Needs Assessment on PNH and aHUS - CARE Hematology Faculty Update

Rare Hematological Disorders — Focus on PNH and aHUS

Both Paroxysmal Nocturnal Hemoglobinuria (PNH) and Atypical Hemolytic Uremic Syndrome (aHUS) are extremely rare, chronic, debilitating disorders.

While PNH is rare, it warrants our attention because PNH kills. It is diagnosed at all ages with the median age being early 30's. There is a 5 year mortality rate of 35%, which may come as a result of being undiagnosed for years. It is possible that PNH may be overlooked or even misdiagnosed as the signs and symptoms are nonspecific, heterogeneous, and often similar to those of other diseases.

aHUS is similar to PNH in that it is often undiagnosed or misdiagnosed given the heterogeneity and non-specificity of symptoms. aHUS can be genetic, acquired, or idiopathic with  more 50% of all patients dying, requiring kidney dialysis or having permanent kidney damage within 1 year of diagnosis.

In early November of 2013, a needs assessment on PNH and aHUS was distributed by CARE Faculty to Canadian hematologists.

This questionnaire focused on; testing and identification of these rare hematological disorders, current therapy choices, and current level of comfort/experience in treating and diagnosing these disorders. Select results of this needs assessment can be found below.

PNH

What is your comfort level in treating patients diagnosed with PNH?

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Do you believe there is a standard treatment for PNH?


Part two of this question asked, "If yes, what is it?":

Of those who responded yes, 100% indicated they believe the standard of care is eculizumab. One responder indicated that in addition to eculizumab, they would use anti-coagulants to treat VTE.

It is surprising that the majority of responders (60%) have a low to average comfort level with treating patients diagnosed with PNH, as there is therapy available. This level of comfort could be attributed to the rarity of the disease, with many physicians seeing few to no PNH patients in a given year. Eculizumab dramatically alters the natural course of PNH, reducing symptoms and disease complications as well as improving survival to the extent that it is equivalent to that of the general population. It reduces hemolysis and transfusion requirements, and improves measures of fatigue, when added to ongoing immunosuppressive therapy (IST) in patients with both paroxysmal nocturnal hemoglobinuria (PNH) and bone marrow insufficiency (BMI), including aplastic anemia (AA). These conditions must be treated simultaneously.
— CARE Hematology Faculty

ASH 2013 Abstract of Interest

ASH 2013 Abstract 1242: Paroxysmal Nocturnal Hemoglobinuria and Thrombosis Before and After Eculizumab. Cristina Muñoz-Linaresw et al.

Conclusions: After introduction of Eculizumab, sixteen patients have been treated with this drug and active thrombosis resolved in all cases, as was the case of a patient with a large persistent thrombosis in the inferior cava vein despite the isolated anticoagulation therapy. Only one patient on Eculizumab therapy experienced a thrombotic event and suffered a transient ischemic attack with aphasia after a prolonged catheter ablation procedure for an atrial fibrillation. This patient had previous signs of small vessel disease in MR imaging techniques. The episode occurs despite heparin anticoagulation and anticipated additional Eculizumab dose and resolves thereafter.

Eculizumab had a clear favourable impact in preventing thrombosis complications in our series of PNH patients. Careful monitoring of LDH levels and shortening the Eculizumab interval doses it is indicated in any chirurgical or invasive procedures in these patients.


aHUS

To what extent do you agree with the following: There is sufficient testing and diagnosis of aHUS.

What is your comfort level in treating patients diagnosed with aHUS?

Again, with the rarity and difficult identification of aHUS symptoms, the results of the above questions are not surprising. It is possible that an increased understanding of pathophysiology may directly improve the diagnosis, care, and treatment of aHUS. For this reason it is clear that there is a need for more education on how to identify and treat this rare disorder.
— CARE Hematology Faculty

ASH 2013 Abstract of Interest

ASH 2013 Abstract 1242:  Alternative and Terminal Complement Pathway Biomarkers At Presentation More Precisely Define The Clinical Diagnosis Of aHUS. Spero R Cataland et al.

Conclusions: Complement biomarkers of the alternative and terminal complement pathway may more precisely define the diagnosis of aHUS.  These hypothesis generating data suggest that pre-treatment complement biomarkers provide valuable information in the diagnosis of aHUS and could be useful in the prediction of response to eculizumab.