heparin

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Function

In intact tissue, heparin is confined to mast cells where it is stored in cytoplasmic granules[1]. It serves to neutralize positive charge of histamine within the granules.

Structure

Heparin has the highest density of negative charge of any biological macromolecule[2]. It is composed of alternating sulfated (2,6)-glucosamine & glucuronate-2-sulfate residues (1,4 alpha linkage). Iduronate & its 2-sulfate are present in variable amounts. Heparan sulfate is like heparin, but contains fewer N- & O-linked sulfates (1,4 alpha linkage). The core protein of heparin is exclusively serglycin in contrast to heparan sulfate which contains a variety of core proteins (see heparan sulfate).

Compartment

cytoplasmic granule

Expression

mast cell

Indications

* LMW heparin is better than unfractionated heparin except if emergent surgery or thrombolysis is planned

Contraindications

Caution:

* variations in the bioavailability of unfractionated heparin result in a delays in attaining therapeutic levels vs LMW heparin[9]

Dosage

aPTT rate change additional action
<45 sec + 6 mL/hr rebolus with 5000 U
45-54 sec + 3 mL/hr none
55-85 sec none none
86-110 sec - 3 mL/hr stop infusion 1 hr > 110 sec - 6 mL/hr stop infusion 1 hr

Injection: 1000 units/mL (1 mL, 10 mL, 30 mL) 5000 units/mL (1 mL) 10,000 units/mL (1 mL, 4 mL) 20,000 units/mL (1 mL)

Solution: (lock flush) 10 units/mL (1 mL Tubex) 100 units/mL (1 mL Tubex, 10 mL vial)

* in patients for whom heparin is initiated for anticoagulation, & titration to therapeutic effect is difficult, consider antithrombin-3 deficiency

Pharmacokinetics

Monitor

*anti-factor Xa heparin assay instead of aPTT

Adverse effects

Drug interactions

Laboratory

interactions

Mechanism of action

Notes

  • isolated on a commercial basis from pig intestinal mucosa & bovine lung.
  • effective October 1, 2009, a change, which will also harmonize the USP unit dose with the WHO International Standard unit dose, will result in approximately a 10% reduction in the potency of the heparin marketed in the United States.[6]
  • total drug strength of entire container on label required by FDA[7]

More general terms

More specific terms

Additional terms

References

  1. 1.0 1.1 Salmivirta M, Lidholt K, Lindahl U. Heparan sulfate: a piece of information. FASEB J. 1996 Sep;10(11):1270-9. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8836040
  2. 2.0 2.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. 4.0 4.1 4.2 4.3 4.4 Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2022.
  5. 5.0 5.1 FDA Medwatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#Heparin
    Prescriber's Letter 15(5): 2008 Heparin Contamination and Shortage Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240512&pb=PRL (subscription needed) http://www.prescribersletter.com
  6. 6.0 6.1 FDA MedWatch Heparin: Change in Reference Standard http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm184687.htm
  7. 7.0 7.1 FDA MedWatch: 12/06/2012 Heparin: Drug Safety Communication - Important change to heparin container labels to clearly state the total drug strength http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm331168.htm
  8. 8.0 8.1 8.2 8.3 Deprecated Reference
  9. 9.0 9.1 9.2 Medical Knowledge Self Assessment Program (MKSAP) 18, 19. American College of Physicians, Philadelphia 2018, 2022.
  10. 10.0 10.1 NEJM Knowledge+ Hematology
    Guervil DJ, Rosenberg AF, Winterstein AG et al Activated partial thromboplastin time versus antifactor Xa heparin assay in monitoring unfractionated heparin by continuous intravenous infusion. Ann Pharmacother. 2011 Jul;45(7-8):861-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21712506

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