2. Brief overview of presentation
Hemostasis & basic coagulation
cascade
Conventional anticoagulants
Newer drugs
Evidence based medicine
3. Introduction- Hemostasis
Hemostasis is defined as process of
platelet – fibrin thrombus formation to seal a site
of vascular injury without resulting in total
occlusion of the vessel
4.
5.
6. On hemodialysis
• All the part of the extracorporeal circuit are
thrombogenic.
• Intrinsic coagulation pathway is invariably
activated at all times patient is taken on HD.
• Without anticoagulation, 4 hrs HD will lead to
a) 5-10 % cases to have clotting
b) loss of 100-150ml blood loss
c) Early loss of the dialyser
7. Factors favouring increased clotting
• Low blood flow rates
• High UF rate
• Intradialytic blood, blood products,albumin
and lipid infusion, iv drips – infusions
• Dialysis access recirculation
• High hematocrit of patient
• Retained air in dialyser, inadequate priming
8. Signs of clotting
• Extremely dark blood in circuit
• Black streaks in dialyser- clotted fibres
Grade I clotting- < 10 % fibres
Grade II clotting- 10- 50 % fibres
Grade III clotting- > 50 % fibres
• Clots in arterial side header
• Foaming and clot in drip chamber and venous
trap
• Rapid filling of the transducer monitors with
blood
13. Routine heparin
A) Bolus f/b constant infusion
Bolus - 1000 U from the venous acsess tubing
f/b saline flush and wait for 3- 5 min before
initiating HD
Infusion - 1000 U/hr from the arterial line
14. B) Bolus f/b intermittent boluses
Bolus - 4000 U from the venous acsess tubing
f/b saline flush and wait for 3- 5 min before
initiating HD
Intermittent boluses - 1000 – 2000 U if
necessary from the arterial line
15. Tight heparin
Bolus - 750 U from the venous access tubing f/b
saline flush .
Check WBPTT/ACT after 3 min
• If levels not upto baseline + 40% give more
bolus
• If yes then start HD
Infusion - 600 U/hr from the arterial line
Continue till the termination
16. Target to achieve- by WBPTT/ACT
Regular heparin Tight heparin
Predialysis Post dialysis Predialysis Post dialysis
Baseline +
80 %
Baseline +
40 %
Baseline +
40 %
Baseline +
40 %
WBPTT- 60-80 sec
ACT – 120-150 sec
17. When to terminate the heparin
Regular with continous infusion or int. bolus
1 hour before termination – AVF/Graft
Till the end – Catheter
Tight heparin – Till the end
18. Normal heparin vs low dose heparin
Normal heparin - Infusion rates of 1000 u/hr
Low dose heparin - Infusion rates of 500 u/hr
21. Heparin free HD
Initial rinse – Rinse the extracorporeal circuit
with 3000 units UFH in 1 litre saline.
Drain- allow the heparinised saline to drain out
completely before venous return to patient by
filling the circuit with patients blood or normal
saline
22. Blood flow rates- 400ml/min
Periodic saline rinse – 250 ml every 15 min
• To reduce clot formation ??????
• To inspect if there is ongoing clot formation
23. Disadvantages
• Partial clotting - 20% of cases
• Complete clotting - 7%
• Catheter clotting
• Inadequate HD
• Labour and cost intensive
24. Low molecular weight heparin (LMWH)
• Superior pharmacokinetics,
• Higher bioavailability,
• Less non-specific binding
(Xa: Antithrombin activity = 3:1,
Heparin has 1:1 and added inhib of TFPI)
• Hence predictable dosing
• Longer half-life
25. Other advantages
• Less dyslipidemia
• Less pruritus
• Less hyperkalemia
• Less osteoporosis
• Less HITT
26. Dose
Single loading dose of 125-250 anti factor XA
Institute Choay Units (aXa ICU)/kg at the start of
hemodialysis .
No monitoring needed.
28. Is LMWH better?
A meta-analysis including 11 studies published
in 2004 -
“LMWH and UF heparin were similarly safe and
effective in preventing extracorporeal circuit
thrombosis, with no significant difference in
terms of bleeding, vascular compression time
or thrombosis”
J. Am. Soc. Nephrol. 2004; 15: 3192–206.
29. Is LMWH better?
LMWH is however recommended as the agent of
choice for routine haemodialysis by the
European Best Practice Guidelines
“The single factor weighing against the use of LMWH as
the routine form of anticoagulation for dialysis
is cost”
USFDA has still not approved it for HD
Nephrology 2010;15:386–392
30. Heparinoids - Danaparoid
• Extracted from pig gut mucosa
• Heparinoid of molecular weight of 5.5 kDa,
mixture of
84% heparan sulphate,
12% dermatan sulphate and
4% chondroitin sulphate
31. Danaparoid
• Binds to antithrombin but minimal impact on
platelets and a low affinity for PF4
• More selective for Xa than even the LMWH
Xa : thrombin binding
Danaparoid- 22–28 : 1
LMWH - 3:1
UFH – 1:1
• Low cross-reactivity with HIT antibodies (6.5–10%)
although recommended to test for cross-reactivity
before use of Danaparoid in acute HIT Type II
32. Dose –
Bolus dose- 750 IU for wt >55kg
Intermittent boluses – to achieve anti – Xa activity of
0.25-0.35
Disadvantage-
No reversal agent
Long action (30 hrs)
10 % risk of HITT
Fondaparinux 7.5 mg s/c can be used - a synthetic
pentasaccharide which is safe in HITT (do not cross
react with PF4 antibodies)
33. Direct thrombin inhibitors- DTI’s
HIRUDIN
• Originally discovered in the saliva of leeches
• Binds thrombin irreversibly at its active site and the
fibrin-binding site
• Recombinant variants are also available
– Lepirudin,
– Desirudin and
– Bivalirudin
34. Argatroban
• Synthetic derivative of L-arginine
• Binds irreversibly to the catalytic site
• Short half-life of 40–60 min
• Not effected by renal function
• Hepatic clearance means prolonged duration
of action in patients with liver failure
• Bolus- 250 mcg/kg f/b 0.5 -2 mcg/kg/min to
titrate to level of aPTT 1.5 -2 times normal
35. Argatroban
• Anticoagulant effect can be monitored by a
variant of the APTT – the ecarin clotting time
• No available reversal agent
36. Melagatran
• Experimental
• Available orally as a prodrug, which is taken twice a day
• Renally cleared and has a prolonged half-life
• No antidote
• Hepatotoxic
37. Citrasate / citricon dialysate solution
• Bicarbonate dialysis solution with low citrate
concentration (2.4 meq/l)
• Done by adding citric acid instead of acetic
acid at a low dose.
• Citrate chelates calcium and inhibits
coagulation.
• As a part of low or heparin free HD
38. Regional anticoagulation for HD
To restrict the anticoagulant effect to the dialysis
circuit and prevent systemic anticoagulation in
patients at increased risk of bleeding.
39. 1) UF heparin/protamine
• Historically, the use of UF heparin/protamine
was prototypical of regional anticoagulation
• UF heparin is infused into the arterial line and
protamine into the venous line
• Dose of 1 mg protamine/100 units heparin
40. 1) UF heparin/protamine
• Procedure can be technically challenging and
• No significant advantage over ‘low-dose’
heparin regimens
• Reactions to protamine are not uncommon
and may be serious
• Can’t be used in HITT syndrome
41. 2) Citrate regional anticoagulation
• Isoosmotic trisodium citrate infusion is given
into the arterial side of the dialysis circuit
• It chelates calcium and decreases coagulation
in the extracorporeal circuit.
• But to avoid patient landing up with
hypocalcemia, calcium chloride is infused at
the venous end
42. Advantages over heparin free HD
• No need of very high blood flow rates
• Better outcomes as compared to heparin free
method for avoiding clotting
43. Disadvantages
• Risk of alkalemia as citrate metabolises to
bicarbonate – dialysate bicarb shoud be
reduced
• Risk of hypernatremia
• Need hourly monitoring of ionised calcium,
either hyper or hypocalcemia is dangerous
• Need two infusions- TSC and CaCl3
44. 3) Prostacyclin regional anticoagulation
• Vasodilator and platelet aggregation inhibitor
• Very short half-life of 3–5 min
• Infused into the arterial line
• Side effects
Headache, light headedness,
facial flushing,
hypotension
prohibitive cost
