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European Journal of Trauma and Emergency Surgery
Published in: European Journal of Trauma and Emergency Surgery 6/2014

01-12-2014 | Review Article

The epidemic of pre-injury oral antiplatelet and anticoagulant use

Authors: A. E. Berndtson, R. Coimbra

Published in: European Journal of Trauma and Emergency Surgery | Issue 6/2014

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Abstract

Background

As the population ages, an increasing number of trauma patients are taking antiplatelet and anticoagulant medications (ACAP) prior to their injuries. These medications increase their risk of hemorrhagic complications, particularly intracerebral hemorrhage. Clopidogrel and warfarin are common and their mechanisms well understood, but optimal reversal methods continue to evolve. The novel direct thrombin and factor Xa inhibitors are less well described and do not have existing antidotes.

Methods

This article reviews the relevant literature on traumatic outcomes with use of ACAP medications, as well as data on ideal reversal strategies. Suggested algorithms are introduced, and future research directions discussed.

Results

Although they are beneficial in preventing clot formation, once bleeding occurs ACAP medications contribute to increased morbidity and mortality, particularly in geriatric patient populations. The efficacy of clopidogrel reversal with platelet transfusions and DDAVP remains unclear. Warfarin use is best treated with the algorithm-driven use of plasma, vitamin K, prothrombin complex concentrates (PCCs) and possibly recombinant factor VIIa depending upon specific patient and injury factors. Optimal treatment for direct thrombin and factor Xa inhibitors has yet to be developed, but PCCs are promising for rivaroxaban and apixaban while dabigatran is best treated with medication cessation and the possible addition of activated PCCs or hemodialysis.

Conclusion

New developments in reversal of the ACAP medications are promising, particularly PCCs for warfarin and the factor Xa inhibitors. Function assays and clear antidotes are needed for the thrombin and Xa inhibitors. Research on outcomes and appropriate treatments is actively ongoing.
Literature
1.
2.
Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med. 2007;146:857–67.PubMed
3.
4.
Bauer KA. Dabigatran, ROCKET atrial fibrillation, and beyond: basic science, mechanisms of agents, monitoring, and reversal. Stroke. 2013;44:S38–40.PubMed
5.
Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D’Angelo A, et al. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy. Lancet. 1996;348:423–8.PubMed
6.
Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51.PubMed
7.
Xu YHA, Simpson CS, Dowlatshahi D, Johnson AP. Prescribing patterns of novel oral anticoagulants following regulatory approval for atrial fibrillation in Ontario, Canada: a population-based descriptive analysis. CMAJ Open. 2013;1:E115–9.PubMedCentralPubMed
8.
Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883–91.PubMed
9.
Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.PubMed
10.
11.
12.
Ott MM, Eriksson E, Vanderkolk W, Christianson D, Davis A, Scholten D. Antiplatelet and anticoagulation therapies do not increase mortality in the absence of traumatic brain injury. J Trauma. 2010;68:560–3.PubMed
13.
Bonville DJ, Ata A, Jahraus CB, Arnold-Lloyd T, Salem L, Rosati C, et al. Impact of preinjury warfarin and antiplatelet agents on outcomes of trauma patients. Surgery. 2011;150:861–8.PubMed
14.
Moore MM, Pasquale MD, Badellino M. Impact of age and anticoagulation: need for neurosurgical intervention in trauma patients with mild traumatic brain injury. J Trauma Acute Care Surg. 2012;73:126–30.PubMed
15.
Garra G, Nashed AH, Capobianco L. Minor head trauma in anticoagulated patients. Acad Emerg Med. 1999;6:121–4.PubMed
16.
Gittleman AM, Ortiz AO, Keating DP, Katz DS. Indications for CT in patients receiving anticoagulation after head trauma. AJNR Am J Neuroradiol. 2005;26:603–6.PubMed
17.
Kaen A, Jimenez-Roldan L, Arrese I, Delgado MA, Lopez PG, Alday R, et al. The value of sequential computed tomography scanning in anticoagulated patients suffering from minor head injury. J Trauma. 2010;68:895–8.PubMed
18.
Levine M, Wyler B, Lovecchio F, Roque P, Raja AS. Risk of intracranial injury after minor head trauma in patients with pre-injury use of clopidogrel. Am J Emerg Med. 2014;32:71–4.PubMed
19.
Brewer ES, Reznikov B, Liberman RF, Baker RA, Rosenblatt MS, David CA, et al. Incidence and predictors of intracranial hemorrhage after minor head trauma in patients taking anticoagulant and antiplatelet medication. J Trauma. 2011;70:E1–5.PubMed
20.
Nishijima DK, Offerman SR, Ballard DW, Vinson DR, Chettipally UK, Rauchwerger AS, et al. Risk of traumatic intracranial hemorrhage in patients with head injury and preinjury warfarin or clopidogrel use. Acad Emerg Med. 2013;20:140–5.PubMedCentralPubMed
21.
Nishijima DK, Offerman SR, Ballard DW, Vinson DR, Chettipally UK, Rauchwerger AS, et al. Immediate and delayed traumatic intracranial hemorrhage in patients with head trauma and preinjury warfarin or clopidogrel use. Ann Emerg Med. 2012;59(460–8):e1–7.PubMed
22.
Peck KA, Sise CB, Shackford SR, Sise MJ, Calvo RY, Sack DI, et al. Delayed intracranial hemorrhage after blunt trauma: are patients on preinjury anticoagulants and prescription antiplatelet agents at risk? J Trauma. 2011;71:1600–4.PubMed
23.
Menditto VG, Lucci M, Polonara S, Pomponio G, Gabrielli A. Management of minor head injury in patients receiving oral anticoagulant therapy: a prospective study of a 24-hour observation protocol. Ann Emerg Med. 2012;59:451–5.PubMed
24.
Choudhry OJ, Prestigiacomo CJ, Gala N, Slasky S, Sifri ZC. Delayed neurological deterioration after mild head injury: cause, temporal course, and outcomes. Neurosurgery. 2013;73:753–60 (discussion 60).PubMed
25.
Cohen DB, Rinker C, Wilberger JE. Traumatic brain injury in anticoagulated patients. J Trauma. 2006;60:553–7.PubMed
26.
Patel NY, Hoyt DB, Nakaji P, Marshall L, Holbrook T, Coimbra R, et al. Traumatic brain injury: patterns of failure of nonoperative management. J Trauma. 2000;48:367–74 (discussion 74–75).PubMed
27.
Washington CW, Grubb RL Jr. Are routine repeat imaging and intensive care unit admission necessary in mild traumatic brain injury? J Neurosurg. 2012;116:549–57.PubMed
28.
Sifri ZC, Homnick AT, Vaynman A, Lavery R, Liao W, Mohr A, et al. A prospective evaluation of the value of repeat cranial computed tomography in patients with minimal head injury and an intracranial bleed. J Trauma. 2006;61:862–7.PubMed
29.
Fabbri A, Servadei F, Marchesini G, Bronzoni C, Montesi D, Arietta L. Antiplatelet therapy and the outcome of subjects with intracranial injury: the Italian SIMEU study. Crit Care. 2013;17:R53.PubMedCentralPubMed
30.
Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004;63:1059–64.PubMed
31.
Wang MC, Linnau KF, Tirschwell DL, Hollingworth W. Utility of repeat head computed tomography after blunt head trauma: a systematic review. J Trauma. 2006;61:226–33.PubMed
32.
Karni A, Holtzman R, Bass T, Zorman G, Carter L, Rodriguez L, et al. Traumatic head injury in the anticoagulated elderly patient: a lethal combination. Am Surg. 2001;67:1098–100.PubMed
33.
Mina AA, Bair HA, Howells GA, Bendick PJ. Complications of preinjury warfarin use in the trauma patient. J Trauma. 2003;54:842–7.PubMed
34.
Lavoie A, Ratte S, Clas D, Demers J, Moore L, Martin M, et al. Preinjury warfarin use among elderly patients with closed head injuries in a trauma center. J Trauma. 2004;56:802–7.PubMed
35.
Ohm C, Mina A, Howells G, Bair H, Bendick P. Effects of antiplatelet agents on outcomes for elderly patients with traumatic intracranial hemorrhage. J Trauma. 2005;58:518–22.PubMed
36.
Franko J, Kish KJ, O’Connell BG, Subramanian S, Yuschak JV. Advanced age and preinjury warfarin anticoagulation increase the risk of mortality after head trauma. J Trauma. 2006;61:107–10.PubMed
37.
Pieracci FM, Eachempati SR, Shou J, Hydo LJ, Barie PS. Degree of anticoagulation, but not warfarin use itself, predicts adverse outcomes after traumatic brain injury in elderly trauma patients. J Trauma. 2007;63:525–30.PubMed
38.
Mina AA, Knipfer JF, Park DY, Bair HA, Howells GA, Bendick PJ. Intracranial complications of preinjury anticoagulation in trauma patients with head injury. J Trauma. 2002;53:668–72.PubMed
39.
Jones K, Sharp C, Mangram AJ, Dunn EL. The effects of preinjury clopidogrel use on older trauma patients with head injuries. Am J Surg. 2006;192:743–5.PubMed
40.
Ivascu FA, Howells GA, Junn FS, Bair HA, Bendick PJ, Janczyk RJ. Rapid warfarin reversal in anticoagulated patients with traumatic intracranial hemorrhage reduces hemorrhage progression and mortality. J Trauma. 2005;59:1131–7 (discussion 7–9).PubMed
41.
Nishijima DK, Shahlaie K, Sarkar K, Rudisill N, Holmes JF. Risk of unfavorable long-term outcome in older adults with traumatic intracranial hemorrhage and anticoagulant or antiplatelet use. Am J Emerg Med. 2013;31:1244–7.PubMedCentralPubMed
42.
Wong DK, Lurie F, Wong LL. The effects of clopidogrel on elderly traumatic brain injured patients. J Trauma. 2008;65:1303–8.PubMed
43.
Livingston DH, Lavery RF, Mosenthal AC, Knudson MM, Lee S, Morabito D, et al. Recovery at one year following isolated traumatic brain injury: a Western Trauma Association prospective multicenter trial. J Trauma. 2005;59:1298–304 (discussion 304).PubMed
44.
Cotton BA, McCarthy JJ, Holcomb JB. Acutely injured patients on dabigatran. N Engl J Med. 2011;365:2039–40.PubMed
45.
Garber ST, Sivakumar W, Schmidt RH. Neurosurgical complications of direct thrombin inhibitors–catastrophic hemorrhage after mild traumatic brain injury in a patient receiving dabigatran. J Neurosurg. 2012;116:1093–6.PubMed
46.
Wassef SN, Abel TJ, Grossbach A, Viljoen SV, Jackson AW, Howard MA 3rd, et al. Traumatic intracranial hemorrhage in patients taking dabigatran: report of 3 cases and review of the literature. Neurosurgery. 2013;73:E368–73 (discussion E73–E74).PubMed
47.
Inui TS, Parina R, Chang DC, Coimbra R. Mortality after ground-level fall in the elderly patient taking oral anticoagulation for atrial fibrillation/flutter: a long-term analysis of risk versus benefit. J Trauma Acute Care Surg. 2014;76:642–50.PubMed
48.
Coimbra R, Hoyt DB, Anjaria DJ, Potenza BM, Fortlage D, Hollingsworth-Fridlund P. Reversal of anticoagulation in trauma: a North-American survey on clinical practices among trauma surgeons. J Trauma. 2005;59:375–82.PubMed
49.
50.
51.
52.
53.
54.
55.
Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354–62.PubMed
56.
Bansal V, Fortlage D, Lee J, Doucet J, Potenza B, Coimbra R. A new clopidogrel (Plavix) point-of-care assay: rapid determination of antiplatelet activity in trauma patients. J Trauma. 2011;70:65–9 (discussion 9–70).PubMed
57.
Short S, Kram B, Taylor S, Cheng J, Ali K, Vasquez D. Effect of platelet inhibition on bleeding complications in trauma patients on preinjury clopidogrel. J Trauma Acute Care Surg. 2013;74:1419–24.PubMed
58.
Nishijima DK, Zehtabchi S, Berrong J, Legome E. Utility of platelet transfusion in adult patients with traumatic intracranial hemorrhage and preinjury antiplatelet use: a systematic review. J Trauma Acute Care Surg. 2012;72:1658–63.PubMed
59.
McMillian WD, Rogers FB. Management of prehospital antiplatelet and anticoagulant therapy in traumatic head injury: a review. J Trauma. 2009;66:942–50.PubMed
60.
Downey DM, Monson B, Butler KL, Fortuna GR Jr, Saxe JM, Dolan JP, et al. Does platelet administration affect mortality in elderly head-injured patients taking antiplatelet medications? Am Surg. 2009;75:1100–3.PubMed
61.
Taylor G, Osinski D, Thevenin A, Devys JM. Is platelet transfusion efficient to restore platelet reactivity in patients who are responders to aspirin and/or clopidogrel before emergency surgery? J Trauma Acute Care Surg. 2013;74:1367–9.PubMed
62.
Levine M, Swenson S, McCormick T, Henderson SO, Thomas SH, Markland FS. Reversal of thienopyridine-induced platelet dysfunction following desmopressin administration. J Med Toxicol. 2013;9:139–43.PubMedCentralPubMed
63.
Ranucci M, Nano G, Pazzaglia A, Bianchi P, Casana R, Tealdi DG. Platelet mapping and desmopressin reversal of platelet inhibition during emergency carotid endarterectomy. J Cardiothorac Vasc Anesth. 2007;21:851–4.PubMed
64.
Leithauser B, Zielske D, Seyfert UT, Jung F. Effects of desmopressin on platelet membrane glycoproteins and platelet aggregation in volunteers on clopidogrel. Clin Hemorheol Microcirc. 2008;39:293–302.PubMed
65.
Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S–98S.PubMed
66.
Lubetsky A, Yonath H, Olchovsky D, Loebstein R, Halkin H, Ezra D. Comparison of oral vs intravenous phytonadione (vitamin K1) in patients with excessive anticoagulation: a prospective randomized controlled study. Arch Intern Med. 2003;163:2469–73.PubMed
67.
Stein DM, Dutton RP, Hess JR, Scalea TM. Low-dose recombinant factor VIIa for trauma patients with coagulopathy. Injury. 2008;39:1054–61.PubMed
68.
Harrison TD, Laskosky J, Jazaeri O, Pasquale MD, Cipolle M. “Low-dose” recombinant activated factor VII results in less blood and blood product use in traumatic hemorrhage. J Trauma. 2005;59:150–4.PubMed
69.
Narayan RK, Maas AI, Marshall LF, Servadei F, Skolnick BE, Tillinger MN. Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial. Neurosurgery. 2008;62:776–86 (discussion 86–88).PubMed
70.
Brody DL, Aiyagari V, Shackleford AM, Diringer MN. Use of recombinant factor VIIa in patients with warfarin-associated intracranial hemorrhage. Neurocrit Care. 2005;2:263–7.PubMedCentralPubMed
71.
Ilyas C, Beyer GM, Dutton RP, Scalea TM, Hess JR. Recombinant factor VIIa for warfarin-associated intracranial bleeding. J Clin Anesth. 2008;20:276–9.PubMed
72.
Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, et al. Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med. 2008;358:2127–37.PubMed
73.
Thomas GO, Dutton RP, Hemlock B, Stein DM, Hyder M, Shere-Wolfe R, et al. Thromboembolic complications associated with factor VIIa administration. J Trauma. 2007;62:564–9.PubMed
74.
Levi M, Peters M, Buller HR. Efficacy and safety of recombinant factor VIIa for treatment of severe bleeding: a systematic review. Crit Care Med. 2005;33:883–90.PubMed
75.
Taketomi T, Szlam F, Levy JH, Tanaka KA. Warfarin reversal with prothrombin complex concentrate confers better antifibrinolytic activity compared with recombinant activated factor VII. Blood Coagul Fibrinolysis. 2008;19:106–8.PubMed
76.
Stein DM, Dutton RP, Kramer ME, Scalea TM. Reversal of coagulopathy in critically ill patients with traumatic brain injury: recombinant factor VIIa is more cost-effective than plasma. J Trauma. 2009;66:63–72 (discussion 3–5).PubMed
77.
Schulman S, Bijsterveld NR. Anticoagulants and their reversal. Transfus Med Rev. 2007;21:37–48.PubMed
78.
Switzer JA, Rocker J, Mohorn P, Waller JL, Hughes D, Bruno A, et al. Clinical experience with three-factor prothrombin complex concentrate to reverse warfarin anticoagulation in intracranial hemorrhage. Stroke. 2012;43:2500–2.PubMed
79.
Holland L, Warkentin TE, Refaai M, Crowther MA, Johnston MA, Sarode R. Suboptimal effect of a three-factor prothrombin complex concentrate (Profilnine-SD) in correcting supratherapeutic international normalized ratio due to warfarin overdose. Transfusion. 2009;49:1171–7.PubMed
80.
Sarode R, Matevosyan K, Bhagat R, Rutherford C, Madden C, Beshay JE. Rapid warfarin reversal: a 3-factor prothrombin complex concentrate and recombinant factor VIIa cocktail for intracerebral hemorrhage. J Neurosurg. 2012;116:491–7.PubMed
81.
Baggs JH, Patanwala AE, Williams EM, Erstad BL. Dosing of 3-factor prothrombin complex concentrate for international normalized ratio reversal. Ann Pharmacother. 2012;46:51–6.PubMed
82.
Vigue B, Ract C, Tremey B, Engrand N, Leblanc PE, Decaux A, et al. Ultra-rapid management of oral anticoagulant therapy-related surgical intracranial hemorrhage. Intensive Care Med. 2007;33:721–5.PubMed
83.
Evans G, Luddington R, Baglin T. Beriplex P/N reverses severe warfarin-induced over anticoagulation immediately and completely in patients presenting with major bleeding. Br J Haematol. 2001;115:998–1001.PubMed
84.
Wong Y. Use of prothrombin complex concentrate for vitamin K antagonist reversal before surgical treatment of intracranial hemorrhage. Clin Med Insights Case Rep. 2011;4:1–6.PubMedCentralPubMed
85.
Pabinger-Fasching I. Warfarin-reversal: results of a phase III study with pasteurised, nanofiltrated prothrombin complex concentrate. Thromb Res. 2008;122(Suppl 2):S19–22.PubMed
86.
Ostermann H, Haertel S, Knaub S, Kalina U, Jung K, Pabinger I. Pharmacokinetics of Beriplex P/N prothrombin complex concentrate in healthy volunteers. Thromb Haemost. 2007;98:790–7.PubMed
87.
Song MM, Warne CP, Crowther MA. Prothrombin complex concentrate (PCC, Octaplex) in patients requiring immediate reversal of vitamin K antagonist anticoagulation. Thromb Res. 2012;129:526–9.PubMed
88.
Gatt A, Riddell A, van Veen JJ, Kitchen S, Tuddenham EG, Makris M. Optimizing warfarin reversal—an ex vivo study. J Thromb Haemost. 2009;7:1123–7.PubMed
89.
Pabinger I, Brenner B, Kalina U, Knaub S, Nagy A, Ostermann H. Prothrombin complex concentrate (Beriplex P/N) for emergency anticoagulation reversal: a prospective multinational clinical trial. J Thromb Haemost. 2008;6:622–31.PubMed
90.
Bhardwaj M, Bunsell R. Beriplex P/N: an alternative to fresh frozen plasma in severe haemorrhage. Anaesthesia. 2007;62:832–4.PubMed
91.
Schick KS, Fertmann JM, Jauch KW, Hoffmann JN. Prothrombin complex concentrate in surgical patients: retrospective evaluation of vitamin K antagonist reversal and treatment of severe bleeding. Crit Care. 2009;13:R191.PubMedCentralPubMed
92.
Cabral KP, Fraser GL, Duprey J, Gibbons BA, Hayes T, Florman JE, et al. Prothrombin complex concentrates to reverse warfarin-induced coagulopathy in patients with intracranial bleeding. Clin Neurol Neurosurg. 2013;115:770–4.PubMed
93.
Scott LJ. Prothrombin complex concentrate (Beriplex P/N). Drugs. 2009;69:1977–84.PubMed
94.
Dickneite G. Prothrombin complex concentrate versus recombinant factor VIIa for reversal of coumarin anticoagulation. Thromb Res. 2007;119:643–51.PubMed
95.
Sorensen B, Spahn DR, Innerhofer P, Spannagl M, Rossaint R. Clinical review: prothrombin complex concentrates—evaluation of safety and thrombogenicity. Crit Care. 2011;15:201.PubMedCentralPubMed
96.
Makris M, Watson HG. The management of coumarin-induced over-anticoagulation Annotation. Br J Haematol. 2001;114:271–80.PubMed
97.
Wojcik C, Schymik ML, Cure EG. Activated prothrombin complex concentrate factor VIII inhibitor bypassing activity (FEIBA) for the reversal of warfarin-induced coagulopathy. Int J Emerg Med. 2009;2:217–25.PubMedCentralPubMed
98.
Stangier J, Clemens A. Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor. Clin Appl Thromb Hemost. 2009;15(Suppl 1):9S–16S.PubMed
99.
Stangier J, Rathgen K, Stahle H, Gansser D, Roth W. The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects. Br J Clin Pharmacol. 2007;64:292–303.PubMedCentralPubMed
100.
Stangier J, Rathgen K, Stahle H, Mazur D. Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet. 2010;49:259–68.PubMed
101.
van Ryn J SP, Kink-Eiband M, Gansser D, Clemens A. Adsorption of dabigatran etexilate in water or dabigatran in pooled human plasma by activated charcoal in vitro. In: American Society of Hematology Annual Meeting; 05 Dec 2009.
102.
Eerenberg ES, Kamphuisen PW, Sijpkens MK, Meijers JC, Buller HR, Levi M. Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects. Circulation. 2011;124:1573–9.PubMed
103.
Majeed A, Schulman S. Bleeding and antidotes in new oral anticoagulants. Best Pract Res Clin Haematol. 2013;26:191–202.PubMed
104.
Lillo-Le Louet A, Wolf M, Soufir L, Galbois A, Dumenil AS, Offenstadt G, et al. Life-threatening bleeding in four patients with an unusual excessive response to dabigatran: implications for emergency surgery and resuscitation. Thromb Haemost. 2012;108:583–5.PubMed
105.
Wychowski MK, Kouides PA. Dabigatran-induced gastrointestinal bleeding in an elderly patient with moderate renal impairment. Ann Pharmacother. 2012;46:e10.PubMed
106.
Zhou W, Schwarting S, Illanes S, Liesz A, Middelhoff M, Zorn M, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with the direct thrombin inhibitor dabigatran. Stroke. 2011;42:3594–9.PubMed
107.
Marlu R, Hodaj E, Paris A, Albaladejo P, Cracowski JL, Pernod G. Effect of non-specific reversal agents on anticoagulant activity of dabigatran and rivaroxaban: a randomised crossover ex vivo study in healthy volunteers. Thromb Haemost. 2012;108:217–24.PubMed
108.
Dager WE, Gosselin RC, Roberts AJ. Reversing dabigatran in life-threatening bleeding occurring during cardiac ablation with factor eight inhibitor bypassing activity. Crit Care Med. 2013;41:e42–6.PubMed
109.
Ehrlich HJ, Henzl MJ, Gomperts ED. Safety of factor VIII inhibitor bypass activity (FEIBA): 10-year compilation of thrombotic adverse events. Haemophilia. 2002;8:83–90.PubMed
110.
Truumees E, Gaudu T, Dieterichs C, Geck M, Stokes J. Epidural hematoma and intraoperative hemorrhage in a spine trauma patient on Pradaxa (dabigatran). Spine (Phila Pa 1976). 2012;37:E863–5.
111.
Warkentin TE, Margetts P, Connolly SJ, Lamy A, Ricci C, Eikelboom JW. Recombinant factor VIIa (rFVIIa) and hemodialysis to manage massive dabigatran-associated postcardiac surgery bleeding. Blood. 2012;119:2172–4.PubMed
112.
Wanek MR, Horn ET, Elapavaluru S, Baroody SC, Sokos G. Safe use of hemodialysis for dabigatran removal before cardiac surgery. Ann Pharmacother. 2012;46:e21.PubMed
113.
Mueck W, Schwers S, Stampfuss J. Rivaroxaban and other novel oral anticoagulants: pharmacokinetics in healthy subjects, specific patient populations and relevance of coagulation monitoring. Thromb J. 2013;11:10.PubMedCentralPubMed
114.
115.
Mueck W, Eriksson BI, Bauer KA, Borris L, Dahl OE, Fisher WD, et al. Population pharmacokinetics and pharmacodynamics of rivaroxaban—an oral, direct factor Xa inhibitor–in patients undergoing major orthopaedic surgery. Clin Pharmacokinet. 2008;47:203–16.PubMed
116.
Korber MK, Langer E, Ziemer S, Perzborn E, Gericke C, von Heymann C. Measurement and reversal of prophylactic and therapeutic peak levels of rivaroxaban: an in vitro study. Clin Appl Thromb Hemost. 2013 [Epub ahead of print].
117.
Escolar G, Fernandez-Gallego V, Arellano-Rodrigo E, Roquer J, Reverter JC, Sanz VV, et al. Reversal of apixaban induced alterations in hemostasis by different coagulation factor concentrates: significance of studies in vitro with circulating human blood. PLoS One. 2013;8:e78696.PubMedCentralPubMed
118.
Wong PC, Crain EJ, Xin B, Wexler RR, Lam PY, Pinto DJ, et al. Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Thromb Haemost. 2008;6:820–9.PubMed
119.
Samama MM, Contant G, Spiro TE, Perzborn E, Le Flem L, Guinet C, et al. Laboratory assessment of rivaroxaban: a review. Thromb J. 2013;11:11.PubMedCentralPubMed
120.
Perzborn E, Roehrig S, Straub A, Kubitza D, Mueck W, Laux V. Rivaroxaban: a new oral factor Xa inhibitor. Arterioscler Thromb Vasc Biol. 2010;30:376–81.PubMed
121.
Kubitza D, Becka M, Mueck W, Halabi A, Maatouk H, Klause N, et al. Effects of renal impairment on the pharmacokinetics, pharmacodynamics and safety of rivaroxaban, an oral, direct factor Xa inhibitor. Br J Clin Pharmacol. 2010;70:703–12.PubMedCentralPubMed
122.
Raghavan N, Frost CE, Yu Z, He K, Zhang H, Humphreys WG, et al. Apixaban metabolism and pharmacokinetics after oral administration to humans. Drug Metab Dispos. 2009;37:74–81.PubMed
123.
Perzborn E, Gruber A, Tinel H, Marzec UM, Buetehorn U, Buchmueller A, et al. Reversal of rivaroxaban anticoagulation by haemostatic agents in rats and primates. Thromb Haemost. 2013;110:162–72.PubMed
124.
Godier A, Miclot A, Le Bonniec B, Durand M, Fischer AM, Emmerich J, et al. Evaluation of prothrombin complex concentrate and recombinant activated factor VII to reverse rivaroxaban in a rabbit model. Anesthesiology. 2012;116:94–102.PubMed
125.
Wong PC, White A, Luettgen J. Inhibitory effect of apixaban compared with rivaroxaban and dabigatran on thrombin generation assay. Hosp Pract. 1995;2013(41):19–25.
126.
Zhou W, Zorn M, Nawroth P, Butehorn U, Perzborn E, Heitmeier S, et al. Hemostatic therapy in experimental intracerebral hemorrhage associated with rivaroxaban. Stroke. 2013;44:771–8.PubMed
127.
Martin AC, Le Bonniec B, Fischer AM, Marchand-Leroux C, Gaussem P, Samama CM, et al. Evaluation of recombinant activated factor VII, prothrombin complex concentrate, and fibrinogen concentrate to reverse apixaban in a rabbit model of bleeding and thrombosis. Int J Cardiol. 2013;168:4228–33.PubMed
128.
Lu G, DeGuzman FR, Hollenbach SJ, Karbarz MJ, Abe K, Lee G, et al. A specific antidote for reversal of anticoagulation by direct and indirect inhibitors of coagulation factor Xa. Nat Med. 2013;19:446–51.PubMed
129.
Millar CM, Lane DA. Blocking direct inhibitor bleeding. Blood. 2013;121:3543–4.PubMed
Metadata
Title
The epidemic of pre-injury oral antiplatelet and anticoagulant use
Authors
A. E. Berndtson
R. Coimbra
Publication date
01-12-2014
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Trauma and Emergency Surgery / Issue 6/2014
Print ISSN: 1863-9933
Electronic ISSN: 1863-9941
DOI
https://doi.org/10.1007/s00068-014-0404-9

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