Laboratory Evaluation of Hypercoagulability

Clinics in Laboratory Medicine

Volumn 29, Issue 2, 2009, Pages 339-366

  Khor, Bernard ^a   Van Cott, Elizabeth M ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Activated protein C resistance; Antiphospholipid antibodies; Antithrombin III; Factor V Leiden; Protein C; Protein S; Prothrombin G20210A

Indexed keywords

ACTIVATED PROTEIN C; BLOOD CLOTTING FACTOR 5 LEIDEN; PHOSPHOLIPID ANTIBODY; PROTEIN C; PROTEIN S; PROTHROMBIN;

ACTIVATED PROTEIN C RESISTANCE; ANTITHROMBIN DEFICIENCY; DISEASE PREDISPOSITION; FAMILY HISTORY; HUMAN; HYPERCOAGULABILITY; LABORATORY DIAGNOSIS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN C DEFICIENCY; PROTEIN S DEFICIENCY; RECURRENT DISEASE; REVIEW; THROMBOSIS;

ADOLESCENT; ADULT; BLOOD COAGULATION DISORDERS, INHERITED; BLOOD COAGULATION TESTS; CHILD; CHILD, PRESCHOOL; HUMANS; INFANT; THROMBOPHILIA;

EID: 68249151034     PISSN: 02722712     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cll.2009.03.002     Document Type: Review

References (179)

1. Griffin J.H., Fernandez J.A., Gale A.J., et al. Activated protein C. J Thromb Haemost 1 Suppl 5 (2007) 73-80
2. Nesheim M., Wang W., Boffa M., et al. Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis. Thromb Haemost 78 (1997) 386-391
3. Dahlback B. Resistance to activate protein C, the Arg506 to Gln mutation in the factor V gene, and venous thrombosis. Functional tests and DNA-based assays, pros and cons. Thromb Haemost 73 (1995) 739-742
4. Dahlback B., Carlsson M., and Svensson P.J. 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 U S A 90 (1993) 1004-1008
5. Griffin J.H., Evatt B., Wideman C., et al. Anticoagulant protein C pathway defective in majority of thrombophilic patients. Blood 82 (1993) 1989-1993
6. Koster T., Rosendaal F.R., de Ronde H., et al. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 342 (1993) 1503-1506
7. Svensson P.J., and Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 330 (1994) 517-522
8. Bertina R.M., Koeleman B.P., Koster T., et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369 (1994) 64-67
9. Greengard J.S., Sun X., Xu X., et al. Activated protein C resistance caused by Arg506Gln mutation in factor Va. Lancet 343 (1994) 1361-1362
10. Zoller B., and Dahlback B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 343 (1994) 1536-1538
11. Zivelin A., Mor-Cohen R., Kovalsky V., et al. Prothrombin 20210G>A is an ancestral prothrombotic mutation that occurred in whites approximately 24,000 years ago. Blood 107 (2006) 4666-4668
12. Voorberg J., Roelse J., Koopman R., et al. Association of idiopathic venous thromboembolism with single point-mutation at Arg506 of factor V. Lancet 343 (1994) 1535-1536
13. Chan L.C., Bourke C., Lam C.K., et al. Lack of activated protein C resistance in healthy Hong Kong Chinese blood donors-correlation with absence of Arg506-Gln mutation of factor V gene. Thromb Haemost 75 (1996) 522-523
14. Hooper W.C., Dilley A., Ribeiro M.J., et al. A racial difference in the prevalence of the Arg506->Gln mutation. Thromb Res 81 (1996) 577-581
15. Kohler H.P., Boothby M., McCormack L., et al. Incidence of Arg506-> Gln mutation (factor V Leiden) in Pima Indians. Thromb Haemost 78 (1997) 961-962
16. Ozawa T., Niiya K., and Sakuragawa N. Absence of factor V Leiden in the Japanese. Thromb Res 81 (1996) 595-596
17. Rees D.C., Cox M., and Clegg J.B. World distribution of factor V Leiden. Lancet 346 (1995) 1133-1134
18. Ridker P.M., Miletich J.P., Hennekens C.H., et al. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. JAMA 277 (1997) 1305-1307
19. Ridker P.M., Hennekens C.H., Lindpaintner K., et al. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men. N Engl J Med 332 (1995) 912-917
20. Rosendaal F.R., Koster T., Vandenbroucke J.P., et al. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood 85 (1995) 1504-1508
21. Bloemenkamp K.W., Rosendaal F.R., Helmerhorst F.M., et al. Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen. Lancet 346 (1995) 1593-1596
22. Dizon-Townson D.S., Nelson L.M., Jang H., et al. The incidence of the factor V Leiden mutation in an obstetric population and its relationship to deep vein thrombosis. Am J Obstet Gynecol 176 (1997) 883-886
23. Koeleman B.P., van Rumpt D., Hamulyak K., et al. Factor V Leiden: an additional risk factor for thrombosis in protein S deficient families?. Thromb Haemost 74 (1995) 580-583
24. Ridker P.M., Glynn R.J., Miletich J.P., et al. Age-specific incidence rates of venous thromboembolism among heterozygous carriers of factor V Leiden mutation. Ann Intern Med 126 (1997) 528-531
25. Emmerich J., Rosendaal F.R., Cattaneo M., et al. Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism-pooled analysis of 8 case-control studies including 2310 cases and 3204 controls. Study Group for Pooled-Analysis in Venous Thromboembolism. Thromb Haemost 86 (2001) 809-816
26. de Paula Sabino A., Ribeiro D.D., Carvalho M.G., et al. Factor V Leiden and increased risk for arterial thrombotic disease in young Brazilian patients. Blood Coagul Fibrinolysis 17 (2006) 271-275
27. Juul K., Tybjaerg-Hansen A., Steffensen R., et al. Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses. Blood 100 (2002) 3-10
28. Rahemtullah A., and Van Cott E.M. Hypercoagulation testing in ischemic stroke. Arch Pathol Lab Med 131 (2007) 890-901
29. Segers K., Dahlback B., and Nicolaes G.A. Coagulation factor V and thrombophilia: background and mechanisms. Thromb Haemost 98 (2007) 530-542
30. Van Cott E.M., Laposata M., and Prins M.H. Laboratory evaluation of hypercoagulability with venous or arterial thrombosis. Arch Pathol Lab Med 126 (2002) 1281-1295
31. Castoldi E., Brugge J.M., Nicolaes G.A., et al. Impaired APC cofactor activity of factor V plays a major role in the APC resistance associated with the factor V Leiden (R506Q) and R2 (H1299R) mutations. Blood 103 (2004) 4173-4179
32. Bernardi F., Faioni E.M., Castoldi E., et al. A factor V genetic component differing from factor V R506Q contributes to the activated protein C resistance phenotype. Blood 90 (1997) 1552-1557
33. Biswas A., Bajaj J., Ranjan R., et al. Factor V Leiden: is it the chief contributor to activated protein C resistance in Asian-Indian patients with deep vein thrombosis?. Clin Chim Acta 392 (2008) 21-24
34. de Visser M.C., Guasch J.F., Kamphuisen P.W., et al. The HR2 haplotype of factor V: effects on factor V levels, normalized activated protein C sensitivity ratios and the risk of venous thrombosis. Thromb Haemost 83 (2000) 577-582
35. Steen M., Norstrom E.A., Tholander A.L., et al. Functional characterization of factor V-Ile359Thr: a novel mutation associated with thrombosis. Blood 103 (2004) 3381-3387
36. Franco R.F., Elion J., Tavella M.H., et al. The prevalence of factor V Arg306->Thr (factor V Cambridge) and factor V Arg306->Gly mutations in different human populations. Thromb Haemost 81 (1999) 312-313
37. Norstrom E., Thorelli E., and Dahlback B. Functional characterization of recombinant FV Hong Kong and FV Cambridge. Blood 100 (2002) 524-530
38. Chan W.P., Lee C.K., Kwong Y.L., et al. A novel mutation of Arg306 of factor V gene in Hong Kong Chinese. Blood 91 (1998) 1135-1139
39. de Visser M.C., Rosendaal F.R., and Bertina R.M. A reduced sensitivity for activated protein C in the absence of factor V Leiden increases the risk of venous thrombosis. Blood 93 (1999) 1271-1276
40. Kamphuisen P.W., Haan J., Rosekrans P.C., et al. Deep-vein thrombosis and coumarin skin necrosis associated with a factor V inhibitor with lupus-like features. Am J Hematol 57 (1998) 176-178
41. Ortel T.L. Clinical and laboratory manifestations of anti-factor V antibodies. J Lab Clin Med 133 (1999) 326-334
42. Ortel T.L., Charles L.A., Keller F.G., et al. Topical thrombin and acquired coagulation factor inhibitors: clinical spectrum and laboratory diagnosis. Am J Hematol 45 (1994) 128-135
43. Negaard H.F., Iversen P.O., Ostenstad B., et al. Increased acquired activated protein C resistance in unselected patients with hematological malignancies. J Thromb Haemost 6 (2008) 1482-1487
44. Andre E., Hacquard M., Alnot Y., et al. Activated protein C resistance test using factor VIII-deficient plasma: a new approach to the venous thrombotic risk?. Thromb Haemost 98 (2007) 693-694
45. Mosnier L.O., Zlokovic B.V., and Griffin J.H. The cytoprotective protein C pathway. Blood 109 (2007) 3161-3172
46. Domotor E., Benzakour O., Griffin J.H., et al. Activated protein C alters cytosolic calcium flux in human brain endothelium via binding to endothelial protein C receptor and activation of protease activated receptor-1. Blood 101 (2003) 4797-4801
47. Riewald M., Petrovan R.J., Donner A., et al. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science 296 (2002) 1880-1882
48. Riewald M., and Ruf W. Protease-activated receptor-1 signaling by activated protein C in cytokine-perturbed endothelial cells is distinct from thrombin signaling. J Biol Chem 280 (2005) 19808-19814
49. Toltl L.J., Beaudin S., and Liaw P.C. Activated protein C up-regulates IL-10 and inhibits tissue factor in blood monocytes. J Immunol 181 (2008) 2165-2173
50. Xue M., March L., Sambrook P.N., et al. Differential regulation of matrix metalloproteinase 2 and matrix metalloproteinase 9 by activated protein C: relevance to inflammation in rheumatoid arthritis. Arthritis Rheum 56 (2007) 2864-2874
51. Rosendorff A., and Dorfman D.M. Activated protein C resistance and factor V Leiden: a review. Arch Pathol Lab Med 131 (2007) 866-871
52. Strobl F.J., Hoffman S., Huber S., et al. Activated protein C resistance assay performance: improvement by sample dilution with factor V-deficient plasma. Arch Pathol Lab Med 122 (1998) 430-433
53. Sweeney J.D., Blair A.J., and King T.C. Comparison of an activated partial thromboplastin time with a Russell viper venom time test in screening for factor V(Leiden) (FVR506Q). Am J Clin Pathol 108 (1997) 74-77
54. Zehnder J.L., and Benson R.C. Sensitivity and specificity of the APC resistance assay in detection of individuals with factor V Leiden. Am J Clin Pathol 106 (1996) 107-111
55. de Ronde H., and Bertina R.M. Laboratory diagnosis of APC-resistance: a critical evaluation of the test and the development of diagnostic criteria. Thromb Haemost 72 (1994) 880-886
56. Trossaert M., Conard J., Horellou M.H., et al. Influence of storage conditions on activated protein C resistance assay. Thromb Haemost 73 (1995) 163-164
57. Jorquera J.I., Montoro J.M., Fernandez M.A., et al. Modified test for activated protein C resistance. Lancet 344 (1994) 1162-1163
58. Trossaert M., Conard J., Horellou M.H., et al. The modified APC resistance test in the presence of factor V deficient plasma can be used in patients without oral anticoagulant. Thromb Haemost 75 (1996) 521-522
59. Rosen S., Andersson N.-E., Andersson M., et al. Modified COATEST(R) APCTM resistance assay including V-DEF plasma with a heparin antagonist: analysis of heparin and OAC plasmas and influence of preanalytical variables. Blood Coagul Fibrinolysis 7 (1996) 390
60. Shaikh S., and Van Cott E.M. The effect of argatroban on activated protein C resistance. Am J Clin Pathol 131 (2009) 828-833
61. Saenz A.J., and Van Cott E.M. Clinical significance of acquired activated protein C resistance caused by lupus anticoagulants. Mod Pathol 21 (2008) 273A
62. Coatest APC Resistance V assay. Chromogenix/Instrumentation Laboratory. Milano, Italy; 2008 [package insert].
63. Ragland B.D., Reed C.E., Eiland B.M., et al. The effect of lupus anticoagulant in the second-generation assay for activated protein C resistance. Am J Clin Pathol 119 (2003) 66-71
64. Martorell J.R., Munoz-Castillo A., and Gil J.L. False positive activated protein C resistance test due to anti-phospholipid antibodies is corrected by platelet extract. Thromb Haemost 74 (1995) 796-797
65. Brandt G., Gruppo R., Glueck C.J., et al. Sensitivity, specificity and predictive value of modified assays for activated protein C resistance in children. Thromb Haemost 79 (1998) 567-570
66. Tripodi A., Chantarangkul V., Negri B., et al. Standardization of the APC resistance test. Effects of normalization of results by means of pooled normal plasma. Thromb Haemost 79 (1998) 564-566
67. Voelkerding K.V., Wu L., Williams E.C., et al. Factor V R506Q gene mutation analysis by PCR-RFLP: optimization, comparison with functional testing for resistance to activated protein C, and establishment of cell line controls. Am J Clin Pathol 106 (1996) 100-106
68. Wilmer M., Stocker C., Buhler B., et al. Improved distinction of factor V wild-type and factor V Leiden using a novel prothrombin-based activated protein C resistance assay. Am J Clin Pathol 122 (2004) 836-842
69. Le D.T., Griffin J.H., Greengard J.S., et al. Use of a generally applicable tissue factor-dependent factor V assay to detect activated protein C-resistant factor Va in patients receiving warfarin and in patients with a lupus anticoagulant. Blood 85 (1995) 1704-1711
70. van Oerle R., van Pampus L., Tans G., et al. The clinical application of a new specific functional assay to detect the factor V(Leiden) mutation associated with activated protein C resistance. Am J Clin Pathol 107 (1997) 521-526
71. Male C., Mitchell L., Julian J., et al. Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus. Blood 97 (2001) 844-849
72. Schrijver I., Lay M.J., and Zehnder J.L. Diagnostic single nucleotide polymorphism analysis of factor V Leiden and prothrombin 20210G > A. A comparison of the Nanogen Eelectronic Microarray with restriction enzyme digestion and the Roche LightCycler. Am J Clin Pathol 119 (2003) 490-496
73. Liebman H.A., Sutherland D., Bacon R., et al. Evaluation of a tissue factor dependent factor V assay to detect factor V Leiden: demonstration of high sensitivity and specificity for a generally applicable assay for activated protein C resistance. Br J Haematol 95 (1996) 550-553
74. Uttenreuther-Fischer M.M., Ziemer S., and Gaedicke G. Resistance to activated protein C (APCR): reference values of APC-ratios for children. Thromb Haemost 76 (1996) 813-814
75. Nowak-Gottl U., Kohlhase B., Vielhaber H., et al. APC resistance in neonates and infants: adjustment of the APTT-based method. Thromb Res 81 (1996) 665-670
76. Inbal A., Kenet G., Zivelin A., et al. Purpura fulminans induced by disseminated intravascular coagulation following infection in 2 unrelated children with double heterozygosity for factor V Leiden and protein S deficiency. Thromb Haemost 77 (1997) 1086-1089
77. Pipe S.W., Schmaier A.H., Nichols W.C., et al. Neonatal purpura fulminans in association with factor V R506Q mutation. J Pediatr 128 (1996) 706-709
78. Press R.D., Bauer K.A., Kujovich J.L., et al. Clinical utility of factor V leiden (R506Q) testing for the diagnosis and management of thromboembolic disorders. Arch Pathol Lab Med 126 (2002) 1304-1318
79. Taylor L.J., Oster R.A., Fritsma G.A., et al. Screening with the activated protein C resistance assay yields significant savings in a patient population with low prevalence of factor V leiden. Am J Clin Pathol 129 (2008) 494-499
80. Stenflo J. A new vitamin K-dependent protein. Purification from bovine plasma and preliminary characterization. J Biol Chem 251 (1976) 355-363
81. Miletich J., Sherman L., and Broze Jr. G. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Engl J Med 317 (1987) 991-996
82. Tait R.C., Walker I.D., Reitsma P.H., et al. Prevalence of protein C deficiency in the healthy population. Thromb Haemost 73 (1995) 87-93
83. van der Meer F.J., Koster T., Vandenbroucke J.P., et al. The Leiden Thrombophilia Study (LETS). Thromb Haemost 78 (1997) 631-635
84. Melissari E., Monte G., Lindo V.S., et al. Congenital thrombophilia among patients with venous thromboembolism. Blood Coagul Fibrinolysis 3 (1992) 749-758
85. Vossen C.Y., Conard J., Fontcuberta J., et al. Familial thrombophilia and lifetime risk of venous thrombosis. J Thromb Haemost 2 (2004) 1526-1532
86. Mahmoodi B.K., Brouwer J.L., Veeger N.J., et al. 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 118 (2008) 1659-1667
87. Finazzi G., and Barbui T. Different incidence of venous thrombosis in patients with inherited deficiencies of antithrombin III, protein C and protein S. Thromb Haemost 71 (1994) 15-18
88. Reitsma P.H. Protein C deficiency: from gene defects to disease. Thromb Haemost 78 (1997) 344-350
89. Reitsma P.H., Bernardi F., Doig R.G., et al. Protein C deficiency: a database of mutations, 1995 update. On behalf of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardization Committee of the ISTH. Thromb Haemost 73 (1995) 876-889
90. Ireland H., Bayston T., Thompson E., et al. Apparent heterozygous type II protein C deficiency caused by the factor V 506 Arg to Gln mutation. Thromb Haemost 73 (1995) 731-732
91. Vasse M., Borg J.Y., and Monconduit M. Protein C: Rouen, a new hereditary protein C abnormality with low anticoagulant but normal amidolytic activities. Thromb Res 56 (1989) 387-398
92. Wojcik E.G., Simioni P., d Berg M., et al. Mutations which introduce free cysteine residues in the Gla-domain of vitamin K dependent proteins result in the formation of complexes with alpha 1-microglobulin. Thromb Haemost 75 (1996) 70-75
93. Meijer P., Kluft C., Haverkate F., et al. 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 1 (2003) 748-753
94. Mitchell C.A., Rowell J.A., Hau L., et al. A fatal thrombotic disorder associated with an acquired inhibitor of protein C. N Engl J Med 317 (1987) 1638-1642
95. Malm J., Laurell M., and Dahlback B. Changes in the plasma levels of vitamin K-dependent proteins C and S and of C4b-binding protein during pregnancy and oral contraception. Br J Haematol 68 (1988) 437-443
96. Henkens C.M., Bom V.J., Van der Schaaf W., et al. Plasma levels of protein S, protein C, and factor X: effects of sex, hormonal state and age. Thromb Haemost 74 (1995) 1271-1275
97. Andrew M., Paes B., Milner R., et al. Development of the human coagulation system in the full-term infant. Blood 70 (1987) 165-172
98. Andrew M., Vegh P., Johnston M., et al. Maturation of the hemostatic system during childhood. Blood 80 (1992) 1998-2005
99. Monagle P., Barnes C., Ignjatovic V., et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 95 (2006) 362-372
100. Toh C.H., Samis J., Downey C., et al. Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca(++)-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation. Blood 100 (2002) 2522-2529
101. Maurissen L.F., Thomassen M.C., Nicolaes G.A., et al. Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation. Blood 111 (2008) 3034-3041
102. Yegneswaran S., Hackeng T.M., Dawson P.E., et al. The thrombin-sensitive region of protein S mediates phospholipid-dependent interaction with factor Xa. J Biol Chem 283 (2008) 33046-33052
103. Garcia de Frutos P., Fuentes-Prior P., Hurtado B., et al. Molecular basis of protein S deficiency. Thromb Haemost 98 (2007) 543-556
104. Rosing J., Maurissen L.F., Tchaikovski S.N., et al. Protein S is a cofactor for tissue factor pathway inhibitor. Thromb Res 1 Suppl 122 (2008) S60-S63
105. Castoldi E., and Hackeng T.M. Regulation of coagulation by protein S. Curr Opin Hematol 15 (2008) 529-536
106. Dykes A.C., Walker I.D., McMahon A.D., et al. 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 113 (2001) 636-641
107. Ten Kate M.K., Platteel M., Mulder R., et al. PROS1 analysis in 87 pedigrees with hereditary protein S deficiency demonstrates striking genotype-phenotype associations. Hum Mutat 29 (2008) 939-947
108. Strater R., Becker S., von Eckardstein A., et al. Prospective assessment of risk factors for recurrent stroke during childhood-a 5-year follow-up study. Lancet 360 (2002) 1540-1545
109. Aillaud M.F., Pouymayou K., Brunet D., et al. New direct assay of free protein S antigen applied to diagnosis of protein S deficiency. Thromb Haemost 75 (1996) 283-285
110. Pegelow C.H., Ledford M., Young J.N., et al. Severe protein S deficiency in a newborn. Pediatrics 89 (1992) 674-676
111. Carter I.S., Hewitt J., Pu C.H., et al. Severe protein S deficiency resulting from two novel mutations in PROS1 presenting with a relatively mild clinical phenotype. J Thromb Haemost 6 (2008) 1237-1239
112. Heeb M.J., Gandrille S., Fernandez J.A., et al. Late onset thrombosis in a case of severe protein S deficiency due to compound heterozygosity for PROS1 mutations. J Thromb Haemost 6 (2008) 1235-1237
113. Simmonds R.E., Zoller B., Ireland H., et al. Genetic and phenotypic analysis of a large (122-member) protein S-deficient kindred provides an explanation for the familial coexistence of type I and type III plasma phenotypes. Blood 89 (1997) 4364-4370
114. Goodwin A.J., Rosendaal F.R., Kottke-Marchant K., et al. A review of the technical, diagnostic, and epidemiologic considerations for protein S assays. Arch Pathol Lab Med 126 (2002) 1349-1366
115. D'Angelo S.V., Mazzola G., Della Valle P., et al. Variable interference of activated protein C resistance in the measurement of protein S activity by commercial assays. Thromb Res 77 (1995) 375-378
116. Faioni E.M., Boyer-Neumann C., Franchi F., et al. Another protein S functional assay is sensitive to resistance to activated protein C. Thromb Haemost 72 (1994) 648
117. Jennings I., Kitchen S., Cooper P., et al. Sensitivity of functional protein S assays to protein S deficiency: a comparative study of three commercial kits. J Thromb Haemost 1 (2003) 1112-1114
118. Carr Jr. M.E., Steingold K.A., and Zekert S.L. Protein S levels during the normal menstrual cycle and during estrogen therapy for premature ovarian failure. Am J Med Sci 306 (1993) 212-217
119. Gilabert J., Estelles A., Cano A., et al. The effect of estrogen replacement therapy with or without progestogen on the fibrinolytic system and coagulation inhibitors in postmenopausal status. Am J Obstet Gynecol 173 (1995) 1849-1854
120. Hughes Q., Watson M., Cole V., et al. Upregulation of protein S by progestins. J Thromb Haemost 5 (2007) 2243-2249
121. Stahl C.P., Wideman C.S., Spira T.J., et al. Protein S deficiency in men with long-term human immunodeficiency virus infection. Blood 81 (1993) 1801-1807
122. Nguyen P., Reynaud J., Pouzol P., et al. Varicella and thrombotic complications associated with transient protein C and protein S deficiencies in children. Eur J Pediatr 153 (1994) 646-649
123. Peyvandi F., Faioni E., Alessandro Moroni G., et al. Autoimmune protein S deficiency and deep vein thrombosis after chickenpox. Thromb Haemost 75 (1996) 212-213
124. Aadland E., Odegaard O.R., Roseth A., et al. Free protein S deficiency in patients with chronic inflammatory bowel disease. Scand J Gastroenterol 27 (1992) 957-960
125. Koutroubakis I.E., Sfiridaki A., Mouzas I.A., et al. Resistance to activated protein C and low levels of free protein S in Greek patients with inflammatory bowel disease. Am J Gastroenterol 95 (2000) 190-194
126. Sorice M., Arcieri P., Griggi T., et al. Inhibition of protein S by autoantibodies in patients with acquired protein S deficiency. Thromb Haemost 75 (1996) 555-559
127. Fernandez J.A., Estelles A., Gilabert J., et al. Functional and immunologic protein S in normal pregnant women and in full-term newborns. Thromb Haemost 61 (1989) 474-478
128. Melissari E., Nicolaides K.H., Scully M.F., et al. Protein S and C4b-binding protein in fetal and neonatal blood. Br J Haematol 70 (1988) 199-203
129. Kottke-Marchant K., and Duncan A. Antithrombin deficiency: issues in laboratory diagnosis. Arch Pathol Lab Med 126 (2002) 1326-1336
130. Dahlback B. Advances in understanding pathogenic mechanisms of thrombophilic disorders. Blood 112 (2008) 19-27
131. Okajima K., and Uchiba M. The anti-inflammatory properties of antithrombin III: new therapeutic implications. Semin Thromb Hemost 24 (1998) 27-32
132. Picard V., Nowak-Gottl U., Biron-Andreani C., et al. Molecular bases of antithrombin deficiency: twenty-two novel mutations in the antithrombin gene. Hum Mutat 27 (2006) 600
133. De Stefano V., Finazzi G., and Mannucci P.M. Inherited thrombophilia: pathogenesis, clinical syndromes, and management. Blood 87 (1996) 3531-3544
134. Rodeghiero F., and Tosetto A. The epidemiology of inherited thrombophilia: the VITA Project. Vicenza Thrombophilia and Atherosclerosis Project. Thromb Haemost 78 (1997) 636-640
135. Tait R.C., Walker I.D., Perry D.J., et al. Prevalence of antithrombin deficiency in the healthy population. Br J Haematol 87 (1994) 106-112
136. Demers C., Ginsberg J.S., Hirsh J., et al. Thrombosis in antithrombin-III-deficient persons. Report of a large kindred and literature review. Ann Intern Med 116 (1992) 754-761
137. Duhl A.J., Paidas M.J., Ural S.H., et al. Antithrombotic therapy and pregnancy: consensus report and recommendations for prevention and treatment of venous thromboembolism and adverse pregnancy outcomes. Am J Obstet Gynecol 197 (2007) 457 e451-421
138. Lane D.A., Bayston T., Olds R.J., et al. Antithrombin mutation database: 2nd (1997) update. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost 77 (1997) 197-211
139. Rossi E., Chiusolo P., Za T., et al. Report of a novel kindred with antithrombin heparin-binding site variant (47 Arg to His): demand for an automated progressive antithrombin assay to detect molecular variants with low thrombotic risk. Thromb Haemost 98 (2007) 695-697
140. Lane D.A., Olds R.J., Conard J., et al. Pleiotropic effects of antithrombin strand 1C substitution mutations. J Clin Invest 90 (1992) 2422-2433
141. Girolami A., Lazzaro A.R., and Simioni P. The relationship between defective heparin cofactor activities and thrombotic phenomena in AT III abnormalities. Thromb Haemost 59 (1988) 121
142. Wells P.S., Blajchman M.A., Henderson P., et al. Prevalence of antithrombin deficiency in healthy blood donors: a cross-sectional study. Am J Hematol 45 (1994) 321-324
143. Demers C., Henderson P., Blajchman M.A., et al. An antithrombin III assay based on factor Xa inhibition provides a more reliable test to identify congenital antithrombin III deficiency than an assay based on thrombin inhibition. Thromb Haemost 69 (1993) 231-235
144. Ungerstedt J.S., Schulman S., Egberg N., et al. Discrepancy between antithrombin activity methods revealed in Antithrombin Stockholm: do factor Xa-based methods overestimate antithrombin activity in some patients?. Blood 99 (2002) 2271-2272
145. Odegard O.R., Lie M., and Abildgaard U. Antifactor Xa activity measured with amidolytic methods. Haemostasis 5 (1976) 265-275
146. Sas G., Pepper D.S., and Cash J.D. Further investigations on antithrombin III in the plasmas of patients with the abnormality of antithrombin III Budapest. Thromb Diath Haemorrh 33 (1975) 564-572
147. Downing M.R., Bloom J.W., and Mann K.G. Comparison of the inhibition of thrombin by three plasma protease inhibitors. Biochemistry 17 (1978) 2649-2653
148. Bayston T.A., and Lane D.A. Antithrombin: molecular basis of deficiency. Thromb Haemost 78 (1997) 339-343
149. Corral J., Hernandez-Espinosa D., Soria J.M., et al. Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis. Blood 109 (2007) 4258-4263
150. Rao A.K., Niewiarowski S., Guzzo J., et al. Antithrombin III levels during heparin therapy. Thromb Res 24 (1981) 181-186
151. Meade T.W., Dyer S., Howarth D.J., et al. Antithrombin III and procoagulant activity: sex differences and effects of the menopause. Br J Haematol 74 (1990) 77-81
152. Iba T., Gando S., Murata A., et al. Predicting the severity of systemic inflammatory response syndrome (SIRS)-associated coagulopathy with hemostatic molecular markers and vascular endothelial injury markers. J Trauma 63 (2007) 1093-1098
153. Opal S.M., Kessler C.M., Roemisch J., et al. Antithrombin, heparin, and heparan sulfate. Crit Care Med 30 (2002) S325-S331
154. Dunzendorfer S., Kaneider N., Rabensteiner A., et al. Cell-surface heparan sulfate proteoglycan-mediated regulation of human neutrophil migration by the serpin antithrombin III. Blood 97 (2001) 1079-1085
155. Souter P.J., Thomas S., Hubbard A.R., et al. Antithrombin inhibits lipopolysaccharide-induced tissue factor and interleukin-6 production by mononuclear cells, human umbilical vein endothelial cells, and whole blood. Crit Care Med 29 (2001) 134-139
156. Oelschlager C., Romisch J., Staubitz A., et al. Antithrombin III inhibits nuclear factor kappaB activation in human monocytes and vascular endothelial cells. Blood 99 (2002) 4015-4020
157. Ling X., Delorme M., Berry L., et al. alpha 2-Macroglobulin remains as important as antithrombin III for thrombin regulation in cord plasma in the presence of endothelial cell surfaces. Pediatr Res 37 (1995) 373-378
158. Poort S.R., Rosendaal F.R., Reitsma P.H., et al. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88 (1996) 3698-3703
159. Gehring N.H., Frede U., Neu-Yilik G., et al. Increased efficiency of mRNA 3' end formation: a new genetic mechanism contributing to hereditary thrombophilia. Nat Genet 28 (2001) 389-392
160. Pollak E.S., Lam H.S., and Russell J.E. The G20210A mutation does not affect the stability of prothrombin mRNA in vivo. Blood 100 (2002) 359-362
161. Colucci M., Binetti B.M., Tripodi A., et al. Hyperprothrombinemia associated with prothrombin G20210A mutation inhibits plasma fibrinolysis through a TAFI-mediated mechanism. Blood 103 (2004) 2157-2161
162. Eikelboom J.W., Ivey L., Ivey J., et al. Familial thrombophilia and the prothrombin 20210A mutation: association with increased thrombin generation and unusual thrombosis. Blood Coagul Fibrinolysis 10 (1999) 1-5
163. Ripoll L., Paulin D., Thomas S., et al. Multiplex PCR-mediated site-directed mutagenesis for one-step determination of factor V Leiden and G20210A transition of the prothrombin gene. Thromb Haemost 78 (1997) 960-961
164. McNeil H.P., Chesterman C.N., and Krilis S.A. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 49 (1991) 193-280
165. Miyakis S., Lockshin M.D., Atsumi T., et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4 (2006) 295-306
166. Galli M., Luciani D., Bertolini G., et al. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 102 (2003) 2717-2723
167. Galli M., Luciani D., Bertolini G., et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 101 (2003) 1827-1832
168. Finazzi G., Brancaccio V., Moia M., et al. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry. Am J Med 100 (1996) 530-536
169. Bates S.M., Greer I.A., Pabinger I., et al. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. 8th edition. Chest 133 (2008) 844S-886S
170. Robertson L., Wu O., Langhorne P., et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol 132 (2006) 171-196
171. Zhang L., Whitis J.G., Embry M.B., et al. A simplified algorithm for the laboratory detection of lupus anticoagulants: utilization of two automated integrated tests. Am J Clin Pathol 124 (2005) 894-901
172. Brandt J.T., Triplett D.A., Alving B., et al. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost 74 (1995) 1185-1190
173. Genzen J.R., and Miller J.L. Presence of direct thrombin inhibitors can affect the results and interpretation of lupus anticoagulant testing. Am J Clin Pathol 124 (2005) 586-593
174. Bahar A.M., Kwak J.Y., Beer A.E., et al. Antibodies to phospholipids and nuclear antigens in non-pregnant women with unexplained spontaneous recurrent abortions. J Reprod Immunol 24 (1993) 213-222
175. Spadaro A., Riccieri V., Terracina S., et al. Class specific rheumatoid factors and antiphospholipid syndrome in systemic lupus erythematosus. Lupus 9 (2000) 56-60
176. Favaloro E.J., Wong R.C., Jovanovich S., et al. A review of beta2 -glycoprotein-l antibody testing results from a peer-driven multilaboratory quality assurance program. Am J Clin Pathol 127 (2007) 441-448
177. Kutteh W.H., and Franklin R.D. Assessing the variation in antiphospholipid antibody (APA) assays: comparison of results from 10 centers. Am J Obstet Gynecol 191 (2004) 440-448
178. Avcin T., and Silverman E.D. Antiphospholipid antibodies in pediatric systemic lupus erythematosus and the antiphospholipid syndrome. Lupus 16 (2007) 627-633
179. Avcin T., Cimaz R., Silverman E.D., et al. Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics 122 (2008) e1100-1107