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heparin

heparin

Clinical usage:

  • prior to commencement take bloods for APTT, INR, FBE, LFT's

full IV heparin Rx where increased risk of bleeding

  • eg. as adjunct to thrombolysis, the elderly, anti-platelet medications, post-op.
  • target APTT reduced to 50-75secs
  • 5000IU (4000U if < 67kg) stat then 12-15units/kg/hr
  • 25000IU in 500ml NS (=50U/ml):
    • if > 100kg, then 26ml/hr,
    • if 80kg, then 20ml/hr,
    • if 60kg, then 16ml/hr
    • NB. Metalyse (tenectaplase), product information recommends:
      • heparin 5000U IV stat (4000U if < 67kg) then 
      • infusion 25000U in 500ml NS @ 16ml/hr (<67kg) or 20ml/hr (>67kg)

full IV heparin Rx (eg. extensive DVT or PE):

  • target APTT with full heparinisation is usually 60-80secs
  • 80U/kg to max. 8000U stat 
  • larger clot burdens may require higher doses
  • raised initial APTT may require lower bolus or none
  • 25000IU in 500ml NS (=50U/ml) at 20U/kg/hour (to max. 2,000U/hr) initially then titrate according to APTT.
  • if maintenance dose > 35,000U/24h then check anti-Xa levels:
  • if anti-Xa levels are 0.5-0.8IU/ml then indicates therapeutic levels & heparin dose should NOT be increased.
  • if in doubt, consult haematology 
  • check platelets 3x/week
  • commence warfarin Rx within 72hrs of heparin commencement unless otherwise contraindicated
  • cease when warfarin Rx has been commenced AND INR > 2.5 (or within therapeutic range) for 2 consecutive days, ie. heparin must usually be continued for at least 4 days from onset of warfarin Rx

heparin Rx and invasive procedures

  • patients who are on full dose heparin and who need invasive procedures need to have heparin with-held:
    • for surgery, usually cease 6 hrs prior and restart 12hrs after if no evidence of bleeding
    • for procedures, may be possible to cease only 2-4hrs prior and re-start 2-6hrs after procedure if no bleeding
    • if on warfarin, warfarin can usually be re-started same night of surgery or procedure.

mini-dose prophylactic Rx:

  • 5000IU s/c 8h
  • start 1-2 h prior to surgery
  • NB. LMW heparin preferred in hip/knee replacement surgery when they are usually given on the night before surgery to minimise bleeding risk.

Complications of heparin Rx:

subtherapeutic levels:

  • pts whose APTT levels are subtherapeutic in 1st 24hrs may have DVT recurrence rates 15x higher than pts with Rx levels. (2nd 24hrs of Rx not as important)
  • some suggest starting infusion rates at least 30000IU/day

resistance to heparin:

  • this is arbitarily defined as those pts requiring > 40,000 IU/day to maintain Rx level
  • these pts have increased levels of factor VIII & heparin-binding proteins
  • this often occurs in pts with inflammatory diseases
  • elevated factor VIII levels cause dissociation b/n APTT & heparin values causing “subtherapeutic” APTT values when in fact heparin values are therapeutic.
  • solutions:
    • monitor with anti-factor Xa chromogenic assay instead of APTT, or,
    • use LMW heparins instead (bind less to heparin-binding proteins)

bleeding on heparin:

  • approx. 5% of pts Rx with IV or SC heparin have major bleeding, although excessive prolongation of APTT probably increases the risk, clinical characteristics such as recent surgery, liver disease, severe thrombocytopenia & concomitant platelet Rx are stronger predictors.
  • risk is higher than for LMW heparins
  • risk correlates with presence & degree of excessive prolongation of prothrombin time as indicated by higher INR caused by warfarin.
management:

immune heparin-induced thrombocytopenia (HITS):

  • approx. 3% of pts on heparin Rx have immune IgG-mediated thrombocytopenia which is frequently complicated by paradoxical extension of pre-existing venous thromboembolism or new arterial thrombosis!!
  • suspect if platelet count falls < 100,000 per cu.mm or < 50% of baseline value 5-15 days after Rx is begun, or sooner in a pt who received heparin in the recent past
  • minimise risk of occurrence by:
    • initiating warfarin Rx early to reduce exposure to heparin
    • use LMW heparins instead
  • management options (after ceasing heparin):
      • problem in that it is slow-acting & can cause early transient hypercoagulability
    • caval filter:
      • prevent embolisation of pre-existing thrombi, but do not prevent extension up to the filter, thrombosis above it, or arterial thrombosis
    • rapid-acting anticoagulants:
      • danaparoid sodium - may cross-react with heparin in < 5% pts
      • BUT NOT LMW heparins - may cross-react with heparin commonly so should be avoided in this condition
      • defibrinogenating snake venom ancrod (Arvin)
      • hirudin

heparin-induced osteoporosis:

  • occurs in ~30% with Rx duration > 1 month (eg. in pregnancy where warfarin C/I)
  • risk may be lower with LMW heparins
heparin.txt · Last modified: 2021/04/09 03:40 by gary1

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