Download PDF
Thromb Haemost 1999; 82(02): 695-705
DOI: 10.1055/s-0037-1615899
Research Article
Schattauer GmbH

Disseminated Intravascular Coagulation

Marcel Levi
1   Department of Vascular Medicine, Slotervaart Hospital, Amsterdam, THE NETHERLANDS
2   Department of Internal Medicine, Slotervaart Hospital, Amsterdam, THE NETHERLANDS
,
Evert de Jonge
3   Intensive Care, Slotervaart Hospital, Amsterdam, THE NETHERLANDS
,
Tom van der Poll
2   Department of Internal Medicine, Slotervaart Hospital, Amsterdam, THE NETHERLANDS
3   Intensive Care, Slotervaart Hospital, Amsterdam, THE NETHERLANDS
,
Hugo ten Cate
1   Department of Vascular Medicine, Slotervaart Hospital, Amsterdam, THE NETHERLANDS
5   Department of Internal Medicine, Slotervaart Hospital, Amsterdam, THE NETHERLANDS
› Author Affiliations
Further Information

Publication History

Publication Date:
09 December 2017 (online)

    Permissions and Reprints

Introduction

A quick literature search in the MEDLINE databases from 1966 to 1998 using the search term disseminated intravascular coagulation (DIC) and related key words yields an impressive 11,921 manuscripts. Most of the published literature concerns the pathophysiology of DIC, which in its main features is now well understood. Other aspects of DIC, however, particularly those related to the definition, the relevance of the syndrome, and clinical management, remain unclear. Taking an evidence-based approach to the appropriate diagnosis and treatment of patients with DIC is difficult, in view of the lack of sound clinical trials. This is probably due to the fact that DIC is a poorly-defined syndrome with a widely variable intensity, often complicating a diversity of severe disorders that are themselves related to extensive morbidity and mortality.1,2 This chapter briefly reviews the clinical setting, incidence, and relevance of DIC and current insights into the pathogenesis of DIC. It also discusses the available knowledge on the clinical management of patients with this syndrome.

DIC is not a disease or a symptom but rather a syndrome, which is always secondary to an underlying disorder. The syndrome is characterized by a systemic activation of the blood coagulation system, which results in the generation and deposition of fibrin, leading to microvascular thrombi in various organs and contributing to the development of multiorgan failure. Consumption and subsequent exhaustion of coagulation proteins and platelets, due to the ongoing activation of the coagulation system, may induce severe bleeding complications, although microclot formation may occur in the absence of severe clotting factor depletion and bleeding.3 Derangement of the fibrinolytic system further contributes to intravascular clot formation (discussed later), but in some cases accelerated fibrinolysis (e.g., due to consumption of α2-antiplasmin) may cause severe bleeding. Hence, a patient with DIC can present with simultaneous thrombotic and bleeding problems, which obviously complicates treatment. Although there is no general consensus regarding the definition of DIC, the definition as put forward by Müller-Berghaus and colleagues in 1995 might be most appropriate: “Disseminated intravascular coagulation is an acquired syndrome characterized by the activation of intravascular coagulation up to intravascular fibrin formation. The process may be accompanied by secondary fibrinolysis or inhibited fibrinolysis.”4

 

  • References

  • 1 Marder VJ, Martin SE, Francis CW, Colman RW. Consumptive thrombohemorrhagic disorders. In: Colman RW, Hirsh J, Marder VJ, Salzman EW. eds. Hemostasis and Thrombosis. Basic Principles and Clinical Practice. Philadelphia: JB Lippincott Co; 1987: 975-1015.
    Google Scholar
  • 2 Williams EC, Mosher DF. Disseminated intravascular coagulation. In: Hoffman R, Benz Jr EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE. eds. Hematology. Basic principles and practice. New York: Churchill Livingstone; 1995: 1758-1769.
    Google Scholar
  • 3 Baglin T. Disseminated intravascular coagulation: diagnosis and treatment. Br Med J 1996; 312: 683-687.
    CrossrefPubMedGoogle Scholar
  • 4 Müller-Berghaus G, Madlener K, Blombäck M, ten Cate JW. eds. DIC. Pathogenesis, Diagnosis and Therapy of Disseminated Intravascular Fibrin Formation. New York: Elsevier Science Publishers; 1993
    Google Scholar
  • 5 Levi M, van der Poll T, ten Cate H, van Deventer SJH. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxemia. Eur J Clin Invest 1997; 27: 3-9.
    PubMedGoogle Scholar
  • 6 Bick RL. Disseminated intravascular coagulation: a common complication of trauma and shock. In: Borris LC, Lassen MR, Bergqvist D. eds. The Traumatized Patient. City: Romer Grafik; 1992: 33-53.
    Google Scholar
  • 7 Gando S, Kameue T, Nanzaki S, Nakanishi Y. Disseminated intravascular coagulation is a frequent complication of systemic inflammatory response syndrome. Thromb Haemost 1996; 75: 224-228.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Roumen JMH, Hendriks T, van der Ven J, Nieuwenhuijzen GAP, Sauerwein RW, van der Meer JWWM, Goris RJA. Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Ann Surg 1993; 6: 769-776.
    PubMedGoogle Scholar
  • 9 Contrino J, Hair G, Kreutzer D, Rickles FR. In situ detection of expression of tissue factor in vascular endothelial cells: correlation with the malignant phenotype of human breast tissue. Nature Med 1996; 2: 209-215.
    CrossrefPubMedGoogle Scholar
  • 10 Zhang Y, Deng Y, Luther T, Muller M, Ziegler R, Waldherr R, Stern DM, Nawroth PP. Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice. J Clin Invest 1994; 94: 1320-1327.
    CrossrefPubMedGoogle Scholar
  • 11 Falanga A, Consonni R, Marchetti M, Locatelli G, Garattini E, Passerini CG, Gordon SG, Barbui T. Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic acid in acute promyelocytic leukemia cells. Blood 1998; 92: 143-151.
    PubMedGoogle Scholar
  • 12 Albarracin NS, Haust MD. Intravascular coagulation in promyeolocytic leukemia: a case study including ultrastructure. Am J Clin Pathol 1971; 55: 677-679.
    CrossrefPubMedGoogle Scholar
  • 13 Weiner CP. The obstetric patient and disseminated intravascular coagulation. Clin Perinatol 1986; 13: 705-717.
    PubMedGoogle Scholar
  • 14 Martin JN, Stedman CM. Imitators of preeclampsia and HELLP syndrome. Obstet Gynecol Clin North Am 1991; 18: 181-198.
    PubMedGoogle Scholar
  • 15 Gibney EJ, Bouchier-Hayes D. Coagulopathy and abdominal aortic aneurysm. Eur J Vasc Surg 1990; 4: 557-562.
    CrossrefPubMedGoogle Scholar
  • 16 Szlachetka DM. Kasabach-Merrit syndrome: a case review. Neonat Network 1998; 17: 7-15.
    PubMedGoogle Scholar
  • 17 Ruggenenti P, Lutz J, Remuzzi G. Pathogenesis and treatment of thrombotic microangiopathy. Kidney Int 1997; 58: S97-S101.
    PubMedGoogle Scholar
  • 18 Bone RC. Gram-positive organisms and sepsis. Arch Intern Med 1994; 154: 26-34.
    CrossrefPubMedGoogle Scholar
  • 19 Scherer RU, Spangenberg P. Procoagulant activity in patients with isolated head trauma. Crit Care Med 1998; 26: 149-156.
    CrossrefPubMedGoogle Scholar
  • 20 Sarris AH, Kempin S, Berman E, Michaeli J, Little C, Andreeff M, Gee T, Straus D, Gansbacher B, Filippa D, et al. High incidence of disseminated intravascular coagulation during remission induction of adult patients with acute lymphoblastic leukemia. Blood 1992; 79: 1305-1310.
    PubMedGoogle Scholar
  • 21 Aboulafia DM, Aboulafia ED. Aortic anurysma–induced disseminated intravascular coagulation. Ann Vasc Surg 1996; 10: 396-405.
    CrossrefPubMedGoogle Scholar
  • 22 Coalson JJ. Pathology of sepsis, septic shock, and multiple organ failure. In: Perspective on Sepsis and Septic Shock. Fullerton, CA: Society of Critical Care Medicine; 1986: 27-59.
    Google Scholar
  • 23 Creasey AA, Chang ACK, Feigen L, Wun TC, Taylor Jr FB, Hinshaw LB. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock. J Clin Invest 1993; 91: 2850-2860.
    CrossrefPubMedGoogle Scholar
  • 24 Kessler C, Tang Z, Jacobs HM, Szymanski LM. The suprapharmacological dosing of antithrombin concentrate for Staphylococcus aureus–induced disseminated intravascular coagulation in guinea pigs; substantial reduction in mortality and morbidity. Blood 1997; 89: 4393-4401.
    PubMedGoogle Scholar
  • 25 Fourrier F, Chopin C, Goudemand J, Hendryex S, Caron C, Rime A, Marey A, Lestavel P. Septic shock, multiple organ failure, and disseminated intravascular coagulation. Compared patterns of antithrombin III, protein C and protein S deficiencies. Chest 1992; 101: 816-823.
    CrossrefPubMedGoogle Scholar
  • 26 van Deventer SJH, Büller HR, ten Cate JW, Aarden LA, Hack CE, Sturk A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood 1990; 76: 2520-2526.
    PubMedGoogle Scholar
  • 27 Taylor Jr. FB. Role of tissue factor in the coagulant and inflammatory response to LD100 E coli sepsis and in the early diagnosis of DIC in the baboon. In: Muller-Berghaus GM, Madlener K, Blomback M, ten Cate JW. eds. DIC. Pathogenesis, Diagnosis and Therapy of Disseminated Intravascular Fibrin Formation. Amsterdam: Excerpta Medica; 1993: 19-32.
    Google Scholar
  • 28 van der Poll T, Buller HR, ten Cate H, Wortel CH, Bauer KA, van Deventer SJ, Hack CE, Sauerwein HP, Rosenberg RD, ten Cate JW. Activation of coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 1990; 322: 1622-1627.
    CrossrefPubMedGoogle Scholar
  • 29 Pixley RA, de la Cadena R, Page J, Kaufman N, Wyshock EG, Chang A, Taylor Jr FB, Coman RW. The contact system contributes to hypotension but not disseminated intravascular coagulation in lethal bacteremia: in vivo use of a monoclonal anti-factor XII antibody to block contact activation in baboons. J Clin Invest 1993; 92: 61-68.
    PubMedGoogle Scholar
  • 30 Levi M, ten Cate H, Bauer KA, van der Poll T, Edgington TS, Buller HR, van Deventer SJ, Hack CE, ten Cate JW, Rosenberg RD. Inhibiton of endotoxin-induced activation of coagulation and fibrinolysis by pentoxiphylline or by a monoclonal anti-tissue factor antibody in a chimpanzee model. J Clin Invest 1994; 93: 114-120.
    CrossrefPubMedGoogle Scholar
  • 31 Biemond BJ, Levi M, ten Cate H, Soule HR, Morris LD, Foster DL, Bogowitz CA, van der Poll T, Buller HR, ten Cate JW. Complete inhibition of endotoxin-induced coagulation activation in chimpanzees with a monclonal antibody to factor VII/VIIa. Thromb Haemost 1995; 73: 223-230.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 32 Taylor Jr FB, Chang A, Ruf W, Morrissey JH, Hinshaw L, Catlett R, Blick K, Edgington TS. Lethal E coli septic shock is prevented by blocking tissue factor with monoclonal antibody. Circ Shock 1991; 33: 127-134.
    PubMedGoogle Scholar
  • 33 Wada H, Nakase T, Nakaya R, et al. Elevated plasma tissue factor antigen level in patients with disseminated intravascular coagulation. Am J Hematol 1996; 52: 165-170.
    CrossrefPubMedGoogle Scholar
  • 34 Osterud B, Flaegstad T. Increased tissue thromboplastin activity in monocytes of patients with meningococcal infections related to unfavourable prognosis. Thromb Haemost 1983; 49: 5-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Buller HR, ten Cate JW. Acquired antithrombin III deficiency: laboratory diagnosis, incidence, clinical implications, and treatment with antithrombin III concentrate. Am J Med. 1989; 87: 44S-48S.
    PubMedGoogle Scholar
  • 36 Conway EM, Rosenberg RD. Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. Mol Cell Biol 1988; 8: 5588-5592.
    CrossrefPubMedGoogle Scholar
  • 37 Taylor FB, Chang Jr A, Esmon CT, D’Angelo A, Vigano-D’Angelo S, Blick KE. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest 1987; 79: 918-925.
    CrossrefPubMedGoogle Scholar
  • 38 Garcia de Frutos P, Alim RIM, Härdig Y, Zöller B, Dahlbäck B. Differential regulation of aa and bb chains of C4b-binding protein during acute phase response resulting in stable plasma levels of free anticoagulant protein S. Blood 1994; 84: 815-822.
    PubMedGoogle Scholar
  • 39 Taylor FB, Chang A, Ferrel G, Mather T, Catlett R, Blick K, Esmon CT. C4b-binding protein exacerbates the host response to Escherichia coli . Blood 1991; 78: 357-363.
    PubMedGoogle Scholar
  • 40 Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze Jr. GJ. Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. Blood 1991; 78: 387-393.
    PubMedGoogle Scholar
  • 41 Suffredini AF, Harpel PC, Parillo JE. Promotion and subsequent inhibition of plasminogen activator after administration of intravenous endotoxin to normal subjects. N Engl J Med 1989; 320: 1165-1172.
    CrossrefPubMedGoogle Scholar
  • 42 Biemond BJ, Levi M, ten Cate H, van der Poll T, Buller HR, Hack CE, ten Cate JW. Plasminogen activator and plasminogen activator inhibitor I release during experimental endotoxaemia in chimpanzees: effect of interventions in the cytokine and coagulation cascades. Clin Sci 1995; 88: 587-594.
    CrossrefPubMedGoogle Scholar
  • 43 Minnema MC, Pajkrt D, Wuillemin WA, Roem D, Bleeker WK, Levi M, van Devente SJ, Hack CE, ten Cate H. Activation of coagulation factor XI without detectable contact activation in experimental human endotoxemia. Blood 1998; 92: 3294-3301.
    PubMedGoogle Scholar
  • 44 Bouma BN, van der Borne PA, Meijers JCM. Factor XI and protection of the fibrin clot against lysis-a role for the intrinsic pathway of coagulation in fibrinolyis. Thromb Haemost 1998; 80: 24-27.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Braat EAM, Levi M, Bos R, Haverkate F, de Maat MPM, Rijken DC. The occurrence of the inactivation of single-chain urokinase-type plasminogen activator by thrombin in vivo. J Lab Clin Med. In press.
    PubMedGoogle Scholar
  • 46 Hack CE, Aarden LA, Thijs LG. Role of cytokines in sepsis. Adv Immunol 1997; 66: 101-195.
    PubMedGoogle Scholar
  • 47 Fischer E, Marano MA, van Zee KJ, Rock CS, Hawes AS, Thompson WA, DeForge L, Kenney JS, Remick DG, Bloedow DC, et al. Interleukin-1 receptor blockade improves survival and hemodynamic performance in Escherichia coli septic shock but fails to alter host-responses to sublethal endotoxemia. J Clin Invest 1992; 89: 1551-1557.
    CrossrefPubMedGoogle Scholar
  • 48 Boermeester MA, van Leeuwen PAM, Coyle SM, Wolbink GJ, Hack CE, Lowry SF. Interleukin-1 receptor blockade in patients with sepsis syndrome: evidence that interleukin-1 contributes to the release of interleukin-6, elastase and phospholipase A2, and to the activation of the complement, coagulation and fibrinolytic systems. Arch Surg 1995; 130: 739-748.
    CrossrefPubMedGoogle Scholar
  • 49 Bauer KA, ten Cate H, Barzegar S, Spriggs DR, Sherman ML, Rosenberg RD. Tumor necrosis factor infusions have a procoagulant effect on the hemostatic mechanism of humans. Blood 1989; 74: 165-172.
    PubMedGoogle Scholar
  • 50 van der Poll T, Levi M, van Deventer SJ, ten Cate H, Haagmans BL, Biemond BJ, Buller HR, Hack CE, ten Cate JW. Differential effects of anti–tumor necrosis factor monoclonal antibodies on systemic inflammatory responses in experimental endotoxemia in chimpanzees. Blood 1994; 83: 446-451.
    PubMedGoogle Scholar
  • 51 Hinshaw LB, Tekamp-Olson P, Chang ACK. Survival of primates in LD100 septic shock following therapy with antibody to tumor necrosis factor (TNF). Circ Shock 1990; 30: 279-292.
    PubMedGoogle Scholar
  • 52 van der Poll T, Levi M, Hack CE, ten Cate H, van Deventer SJ, Eerenberg AJ, de Groot ER, Jansen J, Gallati H, Buller HR. et al. Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med 1994; 179: 1253-1259.
    CrossrefPubMedGoogle Scholar
  • 53 Stouthard J, Levi M, Hack CE, Veenhof CHN, Romijn JA, Sauerwein HP, van der Poll T. Interleukin 6 stimulates coagulation but not fibrinolysis in humans. Thromb Haemost 1996; 76: 738-742.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Creasey AA, Chang ACK, Feigen L, Wun TC, Taylor Jr FB, Hinshaw LB. Tissue factor pathway inhibitor reduces mortality from Eschericia coli septic shock. J Clin Invest 1993; 91: 2850-2855.
    CrossrefPubMedGoogle Scholar
  • 55 Mestries JC, Kruithof EK, Gascon MP, Herodin F, Agay D, Ythier A. In vivo modulation of coagulation and fibrinolysis by recombinant glycosylated human interleukin-6 in baboons. Eur Cytokine Network 1994; 5: 275-281.
    PubMedGoogle Scholar
  • 56 Pajkrt D, van der Poll T, Levi M, Cutler DL, Affrime MB, van den Ende A, ten Cate JW, van Deventer SJ. Interleukin-10 inhibits activation of coagulation and fibrinolysis during human endotoxemia. Blood 1997; 89: 2701-2705.
    PubMedGoogle Scholar
  • 57 Yamamoto K, Loskutoff DJ. Fibrin deposition in tissues from endotoxin-treated mice correlates with decreases in the expression of urokinase-type but not tissue-type plasminogen activator. J Clin Invest 1996; 97: 2440-2451.
    CrossrefPubMedGoogle Scholar
  • 58 Levi M, van der Poll T, ten Cate H, Kuipers B, Biemond BJ, Jansen HM, ten Cate JW. Differential effect of anti-cytokine treatment on bronchoalveolar hemostasis in endotoxemic chimpanzees. Am J Respir Crit Care Med 1998; 158: 92-98.
    CrossrefPubMedGoogle Scholar
  • 59 Bick RL. Disseminated intravascular coagulation: objective clinical and laboratory diagnosis, treatment, and assessment of therapeutic response. Semin Thromb Hemostas 1996; 22: 69-88.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 60 Bick RL. Disseminated intravascular coagulation: pathophysiological mechanisms and manifestations. Semin Thromb Hemostas 1998; 24: 3-15.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 61 Alving BM, Spivak JL, DeLoughery TG. Consultative hematology: hemostasis and transfusion issues in surgery and critical care medicine. In: McArthur JR, Schechter GP, Schrier SL. eds. Hematology. City: American Society of Hematology; 1998: 320-341.
    Google Scholar
  • 62 Gross SJ, Filston HC. Controlled study of treatment for disseminated intravascular coagulation in the neonate. J Pediatr 1982; 100: 445-448.
    CrossrefPubMedGoogle Scholar
  • 63 du Toit HJ, Coetzee AR, Chalton DO. Heparin treatment in thrombin-induced disseminated intravascular coagulation in the baboon. Crit Care Med 1991; 19: 1195-1200.
    CrossrefPubMedGoogle Scholar
  • 64 Corrigan Jr JJ. Heparin therapy in bacterial septicemia. J Pediatr 1977; 91: 695-700.
    CrossrefPubMedGoogle Scholar
  • 65 Feinstein DI. Diagnosis and management of disseminated intravascular coagulation: the role of heparin therapy. Blood 1982; 60: 284-287.
    PubMedGoogle Scholar
  • 66 Goldhaber SZ. Venous thromboembolism in the intensive care unit: the last frontier. Chest 1998; 113: 5-7.
    CrossrefPubMedGoogle Scholar
  • 67 Audibert G, Lambert H, Toulemonde F, Alexandre P, Laprevote-Heully MC, Bollaert PE, Bauer P, Larcan A. Utilisation d’une heparine de bas poids moleculaire, la CY 222, dans le traitement des coagulopathies de consommation. J Mal Vasc 1987; 12 (Suppl) 147-151.
    PubMedGoogle Scholar
  • 68 Gillis S, Dann EJ, Eldor A. Low molecular weight heparin in the prophylaxis and treatment of disseminated intravascular coagulation in acute promyelocytic leukemia. Eur J Haematol 1995; 54: 59-60.
    PubMedGoogle Scholar
  • 69 Sakuragawa N, Hasegawa H, Maki M, Nakagawa M, Nakashima M. Clinical evaluation of low–molecular-weight heparin (FR-860) on disseminated intravascular coagulation (DIC)-a multicenter co-operative double-blind trial in comparison with heparin. Thromb Res 1993; 72: 475-500.
    CrossrefPubMedGoogle Scholar
  • 70 Hermida J, Montes R, Paramo JA, Rocha E. Endotoxin-induced disseminated intravascular coagulation in rabbits: effect of recombinant hirudin on hemostatic parameters, fibrin deposits and mortality. J Lab Clin Med 1998; 131: 77-83.
    CrossrefPubMedGoogle Scholar
  • 71 Saito M, Asakura H, Jokaji H, Uotani C, Kumabashiri I, Morishita E, Yamazaki M, Aoshima K, Matsuda T. Recombinant hirudin for the treatment of disseminated intravascular coagulation in patients with haematological malignancy. Blood Coagul Fibrinolysis 1995; 6: 60-64.
    CrossrefPubMedGoogle Scholar
  • 72 Bergum P, Cruikshank A, Maki S, Ruf W, Vlasuk G. The potent, factor X(a)–dependent inhibition by rNAPc2 of factor VIIa/tissue factor involves the binding of its cofactor to a exosite on factor VII, followed by occupation of the active site. Blood 1998; 92 (Suppl) 2760a.
    PubMedGoogle Scholar
  • 73 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
  • 74 Vinazzer H. Therapeutic use of antithrombin III in shock and disseminated intravascular. Semin Thromb Hemostas 1989; 15: 347-352.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 75 Fourrier F, Chopin C, Huart JJ, Runge I, Caron C, Goudemand J. Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation. Chest 1993; 104: 882-888.
    CrossrefPubMedGoogle Scholar
  • 76 Baudo F, Caimi TM, de Cataldo F, Ravizza A, Arlati S, Casella G, Carugo D, Palareti G, Legnani C, Ridolfi L, Rossi R, D’Angelo A, Crippa L, Giudici D, Gallioli G, Wolfler A, Calori G. Antithrombin III replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study. Intensive Care Med 1998; 24: 336-342.
    CrossrefPubMedGoogle Scholar
  • 77 Eisele B, Lamy M, Thijs LG, Keinecke HO, Schuster HP, Matthias FR, Fourrier F, Heinrichs H, Delvos U. Antithrombin III in patients with severe sepsis. A randomized placebo-controlled, double-blind multicenter trial plus meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med 1998; 24: 663-672.
    CrossrefPubMedGoogle Scholar
  • 78 Schuster HP, Matthias FR. Antithrombin III in severe sepsis. Presented at the 15th International Symposium on Intensive Care and Emergency Medicine; Month. 1995. Brussels, Belgium:
    Google Scholar
  • 79 Smith OP, White B, Vaughan D, Rafferty M, Claffey L, Lyons B, Casey W. Use of protein C concentrate, heparin, and haemodiafiltration in meningococcus-induced purpura fulminans. Lancet 1997; 350: 1590-1593.
    CrossrefPubMedGoogle Scholar
  • 80 Schwartz BS, Williams EC, Conlan MG, Mosher DF. Epsilonaminocaproic acid in the treatment of patients with acute promyelocytic leukemia and acquired alpha-2-plasmin inhibitor deficiency. Ann Intern Med 1986; 105: 873-877.
    CrossrefPubMedGoogle Scholar
  • 81 Avvisati G, ten Cate JW, Buller HR, Mandelli F. Tranexamic acid for control of haemorrhage in acute promyelocytic leukaemia. Lancet. 1989; 334: 122-124.
    CrossrefPubMedGoogle Scholar