Blood Clots in Patients with PNH, with Dr. Maxim Norkin | Aplastic Anemia and MDS International Foundation (AAMDSIF) Return to top.

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

Dr. Norkin explains why and how patients with PNH can develop blood clots, as well as prevention and treatment.


Leigh Clark:    00:00    Hi, everyone. This is Podcast for Patients, with the Aplastic Anemia & 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 oncologist 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?
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, 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, abdominal pain, enlarged liver, and fluid accumulation in the abdomen. Uh, sometimes thrombosis 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, inflammation within the lining of the blood vessels and platelet 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. 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 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, 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, or Coumadin, uh, which is preferred drug for- for treatment of the blood clots. Uh, Lovenox, uh, injects, it's called. Uh, low molecular weight heparin, 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 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 disease, you can find information on our website, at 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.