Blood Clots in Patients with PNH, with Dr. Maxim Norkin

Leigh Clark:    00:00    Hi, everyone. This is Podcast for Patients, with the Aplastic Anemia Aplastic Anemia: (ay-PLASS-tik uh-NEE_mee-uh) A rare and serious condition in which the bone marrow fails to make enough blood cells - red blood cells, white blood cells, and platelets. The term aplastic is a Greek word meaning not to form. Anemia is a condition that happens when red blood cell count is low. Most… & MDS International Foundation. My name is Leigh Clark, Director of Patient Services, and I'll be moderating the podcast today. Our podcast series is brought to you with thanks to our generous support from patients, families, and caregivers like you, and our generous corporate sponsors. I'd like to thank everyone for supporting the podcast series. 
Today we're going to be talking about blood clots in PNH with Dr. Maxim Norkin, who is a hematologist hematologist: (hee-muh-TOL-uh-jist) A doctor who specializes in treating blood diseases and disorders of blood producing organs. oncologist oncologist: (on-KAH-luh-jist) A doctor who specializes in the treatment and prevention of cancer. with Baptist MD- MD Anderson Cancer Center, located in Jacksonville, Florida. Welcome, Dr. Norkin.
Dr. Maxim Norkin:    00:52    Thank you for having me.
Leigh Clark:    00:54    Thank you so much. So what is a blood clot blood clot: A mass of blood that forms when platelets stick together. Harmful blood clots are more likely to happen in PNH. The term thrombus describes a blood clot that develops and attaches to a blood vessel. The term embolus describes a blood clot or other foreign matter that gets into the bloodstream and… ?
Dr. Maxim Norkin:    00:58    One of the most frequent and feared complication of- of PNH is formation of blood clots. And in patients with PNH, uh, without treatment, blood clots are frequent. It could be quite extensive. It can develop in unusual places and can often be life-threatening. 
So blood clots are gel-like collections of blood, that form in your veins and arteries, uh, when blood changes from liquid to partially solid form. Uh, blood clotting is also called coagulation. Um, it's an important process that under normal conditions, prevents excessive bleeding after an injury of a blood vessel.
So that's a good thing. But unfortunately, it can be a- abnormal. In normal conditions, we dissolve the clot after injury has healed. However, uh, blood clots can form inside the vessels without an obvious injury. And that's abnormal, uh, situation. 
So and this situation can be quite dangerous and require accurate and timely diagnosis and appropriate treatment.
Leigh Clark:    02:05    Thank you. Uh, what are the signs and symptoms of a blood clot?
Dr. Maxim Norkin:    02:10    Yeah. They- the signs and symptoms can vary, uh, quite dramatically, depending on where the blood clot has developed. Um, abnormal blood clotting can occur commonly in veins, uh, and less frequently in arteries. Um, and abnormal, uh, blood clots, they can develop in the vein, may restrict return of the blood, uh, to the heart, and can often cause, uh, pain and swelling. So pain and swelling, the most common signs of the blood clot. And typically and happen in the leg, and less typically they happen in the arm.
Dr. Maxim Norkin:    02:51    In the worst case scenario, the blood clot can detach from the point of origin, and travel through, uh, their vessels, uh, to the lungs. And can block the blood supply to the lungs, and can some- add some pressure to the heart. This is a very dangerous, uh, condition, and can be quite life threatening. And it's causes,   pulmonary embolism pulmonary embolism: (PULL-muh-nerr-ee EM-buh-liz-um) A blockage of an artery that carries blood to the lungs. See Embolism. , uh, PE. In- in this situation, uh, symptoms include shortness of breath, uh, chest pain, and this is a medical emergency and requires urgent therapy. 'Cause it's life threatening.
Interesting in some patients with PNH, blood clots, uh, can often develop in unusual places, including liver, is called Budd-Chiary Syndrome. And this is associated with jaundice jaundice: A yellow coloring to the eyes and/or skin due to an increased level of bilirubin, which is a breakdown product of hemoglobin. , abdominal pain, enlarged liver, and fluid accumulation in the abdomen. Uh, sometimes thrombosis thrombosis: (throm-BOE-suss) A blood clot (thrombus) that develops and attaches to a blood vessel. in patients with PNH can happen in veins, uh, that's, in the abdomen. In the belly. And it can lead to bowel infarction, and maybe require surgery.
Uh, blood clots in the vein around the brain can happen. Not frequently, but can happen. And can lead to headaches and some brain swelling. And sometimes, uh, blood clots can, uh, happen in blood vessels of the skin, can cause painful rash and bruising. 
Leigh Clark:    04:22    Thank you. Why are PNH patients so susceptible to developing blood clots?
Dr. Maxim Norkin:    04:31    Yeah. PNH is a condition in which uncontrolled compliment activity, leads to excessive breakage of the red cells. So it's called hemolysis hemolysis: (hi-MOL-uh-suss) The destruction of red blood cells. , inflammation within the lining of the blood vessels and platelet platelet: The smallest type of blood cell. Platelets help the blood to clot and stop bleeding. Also called a thrombocyte. activation. So all of these three things,  significantly increase, uh, chance for abnormal blood clot formation. And that's why the patients with PNH, uh, are very prone to develop blood clots. Sometimes very extensive blood clots, and blood clots in unusual places.
It was shown that development of, uh, blood clots is associated with fear of prognosis in the patients with PNH, before the introduction of compliment inhibitors, such as, uh, Soliris, um, or Eculizumab Eculizumab: Eculizumab (Soliris ®) is given as an IV into a vein at the doctor’s office or at a special center. The procedure usually takes about 35 minutes. You will probably get an IV once a week for the first 4 weeks. Starting in the 5th week, you will get a slightly higher dose of Soliris every 2 weeks. … . Uh, blood clots happen in up to 30 to 45% of, uh, all PNH patients. So almost half of the patients with PNH, they had a history of blood clots before the novel treatments were introduced. Well actually, with new treatments now, we have much less incidents of the blood clots in the patients. And usually blood clots, uh, happen in patients with high, um, number of PNH cells, when PNH clone clone: To make copies. Bone marrow stem cells clone themselves all the time. The cloned stem cells eventually become mature blood cells that leave the bone marrow and enter the bloodstream. exceeds 50% or more.
Leigh Clark:    05:55    Thank you for that. You mentioned about the current treatments, um, helping to reduce the likelihood of PNH patients developing blood clots. Is there anything else PNH patients can do to reduce their risk of developing blood clots?
Dr. Maxim Norkin:    06:13    Yeah. I think the successful treatment, and to start the therapy and be compliant with therapy, is very, very important. Again, the novel treatments  that's available would only reduce the symptoms, um, and hemolysis. But they prevent life threatening complications including, uh, blood clot formation.
Leigh Clark:    06:36    Thank you. Is there anything else PNH patients should know about blood clots? 
Dr. Maxim Norkin:    06:41    So I think we, uh, probably can talk about the inhibitors first. So the- PNH therapy with compliment inhibitors now available as Eculizumab, or Soliris, or Ravulizumab, or Ultomiris, was shown that they're to significantly reduce incidents of the blood clots. There was recently approved C3 inhibitor, um, Pegcetacoplan Pegcetacoplan: EMPAVELI® is the first PNH treatment that binds to complement protein C3. It was approved by the Food and Drug Administration in May 2021 for treating adult patients with paroxysmal nocturnal hemoglobinuria (PNH). EMPAVELI is given skin (subcutaneously) by using the Empaveli injector or with an… , uh, or EMPAVELI, also reduce the incidents of the blood clot. Which is a, is a very good thing. 
Uh, blood thinners, uh, very often used, in different group of patient, not PNH patient for prevention of the blood clots. But in PNH patients, the blood thinners for prevention of the blood clots, not very o- often used, because there- there are risks that exceed their benefits. However, eh, in patients, with PNH, in situation when the, uh, risk of the blood clots are pretty high... Such as during the surgeries, uh, prolonging immobilization. Um, and when PNH clone is quite high, uh, blood thinners can be considered for short term to prevent, uh, blood clot formation.
Uh, if blood clots already happened, and unfortunately, despite the use of the treatments, then the blood thinners, uh, such as warfarin warfarin: It is used to prevent blood clots from forming. Warfarin is a tablet that is taken by mouth. , or Coumadin Coumadin: Coumadin (warfarin) is an anticoagulant (blood thinner). Reduces the formation of blood clots, which is important in the prevention of heart attacks, strokes and blockage of major veins and arteries. , uh, which is preferred drug for- for treatment of the blood clots. Uh, Lovenox, uh, injects, it's called. Uh, low molecular weight heparin heparin: Heparin is in a class of medications called anticoagulants ('blood thinners'). It works by decreasing the clotting ability of the blood. Heparin is also used to stop the growth of clots that have already formed in the blood vessels, but it cannot be used to decrease the size of clots that have… , um, can be also indicated. And typically, uh, the treatment, um, is- lasts for three to six months, uh, to get rid of the blood clots.
There are some oral formulation, oral blood thinners, uh, such as apixaban, or Eliquis, Dabigatran, or prodaxa, or rivaroxaban, or Xarelto. They can be also effective, um, in treatment of the blood clots in patients with PNH. But still, uh, we don't have enough data, and these drugs are not approved for, um, PNH related thrombosis.
So the patients who when they, uh, develop with a well-controlled on, uh, oral compliment inhibitor. And it appears to be safe to just continue blood thinner blood thinner: A medicine used to stop blood clots from forming. Blood thinners can be used to treat or prevent clots. Some common blood thinners are enoxaprin (Lovenox), heparin (Calciparine or Liquaemin), and warfarin (Coumadin). Also called and anticoagulant or thrombopoiesis inhibitor. after blood, after treatment for three to six months, if blood clot disappears. However, some patients with who develop the, uh, blood clots, while being on compliment inhibitor, uh, usually we'll recommend to continue a blood thinner indefinitely, because the risk of recurrent thrombosis is very, very high. In patients with recurrent blood clots, they require blood thinners, indefinitely.
 And I just want to emphasize in terms of their, uh... That abnormal, blood clotting has been recognized, one of the leading causes of death in patients with PHN. So it's very important to be aware of those, and uh, prevent their formation as much as possible. And so prevention and effective early treatment of thrombosis is very, very important. Currently approved therapies, and several investigational therapies that will be approved in the future, uh, show to effectively prevent development, uh, of these life-threatening conditions.
Leigh Clark:    10:09    Cool. Thank you so much, Dr. Norkin, for sharing your time and your expertise with all of us today. And if you'd like to find out more about PNH or any other bone marrow failure bone marrow failure: A condition that occurs when the bone marrow stops making enough healthy blood cells. The most common of these rare diseases are aplastic anemia, myelodysplastic syndromes (MDS) and paroxysmal nocturnal hemoglobinuria (PNH). Bone marrow failure can be acquired (begin any time in life) or can be… disease, you can find information on our website, at aamds.org. You can also follow us on our social media. Facebook, Instagram, or Twitter. And you can also give us a call on our help line, at 800-747-2820. This concludes our podcast.
Thank you, Dr. Norkin.
Dr. Maxim Norkin:    10:46    Thank you.