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Anticoagulation 

Heparin

LMW = low molecular weight. UF = unfractionated.
Features: Parental administration (not oral). A glycosaminoglycan (naturally occurring). Unfractionated means a mixture of chain lengths whereas LMW has a uniform smaller chain length.
Mechanism: ↑Activity of plasma antithrombin. Inhibits active clotting factors esp IIa and Xa. LMW has more anti-Xa activity than UF.

Comparison of Unfractionated vs. Fractionated

Unfractionated Low Molecular Weight
Route IV Subcutaneous
Bioavailability Poor, unpredictable Good, predictable
Monitoring aPTT ratio Not needed
Metabolism Complex Simple
Half-life 1-2h 4-6h
Indications Rapid onset/offset: surgery Initially for DVT/PE, ACS, warfarin unsuitable

Adverse Reactions

Interactions:
Cautions: Renal failure, coagulopathy (eg liver disease)
Side Effects: (UF > LMW)

Monitoring

UF: Inhibition of IIa (common) causes ↑aPTT and ↑PT. But aPTT best. Expressed as: aPTT ratio = Patient's aPTT/normal aPTT
LMW: At therapeutic levels neither aPTT or PT will be prolonged, so measure with anti-Xa assay (very rarely needed).

Administration of UF

Therapeutic range: 1.5-2.5 (but ↑ needed in arterial thrombosis). Giving:
  1. IV bolus 5000 IU
  2. IV infusion 15,000 IU over 12 h
  3. Check aPTT ratio: 4 h after started and after every dose change, daily if infusion rate stable. Check patients platelet count 4 days after start (heparin-induced-thrombocytopenia)

Administration of LMW

Empirical Prophylaxis eg. clexane. Can monitor with assay, but most don't need.
Over coagulation treatment :

Warfarin

The only oral anticoagulant. 100% bio-availability, metabolized by liver. But variation in pharmacokinetics/pharmacodynamics, ↓therapeutic window, and half life only 36 hours: means close monitoring required.
Mechanism: Inhibits recycling of vit K (needed for factors 2, 7, 9, 10).
Doses: Typically 1-10 mg po once daily

Indications

Long term antithrombotic:

Interactions

(Assume all drugs will!)
Causes overcoagulation with: amiodarone, PPI, statin, fluconzole
Causes undercoagulation with: barbiturates, carbamezepine, cholestyramine
Causes ↑bleeding with: Antiplatelet agents

Adverse Reactions

  1. Bleeding
  2. Rarely: thrombosis if protein C/S deficient (paradoxically! these are also vit k dependent), fetal warfarin syndrome

Cautions

Previous coagulopathy including liver disease, renal failure

Monitoring

Depletes factors in common pathway therefore PT and aPPT affected. But PT used to monitor.
INR = Patient's PT/normal PT
Target INR usually 2-3 (3-4 in: prosthetic hrt valve, or DVT/PE during anticoagulation)

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Treatment of overcoagulation

Causes serious morbidity and mortality. Reasons: poor patient understanding, drift in dose-response.

Surgery and warfarin

Principles: therapeutic INR may cause surgical bleeding, risk depends on INR and procedure, short term cessation of warfarin is not risky
  1. Routine INR check 1 w before (to make sure INR is therapeutic)
  2. Omit warfarin 2-3 d before
  3. Check INR evening before
  4. Consider 1 mg vit k if INR still > 2-5 (?)
  5. Most procedures ok w INR < 2
  6. Restart warfarin 2-3 d after surgery
Surgery and thrombotic risky patient: Give UF heparin, and admit 3d before. Consider rescheduling surgery
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