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Procoagulant Drugs

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Perioperative Hemostasis

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Abstract

Procoagulant drugs are non-transfusional agents that are primarily used when bleeding is the consequence of a specific defect of hemostasis. In this chapter, the pharmacological properties and uses of desmopressin, antifibrinolytics, and vitamin K will be reviewed. Desmopressin, with its various procoagulant pharmacological effects, is used in the prevention and treatment of bleeding related to congenital and acquired coagulation factor deficiencies or platelet function disorders. Antifibrinolytics (inhibitors in particular steps of fibrinolysis) are the treatment of choice in bleeding caused by hyperfibrinolysis. Because of their low cost and their mild side effects, desmopressin and antifibrinolytics are also used as blood-saving agents in surgery. Vitamin K is given in states of vitamin K deficiency which lead to vitamin K deficiency bleedings. This is relevant to patients taking vitamin K antagonists in cases of urgent invasive procedures, asymptomatic and excessively elevated INR values, and bleeding.

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References

  • Ageno W, Gallus AS, Wittkowsky A et al (2012) Oral anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141:e44S–e88S

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Agnelli G, Parise P, Levi M et al (1995) Effects of desmopressin on hemostasis in patients with liver cirrhosis. Haemostasis 25:241–247

    PubMed  CAS  Google Scholar 

  • Balduini CL, Noris P, Belletti S et al (1999) In vitro and in vivo effects of desmopressin on platelet function. Haematologica 84:891–896

    PubMed  CAS  Google Scholar 

  • Baudo F, Collins P, Huth-Kühne A et al (2012) Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood 120:39–46

    Article  PubMed  CAS  Google Scholar 

  • Bonnar J, Sheppard BL (1996) Treatment of menorrhagia during menstruation: randomised controlled trial of ethamsylate, mefenamic acid, and tranexamic acid. Br Med J 313:579–582

    Article  CAS  Google Scholar 

  • Brem E, Koyfman A, Foran M (2013) Review of recently approved alternatives to anticoagulation with warfarin for emergency clinicians. J Emerg Med 45:143–149

    Article  PubMed  Google Scholar 

  • Burke CW (2013) Vitamin k deficiency bleeding: overview and considerations. J Pediatr Health Care 27:215–221

    Article  PubMed  Google Scholar 

  • Burroughs AK, Matthews K, Qadiri M et al (1985) Desmopressin and bleeding time in patients with cirrhosis. Br Med J 291:1377–1381

    Article  CAS  Google Scholar 

  • Carless PA, Henry DA, Moxey AJ et al (2004) Desmopressin for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev (1):CD001884

    Google Scholar 

  • Cash JD, Gader AM, da Costa J (1974) Proceedings: the release of plasminogen activator and factor VIII to lysine vasopressin, arginine vasopressin, I-desamino-8-d-arginine vasopressin, angiotensin and oxytocin in man. Br J Haematol 27:363–364

    PubMed  CAS  Google Scholar 

  • Casonato A, Pontara E, Dannhaeuser D et al (1994) Re-evaluation of the therapeutic efficacy of DDAVP in type IIB von Willebrand’s disease. Blood Coagul Fibrinolysis 5:959–964

    Article  PubMed  CAS  Google Scholar 

  • Castaman G (2008) Desmopressin for the treatment of haemophilia. Haemophilia 14:15–20

    Article  PubMed  CAS  Google Scholar 

  • Cattaneo M (2002) Desmopressin in the treatment of patients with defects of platelet function. Haematologica 87:1122–1124

    PubMed  Google Scholar 

  • Coppola A, Di Minno G (2008) Desmopressin in inherited disorders of platelet function. Haemophilia 14:31–39

    Article  PubMed  CAS  Google Scholar 

  • CRASH-2 Collaborators (Intracranial Bleeding Study) (2011) Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). BMJ 343:d3795

    Article  Google Scholar 

  • Crescenzi G, Landoni G, Biondi-Zoccai G et al (2008) Desmopressin reduces transfusion needs after surgery: a meta-analysis of randomized clinical trials. Anesthesiology 109:1063–1076

    Article  PubMed  CAS  Google Scholar 

  • De Simone N, Sarode R (2013) Diagnosis and management of common acquired bleeding disorders. Semin Thromb Hemost 39:172–181

    Article  PubMed  Google Scholar 

  • Favaloro EJ (2011) Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays. Blood Coagul Fibrinolysis 22:553–564

    Article  PubMed  CAS  Google Scholar 

  • Federici AB, Budde U, Castaman G et al (2013) Current diagnostic and therapeutic approaches to patients with acquired von Willebrand syndrome: a 2013 update. Semin Thromb Hemost 39:191–201

    Article  PubMed  CAS  Google Scholar 

  • Fergusson DA, Hebert PC, Mazer CD et al (2008) A comparison of aprotinin and lysine analogues in high-risk cardiac surgery. N Engl J Med 358:2319–2331

    Article  PubMed  CAS  Google Scholar 

  • Ferland G (2012) The discovery of vitamin K and its clinical applications. Ann Nutr Metab 61:213–218

    Article  PubMed  CAS  Google Scholar 

  • Franchini M (2007) The use of desmopressin as a hemostatic agent: a concise review. Am J Hematol 82:731–735

    Article  PubMed  CAS  Google Scholar 

  • Franchini M, Lippi G (2011) The use of desmopressin in acquired haemophilia A: a systematic review. Blood Transfus 9:377–382

    PubMed  PubMed Central  Google Scholar 

  • Franchini M, Manzato F, Salvagno GL et al (2009) The use of desmopressin in congenital factor XI deficiency: a systematic review. Ann Hematol 88:931–935

    Article  PubMed  CAS  Google Scholar 

  • Galvez A, Gomez-Ortiz G, Diaz-Ricart M et al (1997) Desmopressin (DDAVP) enhances platelet adhesion to the extracellular matrix of cultured human endothelial cells through increased expression of tissue factor. Thromb Haemost 77:975–980

    PubMed  CAS  Google Scholar 

  • Gluud LL, Klingenberg SL, Langholz E (2012) Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database of Syst Rev 1:CD006640

    Google Scholar 

  • Gralnick HR, Williams SB, McKeown LP et al (1986) DDAVP in type IIa von Willebrand’s disease. Blood 67:465–468

    PubMed  CAS  Google Scholar 

  • Henry DA, Oconnell DL (1989) Effects of fibrinolytic inhibitors on mortality from upper gastrointestinal hemorrhage. Br Med J 298:1142–1146

    Article  CAS  Google Scholar 

  • Henry D, Carless P, Fergusson D et al (2009) The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis. Can Med Assoc J 180:183–193

    Article  Google Scholar 

  • Henry DA, Carless PA, Moxey AJ et al (2011) Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev (1):CD001886

    Google Scholar 

  • Hutton B, Joseph L, Fergusson D et al (2012) Risks of harms using antifibrinolytics in cardiac surgery: systematic review and network meta-analysis of randomised and observational studies. Br Med J 345:e5798

    Article  Google Scholar 

  • Irigoyen JP, Munoz-Canoves P, Montero L et al (1999) The plasminogen activator system: biology and regulation. Cell Mol Life Sci 56:104–132

    Article  PubMed  CAS  Google Scholar 

  • Kalavrouziotis D, Voisine P, Mohammadi S et al (2012) High-dose tranexamic acid is an independent predictor of early seizure after cardiopulmonary bypass. Ann Thorac Surg 93:148–154

    Article  PubMed  Google Scholar 

  • Kaufmann JE, Vischer UM (2003) Cellular mechanisms of the hemostatic effects of desmopressin (DDAVP). J Thromb Haemost 1:682–689

    Article  PubMed  CAS  Google Scholar 

  • Kohler M, Harris A (1988) Pharmacokinetics and haematological effects of desmopressin. Eur J Clin Pharmacol 35:281–285

    Article  PubMed  CAS  Google Scholar 

  • Koster A, Borgermann J, Zittermann A et al (2013) Moderate dosage of tranexamic acid during cardiac surgery with cardiopulmonary bypass and convulsive seizures: incidence and clinical outcome. Br J Anaesth 110:34–40

    Article  PubMed  CAS  Google Scholar 

  • Lee HK, Kim YJ, Jeong JU et al (2010) Desmopressin improves platelet dysfunction measured by in vitro closure time in uremic patients. Nephron Clin Pract 114:c248–c252

    Article  PubMed  CAS  Google Scholar 

  • Lethagen S (1997) Desmopressin–a haemostatic drug: state-of-the-art review. Eur J Anaesthesiol Suppl 14:1–9

    Article  PubMed  CAS  Google Scholar 

  • Levi M, Eerenberg E, Kamphuisen PW (2011) Bleeding risk and reversal strategies for old and new anticoagulants and antiplatelet agents. J Thromb Haemost 9:1705–1712

    Article  PubMed  CAS  Google Scholar 

  • Lukes AS, Moore KA, Muse KN et al (2010) Tranexamic acid treatment for heavy menstrual bleeding a randomized controlled trial. Obstet Gynecol 116:865–875

    Article  PubMed  Google Scholar 

  • Mannucci PM (1997) Desmopressin (DDAVP) in the treatment of bleeding disorders: the first 20 years. Blood 90:2515–2521

    PubMed  CAS  Google Scholar 

  • Mannucci PM (1998) Hemostatic drugs. N Engl J Med 339:245–253

    Article  PubMed  CAS  Google Scholar 

  • Mannucci PM (2001) How I treat patients with von Willebrand disease. Blood 97:1915–1919

    Article  PubMed  CAS  Google Scholar 

  • Mannucci PM (2008) Desmopressin: an historical introduction. Haemophilia 14:1–4

    Article  PubMed  CAS  Google Scholar 

  • Mannucci PM, Levi M (2007) Prevention and treatment of major blood loss. N Engl J Med 356:2301–2311

    Article  PubMed  CAS  Google Scholar 

  • Mannucci PM, Aberg M, Nilsson IM et al (1975) Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 30:81–93

    Article  PubMed  CAS  Google Scholar 

  • Mannucci PM, Remuzzi G, Pusineri F et al (1983) Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med 308:8–12

    Article  PubMed  CAS  Google Scholar 

  • Mannucci PM, Vicente V, Vianello L et al (1986) Controlled trial of desmopressin in liver cirrhosis and other conditions associated with a prolonged bleeding time. Blood 67:1148–1153

    PubMed  CAS  Google Scholar 

  • Marti-Carvajal AJ, Sola I (2012) Vitamin K for upper gastrointestinal bleeding in patients with acute or chronic liver diseases. Cochrane Database Syst Rev (9):CD004792

    Google Scholar 

  • Marti-Carvajal AJ, Sola I, Marti-Carvajal PI (2012) Antifibrinolytic amino acids for upper gastrointestinal bleeding in patients with acute or chronic liver disease. Cochrane Database Syst Rev (9):CD006007

    Google Scholar 

  • Morrison JJ, Dubose JJ, Rasmussen TE et al (2012) Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg 147:113–119

    Article  PubMed  CAS  Google Scholar 

  • Murphy GJ, Reeves BC, Rogers CA et al (2007) Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation 116:2544–2552

    Article  PubMed  Google Scholar 

  • Nurden AT, Freson K, Seligsohn U (2012) Inherited platelet disorders. Haemophilia 18:154–160

    Article  PubMed  Google Scholar 

  • Pereira A, del Valle OM, Sanz C (2003) DDAVP enhances the ability of blood monocytes to form rosettes with activated platelets by increasing the expression of P-selectin sialylated ligands on the monocyte surface. Br J Haematol 120:814–820

    Article  PubMed  CAS  Google Scholar 

  • Perel P, Ker K, Morales Uribe CH et al (2013) Tranexamic acid for reducing mortality in emergency and urgent surgery. Cochrane Database Syst Rev (1):CD010245

    Google Scholar 

  • Pivalizza EG, Warters RD, Gebhard R (2003) Desmopressin before liver transplantation. Can J Anaesth 50:748–749

    Article  PubMed  Google Scholar 

  • Podda G, Femia EA, Pugliano M et al (2012) Congenital defects of platelet function. Platelets 23:552–563

    Article  PubMed  CAS  Google Scholar 

  • Puckett RM, Offringa M (2009) Prophylactic vitamin K for vitamin K deficiency bleeding in neonates. Cochrane Database Syst Rev (4):CD002776

    Google Scholar 

  • Quinton TM, Kim S, Derian CK et al (2004) Plasmin-mediated activation of platelets occurs by cleavage of protease-activated receptor 4. J Biol Chem 279:18434–18439

    Article  PubMed  CAS  Google Scholar 

  • Ragni MV, Novelli EM, Murshed A et al (2013) Phase II prospective open-label trial of recombinant interleukin-11 in desmopressin-unresponsive von Willebrand disease and mild or moderate haemophilia A. Thromb Haemost 109:248–254

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Rappold JF, Pusateri AE (2013) Tranexamic acid in remote damage control resuscitation. Transfusion 53:96S–99S

    Article  PubMed  Google Scholar 

  • Roberts I, Shakur H, Ker K et al (2011) Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst Rev (1):CD004896

    Google Scholar 

  • Sabate A, Dalmau A, Koo M et al (2012) Coagulopathy management in liver transplantation. Transplant Proc 44:1523–1525

    Article  PubMed  CAS  Google Scholar 

  • Sadler JE (1998) Biochemistry and genetics of von Willebrand factor. Annu Rev Biochem 67:395–424

    Article  PubMed  CAS  Google Scholar 

  • Sakariassen KS, Cattaneo M, vd Berg A et al (1984) DDAVP enhances platelet adherence and platelet aggregate growth on human artery subendothelium. Blood 64:229–236

    PubMed  CAS  Google Scholar 

  • Salzman EW, Weinstein MJ, Weintraub RM et al (1986) Treatment with desmopressin acetate to reduce blood-loss after cardiac-surgery - a double-blind randomized trial. N Engl J Med 314:1402–1406

    Article  PubMed  CAS  Google Scholar 

  • Schulman S (2012) Pharmacologic tools to reduce bleeding in surgery. Hematology Am Soc Hematol Educ Program 2012:517–521

    PubMed  Google Scholar 

  • Seligsohn U (2012) Treatment of inherited platelet disorders. Haemophilia 18:156

    Article  Google Scholar 

  • Shakur H, Roberts I, Bautista R et al (2010) 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 376:23–32

    Article  PubMed  CAS  Google Scholar 

  • Sucker C, Michiels JJ, Zotz RB (2009) Causes, etiology and diagnosis of acquired von Willebrand disease: a prospective diagnostic workup to establish the most effective therapeutic strategies. Acta Haematol 121:177–182

    Article  PubMed  CAS  Google Scholar 

  • Tiede A, Rand JH, Budde U et al (2011) How I treat the acquired von Willebrand syndrome. Blood 117:6777–6785

    Article  PubMed  CAS  Google Scholar 

  • Trigg DE, Stergiotou I, Peitsidis P et al (2012) A systematic review: the use of desmopressin for treatment and prophylaxis of bleeding disorders in pregnancy. Haemophilia 18:25–33

    Article  PubMed  CAS  Google Scholar 

  • Vavra I, Machova A, Holeced V et al (1968) Effect of a synthetic analogue of vasopressin in animals and in patients with diabetes insipidus. Lancet 1:948–952

    Article  PubMed  CAS  Google Scholar 

  • Vicente V, Estelles A, Laso J et al (1993) Repeated infusions of Ddavp induce low response of Fviii and Vwf but not of plasminogen activators. Thromb Res 70:117–122

    Article  PubMed  CAS  Google Scholar 

  • Villar A, Jimenez-Yuste V, Quintana M et al (2002) The use of haemostatic drugs in haemophilia: desmopressin and antifibrinolytic agents. Haemophilia 8:189–193

    Article  PubMed  CAS  Google Scholar 

  • Watts CD, Pagnano MW (2012) Minimising blood loss and transfusion in contemporary hip and knee arthroplasty. J Bone Joint Surg Br 94B:8–10

    Article  Google Scholar 

  • Weiss HJ, Sussman II, Hoyer LW (1977) Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand’s disease. J Clin Invest 60:390–404

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Wise RJ, Dorner AJ, Krane M et al (1991) The role of von Willebrand factor multimers and propeptide cleavage in binding and stabilization of factor VIII. J Biol Chem 266:21948–21955

    PubMed  CAS  Google Scholar 

  • Wong AYC, Irwin MG, Hui TWC et al (2003) Desmopressin does not decrease blood loss and transfusion requirements in patients undergoing hepatectomy. Can J Anaesth 50:14–20

    Article  PubMed  Google Scholar 

  • Zotz RB (2009) A Stratified Metaanalysis of Desmopressin (DDAVP) for Minimising Perioperative Allogeneic Blood Transfusion. Blood (ASH Annual Meeting Abstracts), 2009;114:1306

    Google Scholar 

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Authors and Affiliations

  1. Centrum für Blutgerinnungsstörungen und Transfusionsmedizin (CBT), Immermannstrasse 65 a, Düsseldorf, 40210, Germany

    Rainer B. Zotz & Nikola Zotz

  2. LaboMed Gerinnungszentrum Berlin, Tauentzienstrasse 7 b/c, Berlin, 10789, Germany

    Christoph Sucker

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  1. Rainer B. Zotz
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  2. Nikola Zotz
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Correspondence to Rainer B. Zotz .

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  1. Department of Anesthesiology, University Hospital of Lausanne, Lausanne, Switzerland

    Carlo Enrique Marcucci

  2. Department of Anesthesiology, University Hospital of Lausanne, Lausanne, Switzerland

    Patrick Schoettker

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Zotz, R.B., Zotz, N., Sucker, C. (2015). Procoagulant Drugs. In: Marcucci, C., Schoettker, P. (eds) Perioperative Hemostasis. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55004-1_12

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