title: Neoplasm-induced bleeding in inherited, heterozygous FXIII-A deficiency.
abstract: Inherited mild factor XIII deficiency belongs to one of the most underdiagnosed bleeding disorders so far. This is, because most patients do not develop bleeding complications in daily life. Patient, methods: A man (age: 64 years) without a history of bleeding presented with painful swelling of neck, weight loss, anemia and episodic bleeding from the right tonsil necessitating tonsillectomy. Histologic and immunohistochemical evaluation revealed cytokeratin-positive epitheloid angiosarcoma. Blood coagulation status showed significantly elevated D-dimer and decreased FXIII levels (FXIII-activity 35%, FXIIIA-Ag 16-26%). Plasma mixing studies excluded neutralizing antibodies against FXIII.
  
  
  RESULTS
  A novel heterozygous F13A1 gene nonsense mutation (p.Glu103Ter, c.307G>T) was found confirming heterozygous FXIII-A deficiency. The same mutation was detected in two further asymptomatic relatives. For further clinical management the patient was transfused with FXIII-concentrate and showed an adequate increase of FXIII ruling out FXIII deficiency to be induced by increased turnover. Despite this haemostatic management and antifibrinolytic treatment the patient had to undergo several revisions due to delayed, Hb relevant bleeding after cervical lymph nodes extirpation and resection of tonsil. Two chemotherapy cycles with paclitaxel and palliative radiotherapy of the neck area were performed, but the patient died unfortunately two months after diagnosis.
  
  
  CONCLUSIONS
  It is a unique case showing the combination of a highly aggressive angiosarcoma and presence of inherited FXIII deficiency. It is also a rare example demonstrating the benefit of FXIII genotyping besides the expected acquired FXIII deficiency possibly due to neoplasm induced increased consumption by elevated crosslinking of fibrin fibers.
authors.affiliation: Vytautas Ivaškevičius, Institute of experimental Haematology and Transfusion Medicine, University Clinic Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany,, Tel. +49/(0)228/28 71 51 75, Fax +49/(0)228/28 71 43 20, vytautas.ivaskevicius@ukb.uni-bonn.de.
authors.forename: V
authors.initials: V
authors.lastname: Ivaškevičius
authors.forename: G
authors.initials: G
authors.lastname: Goldmann
authors.forename: A
authors.initials: A
authors.lastname: Biswas
authors.forename: P
authors.initials: P
authors.lastname: Westhofen
authors.forename: A
authors.initials: A
authors.lastname: Thomas
authors.forename: N
authors.initials: N
authors.lastname: Marquardt
authors.forename: S
authors.initials: S
authors.lastname: Horneff
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: H
authors.initials: H
authors.lastname: Rühl
authors.forename: B
authors.initials: B
authors.lastname: Pötzsch
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
mesh_terms: D003937:Diagnosis, Differential; D005176:Factor XIII / Q000235:genetics*; D005177:Factor XIII Deficiency / Q000151:congenital / Q000175:diagnosis* / Q000235:genetics*; D026122:Factor XIIIa / Q000235:genetics; D017809:Fatal Outcome; D006258:Head and Neck Neoplasms / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D006470:Hemorrhage / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: C064015:factor XIII subunit A; D005176:Factor XIII; D026122:Factor XIIIa
keywords: F13A1; F13B; FXIII; acquired FXIII deficiency; inherited FXIII deficiency