New Therapies To Decrease Bleeding Risk In Liver Disease

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People with cirrhosis often are noted to have a low platelet count. Platelets are essentially blood cells that are involved with clotting. While low platelets are not inherently dangerous, people with low platelets are at increased risk of bleeding when they undergo any type of procedure that involves cutting the skin, mucosa or any type of interventional procedure.

Low platelets in liver disease are a result of a combination of splenic sequestration and decreased bone marrow production. Of these two mechanisms, splenic sequestration makes up the largest percentage. The hardened liver of cirrhosis leads to decreased blood flow through the liver and back up of blood into the veins which feed the liver and blood pools in the spleen. This is called portal hypertension. The spleen functions to take up old platelets and the number of platelets it removes from the blood stream is dependent upon the blood flow through it. The slower the flow, the more the spleen takes up. This results in a large spleen and low platelet count.

People with cirrhosis are often in need of basic surgical and interventional procedures. For example, cirrhotic patients often need skin biopsies, dental cleaning and extraction, cardiac catheterizations, paracenteses, liver biopsies or surgeries such as gallbladder removal, etc. If the platelet count is below 50-70,000, as in many people with cirrhosis, the risk of significant bleeding increases dramatically and that bleeding can even be life threatening. Up to now, the only treatment that medicine had for low platelets was to give platelet transfusions before any scheduled procedure or emergency procedure. Platelet transfusion, while the gold standard, is far from golden and certainly not risk free. These transfusions increase plasma volume which can paradoxically increase portal hypertension and the risk of bleeding. Platelet transfusions can also cause systemic reactions such as fever, shortness of breath, rash and even anaphylaxis. As platelets come from human donors, the chance of passing a blood born infection is miniscule but certainly not zero.

There is a lot of research into finding a replacement option for the use of platelets in patients with cirrhosis and low platelets who need elective procedures. A new class of agents are being developed called TPO agonists. These medications work by boosting the body’s ability to make platelets in a predictable and dose dependent fashion. There are several of these compounds being tested for use in liver disease and it is exciting. The have tongue twisting names such as avatrombopag, eltrombopag, lusutrombopag and romiplastin. These agents are given by either mouth or infusion. So far, they appear to be safe. The hope is that they will replace platelet transfusions and allow more patients to safely get the medical and dental treatments that they need.

While several of these agents are currently available, the oral agents are still not FDA approved for use prior to elective procedures in patients with cirrhosis. I hope that very shortly, these agents will be available as they fulfill a current unmet medical need.

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