Article information
Resumen
Se revisan los factores trombofílicos, tanto congénitos como adquiridos, y se definen la prevalencia y el riesgo trombótico de cada uno: déficit de antitrombina III, de proteínas C y S, factor V Leiden y mutación de la protrombina 20210, entre las anomalías con una probada base genética; hiperhomocistinemia, aumento de los factores VIII, IX, X y XI, disminución del receptor de la proteína C activada, aumento del inhibidor de la fibrinólisis activable por trombina, resistencia a la proteína C activada no vinculada al Leiden y deéficit de factor XII, en los que es bastante probable que exista un determinante genético.
La justificación del estudio de trombofilia en un individuo que ha presentado un episodio de trombosis es la valoración del riesgo trombótico en relación con la posibilidad de retrombosis.
El cribado de hipercoagulabilidad puede estar justificado en mujeres con pérdidas fetales y otras patologías del embarazo, si se considera el tratamiento con heparina de bajo peso molecular en posteriores gestaciones en las que sean portadoras de trombofilia.
En los pacientes con enfermedad tromboembólica (ETE), en los que se haya detectado alguna trombofilia congénita en el estudio familiar, se trata de identificar entre los familiars en primera línea a los portadores asintomáticos de cada anomalía, a fin de realizar en ellos una adecuada profilaxis en las situaciones de riesgo trombótico. La ETE es una enfermedad frecuente y potencialmente mortal, y, a menudo, la muerte súbita es una forma de presentación. Solamente con la valoración del riesgo y la aplicación de una correcta profilaxis se podrá disminuir su incidencia.
Palabras clave:
Trombofilia
Riesgo trombótico
Cribado de hipercoagulabilidad
Abstract
Hereditary and acquired thrombophilic factors are reviewed. The following deficits are commented: antithrombin III deficit. proteins C and S deficit, factor V Leiden deficit, prothrombin 20210 mutation, hiperhomocistein, increased of factors VIII, IX, X, XI, decreased of the activated protein C receptor, increased of thrombin activatable fibrinolysis inhibitor (TAFI), resistance to activated protein C and joint to factor V Leiden, and low levels of factor XII, emphasizing the prevalence and risks factors. The value of the thrombotic risk in relation to recurrent event is the justification of study of thrombophilia, in the subject who had suffered a thrombosis.
Screening of thrombophilia in women with fetal loss and other obstetric complications is justificated.
Treatment with heparin in those pregnant woman who are thrompbophilic is emphasized. In those patients with thrombosis and hereditary thrombophilia a family study to detect asyntomatic carriers is suggested in order to implement therapy to avoid thrombophilic risk. The thromboembolic venous disease is common and deadly condiition that often causes sudden dead. To known the thrombophilic risk and to make a correct prophylaxis may decrease the incidence.
Key words:
Thrombophilia
Thrombophilic risk
Screening of thrombophilia
Full text is only aviable in PDF
Bibliografía
[1.]
D.A. Lane, P.M. Mannucci, K.A. Bauer, R.M. Bertina, N.P. Bochokov, V. Boulyjenkov, et al.
Inherited thrombophilia.
Part I Thromb Haemost, 76 (1996), pp. 651-652
[2.]
D.A. Lane, R. Olds, M. Boisclair.
Antithrombin III mutation database: first update.
Thromb Haemost, 70 (1993), pp. 361-369
[3.]
D.A. Lane, T. Bayston, R. Olds.
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), pp. 197-211
[4.]
T.A. Bayston, D.A. Lane.
Antithrombin: molecular basis of deficiency.
Thromb Haemost, 78 (1997), pp. 339-343
[5.]
M. Takenaga, K. Horinouchi, K. Shirieda, T. Fukudome, T. Fujimoto.
A novel nonsense mutation in the AntiTrombina III gene (Ser365to Stop) causing Deep and Mesenteric Venous Thromboses.
Thromb Haemost, 85 (2001), pp. 570-571
[6.]
T. Koster, F.R. Rosendaal, E. Briet, 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, 85 (1995), pp. 2756-2761
[7.]
P.H. Reitsma, F. Bernardi, R.G. Doig, et al.
Protein C deficiency: a database of mutation, 1995 update. On behalf of the Subcommittee On Plasma coagulation Inhibir of the Scientific and Standardization Committee of the ISTH.
Thromb Haemost, 73 (1995), pp. 876-889
[8.]
B.P. Koleman, P.H. Reitsma, R.M. Bertina.
Familial thrombophilia: a complex genetic disorder.
Seminar in Haematology, 34 (1997), pp. 256-264
[9.]
T.B. Scott, E.G. Bovill, P.W. Callas, et al.
Genetic screening of candidates genes for a prothrombotic interaction with type I Protein C.
Thromb Haemostas, 85 (2001), pp. 82-87
[10.]
M.R. Gutiérrez Tous, C. Couto Caro, I. Simón Pilo, C. Urdanbidelus Aza.
Déficit de proteina C, polimorfismos de la protrombina G20210A y de la metilenetetrahidrofolatoreductasa C677T: Estudio familiar.
Jornadas de la AAHH, (2004),
[11.]
J.L.M. Van der Meer, T. Koster, J.P. Brandenbroucke, E. Briet, F.R. Rosendaal.
The Leiden Thrombophilia Study (LETS).
Thromb Haemost, 78 (1997), pp. 631-635
[12.]
S. Grandville, D. Borgel, H. Ireland, et al.
Protein S deficiency: a database of mutation. For the Plasma Coagulation Inhibitors Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.
Thromb Haemost, 77 (1997), pp. 1201-1214
[13.]
P. Simioni.
The molecular genetics of familial venous thrombosis.
Bailliere's Clinical Haematology, 12 (1999), pp. 479-503
[14.]
M. Makris, M. Leach, N.J. Beauchamp, et al.
Genetic analysis, phenotypic diagnosis and risk of venous thrombosis in families with inherited deficiencies of Protein S.
Blood, 95 (2000), pp. 1935-1941
[15.]
I. Martinelli, P.M. Mannucci, V. De Stefano, et al.
Different risk of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families.
Blood, 92 (1998), pp. 2353-2358
[16.]
R.M. Bertina, B.P. Koeleman, T. Koster, et al.
Mutation in blood coagulation Factor V associated with resistance to activated protein C.
Nature, 369 (1994), pp. 64-67
[17.]
D.C. Rees.
The population genetics of Factor V Leiden (Arg506Gln).
Br J Haematol, 95 (1996), pp. 579-586
[18.]
V. De Stefano, P. Chiusolo, K. Paciaroni, G. Leone.
Epidemiology of factor V Leiden: clinical implications.
Sem Thromb Haemost, 24 (1998), pp. 367-379
[19.]
A. Taher, I. Khalil, A. Shamseddine, F. El-Ahdab, A. Bazarbachi.
High prevalence of Factor V Leiden Mutation among healthy individuals and patients with deep venous thrombosis in Lebanon: in the Eastern Mediterranean region the area of origin of this mutation?.
Thromb Haemost, 86 (2001), pp. 723-724
[20.]
J.A. Bennett, L.J. Palmer, A.W. Musk, W.N. Erber.
Prevalence of Factor V Leiden and Prothrombin 20210 Mutations in indigenous Australians.
Tromb Haemost, 86 (2001), pp. 1592-1593
[21.]
M.R. Gutiérrez Tous, M.C. Couto Caro, G. García-Donas, I. Simón Pilo.
Prevalencia de los polimorfismos genéticos asociados a trombofilia en población sana del sur de España.
Med Clin, 122 (2004), pp. 556-557
[22.]
M.R. Gutiérrez, G. García-Donas, C. Couto, I. Simón, C. Urdanbidelus.
Factor de riesgo trombofílico en polimorfismos.
Haematologica, 89 (2004), pp. 161
[23.]
T. Koster, F.R. Rosendaal, P.H. Reitsma, R.M. Bertina.
Venous Thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study.
Lancet, 342 (1993), pp. 1503-1506
[24.]
P. Simioni, B.J. Sanson, P. Prandoni, et al.
Incidence of venous thromboembolism in families with inherited thrombophilia.
Thromb Haemost, 81 (1999), pp. 198-202
[25.]
J. Emmerich, F.R. Rosendaal, M. Castanet, et al.
Combined effect of Factor V Leiden and Prothrombin 20210 on the risk of venous thromboembolism.
Thromb Haemost, 86 (2001), pp. 809-816
[26.]
S. Middeldorp, C.M. Henkens, M.M. Koopman, et al.
The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis.
Ann Intern Med, 128 (1998), pp. 15-20
[27.]
P. Simioni, D. Tormene, P. Prandoni, et al.
Incidence of venous thromboembolism in asyntomatic family members who are carriers of factor V Leiden: a prospective cohort study.
Blood, 99 (2002), pp. 1938-1942
[28.]
F.R. Rosendaal, T. Koster, J.P. Vandenbrouke, P.H. Reitsma.
High risk of thrombosis in patients homozygous for factors V Leiden.
Blood, 85 (1995), pp. 1504-1508
[29.]
E.M. Ekhoff, F.R. Rosendaal, J.P. Vandenbrouke.
Minor evens and the risk of deep venous thrombosis.
Thromb Haemost, 83 (2000), pp. 408-411
[30.]
B. Manten, R.G. Westendorp, T. Koster, P.H. Reitsma, F.R. Rosendaal.
Risk factor profiles in patients with different clinical manifestation of venous thromboembolism: a focus on the factor V Leiden mutation.
Thromb Haemost, 76 (1996), pp. 510-513
[31.]
L. Hoekema, E. Castoldi, G. Tans, et al.
Functional properties of Factor V and Factor Va encoded by the R2 gene.
Thromb Haemost, 85 (2001), pp. 75-81
[32.]
J.M. Benson, D. Ellingsen, M. El-Jamil, et al.
Factor V Leiden and Factor V R2 allele: High-throughput analysis and association with venous thromboembolism.
Thromb Haemost, 86 (2001), pp. 1188-1192
[33.]
D. Williamson, K. Brown, R. Ludington, C. Baglin, T. Baglin.
Factor V Cambridge: a new mutation (Arg306Thr) associated with resistance to activated protein C.
Blood, 91 (1998), pp. 1140-1144
[34.]
A.J. Ten Cate, Y.T. Van de Hock, P.H. Reitsma, H. Ten Cate, P. Smits.
Mutation screening for thrombophilia: two cases with Factor V Cambridge without activated Protein C resistance.
Thromb Haemost, 87 (2002), pp. 919-920
[35.]
Lunghi B, Scanavbini D, Castoldi E, et al. The factor V Glu 1608 Lys mutation is recurrent in familial thrombophilia. J Thromb Haemost. En prensa 2005.
[36.]
E.M. Faioni, G. Castaman, D. Asti, F. Lussana, F. Rodeghiero.
Association of factor V deficiency with factor V HR2.
Haematologica, 89 (2004), pp. 195-200
[37.]
S.R. Poort, F.R. Rosendaal, P.H. Reitsma, R.M. Bertina.
A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and increase in venous thrombosis.
Blood, 88 (1996), pp. 3698-3703
[38.]
A. Zivelin, N. Rosenberg, S. Faier, et al.
A single genetic origin for the common prothrombotic G20210A polymorphism in the prothrombin gene.
Blood, 92 (1998), pp. 1119-1124
[39.]
H. Ceelie, R.M. Bertina, A. Van Hylckama Vlieg, F.R. Rosendaal, H.L. Vos.
Polymorphism in the prothrombin gene and their association with plasma prothrombin levels.
Thromb Haemost, 85 (2001), pp. 1066-1070
[40.]
M. Wylenzek, C. Geinsen, L. Stapenhorst, K. Wielckens, K.R. Klingler.
A novel point mutation in the 3’region of the Prothrombin gene at position 20221 in a Lebanese/Syrian family.
Thromb Haemost, 85 (2001), pp. 943-944
[41.]
F.R. Rosendaal, C.J. Doggen, A. Zivelin, et al.
Geographic distribution of the 20210 G to A prothrombin variant.
Thromb Haemost, 79 (1998), pp. 706-708
[42.]
I. Martinelli, P. Bucciarelli, M. Margaglione, V. De Stefano, G. Castaman, P.M. Mannucci.
The risk of venous thromboembolism in family members with mutation in the gene of Factor V or Prothrombin or both.
Br J Haematol, 111 (2000), pp. 1223-1229
[43.]
P.M. Mannucci.
Aspects of the clinical management of hereditary thrombophilia: a personal perspective.
Haemostasis, 30 (2000), pp. 11-15
[44.]
L.L. Kluijtmans, M. Den Heijer, P.H. Reitsma, et al.
Thermolabile methylenetetrahydrofolate reductase and factor V Leiden in the risk of deep-vein thrombosis.
Thromb Haemost, 79 (1998), pp. 254-258
[45.]
M.M. Rees, G.M. Rodgers.
Homocysteinemia: association of a metabolic disorder with vascular disease and thrombosis.
Thromb Reseach, 71 (1993), pp. 337-359
[46.]
M. Cattaneo.
Hyperhomocysteinemia, atherosclerosis and thrombosis.
Thromb Haemost, 81 (1999), pp. 165-179
[47.]
S.C. Guba, V. Fonseca, L.M. Fink.
Hyperhomocisteinemia and thrombosis.
Sem Thromb Haemost, 25 (1999), pp. 291-309
[48.]
P. Froot, H. Blom, R. Milos, et al.
A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate eductase.
Nature Genetics, 10 (1995), pp. 111-113
[49.]
V. De Stefano, I. Casorelli, E. Rossi, B. Zappacosta, G. Leone.
Interaction between hyperhomocysteinemia and inherited thrombophilic factors in venous thromboembolism.
Sem Thromb Haemost, 26 (2000), pp. 305-311
[50.]
H. Mandel, B. Brenner, M. Berant, et al.
Coexistence of hereditary homocystinuria and factor V Leiden-effect of thrombosis.
N England J Med, 334 (1996), pp. 763-768
[51.]
V. De Stefano, B. Zap Acosta, S. Persichilli, et al.
Prevalence of mild hyperhomocysteinaemia and association with thrombophilic genotypes (factor V Leiden and prothrombin G20210A) in Italian patients with venous thromboembolic disease.
Br J Haematol, 106 (1999), pp. 564-568
[52.]
T. Koster, A.D. Blann, E. Briet, et al.
Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis.
Lancet, 345 (1995), pp. 152-155
[53.]
J. O’Donnell, E.G. Tuddenham, R. Manning.
Higt prevalence of elevated factor levels in patients referred for thrombophilia screening.
Thromb Haemost, 77 (1997), pp. 825-828
[54.]
P.W. Kamphuisen, J.C. Eikenboom, H.L. Vos, et al.
Incresed levels of Factor VIII and Fibrinogen in patients with venous hrombosis are not caused by acute phase reactions.
Thromb Haemost, 81 (1999), pp. 680-683
[55.]
A. Tripodi.
Levels of coagulation factors and venous thromboembolism.
Haematologica, 88 (2003), pp. 705-711
[56.]
P.W. Kamphuisen, J.C. Eikenboom, F.R. Rosendaal, et al.
High Factor VIII antigen levels increase the risk of venous thrombosis but are nor associated with polymorphism in the von Willebrand factor and factor VIII gene.
Br J Haematol, 115 (2001), pp. 156-158
[57.]
P.A. Kyrle, E. Minar, M. Hirschl, et al.
High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.
N Engl J Med, 343 (2000), pp. 457-462
[58.]
A. Van Hylckama Vlieg, I.K. Van der Linden, R.M. Bertina, F.R. Rosendaal.
High levels of Factor IX increase the risk of venous thrombosis.
Blood, 95 (2000), pp. 3678-3682
[59.]
J.C. Meijers, W.L. Tekelenburg, B.N. Bouma, R.M. Bertina, F.R. Rosendaal.
High levels of coagulation factor XI as a risk factor for venous thrombosis.
N Engl J Med, 324 (2000), pp. 696-701
[60.]
M.C.H. De Viser, S.R. Poort, H.L. Vos, F.R. Rosendaal, R.M. Bertina.
Factor X levels, Polymorphism in the promoter region of factor X, and the risk of venous thrombosis.
Thromb Haemost, 85 (2001), pp. 1011-1017
[61.]
F. Rodeghiero, A. Tosetto.
Activated Protein C Resistance and Factor V Leiden mutation are independent risk factor for venous thromboembolism.
Ann Intern Med, 130 (1999), pp. 643-650
[62.]
M.C.H. De Viser, F.R. Rosendaal, R.M. Bertina.
A reduced sensitivity for activated Protein C in the absense of Factor V Leiden increases the risk of venous thrombosis.
Blood, 93 (1999), pp. 1271-1276
[63.]
M.C.H. De Viser, J.F. Guash, P.W. Kamphuisen, H.L. Vos, F.R. Rosendaal, R.M. Bertina.
The HR2 haplotype of factor V: effects on Factor V levels, normalizad activated protein C sensitivity ratios and the risk of venous thrombosis.
Thromb Haemost, 83 (2000), pp. 577-582
[64.]
I.A. Greer.
Thrombosis in Pregnancy: maternal and fetal issues.
Lancet, 353 (1999), pp. 1258-1265
[65.]
M. Greaves, F.E. Preston.
Rebuttal to: oral contraceptives and venous thromboembolism.
Thromb Haemost, 85 (2001), pp. 932-934
[66.]
N.H. Van Tilburg, F.R. Rosendaal, R.M. Bertina.
Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis.
Blood, 95 (2000), pp. 2855-2859
[67.]
M. Henry, H. Aubert, P.E. Morange, et al.
Identification of Polymorphism in the promoter and the 3’region of the TAFI gene: evidence the plasma TAFI antigen levels are strongly genetically controlled.
Blood, 977 (2001), pp. 2053-2058
[68.]
D.A. Tregouet, H. Aubrt, M. Henry, et al.
Combined segregation- linkage analysis of plasma thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels with TAFI gen polymorphism.
Him Genet, 109 (2001), pp. 191-197
[69.]
R.E. Simmonds, D.A. Lane.
The endothelial cell protein C receptor: a candidate genetic risk factor for thrombosis.
Thromb Haemost, 86 (2001), pp. 939-941
[70.]
M. Von Depka, A. Czwalinna, E. Roswith, et al.
Prevalence of a 23bp insertion in exon of the endothelial cell Protein C Receptor gene in venous thrombophilia.
Thromb Haemost, 86 (2001), pp. 1360-1362
[71.]
T. Kanaji, T. Okamura, K. Osaki, M. Kuroiwa, K. Shimoda, N. Hamasaki, et al.
A common genetic polymorphism (46 C to T substitution) in the 5’-Untranslated region of the coagulation factor XII gene is associated with low translation efficiency and decrease in plasma factor XII level.
Blood, 91 (1998), pp. 2010-2014
[72.]
R.M. Bertina, S.R. Poort, H.L. Vos, F.R. Rosendaal.
The 46 C-T polymorphism in the factor XII gene (F 12) and the risk of venous thrombosis.
J Thromb Haemost, 3 (2005), pp. 597
[73.]
Soria.
A quantitative trait locus in the human factor XII gene influences both plasma factor XII levels and susceptibility to thrombosis disease.
Am J Human Genet, 70 (2002), pp. 567-574
[74.]
R.G. Farquharson, Q. Siobhan, M. Greves.
Antiphospholipid Syndrom in pregnancy: a randomized, controlled trial of treatment.
Obstet Gynecol, 100 (2002), pp. 408-413
[75.]
S.L. Field, T.A. Brighton, H.P. McNeil, C.N. Chesterman.
Recent insight into antiphospholipid antibody-mediated thrombosis.
Baillier's Clinical Haematology, 12 (1999), pp. 407-422
[76.]
J.T. Brandt, D.A. Triplett, B. Alving, I. Scharren.
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), pp. 1885-1890
[77.]
W.A. Wilson, A.E. Gharavi, T. Koike, M.D. Lockshin, D.W. Branch, J.C. Piette, et al.
International consensus statement on preliminary classification criteria for definitive Antiphospholipid syndrome.
Arthritis Rheum, 42 (1999), pp. 1309-1311
[78.]
I. Martinelli, V. De Stefano, E. Taioli, K. Paciaroni, E. Rossi, P.M. Mannucci.
Inherited thrombophilia and first venous thromboembolism during pregnancy and puerperium.
Thromb Haemost, 87 (2002), pp. 791-795
[79.]
I. Martinelli, C. Legnani, P. Bucciarelli, E. Grandone, V. De Stefano, P.M. Mannucci.
Risk of Pregnancy-related venous Thrombosis in carriers of severe inherited thrombophilia.
Thromb Haemost, 86 (2001), pp. 800-803
[80.]
Zuazu-Jausoro, E. Pérez-Ceballos, M.J. Candela-García, M.L. Lozano.
Tratamiento de la enfermedad tromboembólica durante la gestación y en pediatría.
Angiología, 55 (2003), pp. 94-99
[81.]
A. Gerhadt, R.E. Scharf, M.W. Beckman.
Phrotrombin and Factor V Mutation in women with a history of thrombosis during pregnancy and the puerperium.
N Engl J Med, 342 (2000), pp. 374-380
[82.]
J.H. Rand, X.X. Wu, H.A.M. Andree, C.J. Lockwood, S. Guller, J. Scher, et al.
Pregnancy loss in the Antiphospholipid antibody syndrome a possible thrombogenic mechanism.
N Engl J Med, 337 (1997), pp. 154-160
[83.]
W.J. Polzin, J.N. Kopelman, R.D. Robinson, J.A. Read, K. Brady.
The association of Antiphospholipid Antibodies with pregnancies complicated by fetal growth restriction.
Ostet Gynecol, 78 (1991), pp. 1108-1111
[84.]
M.J. Kupferminc, G. Fait, A. Many, D. Gordon, A. Eldor, J.B. Lessing.
Severe preeclampsia and high frequency of genetic thrombophilic mutations.
Obstet Gynecol, 96 (2000), pp. 45-49
[85.]
E. Graandone, M. Margaglione, D. Colaizzo, G. Pavone, D. Paladini, P. Martinelli, et al.
Lower birth weight in neonates of mothers carrying factor V G1691A and factor IIA20210 mutations.
Haematologica, 87 (2002), pp. 177-181
[86.]
R. Von Kries, R. Junker, D. Oberle, A. Kosch, U. Nowak-Gottl.
Foetal Growth Restriction in children with prothrombotic risk factors.
Thromb Haemost, 86 (2001), pp. 1012-1016
[87.]
Z. Wiener-Megnagi, I. Ben-Shlomo, Y. Golberg, E. Shalev.
Resistence to activated protein C and the Leiden mutation: high prevalence in patients with abhruptio placentae.
Am J Obstet Gynecol, 179 (1998), pp. 1565-1567
[88.]
C. Infante-Rivard, G.E. Rivard, W.V. Yotov, E. Genin, M. Guiguet, C. Weinberg, et al.
Absence of association of thrombophilia polymorphisms with intrauterine growth restriction.
N Engl J Med, 347 (2002), pp. 19-25
[89.]
J.L. Kujovich.
Thrombophilia and pregnancy complications.
Am J Obstet Gynecol, 191 (2004), pp. 412-424
[90.]
M.R. Gutiérrez Tous, I. Simón, M.C. Couto, et al.
Genetic polymorphism Factor XII 46C-T and obstetric complications.
Haematologica, 90 (2005), pp. 35
[91.]
E. Hoibraaten, E. Quigstad, T.O. Andersen, M.C. Mowinckel, P.M. Sandsef.
The effect of hormone replacement therapy (HRT) on haemostatic variables in women with previous venous thromboembolism-results from a randomized, double-blind, clinical trial.
Thromb Haemost, 85 (2001), pp. 775-781
[92.]
S. Vehkavaara, A. Silveira, T. Hakala-Ala-Pietila, et al.
Effect of oral and transdermal estrogen replacement therapy on markers of coagulation, fibrinolysis, inflamation and serun lipid and lipoproteins in postmenopausal women.
Thromb Haemost, 85 (2001), pp. 619-625
[93.]
V. Marque, M. Alhenc-Gelas, G. Plu-Bureau, E. Oger, P.Y. Scarabin.
The effects of transdermal and oral estrogen/progesterone regimens on Free and Total Protein S in postmenopausal women.
Thromb-Haemost, 86 (2001), pp. 713-714
[94.]
I. Pabinger, B. Schneider.
Thrombotic risk in hereditary Antithrombin III, Protein C, or Protein S deficiency.
Arterioscler Thromb Vasc Biol, 16 (1996), pp. 742-748
[95.]
T. Baglin, R. Luddington, K. Brown, C. Baglin.
Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study.
Lancet, 362 (2003), pp. 523-526
[96.]
F.A. Anderson, F.A. Spencer.
Risk factor for venous thromboembolism.
Circulation, 107 (2003), pp. 9-16
[97.]
V. Stefano, E. Rossi, K. Paciaroni, G. Leone.
Screening for inherited thrombophilia: indications and therapeutic implications.
Haematologica, 87 (2002), pp. 1095-1108
[98.]
R. Lecumberri, R. Gutiérrez, E. Rocha.
Trombofilia: resultados en los pacientes del registro RIETE.
Haematologica, 89 (2004), pp. 229-232
[99.]
C.Y. Vossen, J. Conard, J. Fontcuberta, et al.
Risk of first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT).
J Thromb Haemost, 3 (2005), pp. 459
[100.]
I. Pabinger, R. Vormittag.
Thrombophilia and complications of pregnancy.
Hematology, 1 (2005), pp. 231-234
[101.]
F.R. Rosendaal.
Venous thrombosis: a multicausal disease.
Lancet, 353 (1999), pp. 1167-1173
Copyright © 2005. Sociedad Española de Reumatología