Anticoagulants Protamine

Protamine. Protamine, whose use to reverse heparin anticoagulation has increased over the last two decades, has also been incriminated. Reactions may involve a number of mechanisms including IgE, IgG and complement. The incidence of anaphylactic reactions is estimated at 0.19% (retrospective studies) and 0.69% (prospective studies), respectively [27]. 

The answer is d. (Hardman, p 1346.) A slow intravenous infusion of protamine sulfate will quickly reverse the bleeding. Protamine binds to heparin to form a stable complex with no anticoagulant activity It may also have its own anticoagulant effect by binding with platelets and fibrinogen. 

The agents like protamine sulfate react with the strongly acidic groups of heparin and can abolish its anticoagulant activity. Approximately 1 mg of protamine sulfate neutralizes 80 to 100 units of heparin. It is used only in severe bleeding or when heparin action needs to be terminated rapidly e.g. after cardiac or vascular surgery. 

Activated clotting time (ACT) and activated partial thromboplastin time (aPTT) are relatively unaffected by LMWH. Anti-Xa activity can be used to monitor anticoagulation activity, but this is expensive and time-consuming and is seldom indicated. Although protamine has some effect on LMWH, about 60-80% of the antithrombotic activity will persist. This is because of the reduced protamine binding to these drugs and because only the anti-IIa activity is completely reversed whereas anti-Xa activity is only partially neutralised. 

Excessive anticoagulant action of heparin is treated by discontinuance of the drug. If bleeding occurs, administration of a specific antagonist such as protamine sulfate is indicated. Protamine is a highly basic peptide that combines with heparin as an ion pair to form a stable complex devoid of anticoagulant activity. For every 100 units of heparin remaining in the... 

The indications for the use of heparin are described in the section on clinical pharmacology. A plasma concentration of heparin of 0.2-0.4 unit/mL (by protamine titration) or 0.3-0.7 unit/mL (anti-Xa units) usually prevents pulmonary emboli in patients with established venous thrombosis. This concentration of heparin will prolong the activated partial thromboplastin time (aPTT) to 2-2.5 times that of the control value. This degree of anticoagulant effect should be maintained throughout the course of continuous intravenous heparin therapy. When intermittent heparin administration is used, the aPTT should be measured 6 hours after the administered dose to maintain prolongation of the aPTT to 2-2.5 times that of the control value. 

The primary advantage of UFH as an anticoagulant is the relatively low unit cost and familiarity with its use and monitoring by staff members during the intervention. Another important consideration in the selection of UFH is the availability of a reversal agent, protamine, in an unfortunate event of major bleeding due to a procedural vascular perforation. 

If an anticoagulant has been added to the blood and the plasma isolated, it may be advisable to defibrinate the plasma to yield a serum analog. The method for this varies according to the anticoagulant for citrate, add 1 % of a solution of thrombin (lOOIU/mLin IMCaClg). For heparin, add 1% protamine sulfate solution (5 mg/mL) and thrombin as above. 

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