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Coagulation Cascade and Fibrinolysis Pathway: Assessment in the Laboratory

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Nonmalignant Hematology

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Abstract

Hemostasis is maintained through interactions between whole-blood cellular components, the vascular endothelium, and pro- and anticoagulant plasma proteins such that net hemostasis is the result of the competing physiology of coagulation and fibrinolysis. Traditional hemostatic assessment involves plasma-based assays of coagulation proteins and evaluation of platelet number and function. This testing may not accurately reflect net hemostasis as each test evaluates variables semi-independently and provides minimal/no information about fibrinolysis. Classic coagulation tests, including the prothrombin time (PT) and activated partial thromboplastin time (aPTT), were developed in the mid-twentieth century with little alteration other than automation since then (Martin et al. 1947; Goulian and Beck 1965). The PT measures the activity of the so-called extrinsic and common pathways of coagulation (Fig. 1), while the aPTT measures the intrinsic and common pathways. Thrombin time (TT) measures the common pathway and reflects the conversion of fibrinogen to fibrin. The division of the clotting cascade into the intrinsic, extrinsic, and common pathways has little in vivo validity, but has some conceptual utility in the interpretation of the results of laboratory investigation.

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References

  • Anderson JA, Saenko EL. Heparin resistance. Br J Anaesth. 2002;88(4):467–9.

    Article  CAS  PubMed  Google Scholar 

  • Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, Powers P. Development of the human coagulation system in the full-term infant. Blood. 1987;70(1):165–72.

    CAS  PubMed  Google Scholar 

  • Bay A, Oner AF, Celebi V, Uner A. Evaluation of vitamin K deficiency in children with acute and intractable diarrhea. Adv Ther. 2006;23(3):469–74.

    Article  CAS  PubMed  Google Scholar 

  • Bembea MM, Annich G, Rycus P, Oldenburg G, Berkowitz I, Pronovost P. Variability in anticoagulation management of patients on extracorporeal membrane oxygenation: an international survey. Pediatr Crit Care Med. 2013;14(2):e77–84.

    Article  PubMed  PubMed Central  Google Scholar 

  • Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Transfus Med Rev. 2012;26(1):1–13.

    Article  PubMed  Google Scholar 

  • Chitlur M, Rivard GE, Lillicrap D, Mann K, Shima M, Young G, Factor Viii FIX, S. Rare Coagulation Disorders Subcommittee of the, T. Standardisation Committee of the International Society on and Haemostasis. Recommendations for performing thromboelastography/thromboelastometry in hemophilia: communication from the SSC of the ISTH. J Thromb Haemost. 2014;12(1):103–6.

    Article  CAS  PubMed  Google Scholar 

  • Coakley M, Reddy K, Mackie I, Mallett S. Transfusion triggers in orthotopic liver transplantation: a comparison of the thromboelastometry analyzer, the thromboelastogram, and conventional coagulation tests. J Cardiothorac Vasc Anesth. 2006;20(4):548–53.

    Article  PubMed  Google Scholar 

  • collaborators, C.-t, Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, El-Sayed H, Gogichaishvili T, Gupta S, Herrera J, Hunt B, Iribhogbe P, Izurieta M, Khamis H, Komolafe E, Marrero MA, Mejia-Mantilla J, Miranda J, Morales C, Olaomi O, Olldashi F, Perel P, Peto R, Ramana PV, Ravi RR, Yutthakasemsunt S. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23–32.

    Article  Google Scholar 

  • Finley A, Greenberg C. Review article: heparin sensitivity and resistance: management during cardiopulmonary bypass. Anesth Analg. 2013;116(6):1210–22.

    Article  CAS  PubMed  Google Scholar 

  • Goulian M, Beck WS. The partial thromboplastin time test. Modification of the procedure, and study of the sensitivity and optimal conditions. Tech Bull Regist Med Technol. 1965;35:97–103.

    CAS  PubMed  Google Scholar 

  • Greene LA, Law C, Jung M, Walton S, Ignjatovic V, Monagle P, Raffini LJ. Lack of anti-factor Xa assay standardization results in significant low molecular weight heparin (enoxaparin) dose variation in neonates and children. J Thromb Haemost. 2014;12(9):1554–7.

    Article  CAS  PubMed  Google Scholar 

  • Ignjatovic V, Summerhayes R, Gan A, Than J, Chan A, Cochrane A, Bennett M, Horton S, Shann F, Lane G, Ross-Smith M, Monagle P. Monitoring unfractionated heparin (UFH) therapy: which anti-factor Xa assay is appropriate? Thromb Res. 2007;120(3):347–51.

    Article  CAS  PubMed  Google Scholar 

  • Jackson GN, Ashpole KJ, Yentis SM. The TEG vs. the ROTEM thromboelastography/thromboelastometry systems. Anaesthesia. 2009;64(2):212–5.

    Article  CAS  PubMed  Google Scholar 

  • Kashuk JL, Moore EE, Sawyer M, Wohlauer M, Pezold M, Barnett C, Biffl WL, Burlew CC, Johnson JL, Sauaia A. Primary fibrinolysis is integral in the pathogenesis of the acute coagulopathy of trauma. Ann Surg. 2010;252(3):434–42. discussion 443–434.

    PubMed  Google Scholar 

  • Kenet G, Chan AK, Soucie JM, Kulkarni R. Bleeding disorders in neonates. Haemophilia. 2010;16 Suppl 5:168–75.

    Article  PubMed  Google Scholar 

  • Khaja WA, Bilen O, Lukner RB, Edwards R, Teruya J. Evaluation of heparin assay for coagulation management in newborns undergoing ECMO. Am J Clin Pathol. 2010;134(6):950–4.

    Article  CAS  PubMed  Google Scholar 

  • Kitchens CS. To bleed or not to bleed? Is that the question for the PTT? J Thromb Haemost. 2005;3(12):2607–11.

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni R, Lusher J. Perinatal management of newborns with haemophilia. Br J Haematol. 2001;112(2):264–74.

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni R, Soucie JM, Lusher J, Presley R, Shapiro A, Gill J, Manco-Johnson M, Koerper M, Mathew P, Abshire T, Dimichele D, Hoots K, Janco R, Nugent D, Geraghty S, Evatt B, I. Haemophilia Treatment Center Network. Sites of initial bleeding episodes, mode of delivery and age of diagnosis in babies with haemophilia diagnosed before the age of 2 years: a report from The Centers for Disease Control and Prevention’s (CDC) Universal Data Collection (UDC) project. Haemophilia. 2009;15(6):1281–90.

    Article  CAS  PubMed  Google Scholar 

  • Luddington RJ. Thromboelastography/thromboelastometry. Clin Lab Haematol. 2005;27(2):81–90.

    Article  CAS  PubMed  Google Scholar 

  • Martin JW, Curfman Jr GH, Cavano FL. The prothrombin time and variables in the method. J Lab Clin Med. 1947;32(5):554–65.

    CAS  PubMed  Google Scholar 

  • Paden ML, Conrad SA, Rycus PT, Thiagarajan RR, Registry E. Extracorporeal life-support organization registry report 2012. ASAIO J. 2013;59(3):202–10.

    Article  PubMed  Google Scholar 

  • Perry DJ, Fitzmaurice DA, Kitchen S, Mackie IJ, Mallett S. Point-of-care testing in haemostasis. Br J Haematol. 2010;150(5):501–14.

    Article  PubMed  Google Scholar 

  • Rahe-Meyer N, Solomon C, Winterhalter M, Piepenbrock S, Tanaka K, Haverich A, Pichlmaier M. Thromboelastometry-guided administration of fibrinogen concentrate for the treatment of excessive intraoperative bleeding in thoracoabdominal aortic aneurysm surgery. J Thorac Cardiovasc Surg. 2009;138(3):694–702.

    Article  PubMed  Google Scholar 

  • Schochl H, Nienaber U, Hofer G, Voelckel W, Jambor C, Scharbert G, Kozek-Langenecker S, Solomon C. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit Care. 2010;14(2):R55.

    Article  PubMed  PubMed Central  Google Scholar 

  • Society of Thoracic Surgeons Blood Conservation Guideline Task, F, Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, Song HK, Clough ER, T. Society of Cardiovascular Anesthesiologists Special Task Force on Blood, Shore-Lesserson LJ, Goodnough LT, Mazer CD, Shander A, Stafford-Smith M, Waters J, P. International Consortium for Evidence Based, Baker RA, Dickinson TA, FitzGerald DJ, Likosky DS, Shann KG. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011;91(3):944–82.

    Article  Google Scholar 

  • Sulkowski JP, Preston TJ, Cooper JN, Duffy VL, Deans KJ, Chicoine LG, Minneci PC. Comparison of routine laboratory measures of heparin anticoagulation for neonates on extracorporeal membrane oxygenation. J Extra Corpor Technol. 2014;46(1):69–76.

    PubMed  PubMed Central  Google Scholar 

  • Tcherniantchouk O, Laposata M, Marques MB. The isolated prolonged PTT. Am J Hematol. 2013;88(1):82–5.

    Article  PubMed  Google Scholar 

  • Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol. 2014;89(2):228–32.

    Article  CAS  PubMed  Google Scholar 

  • Wikkelsoe AJ, Afshari A, Wetterslev J, Brok J, Moeller AM. Monitoring patients at risk of massive transfusion with thromboelastography or thromboelastometry: a systematic review. Acta Anaesthesiol Scand. 2011;55(10):1174–89.

    Article  CAS  PubMed  Google Scholar 

  • Young G, Sorensen B, Dargaud Y, Negrier C, Brummel-Ziedins K, Key NS. Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: current state of art and future perspectives. Blood. 2013;121(11):1944–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zia A, O’Brien SH. Global coagulation assays: a clinical perspective. J Thromb Thrombolysis. 2015;39(1):89–94.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology, The Children’s Hospital of Philadelphia, 3615 Civic Center Blvd, Abramson Research Building Room 316G, Philadelphia, PA, USA

    Lindsey A. George MD & Michele P. Lambert MD, MTR (Medical Director)

  2. Department of Pediatrics, Center for Cellular and Molecular Therapeutics, The Children’s Hospital of Philadelphia, 3615 Civic Center Blvd, Abramson Research Building Room 316G, Philadelphia, PA, USA

    Lindsey A. George MD

  3. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Michele P. Lambert MD, MTR (Medical Director)

  4. Special Coagulation Laboratory, The Children’s Hospital of Philadelphia, 3615 Civic Center Blvd, Abramson Research Building Room 316G, Philadelphia, PA, USA

    Michele P. Lambert MD, MTR (Medical Director)

Authors
  1. Lindsey A. George MD
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  2. Michele P. Lambert MD, MTR
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Correspondence to Lindsey A. George MD .

Editor information

Editors and Affiliations

  1. Cancer Treatment Centers of America, Department of Hematology and Bone Marrow Transplantion, Zion, Illinois, USA

    Syed A. Abutalib

  2. Dana-Farber Cancer Institute, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Jean M. Connors

  3. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

    Margaret V. Ragni

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George, L.A., Lambert, M.P. (2016). Coagulation Cascade and Fibrinolysis Pathway: Assessment in the Laboratory. In: Abutalib, S., Connors, J., Ragni, M. (eds) Nonmalignant Hematology. Springer, Cham. https://doi.org/10.1007/978-3-319-30352-9_20

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  • DOI: https://doi.org/10.1007/978-3-319-30352-9_20

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-30350-5

  • Online ISBN: 978-3-319-30352-9

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