ANTICOAGULATIONPCRRT 2008 Orlando

Patrick Brophy MDDirector Pediatric NephrologyUniversity of Iowa- Children’s Hospital

Normal CoagulationContact Phase (intrinsic)Contact Phase (intrinsic)

XII activationXII activationXI IXXI IX

Tissue Factor (extrinsic)Tissue Factor (extrinsic)TF:VIIaTF:VIIa

THROMBINTHROMBIN

fibrinogenfibrinogen

prothrombinprothrombin

XX XaXa Va Va VIIIa VIIIa CaCa++++ plateletsplatelets

CLOTCLOT

platelets / monocytes / macrophages platelets / monocytes / macrophages

Sites of Thrombus Formation

Any blood surface interface Hemofilter Bubble trap Catheter (Especially

Pediatrics) Areas of turbulence

resistance Luer lock connections / 3

way stopcocks

Anticoagulants

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 HeparinContact Phase (intrinsic)Contact Phase (intrinsic)

XII activationXII activationXI IXXI IX

Tissue Factor (extrinsic)Tissue Factor (extrinsic)TF:VIIaTF:VIIa

THROMBINTHROMBIN

fibrinogenfibrinogen

prothrombinprothrombin

XX XaXa Va Va VIIIa VIIIa CaCa++++ plateletsplatelets

CLOTCLOT

platelets / monocytes / macrophages platelets / monocytes / macrophages

UF HEPARINUF HEPARIN

LMWHLMWH

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

Heparin Protocols Benefit and Risks BenefitsBenefits Heparin infusion prior

to filter with post filter ACT measurement

Bolus with 10-20 units/kg Infuse at 10-20 units/kg/hr

Adjust post filter ACT 180-200 secs

RisksRisks Patient Bleeding Unable to inhibit clot

bound thrombin Ongoing thrombin

generation Activates - damages

platelets / thrombocytopenia

Citrate

Sites of Action of CitrateCONTACT PHASECONTACT PHASE

XII activationXII activationXI IXXI IX

TISSUE FACTOR TISSUE FACTOR TF:VIIaTF:VIIa

THROMBINTHROMBIN

fibrinogenfibrinogen

prothrombinprothrombin

XaXa

Va Va VIIIa VIIIa CaCa++++ plateletsplatelets

CLOTCLOT

monocytemonocyte/ / platelets / platelets / macrophagemacrophage

FIBRINOLYSIS ACTIVATIONFIBRINOLYSIS ACTIVATION

FIBRINOLYSIS INHIBITIONFIBRINOLYSIS INHIBITION

NATURAL NATURAL ANTICOAGULANTANTICOAGULANT(APC, ATIII)(APC, ATIII)

XX

Phospholipid Phospholipid surfacesurface

CaCa++

++CaCa++

++CaCa++

++CaCa++

++CaCa++

++CaCa++

++

CITRATECITRATE

How does citrate work

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

Citrate: Technical Considerations Measure patient and system iCa in 2 hours then

at 6 hr increments Pre-filter infusion of Citrate

Aim for system iCa of 0.3-0.4 mmol/l Adjust for levels

Systemic calcium infusion Aim for patient iCa of 1.1-1.3 mmol/l

Adjust for levels

Citrate: Advantages

No need for heparin Commercially available solutions

exist (ACD-citrate-Baxter) Less bleeding risk Simple to monitor Many protocols exist

Advantages of Citrate

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

Metabolic alkalosis Metabolized in liver / other tissues

Electrolyte disorders Hypernatremia Hypocalcemia Hypomagnesemia

Cardiac toxicity Neonatal hearts

Complications of Citrate:Metabolic alkalosis

Metabolic alkalosis due to citrate conversion to HCO3 Solutions with 35 meq/l HCO3 NG losses TPN with acetate component

Treatment Solutions with 35 meq/l HCO3

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

NG losses Replace with ½-2/3 NS

TPN with acetate component Use high Cl ratio

Complications of Citrate: “Citrate Lock”

Seen with rising total calcium with dropping/Stable patient ionized calciumEssentially delivery of citrate exceeds hepatic

metabolism and CRRT clearance 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.Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.

Citrate Unfractionated Heparin

Anticoagulation 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?. single center - 209 adults regional anticoagulation : trisodium citrate vs standard heparin

protocol ( customized calcium-free dialysate)

CitACG was the sole anticoagulant in 37 patients, 87 patients received low-dose heparin plus citrate, and 85 patients received only hepACG.

Both groups receiving citACG had prolonged filter life when compared to the hepACG group.

significant cost saving due to prolonged filter life when using citACG.

Morgera S, et.al. Nephron Clin Pract. 2004; 97(4):c131-6.

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).

Brophy et.al. NDT 2005 Jul;20(7):1416-21

None

Cit

Hep

Circuit Functional Survival (Hours)

Cum

ulat

ive

Prop

ortio

n Su

rviv

ing

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 20 40 60 80 100 120 140 160 180 200 220

None

Citrate

Heparin

ppCRRT ACG Side Effects Heparin

11 cases of systemic bleeding on heparin5 cases no ACG used secondary to bleeding1 case of HIT

Citrate19 cases of metabolic alkalosis

1 change to heparin for hyperglycemia 1 change to heparin for alkalosis

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)

Thanks

ppCRRT members Bedside ICU and Dialysis Nurses Mary Lee Neuberger Dr. Noel Gibney (for the slide master) patients