur J Cancer. 2004; 40: 2253-9Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar]. Besides, there was a trend for reduced risk of catheter‐related bacteremia (RR, 0.26; 95% CI 0.07–1.03) as well as a reduction in CVC‐related thrombosis (RR, 0.43, 95% CI 0.23 –0.78). In summary, routine prophylaxis with either low‐dose warfarin or (LMW) heparin in patients with hemato‐oncological diseases with CVCs is currently not indicated, given the results of the recently performed studies. In the 2004 ACCP guidelines on antithrombotic therapy, it is suggested that clinicians do not routinely use prophylaxis to try to prevent thrombosis related to long‐term indwelling CVCs in cancer patients [1Geerts W.H. Pineo G.F. Heit J.A. Bergqvist D. Lassen M.R. Colwell C.W. Ray J.G. Prevention of venous thromboembolism.Chest. 2004; 126: 338S-400SAbstract Full Text Full Text PDF PubMed Scopus (2828) Google Scholar]. It is well possible, however, that certain patient groups, including those with a hematological malignancy undergoing intensive chemotherapy as well as those with a hereditary thrombophilia or with a prior history of unprovoked thrombosis, may have an elevated risk of developing symptomatic VTE, making them reasonable candidates for prophylaxis. If future trials evaluating antithrombotic prophylaxis in these special patient groups are designed, the potential reduction in risk of bacterial colonization and catheter‐related infection by (LMW) heparin should also be considered.