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Alternatives to standard unfractionated heparin for pediatric hemodialysis treatments

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Abstract

Despite advances in biomaterials and dialyzer design, thrombin generation occurs in the dialysis circuit because of platelet and leukocyte activation. As such, anticoagulation is required by the majority of children for successful dialysis to prevent clotting in the venous air detector and the capillary dialyzer, particularly for small children with slower blood flow rates. For many years unfractionated heparin has been the standard anticoagulant of choice, but is now being challenged by low-molecular-weight heparins (LMWHs) because they are simple to administer and reliable, particularly as the cost differential has been eroded. Alternative, nonheparin anticoagulants are more frequently available, but are often restricted to special circumstances: patients at high risk of hemorrhage; heparin allergy; or heparin-induced thrombocytopenia. These nonheparin alternatives are significantly more expensive than heparins, and may add a degree of complexity, such as citrate, which is a regional anticoagulant, although citrate-containing dialysate may permit short anticoagulant-free dialysis sessions. Systemic anticoagulants required for immune-mediated, heparin-induced thrombocytopenia are expensive and either have short half-lives, and therefore require continuous infusions, or prolonged half-lives, which, although allowing simple bolus administration, increases the risk of drug accumulation, over-dosage and hemorrhage.

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Acknowledgements

I am indebted to Professors Michel Fischbach, Stuart Goldstein, and Drs Patrick Brophy and Deepa Chand.

Competing interests

The author declares no competing interests.

Author information

Authors and Affiliations

  1. UCL Centre for Nephrology, Royal Free Hospital, University College London Medical School, Rowland Hill Street, London, NW3 2PF, UK

    Andrew Davenport

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  1. Andrew Davenport
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Correspondence to Andrew Davenport.

Additional information

Answers

MCQ 1 Answer 2: Have an increased half-life compared with unfractionated heparin

MCQ 2 Answer 3: Which may cause hypomagnesemia

MCQ 3 Answer 4: Which can disrupt heparin-platelet factor 4 antibody complexes

MCQ 4 Answer 1: Can be cleared during hemodiafiltration

MCQ 5 Answer 2: Can be monitored by the activated partial thromboplastin time

Appendices

Key summary points

Low molecular weight heparins have a more rapid onset of action, a more predictable anticoagulant effect and a reduced deposition of platelets and thrombin on dialyzer surfaces compared with unfractionated heparin.

Citrate is a potent regional anticoagulant, but adds a degree of complexity requiring a zero calcium dialysate for best results, regulation of citrate infusion by monitoring ionized to total serum calcium, and a central calcium infusion to prevent hypocalcemia.

Danaparoid, argatroban, and lepirudin provide systemic anticoagulation for cases of immune-mediated heparin-induced thrombocytopenia, but availability and licensing for pediatric patients vary between countries. They are expensive, and both lepirudin and argatroban increase the risk of hemorrhage.

Research points

Continued research is required to develop biomaterials for the dialysis circuit that do not activate platelet and leukocytes to permit future anticoagulation free dialysis.

Newer oral anticoagulants that act as thrombin inhibitors or anti-factor Xa antagonists are being developed for clinical practice, and research is required to determine whether patients prescribed these agents require reduced or no additional anticoagulation for dialysis.

As low molecular weight heparins and heparinoids become more readily used in clinical practice, more rapid or bedside tests of anti-Xa activity need to be developed to allow monitoring of hospital patients given low molecular weight heparin prophylaxis or treatment, who then require dialysis.

Development of specific treatments to manage bleeding in patients over-anticoagulated with direct thrombin inhibitors.

Multiple choice questions (Answers are provided following the reference list.)

  1. MCQ 1:

    Low molecular weight heparins:

  1. 1.

    Have an increased half-life compared with unfractionated heparin

  2. 2.

    Carry a similar risk to unfractionated heparin of causing immune-mediated thrombocytopenia

  3. 3.

    Are suitable for short (≤ 2 h) dialysis sessions

  4. 4.

    Should be monitored by the activated partial thromboplastin time

  1. MCQ 2:

    Citrate is a regional anticoagulant:

  1. 1.

    ACD-A citrate is a more effective anticoagulant than trisodium citrate

  2. 2.

    Which must only be used with a special calcium free dialysate

  3. 3.

    Which may cause hypomagnesemia

  4. 4.

    Which should be adjusted according to postdialyzer serum calcium

  1. MCQ 3:

    Danaparoid is a naturally occurring heparinoid:

  1. 1.

    Which has a similar half-life to unfractionated heparin

  2. 2.

    Can be monitored by measuring the activated partial thromboplastin time

  3. 3.

    Which is made up of heparan and dermatan sulfate

  4. 4.

    Which can disrupt heparin-platelet factor 4 antibody complexes

  1. MCQ 4:

    Lepirudin is a recombinant form of hirudin which:

  1. 1.

    Can be cleared during hemodiafiltration

  2. 2.

    Reversibly binds to thrombin

  3. 3.

    Should be administered by continuous infusion

  4. 4.

    Carries a reduced risk of bleeding compared with unfractionated heparin

  1. MCQ 5:

    Argatroban is a synthetic peptide derived from arginine which:

  1. 1.

    Is predominantly metabolized by the kidney

  2. 2.

    Can be monitored by the activated partial thromboplastin time

  3. 3.

    Interacts with warfarin to prolong the international normalized ratio

  4. 4.

    Can cause anaphylactoid reactions

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Davenport, A. Alternatives to standard unfractionated heparin for pediatric hemodialysis treatments. Pediatr Nephrol 27, 1869–1879 (2012). https://doi.org/10.1007/s00467-012-2129-5

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