PURPOSEFibrin sheaths are a significant cause of dialysis catheter dysfunction. This study aimed to determine the role of anticoagulation, antiplatelet medications, and other factors in delaying fibrin sheath formation.METHODSAn institutional review board-approved retrospective review of all patients treated for tunneled dialysis catheter fibrin sheaths from January 2014 to January 2020 was undertaken. All catheters were symmetric tipped, 14.5 F in diameter, and placed via the internal jugular vein. Seventy patients with venographically confirmed fibrin sheaths that developed after de novo catheter placement were identified. Recurrent fibrin sheaths were excluded. The impact of anticoagulation and antiplatelet therapy, as well as statin therapy, catheter side (right or left), hematocrit, platelet count, prothrombin time (PT), and international normalized ratio (INR), on the time to fibrin sheath formation was determined.RESULTSPatients on anticoagulation had a longer median catheter implantation time of 109.2 days (interquartile range (IQR): 29.3-178.5 days) compared to 80.7 days (IQR: 28.0-168.6 days) among patients not on anticoagulation. Catheter dwell time among patients taking antiplatelet therapy was 86.0 days (IQR: 31.5-160.7 days) versus 74.4 days (IQR: 27.5-202.4 days) for patients not on antiplatelet medication. Patients taking statins versus those not taking statins had median catheter dwell times of 97.5 days (IQR: 27.5-138.5 days) and 62.4 days (IQR: 29.9-259.6 days), respectively. Time to fibrin sheath formation was not significantly associated with hematocrit (P =.16), platelet count (0.12), PT (P =.51), or INR (P =.74).CONCLUSIONAnticoagulation has no significant benefit in delaying sheath formation in patients with tunneled dialysis catheters. Hematologic and coagulation parameters at the time of catheter placement were also not associated with catheter dwell time

Christopher J. Reisenauer

Edwin A. Takahashi

Forrest B. Linch

Mauricio F. Jin

Richard G. Frimpong

Scott M. Thompson

Diagnostic and Interventional Radiology

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593Impact of anticoagulation and antiplatelet therapy on dialysis catheter fibrin sheath formationLinch et al.PURPOSEFibrin sheaths are a significant cause of dialysis catheter dysfunction. This study aimed to deter-mine the role of anticoagulation, antiplatelet medications, and other factors in delaying fibrin sheath formation.METHODSAn institutional review board-approved retrospective review of all patients treated for tunneled dialysis catheter fibrin sheaths from January 2014 to January 2020 was undertaken. All cath-eters were symmetric tipped, 14.5 F in diameter, and placed via the internal jugular vein. Seventy patients with venographically confirmed fibrin sheaths that developed after de novo catheter placement were identified. Recurrent fibrin sheaths were excluded. The impact of anticoagula-tion and antiplatelet therapy, as well as statin therapy, catheter side (right or left), hematocrit, platelet count, prothrombin time (PT), and international normalized ratio (INR), on the time to fibrin sheath formation was determined.RESULTSPatients on anticoagulation had a longer median catheter implantation time of 109.2 days (interquartile range (IQR): 29.3-178.5 days) compared to 80.7 days (IQR: 28.0-168.6 days) among patients not on anticoagulation. Catheter dwell time among patients taking antiplatelet therapy was 86.0 days (IQR: 31.5-160.7 days) versus 74.4 days (IQR: 27.5-202.4 days) for patients not on antiplatelet medication. Patients taking statins versus those not taking statins had median cath-eter dwell times of 97.5 days (IQR: 27.5-138.5 days) and 62.4 days (IQR: 29.9-259.6 days), respec-tively. Time to fibrin sheath formation was not significantly associated with hematocrit (P  = .16), platelet count (0.12), PT (P  = .51), or INR (P  = .74).CONCLUSIONAnticoagulation has no significant benefit in delaying sheath formation in patients with tun-neled dialysis catheters. Hematologic and coagulation parameters at the time of catheter place-ment were also not associated with catheter dwell time.Tunneled dialysis catheters are frequently the initial access for patients requiring dialy-sis.1,2 According to the United States Renal Data System, 80% of end-stage renal dis-ease patients require a catheter when starting dialysis. At 90 days after the start of dialysis, 68.5% of patients are still reliant on catheters.3Fibrin sheaths are a significant cause of catheter dysfunction. Increased catheter infection risk and persistent bacteremia are also associated with fibrin sheaths.4 Studies have demonstrated fibrin sheaths can develop within 24 hours of catheter placement and may affect up to 47% of catheters.5,6 When thrombolytic treatment fails, patients have to undergo additional procedures to exchange the catheter, disrupt the sheath, or strip the sheath, which contribute to patient morbidity.7-10Prevention of fibrin sheath formation would be expected to have a beneficial impact on satisfactory dialysis maintenance. Placing patients on anticoagulation is a potential strategy that may decrease the risk for catheter dysfunction secondary to fibrin sheaths.11 The aim of this study is to determine whether anticoagulation, antiplatelet medication, or other factors Forrest B. Linch  Scott M. Thompson  Mauricio F. Jin  Richard G. Frimpong  Christopher J. Reisenauer  Edwin A. Takahashi Impact of anticoagulation and antiplatelet therapy on dialysis catheter fibrin sheath formationO R I G I N A L  A R T I C L E628You may cite this article as: Linch FB, Thompson SM, Jin MF, Frimpong RG, Reisenauer CJ, Takahashi EA. Impact of anticoagulation and antiplatelet therapy on dialysis catheter fibrin sheath formation. Diagn Interv Radiol. 2022;28(6):593-596.I N T E R V E N T I O N A L  R A D I O LO G YDiagn Interv Radiol 2022; DOI: 10.5152/dir.2022.21353From the Division of Vascular and Interventional Radiology, (F.B.L., S.M.T., R.G.F., C.J.R., E.A.T.  takah ashi. edwin @mayo .edu) , Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA and Mayo Clinic Alix School of Medicine (M.F.J.), Minnesota, USA.Received 4 April 2021; revision requested 15 June 2021; last revision received 26 August 2021; accepted 2 September 2021.Publication date: 7 October 2022.DOI: 10.5152/dir.2022.21353Copyright@Author(s) - Available online at dirjournal.org.  Content of this journal is licensed under a Creative Commons  Attribution-NonCommercial 4.0 International License.594 • November 2022 • Diagnostic and Interventional Radiology Linch et al.may influence the rate of fibrin sheath development in patients with tunneled dialysis catheters.MethodsThis is an institutional review board (IRB)-approved Health Care Portability and Accountability Act-compliant study (IRB# 20-003224). A waiver for informed consent was approved by the IRB for this retrospec-tive review. All patients treated for tunneled dialysis catheter fibrin sheaths from January 2014 to January 2020 were reviewed. Seventy patients with venographically con-firmed fibrin sheaths that developed after de novo catheter placement were identified. All catheters were symmetric tipped, 14.5 F in diameter (Palindrome), and placed via the internal jugular vein.The impact of anticoagulation and anti-platelet therapy, as well as statin therapy, catheter side (right or left), hematocrit, platelet count, prothrombin time (PT), and international normalized ratio (INR), on catheter dwell time was determined. Catheter dwell time, or time to fibrin sheath formation, was defined as the time between catheter placement and exchange. Only patients on anticoagulation, antiplatelet therapy, or statin therapy for the entire duration of time between catheter place-ment and fibrin sheath formation were ana-lyzed. Laboratory parameters from the time of catheter placement were reviewed.Statistical analyses were performed with JMP 13.0 (SAS). Parametric data were presented with mean and standard devia-tion. Non-parametric data were presented as median and interquartile (IQR) range. Linear regression analysis was used to determine the association between labo-ratory values and time to catheter mal-function. Mann–Whitney U test was used to compare dwell time among catheters placed in the right versus left internal jugular vein. Kruskal–Wallis test was used to compare catheter dwell time among patients taking anticoagulation, antiplate-lets, and statins. A P-value less than or equal to .05 was considered statistically significant.ResultsPatient characteristics and baseline laboratory parameters are summarized in Table 1. Mean patient age was 61.2  ± 15.0  years. There were 39 males and 31  females. All patients had their catheter exchanged. Patients with recurrent fibrin sheaths were excluded from analysis.The median catheter dwell time for the cohort was 85.1 days (IQR: 28.0-168.6 days). There were no procedural complica-tions associated with catheter placement or exchange. There were 61 catheters placed in the right internal jugular vein and 9  placed on the left. Right-sided catheters had a longer mean dwell time of 88.4 days (IQR: 28.7-212.9 days) versus 51.6 days (IQR: 9.5-133.3 days) for left-sided catheters (P  = .19) (Table 2).Patients on anticoagulation had a lon-ger median catheter implantation time of 109.2 days (IQR: 29.3-178.5 days) compared to 80.7 days (IQR: 28.0-168.6 days) among patients not on anticoagulation. Nine patients were on warfarin and 3 were on heparin. All patients taking warfarin were on standard intensity dosing with goal INRs of 2-3. The 3 patients on heparin were inpa-tients on prophylactic dosing. No patient was on direct oral anticoagulation.A total of 38 patients were on antiplatelet therapy at the time of catheter placement; all 38 patients were taking aspirin, 5 of whom were on dual-antiplatelet therapy with the addition of clopidogrel. Patients on antiplatelet therapy had a median catheter dwell time of 86.0 days (IQR: 31.5-160.7  days), compared to 74.4 days (IQR: 27.5-202.4 days) for patients not on anti-platelet medication.Median catheter dwell time among patients taking statins was 97.5 days (IQR: 27.5-138.5 days) versus 62.4 days (IQR: 29.9-259.6 days). There was no significant dif-ference in dwell time among patients on anticoagulation, antiplatelet medication, or statins (P  = .41). No statistically significant relationship was found between baseline laboratory parameters and catheter dwell time including hematocrit (P  = .16), platelet count (P  = .12), PT (P  = .51), or INR (P  = .74).DiscussionThe findings in this study suggest anti-coagulation has a limited role in prevent-ing fibrin sheath formation in patients with tunneled dialysis catheters. Other medica-tions, including antiplatelet drugs, as well as hematologic laboratory parameters at the time of catheter placement, did not correlate with catheter dwell time prior to catheter exchange due to fibrin sheath. Right-sided catheters had longer time to fibrin sheath formation compared to left-sided catheters, which supports prior data favoring right internal jugular vein access.12Main points• Tunneled dialysis catheter dwell time was not significantly longer with anticoagula-tion, antiplatelet or statin therapy.• There is no association between baseline coagulation profile and clinically signifi-cant fibrin sheath formation.Table 1. Baseline patient characteristicsCharacteristic n = 70Female, n (%) 31 (44.3)Age, mean, years (SD) 60.5 (16.1)Medication at time of catheter placement, n (%) Anticoagulation therapy 12 (17.1) Antiplatelet therapy 38 (54.3) Statin therapy 45 (64.3)Catheter dwell time (days), median (IQR) 85.1 (28.0-168.6)Hematocrit (%), mean (SD) 29.5 (4.8)Prothrombin time (s), mean (SD) 12.8 ± 3.3International normalized ratio, mean (SD) 1.1 (0.29)Platelet count (109/L), mean (SD) 249.6 ± 100.0Presence of additional central venous catheter or pacemaker, n (%) 13 (18.6)Catheter laterality, n (%) Right 61 (87.1) Left 9 (12.9)SD, standard deviation; IQR, interquartile range.Impact of anticoagulation and antiplatelet therapy on dialysis catheter fibrin sheath formation • 595To date, there are limited data on the util-ity of anticoagulation for the prevention of fibrin sheath formation. In a prospective trial on cancer patients with totally implanted central venous catheters, 25 patients with fibrin sheaths detected by ultrasound at 6 months after catheter placement were placed on low-molecular-weight heparin.11 Thirteen of these 25 patients had no detect-able fibrin sheath by ultrasound at 6-month follow-up, while persistent sheaths were detected in 11 patients, and 1 patient devel-oped subocclusive deep vein thrombosis. A prospective randomized control study by Mokrzycki et al.13 investigated the potential benefit of minidose (1 mg) warfarin against placebo for late malfunction of tunneled dialysis catheters. The authors reported fewer fibrin sheath-stripping procedures in the warfarin group than in the placebo group, though the difference was not sta-tistically significant (P  = .14). There are no prior studies that have investigated thera-peutic dose anticoagulation for the specific prevention of fibrin sheaths. Furthermore, anticoagulation and antiplatelet medica-tions have not been shown to have consis-tent benefit for the prevention of catheter thrombosis.14The limited efficacy of anticoagulants for deterring fibrin sheath formation may be attributed to the complex makeup of the sheaths. Fibrin sheaths are comprised of a heterogeneous composition of cells, thrombus, and proteinaceous material. Soujanen et  al.15 found that fibrin sheaths obtained from stripping dialysis catheters had several different histologic patterns with varying amounts of eosinophilic material, inflammatory cells, organized fibrous tissue, endothelial proliferation, and thrombus. Xiang et al.16 reported the sleeve around central venous catheters in a rat model was composed of cellular-collagen tissue covered by endothelium formed by smooth muscle cells migrating from the injured vein wall into early pericatheter thrombus. The findings in the latter study suggest that if pericatheter thrombus can be mitigated, then there could be a lower likelihood of sleeve formation around cath-eters. Nevertheless, the terms “fibrin sleeve” or “fibrin sheath” inadequately recognize the complex composition of the material forming the sheath.Catheters placed in the right internal jugular vein had longer implantation times compared to those placed on the left. This finding was not statistically significant, though this analysis was underpowered with only 9 catheters placed on the left. Right-sided dialysis catheter placements are associated with fewer early malfunction issues, including thrombosis, central venous stenosis, and infections.12,17,18 However, the rate of fibrin development was previously shown to be equivalent among differ-ent access sites.12 The higher rate of fibrin sheath development in left-sided catheters observed in the current study may be a result of the fact that fibrin sheaths are a result of smooth muscle cell migration from the injured vein wall.16 Catheters placed on the left are associated with higher rates of vascular erosion, which is likely due to the more acute angle of the catheters as they pass through the left brachiocephalic vein into the superior vena cava.19,20This study has several limitations as a result of the retrospective design. Clinical characteristics such as comorbidity and medications were not standardized. Given the variable follow-up inherent in retro-spective designs, this study focused on patients with confirmed fibrin sheaths rather than all patients who had a catheter placed. Furthermore, only patients with catheters placed with new venous access were included. Patients with prior catheter exchanges from the same access site were excluded due to the potential for residual sheath material in the vein that could lead to premature dysfunction from sheath recurrence.21This study found no statistical benefit of anticoagulation or antiplatelet medica-tion in delaying clinically significant fibrin sheath formation around tunneled dialysis catheters. Hematologic and coagulation parameters at the time of catheter place-ment were also not associated with catheter dwell time suggesting limited benefit for optimization strategies from a fibrin sheath prevention standpoint.Conflict of interest disclosureThe authors declared no conflicts of interest.References1. Adeb M, Baskin KM, Keller MS, et al. Radiologi-cally placed tunneled hemodialysis catheters: a single pediatric institutional experience of 120 patients. J Vasc Interv Radiol. 2012;23(5): 604-612. [CrossRef]2. Coryell  L, Lott  JP, Stavropoulos  SW, et al. The case for primary placement of tunneled hemodi-alysis catheters in acute kidney injury. J Vasc Interv Radiol. 2009;20(12):1578-1582. [CrossRef]3. 2017 USRDS Annual Data Report: Executive Summary. Am J Kidney Dis. 2018;71(3):S1-S8.4. Mehall JR, Saltzman DA, Jackson RJ, Smith SD. Fibrin sheath enhances central venous cathe-ter infection. Crit Care Med. 2002;30(4):908-912. [CrossRef]5. Shanaah A, Brier M, Dwyer A. Fibrin sheath and its relation to subsequent events after tun-neled dialysis catheter exchange. Semin Dial. 2013;26(6):733-737. [CrossRef]6. Hoshal  VL, Jr, Ause  RG, Hoskins  PA. Fibrin sleeve formation on indwelling subclavian central venous catheters. Arch Surg. 1971;102(4):353-358. [CrossRef]7. Savader  SJ, Ehrman  KO, Porter  DJ, Haikal  LC, Oteham AC. Treatment of hemodialysis cathe-ter-associated fibrin sheaths by rt-PA infusion: critical analysis of 124 procedures. J Vasc Interv Radiol. 2001;12(6):711-715. [CrossRef]8. Watorek E, Golebiowski T, Letachowicz K, et al. Balloon angioplasty for disruption of tunneled dialysis catheter fibrin sheath. J Vasc Access. 2012;13(1):111-114. [CrossRef]Table 2. Impact of medications and catheter parameters on catheter dwell timeDwell time median (interquartile range)Anticoagulation therapy Yes 109.2 days (IQR: 29.3-178.5 days) No 80.7 days (IQR: 28.0-168.6 days)Antiplatelet therapy Yes 86.0 days (IQR: 31.5-160.7 days) No 74.4 days (IQR: 27.5-202.4 days)Statin therapy Yes 97.5 days (IQR: 27.5-138.5 days) No 62.4 days (IQR: 29.9-259.6 days)Catheter laterality Right 88.4 days (IQR: 28.7-212.9 days) Left 51.6 days (IQR: 9.5-133.3 days)IQR, iInterquartile range.596 • November 2022 • Diagnostic and Interventional Radiology Linch et al.9. Valliant AM, Chaudhry MK, Yevzlin AS, Astor B, Chan MR. Tunneled dialysis catheter exchange with fibrin sheath disruption is not associated with increased rate of bacteremia. J Vasc Access. 2015;16(1):52-56. [CrossRef]10. Janne d’Othée B, Tham JC, Sheiman RG. Resto-ration of patency in failing tunneled hemodialy-sis catheters: a comparison of catheter exchange, exchange and balloon disruption of the fibrin sheath, and femoral stripping. J Vasc Interv Radiol. 2006;17(6):1011-1015. [CrossRef]11. Boddi M, Villa G, Chiostri M, et al. Incidence of ultrasound-detected asymptomatic long-term central vein catheter-related thrombosis and fibrin sheath in cancer patients. Eur J Haematol. 2015;95(5):472-479. [CrossRef]12. Wang K, Wang P, Liang X, Lu X, Liu Z. Epidemi-ology of haemodialysis catheter complica-tions: a survey of 865 dialysis patients from 14 haemodialysis centres in Henan Province in China. BMJ Open. 2015;5(11):e007136. [CrossRef]13. Mokrzycki  MH, Jean-Jerome  K, Rush  H, Zdunek MP, Rosenberg SO. A randomized trial of minidose warfarin for the prevention of late malfunction in tunneled, cuffed hemodialysis catheters. Kidney Int. 2001;59(5):1935-1942. [CrossRef]14. Chan MR. Hemodialysis central venous cathe-ter dysfunction. Semin Dial. 2008;21(6):516-521. [CrossRef]15. Suojanen JN, Brophy DP, Nasser I. Thrombus on indwelling central venous catheters: the histo-pathology of “fibrin sheaths”. Cardiovasc Inter Radiol. 2000;23(3):194-197. [CrossRef]16. Xiang  DZ, Verbeken  EK, Van Lommel  AT, Stas  M, De Wever  I. Intimal hyperplasia after long-term venous catheterization. Eur Surg Res. 2000;32(4):236-245. [CrossRef]17. Engstrom BI, Horvath JJ, Stewart JK, et al. Tun-neled internal jugular hemodialysis catheters: impact of laterality and tip position on catheter dysfunction and infection rates. J Vasc Interv Radiol. 2013;24(9):1295-1302. [CrossRef]18. Salgado  OJ, Urdaneta  B, Colmenares  B, García  R, Flores  C. Right versus left internal jugular vein catheterization for hemodialysis: complications and impact on ipsilateral access creation. Artif Organs. 2004;28(8):728-733. [CrossRef]19. Duntley P, Siever J, Korwes ML, Harpel K, Hef-fner  JE. Vascular erosion by central venous catheters. Clinical features and outcome. Chest. 1992;101(6):1633-1638. [CrossRef]20. Walshe C, Phelan D, Bourke J, Buggy D. Vascu-lar erosion by central venous catheters used for total parenteral nutrition. Intensive Care Med. 2007;33(3):534-537. [CrossRef]21. Beathard GA. Dysfunction of new catheters by old fibrin sheaths. Semin Dial. 2004;17(3):243-244. [CrossRef]

Impact of anticoagulation and antiplatelet therapy on dialysis catheter fibrin sheath formation

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Impact of anticoagulation and antiplatelet therapy on dialysis catheter fibrin sheath formation

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