Anticoagulation for PCRRT Dr. Peter Skippen, PICU. BC Children’s Hospital, Vancouver. CANADA.

Anticoagulation Anticoagulation

for for

PCRRTPCRRT

Dr. Peter Skippen, PICU. Dr. Peter Skippen, PICU.

BC Children’s Hospital,BC Children’s Hospital,

Vancouver. CANADA.Vancouver. CANADA.

Anticoagulation - PCRRTAnticoagulation - PCRRT

OutlineOutline

• Normal CoagulationNormal Coagulation

• Anticoagulation: OptionsAnticoagulation: Options

– HeparinHeparin

– CitrateCitrate

– OthersOthers

• ConclusionsConclusions


Mechanisms of Filter Thrombosis Mechanisms of Filter Thrombosis

CONTACT PHASECONTACT PHASEXII activationXII activation

XI IXXI IX

TISSUE FACTOR TISSUE FACTOR TF:VIIaTF:VIIa

THROMBINTHROMBIN

fibrinogenfibrinogen

prothrombinprothrombin

XaXaVa Va VIIIa VIIIa CaCa++++ plateletsplatelets

CLOTCLOT

monocytesmonocytes / / platelets / platelets / macrophages macrophages

FIBRINOLYSIS ACTIVATIONFIBRINOLYSIS ACTIVATION

FIBRINOLYSIS INHIBITIONFIBRINOLYSIS INHIBITION

NATURAL NATURAL ANTICOAGULANTSANTICOAGULANTS(APC, ATIII)(APC, ATIII)

XX

Phospholipid Phospholipid surfacesurface

CaCa++++

CaCa++++

CaCa++++

CaCa++++

CaCa++++

CaCa++++


Coagulation in Critically Ill ChildCoagulation in Critically Ill Child

• Pre-existing inflammatory statesPre-existing inflammatory states– sepsissepsis

– traumatrauma

– shockshock

• hypercoagulable / thrombohemorrhagic stateshypercoagulable / thrombohemorrhagic states

• Organ failure statesOrgan failure states– liver / renal (2˚ coagulation abnormalities) liver / renal (2˚ coagulation abnormalities)

– blood oncology / marrow failureblood oncology / marrow failure

• PerioperativePerioperative– cardiopulmonary bypasscardiopulmonary bypass

• MedicationsMedications– platelet effectsplatelet effects

– immunosuppressive / oncologic immunosuppressive / oncologic

• thrombogenic / fibrinolyticthrombogenic / fibrinolytic


Factors Affecting Filter LifeFactors Affecting Filter Life

• Pre-existing condition of patient’s coag /anticoag systemPre-existing condition of patient’s coag /anticoag system

• Treatment characteristicsTreatment characteristics

– A-V vs. V-VA-V vs. V-V

– vascular accessvascular access

– diffusion vs. convectiondiffusion vs. convection

– filtration fractionfiltration fraction

– blood flowblood flow

– membrane material and geometrymembrane material and geometry

– circuit alarmscircuit alarms


Sites of Thrombus FormationSites of Thrombus Formation

• any blood surface interfaceany blood surface interface– hemofilterhemofilter

– bubble trapbubble trap

– cathetercatheter

– areas of turbulence / resistanceareas of turbulence / resistance

• very high blood flow ratesvery high blood flow rates

• luer lock connections / 3 way stopcocksluer lock connections / 3 way stopcocks


Anticoagulation: OptionsAnticoagulation: Options

• Technical aspects Technical aspects

– cannulaecannulae

– cannulation sitecannulation site

– circuitrycircuitry

– blood flow rateblood flow rate

– FF FF

– predilution?predilution?

• No anticoagulationNo anticoagulation

• Saline flush?Saline flush?

• Hemodilution?Hemodilution?

• HeparinHeparin

– unfractionatedunfractionated

– LMWHLMWH

• CitrateCitrate

• OthersOthers

– prostacyclinprostacyclin

– danaparoiddanaparoid

– hirudinhirudin

– nafamostate mesylatenafamostate mesylate


Unfractionated HeparinUnfractionated Heparin


Sites of Action of HeparinSites of Action of Heparin


XI IXXI IX


THROMBINTHROMBIN



XaXa

Va Va VIIIa VIIIa CaCa++++ plateletsplatelets

CLOTCLOT

monocytesmonocytes platelets platelets macrophagesmacrophages




XX


CaCa++++

CaCa++++

CaCa++++

CaCa++++

CaCa++++

CaCa++++

UF HEPARINUF HEPARIN

LMWHLMWH

ATIIIATIII


Heparin - ProblemsHeparin - Problems

• bleeding bleeding

• unable to inhibit thrombin bound to clotunable to inhibit thrombin bound to clot

• unable to inhibit Xa bound to clotunable to inhibit Xa bound to clot

• ongoing thrombin generationongoing thrombin generation

• direct activation of platelets direct activation of platelets

• thrombocytopeniathrombocytopenia

• extrinsic pathway unaffectedextrinsic pathway unaffected

No Heparin Systemically Heparinized

NO surface - no heparin NO surface - heparinized

Compliments of Dr. Gail Annich, University of MichiganCompliments of Dr. Gail Annich, University of Michigan

Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.

Unfractionated HeparinUnfractionated Heparin


LMWH: Theoretic AdvantagesLMWH: Theoretic Advantages

• Reduced risk of bleedingReduced risk of bleeding

• Less risk of HITLess risk of HIT

LMWHLMWH



LMWHLMWH

• no difference in filter lifeno difference in filter life

• no difference in risk of bleedingno difference in risk of bleeding

• no quick antidoteno quick antidote

• need to monitor levelsneed to monitor levels

• risk of accumulation risk of accumulation

– renal clearancerenal clearance

– minimal filter clearanceminimal filter clearance

• increased costincreased cost


CitrateCitrate


Citrate: Mechanism of ActionCitrate: Mechanism of Action

• Binds calcium - essential coagulation co-factorBinds calcium - essential coagulation co-factor

Relationship of Prefilter [Citrate] to Prefilter iCa

0

0.2

0.4

0.6

0.8

1

1.2

0 1 2 3 4 5 6 7 8

Prefilter [Citrate] mmol/L

Prefilter iCa mmol/L


Citrate: Clinical DataCitrate: Clinical Data

Citrate / iCa++

00.050.1

0.150.2

0.250.3

0.350.4

0.450.5

0 2 4 6 8

Citrate (mmol/L)

iCa+

+ (

mm

ol/L)


Sites of Action of CitrateSites of Action of Citrate


XI IXXI IX


THROMBINTHROMBIN



XaXa

Va Va VIIIa VIIIa CaCa++++ plateletsplatelets

CLOTCLOT

monocytesmonocytes / / platelets / platelets / macrophages macrophages




XX


CaCa++++

CaCa++++

CaCa++++

CaCa++++

CaCa++++

CaCa++++

CITRATECITRATE


Citrate: AdvantagesCitrate: Advantages

• No need for heparinNo need for heparin

• Less bleeding riskLess bleeding risk

• Simple to monitorSimple to monitor

CitrateCitrate



Citrate: Technical ConsiderationsCitrate: Technical Considerations

• ensure catheter patencyensure catheter patency

• establish desired blood flowestablish desired blood flow

• pre-filter infusion pre-filter infusion

– initial citrate flow = x 2 (mls/hr) BFR (mls/min)initial citrate flow = x 2 (mls/hr) BFR (mls/min)

• systemic calcium infusionsystemic calcium infusion

• aim for pre-filter ionized Caaim for pre-filter ionized Ca++++ < 0.4mmol/L < 0.4mmol/L

• adjust dialysate as neededadjust dialysate as needed

– anticipate alkalosisanticipate alkalosis

• adjust electrolyte replacements as necessaryadjust electrolyte replacements as necessary

– NaNa++ / PO / PO44---- / Ca / Ca++++ / Mg / Mg++++


Citrate: ProblemsCitrate: Problems

• metabolic alkalosismetabolic alkalosis

– metabolized in liver / skeletal muscle / other tissuesmetabolized in liver / skeletal muscle / other tissues

• electrolyte disorderselectrolyte disorders

– hypernatremiahypernatremia

– hypocalcemiahypocalcemia

– hypomagnesemiahypomagnesemia

• sugar loadsugar load

• ““citrate lock”?citrate lock”?

– hepatic failurehepatic failure

• ?cardiac toxicity?cardiac toxicity

– neonatal heartsneonatal hearts


Citrate: Clinical DataCitrate: Clinical Data

Patient Citrate

0

1

2

3

4

5

6

7

8

9

10

0 1 2 3 4 5 6

Patient Citrate (mmol/l)

Pre

-Filte

r C

itra

te


Citrate: Caution?Citrate: Caution?

• Congenital metabolic diseases?Congenital metabolic diseases?

– ? mitochondropathies? mitochondropathies

• Severe liver disease / hepatic failureSevere liver disease / hepatic failure

• Excessive calcium requirementsExcessive calcium requirements

• Massive blood transfusionsMassive blood transfusions


HirudinHirudin

• Highly selective / specific thrombin inhibitorHighly selective / specific thrombin inhibitor

• Minimal non-renal clearanceMinimal non-renal clearance

• Long actingLong acting

• No specific antagonistNo specific antagonist


Nafamostate MesylateNafamostate Mesylate

• Synthetic protease inhibitorSynthetic protease inhibitor

– Inhibits thrombin, Xa, XIIa, TF-VIIa complexInhibits thrombin, Xa, XIIa, TF-VIIa complex

• Low MW Low MW high EC clearance high EC clearance

• ACT for monitoringACT for monitoring

• No antidote but short half lifeNo antidote but short half life


ConclusionsConclusions

• Wide range of practiceWide range of practice

• UF heparin most commonly used anticoagulantUF heparin most commonly used anticoagulant

• Citrate may be agent of choice in most situations?Citrate may be agent of choice in most situations?

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Anticoagulation for PCRRT Dr. Peter Skippen, PICU. BC Children’s Hospital, Vancouver. CANADA.

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