Addressing the Heparin Drug Shortage
Dr. Manesh R. Patel and Sarah A. Spinler react to the recent shortage of heparin in the United States and consider how the approval of direct oral anticoagulants can potentially serve as an alternative for appropriate patients.
Manesh R. Patel, MD: In light of these findings, how do we get to where the heparin shortage occurred this time? What were the things that led to that, and how would we manage that current shortfall?
Sarah A. Spinler, FCCP, FAHA, FASHP, AACC, BCPS, AQ-Cardiology: Well, I think sometimes they’re multifactorial. I said sometimes there’s a layer in the manufacturing practices. For instance, 1 company, Pfizer Inc, manufactured heparin in Puerto Rico. When Hurricane Maria hit, there was a shortage in the delay as the plant came on board. But about 80% of the porcine heparin in the US is manufactured in China. As you mentioned before, the outbreak of African swine fever has led to many swine, both naturally dying and then as a preventive measure, the Chinese government has called a large number of hogs that are related to the production of heparin.
There are some estimates that 25% to 35% of all the pork mucosal intestine available for production of heparin in China will be lost secondary to this outbreak. Also, prospectively the Chinese government is calling the hog production secondary to the prevention, especially in the northeast regions of China. In total, I think they estimate more than 150 million animals will be euthanized, or lost, secondary to the deadly disease.
Manesh R. Patel, MD: Wow, quite a devastating thing, not only for the animals but for the production of this. And it does highlight for us how dependent we are sometimes on these products that are coming from animals, on environment, natural disaster disease states where it might affect it. You know in the catheterization lab where we use the heparin, we often check the ACT [activated clotting time] and think about ways to know that we’re getting the effect we want. But these shortages hit us pretty quickly, I think. In clinical practice in the hospital or in other parts of our care, are there, in your opinion, opportunities with some of the DOACs [direct oral anticoagulants], such as betrixaban and rivaroxaban, that change the treatment landscape? Because those agents have not been approved for [the] medically ill population, and there could be an overlap. What are your thoughts about that?
Sarah A. Spinler, PharmD, FCCP, FAHA, FASHP, AACC, BCPS, AQ-Cardiology: One of the largest uses of heparin in the hospital is for venous thromboembolism prophylaxis. As the shortage has come in, the institutions are notified. You move your response in kind of a serial way. The first response is that, and you can notify people of the shortage, so you can try [to] switch. You mentioned in the catheterization lab. For instance, you could use bivalirudin more, even though 10 years ago it was like, don’t use bivalirudin, and the pharmacy department would tell you, use heparin. But now it’s more, “OK, use more bivalirudin and less heparin.” Because you want to restrict the heparin use for important things, like for cardiopulmonary bypass or ECMO [extracorporeal membrane oxygenation] or places [that] it’s critically ill.
When you have a high number of units of use, being in venous thromboembolism prophylaxis, you can look for alternatives in that scenario as well. You’re correct that rivaroxaban and its new approval could be 1 of those agents. There is also a move to switch use to enoxaparin. If you use unfractionated heparin for a venous thromboembolism prophylaxis, you could use enoxaparin. It is not yet listed on the website for the FDA, but it is listed on the ASHP [American Society of Health-System Pharmacists] website that enoxaparin is certainly also undershorted. One of the responses is that you saw as the heparin became undershorted, institutions switched to enoxaparin undershorted, which will then create enoxaparin shortage. It’s kind of a moving target as practitioners switch.
Manesh R. Patel, MD: Yeah, so a lot like we’ve discussed. One is knowing about a shortage. The second is trying to prevent or at least think about agents. In this case, at least in the hospital, where—as you said, and in our cardiovascular practice it’s true too—there are many places where we have to have heparin. There really [are] not a lot of other things. We’re used to doing cardiopulmonary bypasses, and that’s a classic example. That’s something that urgently might need to be done.