Conservation Measures Reduce Impacts of Heparin Shortage

Facing a global heparin shortage resulting from an outbreak of African swine fever in China, Massachusetts General Hospital leaders have come together to proactively mitigate harm and reduce hospital and patient impacts. Heparin stakeholders, including leaders from cardiac surgery, perfusion, hematology and dialysis comprise the hospital-wide working group. The heparin working group is a subset of Mass General's larger emergency preparedness team.

At Mass General and in hospitals worldwide, the stakes are high. "If it were to get worse, in theory, we would have to cancel elective cardiac surgeries," says surgeon Nathaniel Langer, MD, MSc, of the Cardiac Surgery Division at Mass General. "We've made significant changes to protect those patients whose care would be compromised without heparin. We already have a good system in place."

Heparin's Critical Role in the Clinical Setting

Clinicians prescribe heparin to 10 to 12 million people annually. As an anticoagulant, its many indications include:

• Blood clot reduction in patients with blood vessel, heart and lung conditions
• Clot prevention during cardiac procedures, dialysis and blood transfusions
• Deep vein thrombosis (DVT) prophylaxis in an inpatient setting

Heparin comes in two main forms: unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). "Unfractionated heparin is just the bulk, whereas low-molecular weight heparin is a grouping or isolation of the low-molecular weight heparin molecules," says Dr. Langer. "Unfractionated heparin is the workhorse."

Dr. Langer attributes unfractionated heparin's widespread use to its:

• Short half-life: Doctors can administer unfractionated heparin up to an hour before surgery. When clinicians turn off a heparin infusion, the body breaks it down quickly and its effects wear off quickly. Surgeons use it because they can turn it off if there is a bleeding event or a patient needs to be rushed to the operating room (OR)
• Antidote availability: Protamine sulfate is an intravenous drug that reverses the effects of heparin. When patients have acute bleeding problems, clinicians can give them protamine to "turn off" the heparin. Surgeons also use protamine in the OR to control heparin's effects after cardiac surgery

Repeating History: Examining the Heparin Shortage Due to Swine Flu

Manufacturers source heparin from animal tissue. Historically, cow lung tissue was used until a bovine spongiform encephalopathy (mad cow disease) outbreak in the 1990s. "There was concern about using medications derived from cows, so there was a big push to move towards heparin derived from pigs," Dr. Langer says. "As a result, the most common source for heparin is pig intestinal tissue, with the vast majority of the world's supply coming from China."

China is responsible for 80% of the global crude heparin supply and 50% of the world's pig population. But an outbreak of African swine fever in August 2018 led to the culling of 40% of the Chinese pig population. "There was a concern that the world supply of unfractionated heparin could be cut massively," says Dr. Langer. In late 2019, pharmaceutical companies around the world attributed rising heparin prices to shortages resulting from the swine fever and some placed the drug on protective allocation lists.

Heparin-less Cardiac Surgery: Examining the Potential Impacts

Dr. Langer says that unfractionated heparin is the foundational drug enabling patients to go on cardiopulmonary bypass, the standard protocol for patients undergoing open-heart surgery.

"Cardiopulmonary bypass means exposing the patient's blood to the world: to air, the plastic tubing that the blood runs through, the oxygenator that we use to remove carbon dioxide and reoxygenate the blood, and to the heater-cooler. All aspects of the cardiopulmonary bypass machine are not normal human tissue," he says. "If blood was just allowed to contact them in its normal state, it would clot and then potentially get pumped back to the patient and cause strokes or ischemia to other organs."

To prevent these complications, clinicians use high doses of unfractionated heparin to thin the blood at the beginning of the procedure. They check the activated clotting time every 30 minutes to determine the level of anticoagulation while on the heart-lung machine. Heparin is then re-dosed to maintain the ideal level of anticoagulation.

"In an absolute emergency, there are other drug options, but nobody has extensive experience with them. The ability to turn them on and off is also much less," says Dr. Langer. "When patients come off the heart-lung machine, we give them protamine to stop the bleeding and reverse the effects of the heparin within minutes. Not having heparin available would significantly limit the amount of heart surgery we can do."

Implementing Proactive Heparin Conservation Measures

To prepare for the heparin shortage, Mass General activated its Hospital Incident Command System. Hospital leaders engaged with heparin manufacturers to understand the ramifications of shipping delays and cancellations and reviewed all conservation measures.

"As a group, we've sought to totally rethink our use of unfractionated heparin to protect it for when we absolutely need it, including cardiopulmonary bypass and patients at high risk for major heart attacks and blood clots due to other medical problems," says Dr. Langer. "For example, during a lot of our transcatheter valve procedures, we would have heparin drawn up and ready to give in case we had to emergently go on bypass. But since that's rare, that heparin would often get wasted."

Conservation strategies include:

• Reducing heparin waste by revisiting all operating room, postoperative and floor management protocols
• Using Lovenox® (generic name: enoxaparin), a LMWH for DVT prophylaxis
• Using other classes of anticoagulants, such as bivalirudin, for procedures that don't require unfractionated heparin

Preparing for the Future with New Heparin Protocols

The proactive conservation measures at Mass General and other U.S. hospitals have been an effective deterrent against the most worrisome potential impacts of a heparin shortage. They also provided Dr. Langer and his colleagues a unique opportunity to reexamine protocols and become more efficient.

"We have a protocol in place now that is just as safe for patients and also conserves a sometimes tenuous resource," he says. "It sets us up well for the future."

Learn more about the Cardiac Surgery Division

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