A short half-life of the administered factor XIII (FXIII) concentrates after the first replacement therapy in a newborn with severe congenital FXIII deficiency.

doi:10.1160/TH11-09-0625 Thromb Haemost 2012; 107: 592–594 Dir Sirs, Factor XIII (FXIII) is a fibrin-stabilising factor which crosslinks fibrin monomers among themselves as well as to α2-plasmin inhibitor and fibronectin, and thus contributes to haemostasis, wound healing, and maintenance of pregnancy (1–3). Congenital FXIII deficiency is a rare haemorrhagic disorder. Umbilical bleeding in the neonatal period is characteristic and the most frequent symptom (4, 5). Intracranial haemorrhage is less frequent but the leading cause of death at all ages. Plasma-derived FXIII concentrates are available for the treatment of congenital FXIII deficiency. The response to infused FXIII is mostly excellent to get a good control of bleeding (6). Regular replacement therapy with FXIII concentrates is recommended for prophylaxis of bleeding (6–9). However, an appropriate interval of FXIII administration is not known in the neonatal period, because to our best knowledge no report has ever been published on the half-life of FXIII during this stage of a patient’s lifetime. Here, we report that the half-life of the administered FXIII concentrates was markedly shortened in a male neonate with severe congenital FXIII deficiency. A Japanese male baby was born after 36 weeks and six days of gestation with a birth weight of 2,446g by normal vaginal delivery. He has no family history of bleeding disorders, and his parents are non-consanguineous. He had hypoglycaemia after birth and received intravenous drip infusion of glucose. He had no problems with haemostasis after venipuncture such as injection and blood collection. However, excessive umbilical bleeding occurred on day 5. Umbilical bleeding stopped temporally after applying pressure, AgNO3, or suturing, but, every time, a large amount of blood was seen on a covering gauze within 12–24 hours after haemostasis. Blood clots were gelatinous and fragile. There were oozing without application of pressure. Laboratory examinations on day 5 revealed that platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, fibrinogen/fibrin degradation products, antithrombin, factors VIII, IX, and von Willebrand factor were within the normal ranges (see Suppl. Table 1, available online at www.thrombo sis-online.com). Umbilical stump bleeding recurred intermittently ( Fig. 1), and the patient developed severe anaemia (haemoglobin; Hb, 5.8 g/dl), and was thus transfused with red blood cell concentrate at 10 ml/kg on day 15. His FXIII activity was only 4% on day 12. Accordingly, he was diagnosed to have FXIII-A deficiency, which was confirmed by an amine incorporation assay, ELISA, and fibrin-crosslinking test (data not shown). In addition, Western blot analysis showed virtually no FXIII-A antigen in the patient’s plasma (see Suppl. Fig. 1, available online at www.thrombosis-online. com). Dot blot analyses using recombinant FXIII-A and FXIII-B (10) demonstrated negative results for anti-FXIII antibodies (data not shown). He was injected with FXIII concentrates at 80 U/kg on day 15 immediately after receiving the FXIII result. His umbilical bleeding stopped promptly. Thereafter, he did not show any sign of bleeding, judging by any measure including magnetic resonance imaging, ultrasonography as well as