Question 17

Advantages

Limitations

Systemic heparin (low to medium dose)

Easy to administer, cheap,
may not have a significant systemic anticoagulation, effectively antagonized by protamine, physician familiarity

Anticoagulation with this 
dose not always successful, may need higher doses,
risk of bleeding, pharmacokinetics altered
in critiillness, need to monitor APTT, Risk of· HITTS.

Regional heparin (pre
filter) with post filter protamine

More complex to administer, monitoring, allergy to protamine

LMWheparin

Easy to use, expensive, useful if patients has associated HITTS

Need to measure Xa levels.
Protamine not effective

Regional Citrate (pre
filter) with post filter Ca

Very effective, can be used 
in HITTS

Clinician unfamiliarity,
need for Ca free special dialysate, metabolic alkalosis, hypocalcemia,
need for systemic DVT
. prophylaxis still.

Prostacyclin

Useful if patient has
associated HITTS

Hypotensio platelet
dysfunction and risk of bleeding

Heparinoids

Useful if patient has associated HITTS

• Circuit lifespan may still be acceptable for patients at high risk of bleeding (i.e. those who have "anticoagulated" themselves)

• This will not benefit patients with HIT who are actually prothrombotic; another systemic anticoagulant will be required.
• May not be suitable for patients with a normal or mildly impaired clotting function

• Easy and cheap
• Safe - no added pharmacological complications

• Relies on a good vas cath position and a calm compliant patient.
• The vas cath has to be reasonably widebore, which can increase the risk of vascular complications
• The higher flow rate may not be tolerated by hemodynamically unstable patients

• Routine and well-rehearsed modality
• Reasonably safe in most patient groups
• Cheap

• Reduces small solute clearance; thus:
• Reduces CVVHDF efficiency

• Routine and well-rehearsed modality
• Reasonably safe in most patient groups
• Cheap
• Anticoagulation is easily reversible
• Anticoagulation is short-term
• Does not rely on renal clearance

• Unsuitable for HIT patients
• May cause HIT
• May be unsuitable for patients at high risk of bleeding

• Advantageous for patients at high risk of bleeding in whom filter lifespan is still reduced due to clotting
• Reversal of anticoagulation at the end of the circuit decreases the risk of bleeding complications

• Unsuitable for HIT patients
• Cumbersome protocols, greatly increased workload
• The heparin–protamine complex is taken up
  by the reticuloendothelial system and broken down, but
  then heparin and protamine are released back into the
  circulation.
• Protamine has known disadvantages:
  • Protamine can act as an anticoagulant
  • Protamine causes pulmonary hypertension

• More convenient (boluses vs. infusion)
• Identical filter life to unfractionated heparin
• May be safer in terms of bleeding risk.
• Lower incidence of HIT
• No need for monitoring (or, rather, monitoring is too difficult and we give up)
•  

• More expensive compared to unfractionated heparin
• Clearance is renal; there is the potential for accumulation
• May be unsafe in patients at high risk of bleeding

• Cheap
• The patient may already be warfarinised

• No evidence for benefit in preventing catheter thrombosis
• Difficult to initiate
• Slow to reverse
• Metabolism affected by numerous factors

• Not totally experimental
• Many patients are already on these drugs

• Difficult to monitor
• No reversal agent - irreversible inhibition
• Long term effects
• Many of these drugs rely on renal clearance

• Reversible
• Effective
• Pre-mix solutions have simplified this process; protocols exist to guide the inexperienced

• Cumbersome protocol; greatly increased workload
• Requires frequent monitoring:
  • Sodium
  • Calcium
  • Bicarbonate (or pH)
• If you are using trisodium citrate, you end up giving a massive amount of sodium
• Acidosis may result due to excess citrate
• Alkalosis may result when that citrate is metabolised
• In hepatic failure, this is contraindicated (as citrate is metabolised mainly by the liver)
• Special calcium-free hyponatraemic and bufferless dialysate is required
• If the patient has HITTS, they will still require some sort of systemic anticoagulation
• Risk of toxicity
  • High anion gap metabolic acidosis
  • Ionised hypocalcemia

• Alternative to heparin in HIT
• Argatroban has a short halflife and is metabolised by the liver
• There is a predictable near-linear relationship between hirudin levels and APTT

• Expensive
• Hirudin, lepirudin and bivalirudin are renally excreted; halflife will be prolonged
• Argobatran is metabolised by the liver - halflife will be prolonged in liver failure
• Argatroban falsely raises PT and INR.
• All these molecules are too large to be removed by CRRT membranes, and will accumulate.
• No reversal agent

• Alternative to heparin in HIT
• Probably safe in most cases

• Expensive
• Cross-reactivity with heparin/platelet antibodies (in 5%)
• Long half life (48 hrs)
• No reversal agent
• Higher risk of bleeding than with heparin

• Alternative to heparin in HIT
• Probably safe

• Renally cleared; may accumulate in high doses
• Long halflife (15-20hrs)
• No reversal agent

• Very short half-life (8 min)
• Regional anticoagulation only
• Probably safe

• Suppresses neutrophil activity and may cause agranulocytosis
• May cause increased bilirubin levels
• Clearance relies on serum esterases, which may be decreased in chronic liver disease
• May decrease protein C activity, leading to paradoxically increased circuit clotting
• May cause anaphylaxis
• May cause hyperkalemia

• Very short half life (90 seconds)
• Probably safe
• Decreases platelet consumption in the circuit
• Can be used together with heparin for a combined effect, as a "heparin-sparing" agent.

• Hypotension from vasodilation
• Ridicuously expensive
• If the patient has HITTS, they will still require some sort of systemic anticoagulation