Expert Sheds Light on Rare Complement-Mediated Hematologic Disorders

Gina Columbus @ginacolumbusonc
Published Online: Thursday, May 18, 2017

Ronald S. Go, MD

Ronald S. Go, MD

Thrombotic microangiopathy (TMA) and paroxysmal nocturnal hemoglobinuria (PNH) are 2 of several rare hematologic disorders that, although not malignant, can lead to extreme complications for patients.

The causes vary, but these complement-mediated hematologic disorders have treatments lined up if diagnosed accurately and in a timely fashion. Moreover, to build awareness and educate the public further on these rare diseases, Mayo Clinic researchers published a Mayo Clinic Proceedings consensus statement on the complement alternative pathway and TMA diagnosis and management.

“These are rare diseases we should always be on the lookout for,” said Ronald S. Go, MD. “However, we shouldn’t be overly enthusiastic to make a diagnosis, because they are rare. Many common diseases will present the same way, and probably 9 out of 10 times it is going to be the common diseases, rather than these rare diseases. However, once we make a diagnosis, it is very helpful to know what is the right approach and what is the right treatment.”

In an interview with OncLive, Go, an associate professor of medicine at Mayo Clinic, provided perspective on these rare hematologic diseases, including how community physicians can properly diagnose and treat them. Go lectured on the topic during the 2017 OncLive® State of the Science Summit on Hematologic Malignancies.

OncLive: Can you provide some information on these rare disorders?

Go: My task was to talk about the complement-mediated hematologic diseases. It is not exactly cancer or malignancies, but these are not-so-common conditions that are seen in practice but can be very challenging to treat.

First, I spoke briefly about the complement pathway and some of the diseases, particularly hemolytic anemias that have pathogenesis or pathophysiology related to the complement pathway, and how current research and even clinical practice is utilizing drugs that target complement to treat these disorders. The 2 main disorders I discussed are TMA and PNH.

The bottom line here is, at our group at Mayo Clinic, we have developed a working group to address how to approach patients presenting with a TMA-like picture. TMA is a complicated condition because it can be due to a dozen disorders and treatment can vary according to the causes or the types. 

It is a broad differential diagnosis and you need to know what labs to order, how to diagnosis and, when the diagnosis is made, how to treat the conditions.

For PNH, the diagnosis is more straightforward. I spoke about how patients present and how they are diagnosed but went straight to how physicians treat these patients. 

Where exactly do these disorders stem from?

These are rare disorders. There are probably a couple hundred—if not less than 1000—overall cases in the country every year. Where do they come from? These are conditions in which the red cells are destroyed so there is hemolysis and platelets are consumed.

The commonality is, at least for TMA, clots are formed in the body so there is thrombosis and organ damage—whether it is the heart, myocardinfarct, prominent renal failure, or a stroke. Those are the consequences.

PNH can affect the kidneys, [cause] blood clots, and not so much affect the brain, but it can have a lot of complications. 

Can these conditions transform to hematologic malignancies?

That is a very good question. For the most, part, with TMA, the disease is not associated with cancer, although it can occur in the setting of a cancer. For PNH, it is actually not uncommonly associated with some hematologic malignancies, including myelodysplastic syndromes and aplastic anemia—which is not malignant but the treatment is actually bone marrow transplant, so it is very similar to hematologic malignancies.

Are these types of disorders often misdiagnosed? 

I have to say that, yes, the diagnosis can be missed, especially for PNH, because it is so rare. It is likely that, for a community hematologist who is not specializing in PNH, one may see 1 case in 10 years. For TMA, it is also very uncommon and [physicians may see] probably 1 case per year. It is that rare.

However, for most clinicians it would be easy to suspect TMA because there are signs in the blood smear, histiocytosis, low platelets, and hemolytic anemia. Therefore, it is frequently suspected to be TMA, but most of the time it is not TMA because it is such a rare disease. 


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