The PB blood smear: frequent schistocytes, polychromasia and decreased platelets with increased proportion of large platelets. Kidney biopsy: fibrin thrombi. These findings indicate thrombotic microangiopathic anemia.
Shiga toxin test is negative.
ADAMTS13 WNL.
Factor H level decreased, Total complement Bb increased, soluble MAC (C5b-9) increased.
Diagnosis: Atypical Hemolytic Uremic Syndrome ( aHUS)
Shiga toxin test is negative.
ADAMTS13 WNL.
Factor H level decreased, Total complement Bb increased, soluble MAC (C5b-9) increased.
Diagnosis: Atypical Hemolytic Uremic Syndrome ( aHUS)
Lab workup diagnostic criteria for aHUS
• Nonautoimmune hemolytic anemia: CBC showing low hemoglobin levels, negative direct coombs test, positive test result for schistocytes in peripheral blood, low haptoglobin, increased serum lactate dehydrogenase (LDH) levels;
• Thrombocytopenia: CBC showing thrombocytopenia (count < 150,000/mm3 or drop greater than 25% from previous measure);
• Renal involvement: may be present with hematuria, proteinuria, edema, oliguria, hypertension, increased serum levels of urea and creatinine;
• Tests for involvement of other organs and systems should be carried out depending on clinical findings; TMA can affect any organ, the neurological system, the gastrointestinal tract, the heart, pancreas, liver etc.;
• Negative test results for STEC-HUS; rule out other causes of typical HUS;
• ADAMTS13 activity > 5%; if value is under 5, look for anti-ADAMTS13 antibodies;
• AH50, CH50, C3, and C4 activity: aHUS may be accompanied by decreased serum C3 and reduced alternative pathway activity measured by AH50; these findings, however, are not definitive, as even normal levels do not rule aHUS out.
• Nonautoimmune hemolytic anemia: CBC showing low hemoglobin levels, negative direct coombs test, positive test result for schistocytes in peripheral blood, low haptoglobin, increased serum lactate dehydrogenase (LDH) levels;
• Thrombocytopenia: CBC showing thrombocytopenia (count < 150,000/mm3 or drop greater than 25% from previous measure);
• Renal involvement: may be present with hematuria, proteinuria, edema, oliguria, hypertension, increased serum levels of urea and creatinine;
• Tests for involvement of other organs and systems should be carried out depending on clinical findings; TMA can affect any organ, the neurological system, the gastrointestinal tract, the heart, pancreas, liver etc.;
• Negative test results for STEC-HUS; rule out other causes of typical HUS;
• ADAMTS13 activity > 5%; if value is under 5, look for anti-ADAMTS13 antibodies;
• AH50, CH50, C3, and C4 activity: aHUS may be accompanied by decreased serum C3 and reduced alternative pathway activity measured by AH50; these findings, however, are not definitive, as even normal levels do not rule aHUS out.
Figure1. Diagnostic algorithm for the differential diagnosis of thrombotic microangiopathy. Abbreviations: TTP- thrombotic thrombocytopenic purpura; HUS- hemolytic uremic syndrome; HIV- human immunodeficiency virus; SLE- systemic lupus erythematous; APL- antiphospholipid syndrome; DIC- disseminated intravascular coagulation; STEC- Shiga toxin producing Escherichia coli; CFH- factor H, CFI- factor I; CFB- factor B; MCP- membrane cofactor protein; THBD-thrombomodulin; CFHR- CFH related gene; MLPA- multiplex ligation dependent probe amplification; DGKE -diacylglycerol kinase ɛ.
Treatment: Plasma exchange and complement inhibitor (Eculizumab).
http://www.ncbi.nlm.nih.gov/books/NBK1367/: Gene Review
Disease characteristics. Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. Typical (acquired) HUS is triggered by infectious agents such as strains of E. coli (Stx-E. coli) that produce powerful Shiga-like exotoxins, whereas atypical HUS (aHUS) can be genetic, acquired, or idiopathic (of unknown cause). Onset of atypical HUS ranges from prenatal to adulthood. Individuals with genetic atypical HUS frequently experience relapse even after complete recovery following the presenting episode. Sixty percent of genetic aHUS progresses to end-stage renal disease (ESRD).
Diagnosis/testing. Atypical HUS is considered genetic when two or more members of the same family are affected by the disease at least six months apart and exposure to a common triggering infectious agent has been excluded, or when disease-causing mutation(s) are identified in one of the ten genes in which mutations are known to be associated with aHUS, irrespective of familial history. The genes:
Treatment: Plasma exchange and complement inhibitor (Eculizumab).
http://www.ncbi.nlm.nih.gov/books/NBK1367/: Gene Review
Disease characteristics. Hemolytic-uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney and other organs. Typical (acquired) HUS is triggered by infectious agents such as strains of E. coli (Stx-E. coli) that produce powerful Shiga-like exotoxins, whereas atypical HUS (aHUS) can be genetic, acquired, or idiopathic (of unknown cause). Onset of atypical HUS ranges from prenatal to adulthood. Individuals with genetic atypical HUS frequently experience relapse even after complete recovery following the presenting episode. Sixty percent of genetic aHUS progresses to end-stage renal disease (ESRD).
Diagnosis/testing. Atypical HUS is considered genetic when two or more members of the same family are affected by the disease at least six months apart and exposure to a common triggering infectious agent has been excluded, or when disease-causing mutation(s) are identified in one of the ten genes in which mutations are known to be associated with aHUS, irrespective of familial history. The genes:
- CFH (encoding complement factor H and accounting for ~30% of aHUS;
- CD46 (MCP) (encoding membrane cofactor protein and accounting for ~12% of aHUS);
- CFI (encoding complement factor I; ~5%-10% of aHUS),
- C3 (encoding the third component of complement C3; ~5% of aHUS);
- CFB (encoding complement factor B; rare);
- THBD (encoding thrombomodulin; ~3%-5% of aHUS);
- DGKE (encoding diacylglycerol kinase; ~27% of aHUS manifesting before age 1 year)
- CFHR3, CFHR1, and CFHR4; deletions involving CFHR1 and CFHR3 or CFHR1 and CFHR4 account for ~5%-15% of aHUS