D-Dimer Rapid Test

Congenital hypofibrinogenemia is a rare disorder caused by a number of different mutations in the fibrinogen genes. The aim of the study was the elucidation of molecular defects in two unrelated families with hypofibrinogenemia. DNA samples from the patients were screened for mutations in the fibrinogen genes by direct sequencing of polymerase chain reaction-amplified gene segments. Isolated plasma fibrinogen was studied by sodium dodecyl sulfate electrophoresis and electrospray ionization mass spectrometry in order to detect variant polypeptides. Fibrin polymerization was analyzed both in plasma and using purified fibrinogen samples. A novel mutation in the FGG gene (G7590A) was found in all patients from the two families with hypofibrinogenemia. This mutation causes the amino acid exchange 313 Ser -> Asn in the gamma chain. When plasma fibrinogen from a heterozygous individual was analyzed for the presence of variant gamma chains by reverse-phase high-performance liquid chromatography and electrospray ionization mass spectrometry, only normal gamma chains could be detected. The molecular defect affecting an evolutionary highly conserved amino acid residue in human fibrinogen interferes with plasma expression of the variant molecules and is causative for the observed hypofibrinogenemic phenotype.

Corticosteroids are extensively used in pediatrics, yet the burden of side effects is significant. Availability of a simple, fast, and reliable biochemical read out of steroidal drug pharmacodynamics could enable a rapid and objective assessment of safety and efficacy of corticosteroids and aid development of corticosteroid replacement drugs. To identify potential corticosteroid responsive biomarkers we performed proteome profiling of serum samples from DMD and IBD patients with and without corticosteroid treatment using SOMAscan aptamer panel testing 1,129 proteins in <0.1 cc of sera. Ten pro-inflammatory proteins were elevated in untreated patients and suppressed by corticosteroids (MMP12, IL22RA2, CCL22, IGFBP2, FCER2, LY9, ITGa1/b1, LTa1/b2, ANGPT2 and FGG). These are candidate biomarkers for anti-inflammatory efficacy of corticosteroids. Known safety concerns were validated, including elevated non-fasting insulin (insulin resistance), and elevated angiotensinogen (salt retention). These were extended by new candidates for metabolism disturbances (leptin, afamin), stunting of growth (growth hormone binding protein), and connective tissue remodeling (MMP3). Significant suppression of multiple adrenal steroid hormones was also seen in treated children (reductions of 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol and testosterone). A panel of new pharmacodynamic biomarkers for corticosteroids in children was defined. Future studies will need to bridge specific biomarkers to mechanism of drug action, and specific clinical outcomes.