Central Venous Catheters and Thrombosis in Cancer Patients

							Central Venous Catheters
    and Thrombosis
   in Cancer Patients

Anita Ashton, Annie Young, Sue Anderson, Sue Wronski,
              Jon Burford, Gulnaz Begum
     3 Counties Cancer Network, University of Warwick
     Central Venous Catheters

Broviac 1973
“But the most considerable [experiment] I have made of
late of this, I have injected Wine and Ale in a living dog
into the Mass of Blood by a Veine, in Good Quantities, till
I have made him extremely drunk, but soon he pisseth it
out”
                 Sir Christopher Wren , 1655
Hickman – late 1970s
Implantable Ports 1980s
PICCs 1990s
      Central Venous Catheters

Type of catheter, suit the function

  Administration of chemotherapy
  Blood transfusions
  Parenteral Nutrition
  Blood Sampling

+ SUIT the patient’s lifestyle
   Catheter-related Thrombosis
          Epidemiology
Central Venous Catheters are known independent risk
factor for thrombosis

Rates of venographically documented venous
thrombosis range from 27-66%

Majority of VTEs are asymptomatic

Symptomatic rates are lower – range 0.3-28.3%
    Initiation of thrombosis
  following catheter insertion

Damage vessel wall
Altered blood flow or stasis around
catheter
Hypercoaguable state
Types of Thrombotic Catheter Occlusions
     Central Venous Catheter
Thrombosis – Presentation and Signs

 Swelling / Cyanosis of cannulated arm
 Erythema and pain
 Distal paraesthesias
 Neck swelling
 Collateral veins on chest
 Headache
 Leakage at insertion site
 Inability to flush line
     Thrombotic Risk Factors
      associated with CVCs
EARLY
  Insertion procedure

LATER
  CVC biocompatability
  No of lumens
  Infection
  ? Peripheral (PICC lines) vs centrally placed
  Left vs Right
  Catheter tip position

  Poor catheter management
           Optimal Tip Placement
         Upper portion of the lower 1/3rd of SVC




RCT     Kearns et al (1996)

21% - tip in SVC;
60% midclavicular placements:
p< 0.05
        Complications of
       Catheter-related DVT


Upper extremity deep vein thromboses
(DVTs) carry significant risk for pulmonary
embolus (15-25%) as well as local morbidity
Nidus for infection
(Postphlebitic syndrome)
      Central Venous Catheter
      Thrombosis Prophylaxis
Appropriate device
Skilled placement
Correct placement
Constant assessment of catheter function
Meticulous flushing
Fibrinolytic locks?
Anticoagulation……………
    Thrombosis Prophylaxis with
Low Molecular Weight Heparin (LMWH)
    in Cancer Patients with CVCs

 Monreal et al. Journal of Thrombosis
 Haemostasis 1996: 75(2) 251-253
                   29 patients
  Dalteparin 2500iu daily for 90 days vs control
          Overall thrombosis rate of 31%
- 6% dalteparin vs 62% in untreated control group
    CVCs, Cancer and LMWH

2005 Verso et al. JCO 2005 22(18)
385 patients of which 321 underwent
venography at 42 days;
Enoxoparin (40mg) for 6 weeks vs placebo
Rates of VTE 14.1% in enoxaparin arm (40
mg once a day) and 18% in placebo
No difference in rate of CVC-related VTE
was detected between patients receiving
enoxaparin and placebo
   CVCs, Cancer and LMWH

2006 Karthaus; Annals of Oncology 17, 289-296


 439 patients
 5000iu dalteparin vs placebo – 3.7% vs 3.4%
 (p=0.88)

 NB    endpoint - CVC complications
  Prophylaxis of thrombosis in cancer
    patients with CVCs with warfarin
          Randomised Studies

1990: Bern MM, Lockich JJ, Wallach et al.
 Ann Intern Med 112; 423-428
(with only 82 patients completing the trial - thrombosis
rates were 37.5% no warfarin vs 9.5% 1mg warfarin)
1998: Wake Forest Cancer Centre, USA –
unpublished; we have data?
1999: Park et al. Proc ASCO (abstr 2330)
80 patients – 1mg warfarin significantly superior to
no warfarin
More recent RCTs of warfarin
      1mg vs placebo
2002: Heaton et al. Journal Internal Medicine 32:
84-88
Intern Med J Mar; 32 (3); 84-8 all 88 patients had
 haematologic malignancy 1mg warfarin vs no treatment
 NO significant difference in thrombosis rates
 2005: Couban S, Goodyear M, Burnell M et al
JCO 2005: 23 (10)
Randomised Placebo-Controlled Study of Low-Dose
 Warfarin for the Prevention of CVC-Associated
 Thrombosis in Patients with Cancer
80% of 255 patients had haematologic malignancy ; 4% overall thrombosis
rate
Couban 2005 study

 255 patients who required CVC for >7days
 1mg warfarin vs placebo
 4.3% overall thrombosis
 - 4.6% in warfarin arm vs 4% in placebo

 Warfarin had no effect on CVC life span and
 did not effect the no. of premature CVC
 removals or frequency of major bleeding
 episodes
Background – Warfarin and CVCs

 After Bern study in 1990, low dose warfarin was
 used in some clinical practices
 Survey done in 1999 in UK demonstrated that 60%
 of clinicians used warfarin – 95% of these, 1mg;
 40% - no warfarin. In USA, warfarin not widely
 used
 Event rates have decreased over last decade
 whether measured clinically or radiographically
 Study Design
         Uncertain
          n = 811
         Randomise                     Certain

                                       n = 778
No Warfarin      Warfarin          Randomise
   403            408



                            Warfarin      Dose adjusted
                             1mg          warfarin (DAW)
                             471                 473
CVC-related Thrombotic Events
No Warfarin vs Warfarin

                  No Warfarin           Warfarin
                    (N=404)              (N=408)
        Event      24 (5.9%)            24 (5.9%)



     Relative Risk = 0.99 (95% CI: 0.57, 1.72)
           Chi-square test p-value =0.98
CVC-related Thrombotic Events
Warfarin 1mg vs Warfarin DAW


                 Warfarin 1mg         Warfarin DAW
                   (N=471)              (N=473)
       Event      34 (7.2%)            13 (2.8%)




      Relative Risk = 0.38(95% CI: 0.20, 0.7..)
          Chi-square test p-value <0.002
     Worst Reported Toxicity
     No Warfarin vs Warfarin


                    No Warfarin   Warfarin
                      n=404        n=408      p
  Major Bleeding         1           3
+ No Raised INR
 Major Bleeding          0           4
+ Raised INR
 Total Major Bleeding    1           7       0.07
 Worst Reported Toxicity
 Warfarin 1mg vs Warfarin DAW

                       Warfarin 1mg   Warfarin DAW
                         n=471           n=473        p

Major Bleeding              5              7
+ no Raised INR
Major Bleeding              2              9
& Raised INR
Total Major Bleeding        7             16         0.09
      WARP Catheter Data I

916 (58%) PICCs
662 (42%) centrally placed
No implantable catheters were used

78% single lumen
92% silicone
56% non return valves (Groshong)
32% flushed routinely with heparin
40% >4Fr
    WARP Catheter Data II

21% of WARP patients had at least one
non-thrombotic catheter complication

37% of those patients had infection

Of 86 patients who had a thrombosis, 8 (9%) also
had CVC diagnosed infections

 Median time to thrombosis was 32 days
(IQR 13-76 days)
              WARP Catheter Data III
      Association between CVCs and thrombosis

 Logistic regression demonstrated:
   Patients with double lumen CVCs were more likely
    to develop a CVC-related thrombosis than those
    with single lumen
  CVC material showed some importance – silicone less likely risk of
  thrombosis than polyurethane

Risk Factors
Insertion Site – PICC vs centrally placed
Valve design
Heparin flushing
CVC size (Fr)
Infection Rate
   were all unconnected to the occurrence of CVC-related thrombotic
   events
Conclusion

• There is no apparent benefit in using low dose
    warfarin for prophylaxis of symptomatic CVC-
    related thrombosis in patients with cancer.
•   Time to move on from warfarin


• Patients with double lumen catheters are at
    significantly greater risk of thrombosis than
    those with single lumen
       Recommendations

On basis of recent trials, it is difficult to
recommend routine antithrombotic prophylaxis
in cancer patients with CVCs

Further trials with modern anticoagulants in
large studies

Young et al. Lancet 2008 (in press)