In this episode, I’ll discuss the protamine shortage.
In March 2021 the ASHP Shortage list reported that the manufacturer of protamine was experiencing delays leading to a shortage.
Protamine can be used as an emergency reversal agent for heparin and partial reversal agent for low molecular weight heparin. Significant amounts of protamine are also used in cardiac surgery to reverse the large amounts of heparin given to facilitate that procedure.
The manufacturer of protamine has provided a letter to customers stating that they have set aside a supply of previously manufactured product for medically necessary direct orders. Ordering information can be obtained from a customer service representative using the number on the manufacturer’s product availability page.
Key stakeholders to involve in managing alternatives to this shortage include your hospital’s cardiac surgery anesthesiologists and cardiac surgeons as they are likely the biggest users of protamine.
The 2018 guidelines on Anticoagulation During Cardiopulmonary Bypass do suggest an alternative that doesn’t require protamine when patients with heparin-induced thrombocytopenia require bypass surgery. They state:
For patients with a diagnosis of HIT and in need of an urgent operation requiring CPB, anticoagulation with bivalirudin is a reasonable option. (Level of Evidence B)
The discussion section of the guidelines reviews the available evidence supporting bivalirudin’s use as an alternative to heparin with protamine reversal, including two major trials (CHOOSE-ON and EVOLUTION-ON). The ASHP shortage page also references these studies for bivalirudin as an alternative.
Ideally between the manufacturer’s reserved supply and using bivalrudin for cardiac surgery the shortage can be managed without running out of protamine completely. This will allow for some to be kept in the event of urgent reversal of heparin or partial reversal of enoxaparin due to life-threatening bleeding.
In the event of a life-threatening bleed and a complete unavailability of protamine, there are some options that can be considered.
An article in Annals of Pharmacotherapy describes the use of andexanet alfa to reverse heparin. While not a practical alternative due to cost and availability, it may be considered in the event of a life-threatening bleed.
The SCCM’s Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage states the following:
We suggest considering rFVIIa (90 μg/kg IV) if protamine is contraindicated (Conditional recommendation, very low quality evidence)
Being an activated clotting factor, rFVIIa does present a theoretical thrombogenic risk, so the risk:benefit should be carefully evaluated before deciding on this strategy for heparin reversal.
If you have any other strategies for managing the protamine shortage, please share in the comment section below.
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