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Thromb Haemost 1995; 73(03): 340-348
DOI: 10.1055/s-0038-1653778
Review Articles
Schattauer GmbH Stuttgart

Antithrombin III Concentrates-Are they Clinically Useful?

K Lechner
The Department of Medicine I, Division of Hematology/Blood Coagulation, University of Vienna, Vienna, Austria
,
P A Kyrle
The Department of Medicine I, Division of Hematology/Blood Coagulation, University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

Received14 September 1994

Accepted after revision 15 November 1994

Publication Date:
09 July 2018 (online)

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Summary

Treatment with AT III concentrates is a good example for the discrepancy between the optimistic expectations based on theoretical considerations or animal experiments and the result of clinical studies. 15 years after the introduction into clinical practice, a benefit for patients treated with AT III concentrates has not been proven. In hereditary antithrombin III deficiency, randomized clinical trials are completely lacking and only few and small sized randomized studies were performed in patients with acquired AT III deficiency. In none of these trials, a significant clinical benefit with regard to reduction of morbidity or mortality was detectable. Based on the published data, one can state that AT III concentrates may be beneficial in some special clinical situations in patients with hereditary antithrombin III deficiency (such as delivery, acute serious thromboembolic complications and postoperative thromboprophylaxis). In acquired AT III deficiency, there is no proven indication for the use of AT III concentrates.

 

  • References

  • 1 Rosenberg RD. Actions and interactions of antithrombin and heparin. N Engl J Med 1975; 292: 146-151
    CrossrefPubMedGoogle Scholar
  • 2 Egeberg O. Inherited antithrombin deficiency causing thrombophilia. Thromb Diath Haemorrh 1965; 13: 516-530
    PubMedGoogle Scholar
  • 3 Thaler E, Lechner K. Antithrombin III deficiency and thromboembolism. Clin Haematol 1981; 10: 369-390
    PubMedGoogle Scholar
  • 4 Hirsh J, Piovella F, Pini M. Congenital antithrombin III deficiency. Am J Med 1989 87 suppl (Suppl. 03) B 34S-38S
    PubMedGoogle Scholar
  • 5 Büller H, ten Cate JW. Acquired antithrombin III deficiency: laboratory diagnosis, incidence, clinical implications, and treatment with antithrombin III concentrate. Am J Med 1989; 87 suppl (Suppl. 03) B 44S-48S
    PubMedGoogle Scholar
  • 6 Miller-Andersson M, Borg H, Andersson LO. Purification of antithrombin III by affinity chromatography. Thromb Res 1974; 5: 439-452
    CrossrefPubMedGoogle Scholar
  • 7 Karges HE, Fuhge P, Heimburger N. Eigenschaften und Virussicherheit eines pasteurisierten Antithrombin III-Konzentrates. Arzneim.-Forsch 1987; 37: 756-758
    PubMedGoogle Scholar
  • 8 Hoffman DL. Purification and large-scale preparation of antithrombin III. Am J Med 1989; 87 suppl (Suppl. 03) B 23S-26S
    PubMedGoogle Scholar
  • 9 Schwartz RS, Bauer KA, Rosenberg RD, Kavanaugh EJ, Davies DC, Bogdanoff DA. Clinical experience with antithrombin III concentrate in treatment of congenital and acquired deficiency of antithrombin. Am J Med 1989; 87 suppl (Suppl. 03) B 53S-60S
    PubMedGoogle Scholar
  • 10 Menache D, O’Malley JP, Schorr JB, Wagner B, Williams C. The Cooperative Study Group Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Blood 1990; 75: 33-39
    PubMedGoogle Scholar
  • 11 Straub H, Risse U, Braun BE, Schlösser S, Barth J, Drews S, May B. In-vivo-recovery bei Antithrombin-III-Substitution. Arzneimitteltherapie 1989; 1: 6-9
    PubMedGoogle Scholar
  • 12 Handeland GF, Abildgaard U. In vivo recovery of antithrombin concentrates. Thromb Res 1985; 39: 133-138
    CrossrefPubMedGoogle Scholar
  • 13 Rodeghiero F, Castaman G, Gugliotta L, Mattioli BelmonteM, Falanga A, Bottasso B, Barbui T, Mannucci PM. Supranormal antithrombin III levels induced by concentrate administration are ineffective in quenching thrombin generation in acute promyelocytic leukemia. Thromb Res 1993; 69: 377-385
    CrossrefPubMedGoogle Scholar
  • 14 De Swart CA M, Nijmeyer B, Andersson LO, Holmer E, Sixma JJ, Bouma BN. Elimination of intravenously administered radiolabelled antithrombin III and heparin in humans. Thromb Haemost 1984; 52: 66-70
    PubMedGoogle Scholar
  • 15 Knot EA R, de JongE, ten CateJ, Gie LK, van RoyenE. Antithrombin III: Biodistribution in healthy volunteers. Thromb Haemost 1987; 58: 1008-1011
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Collen D, Schetz J, de CockF, Holmer E, Verstraete M. Metabolism of antithrombin III (heparin cofactor) in man: effects of venous thrombosis and of heparin administration. Eur J Clin Invest 1977; 7: 27-35
    CrossrefPubMedGoogle Scholar
  • 17 Knot EA R, de JongE, ten CateJ, Iburg AH C, Henny CP, Bruin T, Stibbe J. Purified radiolabeled antithrombin III metabolism in three families with hereditary AT III deficiency: application of a three-compartment model. Blood 1986; 67: 93-98
    PubMedGoogle Scholar
  • 18 Tengbom L, Frohm B, Nilsson LE, Johansson L, Andersson LO. Properties and catabolism of heat treated antithrombin III concentrate. Thromb Res 1987; 48: 701-711
    CrossrefPubMedGoogle Scholar
  • 19 Weiner CP, Herrig JE, Pelzer GD, Heilskov J. Elimination of antithrombin III concentrate in healthy pregnant and preeclamptic women with an acquired antithrombin III deficiency. Thromb Res 1990; 58: 395-401
    CrossrefPubMedGoogle Scholar
  • 20 Hirsh J. Anticoagulant therapy in venous thromboembolism. Bailliére’s Clin Haematol 1990; 3: 685-690
    PubMedGoogle Scholar
  • 21 Ofosu FA, Barrowcliffe TW. Interaction of unfractionated and LMW heparins with other plasma proteins. Clin Haematol 516-523
    PubMedGoogle Scholar
  • 22 Levine SP, Sorenson RR, Harris MA, Knieriem LK. The effect of platelet factor 4 (PF4) on assays of plasma heparin. Br J Haematol 1984; 57: 585-596
    CrossrefPubMedGoogle Scholar
  • 23 Lijnen HR, Hoylaerts M, Collen D. Heparin binding properties of human histidine-rich glycoprotein. J Biol Chem 1983; 258: 3803-3808
    PubMedGoogle Scholar
  • 24 Young E, Prins M, Levine MN, Hirsh J. Heparin binding to plasma proteins, an important mechanism for heparin resistance. Thromb Haemost 1992; 67: 639-643
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Langley PG, Keays R, Hughes RD, Forbes A, Delvos U, Williams R. Antithrombin III supplementation reduces heparin requirement and platelet loss during hemodialysis of patients with fulminant hepatic failure. Hepatology 1991; 14: 251-256
    CrossrefPubMedGoogle Scholar
  • 26 Thaler E, Niessner H, Kleinberger G, Gassner A. Antithrombin III replacement in patients with congenital and acquired antithrombin III deficiency. Thromb Haemost 1979; 42: 327 abstract
    PubMedGoogle Scholar
  • 27 Schrader J, Köstering H, Kramer P, Scheler F. Antithrombin-III-Substitution bei dialysepflichtiger Niereninsuffizienz. Dtsch Med Wochenschr 1982; 107: 1847-1850
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Soloway HB, Christiansen TW. Heparin anticoagulation during cardiopulmonary bypass in an antithrombin-III deficient patient Implications relative to the etiology of heparin rebound. Am Soc Clin Pathol 1980; 73: 723-725
    PubMedGoogle Scholar
  • 29 Cruickshank MK, Levine MN, Hirsh H, Roberts R, Siguenza M. A standard heparin nomogram for the management of heparin therapy. Arch Intern Med 1991; 151: 333-337
    CrossrefPubMedGoogle Scholar
  • 30 Schulman S, Tengborn L. Treatment of venous thromboembolism in patients with congenital deficiency of antithrombin III. Thromb Haemost 1992; 68: 634-366
    Article in Thieme ConnectPubMedGoogle Scholar
  • 31 Schramm W. Erfahrungen mit der Substitution von Antithrombin III-Kon- zentraten bei angeborenen und erworbenen Mangelzuständen. Behring Inst Mitt 1983; 73: 66-78
    PubMedGoogle Scholar
  • 32 Mannucci PM, Boyer C, Wolf M, Tripodi A, Larrieu MJ. Treatment of congenital antithrombin III deficiency with concentrates. Br J Haematol 1982; 50: 531-535
    CrossrefPubMedGoogle Scholar
  • 33 Hambley H, Davidson JF, Walker ID, Menzies T. Prophylactic use of an tithrombin III concentrate following surgery in congenital antithrombin III deficiency. Clin Lab Haemat 1987; 9: 27-31
    CrossrefPubMedGoogle Scholar
  • 34 Tengborn L, Bergqvist D. Surgery in patients with congenital antithrombin III deficiency. Acta Chir Scand 1988; 154: 179-183
    PubMedGoogle Scholar
  • 35 Jespersen J, Gram J, Kluft C, Astrup T. Protection against venous thrombosis in an antithrombin-III deficient patient suffering from episodes of arterial thrombosis requiring major surgery. Am J Clin Pathol 1985; 83: 768-771
    CrossrefPubMedGoogle Scholar
  • 36 Gallus A, Cade J, Ockelford P, Hepburn S, Maas M, Magnani H, Bucknall T, Stevens J, Porteous F. Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease. A doubleblind, randomised, multicentre comparison Thromb Haemost 1993; 70: 562-567
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 Imbimbo BP, Sié P, Agnelli G, Saivin S, Dupouy D, Damiani M, Houin G, Gianese F. Intramuscular dermatan sulfate MF701 in patients with hip fracture: relationship between pharmacokinetics and antithrombotic efficacy. Thromb Haemost 1994; 71: 553-557
    Article in Thieme ConnectPubMedGoogle Scholar
  • 38 Hellgren M, Tengborn L, Abildgaard U. Pregnancy in women with congenital antithrombin III deficiency: experience of treatment with heparin and antithrombin. Gynecol Obstet Invest 1982; 14: 127-141
    CrossrefPubMedGoogle Scholar
  • 39 Conard J, Horellou MH, van DredenP, Lecompte T, Samama M. Thrombosis and pregnancy in congenital deficiencies in AT III, protein C or protein S: study of 78 women. Thromb Haemost 1990; 63: 319-320
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 De StefanoV, Leone G, Mastrangelo S, Tripodi A, Rodeghiero F, Castaman G, Barbui T, Finazzi G, Bizzi B, Mannucci PM. Thrombosis during pregnancy and surgery in patients with congenital deficiency of antithrombin III, protein C, protein S. Thromb Haemost 1994; 71: 799-800
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Pabinger I, Schneider B. GTH Study Group on Natural Inhibitors. Clinical manifestations of hereditary antithrombin III-, protein C- and protein S-deficiency. Personal Communication
    PubMedGoogle Scholar
  • 42 Brandt P, Stenbjerg S. Subcutaenous heparin for thrombosis in pregnant women with hereditary antithrombin deficiency. Lancet 1979; 1: 100-101
    PubMedGoogle Scholar
  • 43 Samson D, Stirling Y, Woolf L, Howarth D, Seghatchian MJ, de ChazalR. Management of planned pregnancy in a patient with congenital antithrombin III deficiency. Br J Haematol 1984; 56: 243-249
    CrossrefPubMedGoogle Scholar
  • 44 Leclerc JR, Geerts W, Panju A, Nguyen P, Hirsh J. Management of antithrombin III deficiency during pregnancy without administration of antithrombin III. Thromb Res 1986; 41: 567-573
    CrossrefPubMedGoogle Scholar
  • 45 Schoch U, Zanetti E, von FeltenA. Thromboembolieprophylaxe während der Schwangerschaft bei 3 Schwestern mit kongenitalem Antithrombin III-Mangel und vermindert stimulierbarer Fibrinolyse. Schweiz Med Wschr 1987; 117: 1807-1810
    PubMedGoogle Scholar
  • 46 Blondel-Hill E, Mant MJ. The pregnant antithrombin III deficient patient: management without anti thrombin III concentrate. Thromb Res 1992; 65: 193-198
    CrossrefPubMedGoogle Scholar
  • 47 Neerhof MG, Krewson DP, Haut M, Librizzi RJ. Heparin therapy for congenital antithrombin III deficiency in pregnancy. Am J Perinatol 1993; 10: 311-312
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Zucker ML, Gomperts ED, Marcus RG. Prophylactic and therapeutic use of anticoagulants in inherited antithrombin III deficiency. S Afr Med J 1976; 50: 1743-1748
    PubMedGoogle Scholar
  • 49 Michiels JJ, Stibbe J, Vellenga E, van Vliet HH D M. Prophylaxis of thrombosis in antithrombin Ill-deficient women during pregnancy and delivery. Europ J Obstet Gynec Reprod Biol 1984; 18: 149-153
    CrossrefPubMedGoogle Scholar
  • 50 Nelson DM, Stempel LE, Brandt JT. Hereditary antithrombin III deficiency and pregnancy: report of two cases and review of the literature. Obstet Gynecol 1985; 65: 848-853
    PubMedGoogle Scholar
  • 51 De StefanoV, Leone G, De CarolisS, Ferrelli R, Di DonfrancescoA, Moneta E, Bizzi B. Management of pregnancy in women with antithrombin III congenital defect: report of four cases. Thromb Haemost 1988; 59: 193-196
    Article in Thieme ConnectPubMedGoogle Scholar
  • 52 Megha A, Finzi G, Poli T, Manotti C, Dettori AG. Pregnancy,antithrombin III deficiency and venous thrombosis: report of another case. Acta Haematol 1990; 83: 111
    CrossrefPubMedGoogle Scholar
  • 53 Brenner B, Tavori S, Tatarsky I. Prophylaxis of thromboembolism during pregnancy in hereditary AT-III deficiency. Am J Hematol 1992; 39: 71-72
    CrossrefPubMedGoogle Scholar
  • 54 Kario K, Matsuo T, Kodama K, Matsuo M. Prophylactic antithrombin III administration during pregnancy immediately reduces the thrombin hyperactivity of congenital antithrombin III deficiency by forming thrombinantithrombin III complexes. Thromb Res 1992; 66: 509-515
    CrossrefPubMedGoogle Scholar
  • 55 Brandt P. Observations during the treatment of antithrombin-III deficient women with heparin and antithrombin concentrate during pregnancy, parturition, and abortion. Thromb Res 1981; 22: 15-24
    CrossrefPubMedGoogle Scholar
  • 56 Jespersen J. Termination of pregnancy in a woman with hereditary antithrombin deficiency under antithrombotic protection with subcutaneous heparin and infusion of plasma. Gynecol Obstet Invest 1981; 12: 257-271
    PubMedGoogle Scholar
  • 57 Peters M, Jansen E, ten CateJ, Kahlé LH, Ockelford P, Breederveld C. Neonatal antithrombin III. Br J Haematol 1984; 58: 579-587
    CrossrefPubMedGoogle Scholar
  • 58 Manco-Johnson MJ. Neonatal antithrombin III deficiency. Am J Med 1989; 87 suppl (Suppl. 03) B 49S-52S
    PubMedGoogle Scholar
  • 59 De StefanoV, Leone G, de CarolisM, Ferrelli R, de CarolisS, Pagano L, Tortorolo G, Bizzi B. Antithrombin III in full-term and pre-term newborn infants: three cases of neonatal diagnosis of AT III congenital defect. Thromb Haemost 1987; 57: 329-331
    Article in Thieme ConnectPubMedGoogle Scholar
  • 60 Schnader K, Niesen M, Rehm A, Budde U, Müller N. Diagnose und Therapie eines kongenitalen Antithrombin III-Mangels in der Neonatalperiode. In: Fibrinolyse, Thrombose, Hämostase. Deutsch E, Lechner K. eds Stuttgart; New York: 1980
    Google Scholar
  • 61 Shiozaki A, Arai T, Izumi R, Niiya K, Sakuragawa N. Congenital antithrombin III deficient neonate treated with antithrombin III concentrates. Thromb Res 1993; 70: 211-216
    CrossrefPubMedGoogle Scholar
  • 62 Hakten M, Deniz U, Özbay G, Ulutin ON. Two cases of homozygous antithrombin III deficiency in a family with congenital deficiency of AT III. In: Thrombosis and Hemorrhagic Disorders. Sinzinger H, Vinazzer H. eds Würzburg: Meyer GmbH; 1989: 177-181
    Google Scholar
  • 63 Bjarke B, Herin P, Blombäck M. Neonatal aortic thrombosis. Acta Paedi- at Scand 1974; 63: 297-301
    PubMedGoogle Scholar
  • 64 Rais-Bahrami K, Barry D, Naqvi M, Habersang R. Thrombosis of left heart in a newborn. Clin Pediatr 1992; 31: 508-509
    CrossrefPubMedGoogle Scholar
  • 65 Winter JH, Fenech A, Ridley W, Bennett B, Cumming AM, Mackie M, Douglas AS. Familial antithrombin III deficiency. Q J Med 1982; 204: 373-395
    PubMedGoogle Scholar
  • 66 Brenner B, Fishman A, Goldsher D, Schreibman D, Tavory S. Cerebral thrombosis in a newborn with a congenital deficiency of antithrombin III. Am J Hematol 1988; 27: 209-211
    CrossrefPubMedGoogle Scholar
  • 67 Nouri A, Belghith M, Mekki M, Gargouri A, Rekik A, Catelli R. Neonatal testicular ischemic necrosis without torsion, associated with antithrombin III deficit. Ann Pediatr Paris 1993; 40: 628-630
    PubMedGoogle Scholar
  • 68 Jochmans K, Lissens W, Vervoort R, Peeters S, de Waele M, Liebaers I. Antithrombin-Gly 424 Arg: A novel point mutation responsible for type 1 antithrombin deficiency and neonatal thrombosis. Blood 1994; 83: 146-151
    PubMedGoogle Scholar
  • 69 Peeters S, Vandenplas Y, Jochmans K, Bougatef A, de WaeleM, de WolfD. Myocardial infarction in a neonate with hereditary antithrombin III deficiency. Acta Paediatr 1993; 82: 610-613
    CrossrefPubMedGoogle Scholar
  • 70 Montaner MM I, de Aguilar AV, Arrufal AA. Thrombosis de la arteria pulmonar asociada a deficit materno de antithrombina III. An Esp Pediatr 1987; 26: 115-117
    PubMedGoogle Scholar
  • 71 Seguin J, Weatherstone K, Nanhervis C. Inherited antithrombin III deficiency in the neonate. Arch Pediatr Adolesc Med 1994; 148: 389-393
    CrossrefPubMedGoogle Scholar
  • 72 Henny CP, ten CateH, ten CateJ, Prummel MF, Peters M, Btiller HR. Thrombosis prophylaxis in an AT III deficient pregnant woman: application of a low molecular weight heparinoid. Thromb Haemost 1986; 55: 301-302
    Article in Thieme ConnectPubMedGoogle Scholar
  • 73 Lechner K, Niessner H, Thaler E. Coagulation abnormalities in liver disease. Sem Thromb Haemost 1977; 4: 40-56
    Article in Thieme ConnectPubMedGoogle Scholar
  • 74 Tytgat GN, Collen D, Verstraete M. Metabolism of fibrinogen in cirrhosis of the liver. J Clin Invest 1971; 50: 1690-1701
    CrossrefPubMedGoogle Scholar
  • 75 Schipper HG, ten CateJ. Antithrombin III transfusion in patients with hepatic cirrhosis. Br J Haematol 1982; 52: 25-33
    CrossrefPubMedGoogle Scholar
  • 76 Collen D, Rouvier J, Chamone DA F, Verstraete M. Turnover of radiolabelled plasminogen and prothrombin in cirrhosis of the liver. Eur J Clin Invest 1978; 8: 185-195
    CrossrefPubMedGoogle Scholar
  • 77 Lerner RG, Nelson JC, Corines P, del Buercio LR M. Disseminated intravascular coagulation. Complication of LeVeen peritoneovenous shunts JAMA 1978; 240: 2064-2066
    CrossrefPubMedGoogle Scholar
  • 78 Büller HR, ten CateJ. Antithrombin III infusion in patients undergoing peritoneovenous shunt operation: failure in the prevention of disseminated intravascular coagulation. Thromb Haemost 1983; 49: 128-131
    Article in Thieme ConnectPubMedGoogle Scholar
  • 79 Korninger C, Klepetko W, Miholic J, Schwarz Ch, Lechner K. Randomized trial of antithrombin III versus placebo in patients undergoing peritoneal-venous shunt operation. Thromb Haemost 1987; 58: 426 abstr
    Article in Thieme ConnectPubMedGoogle Scholar
  • 80 Rake MO, Flute PT, Pannell G, Williams R. Intravascular coagulation in acute hepatic necrosis. Lancet 1970; 1: 533-537
    PubMedGoogle Scholar
  • 81 Ronneberger H, Hein B. Wirkung von Antithrombin III auf experimentelle Intoxikationen mit Hepatotoxinen bei Hunden. Arzneim.-Forsch 1984; 34: 277-279
    PubMedGoogle Scholar
  • 82 Fujiwara K, Ogata I, Ohta Y, Hirata K, Oka Y, Yamada S, Sato Y, Masaki N, Oka H. Intravascular coagulation in acute liver failure in rats and its treatment with antithrombin III. Gut 1988; 29: 1103-1108
    CrossrefPubMedGoogle Scholar
  • 83 Langley PG, Hughes RD, Forbes A, Keays R, Williams R. Controlled trial of antithrombin III supplementation in fulminant hepatic failure. J Hepatol 1993; 17: 326-331
    CrossrefPubMedGoogle Scholar
  • 84 Böhmig HJ. The coagulation disorder of orthotopic hepatic transplantation. Semin Thromb Hemost 1977; 4: 57-82
    Article in Thieme ConnectPubMedGoogle Scholar
  • 85 Bakker CM, Metselaar HJ, Gomes MJ, Porte RJ, Groenland TN, Schalm SW, Terpstra OT, Stibbe J. Intravascular coagulation in liver transplantation - Is it present or not. Thromb Haemost 1993; 69: 25-28
    Article in Thieme ConnectPubMedGoogle Scholar
  • 86 Baudo F, DeGasperi A, deCataldo F, Caimi TM, Cattaneo D, Redaelli R, Pannacciulli E, Corti A, Mazza E, Belli L. Antithrombin III supplementation during orthotopic liver transplantation in cirrhotic patients: a randomized trial. Thromb Res 1992; 68: 409-416
    CrossrefPubMedGoogle Scholar
  • 87 Palareti G, Legnani C, Maccaferri M, Gozzetti G, Mazziotti A, Martinelli G, Zanello M, Sama C, Coccheri S. Coagulation and fibrinolysis in orthotopic liver transplantation: role of the recipient’s disease and use of antithrombin III. Haemostasis 1991; 21: 68-76
    PubMedGoogle Scholar
  • 88 Shimada M, Matsumata T, Kamakura T, Hayashi H, Urata K, Sugimachi K. Modulation of coagulation and fibrinolysis in hepatic resection: a randomized prospective control study using antithrombin III concentrates. Thromb Res 1994; 74: 105-114
    CrossrefPubMedGoogle Scholar
  • 89 Laursen B, Mortensen JZ, Frost L, Hansen KB. Disseminated intravascu lar coagulation in hepatic failure treated with antithrombin III. Thromb Res 1981; 22: 701-704
    CrossrefPubMedGoogle Scholar
  • 90 Hellgren M, Hägnevik K, Robbe H, Bjork O, Blombâck M, Eklund J. Severe acquired antithrombin III deficiency in relation to hepatic and renal insufficiency and intrauterine fetal death in late pregnancy. Gynecol Obstet Invest 1983; 16: 107-118
    CrossrefPubMedGoogle Scholar
  • 91 Thaler E, Balzar E, Kopsa H, Pinggera WF. Acquired antithrombin III deficiency in patients with glomerular proteinuria. Haemostasis 1978; 7: 257-272
    PubMedGoogle Scholar
  • 92 Kauffmann RH, Veitkamp JJ, van Tilburg NH, van Es LA. Acquired antithrombin III deficiency and thrombosis in nephrotic syndrome. Am J Med 1978; 65: 607-613
    CrossrefPubMedGoogle Scholar
  • 93 Drijfhout HH, Knot EA R, ten CateJ. Antithrombin III metabolism in two patients with a nephrotic syndrome caused by minimal change nephritis and primary amyloidosis. Haemostasis 1987; 17: 286-292
    PubMedGoogle Scholar
  • 94 Oikawa T, Muramatsu Y, Akashi S, Usui N. Prophylactic use of concentrated antithrombin III preparation in children with nephrotic syndrome. Nippon Jinzo Gakkai Shi 1993; 35: 1163-1169
    PubMedGoogle Scholar
  • 95 Brandt P, Jespersen J, Gregersen G. Post partum haemolytic-uraemic syndrome treated with antithrombin-III. Nephron 1981; 27: 15-18
    CrossrefPubMedGoogle Scholar
  • 96 Emerson TEJ, Fournel MA, Leach WJ, Redens TB. Protection against disseminated intravascular coagulation and death by antithrombin-III in the Escherichia coli endotoxemic rat. Circ Shock 1987; 21: 1-13
    PubMedGoogle Scholar
  • 97 Triantaphyllopoulos DC. Effects of human antithrombin III on mortality and blood coagulation induced in rabbits by endotoxin. Thromb Haemost 1984; 51: 232-235
    Article in Thieme ConnectPubMedGoogle Scholar
  • 98 Emerson Jr TE, Fournel MA, Redens TB, Taylor Jr FB. Efficacy of antithrombin III supplementation in animal models of fulminant Escherichia coli endotoxemia or bacteremia. Am J Med 1989; 87 suppl (Suppl. 03) B 27S-33S
    CrossrefPubMedGoogle Scholar
  • 99 Dickneite G, Pâques EP. Reduction of mortality with anti thrombin III in septicemic rats: a study of Klebsiella pneumoniae induced sepsis. Thromb Haemost 1993; 69: 98-102
    Article in Thieme ConnectPubMedGoogle Scholar
  • 100 Hauptman JG, Hassouna HI, Bell TG, Penner JA, Emerson TE. Efficacy of antithrombin III in endotoxin-induced disseminated intravascular coagulation. Circ Shock 1988; 25: 111-122
    PubMedGoogle Scholar
  • 101 Fourrier F, Chopin C, Goudemand J, Hendrycx S, Caron C, Rime A, Mareu A, Lestavel P. Septic shock, multiple organ failure, and disseminated intravascular coagulation. Chest 1992; 101: 816-823
    CrossrefPubMedGoogle Scholar
  • 102 Fourrier F, Chopin C, Huart JJ, Runge I, Caron C, Goudemand J. Doubleblind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation. Chest 1993; 104: 882-888
    CrossrefPubMedGoogle Scholar
  • 103 Albert J, Blomqvist H, Gårdlund B, Jakobsson J, Svensson J, Blombäck M. Effect of antithrombin concentrate on haemostatic variables in critically ill patients. Acta Anaesthesiol Scand 1992; 36: 745-752
    CrossrefPubMedGoogle Scholar
  • 104 Blauhut B, Kramar H, Vinazzer H, Bergmann H. Substitution of antithrombin III in shock and DIC: a randomized study. Thromb Res 1985; 39: 81-89
    CrossrefPubMedGoogle Scholar
  • 105 Harper PL, Williamson L, Park G, Smith JK, Carrell RW. A pilot study of antithrombin replacement in intensive care management: the effects on mortality, coagulation and renal function. Transfusion Med 1991; 1: 121-128
    CrossrefPubMedGoogle Scholar
  • 106 Nowak-Götti U, Groll A, Kreuz WD, Brand M, Breddin HK, von Loewe-nich, Komhuber B. Behandlung der Verbrauchskoagulopathie mit Antithrombin III-Konzentrat bei Kindern mit nachgewiesener Sepsis. Klin Pädiatr 1992; 204: 134-140
    Article in Thieme ConnectPubMedGoogle Scholar
  • 107 Jespersen J, Rasmussen NR, Toftgaard C. Observations during the treatment with antithrombin-III concentrate of a case of tampon-related toxic shock syndrome and disseminated intravascular coagulation. Discrepancies between functional and immunologic determinations of antithrombin Thromb Res 1982; 26: 457-462
    CrossrefPubMedGoogle Scholar
  • 108 Schipper HG, Jenkins CS P, Kahlé LH, ten Cate JW. Antithrombin-III transfusion in disseminated intravascular coagulation. Lancet 1978; 1: 854-856
    PubMedGoogle Scholar
  • 109 Sakata Y, Yoshida N, Matsuda M, Aoki N. Treatment of DIC with antithrombin III concentrates. Bibl Haematol 1983; 49: 307-316
    PubMedGoogle Scholar
  • 110 Wisecarver JL, Haire WD. Disseminated intravascular coagulation with multiple arterial thromboses responding to antithrombin-III concentrate infusion. Thromb Res 1989; 54: 709-717
    CrossrefPubMedGoogle Scholar
  • 111 Hanada T, Abe T, Takita H. Antithrombin III concentrates for treatment of disseminated intravascular coagulation in children. Am J Pediatr Hematol 1985; 7: 3-8
    PubMedGoogle Scholar
  • 112 Hellgren M, Javelin L, Hägnevik K, Blombéck M, Britth-Medén G. Antithrombin III concentrate as adjuvant in DIC treatment. A pilot study in 9 severely III patients Thromb Res 1984; 35: 459-466
    CrossrefPubMedGoogle Scholar
  • 113 Maki M, Terao T, Ikenoue T, Takemura T, Sekiba K, Shirakawa K, Soma H. Clinical evaluation of antithrombin III concentrate (BI 6.013) for disseminated intravascular coagulation in obstetrics. Gynecol Obstet Invest 1987; 23: 230-240
    CrossrefPubMedGoogle Scholar
  • 114 Liebman HA, Wada K, Patch MJ, McGehee W. Depression of functional and antigenic plasma antithrombin III (ATIII) due to therapy with L-aspa- raginase. Cancer 1982; 50: 451
    CrossrefPubMedGoogle Scholar
  • 115 Leone G, Gugliotta L, Mazzucconi MG, de Stefano V, Mattioli Belmonte M, Dragoni F, Specchia G, Centra A, Gamba G, Camera A, Mandelli F. Evidence of a hypercoagulable state in patients with acute lymphoblastic leukemia treated with low dose of E.coli L-asparaginase: A GIMEMA study. Thromb Haemost 1993; 69: 12-15
    Article in Thieme ConnectPubMedGoogle Scholar
  • 116 Mazzucconi MG, Gugliotta L, Leone G, Dragoni F, Mattioli BelmonteM, de StefanoV, Chistolini A, Tura S, Mandelli F. Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase A Gimema study. Blood Coagulation Fibrinolysis 1994; 5: 23-28
    CrossrefPubMedGoogle Scholar
  • 117 Gugliotta L, d’Angelo A, Mattioli Belmonte M, Viganò-d’Angelo S, Colombo G, Catani L, Gianni L, Laruia F, Tura S. Hypercoagulability during L-asparaginase treatment: the effect of antithrombin III supplementation in vivo. Br J Haematol 1990; 74: 465-470
    CrossrefPubMedGoogle Scholar
  • 118 Zaunschirm A, Muntean W. Correction of hemostatic imbalances induced by L-asparaginase therapy in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol 1986; 3: 19-25
    CrossrefPubMedGoogle Scholar
  • 119 Medén-Britth G, Teien AN. Infusion of purified antithrombin III to patients with fracture of the neck of the femur. Eur Surg Res 1979; 11: 289-295
    CrossrefPubMedGoogle Scholar
  • 120 Francis CW, Pellegrini Jr VD, Marder VJ, Harris CM, Totterman S, Gabriel KR, Baughman DJ, Roemer S, Burke J, Goodman TL, Evarcts CM c C. Prevention of venous thrombosis after total hip arthroplasty. Antithrombin III and low-dose heparin compared with dextran 40 J Bone Joint Surg 1989; 71: 327-335
    CrossrefPubMedGoogle Scholar
  • 121 Schrader J, Köstering H, Kramer P, Scheler F. Antithrombin-III-Substitu- tion bei dialysepflichtiger Niereninsuffizienz. Dtsch Med Wschr 1982; 107: 1847-1850
    Article in Thieme ConnectPubMedGoogle Scholar
  • 122 Soloway HB, Christiansen TW. Heparin anticoagulation during cardiopulmonary bypass in an antithrombin-III deficient patient. Am J Clin Pathol 1980; 73: 723-725
    CrossrefPubMedGoogle Scholar
  • 123 Matsuo T, Yamada T, Matsuo M, Sakai R. Anticoagulant therapy in a congenital antithrombin III (ATIII)-deficient patient with chronic renal failure undergoing regular hemodialysis. Biomater Artif Cells Immobilization Biotechnol 1991; 19: 185-191
    PubMedGoogle Scholar
  • 124 Einarsson M, Perenius L, McDougal JS, Cort S. Heat inactivation of human immunodeficiency virus in solutions of antithrombin III. Transfusion 1989; 29: 148-152
    CrossrefPubMedGoogle Scholar
  • 125 Tabor E, Murano G, Snoy P, Gerety RJ. Inactivation of hepatitis B virus by heat in antithrombin III stabilized with citrate. Thromb Res 1981; 22: 233-238
    CrossrefPubMedGoogle Scholar
  • 126 Clemens R, Weidmann E, Merkle W, Bock HL, Mauler R, Hilfenhaus J. Virus safety of a pasteurized antithrombin III concentrate. Arzneim.Forsch 1987; 37: 759-62
    PubMedGoogle Scholar
  • 127 Preiss DU, Abdullah D, Eberspacher B, Wilhelm K. Safety of virus inactivated antithrombin III concentrate antithrombin III Immuno (AT III). Thromb Res 1992; 65: 677-686
    CrossrefPubMedGoogle Scholar
  • 128 Frickhofen N, Chen ZJ, Young NS, Cohen BJ, Heimpel H, Abkowitz JL. Parvovirus B19 as a cause of acquired chronic pure red cell aplasia. Br J Haematol 1994; 87: 818-824
    CrossrefPubMedGoogle Scholar