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Hemostatic Abnormalities in the Critically Ill

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Hematologic Challenges in the Critically Ill

Abstract

Hemostatic abnormalities in the critically ill are common and range from an isolated single abnormality to diffuse, composite defects. There are many reasons for disturbed hemostasis in these patients, and it often correlates with the primary reason for intensive care. Hemostatic dysfunction and deficiency certainly complicate the clinical course of the patient admitted to the intensive care unit and are associated with increased risk of bleeding, transfusion, and death. Management invariably includes treatment of the primary illness and usually includes targeted therapy for the hemostatic abnormality with either pro- or antithrombotic measures.

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References

  1. Nemeth B, Scheres LJ, Lijfering WM, Rosendaal FR. Bloodcurdling movies and measures of coagulation: fear factor crossover trial. BMJ. 2015;351:h6367.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Thrall G, Lane D, Carroll D, Lip GY. A systematic review of the effects of acute psychological stress and physical activity on haemorheology, coagulation, fibrinolysis and platelet reactivity: implications for the pathogenesis of acute coronary syndromes. Thromb Res. 2007;120(6):819–47.

    Article  CAS  PubMed  Google Scholar 

  3. Kraaijenhagen R, Anker S, Koopman M, Reitsma P, Prins M, van den Ende A, et al. High plasma concentration of factor VIIIc Is a major risk factor for venous thromboembolism. Thromb Haemost. 2000;83(1):5–9.

    Article  CAS  PubMed  Google Scholar 

  4. Ingram GI, Knights SF, Barrow EM, Dejanov II. The rise in factor-8 concentration after infusion of adrenaline. Br J Haematol. 1968;15(3):326.

    CAS  PubMed  Google Scholar 

  5. Levi M, Sivapalaratnam S. Hemostatic abnormalities in critically ill patients. Intern Emerg Med. 2015;10(3):287–96.

    Article  PubMed  Google Scholar 

  6. Vanderschueren S, De Weerdt A, Malbrain M, Vankersschaever D, Frans E, Wilmer A, et al. Thrombocytopenia and prognosis in intensive care. Crit Care. 2000;28:1871–6.

    Article  CAS  Google Scholar 

  7. Strauss R, Wehler M, Mehler K, Kreutzer D, Koebnick C, Hahn E. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome*. Crit Care Med. 2002;30:1765–71.

    Article  PubMed  Google Scholar 

  8. Tripodi A, Mannucci P. The coagulopathy of chronic liver disease. N Engl J Med. 2011;365:147–56.

    Article  CAS  PubMed  Google Scholar 

  9. Hui P, Cook DJ, Lim W, Fraser GA, Arnold DM. The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review. Chest. 2011;139(2):271–8.

    Article  PubMed  Google Scholar 

  10. Williamson D, Lesur O, Te’trault J, Nault V, Pilon D. Thrombocytopenia in the critically ill: prevalence, incidence, risk factors, and clinical outcomes. Can J Anesth. 2013;60:641–51.

    Article  PubMed  Google Scholar 

  11. Williamson DR, Albert M, Heels-Ansdell D, Arnold DM, Lauzier F, Zarychanski R, et al. Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes. Chest. 2013;144(4):1207–15.

    Article  PubMed  Google Scholar 

  12. Baughman RR, Lower EE, Flessa HC, Tollerud DJ. Thrombocytopenia in the intensive care unit. Chest. 1993;104(4):1243–7.

    Article  CAS  PubMed  Google Scholar 

  13. Crowther MA, Cook DJ, Meade MO, Griffith LE, Guyatt GH, Arnold DM, et al. Thrombocytopenia in medical-surgical critically ill patients: prevalence, incidence, and risk factors. J Crit Care. 2005;20(4):348–53.

    Article  PubMed  Google Scholar 

  14. Akca S, Haji-Michael P, de Mendonca A, Suter P, Levi M, Vincent JL. Time course of platelet counts in critically ill patients. Crit Care Med. 2002;30(4):753–6.

    Article  PubMed  Google Scholar 

  15. Smith-Erichsen N. Serial determinations of platelets, leucocytes and coagulation parameters in surgical septicemia. Scand J Clin Lab Invest Suppl. 1985;178:7–14.

    CAS  PubMed  Google Scholar 

  16. Moreau D, Timsit JF, Vesin A, Garrouste-Orgeas M, de Lassence A, Zahar JR, et al. Platelet count decline: an early prognostic marker in critically ill patients with prolonged ICU stays. Chest. 2007;131(6):1735–41.

    Article  PubMed  Google Scholar 

  17. Venkata C, Kashyap R, Farmer JC, Afessa B. Thrombocytopenia in adult patients with sepsis: incidence, risk factors, and its association with clinical outcome. J Intensive care. 2013;1(1):9.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Nijsten MW, ten Duis HJ, Zijlstra JG, Porte RJ, Zwaveling JH, Paling JC, et al. Blunted rise in platelet count in critically ill patients is associated with worse outcome. Crit Care Med. 2000;28(12):3843–6.

    Article  CAS  PubMed  Google Scholar 

  19. Thiery-Antier N, Binquet C, Vinault S, Meziani F, Boisrame-Helms J, Quenot JP. Is Thrombocytopenia an Early prognostic marker in septic shock? Crit Care Med. 2016;44(4):764–72.

    PubMed  Google Scholar 

  20. Lim SY, Jeon EJ, Kim HJ, Jeon K, Um SW, Koh WJ, et al. The incidence, causes, and prognostic significance of new-onset thrombocytopenia in intensive care units: a prospective cohort study in a Korean hospital. J Korean Med Sci. 2012;27(11):1418–23.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lauzier F, Arnold DM, Rabbat C, Heels-Ansdell D, Zarychanski R, Dodek P, et al. Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis. Intensive Care Med. 2013;39(12):2135–43.

    Article  CAS  PubMed  Google Scholar 

  22. Cook D, Meade M, Guyatt G, Walter S, Heels-Ansdell D, Warkentin TE, et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011;364(14):1305–14.

    Article  CAS  PubMed  Google Scholar 

  23. Alhamdi Y, Toh CH. The role of extracellular histones in haematological disorders. Br J Haematol. 2016;173(5):805–11.

    Article  CAS  PubMed  Google Scholar 

  24. Thachil J. Platelets in inflammatory disorders: a pathophysiological and clinical perspective. Semin Thromb Hemost. 2015;41(06):572–81.

    Article  CAS  PubMed  Google Scholar 

  25. Menard C, Kumar A, Rimmer E, et al. Evolution & impact of thrombocytopenia in septic shock. Intensive Care Med Exp. 2016;4(Suppl 1):A586.

    Google Scholar 

  26. Zarychanski R, Houston DS. Assessing thrombocytopenia in the intensive care unit: the past, present, and future. Hematology Am Soc Hematol Educ Program. 2017;2017(1):660–6.

    PubMed  PubMed Central  Google Scholar 

  27. Thachil J, Warkentin TE. How do we approach thrombocytopenia in critically ill patients? Br J Haematol. 2017;177(1):27–38.

    Article  PubMed  Google Scholar 

  28. Semple JW, Italiano JE Jr, Freedman J. Platelets and the immune continuum. Nat Rev Immunol. 2011;11(4):264–74.

    Article  CAS  PubMed  Google Scholar 

  29. Semple JW, Freedman J. Platelets and innate immunity. Cell Mol Life Sci. 2010;67(4):499–511.

    Article  CAS  PubMed  Google Scholar 

  30. Vieira-de-Abreu A, Campbell RA, Weyrich AS, Zimmerman GA. Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum. Semin Immunopathol. 2012;34(1):5–30.

    Article  CAS  PubMed  Google Scholar 

  31. Herter JM, Rossaint J, Zarbock A. Platelets in inflammation and immunity. J Thromb Haemost. 2014;12(11):1764–75.

    Article  CAS  PubMed  Google Scholar 

  32. Morrell CN, Aggrey AA, Chapman LM, Modjeski KL. Emerging roles for platelets as immune and inflammatory cells. Blood. 2014;123(18):2759–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Xu XR, Zhang D, Oswald BE, Carrim N, Wang X, Hou Y, et al. Platelets are versatile cells: new discoveries in hemostasis, thrombosis, immune responses, tumor metastasis and beyond. Crit Rev Clin Lab Sci. 2016;53(6):409–30.

    Article  CAS  PubMed  Google Scholar 

  34. Dewitte A, Tanga A, Villeneuve J, Lepreux S, Ouattara A, Desmouliere A, et al. New frontiers for platelet CD154. Exp Hematol Oncol. 2015;4:6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Thomas MR, Storey RF. The role of platelets in inflammation. Thromb Haemost. 2015;114(3):449–58.

    PubMed  Google Scholar 

  36. Dewitte A, Lepreux S, Villeneuve J, Rigothier C, Combe C, Ouattara A, et al. Blood platelets and sepsis pathophysiology: a new therapeutic prospect in critical ill patients? Ann Intensive Care. 2017;7(1):115.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Hall R, Mazer CD. Antiplatelet drugs: a review of their pharmacology and management in the perioperative period. Anesth Analg. 2011;112(2):292–318.

    Article  CAS  PubMed  Google Scholar 

  38. Azoulay E, Knoebl P, Garnacho-Montero J, Rusinova K, Galstian G, Eggimann P, et al. Expert statements on the standard of care in critically ill adult patients with atypical hemolytic uremic syndrome. Chest. 2017;152(2):424–34.

    Article  PubMed  Google Scholar 

  39. Barcellini W, Fattizzo B, Zaninoni A, Radice T, Nichele I, Di Bona E, et al. Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Blood. 2014;124(19):2930–6.

    Article  CAS  PubMed  Google Scholar 

  40. Masias C, Vasu S, Cataland SR. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood. 2017;129(21):2857–63.

    Article  CAS  PubMed  Google Scholar 

  41. Scully M. Thrombocytopenia in hospitalized patients: approach to the patient with thrombotic microangiopathy. Hematology Am Soc Hematol Educ Program. 2017;2017(1):651–9.

    PubMed  PubMed Central  Google Scholar 

  42. Levi M, van der Poll T. A short contemporary history of disseminated intravascular coagulation. Semin Thromb Hemost. 2014;40(8):874–80.

    Article  PubMed  Google Scholar 

  43. Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. 1999;341(8):586–92.

    Article  CAS  PubMed  Google Scholar 

  44. Levi M. Diagnosis and treatment of disseminated intravascular coagulation. Int J Lab Hematol. 2014;36(3):228–36.

    Article  CAS  PubMed  Google Scholar 

  45. Levi M. Cancer-related coagulopathies. Thromb Res. 2014;133(Suppl 2):S70–5.

    Article  CAS  PubMed  Google Scholar 

  46. Levi M, Schultz M, van der Poll T. Sepsis and thrombosis. Semin Thromb Hemost. 2013;39(5):559–66.

    Article  CAS  PubMed  Google Scholar 

  47. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost. 2001;86(5):1327–30.

    Article  CAS  PubMed  Google Scholar 

  48. Toh CH, Hoots WK, Ssc on Disseminated Intravascular Coagulation of the I. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview1. J Thromb Haemost. 2007;5(3):604–6.

    Article  CAS  PubMed  Google Scholar 

  49. Dhainaut JF, Yan SB, Joyce DE, Pettila V, Basson B, Brandt JT, 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):1924–33.

    Article  CAS  PubMed  Google Scholar 

  50. Levi M, Toh CH, Thachil J, Watson HG. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009;145(1):24–33.

    Article  CAS  PubMed  Google Scholar 

  51. van den Born BJ, Honnebier UP, Koopmans RP, van Montfrans GA. Microangiopathic hemolysis and renal failure in malignant hypertension. Hypertension. 2005;45(2):246–51.

    Article  PubMed  CAS  Google Scholar 

  52. Gernsheimer T, James AH, Stasi R. How I treat thrombocytopenia in pregnancy. Blood. 2013;121(1):38–47.

    Article  CAS  PubMed  Google Scholar 

  53. Fakhouri F, Vercel C, Fremeaux-Bacchi V. Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy. Clin J Am Soc Nephrol. 2012;7(12):2100–6.

    Article  PubMed  Google Scholar 

  54. Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer Hovinga J, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017;15(2):312–22.

    Article  CAS  PubMed  Google Scholar 

  55. Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, et al. Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature. 2001;413(6855):488–94.

    Article  CAS  PubMed  Google Scholar 

  56. Ono T, Mimuro J, Madoiwa S, Soejima K, Kashiwakura Y, Ishiwata A, et al. Severe secondary deficiency of von Willebrand factor-cleaving protease (ADAMTS13) in patients with sepsis-induced disseminated intravascular coagulation: its correlation with development of renal failure. Blood. 2006;107(2):528–34.

    Article  CAS  PubMed  Google Scholar 

  57. Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group. N Engl J Med. 1991;325(6):393–7.

    Article  CAS  PubMed  Google Scholar 

  58. Vendramin C, McGuckin S, Alwan F, Westwood JP, Thomas M, Scully M. A single-center prospective study on the safety of plasma exchange procedures using a double-viral-inactivated and prion-reduced solvent/detergent fresh-frozen plasma as the replacement fluid in the treatment of thrombotic microangiopathy. Transfusion. 2017;57(1):131–6.

    Article  PubMed  Google Scholar 

  59. Adamski J. Thrombotic microangiopathy and indications for therapeutic plasma exchange. Hematology Am Soc Hematol Educ Program. 2014;2014(1):444–9.

    PubMed  Google Scholar 

  60. Loirat C, Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6:60.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Campistol JM, Arias M, Ariceta G, Blasco M, Espinosa M, Grinyo JM, et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia. 2013;33(1):27–45.

    PubMed  Google Scholar 

  62. Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, et al. Terminal complement inhibitor Eculizumab in atypical hemolytic–uremic syndrome. N Engl J Med. 2013;368(23):2169–81.

    Article  CAS  PubMed  Google Scholar 

  63. Riedl M, Fakhouri F, Le Quintrec M, Noone DG, Jungraithmayr TC, Fremeaux-Bacchi V, et al. Spectrum of complement-mediated thrombotic microangiopathies: pathogenetic insights identifying novel treatment approaches. Semin Thromb Hemost. 2014;40(4):444–64.

    Article  PubMed  CAS  Google Scholar 

  64. Noris M, Mele C, Remuzzi G. Podocyte dysfunction in atypical haemolytic uraemic syndrome. Nat Rev Nephrol. 2015;11(4):245–52.

    Article  CAS  PubMed  Google Scholar 

  65. Hofer J, Rosales A, Fischer C, Giner T. Extra-renal manifestations of complement-mediated thrombotic microangiopathies. Front Pediatr. 2014;2:97.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Schmidtko J, Peine S, El-Housseini Y, Pascual M, Meier P. Treatment of atypical hemolytic uremic syndrome and thrombotic microangiopathies: a focus on eculizumab. Am J Kidney Dis. 2013;61(2):289–99.

    Article  CAS  PubMed  Google Scholar 

  67. Sallée M, Ismail K, Fakhouri F, Vacher-Coponat H, Moussi-Francés J, Frémaux-Bacchi V, et al. Thrombocytopenia is not mandatory to diagnose haemolytic and uremic syndrome. BMC Nephrol [Internet]. 2013 2013; 14:[3 p.]. Available from: http://europepmc.org/abstract/MED/23298275; http://europepmc.org/articles/PMC3554580?pdf=render; http://europepmc.org/articles/PMC3554580; https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23298275/pdf/?tool=EBI; https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23298275/?tool=EBI; https://doi.org/10.1186/1471-2369-14-3.

  68. Nester CM, Barbour T, de Cordoba SR, Dragon-Durey MA, Fremeaux-Bacchi V, Goodship TH, et al. Atypical aHUS: state of the art. Mol Immunol. 2015;67(1):31–42.

    Article  CAS  PubMed  Google Scholar 

  69. Laurence J. Atypical hemolytic uremic syndrome (aHUS): making the diagnosis. Clin Adv Hematol Oncol. 2012;10(10 Suppl 17):1–12.

    PubMed  Google Scholar 

  70. Shenkman B, Einav Y. Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: diagnosis and classification. Autoimmun Rev. 2014;13(4–5):584–6.

    Article  CAS  PubMed  Google Scholar 

  71. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaime F, Dragon-Durey MA, Ngo S, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8(4):554–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mele C, Remuzzi G, Noris M. Hemolytic uremic syndrome. Semin Immunopathol. 2014;36(4):399–420.

    Article  CAS  PubMed  Google Scholar 

  73. Franchini M. Atypical hemolytic uremic syndrome: from diagnosis to treatment. Clin Chem Lab Med. 2015;53(11):1679–88.

    Article  CAS  PubMed  Google Scholar 

  74. Mannucci PM. Understanding organ dysfunction in thrombotic thrombocytopenic purpura. Intensive Care Med. 2015;41(4):715–8.

    Article  PubMed  Google Scholar 

  75. Cofiell R, Kukreja A, Bedard K, Yan Y, Mickle AP, Ogawa M, et al. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood. 2015;125(21):3253–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Walle JV, Delmas Y, Ardissino G, Wang J, Kincaid JF, Haller H. Improved renal recovery in patients with atypical hemolytic uremic syndrome following rapid initiation of eculizumab treatment. J Nephrol. 2017;30(1):127–34.

    Article  PubMed  Google Scholar 

  77. Zuber J, Le Quintrec M, Sberro-Soussan R, Loirat C, Fremeaux-Bacchi V, Legendre C. New insights into postrenal transplant hemolytic uremic syndrome. Nat Rev Nephrol. 2011;7(1):23–35.

    Article  PubMed  Google Scholar 

  78. Al-Nouri ZL, Reese JA, Terrell DR, Vesely SK, George JN. Drug-induced thrombotic microangiopathy: a systematic review of published reports. Blood. 2015;125(4):616–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kundra A, Wang JC. Interferon induced thrombotic microangiopathy (TMA): Analysis and concise review. Crit Rev Oncol Hematol. 2017;112:103–12.

    Article  PubMed  Google Scholar 

  80. Chong BH, Pitney WR, Castaldi PA. Heparin-induced thrombocytopenia: association of thrombotic complications with heparin-dependent IgG antibody that induces thromboxane synthesis in platelet aggregation. Lancet. 1982;2(8310):1246–9.

    Article  CAS  PubMed  Google Scholar 

  81. Amiral J, Bridey F, Dreyfus M, Vissoc AM, Fressinaud E, Wolf M, et al. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost. 1992;68(1):95–6.

    Article  CAS  PubMed  Google Scholar 

  82. Greinacher A, Potzsch B, Amiral J, Dummel V, Eichner A, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost. 1994;71(2):247–51.

    CAS  PubMed  Google Scholar 

  83. Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101(5):502–7.

    Article  CAS  PubMed  Google Scholar 

  84. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332(20):1330–6.

    Article  CAS  PubMed  Google Scholar 

  85. Warkentin TE, Roberts RS, Hirsh J, Kelton JG. An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Arch Intern Med. 2003;163(20):2518–24.

    Article  PubMed  Google Scholar 

  86. Linkins L, Lee D. Frequency of heparin-induced thrombocytopeniaWarkentin TE, Greinacher A, Heparin-induced thrombocytopenia. 5. Boca Raton, : CRC Press; 2013. 110–150.

    Google Scholar 

  87. Trehel-Tursis V, Louvain-Quintard V, Zarrouki Y, Imbert A, Doubine S, Stephan F. Clinical and biologic features of patients suspected or confirmed to have heparin-induced thrombocytopenia in a cardiothoracic surgical ICU. Chest. 2012;142(4):837–44.

    Article  CAS  PubMed  Google Scholar 

  88. Warkentin TE. Heparin-induced thrombocytopenia in the ICU. Chest. 2012;142(4):815–6.

    Article  PubMed  Google Scholar 

  89. Selleng S, Selleng K, Friesecke S, Grundling M, Kuhn SO, Raschke R, et al. Prevalence and clinical implications of anti-PF4/heparin antibodies in intensive care patients: a prospective observational study. J Thromb Thrombolysis. 2015;39(1):60–7.

    Article  CAS  PubMed  Google Scholar 

  90. Lo GK, Sigouin CS, Warkentin TE. What is the potential for overdiagnosis of heparin-induced thrombocytopenia? Am J Hematol. 2007;82(12):1037–43.

    Article  CAS  PubMed  Google Scholar 

  91. Warkentin TE, Sheppard JI, Moore JC, Sigouin CS, Kelton JG. Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost. 2008;6(8):1304–12.

    Article  CAS  PubMed  Google Scholar 

  92. Warkentin TE. Heparin-induced thrombocytopenia in critically ill patients. Semin Thromb Hemost. 2015;41(1):49–60.

    Article  CAS  PubMed  Google Scholar 

  93. Warkentin TE, Kelton JG. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001;344(17):1286–92.

    Article  CAS  PubMed  Google Scholar 

  94. Warkentin TE, Sheppard JA. Serological investigation of patients with a previous history of heparin-induced thrombocytopenia who are reexposed to heparin. Blood. 2014;123(16):2485–93.

    Article  CAS  PubMed  Google Scholar 

  95. Warkentin TE. Agents for the treatment of heparin-induced thrombocytopenia. Hematol Oncol Clin North Am. 2010;24(4):755–75. ix

    Article  PubMed  Google Scholar 

  96. Warkentin TE, Kelton JG. Delayed-onset heparin-induced thrombocytopenia and thrombosis. Ann Intern Med. 2001;135(7):502–6.

    Article  CAS  PubMed  Google Scholar 

  97. Kopolovic I, Warkentin TE. Progressive thrombocytopenia after cardiac surgery in a 67-year-old man. CMAJ. 2014;186(12):929–33.

    Article  PubMed  PubMed Central  Google Scholar 

  98. Warkentin TE. Clinical picture of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, editors. Heparin-induced thrombocytopenia. 5th ed. Boca Ranton: CRC Press; 2013. p. 24–76.

    Google Scholar 

  99. Warkentin TE, Hayward CP, Boshkov LK, Santos AV, Sheppard JA, Bode AP, et al. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia. Blood. 1994;84(11):3691–9.

    CAS  PubMed  Google Scholar 

  100. Rauova L, Hirsch JD, Greene TK, Zhai L, Hayes VM, Kowalska MA, et al. Monocyte-bound PF4 in the pathogenesis of heparin-induced thrombocytopenia. Blood. 2010;116(23):5021–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Warkentin TE, Basciano PA, Knopman J, Bernstein RA. Spontaneous heparin-induced thrombocytopenia syndrome: 2 new cases and a proposal for defining this disorder. Blood. 2014;123(23):3651–4.

    Article  CAS  PubMed  Google Scholar 

  102. Jay RM, Warkentin TE. Fatal heparin-induced thrombocytopenia (HIT) during warfarin thromboprophylaxis following orthopedic surgery: another example of ‘spontaneous’ HIT? J Thromb Haemost. 2008;6(9):1598–600.

    Article  CAS  PubMed  Google Scholar 

  103. Krauel K, Weber C, Brandt S, Zahringer U, Mamat U, Greinacher A, et al. Platelet factor 4 binding to lipid A of Gram-negative bacteria exposes PF4/heparin-like epitopes. Blood. 2012;120(16):3345–52.

    Article  CAS  PubMed  Google Scholar 

  104. Warkentin TE, Elavathil LJ, Hayward CP, Johnston MA, Russett JI, Kelton JG. The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia. Ann Intern Med. 1997;127(9):804–12.

    Article  CAS  PubMed  Google Scholar 

  105. Srinivasan AF, Rice L, Bartholomew JR, Rangaswamy C, La Perna L, Thompson JE, et al. Warfarin-induced skin necrosis and venous limb gangrene in the setting of heparin-induced thrombocytopenia. Arch Intern Med. 2004;164(1):66–70.

    Article  PubMed  Google Scholar 

  106. Warkentin TE, Pai M, Cook RJ. Intraoperative anticoagulation and limb amputations in patients with immune heparin-induced thrombocytopenia who require vascular surgery. J Thromb Haemost. 2012;10(1):148–50.

    Article  CAS  PubMed  Google Scholar 

  107. Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106(8):2710–5.

    Article  CAS  PubMed  Google Scholar 

  108. Warkentin TE, Sheppard JA, Sigouin CS, Kohlmann T, Eichler P, Greinacher A. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood. 2006;108(9):2937–41.

    Article  CAS  PubMed  Google Scholar 

  109. Warkentin TE, Pai M, Linkins LA. Direct oral anticoagulants for treatment of HIT: update of Hamilton experience and literature review. Blood. 2017;130(9):1104–13.

    Article  CAS  PubMed  Google Scholar 

  110. Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, et al. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007;109(5):1870–7.

    Article  CAS  PubMed  Google Scholar 

  111. Baudo F, de Cataldo F. The problem of acquired hemophilia. Blood. 2015;125(7):1052–3.

    Article  CAS  PubMed  Google Scholar 

  112. Knoebl P, Marco P, Baudo F, Collins P, Huth-Kühne A, Nemes L, et al. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost. 2012;10(4):622–31.

    Article  CAS  PubMed  Google Scholar 

  113. Tiede A, Scharf R, Dobbelstein C, Werwitzke S. Management of acquired haemophilia A. Hamostaseologie. 2015;35(4):311–8.

    Article  CAS  PubMed  Google Scholar 

  114. Baudo F, Collins P, Huth-Kuehne A, Lévesque H, Marco P, Nemes L, et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood. 2012;120(1):39–46.

    Article  CAS  PubMed  Google Scholar 

  115. Tiede A, Werwitzke S, Scharf RE, editors. Laboratory diagnosis of acquired hemophilia A: limitations, consequences, and challenges. Seminars in thrombosis and hemostasis: Thieme Medical Publishers; Semin Thromb Hemost. 2014;40(7):803–11. http://doi.org/10.1055/s-0034-1390004. Epub 2014 Oct 9.

    Article  PubMed  CAS  Google Scholar 

  116. Collins PW. Management of acquired haemophilia A. J Thromb Haemost. 2011;9(s1):226–35.

    Article  PubMed  Google Scholar 

  117. Callum JL, Rizoli S. Assessment and management of massive bleeding: coagulation assessment, pharmacologic strategies, and transfusion management. Hematology Am Soc Hematol Educ Program. 2012;2012:522–8.

    PubMed  Google Scholar 

  118. Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J Trauma. 2006;60(6 Suppl):S3–11.

    Article  PubMed  Google Scholar 

  119. Cotton BA, Au BK, Nunez TC, Gunter OL, Robertson AM, Young PP. Predefined massive transfusion protocols are associated with a reduction in organ failure and postinjury complications. J Trauma. 2009;66(1):41–48; discussion 8–9.

    Article  Google Scholar 

  120. Cotton BA, Gunter OL, Isbell J, Au BK, Robertson AM, Morris JA, Jr., et al. Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization. J Trauma. 2008;64(5):1177–1182; discussion 82–3.

    Article  Google Scholar 

  121. O'Keeffe T, Refaai M, Tchorz K, Forestner JE, Sarode R. A massive transfusion protocol to decrease blood component use and costs. Arch Surg. 2008;143(7):686–90; discussion 90-1.

    Article  PubMed  Google Scholar 

  122. Ning S, Barty R, Liu Y, Heddle NM, Rochwerg B, Arnold DM. Platelet transfusion practices in the ICU: data from a large transfusion registry. Chest. 2016;150(3):516–23.

    Article  PubMed  Google Scholar 

  123. Aubron C, Flint AW, Bailey M, Pilcher D, Cheng AC, Hegarty C, et al. Is platelet transfusion associated with hospital-acquired infections in critically ill patients? Crit Care. 2017;21:2.

    Article  PubMed  PubMed Central  Google Scholar 

  124. Tariket S, Sut C, Hamzeh-Cognasse H, Laradi S, Pozzetto B, Garraud O, et al. Transfusion-related acute lung injury: transfusion, platelets and biological response modifiers. Expert Rev Hematol. 2016;9(5):497–508.

    Article  CAS  PubMed  Google Scholar 

  125. Kaufman RM, Djulbegovic B, Gernsheimer T, Kleinman S, Tinmouth AT, Capocelli KE, et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Intern Med. 2015;162(3):205–13.

    Article  PubMed  Google Scholar 

  126. Callum JL, Network ORBC, Staff ORBCN. Bloody easy 3: blood transfusions, blood alternatives and transfusion reactions: a guide to transfusion medicine: Ontario Regional Blood Coordinating Network; 2011.

    Google Scholar 

  127. Arnold DM, Lauzier F, Albert M, Williamson D, Li N, Zarychanski R, et al. The association between platelet transfusions and bleeding in critically ill patients with thrombocytopenia. Res Pract Thromb Haemost. 2017;1(1):103–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Thiele T, Selleng K, Selleng S, Greinacher A, Bakchoul T. Thrombocytopenia in the intensive care unit-diagnostic approach and management. Semin Hematol. 2013;50(3):239–50.

    Article  PubMed  Google Scholar 

  129. Lieberman L, Bercovitz RS, Sholapur NS, Heddle NM, Stanworth SJ, Arnold DM. Platelet transfusions for critically ill patients with thrombocytopenia. Blood. 2014;123(8):1146–51; quiz 280.

    Article  PubMed  CAS  Google Scholar 

  130. Liontos L, Fralick M, Longmore A, Hicks LK, Sholzberg M. Bleeding risk using INR/aPTT pre-surgery: systemtic review (BRUISR) (BRUISR). Blood. 2017;130:4654.

    Google Scholar 

  131. Baumann Kreuziger LM, Morton CT, Subramanian AT, Anderson CP, Dries DJ. Not only in trauma patients: hospital-wide implementation of a massive transfusion protocol. Transfus Med. 2014;24(3):162–8.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Michelle Sholzberg MDCM, FRCPC, MSc .

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Sholzberg, M. (2018). Hemostatic Abnormalities in the Critically Ill. In: Shander, A., Corwin, H. (eds) Hematologic Challenges in the Critically Ill. Springer, Cham. https://doi.org/10.1007/978-3-319-93572-0_2

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