Protamine

Protamine
Mass / length primary structure	30-32 amino acids
Drug information
ATC code	V03 AB14
Drug class	Antidota

Protamine is a mixture of strongly basic peptides that is used as a drug . It belongs to the group of substances called protamines and is mainly isolated from the sperm or roe of certain types of salmon - especially ketal salmon ( Oncorhynchus keta ) and king salmon ( Oncorhynchus tshawytcha ) - by extraction with mineral acids. It contains more than two thirds of L - arginine .

In hematology , intensive care medicine , cardiac surgery and vascular surgery , protamine is used to antagonize the heparin effect. The basic protamine itself is not used, but rather neutral solutions of the salts protamine sulfate and protamine hydrochloride .

Cancellation of the effects of heparin

Protamine forms a salt-like compound with heparin without an anticoagulant effect. It is therefore used to quickly cancel the effect of heparin, for example before operations (preoperative), as a countermeasure during operations with heart-lung machines (strong anticoagulation is necessary during the HLM period, afterwards cancellation), in the therapy of heparin overdoses and for heparin-induced bleeding. 1000 IU protamine sulfate or protamine hydrochloride inactivates about 1000 IU heparin. In the case of the low molecular weight heparins, the anti- Xa activity is only partially neutralized. In the case of subcutaneous injections of LMWH , the slow absorption of the same can lead to insufficient inactivation of the heparin, which makes it necessary either to administer protamine again or to administer it slowly over a longer period of time. It works quickly, within 5 to 15 minutes.

The effects of other anticoagulant drugs cannot be reversed with Protamine.

Side effects

Protamine is injected or infused slowly. If the dose is given too quickly, the blood pressure can suddenly drop sharply and the heart rate slows down. The cause is the release of histamine from mast cells . Furthermore, protamine as a foreign protein substance can cause anaphylaxis (recognizable e.g. as reddening of the skin). By complement one can pulmonary hypertension are triggered, which can pose particular patient during heart surgery problems. Ideally, the dose depends on the coagulation status in order to avoid an overdose. Protamine itself also has a slight anticoagulant effect, so that overdosing can lead to bleeding. Presumably, protamine interferes with fibrin polymerization and increases the release of t-PA from the endothelium . A temporary disorder of platelet function has also been described.

Delay in the action of insulin

Protamine is combined with insulin as a pharmaceutical excipient and in connection with zinc ions in order to delay the onset of action and to extend the duration of action. This modified insulin is called NPH insulin (neutral protamine hawthorn - insulin).

Individual evidence

1. ↑ K. Hardtke et al. (Ed.): Commentary on the European Pharmacopoeia Ph. Eur. 5.0, protamine sulfate. Loose-leaf collection, 22nd delivery 2005, Wissenschaftliche Verlagsgesellschaft Stuttgart.
2. ↑ Technical information Protamin ME 1000 IU / ml (Meda, status: 2009), Technical information Protamine sulfate LEO Pharma 1400 Heparin-Antidote IU / ml solution for injection and infusion (LEO Pharma, status: 2014).
3. ↑ Technical information Protamine sulfate LEO Pharma 1400 heparin antidote IU / ml solution for injection and infusion solution, as of September 2006.
4. ↑ Carlo Marcucci: Perioperative hemostasis: coagulation for anesthesiologists . Springer, Berlin, Heidelberg 2014, ISBN 978-3-642-55003-4 .