Transcript ANTICOAGULATION PCRRT 2008 Orlando

ANTICOAGULATION
PCRRT 2008 Orlando
Patrick Brophy MD
Director Pediatric Nephrology
University of Iowa- Children’s
Hospital
Normal Coagulation
Tissue Factor (extrinsic)
TF:VIIa
Contact Phase (intrinsic)
XII activation
XI IX
platelets / monocytes / macrophages
X
Xa
prothrombin
THROMBIN
fibrinogen
CLOT
Va
VIIIa
Ca++
platelets
Sites of Thrombus Formation

Any blood surface
interface
 Hemofilter
 Bubble
trap
 Catheter (Especially
Pediatrics)
 Areas of turbulence
resistance
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Luer lock connections
/ 3 way stopcocks
Anticoagulants
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Saline Flushes
Heparin ### Peds
Citrate regional anticoagulation
### Peds
Low molecular weight heparin
Prostacyclin
Nafamostat mesilate
Danaparoid*
Hirudin/Lepirudin
Argatroban (thrombin
inhibitor)*
* No antidote known
Heparin
Sites of Action of Heparin
Contact Phase (intrinsic)
XII activation
XI IX
Tissue Factor (extrinsic)
TF:VIIa
platelets / monocytes / macrophages
X
Xa
LMWH
UF HEPARIN
prothrombin
THROMBIN
fibrinogen
CLOT
Va
VIIIa
Ca++
platelets
LMWH: Theoretic advantages
Reduced risk of bleeding
 Less risk of HIT

LMWH
 No
difference in risk of bleeding
 No quick antidote
 Increased cost
 No difference in filter life
Heparin Protocols
Heparin infusion prior to filter with post
filter ACT measurement and heparin
adjustment based upon parameters
 Bolus with 10-20 units/kg
 Infuse heparin at 10-20 units/kg/hr
 Adjust post filter ACT 180-200 secs
 Interval of checking is local standard and
varies from 1-4 hr increments
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Heparin Protocols Benefit and
Risks
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Benefits
Heparin infusion prior
to filter with post filter
ACT measurement
Bolus with 10-20
units/kg Infuse at 1020 units/kg/hr
Adjust post filter ACT
180-200 secs
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Risks
Patient Bleeding
Unable to inhibit clot
bound thrombin
Ongoing thrombin
generation
Activates - damages
platelets /
thrombocytopenia
Citrate
Sites of Action of Citrate
TISSUE FACTOR
TF:VIIa
CONTACT PHASE
XII activation
XI IX
monocyte/
X
Va
VIIIa
Ca++
platelets
CITRATE
NATURAL
ANTICOAGULANT
(APC, ATIII)
platelets /
macrophage
Xa
prothrombin
Phospholipid
surface
Ca+
+ +
Ca
+
Ca+
+
Ca+
+
Ca+
+
Ca+
+
THROMBIN
fibrinogen
CLOT
FIBRINOLYSIS ACTIVATION
FIBRINOLYSIS INHIBITION
How does citrate work
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Clotting is a calcium dependent mechanism,
removal of calcium from the blood will inhibit
clotting
Adding citrate to blood will bind the free calcium
(ionized) calcium in the blood thus inhibiting
clotting
Common example of this is blood banked blood
How is citrate used?
In most protocols citrate is infused post
patient but prefilter often at the “arterial”
access of the dual (or triple) lumen access
that is used for hemofiltration (HF)
 Calcium is returned to the patient
independent of the dual lumen HF access
or can be infused via the 3rd lumen of the
triple lumen access
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Citrate: Technical
Considerations
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Measure patient and system iCa in 2 hours then
at 6 hr increments
Pre-filter infusion of Citrate
 Aim for system iCa
 Adjust for levels
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of 0.3-0.4 mmol/l
Systemic calcium infusion
 Aim for patient iCa
 Adjust for levels
of 1.1-1.3 mmol/l
Citrate: Advantages
No need for heparin
 Commercially available solutions
exist (ACD-citrate-Baxter)
 Less bleeding risk
 Simple to monitor
 Many protocols exist
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Advantages of Citrate
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Has zero effect upon patient bleeding as opposed to
heparin which effects system and patient bleeding
Easy to monitor with ionized calcium assay
Activated Clotting Time (ACT) nor PTT needed
Programs report less clotted circuits = less disposable
cost and less overtime nursing hours
Bedside surveys demonstrate less work of machinery
allowing more attention to patient
Citrate: Problems
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Metabolic alkalosis
 Metabolized
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in liver / other tissues
Electrolyte disorders
 Hypernatremia
 Hypocalcemia
 Hypomagnesemia
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Cardiac toxicity
 Neonatal
hearts
Complications of Citrate:
Metabolic alkalosis
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Metabolic alkalosis due to
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citrate conversion to HCO3
 Solutions with 35 meq/l HCO3
 NG losses
 TPN with acetate component
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Treatment
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Solutions with 35 meq/l HCO3
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NG losses
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Decrease bicarbonate dialysis
rate and replace at the same
rate with NS (pH 5) to allow
for the total solution exposure
to be identical (ie no change
in solute clearance) yet this
will give less HCO3 exposure
and an acid replacement
Replace with ½-2/3 NS
TPN with acetate component
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Use high Cl ratio
Complications of Citrate: “Citrate Lock”
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Seen with rising total calcium with
dropping/Stable patient ionized calcium
 Essentially
delivery of citrate exceeds hepatic
metabolism and CRRT clearance
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Treatment of “citrate lock”
 Decrease
or stop citrate for 1 hr then restart
at 70% of prior rate or Increase D or FRF rate
to enhance clearance
Citrate or Heparin: literature
Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.
Citrate
Unfractionated Heparin
Anticoagulation
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In adults: Monchi M et al. Int Care Med 2004;30:260-65
 Median
filter life was 70 hr Citrate, 40 hr Heparin
 Fewer PRBC transfused in Citrate group (surrogate of
bleeding per study) 0.2 units/day of CVVH Citrate vs
1 units/day of CVVH Heparin
Heparin or Citrate?
.
Morgera S, et.al. Nephron Clin Pract. 2004; 97(4):c131-6.
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single center - 209 adults
regional anticoagulation : trisodium citrate vs standard
heparin protocol ( customized calcium-free dialysate)
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CitACG was the sole anticoagulant in 37 patients, 87
patients received low-dose heparin plus citrate, and 85
patients received only hepACG.
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Both groups receiving citACG had prolonged filter life
when compared to the hepACG group.
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significant cost saving due to prolonged filter life when
using citACG.
Brophy et.al. NDT 2005 Jul;20(7):1416-21
1.0
0.9
Cumulative Proportion Surviving
Comparison of CRRT
circuit life for PRISMA
circuits with: no
anticoagulation (filled
squares), heparin
anticoagulation (filled
circles) or citrate
anticoagulation (filled
triangles). Mean circuit
survival was no different
for circuits receiving
hepACG and citACG but
was significantly lower
for circuits with noACG
(P<0.005).
0.8
Heparin
0.7
0.6
0.5
Citrate
0.4
None
0.3
0.2
0
20
40
60
80
100
120
140
Circuit Functional Survival (Hours)
160
180
200
220
None
Cit
Hep
ppCRRT ACG Side Effects
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Heparin
 11
cases of systemic bleeding on heparin
 5 cases no ACG used secondary to
bleeding
 1 case of HIT
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Citrate
 19
cases of metabolic alkalosis
1 change to heparin for hyperglycemia
 1 change to heparin for alkalosis
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3
cases of citrate lock
Reference Tools
Adqi.net-web site for information on CRRT
 Crrtonline.com-web site for info on Dr
Mehta’s meeting
 www.PCRRT.com Pediatric CRRT with
links to other meetings, protocols, industry
 5th International Conf on Pediatric CRRT
June 19-21, 2008 Orlando, Florida
 PCRRT list serve (contact Bunchman)
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Thanks
ppCRRT members
 Bedside ICU and Dialysis Nurses
 Mary Lee Neuberger
 Dr. Noel Gibney (for the slide master)
 patients
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