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1. Anticoagulation
Yousaf khan
Renal Dialysis lecturer
IPMS-KMU

2. • Introduction
• Coagulation cascade
• Hemodialysis and clotting
• Anticoagulation during hemodialysis
• Type, mechanism and regimens administration
• Regional anticoagulation during hemodialysis with high risk of
bleeding

3. Introduction
• Coagulation
• In medicine the clotting of
blood. The process by which
the blood clots to form solid
masses, or clots
• Anticoagulants
• An anticoagulant is a
substance that prevent
coagulation: that is it stop
blood from clotting

4. Coagulation factors

5. The coagulation cascade
• The coagulation cascade is complex and include two pathways
• the intrinsic pathway
• The extrinsic pathway

6. The coagulation cascade

7. Hemodialysis and clotting
• Hemodialysis involve the circulation of whole blood though a
dialysis circuit and artificial kidney, both of which have the tendency
to active coagulation pathway.
• The dialyzer is generally constructed of synthetic microfibers with
narrow lumen, lacking endothelial lining and experiencing
disordered flow.
Factors that determine the thrombogenicity of different dialysis
membrane include:
• Chemical composition
• Charge (+ve/ -ve)
• Ability to adhere or active circulating cellular elements ( including
platelets)

8. Hemodialysis and clotting
• Clotting in the dialysis circuit is triggered by both the extrinsic and
the intrinsic pathways at the same.
Once the blood flow is initiated:
• Plasma protein deposit on the dialyzer surface
• Factor XII and high molecular weight kallikrein accumulate and act
as initiating the intrinsic pathway
• Peripheral blood leucocytes and monocytes, which contact the
dialyzer membrane and activated the extrinsic pathway.
• Fibrin along with activated platelets is deposited on the dialyzer
capillary surface resulting in clot formation.

9. Predisposing factors leading to form clot
in dialysis
• Low blood flow
• Reduced anti coagulant
• High hematocrit
• High ultrafiltration rate
• access recirculation
• Intradialytic blood and blood product transfusion
• Intradialytic lipid infusion
• Use of drip chamber ( air exposure, foam formation, turbulence)

10. Anticoagulation during
hemodialysis• Anticoagulation is routinely required to prevent clotting of the dialysis
lines and dialyzer membrane.
• Thrombus formation in the extracorporeal circuit can cause occlusion and
malfunction ultimately leading to discontinuation of therapy.
• If no anticoagulation is used 5-10 % of dialyzer may clot resulting in loss of
approximately 100 -150 ml of blood.
• Anticoagulation is targeted to prevent activation of the coagulation
cascade during dialysis.

11. Unfractionated heparin (UFH)
• Most commonly used in dialysis
• Easy to administer
• Short life (0.5 h and 2.0 h) and low cost
• It has molecular size from 5-40 kDa.
• Heparin acts indirectly on the coagulation system by binding to
antirhrombin III (heparin binding factor)
• Antithrombin inactivate thrombin, factor Xa, IXa, XIa and XIIa.
• At high doses, heparin also binds to heparin binding factor II and
inhibits the generation of thrombin.

12. Mechanism of UFH

13. UFH
Side effect:
• Increase bleeding risk
• Osteoporosis
• Dyslipidemia
• Pruritus
• Hyperkalemia
• Thrombocytopenia
• Hypotension rarely case
• If HIT is suspected, all heparin use has to be stopped.

14. UFH
• As per the European best practice guidelines heparin is infused an
initial loading dose of 50 IU/kg into the arterial line by heparin
infusion pump.
• The maintenance dose of heparin is 500 to 1500 IU/kg
• This maintenance infusion is stopped 30-90 min before the end of
dialysis to reduce bleeding from needle site.
• Dosing of UFH monitored by one of test
• ACT or aPTT

15. Heparin regimen
Heparin regimen may be administered by
• Initial bolus dose
• Initial bolus + maintenance dose
• Maintenance dose only
• Intermittent doses
There are 3 main regimen used in the administration of heparin
• Routine : patient with low bleeding risks
• Tight ( minimal ) patient with slight risks
• Heparin free: patient with high risk for bleeding

16. Heparin free
• There are different method to used in dialysis units to another
• Common method: no bolus or maintenance dose during dialysis and
saline flush (25-150 ml every 15-30 mint) is required with increase
blood flows rate to 250 to 500 ml/ mint.
• Rinse dialyzer: with 5000-20000 IU of heparin, flush system with
saline (25-150 ml every 15-30 mint) pre dialyzer to minimize
hemoconcentation.
• Administering single bolus dose of heparin, and only giving an
additional second small bolus if thrombus forms in dialyzer.
• Omit the bolus dose and simply administer an infusion of 15IU/kg
per h.

17. Heparin free
Indication:
• Pericarditis
• Recent surgery with bleeding complication or it will be dangerous
• Blood disease: coagulopathy, thrombocytopenia
• Intracerebral hemorrhage
• Any active bleeding

18. LMWHs
• LMWH s are produced by chemical or enzymatic cleavage of UFH to
smaller size 2-9 kda.
• LMWHs contain the key pentasaccharide motif, but are not long enough to
binds anti thrombin III and inhibits factor Xa.
• LMWH monitored by anti factor Xa.
• LMWHs are administered into the venous limb of the dialysis circuit.
• For a 4 four dialysis session dose of 10,000 -15000 anti Xa insitute choay
unit.

19. Advantage of LMWH
• Higher bioavailability
• Less non specific binding to the endothelium, plasma protein and
platelets.
• More rapid action
• Cause less leukocyte and platelet activation and less fibrin
deposition on dialyzer surface.
• Improved lipid profile
• Reduced hyperkalemia
• Reduced risk factor of osteoporosis
• Lower incidence of HIT type II.
• Less pruritus
• Less hair loss
• Less blood transfusion
LMWH side effect
• Allergic reaction
• hypotensive

20. Regional heparinization
• Rarely used now and probably should be avoided.
• Largely replaced by heparin free techniques.
• Protamine binds heparin and prevents its anticoagulant activity.
• Heparin is infused constantly into the dialyzer inlet while protamine
is infused into venous line.
• ACT is maintianed in the circuit at about 200-250 s, and also
monitored in the blood returnring to the patient (should be back to
baseline).
• 1mg protamine reverse approx 100 units of heparin.

21. Regional heparinization
• This is difficult to monitor correctly and provide the correct dose of
protamine.
• More importantly rebound bleeding can occur after 2-4 h ( and up to
10 h) when heparin dissociates from the protamine. Can be severe.
• Protamine can cause flushing, dyspnea, hypotension and
bradycardia.

22. Minimal heparin dose
• Commonly boluses of 500 units of heparin every 30 minutes to keep
ACT ( 150-200 S)
• Continuous infusion: of heparin with frequent ACT monitoring can
be used.
• Advantage: no additional equipment is needed in the dialysis circuit.
• Disadvantage: some minimal degree of anticoagulation of the
patient still occurs.

23. Sign of blood clotting in the
extracorporeal circuit
• Extremely dark colored blood
Dailyzer
• Presence of black streak in the dailyzer
• Reduced residual dialyzer volume
• Presence of clots at arterial header
Lines- foaming at the drip chamber and venous trap
• Clot formation at the drip chambers and venous trap
Pressure: increased difference between the postpump and venous
pressure
• When there is clots at arterial chamber or the dialyzer
• Increase in post pump followed by increase in venous pressure
• If the clots are distal to the venous chamber
• Increased venous pressure when venous needle is clotted.

24. Use of anticoagulants during
dialysis
• 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

25. Monitoring of heparin
Clotting tests used to monitor heparin therapy
• Activated partial thromboplastin time(APTT) – unfractionated
heparin
• Whole-blood partial thromboplastin time (WBPTT) - unfractionated
heparin
• ACT (Activated clotting time ) - unfractionated heparin
• Lee-White Clotting time (LWCT)
• Factor Xa activated ACT – low molecular weight heparin

26. Target Clotting Times During
Dialysis
Test Reagent
Baseline
Value
Routine heparin Tight heparin
Desired range Desired range
During
dialysis
At the end
of dialysis
During
dialysis
At the end
of dialysis
WBPTT Actin FS 60-85 sec
+80%
(120-140)
+40% (85-
105)
+40% (85-
105)
+40% (85-
105)
ACT
Siliceous
earth
120-150
sec
+80%
(200-250)
+40%
(170-190)
+40%
(170-190)
+40%
(170-190)
LWCT None 4-8 min 20-30 9-16
9-16 9-16
Daugirdas, Handbook Dial, 3rd ed, p. 185

27. Thank
you