Effects of Factor XIII Deficiency on Thromboelastography. Thromboelastography with Calcium and Streptokinase Addition is more Sensitive than Solubility Tests

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. CASE: 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. MATERIALS AND 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 CaCl(2) or CaCl(2) + 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.