Acquired factor XIII (FXIII) deficiency due to autoantibody against FXIII is a very rare severe hemorrhagic diathesis. Antibodies directed against the A subunit of FXIII, which interfere with different functions of FXIII, have been described. Here, for the first time, we report an autoantibody against the B subunit of FXIII (FXIII-B) that caused lifethreatening bleeding in a patient with systemic lupus erythematosus. FXIII activity, FXIII-A 2 B 2 complex, and individual FXIII subunits were undetectable in the plasma, whereas platelet FXIII activity and antigen were normal. Neither FXIII activation nor its activity was inhibited by the antibody, which bound to structural epitope(s) on both free and complexed FXIII-B. The autoantibody highly accelerated the elimination of FXIII from the circulation. FXIII supplementation combined with immunosuppressive therapy, plasmapheresis, immunoglobulin, and anti-CD20 treatment resulted in the patient's recovery. FXIII levels returned to around 20% at discharge and after gradual increase the levels stabilized above 50%. IntroductionBlood coagulation factor XIII (FXIII) is a protransglutaminase of tetrameric structure (FXIII-A 2 B 2 ). 1,2 Its potentially active A subunit (FXIII-A) is synthesized in cells of bone marrow origin; it is also present in platelets and monocytes/macrophages in dimeric form (FXIII-A 2 ). The noncatalytic B subunit (FXIII-B) is in excess and it is essential for the stabilization of FXIII-A 2 in plasmatic conditions. FXIII is converted into an active transglutaminase (FXIIIa) by limited proteolysis of FXIII-A and by Ca 2ϩ -induced dissociation of FXIII-B. Cross-linking of fibrin ␣-and ␥-chains and ␣ 2 -plasmin inhibitor to fibrin by FXIIIa stabilizes fibrin and protects it from prompt elimination by plasmin. 3 Inherited FXIII-A deficiency is a severe bleeding diathesis with the high risk of intracranial bleeding in nonsupplemented patients. 4 Only 5 cases of inherited FXIII-B deficiency with mild-to-moderate bleeding tendency have been reported. [5][6][7][8] In the absence of FXIII-B, plasma FXIII activity and FXIII-A concentration were considerably decreased, whereas in platelets a normal amount of FXIII-A was measured. 9 Thirty-six cases of severe FXIII deficiency due to an autoantibody against FXIII-A have been reported. In a few cases, the autoantibody was characterized and classified into subgroups according to its inhibition of FXIII activation, FXIIIa activity, or binding to fibrin. [10][11][12][13][14][15] In about one third of the cases the autoantibody was associated with systemic lupus erythematosus (SLE). No report on an autoantibody directed against FXIII-B has been published so far. MethodsA 28-year-old woman suffering from SLE with end-stage kidney disease was on hemodialysis. For preparation of cubital fistula she was admitted to a county hospital. In the proximity of the surgical wound, hematomas developed that were explored. The wounds showed no tendency of healing and remained open. A few days later extensive intramuscular hematoma ...

Background and Purpose In infants with moderate to severe neonatal encephalopathy, whole body cooling to 33-34°C for 72 hours is standard care with a number needed to treat to prevent one adverse outcome of 6-7. The precise brain temperature providing optimal neuroprotection is unknown. Methods After a quantified global cerebral hypoxic-ischemic insult, 28 piglets aged <24h were randomized (each group n=7) to: (i) normothermia (38.5°C throughout), or whole-body cooling 2-26 h post-insult to (ii) 35°C, (iii) 33.5°C or (iv) 30°C. At 48h post-insult, delayed cell death (TUNEL and cleaved caspase 3) and microglial ramification (Iba-1) were evaluated. Results At 48h post-insult, substantial cerebral injury was found in the normothermia and 30°C-hypothermia groups. However, with 35°C and 33.5°C cooling, a clear reduction in delayed cell death and microglial activation was observed in most brain regions (P<0.05), with no differences between 35°C and 33.5°C cooling groups. A protective pattern was observed, with U-shaped temperature dependence in delayed cell death in periventricular white matter, caudate nucleus, putamen, hippocampus and thalamus. A microglial activation pattern was also seen, with inverted U-shaped temperature dependence in periventricular white matter, caudate nucleus, internal capsule and hippocampus (all P<0.05). Conclusions Cooling to 35°C (an absolute drop of 3.5°C as in therapeutic hypothermia protocols) or to 33.5 °C provided protection in most brain regions after a cerebral hypoxic-ischemic insult in the newborn piglet. While the relatively wide therapeutic range of a 3.5-5°C drop in temperature was reassuring, overcooling (an 8.5°C drop) was clearly detrimental in some brain regions.

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Antiphospholipid (aPL) antibodies entailing anticardiolipin (aCL) and anti-beta2 glycoprotein I (anti-beta2GPI) antibodies may be involved in a number of vascular diseases including coronary artery diseases (CAD) or stroke. Here we assessed the presence of aPL antibodies in acute coronary syndrome (ACS). The frequency of anti-beta2GPI antibodies was significantly higher (14.4%) in ACS in comparison to control healthy subjects (2%). In addition, serum concentrations of anti-beta2GPI antibodies were also increased in ACS. Anti-beta2GPI antibodies of the IgA isotype might be the most relevant for the onset and outcome of ACS. Regarding subclasses of ACS, anti-beta2GPI IgA antibodies were elevated in unstable angina (UA) and myocardial infarction with ST elevation (STEMI), but not in myocardial infarction without ST elevation (NSTEMI). The involvement of anti-beta2GPI antibodies in ACS was more pronounced in men than women, and in younger rather than older patients. Finally, anti-beta2GPI antibodies in ACS were associated with previous stroke, but not with hypertension or previous myocardial infarction. Thus, anti-beta2GPI antibodies may be involved in the thrombotic events underlying ACS.