2004A08 Describe briefly the side effects and complications of heparin therapy.

 

List:

·      Intro

·      Problems

·      Bleeding

·      HITT

·      Other (short term and long term)

 

Problems that aren’t side effects:

Narrow therapeutic index

·  Need monitoring – aPTT

·  Aim 1.5-2.5x baseline approx

Variable effect

·  Variable plasma protein concentration

·  Zero order kinetics at high dose

·  Variable elimination rate by metabolism (heparinase) > excretion (urine unchanged)

·  Heparin resistance

o Variation in concentration of heparin-binding proteins (e.g. albumin)

o ↑Heparin clearance (e.g. splenomegaly in liver disease)

o ↓AT3 (e.g. DIC, bypass circuit, nephrosis, congenital) – Rx AT3 or FFP

 

Bleeding: *Dose-dependent*

Risk

·  1-5% if therapeutic anticoagulation

·  e.g. peptic ulcer bleed, haemorrhagic stroke

Mechanism

·  Heparin binds and potentiates AT3

·  AT3 inactivates IIa, Xa, IXa, XIa, VIIa-TF

 

 

HITT: *Idiosyncratic*

Risk

·  1 in 200 therapeutic doses

·  1 in 10,000 prophylactic doses

·  UFH >> LMWH

Type 1

·  95-99%

·  ↓Platelet count by <10%

·  Onset <4 days

·  Non immune-mediate

·  Low risk complications

Type 2

·  1-5% (<1% LMWH))

·  Onset 4-14 days

·  ↓Platelet count by >50% or to <150

·  Immune-mediated; IgG binds heparin + PF4 = hapten

·  Platelet activation and aggregation, thrombosis

·  50% risk major thrombotic event: ATE, VTE

·  Risk major bleeding: haemorrhagic stroke, classic bilateral adrenal haemorrhage

·  Death 10-30%

·  Diagnosis: “4Ts”, heparin/PF4 assay

·  Rx: stop offender; start alternative e.g. lepirudin, argatroban

·  Do NOT start warfarin; risk skin necrosis, limb gangrene

 

Other side effects: (UFH > LMWH > Fondaparinux):

Short term

·  Hypotension (if rapid injection) – vasodilatation, venodilatation

·  Hypersensitivity

·  Hepatotoxicity

·  Suppression of aldosterone synthesis, ↑K+

·  Skin necrosis

Long term

·  Osteoporosis

·  Alopecia

 

 

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