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Homozygous protein C deficiency in 3 unrelated adults
Vol. 65, Suppl. 1
ABSTRACTS OF 12TH INTNAT’L CONGRESS
S83
Cl61 FAMILIAL DYSFUNCTIONAL PROTEIN S (PS): IDENTIFICATION OF FOUR NJXWCASES CHARACTERIZEDBY REDUCEDCOFACTORACTIVITY AND NORMAL CONCENTRATIONOF THE FREE FORM. F. Franchi, E.M. Faioni, D. Asti, P.M. Mannucci. A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy. A PS-deficient family with a dysfunctional molecule in plasma was first described by Wannucci et al in 1989 (Thromb Haemostas 62: 763). The hallmarks of the diagnosis are: low levels of functional PS (activated protein C cofactor activity); normal concentrations of free and total PS; and a normal PS pattern on crossed immunoelectrophoresis. Since then we included among our routine screening for thrombophilia a fully automated, prothrombin time-based PS functional assay of PS which measures the cofactor activity of PS for activated protein C. Between 1989 and 1991, among 560 patients referred to our center with a positive history of thrombotic disease, we identified four additional patients with dysfunctional PS. Their families were investigated and dominant transmission was confirmed. Median PS levels (range) in patients and their affected relatives were: total PS=94% (69-112); free PS=66% (57-97); cofactor activity = 35% (12-55); C4b-binding protein= 109% (84-208). We suggest that a functional assay for PS should be included in the laboratory screening of thrombophilic patients because: 1) dysfunctional PS is relatively frequent and 2) it can be identified only by the combined results of the immunological and functional assays.
Cl62 HOMOZYGOUSPROTEINCDEFlClENCY1N 3UNRELATEDADULTS J.Conard,S.Poort,M.H. Horell0u.P.H. Reitsma,R.M.Bertina,M.Samama Laboratoire Central d'Hiematologie,H8pital Hbtel-Dieu, Paris,F HomozygousproteinC(PC)deficiencymaybefoundin newbornswithpurpura fulminans andalsoinadultswith venousthrombosis. Weinvestigated3 unrelated adults(2women,l man)withhomozygousPC deficiencyassociatedwithlateonsetof clinicalsymptomsand recurrentcoumarininducedskin necrosis.Theyfirstpresentedwithdeep venousthrombosis at ages 17,24 and 45. The levels of PC antigen and amidolytic activity are between 10 and 23% of normal. Each patient has had repeated episodes of venous thrombosis and also of skin necrosisoccurringat the initiation and during oral anticoagulant treatment, often associated with biological signs of DIC. For this latter reason, 2 of 3 patients have no oral anticoagulants: one is treated with low-molecular weight heparin for 2 years and one receives episodical heparin treatments. The 3rd patient could be successfully anticoagulated by phenprocoumon with an initial intravenous administration at relatively high doses; he has now received oral anticoagulants for 7 years. The DNA analysis of the PC genes demonstrated that the 3 patients are homozygous for a single nucleotide replacement in the PC gene (position 168, 301 and 267 respectively). These findings show the clinical presentation of true homozygous PC deficiency in adults and raises the question of their clinical management.
ABSTRACTS OF 12TH INTNAT’L CONGRESS
S83
Cl61 FAMILIAL DYSFUNCTIONAL PROTEIN S (PS): IDENTIFICATION OF FOUR NJXWCASES CHARACTERIZEDBY REDUCEDCOFACTORACTIVITY AND NORMAL CONCENTRATIONOF THE FREE FORM. F. Franchi, E.M. Faioni, D. Asti, P.M. Mannucci. A. Bianchi Bonomi Hemophilia and Thrombosis Center, University of Milan, Italy. A PS-deficient family with a dysfunctional molecule in plasma was first described by Wannucci et al in 1989 (Thromb Haemostas 62: 763). The hallmarks of the diagnosis are: low levels of functional PS (activated protein C cofactor activity); normal concentrations of free and total PS; and a normal PS pattern on crossed immunoelectrophoresis. Since then we included among our routine screening for thrombophilia a fully automated, prothrombin time-based PS functional assay of PS which measures the cofactor activity of PS for activated protein C. Between 1989 and 1991, among 560 patients referred to our center with a positive history of thrombotic disease, we identified four additional patients with dysfunctional PS. Their families were investigated and dominant transmission was confirmed. Median PS levels (range) in patients and their affected relatives were: total PS=94% (69-112); free PS=66% (57-97); cofactor activity = 35% (12-55); C4b-binding protein= 109% (84-208). We suggest that a functional assay for PS should be included in the laboratory screening of thrombophilic patients because: 1) dysfunctional PS is relatively frequent and 2) it can be identified only by the combined results of the immunological and functional assays.
Cl62 HOMOZYGOUSPROTEINCDEFlClENCY1N 3UNRELATEDADULTS J.Conard,S.Poort,M.H. Horell0u.P.H. Reitsma,R.M.Bertina,M.Samama Laboratoire Central d'Hiematologie,H8pital Hbtel-Dieu, Paris,F HomozygousproteinC(PC)deficiencymaybefoundin newbornswithpurpura fulminans andalsoinadultswith venousthrombosis. Weinvestigated3 unrelated adults(2women,l man)withhomozygousPC deficiencyassociatedwithlateonsetof clinicalsymptomsand recurrentcoumarininducedskin necrosis.Theyfirstpresentedwithdeep venousthrombosis at ages 17,24 and 45. The levels of PC antigen and amidolytic activity are between 10 and 23% of normal. Each patient has had repeated episodes of venous thrombosis and also of skin necrosisoccurringat the initiation and during oral anticoagulant treatment, often associated with biological signs of DIC. For this latter reason, 2 of 3 patients have no oral anticoagulants: one is treated with low-molecular weight heparin for 2 years and one receives episodical heparin treatments. The 3rd patient could be successfully anticoagulated by phenprocoumon with an initial intravenous administration at relatively high doses; he has now received oral anticoagulants for 7 years. The DNA analysis of the PC genes demonstrated that the 3 patients are homozygous for a single nucleotide replacement in the PC gene (position 168, 301 and 267 respectively). These findings show the clinical presentation of true homozygous PC deficiency in adults and raises the question of their clinical management.