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Semin Thromb Hemost 2010; 36(6): 573-574
DOI: 10.1055/s-0030-1262878
PREFACE

© Thieme Medical Publishers

Hemolytic Uremic Syndrome

Emmanuel J. Favaloro1
  • 1Department of Haematology, ICPMR, Westmead Hospital, Westmead, NSW, Australia
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Publication History

Publication Date:
23 September 2010 (online)

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Welcome to another issue of Seminars in Thrombosis and Hemostasis. Reinhard Würzner and Lothar-Bernd Zimmerhackl have gathered together a collection of articles that review several different aspects of the disorder known as hemolytic uremic syndrome (HUS).

Thrombotic microangiopathies (TMAs) are microvascular occlusive disorders characterized by mechanical hemolytic anemia (low level of hemoglobin, high levels of lactate dehydrogenase, undetectable level of haptoglobin, and schizocytes in the peripheral blood smear), thrombocytopenia (low platelet counts), and organ disorders (mainly brain and renal dysfunction).[1] These symptoms are caused by increased platelet aggregation and thrombus formation, leading to hampered microcirculation and reduced organ perfusion. TMA may take several forms but is classically separated into two diseases: thrombotic thrombocytopenic purpura (TTP) and HUS, which are idiopathic or secondary to other diseases.

TTP affects mainly the brain; ~80% of cases are associated with a deficiency of ADAMTS-13, a metalloprotease that otherwise would cleave von Willebrand factor within platelet-rich thrombi to prevent hemolysis, thrombocytopenia, and tissue infarction. The deficiency can be inherited or acquired (anti-ADAMTS-13 autoantibodies).[1] [2]

HUS is characterized by the simultaneous features of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Although HUS has several underlying etiologies, it can generally be classified into three subtypes:

Typical: Representing > 90% of HUS cases in developed countries and mainly found in childhood. This form of HUS follows gastrointestinal infection with enterohemorrhagic Escherichia coli, and the etiology develops largely as a complication of the infection with Shiga toxin–producing bacteria. The many serious consequences of this disease include hematologic, intestinal, renal, and cerebral sequelae. The bacterial infection triggers lesions in the host by the interaction of its factors with host cells, first at the mucosal level, followed by binding to blood cells and transfer to target organs. Ultimately this leads to endothelial cell injury and platelet activation, resulting in a prothrombotic state. Atypical and secondary to other infections: Pneumococcal pneumoniae or HIV, drugs (quinine, calcineurin inhibitors, chemotherapy), superimposed to other pathologies (malignancy, systemic lupus erythematosus, and antiphospholipid antibody syndrome), or, rarely, to defective cobalamin metabolism. Atypical HUS (aHUS) and idiopathic HUS: HUS without any identifiable causes.

aHUS, sometimes referred to as diarrhea-negative HUS, may have a familial or sporadic nature, is often associated with complement disorders, and reflects a differing etiology than typical HUS. However, complement also plays an important role in the etiology of typical HUS and leads to tissue damage predominantly in the kidney, which may also directly or indirectly result in activation of the clotting system. DEAP-HUS (deficiency of CFHR plasma proteins and factor H [FH] autoantibody positive HUS) is a newly identified form of aHUS characterized by a deletion of genes coding for FH–related proteins and the presence of autoantibodies directed to FH. These disease-associated autoantibodies inhibit FH (CFH) surface binding functions, which results in a defective regulation of the alternative pathway and damage of endothelial cells.

In the past 20 years, hereditary or acquired complement abnormalities have been found in most aHUS cases. Typical and atypical HUS share histological lesions of thrombotic microangiopathy that affect kidney mainly glomeruli and arterioles and eventually lead to disturbed microcirculation and reduced organ perfusion. The arterial changes can be assessed in terms of degree, ranging from mild to severe. In contrast to typical HUS, aHUS has a poor outcome and a high risk of recurrence.

The current issue includes articles on diagnosis, pathophysiology, and treatment of both typical HUS and aHUS. The most recent issue of Seminars in Thrombosis and Hemostasis that featured HUS was published in 2006, in a volume on thrombotic microangiopathies.[3] Accordingly, although HUS is a relatively rare disease, this fact, together with the growth of knowledge in this area over the past decade, provides more than enough justification for the publication of this issue. Both guest editors of the current issue contributed to the previous issue published in 2006,[4] with Lothar-Bernd Zimmerhackl contributing additional articles to Seminars in Thrombosis and Hemostasis on this topic over the past decade,[5] [6] [7] [8] and so it is also fitting that they have put together the content of the current issue.

The first three articles in this issue discuss typical HUS. Karpman et al discuss the pathophysiology of typical HUS;[9] Zimmerhackl et al,[10] the bacteriology and clinical presentation of enterohemorrhagic Escherichia coli O26:H11–associated HUS; and Bitzan et al,[11] the treatment of typical HUS. The involvement of complement in HUS is then covered by Oppermann and Würzner[12] and Orth and Würzner.[13] Skerka et al[14] focus on the autoimmune disease DEAP-HUS in the next article, and a review of anti-factor H autoantibodies associated HUS by Dragon-Durey et al follows.[15]

aHUS is covered in articles by Moglie et al,[16] who discuss aHUS associated with mutations in complement regulator genes, and Kavanagh et al,[17] who examine transplantation in aHUS. Addition articles on the treatment of aHUS by Emlen et al,[18] Köse et al,[19] and Loirat et al[20] complete this issue.

I hope the readers of Seminars in Thrombosis and Hemostasis enjoy this compilation of articles on HUS. I am indebted to Reinhard Würzner and Lothar-Bernd Zimmerhackl for putting this interesting issue together, and I thank all the authors for their worthy contributions.

REFERENCES

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