The Atypical HUS Foundation

aHUS Myths vs. Facts

 

Dispelling Common Misperceptions in aHUS

Presented to The Western Pennsylvania-Allegheny Health System (WPAHS)

at Pittsburgh, PA on February 20,2013 (Revised Aug. 2013)

 

by Robert B. Kaplan, MD

             

 

      Within the last two decades, major advances in our understanding of the thrombotic microangiopathies has  greatly expanded the boundaries of our knowledge base and enabled us to view these disorders in a  fresh perspective. Misconceptions existed concerning aspects of the disease relevant to securing the correct diagnosis and selecting the optimal treatment approach. A concise summary of the new disease concepts which have replaced previously held misperceptions should prove useful to both patients and their caretakers struggling to grapple with this perplexing disorder.

 

  1. MYTH: aHUS is predominantly a disease diagnosed in children and adolescents.

FACT:   In the largest European cohort of aHUS patients, 41 % of patients were diagnosed after age 18. Age at   diagnosis can range from infancy to the later decades of life.

 

  1. MYTH: aHUS organ involvement is limited to the kidneys, brain, gastrointestinal system, and heart.

FACT:   aHUS is a systemic disorder which can affect the microvascular bed of every organ.  The most commonly involved organ is the kidney.  Many patients have involvement of the neurologic, cardiovascular and gastrointestinal systems, with other organs affected less frequently. The take away message is that no organ has true immunity to this disease. This is due to the fact that many of the  complement regulatory proteins rendered dysfunctional by the disease play an important regulatory role in the various organs throughout the body.

 

  1. MYTH: Absence of renal failure definitively excludes aHUS.

FACT:   Approximately 20% of patients may have no signs of renal dysfunction at diagnosis. Although all patients ultimately develop renal dysfunction, it may only be detectable by the presence of protein and/or blood in the urine in some patients when still in its early stages.

 

  1. MYTH: As aHUS is primarily a heritable disease, genetic studies of complement-regulatory proteins are required for the diagnosis and play a practical role in diagnostically challenging cases.

 FACT:   Although genetic mutations are estimated to be causal in approximately 90% of patients (10% acquired), in clinical trials, they have been documented in only about 50% of cases and are not necessary to establish the diagnosis. Testing requires several months to complete, is expensive, generally not reimbursed by health insurance, and only performed in  a few facilities in the country. This is not to say that the genetic information will have no utility, but rather, at the current time, it is has no practical role in facilitating the diagnosis.

 

  1. MYTH: Since eculizumab blocks  a key step in the pathway of  complement proteins (an integral component our immune system), drug administration should be deferred whenever the patient encounters a situation which would  pose a  challenge to their immune system (including  the immediate pre-operative and post-operative  periods)

FACT:   Eculizumab was purposefully designed to target only a specific (terminal) component of the complement pathway, i.e, the segment responsible for cell lysis, and does not affect the proximal aspects; therefore, the other functions of the complement system are left unaffected. For this reason, eculizumab should not be grouped in the same category with the more traditional and commonly used immunomodulatory drugs which are known to strongly suppress the immune system and have more dramatic side effects.  Morover, surgery, in general, is known to be one of the major triggers of aHUS disease activity and, consequently, discontinuing the drug in the peri-operative period may allow the disease to flare at a very inopportune time. Although there are currently no evidence-based guidelines regarding the use of eculizumab in the surgical setting (only anecdotal evidence is available), those clinicians who have had significant clinical experience with the drug  have not observed serious infections in their patients who stayed on  treatment schedule and  therefore, do not  routinely advocate treatment interruption in this scenario.

 

  1. MYTH: As aHUS and a related disease,TTP (thrombotic thrombocytopenic  purpura) belong to  the same family  of disorders known as the thrombotic microangiopathies (TMA’S), they  should have similar causes and mechanisms of disease and can therefore be managed with similar treatment strategies.

FACT:   aHUS and TTP do belong to the same family of diseases known as the thrombotic microangiopathies; however, despite having very similar clinical presentations (microangiopathic hemolytic anemia and organ injury), each of the major TMA’s (TTP, aHUS, and STEC-HUS) have a unique pathogenesis. While it is now clear that inherited derangements in complement regulatory proteins are the root cause of aHUS, TTP is believed to be driven by abnormalities in a distinct protein known as von Willbrand factor and, in most cases, is not hereditary. Historically, management did not require a strict distinction as TTP and HUS were commonly grouped as “TTP/HUS” and were treated with the same strategy, plasma-exchange. Today, differentiation is believed to be critical as currently recommended treatment strategies are divergent (eculizumab in aHUS/plasma-exchange in TTP), and the use of plasma-exchange in a substantial proportion of aHUS patients may prove to be wholly ineffective. In some aHUS cases, it is possible that the delay in implementation of eculizumab could potentially compromise outcomes.

 

 

 

Dr. Robert B. Kaplan, MD

Director, Hemostasis-Thrombosis Laboratory
The Western Pennsylvania Hospital

West Penn Allegheny Health System
Pittsburgh, PA 15224
Office PH: 412 -578-1605
Office FAX: 412-578-4391 

 

 

This information was derived from a component of  Dr. Kaplan's  formal  slide  lecture entitled "Dispelling Common Myths in aHUS" presented at The Western Pennsylvania-Allegheny Health System (WPAHS) in  Pittsburgh, PA, 02/20/2013,  as part of the weekly Core Curriculum Conference within  the health system's  hematology-oncology  fellowship program. The target audience included hematology-oncology fellows as well as key faculty members of  the Division of Hematology and Cellular Therapy.

     Dr Kaplan is a key faculty member within the Division of Hematology and Cellular Therapy of The Western Pennsylvania-Allegheny Health System and a member of Alexion's aHUS Speaker's Bureau.

 

 

 

 

 

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NEW DIAGNOSIS OF aHUS?
Be proactive! Get the medical basics of aHUS, what lab values to monitor, and areas of concern...check out the "aHUS Bootcamp" and "About aHUS" tabs at the top of this page!
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Did you know...

CFH (Serum Complement Factor H) is a regulatory protein. The secreted protein product of CFH consists of 20 repetitive units named "short consensus repeats" or SCRs (each approximately 60 amino acids). In patients with aHUS the last 5 "pearls" in the twenty pearl strand protein, SCR16 - SCR20, should bind to protect cells but do not- they are defective in one or more of the last 5 SCR locations. If they cannot bind or stick to the kidney to protect that tissue, the platelets clump into clots that affect the glomeruli of the kidney -potentially causing acute renal failure.
  
• • • • • • • • • • • •
  
It is estimated that there are about 2 cases of aHUS in the U.S. per 1,000,000 of population, and about 60% of aHUS patients are diagnosed as children. The condition is potentially life threatening, and either can be chronic or can recur at intervals.
  
more factoids...

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