CORONARY ARTERIES BY PASS IN A B-HEMOPHILIAC WITH INHIBITOR AGAINST F-IX. PE Makris, Poumbouridou E,

Constantinidis C, Pithara E.. Thromb Haem Unit, A' Med. Prop. Clinic Univ of Thessaloniki- Greece.

It is widely stated that about 10% of all hemophilia patients develop antibodies against coagulation factors given as replacement therapy during bleeding episodes. The molecular mechanisms found responsible in hemophilia B patients are highly heterogeneous. Among them, point mutations are responsible for about 95% of all disorders. The development of FIX inhibitor in no- haemophiliacs is extremely rare, and is mainly reported in multi-parum women and in patients with auto immune diseases. It should be stressed that the titre of the inhibitor is a necessary information either for the treatment of acute situations and especially for the organisation of operations. A great number of sophisticated and expensive strategies have been designed to decrease the titre of the inhibitor such as a) High doses of FIX ,enough to neutralise FIX inhibitor and increase FIX level up to 40% to 80%,an approach extremely expensive. b) Plasmapheresis. c) Immune suppression, of inhibitor' s production. d) Use of agents capable to activate the final common pathway of the coagulation cascade, independently of FVIII or FIX .

Our case. We described a 64 year-old haemophiliac, FIX 9%, with inhibitor, titre 1,5 Oxford units, and occlusion of three coronary arteries, who successfully underwent coronary by-pass. The diagnosis of hemophilia B and FIX inhibitor was made because of an uncontrolled bleeding during the cardiac catheteriazation. He refereed minor hemorrhagic manifestations since his childhood. The operation was performed after successful suppression of inhibitor' s production using a five-days regimen of i.v cyclophosphamide after incubation with concentrated monoclonal FIX. During the operation and until the third postoperative day the patient was given FIX 100 unit/KgBW/8h. No rebound phenomenon was detected in his three month's follow up.

MULTI-POTENTIAL ANTIBODIES AGAINST ACTIVATED PLATELETS ACTIVATION THROUGH Gp-Ib. PE Makris, Gerotjiafas G, Kritsepi M, Zarifi M, Pithara E, Xanthopoulos V, Poumbpouridou E. Thromb Haem Unit, A' Med Prop Clinic of the Univers of Thessaloniki-Macedonia-GRECCE.

The production in rabbits, multi-potential, aggregation stimulating, antibodies against activated human platelets, MaK-1, leads us to try to define their function and molecular structure. It is well-known that monoclonal inhibiting or stimulating antibodies could be revealed in vitro. T he stimulating antibodies act by binding with low molecular weight protein, molecules such as CD9, and induce platelet aggregation, either by activation of the immune response receptors, FcγRII, or by complement activation. These pathways can be checked using a) special monoclonal antibody (Mo- a) the Mo-a IV.3, for the FcγRII receptor, which inhibits the aggregation. b) special Mo-a, the leupeptin, which inactivates the complement, c) having in mind that the functional activation of platelets is based on glycoproteines Gp-Ib-IX, IIb-IIIa, Ia-IIa, Ic-IIa, we used special Mo-abs to trigger or block their activation.

Materials and methods; Mo-abs mouse anti GpIIb-IIIa, GpIb, GpIIIa from DAKO company. Mo-ab IV.3 and Mo-ab Pl2-49 were kindly offered by Dr Lecompte. We checked the functional properties of multipotential Mak-1 in PRP and using the computerised aggregometre platelet ionised calcium Chrono-Log Co.

Results; Platelet aggregation; a) Incubation of Mo-a IV.3 for three minutes in PRP can not inhibit plts aggregation triggered by Mak-1 abs. b) The addition of Pl 2-49 did not modify platelet aggregation induced by Mak-1 abs. c) Addition and incubation, for three minutes, of Mo-ab GpIIb-IIIa did not inhibit aggregation by Mak-1. We have the same results with Mo-ab GIIIa. d) Platelet response was reduced with Mo-a GpIb addition. ATP secretion; We detected ATP release in all experiments resulting in platelet aggregation. The results lead us to conclude that the activation of platelets is mediated through complement and Gp Ib-IX complex.