Heparin: Prevention of Blood Clotting
Guest: Dr. David Kurtz - Division of Basic Sciences/Pharmacology, MUSC
Host: Dr. Linda Austin – Psychiatry, MUSC
Dr. Linda Austin: This is Dr. Linda Austin. I’m interviewing Dr. David Kurtz, who is Professor of Pharmacology at the Medical University of South Carolina. Dr. Kurtz, could you explain, first, what is heparin?
Dr. David Kurtz: Heparin is an anticoagulant. And that means it prevents blood from clotting. It is a very simple sugar, polysaccharide; meaning, many sugars hooked together. It has a very simple way that it works. Blood clotting occurs when a protein called fibrinogen is converted to a protein called fibrin. Fibrin is what the clot is. Fibrinogen is converted to fibrin by another enzyme called thrombin. Now, there are naturally occurring proteins that stop thrombin from acting. These are called antithrombin, just as the name implies. Antithrombin has a certain affinity, ability, to bind to thrombin. When you add this sugar called heparin, it makes the antithrombin bind to the thrombin about a thousand times better. So, you stop clotting from happening.
Dr. Linda Austin: For what clinical reasons will a doctor prescribe heparin for a patient?
Dr. David Kurtz: Patients who have had a tendency to have clots in their veins, sometimes called phlebitis, and patients who have clots in their lungs; pulmonary embolism, would be injected with heparin. The important thing about heparin is that it can’t be taken orally, because it’s not absorbed; it’s digested. The advantage of heparin is that it has a very rapid onset of action. It starts working right away; as soon as you inject it. You have to inject it intravenously, not intramuscularly. So, patients who have a tendency to have clotting happen are given IV injections of heparin. And this is only done in the hospital on an inpatient basis. Heparin is not given by prescription on an outpatient basis.
Dr. Linda Austin: Now, I’m sure the concern, currently, is whether this issue with the possibly contaminated supplies from China will lead to shortages in the United States. If that were to be the case, what could be substituted for heparin?
Dr. David Kurtz: In terms of a rapid-acting drug, there really isn’t anything. There are many oral anticoagulants that are used. The most common is called Coumarin. So, heparin is given while the patient is in the hospital, and then the patient is slowly withdrawn from heparin and put on Coumarin, or an oral anticoagulant. However, the oral anticoagulants act much more slowly. They take almost a week to start working.
I wouldn’t say that heparin is a common molecule. It’s made from pig intestines. In the old days, they used to actually get it from cow lung. And I think you still could if you needed to. It’s not clear to me that there’s going to be a shortage. But, in terms of its rapid-acting ability, there’s really nothing that’s as good. It certainly is cheap, and is controllable. There are some substitutes that have been tried over the years, some of which, believe it or not, are from the medicinal leach proteins, which, as you probably know, prevent clotting. Those have not been as effective as heparin.
Dr. Linda Austin: In the New York Times article, reference was made to earlier concerns about mislabeling.
Dr. David Kurtz: Yes. There was apparently a problem with mislabeling, where there were vials that were supposed to be what were called multidose vials. That is, they were supposed to be given over several days. And the hospitals were either misreading or not paying attention, dissolving the vial up and giving it as one dose, which was, effectively, a massive overdose. By the way, I should mention that the problem with an overdose of heparin is you get internal bleeding. Because it’s so effective at stopping blood clotting, it will stop the clotting from happening even when it should be happening. There is a fairly common antidote, called protamine sulfate. That just binds the heparin and prevents it from acting.
Dr. Linda Austin: But there’s indication from the bits and pieces of information we have at this point that that may not be the current issue, because people are actually becoming ill.
Dr. David Kurtz: Correct. Apparently, from what I can gather, there’s some contaminant in the current source of heparin. The contaminant could be a protein. It, I suppose, could be a toxin, although that’s very unlikely. The reason I say it could be a protein is that heparin is initially synthesized in the pig, attached to proteins. And then, in the normal course of making heparin for therapeutic use, the sugar is removed from the protein, and it’s only the sugar that’s used. It’s conceivable that, if they were being sloppy, they would have large amounts of protein still around. What that can do, certain people would be allergic to it. And the reports are that the deaths are due to some allergic reaction. So, it’s actually probably not to the heparin itself. It could be to some contaminant that’s contained in there.
Dr. Linda Austin: Dr. Kurtz, thank you so much for talking with us today.
Dr. David Kurtz: You’re welcome.
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