Table 1: Studies evaluating therapies for the prevention of HD catheter dysfunction.

ReferenceStudy design N Treatment groupsOutcomeEffectP

Catheter locking agents

HeparinThomas, 2007 [7]P
𝑁 = 2 7 3
Heparin
(1000 U/mL)
Heparin (10 000 U/mL)Catheter dysfunction (per 1000 HD sessions)Low H/high H
6.7 versus 7.6
NS
Thrombolytic therapy (per 1000 HD session)Low H/high H
26.6 versus 8.2
<0.001

HeparinHolley, 2007 [8]R
𝑁 = 6 4
Heparin
(1000 U/mL)
Heparin (10 000 U/mL)Thrombolytic therapy (per 6 months)Low H/high H
63% versus 31%
<0.001

Citrate (4%)Buturovic, 1998 [9]RCT
𝑁 = 3 0
Citrate 4%Heparin
(1666 U/mL)
Polygeline (3.5%)Catheter survival (days)C/H/P 51/23/32<0.01

Citrate (4%) Lok, 2007 [10]P
𝑁 = 2 5 0
Citrate
4%
Heparin (5000 U/mL)Thrombolytic rate (per 1000 days)C/H 3.3 versus 5.5<0.001
Catheter removal for poor flow (per 1000 days)C/H 1.65 versus 2.980.042

Citrate (4%)  Grudzinski, 2007 [11]  R
𝑁 = 3 0 7
Citrate*
4% 
Heparin** (10 000 U/mL)  Thrombolytic rate (per 1000 days)C/H 3.23 versus 4.100.07
Catheter removal for poor flow (per 1000 days)C/H 1.88 versus 1.81NS

Citrate (4%)MacRae, 2008 [12]RCT
𝑁 = 6 1
Citrate
4%
Heparin (5000 U/mL)Thrombolytic therapy
(6 months)
C/H 41% versus 45%NS

Citrate (5%)  Hendrickx, 2001 [13]  RCT
𝑁 = 1 9
Citrate
5% 
Heparin (5000 U/mL)  Thrombolytic therapy (per HD session)C/H 8% versus 1%NS
Aspiration of thrombus (6 months)C/H 14% versus 7%<0.001

Citrate (30%)Stas, 2001 [14]P
𝑁 = 1 1
Citrate
30%
Heparin (5000 U/mL)Aspiration of thrombusC=HNS

Citrate (30%)  Weijmer, 2005 [15]  RCT
𝑁 = 2 9 1
Citrate
30% 
Heparin (5000 U/mL)  Thrombolytic Therapy (6 months)C/H 47% versus 44%NS
Catheter removal for poor flow (per 1000 days)C/H 3.2 versus 3.6NS

Citrate (47%)Bayes 1999 [16]P
𝑁 = 1 0
Citrate,
46.7%
Heparin (5000 U/mL)Blood flow rateC=HNS

Citrate (47%)Power, 2009 [17]RCT
𝑁 = 2 3 2
Citrate,
46.7%
Heparin (5000 U/mL)Thrombolytic therapy (per 1000 days)C/H
8.2 versus 4.3
<0.001

Tissue plasminogen activator  Schenk, 2000 [18]  P
𝑁 = 1 2
r-TPA (1 mg/mL interdialytic lock)  Heparin (1000 U/mL)  Blood flow rate mL/minTPA/H
237 versus 208
0.001
Thrombolytic therapy (4 months)TPA/H
0% versus 20%

Tissue plasminogen activator  Gittins, 2007 [19]  P
𝑁 = 9
r-TPA (1 mg/mL interdialytic lock)  Heparin (1000 U/mL)  Aspiration of thrombusH > rTPA:
O.R. 2.4
0.001
Clot volumeH > rTPA:
O.R.  =  1.9
<0.001

Tissue plasminogen activatorHemmelgarn, 2011 [20]RCT
𝑁 = 2 2 5
r-TPA (1 mg/mL interdialytic lock midweek heparin 5000 U/Ml in other 2 sessions)Heparin (5000 U/mL)Catheter malfunctionrTPA  <  heparin
HR 1.91
0.02

Catheter-related bacteremia (episodes/1000 catheter days)rTPA<Heparin
0.40 versus 1.37
0.02

Modified catheters

Heparin-
coated
catheters 
Clark, 2009 [21]  R
𝑁 = 8 8
Heparin-coated catheter (+ heparin lock 5000 U/mL)  Noncoated catheter (+ heparin lock 5000 U/mL)  Primary patency (at 3 months)HCC/NCC
82% versus 76%
NS
Thrombosis rate (per 1000 days)HCC/NCC
0.8 versus 0.4
NS

Heparin-
coated
catheters 
Jain, 2009 [22]  R
𝑁 = 1 7 5
Heparin-coated Catheter (+ Hepain lock 5000 U/mL)  Non-coated Catheter (+ Hepain lock 5000 U/mL)  Cumulative catheter survival (at 6 months)HCC/NCC
48% versus 41%
NS
Thrombolytic therapy (per 1000 days)HCC/NCC
1.8 versus 1.8
NS

Oral agents

Warfarin (mini dose)  Mokrzycki, 2001 [23]  RCT
𝑁 = 8 5
Warfarin (1 mg)  Placebo Primary catheter patency (at 1 year)W/P
58% versus 48%
NS
Assisted primary catheter patency (at 1 year)W/P
20% versus, 18%
NS

Warfarin (low intensity)   Wilkieson, 2011 [24]   RCT
𝑁 = 1 7 4   
Warfarin (INR 1.5–1.9)   Placebo  Primary catheter patencyW/P
46% versus 47%
NS
Catheter removal for dysfunctionW/P
HR  =  0.87
NS

Warfarin (low intensity)Zellweger, 2005 [25]P
𝑁 = 6 5
Warfarin (INR 1.5–2.0) (high-risk pts)Controls (low-risk pts)Primary catheter patency (at 9 months)Anticoagulation
(adequate versus inadequate)
47% versus 8%
0.01

Warfarin
(high intensity) 
Obialo, 2003 [26]  P
𝑁 = 6 3
Aspirin 325 mg/d  Warfarin (INR 2-3)Control Primary catheter patency (number of days)A/W/C
114/111/68
<0.001
Catheter survival (at 4 months)A/W/C
91%/73%/29%
<0.001

Warfarin
(medium intensity)
and ticlodipine 
Coli, 2006 [27]  RCT
𝑁 = 1 4 4
Primary prevention Warfarin (INR 1.8–2.5) + ticlodipine 250 mg/day (1°W + T)  Secondary prevention (INR 1.8–2.5) + Ticlodipine 250 mg/day (2°W + T)  Catheter dysfunction (1 year) 1°W + T/2°W + T
12% versus 52%
<0.01
Catheter dysfunction (events per pt/year)PWT/RWT
0.16 versus 1.65
<0.001