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DOI: 10.1055/s-0031-1287873
Hematologic Failure
Publication History
Publication Date:
11 October 2011 (online)
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ABSTRACT
Hematologic factors, in particular platelets and the coagulation system, play an important role in the pathogenesis of organ failure in the intensive care unit. Failure of these hematologic systems is common in intensive care patients and may range from isolated thrombocytopenia or prolonged global clotting tests to complex defects, such as disseminated intravascular coagulation. There are many causes for a deranged coagulation in critically ill patients, and each of these underlying disorders may require specific therapeutic management. Hence, a proper differential diagnosis and initiation of adequate (supportive) treatment strategies are crucial to reduce morbidity and mortality in critically ill patients with coagulation abnormalities.
KEYWORDS
Coagulation - platelets - intensive care - disseminated intravascular coagulation - thrombotic microangiopathy - heparin-induced thrombocytopenia - bleeding
REFERENCES
- 1 Levi M, Opal S M. Coagulation abnormalities in critically ill patients. Crit Care. 2006; 10 (4) 222
- 2 Vanderschueren S, De Weerdt A, Malbrain M et al.. Thrombocytopenia and prognosis in intensive care. Crit Care Med. 2000; 28 (6) 1871-1876
- 3 Ahmed A, Kojicic M, Herasevich V, Gajic O. Early identification of patients with or at risk of acute lung injury. Neth J Med. 2009; 67 (9) 268-271
- 4 Schultz M J. Early recognition of critically ill patients. Neth J Med. 2009; 67 (9) 266-267
- 5 Strauss R, Wehler M, Mehler K, Kreutzer D, Koebnick C, Hahn E G. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome. Crit Care Med. 2002; 30 (8) 1765-1771
- 6 Shorr A F, Thomas S J, Alkins S A, Fitzpatrick T M, Ling G S. D-dimer correlates with proinflammatory cytokine levels and outcomes in critically ill patients. Chest. 2002; 121 (4) 1262-1268
- 7 Bernard G R, Vincent J L, Laterre P F Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001; 344 (10) 699-709
- 8 Anas A A, Wiersinga W J, de Vos A F, van der Poll T. Recent insights into the pathogenesis of bacterial sepsis. Neth J Med. 2010; 68 (4) 147-152
- 9 Levi M, van der Poll T. The role of natural anticoagulants in the pathogenesis and management of systemic activation of coagulation and inflammation in critically ill patients. Semin Thromb Hemost. 2008; 34 (5) 459-468
- 10 Levi M, Nieuwdorp M, van der Poll T, Stroes E. Metabolic modulation of inflammation-induced activation of coagulation. Semin Thromb Hemost. 2008; 34 (1) 26-32
- 11 Griffin J H, Fernández J A, Gale A J, Mosnier L O. Activated protein C. J Thromb Haemost. 2007; 5 (Suppl 1) 73-80
- 12 Esmon C T. Role of coagulation inhibitors in inflammation. Thromb Haemost. 2001; 86 (1) 51-56
- 13 Levi M, de Jonge E, van der Poll T. Rationale for restoration of physiological anticoagulant pathways in patients with sepsis and disseminated intravascular coagulation. Crit Care Med. 2001; 29 (7, Suppl) S90-S94
- 14 Esmon C T. The regulation of natural anticoagulant pathways. Science. 1987; 235 (4794) 1348-1352
- 15 Esmon C T. The endothelial cell protein C receptor. Thromb Haemost. 2000; 83 (5) 639-643
- 16 Mesters R M, Helterbrand J, Utterback B G et al.. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications. Crit Care Med. 2000; 28 (7) 2209-2216
- 17 Vary T C, Kimball S R. Regulation of hepatic protein synthesis in chronic inflammation and sepsis. Am J Physiol. 1992; 262 (2 Pt 1) C445-C452
- 18 Eckle I, Seitz R, Egbring R, Kolb G, Havemann K. Protein C degradation in vitro by neutrophil elastase. Biol Chem Hoppe Seyler. 1991; 372 (11) 1007-1013
- 19 Nawroth P P, Stern D M. Modulation of endothelial cell hemostatic properties by tumor necrosis factor. J Exp Med. 1986; 163 (3) 740-745
- 20 Faust S N, Levin M, Harrison O B et al.. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med. 2001; 345 (6) 408-416
- 21 Taylor Jr F BJ, Stearns-Kurosawa D J, Kurosawa S et al.. The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis. Blood. 2000; 95 (5) 1680-1686
- 22 Levi M, van der Poll T, Büller H R. Bidirectional relation between inflammation and coagulation. Circulation. 2004; 109 (22) 2698-2704
- 23 Levi M. Platelets. Crit Care Med. 2005; 33 (12, Suppl) S523-S525
- 24 Levi M, Löwenberg E C. Thrombocytopenia in critically ill patients. Semin Thromb Hemost. 2008; 34 (5) 417-424
- 25 Löwenberg E C, Meijers J C, Levi M. Platelet-vessel wall interaction in health and disease. Neth J Med. 2010; 68 (6) 242-251
- 26 Hawiger J J. Adhesive interactions of blood cells and the vascular wall in hemostasis and thrombosis. In: Colman R W, ed. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 3rd ed. Philadelphia, PA: JB Lippincott; 1994: 639-653
- 27 Ware J A, Heistad D D. Seminars in medicine of the Beth Israel Hospital, Boston. Platelet-endothelium interactions. N Engl J Med. 1993; 328 (9) 628-635
- 28 Woodside D G, Liu S, Ginsberg M H. Integrin activation. Thromb Haemost. 2001; 86 (1) 316-323
- 29 Ruggeri Z M. Platelets in atherothrombosis. Nat Med. 2002; 8 (11) 1227-1234
- 30 Ruggeri Z M. Von Willebrand factor, platelets and endothelial cell interactions. J Thromb Haemost. 2003; 1 (7) 1335-1342
- 31 Arya M, Anvari B, Romo G M et al.. Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers. Blood. 2002; 99 (11) 3971-3977
- 32 Sporn L A, Marder V J, Wagner D D. von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively. Blood. 1987; 69 (5) 1531-1534
- 33 Tsai H M, Nagel R L, Hatcher V B, Sussman I I. Multimeric composition of endothelial cell-derived von Willebrand factor. Blood. 1989; 73 (8) 2074-2076
- 34 George J N, Sadler J E, Lämmle B. Platelets: thrombotic thrombocytopenic purpura. Hematology (Am Soc Hematol Educ Program). 2002; 315-334
- 35 Hurskainen T L, Hirohata S, Seldin M F, Apte S S. ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases. General features and genomic distribution of the ADAM-TS family. J Biol Chem. 1999; 274 (36) 25555-25563
- 36 Moake J L. Thrombotic microangiopathies. N Engl J Med. 2002; 347 (8) 589-600
- 37 Tsai H M, Lian E C. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. 1998; 339 (22) 1585-1594
- 38 Furlan M, Robles R, Galbusera M et al.. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med. 1998; 339 (22) 1578-1584
- 39 Mavrommatis A C, Theodoridis T, Orfanidou A, Roussos C, Christopoulou-Kokkinou V, Zakynthinos S. Coagulation system and platelets are fully activated in uncomplicated sepsis. Crit Care Med. 2000; 28 (2) 451-457
- 40 Folman C C, Linthorst G E, van Mourik J et al.. Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis?. Thromb Haemost. 2000; 83 (6) 923-930
- 41 François B, Trimoreau F, Vignon P, Fixe P, Praloran V, Gastinne H. Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor. Am J Med. 1997; 103 (2) 114-120
- 42 Warkentin T E, Aird W C, Rand J H. Platelet-endothelial interactions: sepsis, HIT, and antiphospholipid syndrome. Hematology (Am Soc Hematol Educ Program). 2003; 497-519
- 43 Verma A K, Levine M, Shalansky S J, Carter C J, Kelton J G. Frequency of heparin-induced thrombocytopenia in critical care patients. Pharmacotherapy. 2003; 23 (6) 745-753
- 44 Warkentin T E. Heparin-induced thrombocytopenia: pathogenesis and management. Br J Haematol. 2003; 121 (4) 535-555
- 45 Tsai H M. Platelet activation and the formation of the platelet plug: deficiency of ADAMTS13 causes thrombotic thrombocytopenic purpura. Arterioscler Thromb Vasc Biol. 2003; 23 (3) 388-396
- 46 van den Born B J, van der Hoeven N V, Groot E et al.. Association between thrombotic microangiopathy and reduced ADAMTS13 activity in malignant hypertension. Hypertension. 2008; 51 (4) 862-866
- 47 Stéphan F, Hollande J, Richard O, Cheffi A, Maier-Redelsperger M, Flahault A. Thrombocytopenia in a surgical ICU. Chest. 1999; 115 (5) 1363-1370
- 48 Greaves M, Preston F E. Approach to the bleeding patient. In: Colman R W, Hirsh J, Marder V J, Clowes A W, George J N, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001: 1031-1043
- 49 Edmunds L H. Hemostatic problems in surgical patients. In: Colman R W, Hirsh J, Marder V J, Clowes A W, George J N, eds. Hemostasis and Thrombosis: Basic Principles and Clinical Practice. 4th ed. Philadelphia, PA: Lippincott William &Wilkins; 2001: 1031-1043
- 50 Bailey B, Amre D K, Gaudreault P. Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Crit Care Med. 2003; 31 (1) 299-305
- 51 Vlaar A P, Schultz M J, Juffermans N P. Transfusion-related acute lung injury: a change of perspective. Neth J Med. 2009; 67 (10) 320-326
- 52 Levi M M, Eerenberg E, Löwenberg E, Kamphuisen P W. Bleeding in patients using new anticoagulants or antiplatelet agents: risk factors and management. Neth J Med. 2010; 68 (2) 68-76
- 53 Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. 1999; 341 (8) 586-592
- 54 Wheeler A P, Bernard G R. Treating patients with severe sepsis. N Engl J Med. 1999; 340 (3) 207-214
- 55 Levi M, Schouten M, van der Poll T. Sepsis, coagulation, and antithrombin: old lessons and new insights. Semin Thromb Hemost. 2008; 34 (8) 742-746
- 56 Levi M, Toh C H, Thachil J, Watson H G. British Committee for Standards in Haematology . Guidelines for the diagnosis and management of disseminated intravascular coagulation. Br J Haematol. 2009; 145 (1) 24-33
- 57 Taylor Jr F BJ, Toh C H, Hoots W K, Wada H, Levi M. Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH) . Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001; 86 (5) 1327-1330
- 58 Dhainaut J F, Yan S B, Joyce D E et al.. Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation. J Thromb Haemost. 2004; 2 (11) 1924-1933
- 59 Hermanides J, Huijgen R, Henny C P et al.. Hip surgery sequentially induces stress hyperglycaemia and activates coagulation. Neth J Med. 2009; 67 (6) 226-229
- 60 Hirsh J, Heddle N, Kelton J G. Treatment of heparin-induced thrombocytopenia: a critical review. Arch Intern Med. 2004; 164 (4) 361-369
- 61 Hellstern P, Muntean W, Schramm W, Seifried E, Solheim B G. Practical guidelines for the clinical use of plasma. Thromb Res. 2002; 107 (Suppl 1) S53-S57
- 62 Mannucci P M, Levi M. Prevention and treatment of major blood loss. N Engl J Med. 2007; 356 (22) 2301-2311
- 63 Mannucci P M. Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood. 1997; 90 (7) 2515-2521
- 64 Levi M, Cromheecke M E, de Jonge E et al.. Pharmacological strategies to decrease excessive blood loss in cardiac surgery: a meta-analysis of clinically relevant endpoints. Lancet. 1999; 354 (9194) 1940-1947
- 65 Porte R J, Molenaar I Q, Begliomini B et al. EMSALT Study Group. Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. Lancet. 2000; 355 (9212) 1303-1309
- 66 Levi M, Levy M, Williams M D et al. Xigris and Prophylactic HepaRin Evaluation in Severe Sepsis (XPRESS) Study Group. Prophylactic heparin in patients with severe sepsis treated with drotrecogin alfa (activated). Am J Respir Crit Care Med. 2007; 176 (5) 483-490
Marcel LeviM.D. Ph.D.
Department of Vascular Medicine/Internal Medicine, Academic Medical Centre F-4
Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Email: m.m.levi@amc.uva.nl