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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. Va

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Anticoagulation pcrrt 2008 orlando

ANTICOAGULATIONPCRRT 2008 Orlando

Patrick Brophy MD

Director Pediatric Nephrology

University of Iowa- Children’s Hospital


Normal coagulation
Normal Coagulation

Tissue Factor (extrinsic)

TF:VIIa

Contact Phase (intrinsic)

XII activation

XI IX

platelets / monocytes / macrophages

X

Xa

Va

VIIIa

Ca++

platelets

prothrombin

THROMBIN

fibrinogen

CLOT


Sites of thrombus formation
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
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



Sites of action of heparin
Sites of Action of Heparin

Contact Phase (intrinsic)

XII activation

XI IX

Tissue Factor (extrinsic)

TF:VIIa

platelets / monocytes / macrophages

X

Xa

Va

VIIIa

Ca++

platelets

LMWH

UF HEPARIN

prothrombin

THROMBIN

fibrinogen

CLOT


Lmwh theoretic advantages
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 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

Benefits

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

Risks

Patient Bleeding

Unable to inhibit clot bound thrombin

Ongoing thrombin generation

Activates - damages platelets / thrombocytopenia

Heparin Protocols Benefit and Risks



Sites of action of citrate

Ca++

Ca++

Ca++

Ca++

Ca++

Ca++

Sites of Action of Citrate

TISSUE FACTOR

TF:VIIa

CONTACT PHASE

XII activation

XI IX

monocyte/ platelets / macrophage

X

Va

VIIIa

Ca++

platelets

Xa

Phospholipid surface

prothrombin

CITRATE

THROMBIN

NATURAL ANTICOAGULANT

(APC, ATIII)

FIBRINOLYSIS ACTIVATION

FIBRINOLYSIS INHIBITION

fibrinogen

CLOT


How does citrate work
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
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
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
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
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
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:Metabolic alkalosis


Complications of citrate citrate lock
Complications of Citrate: “Citrate Lock”

  • Seen with rising total calcium with dropping/Stable patient ionized calcium

    • Essentially 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




Anticoagulation
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
Heparin or Citrate?.

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

  • 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.


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

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).


Ppcrrt acg side effects
ppCRRT ACG Side Effects

  • Heparin

    • 11 cases of systemic bleeding on heparin

    • 5 cases no ACG used secondary to bleeding

    • 1 case of HIT

  • Citrate

    • 19 cases of metabolic alkalosis

      • 1 change to heparin for hyperglycemia

      • 1 change to heparin for alkalosis

    • 3 cases of citrate lock


Reference tools
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
Thanks

  • ppCRRT members

  • Bedside ICU and Dialysis Nurses

  • Mary Lee Neuberger

  • Dr. Noel Gibney (for the slide master)

  • patients


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