calca-protein--human and Hemolytic-Uremic-Syndrome

Thrombotic microangiopathy (TMA) comprises a group of microvascular thrombosis syndromes associated with multiple pathogenic factors. Deficient activity of ADAMTS13 is a pathogenic factor in a subset of TMA patients that provides a strong rationale for plasma exchange treatment. However, the subset of TMA patients with normal ADAMTS13 activity remains a heterogeneous group of patients in which the appropriate treatment is not well understood. In addition to the common forms of TMA thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome, the differential diagnosis of TMA may include sepsis, autoimmune disorders, and disseminated intravascular coagulation. Optimal treatment of TMA depends on timely recognition of treatable pathogenic factors. We hypothesized that sepsis is a rapidly identifiable pathogenic factor in a subset of TMA patients. To test this hypothesis, we retrospectively measured the rapid biomarkers of sepsis C-reactive protein (CRP) and procalcitonin (PCT), in a repository of pretreatment plasma samples from 61 TMA patients treated with plasma exchange. Levels were analyzed in 31 severely ADAMTS13-deficient and 30 ADAMTS13-normal patients. None of the 31 patients with severe deficiency of ADAMTS13 had elevated PCT. However, 11 of 30 (37%) non-ADAMTS13-deficient patient samples were strongly positive for PCT. These patient samples also had a >10-fold higher median CRP level than patients with normal PCT. We conclude that rapid assays may help identify sepsis in a subset of TMA patients.

Topics: ADAM Proteins; ADAMTS13 Protein; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Hemolytic-Uremic Syndrome; Humans; Protein Precursors; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies; Sepsis

Shiga toxin producing Escherichia coli (STEC) are noninvasive enteric pathogens that may cause hemorrhagic colitis (HC) and diarrhea-associated hemolytic uremic syndrome (D+ HUS). We hypothesized that development of D+ HUS is associated with increased serum procalcitonin (PCT) levels. PCT was measured by an immunoluminometric assay in 113 patients. Concentrations of PCT were different in normal controls, disease control groups (rotavirus enteritis, HC due to non-STEC pathogens, chronic renal failure), and children with uncomplicated O157:H7 HC or D+ HUS. Children with D+ HUS showed higher PCT levels than those with uncomplicated O157:H7 HC, and increased concentrations were noted in cases requiring peritoneal dialysis. Severely increased concentrations were observed in children with D+ HUS on d 5 or 6 after the onset of enteritis, whereas serial measurements in those with uncomplicated O157:H7 HC remained within the normal range throughout the first week of illness. PCT was correlated with serum concentrations of lipopolysaccharide (LPS)-binding protein and serum levels of alanine aminotransferase. Using two separate sets of real-time PCR primers, we were unable to detect elevated PCT mRNA transcripts in nonadherent undifferentiated (monocytic) or differentiated (macrophage-like) THP-1 cells stimulated with purified Shiga toxin-1 and/or LPS. Our data show that serum levels of PCT are associated with the severity of illness in children with D+ HUS. Further studies are needed to determine the role of PCT in the pathogenesis of thrombotic microangiopathy associated to childhood D+ HUS.

Topics: Adolescent; Animals; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Escherichia coli O157; Female; Hemolytic-Uremic Syndrome; Humans; Infant; Male; Protein Precursors; Retrospective Studies