Preventing thrombosis

Circulating blood remains fluid but has the capacity to clot (form a thrombus) at sites of injury, foreign materials or where blood flow is either slowed or irregular (due to stasis or turbulence).

A thrombus can arise on the blood vessel wall or on the surface of the catheter and in time, due to cellular factors being deposited, undergo transformation into a fibrin sheath (1). A thrombus within the vessel lumen around a catheter tip can cause temporary blockage (i.e. it is possible to infuse substances but not withdraw blood) or it may cause total blockage (occlusion) if extensive. Minimising the potential for thrombus formation can be achieved by:

  • Selecting materials with low thrombogenicity to minimise thrombus formation on the catheter surface, such as silicone or polyurethane.
  • Using atraumatic surgical technique and suitably flexible ('soft') catheters with low surface friction to minimise vessel trauma which can lead to thrombosis around the implant.
  • Positioning the catheter tip in a flowing blood stream to help prevent thrombosis due to stasis. Some types of catheter have a special tip configuration which acts as a valve preventing ingress of blood and luminal thrombosis (e.g. a Groshong catheter).
  • Good catheter use and management will also minimise the possibility of thrombosis. This involves minimising blood residues in the catheter lumen by careful flushing and locking (see below). Thrombosis risk is greater in arterial catheters due to higher pressure forcing blood into the lumen, so these require particularly careful management.

Catheter locking

During catheter access it is important to minimise the time for which blood remains stationary in the lumen.

Immediately after the blood samples have been collected, the catheter lumen should be flushed thoroughly before blood begins to clot. During the time periods when a catheter is not being accessed, the lumen must be filled with a suitable solution to exclude blood and prevent clotting  - this process is called locking. Locking technique and solutions are also important in preventing infection. A wide range of lock solutions and techniques are used and have been described (see Table 1). The choice of lock solution should be made to ensure that its composition minimises experimental interference (e.g. heparin may be undesirable if blood clotting mechanisms are being studied and taurolidine is an antibacterial compound). 

Table 1. Catheter lock solutions

Lock solution

Advantages

Disadvantages

Notes

0.9% saline

  • Enables filling of the catheter without exogenous chemical matter
  • Cheap and easily obtained
  • Low flow rate 0.9% saline may be used in infusion studies
  • Provides no thrombosis prevention
  • No antibacterial activity
  • Continuous low rate infusion (keep vein open [KVO] setting on infusion pumps) is effective in maintaining catheter patency

0.9% saline with heparin (20-500 IU/ml)

  • The most widely used material, with heparin providing thrombosis prevention
  • This solution provides no antibacterial action
  • Suggested heparin concentration is empirical - low concentrations for frequent flushing and smaller animals
  • Higher concentration for less frequent flushing and larger animals

40% dextrose (glucose)

  • The high osmolarity prevents bacterial colonisation and multiplication.
  • The high osmolarity contributes non-specifically to clot prevention/disruption.
  • Dextrose occurs naturally in blood and is rapidly metabolised.
  • Available cheaply as a pharmaceutical formulation.
  • Crystallisation is a risk.
  • The viscosity of the solution helps to prevent blood accessing the catheter lumen (but makes the lock solution slightly more difficult to withdraw).
  • Adding heparin (100-500 IU/m) will provide additional prevention against thrombus.

50% sucrose (saturated)

  • As for 40% dextrose.
  • Cheap and readily obtained.

 

  • Usually prepared and sterilised in the laboratory by autoclaving (so risk of contamination/pyrogens).

Glycerol

  • High viscosity, high osmotic pressure.
  • Can be difficult to aspirate.

 

Polyvinylpyrrolidone (PVP)

  • High viscosity, high osmotic pressure.
  • Can be difficult to aspirate.

 

Sodium citrate

  • A cheap antithrombotic which can be used where heparin is contraindicated.
  • Heat labile - therefore cannot be sterilised by autoclave.
  • No antibacterial action.

 

Taurolidine citrate solution 6.7%

  • Taurolidine is an effective and convenient antibiotic.
  • Citrate salt provides specific antithrombotic action.
  • Expensive.
  • Supplied commercially for catheter locking in preclinical research.

Resources and references

  1. Peters RW et al. (1973) The development of fibrin sheath on indwelling venous cathetersSurgery, Gynecology and Obstetrics 137: 43-47.

Other resources on vascular catheterisation

Click here for information on the design of catheters for use in laboratory animalsClick here for information on preventing infection when implanting catheters in laboratory animalsClick here for information on planning and designing experiments which will involve implanting catheters into laboratory animalsClick here for a glossary of terms used in our pages on implaning catheters into laboratory animals