Supplemental materials
Suppl. case review
Case 1: A 32-year-old Japanese woman with FXIII-B deficiency (Patient 1 from ref.3), who was born of a consanguineous marriage, had a mild bleeding tendency. She had a low level of FXIII activity (24%) and an undetectable level of FXIII-B antigen (<2%), while her platelet FXIII-A level was normal [50]. At the age of 31, she showed massive vaginal bleeding just before term and abnormal bleeding at the suture site after undergoing an emergency caesarean delivery. She was transfused with 5 units of concentrated red blood cells and 5 units of fresh frozen plasma. The half-life of FXIII-A determined from the disappearance curve of infused placental FXIII-A concentrate was as short as 3 days, and the 1st phase of the half-life seemed to be much shorter than 3 days [50] as observed in Case 9 [46] as well.
Case 2: This patient was a 35-year-old woman (personal communication from Dr. M. Saito of Kanazawa Univ. by E-mail in Feb. 2012), the sister of Case 1 and Case 3. She had low FXIII activity (<10%), and she experienced severe postpartum hemorrhage twice [50].
Case 3: This patient was a 30-year-old man (personal communication from Dr. M. Saito of Kanazawa Univ. in Feb. 2012), the brother of Case 1, and had low FXIII activity (10% of the normal) and an undetectable level of FXIII-B antigen (<2%), although any bleeding symptom was described [50].
Case 4: A 30-year-old Italian woman with a history of mild bleeding events [48] had FXIII-B deficiency (Case II-2 in ref.49). Her FXIII-B antigen level was undetectable (<5%) and she showed an extremely low level of FXIII activity (1%), although the platelet FXIII-A antigen level was within the normal range [49]. She had always had heavy menstruation. At the age of 19 years, she showed vaginal bleeding throughout the pregnancy and profuse postpartum bleeding. She was transfused with 3 units of whole blood to arrest the bleeding. At the age of 20 years, she again showed vaginal bleeding and postpartum hemorrhage, and she received blood transfusion (not specified). She had miscarriages accompanied with profuse bleeding at ages of 23 years and 25 years.
Case 5: A 33-year-old woman, the sister of Case 4 (Case II-1 in ref.49), had a history of mild bleeding [48]. She also had an undetectable FXIII-B antigen level (<5%) and a very low level of FXIII activity (3%), while her platelet FXIII-A antigen level was within the normal range [49]. She developed postpartum hemorrhages and was transfused with 1 unit of fresh whole blood.
Case 6: Another 34-year-old Italian woman (Case II-1 from Family 1 in ref.50) had low levels of both FXIII-A antigen (<10%) and FXIII-B antigen (<10%) along with a low FXIII activity (<10% of normal) [51]. She showed initial symptoms of moderate bleeding tendency at the age of 8 years. Her menstruation cycles had always been prolonged and heavy. She had twice experienced profuse postpartum hemorrhages.
Case 7: A 22-year-old Japanese non-pregnant woman (Patient 4 in ref.3) did not experience any obstetrical problems. Her FXIII activity was less than 10% of the normal, and FXIII-B antigen was undetectable. She was diagnosed with congenital FXIII-B deficiency on the basis of the observation of delayed-bleeding after an orthopedic surgery.
Case 8: This case of complete FXIII-B deficiency was a 1-year-old boy (Patient 5 from ref.3). His FXIII activity was 5-10% of the normal and FXIII-B antigen was undetectable. He was diagnosed with congenital FXIII-B deficiency through umbilical bleeding, which is a typical symptom of severe congenital FXIII-A deficiency but not of congenital FXIII-B deficiency.
Case 9: A Hispanic woman (Patient 7 in ref.46) with no history of obstetrical problems was diagnosed with congenital FXIII-B deficiency, because she had a long history of menorrhagia and postsurgical bleeding. Her age had not been specified (one of 11 subjects; age range, 19-76 years and median age, 21 years; ref.46). She had undetectable FXIII levels (both FXIII-B and A2B2 tetramer). The half-life of FXIII activity in plasma after infusion of 50 U/kg recombinant FXIII-A was about 9 hrs in this patient, although the measurement was discontinued at 24 h [46].
Case 10: A 32-year-old Indian man with congenital FXIII-B deficiency was reported by a German group (Patient D from ref.4). He showed FXIII activity less than 2% of the normal and a FXIII-B antigen level less than 0.1% of the normal. He manifested bleeding symptoms after circumcision and dental extraction. He also showed abnormal wound healing, a symptom never observed in other cases with congenital FXIII-B deficiency. Further investigation of this case may help us understand why only one-third of the cases with congenital FXIII-A deficiency experience abnormal wound healing.
Case 11: A 68-year-old Japanese man showed FXIII activity of 5% of the normal and had an undetectable level of FXIII-B antigen (paper in preparation by Wada and Ichinose). At the age of 74 years, he manifested spontaneous intramuscular bleeding. This is the oldest case of complete congenital FXIII-B deficiency, which has been first diagnosed in the elderly. His bleeding symptoms worsened since he was complicated by thrombocytopenia and FXIII-B alloantibodies.
Suppl. Table 1. FXIII replacement therapy prevents miscarriage in patients with severe congenital FXIII-A deficiency.
*; Personal communication from Dr. V. Schroeder of Bern Univ. by E-mail in Feb. 2012, +; low birth weight (770g) dead of intracranial bleeding after 7 days, Caesar; caesarean section, conc.; concentrates, Cryo.; cryoprecipitate, n.d.; not described
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