Protein C and protein S deficiencies: Similarities and differences between two brothers playing in the same game

Clinical Chemistry and Laboratory Medicine

Volumn 48, Issue SUPPL. 1, 2010, Pages

  Bereczky, Zsuzsanna ^a   Ková, Kitti B ^a   Muszbek, László ^a  

^a UNIVERSITY OF DEBRECEN   (Hungary)

Author keywords

protein C deficiency; protein S deficiency; review; thrombophilia

Indexed keywords

ACTIVATED PROTEIN C; BLOOD CLOTTING FACTOR 5; BLOOD CLOTTING FACTOR 8; PROTEIN C; PROTEIN S; THROMBIN;

ARTICLE; BLOOD CLOTTING; CARDIOVASCULAR RISK; DNA POLYMORPHISM; GENE MUTATION; GENE STRUCTURE; GENOTYPE PHENOTYPE CORRELATION; HUMAN; LABORATORY TEST; MOLECULAR GENETICS; PRIORITY JOURNAL; PROTEIN C DEFICIENCY; PROTEIN S DEFICIENCY; PROTEIN STRUCTURE; VENOUS THROMBOEMBOLISM;

BLOOD COAGULATION; GENOTYPE; HUMANS; PHENOTYPE; PROTEIN C DEFICIENCY; PROTEIN S DEFICIENCY;

EID: 79251610964     PISSN: 14346621     EISSN: 14374331     Source Type: Journal    
DOI: 10.1515/CCLM.2010.369     Document Type: Article

References (116)

1. Reitsma PH, Rosendaal FR. Past and future of genetic research in thrombosis. J Thromb Haemost 2007;5Suppl 1:264-9.
2. Dahlback B. Factor V and protein S as cofactors to activated protein C. Haematologica 1997;82:91-5.
3. Dahlback B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 2008;112:19-27.
4. Esmon NL, Smirnov MD, Safa O, Esmon CT. Lupus anticoagulants, thrombosis and the protein C system. Haematologica 1999;84:446-51.
5. Mosnier LO, Zlokovic BV, Griffin JH. The cytoprotective protein C pathway. Blood 2007;109:3161-72.
6. Heeb MJ, Mesters RM, Tans G, Rosing J, Griffin JH. Binding of protein S to factor Va associated with inhibition of prothrombinase that is independent of activated protein C. J Biol Chem 1993;268:2872-7.
7. van Wijnen M, van't Veer C, Meijers JC, Bertina RM, Bouma BN. A plasma coagulation assay for an activated protein Cindependent anticoagulant activity of protein S. Thromb Haemost 1998;80:930-5.
8. Hackeng TM, Sere KM, Tans G, Rosing J. Protein S stimulates inhibition of the tissue factor pathway by tissue factor pathway inhibitor. Proc Natl Acad Sci USA 2006;103:3106-11.
9. Tuddenham EG, Cooper DN. Protein C and protein C inhibitor. In: Tuddenham EG, Cooper DN, editors. The molecular genetics of haemostasis and its inherited disorders. Oxford: Oxford University Press, 1994:149-63.
10. Esmon CT. Protein C, protein S, and thrombomodulin. In: Colman RW, Marder VJ, Clowes AW, George JN, Goldhaber SZ, editors. Hemostasis and thrombosis, basic principles and clinical practice. Philadelphia: Lippincott and Williams and Wilkins, 2006:249-69.
11. Patracchini P, Aiello V, Palazzi P, Calzolari E, Bernardi F. Sublocalization of the human protein C gene on chromosome 2q13-q14. Hum Genet 1989;81:191-2.
12. Tuddenham EG, Cooper DN. Protein S, C4b-binding protein, and protein Z. In: Tuddenham EG, Cooper DN, editors. The molecular genetics of haemostasis and its inherited disorders. Oxford: Oxford University Press, 1994:164-74.
13. Dahlback B, Stenflo J. High molecular weight complex in human plasma between vitamin K-dependent protein S and complement component C4b-binding protein. Proc Natl Acad Sci USA 1981;78:2512-6.
14. Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C. Deficiency of protein C in congenital thrombotic disease. J Clin Invest 1981;68:1370-3.
15. Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984;311:1525-8.
16. Sakata T, Kario K, Katayama Y, Matsuyama T, Kato H, Miyata T. Studies on congenital protein C deficiency in Japanese: Prevalence, genetic analysis, and relevance to the onset of arterial occlusive diseases. Semin Thromb Hemost 2000;26:11-6.
17. Biguzzi E, Razzari C, Lane DA, Castaman G, Cappellari A, Bucciarelli P, et al. Molecular diversity and thrombotic risk in protein S deficiency: The PROSIT study. Hum Mutat 2005;25: 259-69.
18. Miletich J, Sherman L, Broze G, Jr. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 1987;317:991-6.
19. Tait RC, Walker ID, Reitsma PH, Islam SI, McCall F, Poort SR, et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 1995;73:87-93.
20. Dykes AC, Walker ID, McMahon AD, Islam SI, Tait RC. A study of protein S antigen levels in 3788 healthy volunteers: Influence of age, sex and hormone use, and estimate for prevalence of deficiency state. Br J Haematol 2001;113:636-41.
21. Miyata T, Kimura R, Kokubo Y, Sakata T. Genetic risk factors for deep vein thrombosis among Japanese: Importance of protein S K196E mutation. Int J Hematol 2006;83:217-23. (Pubitemid 44227995)
22. Wysokinska EM, Wysokinski WE, Brown RD, Karnicki K, Gosk-Beirska I, Grill D, et al. Thrombophilia differences in cerebral venous sinus and lower extremity deep venous thrombosis. Neurology 2008;70:627-33.
23. De Stefano V, Simioni P, Rossi E, Tormene D, Za T, Pagnan A, et al. The risk of recurrent venous thromboembolism in patients with inherited deficiency of natural anticoagulants antithrombin, protein C and protein S. Haematologica 2006;91: 695-8.
24. Rossi E, Za T, Ciminello A, Leone G, De Stefano V. The risk of symptomatic pulmonary embolism due to proximal deep venous thrombosis differs in patients with different types of inherited thrombophilia. Thromb Haemost 2008;99:1030-4.
25. Koster T, Rosendaal FR, Briet E, van der Meer FJ, Colly LP, Trienekens PH, et al. Protein C deficiency in a controlled series of unselected outpatients: An infrequent but clear risk factor for venous thrombosis (Leiden Thrombophilia Study). Blood 1995; 85:2756-61.
26. Brouwer JL, Lijfering WM, Ten Kate MK, Kluin-Nelemans HC, Veeger NJ, van der Meer J. High long-term absolute risk of recurrent venous thromboembolism in patients with hereditary deficiencies of protein S, protein C or antithrombin. Thromb Haemost 2009;101:93-9.
27. Vossen CY, Conard J, Fontcuberta J, Makris M, van der Meer FJ, Pabinger I, et al. Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost 2005;3:459-64.
28. Shen MC, Lin JS, Tsay W. Protein C and protein S deficiencies are the most important risk factors associated with thrombosis in Chinese venous thrombophilic patients in Taiwan. Thromb Res 2000;99:447-52.
29. Altinisik J, Ates O, Ulutin T, Cengiz M, Buyru N. Factor V Leiden, prothrombin G20210A, and protein C mutation frequency in Turkish venous thrombosis patients. Clin Appl Thromb Hemost 2008;14:415-20.
30. Tjeldhorn L, Sandset PM, Haugbro K, Skretting G. Hereditary protein C deficiency caused by the Ala267Thr mutation in the protein C gene is associated with symptomatic and asymptomatic venous thrombosis. Thromb Res 2010;125:230-4.
31. Scott BT, Bovill EG, Callas PW, Hasstedt SJ, Leppert MF, Valliere JE, et al. Genetic screening of candidate genes for a prothrombotic interaction with type I protein C deficiency in a large kindred. Thromb Haemost 2001;85:82-7.
32. Matitiau A, Tabachnik E, Sthoeger D, Birk E. Thrombus in the left ventricle of a child with systemic emboli: An unusual presentation of hereditary protein C deficiency. Pediatrics 2001; 107:421-2.
33. Kim MJ, Hur SH, Lee YS, Hyun DW, Han SW, Kim KS, et al. Intracardiac multichamber thrombi in a patient with combined protein C and protein S deficiencies. Int J Cardiol 2005;100: 505-6.
34. Pabinger I, Grafenhofer H. Thrombosis during pregnancy: Risk factors, diagnosis and treatment. Pathophysiol Haemost Thromb 2002;32:322-4.
35. Goldenberg NA, Manco-Johnson MJ. Protein C deficiency. Haemophilia 2008;14:1214-21.
36. Kohler J, Kasper J, Witt I, von Reutern GM. Ischemic stroke due to protein C deficiency. Stroke 1990;21:1077-80.
37. Acar G, Dogan A, Altinbas A, Turker Y. Recurrent acute stent thrombosis associated with protein C and S deficiencies. Int J Cardiovasc Imaging 2006;22:333-7.
38. Cakir O, Ayyildiz O, Oruc A, Eren N. A young adult with coronary artery and jugular vein thrombosis: A case report of combined protein S and protein C deficiency. Heart Vessels 2002;17:74-6.
39. Peterman MA, Roberts WC. Syndrome of protein C deficiency and anterior wall acute myocardial infarction at a young age from a single coronary occlusion with otherwise normal coronary arteries. Am J Cardiol 2003;92:768-70.
40. Mahmoodi BK, Brouwer JL, Veeger NJ, van der Meer J. Hereditary deficiency of protein C or protein S confers increased risk of arterial thromboembolic events at a young age: Results from a large family cohort study. Circulation 2008;118:1659-67.
41. Folsom AR, Ohira T, Yamagishi K, Cushman M. Low protein C and incidence of ischemic stroke and coronary heart disease: The Atherosclerosis Risk in Communities (ARIC) Study. J Thromb Haemost 2009;7:1774-8.
42. Kenet G, Lutkhoff LK, Albisetti M, Bernard T, Bonduel M, Brandao L, et al. Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: A systematic review and meta-analysis of observational studies. Circulation 2010;121:1838-47.
43. Reitsma PH. Protein C deficiency: Summary of the 1995 database update. Nucleic Acids Res 1996;24:157-9.
44. Aiach M, Gandrille S, Emmerich J. A review of mutations causing deficiencies of antithrombin, protein C and protein S. Thromb Haemost 1995;74:81-9.
45. Matsuda M, Sugo T, Sakata Y, Murayama H, Mimuro J, Tanabe S, et al. A thrombotic state due to an abnormal protein C. N Engl J Med 1988;319:1265-8.
46. Millar DS, Johansen B, Berntorp E, Minford A, Bolton-Maggs P, Wensley R, et al. Molecular genetic analysis of severe protein C deficiency. Hum Genet 2000;106:646-53.
47. D'Ursi P, Marino F, Caprera A, Milanesi L, Faioni EM, Rovida E. ProCMD: A database and 3D web resource for protein C mutants. BMC Bioinformatics 2007;8 Suppl 1:S11.
48. Sugahara Y, Miura O, Hirosawa S, Aoki N. Compound heterozygous protein C deficiency caused by two mutations, Arg- 178 to Gln and Cys-331 to Arg, leading to impaired secretion of mutant protein C. Thromb Haemost 1994;72:814-8.
49. Bovill EG, Tomczak JA, Grant B, Bhushan F, Pillemer E, Rainville IR, et al. Protein CVermont: Symptomatic type II protein C deficiency associated with two GLA domain mutations. Blood 1992;79:1456-65.
50. Gandrille S, Alhenc-Gelas M, Gaussem P, Aillaud MF, Dupuy E, Juhan-Vague I, et al. Five novel mutations located in exons III and IX of the protein C gene in patients presenting with defective protein C anticoagulant activity. Blood 1993;82: 159-68.
51. Ido M, Ohiwa M, Hayashi T, Nishioka J, Hatada T, Watanabe Y, et al. A compound heterozygous protein C deficiency with a single nucleotide G deletion encoding Gly-381 and an amino acid substitution of Lys for Gla-26. Thromb Haemost 1993; 70:636-41.
52. Gaussem P, Gandrille S, Duchemin J, Emmerich J, Alhenc- Gelas M, Aillaud MF, et al. Influence of six mutations of the protein C gene on the Gla domain conformation and calcium affinity. Thromb Haemost 1994;71:748-54.
53. Lu D, Bovill EG, Long GL. Molecular mechanism for familial protein C deficiency and thrombosis in protein CVermont (Glu20- >Ala and Val34- >Met). J Biol Chem 1994;269: 29032-8.
54. Faioni EM, Hermida J, Rovida E, Razzari C, Asti D, Zeinali S, et al. Type II protein C deficiency: Identification and molecular modelling of two natural mutants with low anticoagulant and normal amidolytic activity. Br J Haematol 2000;108: 265-71.
55. Preston RJ, Morse C, Murden SL, Brady SK, O'Donnell JS, Mumford AD. The protein C omega-loop substitution Asn2Ile is associated with reduced protein C anticoagulant activity. Br J Haematol 2009;144:946-53.
56. Simioni P, Kalafatis M, Tormene D, Luni S, Zerbinati P, Barzon L, et al. Abnormal propeptide processing resulting in the presence of two abnormal species of protein C in plasma: Characterization of the dysfunctional protein C Padua3 (protein C(R-1L/propeptide)). Thromb Haemost 2001;86:1017-22.
57. Nakabayashi T, Mizukami K, Naitoh S, Takeda M, Shikamoto Y, Nakagawa T, et al. Protein C Sapporo (protein C Glu 25 - > Lys): A heterozygous missense mutation in the Gla domain provides new insight into the interaction between protein C and endothelial protein C receptor. Thromb Haemost 2005;94: 942-50.
58. Marchetti G, Patracchini P, Gemmati D, Castaman G, Rodeghiero F, Wacey A, et al. Symptomatic type II protein C deficiency caused by a missense mutation (Gly 381 - >Ser) in the substrate-binding pocket. Br J Haematol 1993;84:285-9.
59. Doig RG, Begley CG, McGrath KM. Hereditary protein C deficiency associated with mutations in exon IX of the protein C gene. Thromb Haemost 1994;72:203-8.
60. Zheng YZ, Sakata T, Matsusue T, Umeyama H, Kato H, Miyata T. Six missense mutations associated with type I and type II protein C deficiency and implications obtained from molecular modelling. Blood Coagul Fibrinolysis 1994;5:687-96.
61. Levo A, Kuismanen K, Holopainen P, Vahtera E, Rasi V, Krusius T, et al. Single founder mutation (W380G) in type II protein C deficiency in Finland. Thromb Haemost 2000;84:424-8.
62. Tsay W, Shen MC. R147W mutation of PROC gene is common in venous thrombotic patients in Taiwanese Chinese. Am J Hematol 2004;76:8-13.
63. Miyata T, Sakata T, Yasumuro Y, Okamura T, Katsumi A, Saito H, et al. Genetic analysis of protein C deficiency in nineteen Japanese families: Five recurrent defects can explain half of the deficiencies. Thromb Res 1998;92:181-7.
64. Zeegers MP, van Poppel F, Vlietinck R, Spruijt L, Ostrer H. Founder mutations among the Dutch. Eur J Hum Genet 2004;12:591-600.
65. Couture P, Bovill EG, Demers C, Simard J, Delage R, Scott BT, et al. Evidence of a founder effect for the protein C gene 3363 inserted C mutation in thrombophilic pedigrees of French origin. Thromb Haemost 2001;86:1000-6.
66. Koeleman BP, Reitsma PH, Bertina RM. Familial thrombophilia: A complex genetic disorder. Semin Hematol 1997;34: 256-64.
67. Buil A, Soria JM, Souto JC, Almasy L, Lathrop M, Blangero J, et al. Protein C levels are regulated by a quantitative trait locus on chromosome 16: Results from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) Project. Arterioscler Thromb Vasc Biol 2004;24:1321-5.
68. Zoller B, Garcia de Frutos P, Dahlback B. Evaluation of the relationship between protein S and C4b-binding protein isoforms in hereditary protein S deficiency demonstrating type I and type III deficiencies to be phenotypic variants of the same genetic disease. Blood 1995;85:3524-31.
69. Simmonds RE, Ireland H, Lane DA, Zoller B, Garcia de Frutos P, Dahlback B. Clarification of the risk for venous thrombosis associated with hereditary protein S deficiency by investigation of a large kindred with a characterized gene defect. Ann Intern Med 1998;128:8-14.
70. Espinosa-Parrilla Y, Morell M, Souto JC, Tirado I, Fontcuberta J, Estivill X, et al. Protein S gene analysis reveals the presence of a cosegregating mutation in most pedigrees with type I but not type III PS deficiency. Hum Mutat 1999;14:30-9.
71. Ten Kate MK, Platteel M, Mulder R, Terpstra P, Nicolaes GA, Reitsma PH, et al. PROS1 analysis in 87 pedigrees with hereditary protein S deficiency demonstrates striking genotype-phenotype associations. Hum Mutat 2008;29:939-47.
72. Garcia de Frutos P, Fuentes-Prior P, Hurtado B, Sala N. Molecular basis of protein S deficiency. Thromb Haemost 2007;98: 543-56.
73. Baroni M, Mazzola G, Kaabache T, Borgel D, Gandrille S, Vigano' D'Angelo S, et al. Molecular bases of type II protein S deficiency: The I203-D204 deletion in the EGF4 domain alters GLA domain function. J Thromb Haemost 2006;4:186-91.
74. Pintao MC, Garcia AA, Borgel D, Alhenc-Gelas M, Spek CA, de Visser MC, et al. Gross deletions/duplications in PROS1 are relatively common in point mutation-negative hereditary protein S deficiency. Hum Genet 2009;126:449-56.
75. Yin T, Takeshita S, Sato Y, Sakata T, Shin Y, Honda S, et al. A large deletion of the PROS1 gene in a deep vein thrombosis patient with protein S deficiency. Thromb Haemost 2007;98: 783-9.
76. Tatewaki H, Tsuda H, Kanaji T, Yokoyama K, Hamasaki N. Characterization of the human protein S gene promoter: A possible role of transcription factors Sp1 and HNF3 in liver. Thromb Haemost 2003;90:1029-39.
77. de Wolf CJ, Cupers RM, Bertina RM, Vos HL. The constitutive expression of anticoagulant protein S is regulated through multiple binding sites for Sp1 and Sp3 transcription factors in the protein S gene promoter. J Biol Chem 2006;281:17635-43.
78. Hurtado B, Nadal M, Margarit E, Sanchez A, Abasolo N, Garcia N, et al. First case of protein S deficiency due to a translocation t(3;21)(q11.2;q22). Thromb Haemost 2009;101:977-9.
79. Spek CA, Koster T, Rosendaal FR, Bertina RM, Reitsma PH. Genotypic variation in the promoter region of the protein C gene is associated with plasma protein C levels and thrombotic risk. Arterioscler Thromb Vasc Biol 1995;15:214-8.
80. Aiach M, Nicaud V, Alhenc-Gelas M, Gandrille S, Arnaud E, Amiral J, et al. Complex association of protein C gene promoter polymorphism with circulating protein C levels and thrombotic risk. Arterioscler Thromb Vasc Biol 1999;19:1573-6.
81. Pomp ER, Doggen CJ, Vos HL, Reitsma PH, Rosendaal FR. Polymorphisms in the protein C gene as risk factor for venous thrombosis. Thromb Haemost 2009;101:62-7.
82. Kimura R, Kokubo Y, Miyashita K, Otsubo R, Nagatsuka K, Otsuki T, et al. Polymorphisms in vitamin K-dependent gamma- carboxylation-related genes influence interindividual variability in plasma protein C and protein S activities in the general population. Int J Hematol 2006;84:387-97.
83. Giri TK, Yamazaki T, Sala N, Dahlback B, de Frutos PG. Deficient APC-cofactor activity of protein S Heerlen in degradation of factor Va Leiden: A possible mechanism of synergism between thrombophilic risk factors. Blood 2000;96:523-31.
84. Koenen RR, Gomes L, Tans G, Rosing J, Hackeng TM. The Ser460Pro mutation in recombinant protein S Heerlen does not affect its APC-cofactor and APC-independent anticoagulant activities. Thromb Haemost 2004;91:1105-14.
85. Leroy-Matheron C, Duchemin J, Levent M, Gouault-Heilmann M. Genetic modulation of plasma protein S levels by two frequent dimorphisms in the PROS1 gene. Thromb Haemost 1999; 82:1088-92.
86. Heinikari T, Huoponen O, Partanen J, Rasi V, Krusius T. Protein S gene polymorphisms Pro626 and nt2698-no correlation to free protein S levels or protein S activities. Thromb Haemost 2005;94:1340-1.
87. Castaman G, Biguzzi E, Razzari C, Tosetto A, Fontana G, Asti D, et al. Association of protein S p.Pro667Pro dimorphism with plasma protein S levels in normal individuals and patients with inherited protein S deficiency. Thromb Res 2007;120:421-6.
88. Khor B, Van Cott EM. Laboratory tests for protein C deficiency. Am J Hematol 2010;85:440-2.
89. Simioni P, Lazzaro A, Zanardi S, Girolami A. Spurious protein C deficiency due to antiphospholipid antibodies. Am J Hematol 1991;36:299-301.
90. Cooper PC, Cooper SM, Goodfellow KJ, Hickey KP, Kitchen S, Makris M. Evaluation of a new venom-based clotting assay of protein C. Int J Lab Hematol 2008;30:437-43.
91. de Moerloose P, Reber G, Bouvier CA. Spuriously low levels of protein C with a Protac activation clotting assay. Thromb Haemost 1988;59:543.
92. Ireland H, Bayston T, Thompson E, Adami A, Goncalves C, Lane DA, et al. Apparent heterozygous type II protein C deficiency caused by the factor V 506 Arg to Gln mutation. Thromb Haemost 1995;73:731-2.
93. Jennings I, Kitchen S, Cooper PC, Rimmer JE, Woods TA, Preston FE. Further evidence that activated protein C resistance affects protein C coagulant activity assays. Thromb Haemost 2000;83:171-2.
94. Meijer P, Kluft C, Haverkate F, De Maat MP. The long-term within- and between-laboratory variability for assay of antithrombin, and proteins C and S: Results derived from the external quality assessment program for thrombophilia screening of the ECAT Foundation. J Thromb Haemost 2003;1:748-53.
95. Deitcher SR, Kottke-Marchant K. Pseudo-protein S deficiency due to activated protein C resistance. Thromb Res 2003;112: 349-53.
96. Makris M, Leach M, Beauchamp NJ, Daly ME, Cooper PC, Hampton KK, et al. Genetic analysis, phenotypic diagnosis, and risk of venous thrombosis in families with inherited deficiencies of protein S. Blood 2000;95:1935-41.
97. De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: Pathogenesis, clinical syndromes, and management. Blood 1996;87:3531-44.
98. Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V, et al. Inherited thrombophilia: Part 1. Thromb Haemost 1996;76:651-62.
99. Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology. Investigation and management of heritable thrombophilia. Br J Haematol 2001;114:512-28.
100. Deffert C, Esteve F, Grimaux M, Gouault-Heilmann M. A direct, automated, immuno-turbidimetric assay of free protein S antigen in plasma. Blood Coagul Fibrinolysis 2001;12: 137-41. (Pubitemid 32234822)
101. Giri TK, Hillarp A, Hardig Y, Zoller B, Dahlback B. A new direct, fast and quantitative enzyme-linked ligand sorbent assay for measurement of free protein S antigen. Thromb Haemost 1998;79:767-72.
102. Finazzi G, Barbui T. Different incidence of venous thrombosis in patients with inherited deficiencies of antithrombin III, protein C and protein S. Thromb Haemost 1994;71:15-8.
103. Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the full-term infant. Blood 1987;70:165-72.
104. Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992;80:1998-2005.
105. Petaja J, Manco-Johnson MJ. Protein C pathway in infants and children. Semin Thromb Hemost 2003;29:349-62.
106. Monagle P, Barnes C, Ignjatovic V, Furmedge J, Newall F, Chan A, et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 2006;95:362-72.
107. Said JM, Ignjatovic V, Monagle PT, Walker SP, Higgins JR, Brennecke SP. Altered reference ranges for protein C and protein S during early pregnancy: Implications for the diagnosis of protein C and protein S deficiency during pregnancy. Thromb Haemost 2010;103:984-8.
108. Boerger LM, Morris PC, Thurnau GR, Esmon CT, Comp PC. Oral contraceptives and gender affect protein S status. Blood 1987;69:692-4.
109. Pabinger I, Kyrle PA, Speiser W, Stoffels U, Jung M, Lechner K. Diagnosis of protein C deficiency in patients on oral anticoagulant treatment: Comparison of three different functional protein C assays. Thromb Haemost 1990;63:407-12.
110. Demir T, Celkan T, Ahunbay G, Babaoglu A, Besikci R. Venous and intrapericardial thrombosis: Secondary to transient protein C deficiency. Pediatr Cardiol 2006;27:497-9.
111. Richardson MA, Gupta A, O'Brien LA, Berg DT, Gerlitz B, Syed S, et al. Treatment of sepsis-induced acquired protein C deficiency reverses angiotensin-converting enzyme-2 inhibition and decreases pulmonary inflammatory response. J Pharmacol Exp Ther 2008;325:17-26.
112. Bay A, Oner AF, Calka O, Sanli F, Akdeniz N, Dogan M. Purpura fulminans secondary to transient protein C deficiency as a complication of chickenpox infection. Pediatr Dermatol 2006;23:412-3.
113. Mallet VO, Vallet-Pichard A, Pol S. Human immunodeficiency virus-associated obliterative portopathy underlies unexplained aminotransferase elevations under antiretrovirals. Hepatology 2009;50:660.
114. Regnault V, Boehlen F, Ozsahin H, Wahl D, de Groot PG, Lecompte T, et al. Anti-protein S antibodies following a varicella infection: Detection, characterization and influence on thrombin generation. J Thromb Haemost 2005;3:1243-9.
115. Ireland H, Thompson E, Lane DA. Gene mutations in 21 unrelated cases of phenotypic heterozygous protein C deficiency and thrombosis. Protein C Study Group. Thromb Haemost 1996;76:867-73. (Pubitemid 27013620)
116. Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S, et al. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol 2010;149:209-20.