"Pseudo homozygous" activated protein C resistance due to double heterozygous factor V defects (Factor V Leiden mutation and type I quantitative factor V defect) associated with thrombosis: Report of two cases belonging to two unrelated kindreds

Thrombosis and Haemostasis

Volumn 75, Issue 3, 1996, Pages 422-426

  Simioni, Paolo ^a,b   Scudeller, Alberta ^a   Radossi, Paolo ^a   Gavasso, Sabrina ^a   Girolami, Bruno ^a   Tormene, Daniela ^a   Girolami, Antonio ^a  

^a UNIVERSITY OF PADUA MEDICAL SCHOOL   (Italy)

^b Institute of Medical Semeiotics   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVATED PROTEIN C; BLOOD CLOTTING FACTOR 5; HEPARIN; WARFARIN;

ADOLESCENT; ADULT; AGED; ARTICLE; BLOOD CLOTTING; BLOOD CLOTTING FACTOR 5 DEFICIENCY; CHILD; CLINICAL ARTICLE; CONTROLLED STUDY; DEEP VEIN THROMBOSIS; DISEASE PREDISPOSITION; DNA DETERMINATION; FEMALE; GENE MUTATION; GENOTYPE; HETEROZYGOTE; HUMAN; HUMAN CELL; INHERITANCE; ITALY; MALE; PARTIAL THROMBOPLASTIN TIME; PRIORITY JOURNAL; PROTHROMBIN TIME; RISK;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; BASE SEQUENCE; CHILD; CHILD, PRESCHOOL; DRUG RESISTANCE; FACTOR V; FEMALE; HETEROZYGOTE; HOMOZYGOTE; HUMANS; MALE; MIDDLE AGED; MOLECULAR SEQUENCE DATA; MUTATION; PROTEIN C; THROMBOSIS;

EID: 0029872862     PISSN: 03406245     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-0038-1650290     Document Type: Article

References (25)

1. Dahlbäck B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C Proc Natl Acad Sci USA 1993, 90: 1004-8.
2. Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA; Reitsma PH. Mutation in Mood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-7.
3. Marciniak E, Romond EH. Impaired catalytic function of activated protein C: a new in vitro manifestation of lupus anticoagulant. Blood 1989; 74: 2426-32.
4. Malia RG, Kitchen S, Greaves M, Preston FE Inhibition of activated protein C and it cofactor protein S by antiphospholipid antibodies. Br J Haematol 1990; 76: 101-7.
5. Amer L, Kisiel W, Searles RP, Williams RC Jr. Impairment of the protein C anticoagulant pathway in a patient with systemic lupus erythematosus, anticardiolipin antibodies and thrombosis. Thromb Res 1990; 57: 247-58.
6. Simioni P, Lazzaro AR, Zanardi S, Girolami A. Spurious protein C deficiency due to antiphospholipid antibodies. Am J Hematol 1991; 36: 299-300.
7. Griffin JH, Heeb MJ, Kojima Y, Fernandez J, Kojima K. Activated protein C resistance: molecular mechanisms. Thromb Haemost 1995; 74: 444-8.
8. Koster T, Rosendaal FR, de Ronde H, Briét E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C. Leiden Thrombophilia Study. Lancet 1993; 342: 1503-6.
9. Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22.
10. Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. High risk of thrombosis in patients homozygous for F.V Leiden (activated protein C resistance). Blood 1995; 85: 1504-8.
11. Zöller B, Svensson PJ, He X, Dahlbäck B. Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C. J Clin Invest 1994; 94: 2521-4.
12. Simioni P, Scudeller A, Girolami A. Factor V Leiden and thrombophilia. N Eng J Med 1995; 332: 1382. Letter.
13. Greengard JS, Eichinger S, Griffin JH, Bauer KA. Brief report: variability of thrombosis among homozygous siblings with resistance to activated protein C due to an Arg → Gln mutation in the gene of F.V. N Eng J Med 1994; 331: 1559-62.
14. Marlar RA, Neumann A. Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies. Semin Thromb Hemost 1990; 16: 299-309.
15. de Ronde H, Bertina RM. Laboratory diagnosis of APC-resistance: a critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 1994; 72: 880-6.
16. Koeleman BPC, Reitsma PH, Allaart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis m protein C-deficient families. Blood 1994; 84: 1031-5.
17. Koeleman BPC, van Rumpt D, Hamulyàk K, Reitsma PH, Bertina RM. Factor V Leiden: an additional risk factor for thrombosis in protein S deficient families? Thromb Haemost 1995; 74: 580-3.
18. Zöller B, He X, Dahlbäck B. Homozygous APC resistance combined with inherited type I protein S deficiency in a young boy with severe thrombotic disease. Thromb Haemost 1995; 73: 743-5.
19. Zöller B, Bernstdotter A, Garcias de Frutos P, Dahlbäck B. Resistance to activated protein C as an additional genetic risk factor in inherited deficiency of protein S. Blood 1995; 85: 3518-23.
20. Greengard JS, Alhenc-Gelas, Gandrille S, Emmerich J, Aiach M, Griffin J. Pseudo-homozygous protein C resistance due to coinheritance of heterozygous factor V-R506Q and type I factor V deficiency associated with thrombosis. Thromb Haemost 1995; 73: 1361 (Abstract).
21. Simioni P, de Ronde H, Prandoni P, Saladini M, Bertina RM, Girolami A. Ischemic stroke in young patients with activated protein C resistance: a report of three cases belonging to three different kindreds. Stroke 1995; 26: 885-90.
22. Girolami A, Venturelli R, Righini F, Scarpa R. Parahemophilia. A case report. Acta Haemat 1971; 46: 242
23. Faioni EM, Franchi F, Asti D, Sacchi E, Bernardi F, Mannucci PM. Resistance to activated protein C in nine thrombophilic families: interference in a protein S functional assay. Thromb Haemost 1993; 70: 1067-71.
24. Shen L, Dahlbäck B. Factor V and Protein S as synergistic cofactors to activated protein C in the degradation of factor Villa. J Biol Chem 1994; 269: 18735-38.
25. Simioni P, Girolami A. Homozygous factor V-deficient patients show resistance to activated protein C whereas heterozygotes do not. Blood Coag Fibrinol 1994; 5: 825-7.