Download PDF
Thromb Haemost 1995; 74(01): 094-100
DOI: 10.1055/s-0038-1642659
Colloquium
Natural Inhibitors of Blood Cogulation
Schattauer GmbH Stuttgart

Management of Patients with Hereditary Defects Predisposing to Thrombosis Including Pregnant Women

Kenneth A Bauer
Hematology-Oncology Section, Brockton-West Roxbury Department of Veterans Affairs Medical Center, West Roxbury, MA, USA
› Author Affiliations
Further Information

Publication History

Publication Date:
09 July 2018 (online)

Also available at
  PDF Download  Permissions and Reprints
 

  • References

  • 1 Bauer KA. Hypercoagulable states. In: Hematology: Basic Principles and Clinical Practice. Second ed. Hoffman R, Benz Jr. EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE. eds. Churchill Livingstone; New York NY: 1995: 1781-1795
    Google Scholar
  • 2 Heijboer H, Brandjes DP M, Buller HR, Sturk A, ten Cate JW. Deficiencies of coagulation-inhibiting and fibrinolytic proteins in outpatients with deep venous thrombosis. N Eng J Med 1990; 323: 1512 -1516
    CrossrefPubMedGoogle Scholar
  • 3 Dahlback 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: 1004-1008
    PubMedGoogle Scholar
  • 4 Griffin JH, Evatt B, Wideman C, Fernandez JA. Anticoagulant protein C pathway defective in majority of thrombophilic patients. Blood 1993; 82: 1989-1993
    PubMedGoogle Scholar
  • 5 Koster T, Rosendaal FR, de Ronde H, Briet E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden thrombophilia study. Lancet 1993; 342: 1503-1506
    CrossrefPubMedGoogle Scholar
  • 6 Faioni EM, Franchi F, Asti D, Sacchi E, Bemardi F, Mannucci PM. Resistance to activated protein C in nine thrombophihcfamilies: interference in a protein S functional assay. Thromb Haemostas 1993; 70: 1067-1071
    PubMedGoogle Scholar
  • 7 Svensson PJ, Dahlback B. Resistance to activated protein C as a basis for venous thrombosis. N Eng J Med 1994; 330: 517-522
    CrossrefPubMedGoogle Scholar
  • 8 Halbmayer W-M, Haushofer A, Schon R, Fischer M. The prevalence of poor anticoagulant response to activated protein C (APC resistance) among patients suffering from stroke or venous thrombosis and among healthy subjects. Blood Coag Fibrinol 1994; 5: 51-57
    CrossrefPubMedGoogle Scholar
  • 9 Bertina RM, Koeleman BP C, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67
    CrossrefPubMedGoogle Scholar
  • 10 Greengard JS, Sun X, Xu X, Fernandez JA, Griffin J, Evatt B. Activated protein C resistance caused by Arg506Gln mutation in factor Va. Lancet 1994; 343: 1361-1362
    PubMedGoogle Scholar
  • 11 Voorberg J, Roelse J, Koopman R, Buller H, Berends F, ten Cate JW, Mertens K, van Mourik JA. Association of idiopathic venous thromboemboli sm with single point-mutation at Arg506of factor V. Lancet 1994; 343: 1535-1536
    CrossrefPubMedGoogle Scholar
  • 12 Zoller B, Dahlback B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis. Lancet 1994; 343: 1536-1538
    CrossrefPubMedGoogle Scholar
  • 13 Sun X, Evatt B, Griffin JH. Blood coagulation factor Va abnormality associated with resistance to activated protein C in venous thrombophilia. Blood 1994; 83: 3120-3125
    PubMedGoogle Scholar
  • 14 Zdller B, Svensson PJ, He X, Dahlback 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: 2521-2524
    CrossrefPubMedGoogle Scholar
  • 15 Dahlbäck B. Physiological anticoagulation. Resistance to activated protein C and venous thromboembolism. J Clin Invest 1994; 94: 923-927
    CrossrefPubMedGoogle Scholar
  • 16 Vandenbroucke JP, Koster T, Briet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344: 1453-1457
    CrossrefPubMedGoogle Scholar
  • 17 Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. In: Clinics in Haematology. Prentice CR M. ed. Saunders; London: 1981: 369-380
    Google Scholar
  • 18 Demers C, Ginsberg JS, Hirsh J, Henderson P, Blajchman MA. Thrombosis in antithrombin-III-deficient persons. Report of a laige kindred and literature review. Ann Intern Med 1992; 116: 754-761
    CrossrefPubMedGoogle Scholar
  • 19 Greengard JS, Eichinger S, Griffin JH, Bauer KA. Variability of thrombosis among homozygous siblings with resistance to activated protein C due to an Aig to Gin mutation in the gene for factor V. N Eng J Med 1994; 331: 1559-1561
    CrossrefPubMedGoogle Scholar
  • 20 van Boven HH, Reitsma PH, Rosendaal FR, Bayston TA, Chowdbury V, Bauer K, Scharrer I, Lane DA. Interaction of factor V Leiden with inherited antithrombin deficiency. Thromb Haemostas. 1995 73. in press (abstract)
    PubMedGoogle Scholar
  • 21 Koeleman BP C, Reitsma PH, Allaart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families. Blood 1994; 84: 1031-1035
    PubMedGoogle Scholar
  • Lane DA, Ireland H, Olds RJ, Thein SL, Perry DJ, Aiach M. Antithrombin III: a database of mutations. Thromb Haemostas 1991; 66: 657-661
    PubMedGoogle Scholar
  • 23 Finazzi G, Caccia R, Barbui T. Different prevalance of thromboembolism in the subtypes of congenital antithrombin deficiency: review of 404 cases Getter). Thromb Haemostas 1987; 58: 1094-1094
    PubMedGoogle Scholar
  • 24 Sakuragawa N, Takahashi K, Kondo S, Koide T. Antithrombin III Toyama: a hereditary abnormal antithrombin III of a patient with recurrent thrombophlebitis. Thromb Res 1983; 31: 305-317
    CrossrefPubMedGoogle Scholar
  • 25 Chasse JF, Esnard F, Guitton JD, Mouray H, Perigois F, Fauconneau G, Gauiithier F. An abnormal plasma antithrombin with no apparent affinity for heparin. Thromb Res 1984; 34: 297-302
    CrossrefPubMedGoogle Scholar
  • 26 Fischer AM, Comu P, Sternberg C, Meriane F, Dautzenberg MD, Chafa O, Beguin S, Desnos M. Antithrombin III Alger: a new homozygous AT III variant. Thromb Haemostas 1986; 55: 218-221
    PubMedGoogle Scholar
  • 27 Okajima K, Ueyama H, Hashimoto Y, Sasaki Y, Matsumoto K, Okabe H, Inoue M, Araki S, Takatsuki K. Homozygous variant of antithrombin III that lacks affinity forheparin, AT III Kumamato. Thromb Haemostas 1989; 61: 20-24
    PubMedGoogle Scholar
  • 28 Owen MC, Borg JY, Soria J, Caen J, Carrell RW. Heparin binding defect in a new antithrombin III variant: Rouen, 47 Arg to His. Blood 1987; 69: 1275-1279
    PubMedGoogle Scholar
  • 29 Borg JY, Owen MC, Soria C, Soria J, Caen J, Carrell RW. Proposed heparin binding site in antithrombin based on arginine 47. A new variant Rouen-II, 47 arg to ser. J din Invest 1988; 81: 1292-1296
    PubMedGoogle Scholar
  • 30 Boyer C, Wolf M, Vedrenne J, Meyer D, Larrieu MJ. Homozygous variant of antithrombin III: AT III Fountainebleau. Thromb Haemostas 1986; 56: 18-22
    PubMedGoogle Scholar
  • 31 Rosenberg RD. Actions and interaction of antithrombin and heparin. N Eng J Med 1975; 292: 146-151
    CrossrefPubMedGoogle Scholar
  • 32 Odegard OR, Abildgaard U. Antithrombin III: critical review of assay methods. Significance of variations in health and disease. Haemostasis 1978; 7: 127-134
    PubMedGoogle Scholar
  • 33 Meade TW, Dyer S, Howarth DJ, Imeson JD, Stirling Y. Antithrombin III and procoagulant activity; sex differences and effects of the menopause. Br J Haematol 1990; 74: 77-81
    CrossrefPubMedGoogle Scholar
  • 34 Tait C, Walker ID, Davidson JF, Islam SI A, Mitchell R. Antithrombin III activity in healthy blood donors: age and sex related changes and the prevalence of asymptomatic deficiency Getter). Br J Haematol 1990; 75: 141-142
    CrossrefPubMedGoogle Scholar
  • 35 Wells PS, Blajchman MA, Henderson P, Wells MJ, Demers C, Bourque R, McAvoy A. Prevalence of antithrombin deficiency in healthy blood donors: a cross-sectional study. Am J Hematol 1994; 45: 321-324
    CrossrefPubMedGoogle Scholar
  • 36 Tait RC, Walker ID, Perry DJ, Carrell RW, Islam SI A, McCall F, Mitchell R, Davidson JF. Prevalence of antithrombin III deficiency subtypes in 4000 healthy blood donors. Thromb Haemostas 1992; 65: 839 (abstract)
    PubMedGoogle Scholar
  • 37 Broekmans AW, Bertina RM, Protein C. In: Recent Advances in Blood Coagulation. Poller L. ed. Churchill Livingstone,; New York, NY: 1985: 117-137
  • 38 Bertina RM, Broekmans AW, Krommenhoek-van CEs, van Winhgaarden A. The use of a functional and immunolgic assay for plasma protein C in the study of the heterogenecity of congenital protein C deficiency. Thromb Haemostas 1984; 51: 1-5
    PubMedGoogle Scholar
  • 39 Comp PC, Nixon RR, Esmon CT. Determination of functional levels of protein C, an antithrombotic protein, using thrombin-thrombomodulin complex. Blood 1984; 63: 15-21
    PubMedGoogle Scholar
  • 40 D’Angelo SV, Comp PC, Esmon CT, D’Angelo A. Relationship between protein C antigen and anticoagulant activity during oral antiocoagulation and in selected disease states. J Clin Invest 1986; 77: 416-425
    CrossrefPubMedGoogle Scholar
  • 41 Bovill EG, Tomczak JA, Grant B, Bhushan F, Pillemer E, Rainville IR, Long GL. ProteinCVmoat:symptomatic type II protein C deficiency associated with two GLA domain mutations. Blood 1992; 79: 1456-1465
    PubMedGoogle Scholar
  • 42 Sala N, Borrell M, Bauer KA, D’Angelo SV, Fontcuberta J, Felez J, Rutllant ML. Dysfunctional activated protein C (PC Cadiz) in a patient with thrombotic disease. Thromb Haemostas 1987; 57: 183-186
    PubMedGoogle Scholar
  • 43 Faioni EM, Esmon CT, Esmon NL, Mannucci PM. Isolation of an abnormal protein C molecule from the plasma of a patient with thrombotic diathesis. Blood 1988; 71: 940-946
    PubMedGoogle Scholar
  • 44 Miletich JP, Sherman L, Broze Jr. GJ. Absence of thrombosis in subjects with heterozygous protein C deficiency. N Eng J Med 1987; 317: 991-996
    CrossrefPubMedGoogle Scholar
  • 45 Miletich JP, Prescott SM, White R, Majerus PW, Bovill EG. Inherited predisposition to thrombosis. Cell 1993; 72: 477-480
    CrossrefPubMedGoogle Scholar
  • 46 Schwarz HP, Fischer M, Hopmeier P, Batard MA, Griffin JH. Plasma protein S deficiency in familial thrombotic disease. Blood 1984; 64: 1297-1300
    PubMedGoogle Scholar
  • 47 Broekmans AW, Bertina RM, Reinalda-Poot J, Engesser L, Muller HP, Leeuw JA, Michiels JJ, Brommer E JP, Briet E. Hereditary protein S deficiency and venous thrombo-embolism. A study in three Dutch families. Thromb Haemostas 1985; 53: 273-277
    PubMedGoogle Scholar
  • 48 Comp PC, Doray D, Patton D, Esmon CT. An abnormal plasma distribution of protein S occurs in functional protein S deficiency. Blood 1986; 67: 504-508
    PubMedGoogle Scholar
  • 49 Comp PC, Esmon CT. Recurrent venous thromboembolism in patients with a partial deficiency of protein S. N Engl J Med 1984; 311: 1525-1528
    CrossrefPubMedGoogle Scholar
  • 50 Boerger LM, Morris PC, Thumau GR, Esmon CT, Comp PC. Oral contraceptives and gender affect protein S status. Blood 1987; 69: 692-694
    PubMedGoogle Scholar
  • 51 Miletich JP, Broze Jr. GJ. Age and gender dependence of total protein S antigen in the normal adult population. Blood 1988; 72: 371a (abstract)
    PubMedGoogle Scholar
  • 52 Schulman S, Tengbom L. Treatment of venous thromboembolism in patients with congenital deficiency of antithrombin III. Thromb Haemostas 1992; 68: 628-783
    PubMedGoogle Scholar
  • 53 Hoffman DL. Purification and large-scale preparation of antithrombin III. Am J Med 1989; 87: 23S-26S
    PubMedGoogle Scholar
  • 54 Menache D, O’Malley JP, Schorr JB, Wagner B, Williams C. the Cooperative Study Group. Evaluation of the safety, recoveiy, half-life, and cinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Blood 1990; 75: 33-39
    PubMedGoogle Scholar
  • 55 Ambruso DR, Leonard BD, Bies RD, Jacobson L, Hathaway WE, Reeve EB. Antithrombin III deficiency: decreased synthesis of a biochemically normal molecule. Blood 1982; 60: 78-83
    PubMedGoogle Scholar
  • 56 Mannucci PM, Boyer C, Wolf M, Triposi A, Larrieu MJ. Treatment of congenital antithrombin III deficiency with concentrates. Br J Haematol 1982; 50: 531-535
    CrossrefPubMedGoogle Scholar
  • 57 Winter JH. Tranfusion studies in patients with familial antithrombin III deficiency: half disappearance time of infused antithrombin III and influence of such infusions on platelet life span. Br J Haematol 1981; 49: 449-453
    CrossrefPubMedGoogle Scholar
  • 58 Brandt P. Observations during the treatment of antithrombin III deficient women in heparin and antithrombin III during pregnancy, parturition, and abortion. Thromb Res 1981; 22: 15-24
    CrossrefPubMedGoogle Scholar
  • 59 Schwartz RS, Bauer KA, Rosenberg RD, Kavanaugh EJ, Davies DC, Bogdanoff DA. Clinical experience with antithrombin III concentrate in treatment to congenital and acquired deficiency of antithrombin. Am J Med 1989; 87: 53S-60S
    PubMedGoogle Scholar
  • 60 Zauber NP, Stark MW. Successful warfarin anti coagulation despite protein C deficiency and a history of warfarin necrosis. Ann Int Med 1986; 104: 659-660
    CrossrefPubMedGoogle Scholar
  • 61 De Stefano V, Mastrangelo S, Schwarz HP, Pola P, Flore R, Bizzi B, Leone G. Replacement therapy with a purified protein C concentrate during initiation of oral anticoagulation in severe protein C congenital deficiency. Thromb Haemostas 1993; 70: 247-249
    PubMedGoogle Scholar
  • 62 Winter JH, Fenech A, Bennett B, Douglas AS. Prophylactic antithrombotic therapy with stanazolol in patients with familial antithrombin III deficiency. Br J Haematol 1984; 57: 527-537
    CrossrefPubMedGoogle Scholar
  • 63 Eyster ME, Parker ME. Treatment of familial antithrombin III deficiency with danazol. Haemostasis 1985; 15: 119-125
    PubMedGoogle Scholar
  • 64 Gonzalez R, Alberca I, Sala N, Vicente V. Protein C deficiency-reponse to danazol and DDAVP. Thromb Haemostas 1985; 53: 320-322
    PubMedGoogle Scholar
  • 65 Broekmans AW, Conard J, van Weyenberg RG, Horellou MH, Kluft C, Bertina RM. Treatment of hereditary protein C deficiency with stanazololy. Thromb Haemostas 1987; 57: 20-24
    PubMedGoogle Scholar
  • 66 De Stefano V, Leone G, Teofili L, Ferrelli R, Pollari G, Antonini V, Bizzi B. Transient ishemic attack in a patient with congenital protein-C deficiency during treatment with stanazolol. Am J Haematol 1988; 29: 120-121
    CrossrefPubMedGoogle Scholar
  • 67 Broekmans AW, Bertina RM, Loeliger EA, Hofman V, Klingemann HG. Protein C and the development of skin necrosis during anticoagulant therapy Getter). Thromb Haemostas 1983; 49: 244
    PubMedGoogle Scholar
  • 68 McGehee WG, Klotz TA, Epstein DJ, apaport SI. Coumarin necrosis associated with hereditary protein C deficiency. Ann Intern Med 1984; 100: 59-60
    CrossrefPubMedGoogle Scholar
  • 69 Samama M, Horellou MH, Soria J, Conard J, Nicolas G. Successful progressive anticoagulation in a severe protein C deficiency and previous skin necrosis at initiation of oral anticoagulant treatment Getter). Thromb Haemostas 1984; 51: 132-133
    PubMedGoogle Scholar
  • 70 Bauer KA. Coumarin-induced skin necrosis. Arch Dermatol 1993; 129: 766-768
    CrossrefPubMedGoogle Scholar
  • 71 Broekmans AW, Teepe RG C, van der Meer F JM, Briet E, Bertina RM. Protein C (PC) and coumarin-induced skin necrosis. Thromb Res 1986; 6: 137 (abstract)
    PubMedGoogle Scholar
  • 72 Friedman KD, Marlar RA, Houson JG, Montgomery RR. Warfarin-induced skin necrosis in a patient with protein S deficiency. Blood 1986; 68 (01) 333a (abstract)
    PubMedGoogle Scholar
  • 73 Schramm W, Spannagl M, Bauer KA, Rosenberg RD, Biricner B, Linnau Y, Schwarz HP. Treatment of coumarin-induced skin necrosis with a monoclonal antibody purified protein C concentrate. Arch Dermat 1993; 129: 753-756
    CrossrefPubMedGoogle Scholar
  • 74 Branson HE, Katz J, Marble R, Griffin JH. Inherited protein C deficiency and coumarin-responsive chonic relapsing purpura fulminans in a newborn infant. Lancet 1983; 2: 1165-1168
    PubMedGoogle Scholar
  • 75 Estelles A, Garcia-Plaza I, Dasi A, Aznar J, Duart M, Sanz G, Perez-Requejo JL, Espana F, Jimenez C, Abeledo G. Severe inherited ‘homozygous ’ protein C deficiency in a newborn infant. Thromb Haemostas 1984; 52: 53-56
    PubMedGoogle Scholar
  • 76 Sills RH, Marlar RA, Montgomery RR, Desphande GN, Humbert JR. Severe homozygous protein C deficiency. J Pediat 1984; 105: 409-413
    CrossrefPubMedGoogle Scholar
  • 77 Yuen P, Cheung A, Lin HJ, Ho F, Mimuro J, Yoshida N, Aoki N. Purpura fulminans in a Chinese boy with congenital protein C deficiency. Pediatrics 1986; 77: 670-676
    PubMedGoogle Scholar
  • 78 Rappaport ES, Speights VO, Helbert B, Trowbridge A, Kopps B, Montgomeiy RR, Marlar RA. Protein C deficiency. South Med J 1987; 80: 240-242
    CrossrefPubMedGoogle Scholar
  • 79 Marciniak E, Wilson HD, Marlar RA. Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood. Blood 1985; 65: 15-20
    PubMedGoogle Scholar
  • 80 Vigano S, Mannucci PM, Solinas S, Bottasso B, Mariani G. Decrease in protein C antigen and formation of an abnormal protein soon after starting oral anticoagulant therapy. Br J Haematol 1984; 29: 120-121
    PubMedGoogle Scholar
  • 81 Dreyfus M, Magny JF, Bridey F, Schwarz HP, Panche C, Dehan M, Tchemia G. Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Eng J Med 1991; 325: 1565-1568
    CrossrefPubMedGoogle Scholar
  • 82 Peters C, Casella JF, Marlar RA, Montgomery RR, Zinkman WH. Homozygous protein C deficiency: observations on the nature of the molecular abnormality and the effectiveness of warfarin therapy. Pediatrics 1988; 81: 272-276
    PubMedGoogle Scholar
  • 83 Garcia-Plaza I, Jiminez-Astorga C, Borrego D, Marty ML. Coumarin prophylaxis for fulminant purpura syndrome due to homozygous protein C deficiency (Letter). Lancet 1985; 1: 634-635
    PubMedGoogle Scholar
  • 84 Hartman KR, Manco-Johnson M, Rawlings JS, Bower DR, Marlar RA. Homozygous protein C deficiency: early treatment with warfarin. Am J Pediatr Hematol Oncol 1989; 11: 395-401
    Google Scholar
  • 85 Casella JF, Lewis JH, Bontempo FA, Zitelli BJ, Markel H, Starzl TE. Successful treatment of homozygous protein C deficiency by hepatic transplantation. Lancet 1988; 1: 435-438
    PubMedGoogle Scholar
  • 86 Mahasandana C, Suvatte V, Chuansumrit A, Marlar R, Manco-Johnson MJ, Jacobson U, Hathaway WE. Homozygous protein S deficiency in an infant with purpura fulminans. J Pediatr 1990; 117: 750-753
    CrossrefPubMedGoogle Scholar
  • 87 Pegelow CH, Ledford M, Young J, Zilleraelo G. Severe protein S deficiency in a newborn. Pediatrics 1992; 89: 674-676
    PubMedGoogle Scholar
  • 88 Devor M, Barrett-Connor E, Renvall M, Feigal Jr. D, Ramsdell J. Estrogen replacement therapy and the risk of venous thrombosis. Am J Med 1992; 92: 275-285
    CrossrefPubMedGoogle Scholar
  • 89 Hirsh J, Prins MH, Samama M. Approach to the thrombophilic patient for hemostasis and thrombosis: Basic Principles and Clinical Practice. In: Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Third ed. Colman RW, Hirsh J, Marder VJ, Salzman Em. eds. J.B. Lippincott Company; Philadelphia, PA: 1994: 1543-1561
    Google Scholar
  • 90 Hirsh J, Piovella F, Pini M. Congenital antithrombin III deficiency. Incidence and clinical features. Am J Med 1989; 87: 34S-38S
    PubMedGoogle Scholar
  • 91 Conard J, Horellou MH, VanDreden P, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiencies in ATIII, protein C or protein S: study of 78 women (letter). Thromb Haemostas 1990; 63: 319-320
    PubMedGoogle Scholar
  • 92 Ginsberg JS, Hirsh J. Anticoagulants during pregnancy. Annu Rev Med 1989; 40: 79-86
    CrossrefPubMedGoogle Scholar
  • 93 Iturbe-Alessio I, Fonseca MC, Mutchinik O, Santos MA, Zajarias A, Salazar E. Risks of anticoagulant therapy in pregnant women with artificial heart valves. N Eng J Med 1986; 315: 1390-1393
    CrossrefPubMedGoogle Scholar