title: Effects of Factor XIII Deficiency on Thromboelastography. Thromboelastography with Calcium and Streptokinase Addition is more Sensitive than Solubility Tests.
abstract: BACKGROUND
  Homozygous or double heterozygous factor XIII (FXIII) deficiency is characterized by soft tissue hematomas, intracranial and delayed spontaneous bleeding. Alterations of thromboelastography (TEG) parameters in these patients have been reported. The aim of the study was to show results of TEG, TEG Lysis (Lys 60) induced by subthreshold concentrations of streptokinase (SK), and to compare them to the clot solubility studies results in samples of a 1-year-old girl with homozygous or double heterozygous FXIII deficiency.
  
  
  METHODS
  A year one girl with a history of bleeding from the umbilical cord. During her first year of life, several hematomas appeared in soft upper limb tissue after punctures for vaccination and a gluteal hematoma. One additional sample of a heterozygous patient and three samples of acquired FXIII deficiency were also evaluated.
  
  
  METHODS
  Clotting tests, von Willebrand factor (vWF) antigen and activity, plasma FXIII-A subunit (pFXIII-A) were measured by an immunoturbidimetric assay in a photo-optical coagulometer. Solubility tests were performed with Ca(2+)-5 M urea and thrombin-2% acetic acid. Basal and post-FXIII concentrate infusion samples were studied. TEG was performed with CaCl2 or CaCl2 + SK (3.2 U/mL) in a Thromboelastograph.
  
  
  RESULTS
  Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, fibrinogen, factor VIIIc, vWF, and platelet aggregation were normal. Antigenic pFXIII-A subunit was < 2%. TEG, evaluated at diagnosis and post FXIII concentrate infusion (pFXIII-A= 37%), presented a normal reaction time (R), 8 min, prolonged k (14 and 11min respectively), a low Maximum-Amplitude (MA) ( 39 and 52 mm respectively), and Clot Lysis (Lys60) slightly increased (23 and 30% respectively). In the sample at diagnosis, clot solubility was abnormal, 50 and 45 min with Ca-Urea and thrombin-acetic acid, respectively, but normal (>16 hours) 1-day post-FXIII infusion. Analysis of FXIII deficient and normal plasma mixtures (< 2-102% of pFXIII-A), showed that Ca-urea solubility was abnormal at pFXIII-A < 9%, thrombin-acetic acid at pFXIII-A<18%, but TEG MA and elasticity at 23% and Lys60 with SK at pFXIII-A< 40%.
  
  
  CONCLUSIONS
  TEG parameters MA and elasticity, and Lys 60 in TEG either with Ca(2+) or Ca(2+) and SK are more sensitive to low levels of pFXIII than solubility tests. The increased Lys60 induced by a subthreshold concentration of SK could probably reflect the clot characteristics "in vivo" in many patients with pFXIII levels between 5-40% and could be potentially considered as screening test.
authors.affiliation: Grupo Bioquímico. Laboratorio Central del Hospital Italiano de Buenos Aires; Instituto Universitario del Hospital Italiano.
authors.forename: M
authors.initials: M
authors.lastname: Martinuzzo
authors.affiliation: Grupo Bioquímico. Laboratorio Central del Hospital Italiano de Buenos Aires; Instituto Universitario del Hospital Italiano.
authors.forename: L
authors.initials: L
authors.lastname: Barrera
authors.affiliation: Servicio de Hematología y Oncología Pediátrica. Transplante de Médula Ósea del Hospital Italiano de Buenos Aires.
authors.forename: D
authors.initials: D
authors.lastname: Altuna
authors.affiliation: Servicio de Hematología y Oncología Pediátrica. Transplante de Médula Ósea del Hospital Italiano de Buenos Aires.
authors.forename: F Tisi
authors.initials: FT
authors.lastname: Baña
authors.affiliation: Servicio de Pediatría y Hematología del Hospital Iturraspe de Santa Fe.
authors.forename: J
authors.initials: J
authors.lastname: Bieti
authors.affiliation: Grupo Bioquímico. Laboratorio Central del Hospital Italiano de Buenos Aires.
authors.forename: Q
authors.initials: Q
authors.lastname: Amigo
authors.affiliation: Grupo Bioquímico. Laboratorio Central del Hospital Italiano de Buenos Aires.
authors.forename: M
authors.initials: M
authors.lastname: D'Adamo
authors.affiliation: Grupo Bioquímico. Laboratorio Central del Hospital Italiano de Buenos Aires.
authors.forename: M S
authors.initials: MS
authors.lastname: López
authors.affiliation: Grupo Bioquímico. Laboratorio Central del Hospital Italiano de Buenos Aires; Instituto Universitario del Hospital Italiano.
authors.forename: J
authors.initials: J
authors.lastname: Oyhamburu
authors.affiliation: Grupo Bioquímico. Laboratorio Central del Hospital Italiano de Buenos Aires; Instituto Universitario del Hospital Italiano.
authors.forename: J C
authors.initials: JC
authors.lastname: Otaso