Anaphylactic Reaction After Replacement Therapy In Haemophilia B Patient with Inhibitor to Factor IX

Abstract

4662 Replacement therapy is a very hard challenge in haemophilia B with inhibitor. We describe the case of a child with severe haemophilia B and with a family history positive for development of inhibitor to factor IX (FIX) and for occurrence of allergic reaction after replacement therapy. Genetic analysis demonstrated an almost complete deletion of FIX gene. The child received replacement therapy first in his life when he was 5 years old because of the occurrence of a large haematoma of the left thigh. He was treated with recombinant FIX concentrate at the dosage of 30 IU/kg daily for three days and no inhibitor to FIX was evidenced after this therapy. Two months later the patient was treated with a single dose of recombinant FIX concentrate at the same dosage for the occurrence of a post-traumatic joint bleeding of the right knee. An inhibitor towards FIX (1.7 B.U.) was detected two weeks after this treatment and confirmed in a subsequent analysis performed after ten days (1.4 B.U.). One month later the patient was hospitalized for a post traumatic hemarthrosis of the right shoulder. In this occasion it was planned to treat the patient with recombinant FIX under careful monitoring in intensive care unit considering of the inhibitor. After the slow endovenous infusion of 200 IU of recombinant FIX concentrate we stopped immediately the administration because the child presented cough, mild respiratory failure, tachycardia, tongue and lips oedema, lips cyanosis, diffuse vasodilatation, psychomotor agitation. He received also hydrocortisone, antihistaminic by intramuscular injection and oxygen by facial mask. The presence of inhibitor towards FIX and anaphylactic reaction occurrence preclude forever any replacement therapy with FIX both recombinant and plasmatic (PCC and/or aPCC). After this episode the patient needed another hospitalization for a tonsil bleeding with severe anaemization. We treat him with recombinant activated FVII (rFVIIa) first at the dosage of 270 mcg/kg in bolus, and after at the dosage of 90 mcg/kg every three hours for one day with complete bleeding remission. We encourage the careful monitoring of inhibitor towards FIX in haemophilic B patients especially with large FIX gene deletion. It could prevent severe anaphylactic reaction during replacement therapy. Considering the previous anaphylactic reaction, in this child rFVIIa represents the only therapeutic option for bleeding management. Disclosures: No relevant conflicts of interest to declare.

The effect of finite roughness size and bulk thickness on the prediction of rubber friction and contact mechanics

“…In this section, we provide a brief summary of the RMD scheme developed elsewhere. [6][7][8] In particular, we consider the case of a rigid, periodically-rough surface (of L 0 periodic length, in both x-and y-directions, with small wavelength cut-off frequency q 0 ¼ 2=L 0 ) in steady sliding adhesionless contact with a body characterized by linear rheology, under isothermal and frictionless conditions. We assume the small deformation regime to apply, as well as a small square slope roughness h x ð Þ, with Figure 4, we show a schematic representation of the contact interface, in a reference moving with the rough sliding surface.…”

“…Finally, the relation between separation uðxÞ and interaction pressure ðxÞ is calculated within the Derjaguin's approximation, 14 and it can be written in terms of a generic interaction law 6,7 ðuÞ ¼ f ðuÞ ð 12Þ…”

“…However, the theory can be easily extended to other interaction laws. 7 Equations (10) to (12) are discretized on a regular square mesh of grid size in term of a residuals molecular dynamics process, 6,7 resulting in the following set of equations…”

“…Due to the (numerical) complexity of the underlying contact mechanics problem, involving multiple length and time scales, the friction force between viscoelastic solids under real contact conditions has so far only been predicted using mean field formulations of the contact mechanics, such as the one by Persson 1 or Klu¨ppel and Heinrich. 2 However, only very recently numerical procedures have been proposed to study rubber contact mechanics problems, based on a real-space formulation of the linearly viscoelastic half space contact problem [3][4][5] or on a residual molecular dynamics (RMD 6 ) scheme. The RMD method has so far has been successfully applied to the investigation of adhesive contacts between elastic solids with random roughness, 7 and extended to study the case of sliding contact between linear viscoelastic solids with random surface roughness.…”

Rough contact mechanics for viscoelastic graded materials: The role of small-scale wavelengths on rubber friction

“…The Poisson coefficient for the generic layer is assumed frequency-dependent, which makes the theory of more general applicability. This effective surface response will be then implemented in a Fourier-based residuals molecular dynamic (RMD) formulation of the contact mechanics [11][12][13], however, the same function might be easily embedded in the Persson's mean field analytical contact model as well. The RMD model will then be adopted to a focussed investigation of the role of small-scale roughness wavelengths on the rubber friction and contact area.…”