anticoagulation for pcrrt dr. peter skippen, picu. bc children’s hospital, vancouver. canada
TRANSCRIPT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
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++++
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
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 - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
Unfractionated HeparinUnfractionated Heparin
Anticoagulation - PCRRTAnticoagulation - PCRRT
Sites of Action of HeparinSites of Action of Heparin
CONTACT PHASECONTACT PHASEXII activationXII activation
XI IXXI IX
TISSUE FACTOR TISSUE FACTOR TF:VIIaTF:VIIa
THROMBINTHROMBIN
fibrinogenfibrinogen
prothrombinprothrombin
XaXa
Va Va VIIIa VIIIa CaCa++++ plateletsplatelets
CLOTCLOT
monocytesmonocytes platelets platelets macrophagesmacrophages
FIBRINOLYSIS ACTIVATIONFIBRINOLYSIS ACTIVATION
FIBRINOLYSIS INHIBITIONFIBRINOLYSIS INHIBITION
NATURAL NATURAL ANTICOAGULANTSANTICOAGULANTS(APC, ATIII)(APC, ATIII)
XX
Phospholipid Phospholipid surfacesurface
CaCa++++
CaCa++++
CaCa++++
CaCa++++
CaCa++++
CaCa++++
UF HEPARINUF HEPARIN
LMWHLMWH
ATIIIATIII
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
LMWH: Theoretic AdvantagesLMWH: Theoretic Advantages
• Reduced risk of bleedingReduced risk of bleeding
• Less risk of HITLess risk of HIT
LMWHLMWH
Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
CitrateCitrate
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
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)
Anticoagulation - PCRRTAnticoagulation - PCRRT
Sites of Action of CitrateSites of Action of Citrate
CONTACT PHASECONTACT PHASEXII activationXII activation
XI IXXI IX
TISSUE FACTOR TISSUE FACTOR TF:VIIaTF:VIIa
THROMBINTHROMBIN
fibrinogenfibrinogen
prothrombinprothrombin
XaXa
Va 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++++
CITRATECITRATE
Anticoagulation - PCRRTAnticoagulation - PCRRT
Citrate: AdvantagesCitrate: Advantages
• No need for heparinNo need for heparin
• Less bleeding riskLess bleeding risk
• Simple to monitorSimple to monitor
CitrateCitrate
Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.
Anticoagulation - PCRRTAnticoagulation - PCRRT
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++++
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
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
Anticoagulation - PCRRTAnticoagulation - PCRRT
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?