Overdose : מינון יתר

4.9 Overdose
a) Symptoms of an overdose
Bleeding, in most cases from the skin and mucous membranes, wounds, gastrointestinal and urogenital tract (epistaxis [nosebleed], haematuria, melaena, haematomas, petechiae). Fall in blood pressure, decrease in haematocrit or other symptoms may be signs of occult bleeding.
b) Treatment of overdose
Mild bleeding
Reduce the heparin dose if necessary.
Moderate non–life-threatening bleeding
Suspend the heparin therapy.
More serious, life-threatening bleeding
Reverse the effect of heparin with protamine after excluding other causes of bleeding (e.g. consumption coagulopathy, factor deficiency). Protamine should be administered only in the case of life-threatening bleeding, as there is an increased risk of thromboembolic complications once heparin has been completely neutralised. The patient must be monitored and treatment continued in intensive care.
The antidote protamine is an arginine-rich protein which is usually used in the form of a chloride or sulphate. As a general rule, 1 mg of protamine neutralises the effect of about 100 IU of heparin (1 IU of protamine neutralises 1 IU of heparin). The half-life of heparin and the route of administration need to be borne in mind for the treatment, i.e.
- 90 minutes after intravenous heparin administration, only 50% of the calculated protamine dose should be given
-   3 hours after intravenous administration only 25% should be given 
In the event of overtitration, protamine can itself cause an increased bleeding tendency through various mechanisms. If protamine is injected too quickly, there may be a fall in blood pressure, bradycardia, dyspnoea and a feeling of oppression. Protamine is eliminated from the bloodstream more rapidly than heparin. The neutralisation effect must therefore be monitored by regular assays of activated partial thromboplastin time (aPTT). Heparin is not dialysable.