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19 Commonly Prescribed Medications that Aect Clotting: AComprehensive Overview
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Table 19.1 Common antiplatelets and their actions
Drug Mechanism of action Interactions
Aspirin Inhibits COX and the
formation of
thromboxane A2
Clopidogrel Irreversibly inhibits
the ADP P2Y12
receptor
Ticagrelor Reversibly inhibits
P2Y12 receptor
Cilostazol Blocks
phosphodiesterase
Dipyridamole Blocks adenosine
receptor
NSAIDs (except diclofenac,
ketorolac), alcohol,
cigarettes, tamoxifen,
ACE-inhibitors, diuretics,
serotonergic agents (SSRIs)
Omeprazole, esomeprazole,
nicotine, grapefruit juice,
ketoconazole, warfarin,
serotonergic agents (SSRIs)
Statins, serotonergic agents
(SSRIs)
Ketoconazole, itraconazole,
uconazole, miconazole,
uvoxamine, uoxetine,
nefazodone, sertraline,
macrolides, serotonergic
agents (SSRIs), lovastatin
Adenosine, LMWH,
warfarin, clopidogrel,
serotonergic agents (SSRIs)
with cardiac valve replacement and for prevention of secondary stroke [132]. Dipyridamole has multiple drug interactions. Dipyridamole potentiates the effects of adenosine
likely because the inhibition leads to increased intravascular
adenosine concentration and could cause symptomatic bradycardia [157]. It may also increase bleeding risk with low
molecular weight heparin, ticagrelor, and warfarin.
Metformin has been shown to decrease thrombosis by
inhibiting platelet activation through a novel pathway involving mitochondrial DNA release [158]. Fish oil has some evidence of antiplatelet effect and may potentiate the effect of
antiplatelet drugs [159].
Platelet aggregation and coagulation is a complex phenomenon with multiple pharmacologic targets for antithrombus therapy. Despite the complexity, two main drug
classes make up the bulk of antiplatelet therapy, aspirin, and
P2Y12 inhibitors. These drugs also interact with a variety of
other drugs and commonly ingested compounds. Common
antiplatelet drugs, their mechanisms of action, and main
drug interactions are summarized in Table19.1.
Summary andFuture Directions
Anticoagulant, antiplatelet, and antibrinolytic drugs are
some of the most commonly prescribed drugs in the world,
and their concurrent use with other popular drugs may cause
effects that are undesirable. The list of indications for anticoagulant therapy is extensive and warranted for those with
concerns for clotting, but the interactions of these drugs with
other prescription pharmaceuticals or over-the-counter supplements may be associated with an increased risk of bleeding or clotting. Recent studies have begun to uncover
drug-drug interactions with some of the most commonly prescribed medications, such as antidepressants that have serotonin reuptake inhibition as their main mechanism of action,
being associated with an increased risk of bleeding when
taken with aspirin or other NSAIDs [
160]. The current CDC
recommends that all adults 50–69 years old with a ≥10%
risk of cardiovascular disease take a low-dose aspirin daily to
prevent cardiovascular disease and colorectal cancer [161].
In recent years, it has been reported that one in eight
Americans have taken antidepressants within the last month,
and that number has continued to increase consistently since
the 1990s [162]. Ideally, every patient would understand
each medication they are taking, the reason why they are prescribed the medication, and would have informed their primary care physician of every medication and supplement
they are currently taking to decrease drug-drug interactions.
Asking the general population to fully understand the complexity of their medications and disease processes is not feasible, but continually exploring the interactions of popular
medications is of the utmost importance to progress the eld
of medicine and decrease the number of complications that
patients experience.
New commonly used anticoagulants such as rivaroxaban,
dabigatran, apixaban, warfarin, and heparin are a mainstay
treatment for a plethora of afictions, and it is a relatively
common occurrence for these medications to be taken alongside other popular medications. Antidepressants, antiplatelet,
antibiotics, and herbal supplements are very common among
the general population, and these drugs can interact with
anticoagulants to make them function outside of their therapeutic range. Warfarin’s mechanism of action is unique in
that it works by competitively inhibiting the vitamin K epoxide reductase complex 1, an essential enzyme for activating
the vitamin K available in the body [
12]. The action of war-
farin is based on having a consistent amount of vitamin K in
the individual’s diet, and any change in diet or drugs that
alter the amount of available vitamin K changes the efcacy
of warfarin [12]. Bactrim, prednisone, and various SSRIs are
some of the most commonly prescribed medications that
alter the function of warfarin and make obtaining the therapeutic index more difcult.
Antibrinolytics are used to obtain optimal coagulation,
especially in the setting of surgical intervention.
Antibrinolytics inhibit the conversion of plasminogen to
plasmin, which removes excess brin to promote brin clot
forming and wound healing [163]. Aprotinin, tranexamic
acid, and epsilon-aminocaproic acid are a few examples of
antibrinolytics that are used to prevent blood loss in patients
having surgery [164]. These drugs are commonly used in
surgery and also in the setting of acute trauma with blood
loss [165]. Some drugs that affect antibrinolytic therapy are
anti-inhibitor coagulant complex, chlorpromazine, tretinoin,
nicotine, and alcohol. Nicotine and alcohol are some of the
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most commonly used substances in the world, and their
interactions with coagulation pharmaceuticals do not stop at
antibrinolytic therapy. Antiplatelet drugs are also affected
by an array of commonly prescribed medication.
Antiplatelet therapy works by inhibiting the ability of
platelets to participate in the clotting process and some of the
most common antiplatelet drugs being aspirin, clopidogrel,
and ticagrelor. Aspirin has long been recommended by the
CDC as prophylaxis to prevent pathologic thrombus formation and is commonly used on an “as-needed” basis for common aches and pains. Alcohol can cause anincreased risk of
GI bleeding in patients taking aspirin, while cigarette smoking can increase platelet aggregation and suppress the effects
of aspirin [136, 137]. Commonly prescribed hypertension
medications can have drug-drug interactions with antiplatelet drugs, which can hinder both drugs in acting therapeutically [139]. Proton pump inhibitors, metformin, and
antidepressants, (specically selective serotonin reuptake
inhibitors) may affect the efcacy of antiplatelet therapy
when these drugs are given together [158, 166]. With the
high rate of drug-drug interactions with antiplatelet, anticoagulant, and antibrinolytic therapies, progress is being
made to develop newer therapies that decrease the rate of
drug-drug interaction.
A 2017 study looked at the possibility of targeting mast
cell granular content as it plays a role in the formation of
deep venous thrombosis [167]. Current therapies available
for deep venous thrombosis target the coagulation cascade,
and complications can arise from altering this homeostasis
maintenanceprocess. Inammation has been proven to play
a role in triggering deep venous thrombosis, and mast cells
are known to play a major role in allergic inammation, a
risk factor for deep venous thrombosis [167]. Granules
within mast cells are lled with anticoagulants such as heparin and tissue-type plasminogen activator, endothelial activators, and many other enzymes that aid in the anticoagulation
process [167]. In this recent study, the authors looked at the
possibility of targeting mast cells to prevent deep vein thrombosis from occurring as an alternative means to conventional
therapy for patients with anticoagulation concerns. The study
looked at mast cell-decient mice versus wild-type mice,
and their results proved mast cells play a denite role in the
development of deep venous thrombosis [167]. The results
of their study showed that the two strains of mice that were
decient in mast cells were protected from deep vein thrombosis while maintaining their bleeding homeostasis under
the control of the coagulation cascade [167]. The mast cells’
effect wasproven to be a combination of release ofhistamineand mast cell granule constituents [167]. While more
research is needed to determine the efcacy that this study
would have in the human population, this study shows the
potential of a new target in human deep venous thrombosis
prevention [167]. See Fig.19.3.
A. Shelvan et al.
Fig. 19.3 Summary of anticoagulant, antibrinolytic, antiplatelet, and
emerging therapies
References
1. Dahlbäck B.Advances in understanding pathogenic mechanisms of
thrombophilic disorders. Blood. 2008;112(1):19–27.
2. Franchini M, Liumbruno GM, Bonfanti C, Lippi G.The evolution
of anticoagulant therapy. Blood Transfus. 2016;14(2):175–84.
3. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW,
Carson AP, Chamberlain AM, Chang AR, Cheng S, Das SR, Delling
FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Jordan LC,
Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT,
Lewis TT, Lic VS. Heart disease and stroke statistics- 2019 at-aglance heart disease, stroke and other cardiovascular diseases. Am
Hear Assoc. 2019;139:1–5.
4. Raskob GE, Silverstein R, Bratzler DW, Heit JA, White
RH.Surveillance for deep vein thrombosis and pulmonary embolism. Recommendations from a national workshop. Am J Prev
Med. 2010;38(4 SUPPL):S502–9.
5. Moser KM, LeMoine JR.Is embolic risk conditioned by location of
deep venous thrombosis? Ann Intern Med. 1981;94(4 pt 1):439–44.
6. Heit JA, Spencer FA, White RH. The epidemiology of venous
thromboembolism. J Thromb Thrombolysis. 2016;41(1):3–14.
7. Grosse SD, Nelson RE, Nyarko KA, Richardson LC, Raskob
GE. The economic burden of incident venous thromboembolism in the United States: a review of estimated attributable healthcare costs. Thromb Res. 2016;137:3–10. [Internet].
Available from: https://linkinghub.elsevier.com/retrieve/pii/
S0049384815302097
19 Commonly Prescribed Medications that Aect Clotting: AComprehensive Overview
https://t.me/medicina_free
187
8. Heit JA, Ashrani AA, Crusan DJ, McBane RD, Petterson TM,
Bailey KR.Reasons for the persistent incidence of venous thromboembolism. Thromb Haemost. 2017;117(2):390–400.
9. Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux
H, et al. Antithrombotic therapy for VTE disease. Chest.
2016;149(2):315–52.
10. Lauw MN, Büller HR. Treatment of deep vein thrombosis. In:
Current approaches to deep vein thrombosis. Future medicine,
2014. https://www.futuremedicine.comhttps://doi.org/10.2217/
fmeb2013.13.98
11. Gray E, Mulloy B, Barrowcliffe TW.Heparin and low-molecularweight heparin. Thromb Haemost. 2008;99(5):807–18.
12. DeLoughery TG.Warfarin. In: Hemostasis and thrombosis. 3rd ed.
Springer, Cham; 2015.
13. Schrör K. Aspirin and platelets: the antiplatelet action of aspirin and its role in thrombosis treatment and prophylaxis. Semin
Thromb Hemost. 1997;23(4):349–56.
14. Wakeeld TW, Obi AT, Henke PK.An aspirin a day to keep the
clots away. Circulation. 2014;130(13):1031–3.
15. Marik PE, Cavallazzi R. Extended anticoagulant and aspirin treatment for the secondary prevention of thromboembolic
disease: a systematic review and meta-analysis. PLoS One.
2015;10(11):1–12.
16. Mant J, Hobbs FR, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY,
et al. Warfarin versus aspirin for stroke prevention in an elderly
community population with atrial brillation (the Birmingham
atrial brillation treatment of the aged study, BAFTA): a randomised controlled trial. Lancet. 2007;370(9586):493–503.
17. Levy JH, Koster A, Quinones QJ, Milling TJ, Key
NS. Antibrinolytic therapy and perioperative considerations.
Anesthesiology. 2018;128(3):657–70.
18. Kattula S, Byrnes JR, Wolberg AS. Fibrinogen and brin in
hemostasis and thrombosis. Arterioscler Thromb Vasc Biol.
2017;37(3):e13–21.
19. Dhir A Antibrinolytics in cardiac surgery. Ann Card Anaesth.
2013;16(2):117–25.
20. Dunn CJ, Goa KL. Tranexamic acid: a review of its use in surgery and other indications. Drugs. 1999;57(6):1005–32. https://doi.
org/10.2165/00003495-199957060-00017.
21. Lumsden MA, Wedisinghe L. Tranexamic acid therapy
for heavy menstrual bleeding. Expert Opin Pharmacother.
2011;12(13):2089–95.
22. Vojacek J.Clinical monitoring of the antithrombotic treatment. Cor
Vasa. 2012;54(2):e97–103.
23. Weinberger J. Adverse effects and drug interactions of antithrombotic agents used in prevention of ischaemic stroke. Drugs.
2005;65(4):461–71.
24. Hicks RW, Wanzer LJ, Goeckner B. Perioperative pharmacology:
blood coagulation modiers. AORN J. 2011;93(6):726–36.
25. Moore N. Ibuprofen: a journey from prescription to over-thecounter use. J R Soc Med. 2007;100(Suppl 48):2–6.
26. Tsai HH, Lin HW, Lu YH, Chen YL, Mahady GB. A review
of potential harmful interactions between anticoagulant/antiplatelet agents and Chinese herbal medicines. PLoS One.
2013;8(5):e64255.
27. Serebruany VL. Selective serotonin reuptake inhibitors and
increased bleeding risk: are we missing something? Am J Med.
2006;119(2):113–6.
28. Schalekamp T, Klungel OH, Souverein PC, De Boer A.Increased
bleeding risk with concurrent use of selective serotonin reuptake
inhibitors and coumarins. Arch Intern Med. 2008;168(2):180–5.
29. Barnes GD, Ageno W, Ansell J, Kaatz S.Recommendation on the
nomenclature for oral anticoagulants: communication from the
SSC of the ISTH.J Thromb Haemost. 2015;13(6):1154–6.
30. Kane S.NOAC, DOAC, or TSOAC: what should we call novel oral
anticoagulants? Pharm Times. 2016.
.
https://doi.org/10.1007/978-3-319-09312-3.
31. Easton JD, Lopes RD, Bahit MC, Wojdyla DM, Granger CB,
Wallentin L, et al. Apixaban compared with warfarin in patients
with atrial brillation and previous stroke or transient ischaemic
attack: a subgroup analysis of the ARISTOTLE trial. Lancet
Neurol. 2012;11(6):503–11.
32. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD,
Halperin JL, etal. Edoxaban versus warfarin in patients with atrial
brillation. N Engl J Med. 2013;369(22):2093–104.
33. Patel MR, Mahaffey KW, Garg J, Pan G, Singer DE, Hacke W,
etal. Rivaroxaban versus warfarin in nonvalvular atrial brillation.
N Engl J Med. 2011;365(10):883–91.
34. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J,
Parekh A, etal. Dabigatran versus warfarin in patients with atrial
brillation. N Engl J Med. 2009;361(12):1139–51.
35. Joe D.More in-depth version of the coagulation cascade. Wikimedia
Commons. 2007; p. N/A
36. Bowen R.vitamin K.Vivo Pathophysiology. 2019. p. N/A.
37. Shearer MJ. vitamin K deciency bleeding (VKDB) in early
infancy. Blood Rev. 2009;23(2):49–59.
38. Controversies concerning vitamin K and the newborn. American
academy of pediatrics committee on fetus and newborn. Pediatrics.
2003;112(1 Pt 1):191–2.
39. Pirmohamed M.Warfarin: almost 60 years old and still causing
problems. Br J Clin Pharmacol. 2006;62(5):509–11.
40. Higdon J. vitamin K. Linus Pauling Institute. Miconutrient
Information Center. 2000. p. N/A.
41. Leung, LLK, Mannucci, PM, Tirnauer JS.Direct oral anticoagulants and parenteral direct thrombin inhibitors: dosing and adverse
effects- UpToDate. UpToDate. 2019. p. N/A.
42. Mueck W, Stampfuss J, Kubitza D, Becka M. Clinical pharmacokinetic and pharmacodynamic prole of rivaroxaban. Clin
Pharmacokinet. 2014;53(1):1–16.
43. Gerotziafas GT, Elalamy I, Depasse F, Perzborn E, Samama
MM.In vitro inhibition of thrombin generation, after tissue factor
pathway activation, by the oral, direct factor Xa inhibitor rivaroxaban. J Thromb Haemost. 2007;5(4):886–8.
44. Samama MM.The mechanism of action of rivaroxaban– an oral,
direct factor Xa inhibitor – compared with other anticoagulants.
Thromb Res. 2011;127(6):497–504.
45. Mueck W, Lensing AWA, Agnelli G, Decousus H, Prandoni P,
Misselwitz F. Rivaroxaban: population pharmacokinetic analyses
in patients treated for acute deep-vein thrombosis and exposure
simulations in patients with atrial brillation treated for stroke prevention. Clin Pharmacokinet. 2011;50(10):675–86.
46. Kearon C, Akl EA. Duration of anticoagulant therapy for
deep vein thrombosis and pulmonary embolism. Blood.
2014;123(12):1794–801.
47. DeLoughery EP, Shatzel JJ.A comparative analysis of the safety
prole of direct oral anticoagulants using the FDA adverse event
reporting system. Eur J Haematol. 2019 May;103(1):ejh.13240.
48. Shah R, Patel MR.Primary and key secondary results from the
ROCKET AF trial, and their implications on clinical practice. Ther
Adv Cardiovasc Dis. 2017;11(3):105–20.
49. Camm AJ, Bounameaux H.Edoxaban: a new oral direct factor xa
inhibitor. Drugs. 2011;71(12):1503–26.
50. Stacy ZA, Call WB, Hartmann AP, Peters GL, Richter
SK.Edoxaban: a comprehensive review of the pharmacology and
clinical data for the Management of Atrial Fibrillation and Venous
Thromboembolism. Cardiol Ther. 2016;5(1):1–18.
51. Zelniker TA, Ruff CT, Wiviott SD, Blanc J-J, Cappato R, Nordio F,
etal. Edoxaban in atrial brillation patients with established coronary artery disease: insights from ENGAGE AF-TIMI 48. Eur Hear
J Acute Cardiovasc care. 2019;8(2):176–85.
52. Connolly SJ, Eikelboom J, Dorian P, Hohnloser SH, Gretler
DD, Sinha U, et al. Betrixaban compared with warfarin in
patients with atrial fibrillation: results of a phase 2, ran-
188
https://t.me/medicina_free
A. Shelvan et al.
domized, dose-ranging study (Explore-Xa). Eur Heart J.
2013;34(20):1498–505.
53. Skelley JW, Thomason AR, Nolen JC, Candidate P. Betrixaban
(Bevyxxa): a direct-acting Oral anticoagulant factor Xa inhibitor. P
T. 2018;43(2):85–120.
54. Turpie AG, Gallus AS, Hoek JA.A synthetic pentasaccharide for
the prevention of deep-vein thrombosis after total hip replacement.
N Engl J Med. 2001;344(9):619–25.
55. Parody R, Oliver A, Souto JC, Fontcuberta J. Fondaparinux
(ARIXTRA) as an alternative anti-thrombotic prophylaxis when
there is hypersensitivity to low molecular weight and unfractionated heparins. Haematologica. 2003;88(11):ECR32.
56. Lagrange F, Vergnes C, Brun JL, Paolucci F, Nadal T, Leng JJ, etal.
Absence of placental transfer of pentasaccharide (Fondaparinux,
Arixtra) in the dually perfused human cotyledon invitro. Thromb
Haemost. 2002;87(5):831–5.
57. Halton JML, Lehr T, Cronin L, Lobmeyer MT, Haertter S,
Belletrutti M, et al. Safety, tolerability and clinical pharmacology of dabigatran etexilate in adolescents. Thromb Haemost.
2016;116(09):461–71.
58. Eriksson B, Dahl O, Huo M, Kurth A, Hantel S, Hermansson K,
et al. Oral dabigatran versus enoxaparin for thromboprophylaxis
after primary total hip arthroplasty (RE-NOVATE II). Thromb
Haemost. 2011;105(04):721–9.
59. Campbell HA, Link KP.Studies on the hemorrhagic sweet clover
disease. IV. The isolation and crystallization of the hemorrhagic
agent. J Biol Chem. 1941;138(1):21–33.
60. Chan H-T, So L-T, Li S-W, Siu C-W, Lau C-P, Tse H-F. Effect
of herbal consumption on time in therapeutic range of warfarin
therapy in patients with atrial brillation. J Cardiovasc Pharmacol.
2011;58(1):87–90.
61. Wells PS, Prins MH, Levitan B, Beyer-Westendorf J, Brighton TA,
Bounameaux H, etal. Long-term anticoagulation with rivaroxaban
for preventing recurrent VTE: a benet-risk analysis of EINSTEINextension. Chest. 2016;150(5):1059–68.
62. Lippi G, Favaloro E, Mattiuzzi C. Combined Administration
of Antibiotics and Direct Oral Anticoagulants: a renewed indication for laboratory monitoring? Semin Thromb Hemost.
2014;40(07):756–65.
63. Glueck CJ, Khalil Q, Winiarska M, Wang P. Interaction of duloxetine and warfarin causing severe elevation of international normalized ratio. JAMA. 2006;295(13):1517–8.
64. Gurbel PA, Fox KAA, Tantry US, Ten Cate H, Weitz JI.Combination
antiplatelet and Oral anticoagulant therapy in patients with coronary
and peripheral artery disease. Circulation. 2019;139(18):2170–85.
65. Turrentine MA, Braems G, Ramirez MM.Use of thrombolytics for
the treatment of thromboembolic disease during pregnancy. Obstet
Gynecol Surv. 1995;50(7):534–41.
66. Lexicomp. Heparin (unfractionated): Drug information. UpToDate.
2019. p. N/A.
67. Hull, RD, Garcia, DA, Burnett AE. Heparin and LMW heparin:
dosing and adverse effects. UpToDate. 2019. p. N/A.
68. Di Minno A, Frigerio B, Spadarella G, Ravani A, Sansaro D, Amato
M, etal. Old and new oral anticoagulants: food, herbal medicines
and drug interactions. Blood Rev. 2017;31:193–203.
69. Sayal KS, Duncan-McConnell DA, McConnell HW, Taylor
DM. Psychotropic interactions with warfarin. Acta Psychiatr
Scand. 2000;102(4):250–5.
70. Chew DP, Bhatt DL, Kimball W, Henry TD, Berger P, McCullough
PA, etal. Bivalirudin provides increasing benet with decreasing
renal function: a meta-analysis of randomized trials. Am J Cardiol.
2003;92(8):919–23.
71. Koster A, Faraoni D, Levy JH. Argatroban and Bivalirudin for
perioperative anticoagulation in cardiac surgery. Anesthesiology.
2018;128(2):390–400.
72. Di Nisio M, Middeldorp S, Büller HR. Direct thrombin inhibitors. N Engl J Med. 2005;353(10):1028–40. [Internet] [cited 2016
Dec 14]. Available from: http://www.nejm.org/doi/abs/10.1056/
NEJMra044440
73. Swan SK, Hursting MJ. The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender, and hepatic or renal
dysfunction. Pharmacotherapy. 2000;20(3):318–29.
74. Young G, Yonekawa KE, Nakagawa PA, Blain RC, Lovejoy AE,
Nugent DJ.Recombinant activated factor VII effectively reverses
the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin exvivo as measured using thromboelastography. Blood Coagul Fibrinolysis. 2007;18(6):547–53.
75. Carroll RC, Chavez JJ, Simmons JW, Snider CC, Wortham DC,
Bresee SJ, et al. Measurement of patients’ bivalirudin plasma
levels by a thrombelastograph ecarin clotting time assay: a comparison to a standard activated clotting time. Anesth Analg.
2006;102(5):1316–9.
76. Teles JS, Fukuda EY, Feder D. Warfarin: pharmacological prole
and drug interactions with antidepressants. Einstein (Sao Paulo).
2012;10(1):110–5.
77. Saleh MI, Alzubiedi S.Dosage individualization of warfarin using
articial neural networks. Mol Diagn Ther. 2014;18(3):371–9.
78. Hull R, D.Garcia, David A, Vazquez SR.Warfarin and other VKAs:
dosing and adverse effects. UpToDate. 2019. p. N/A.
79. So CH, Eckman MH.Combined aspirin and anticoagulant therapy in patients with atrial brillation. J Thromb Thrombolysis.
2017;43(1):7–17.
80. Roughead EE, Kalisch LM, Barratt JD, Gilbert AL.Prevalence of
potentially hazardous drug interactions amongst Australian veterans. Br J Clin Pharmacol. 2010;70(2):252–7.
81. Moore N, Pollack C, Butkerait P.Adverse drug reactions and drug–
drug interactions with over-the-counter NSAIDs. Ther Clin Risk
Manag. 2015;11:1061.
82. Holm J, Lindh JD, Andersson ML, Mannheimer B.The effect of
amiodarone on warfarin anticoagulation: a register-based nationwide cohort study involving the Swedish population. J Thromb
Haemost. 2017;15(3):446–53.
83. Sanoski CA, Bauman JL. Clinical observations with the amiodarone/warfarin interaction: dosing relationships with long-term therapy. Chest. 2002;121(1):19–23.
84. Carpenter M, Berry H, Pelletier AL. Clinically relevant
drug-drug interactions in primary care. Am Fam Physician.
2019;99(9):558–64.
85. Lam J, Gomes T, Juurlink DN, Mamdani MM, Pullenayegum
EM, Kearon C, et al. Hospitalization for hemorrhage among
warfarin recipients prescribed amiodarone. Am J Cardiol.
2013;112(3):420–3.
86. Miller KE. Amiodarone and warfarin interaction. Am Fam
Physician. 2002;65(8):1669–70.
87. Fischer HD, Juurlink DN, Mamdani MM, Kopp A, Laupacis
A.Hemorrhage during warfarin therapy associated with cotrimoxazole and other urinary tract anti-infective agents: a populationbased study. Arch Intern Med. 2010;170(7):617–21.
88. Lane MA, Devine ST, McDonald JR.High-risk antimicrobial prescriptions among ambulatory patients on warfarin. J Clin Pharm
Ther. 2012;37(2):157–60.
89. Ellis RJ, Mayo MS, Bodensteiner DM. Ciprooxacin-warfarin
coagulopathy: a case series. Am J Hematol. 2000;63(1):28–31.
90. Lane MA, Zeringue A, McDonald JR.Serious bleeding events due
to warfarin and antibiotic co-prescription in a cohort of veterans.
Am J Med. 2014;127(7):657–63. e2
91. Phillips S, Barr A, Wilson E, Rockall TASJF.Two cases of retroperitoneal haematoma caused by interaction between antibiotics
and warfarin. Emerg Med J. 2006;23(1):e08.
92. Al-Jundi W, Rubin N.Cardiac tamponade secondary to haemopericardium in a patient on warfarin. BMJ Case Rep. 2010;2010.
93. Poon M, Moffett BS, Yee DL.Warfarin-Rifampin drug interaction
in a Pediatric patient. J Pediatr Pharmacol Ther: JPPTOff J PPAG
United States. 2017;22:375–7.
19 Commonly Prescribed Medications that Aect Clotting: AComprehensive Overview
https://t.me/medicina_free
189
94. Holt RK, Anderson EA, Cantrell MA, Shaw RF, Egge JA.
Preemptive dose reduction of warfarin in patients initiating metronidazole. Drug Metabol Drug Interact. 2010;25(1–4):35–9.
95. Fischer HD.ACP journal Club: concomitant use of warfarin and
cotrimoxazole or ciprooxacin increased risk for admission for
upper GI hemorrhage. Ann Intern Med. 2010;153(6):JC3–13.
96. Hale SF, Lesar TS. Interaction of vitamin K antagonists and
trimethoprimDrug Metabol Drug Interact. 2014;29(1):53–60.
97. Ahmed A, Stephens JC, Kaus CA, Fay WP. Impact of preemptive warfarin dose reduction on anticoagulation after initiation
of trimethoprim-sulfamethoxazole or levooxacin. J Thromb
Thrombolysis. 2008;26(1):44–8.
98. Shaik AN, Bohnert T, Williams DA, Gan LL, LeDuc
BW.Mechanism of drug-drug interactions between warfarin and
statins. J Pharm Sci. 2016;105(6):1976–86.
99. Schelleman H, Bilker WB, Brensinger CM, Wan F, Yang Y-X,
Hennessy S.Fibrate/statin initiation in warfarin users and gastrointestinal bleeding risk. Am J Med. 2010;123(2):151–7.
100. Mackay JW, Fenech ME, Myint KS. Acute rhabdomyolysis
caused by combination therapy with atorvastatin and warfarin. Br
J Hosp Med (Lond). 2012;73(2):106–7.
101. Mannheimer B, Andersson ML, Jarnbert-Pettersson H, Lindh
JD. The effect of carbamazepine on warfarin anticoagulation: a
register-based nationwide cohort study involving the Swedish
population. J Thromb Haemost. 2016;14(4):765–71.
102. Clark NP, Hoang K, Delate T, Horn JR, Witt DM.Warfarin interaction with hepatic cytochrome P-450 enzyme-inducing anticonvulsants. Clin Appl Thromb Hemost. 2018;24(1):172–8.
103. Dong Y-H, Bykov K, Choudhry NK, Donneyong MM,
Huybrechts KF, Levin R, etal. Clinical outcomes of concomitant
use of warfarin and selective serotonin reuptake inhibitors. J Clin
Psychopharmacol. 2017;37(2):200–9.
104. Quinn GR, Singer DE, Chang Y, Go AS, Borowsky LH, Udaltsova
N, etal. Effect of selective serotonin reuptake inhibitors on bleeding risk in patients with atrial brillation taking warfarin. Am J
Cardiol. 2014;114(4):583–6.
105. Hackam DG, Mrkobrada M. Selective serotonin reuptake
inhibitors and brain hemorrhage: a meta-analysis. Neurology.
2012;79(18):1862–5.
106. Sansone RA, Sansone LA.Warfarin and antidepressants: happiness
without Hemorrhaging. Psychiatry (Edgmont). 2009;6(7):24–9.
107. Lexicomp® Drug Interactions- UpToDate. vitamin K Antagonists
/ Itraconazole. UpToDate. 2019.
108. Niwa T, Shiraga T, Takagi A.Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in
human liver microsomes. Biol Pharm Bull. 2005;28(9):1805–8.
109. Lexicomp® Drug Interactions- UpToDate. vitamin K Antagonists
/ Fluconazole. UpToDate. 2019.
110. Pendlimari R, Anaparthy R, Sugumar A. Drug interaction presenting as acute abdomen. World J Gastrointest Pharmacol Ther.
2010;1(1):40–2.
111. Hellfritzsch M, Pottegard A, Pedersen AJT, Burghle A, Mouaanaki
F, Hallas J, etal. Topical Antimycotics for Oral candidiasis in warfarin users. Basic Clin Pharmacol Toxicol. 2017;120(4):368–72.
112. Purkins L, Wood N, Kleinermans D, Nichols D. Voriconazole
potentiates warfarin-induced prothrombin time prolongation. Br
J Clin Pharmacol. 2003;56(Suppl 1):24–9.
113. Dekhuijzen PNR, Koopmans PP.Pharmacokinetic prole of zarlukast. Clin Pharmacokinet. 2002;41(2):105–14.
114. U.S.Food and Drug Administration. Accolate- zarlukast. 2009.
p.1–9.
115. Liedtke MD, Rathbun RC. Warfarin-antiretroviral interactions.
Ann Pharmacother. 2009;43(2):322–8.
116. Stading JA, Chock A, Faulkner MA, Skrabal MZ.Effects of prednisone on the international normalized ratio. Am J Health Syst
Pharm. 2006;63(23):2354–6.
sulfamethoxazole: ignore at your patient’s risk.
117. Dowd MB, Vavra KA, Witt DM, Delate T, Martinez K.Empiric
warfarin dose adjustment with prednisone therapy. A randomized,
controlled trial. J Thromb Thrombolysis. 2011;31(4):472–7.
118. Yıldırım F, Kara İ, Bilaloğlu B, Erbaş G, Türkoglu M, Aygencel
G. A rare complication with the concomitant use of warfarin
and nonsteroidal anti-inammatory drugs: Hemoperitoneum
and intramural small bowel hematoma. Iran J Med Sci.
2016;41(4):359–60.
119. Tsai H-H, Lin H-W, Simon Pickard A, Tsai H-Y, Mahady
GB.Evaluation of documented drug interactions and contraindications associated with herbs and dietary supplements: a systematic literature review. Int J Clin Pract. 2012;66(11):1056–78.
120. Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan
Y, Wang J-S, et al. Effect of St John’s Wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA.
2003;290(11):1500.
121. Greenblatt DJ, von Moltke LL. Interaction of warfarin with
drugs, natural substances, and foods. J Clin Pharmacol.
2005;45(2):127–32.
122. Chapin JC, Hajjar KA. Fibrinolysis and the control of blood
coagulation. Blood Rev. 2015;29(1):17–24. [Internet]. [cited
2019 Oct 24]. Available from: http://www.ncbi.nlm.nih.gov/
pubmed/25294122
123. Székely A, Lex DJ. Antibrinolytics. Hear lung Vessel.
2014;6(1):5–7. [Internet]. [cited 2019 Oct 24] Available from:
http://www.ncbi.nlm.nih.gov/pubmed/24800192
124. Fergusson DA, Hébert PC, Mazer CD, Fremes S, MacAdams
C, Murkin JM, et al. A comparison of aprotinin and lysine
analogues in high-risk cardiac surgery. N Engl J Med.
2008;358(22):2319–31.
125. Koster A, Faraoni D, Levy JH.Antibrinolytic therapy for cardiac
surgery: an update. Anesthesiology. 2015;123:214–21. Lippincott
Williams and Wilkins
126. Ng W, Jerath A, Wąsowicz M.Tranexamic acid: a clinical review.
Anaesthesiol Intensive Ther. 2015;47(4):339–50. [Internet].
[cited 2019 Oct 24] Available from: http://www.ncbi.nlm.nih.gov/
pubmed/25797505
127. Jimenez JJ, Iribarren JL, Lorente L, Rodriguez JM, Hernandez D,
Nassar I, etal. Tranexamic acid attenuates inammatory response
in cardiopulmonary bypass surgery through blockade of brinolysis: a case control study followed by a randomized double-blind
controlled trial. Crit Care. 2007;11(6):R117. [Internet]. [cited
2019 Oct 24]; Available from:
pubmed/17988379
128. Ker K, Edwards P, Perel P, Shakur H, Roberts I. Effect of
tranexamic acid on surgical bleeding: systematic review and
cumulative meta-analysis. BMJ (Online). 2012;344.
129. Shakur H, Roberts I, Fawole B, Chaudhri R, El-Sheikh M,
Akintan A, etal. Effect of early tranexamic acid administration
on mortality, hysterectomy, and other morbidities in women
with post-partum haemorrhage (WOMAN): an international,
randomised, double-blind, placebo-controlled trial. Lancet.
2017;389(10084):2105–16.
130. Cap AP.CRASH-3: a win for patients with traumatic brain injury.
Lancet [Internet]. 2019 Oct [cited 2019 Oct 24]; Available from:
https://linkinghub.elsevier.com/retrieve/pii/S0140673619323128.
131. Manji RA, Grocott HP, Leake J, Ariano RE, Manji JS, Menkis AH,
etal. Seizures following cardiac surgery: the impact of tranexamic
acid and other risk factors. Can J Anaesth. 2012;59(1):6–13.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/22065333.
[Internet]. [cited 2019 Oct 24].
132. Mega JL, Simon T. Pharmacology of antithrombotic drugs: an
assessment of oral antiplatelet and anticoagulant treatments.
Lancet. 2015;386(9990):281–91.
133. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS,
Van De Putte LB, etal. Cyclooxygenase in biology and disease.
FASEB J. 1998;12(12):1063–73.
http://www.ncbi.nlm.nih.gov/
190
https://t.me/medicina_free
A. Shelvan et al.
134. O’Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK,
de Lemos JA, etal. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary:
a report of the American College of Cardiology Foundation/
American Heart Association task force on practice guidelines. J
Am Coll Cardiol. 2013;61(4):485–510.
135. Saxena A, Balaramnavar VM, Hohlfeld T, Saxena AK.Drug/drug
interaction of common NSAIDs with antiplatelet effect of aspirin
in human platelets. Eur J Pharmacol. 2013;721(1–3):215–24.
136. Strate LL, Singh P, Boylan MR, Piawah S, Cao Y, Chan AT.A
prospective study of alcohol consumption and smoking and
the risk of major gastrointestinal bleeding in men. PLoS One.
2016;11(11):e0165278.
137. Li W-J, Zhang H-Y, Miao C-L, Tang R-B, DU X, Shi J-H,
et al. Cigarette smoking inhibits the anti-platelet activity of
aspirin in patients with coronary heart disease. Chin Med J.
2011;124(10):1569–72.
138. Holmes CE, Jasielec J, Levis JE, Skelly J, Muss HB. Initiation
of aspirin therapy modulates Angiogenic protein levels in women
with breast cancer receiving tamoxifen therapy. Clin Transl Sci.
2013;6(5):386–90.
139. Colwell JA, Nesto RW.The platelet in diabetes: focus on prevention of ischemic events. Diabetes Care. 2003;26:2181–8.
140. Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S.Concurrent use of
diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inammatory drugs
and risk of acute kidney injury: nested case-control study. BMJ.
2013;346:e8525.
141. Vazquez SR.Drug-drug interactions in an era of multiple anticoagulants: a focus on clinically relevant drug interactions.
Hematology. 2018;2018(1):339–47.
142. Cattaneo M. P2Y
receptors: structure and function. J Thromb
12
Haemost. 2015;13:S10–6.
143. Savi P, Pereillo JM, Uzabiaga MF, Combalbert J, Picard C,
Maffrand JP, etal. Identication and biological activity of the active
metabolite of clopidogrel. Thromb Haemost. 2000;84(5):891–6.
144. Angiolillo DJ, Gibson CM, Cheng S, Ollier C, Nicolas O,
Bergougnan L, et al. Differential effects of omeprazole and
pantoprazole on the pharmacodynamics and pharmacokinetics of Clopidogrel in healthy subjects: randomized, placebocontrolled. Crossover Comparison Studies Clin Pharmacol Ther.
2011;89(1):65–74.
145. Sukhovershin RA, Cooke JP. How may proton pump inhibitors impair cardiovascular health? Am J Cardiovasc Drugs.
2016;16(3):153.
146. Gurbel PA, Bliden KP, Logan DK, Kereiakes DJ, Lasseter KC,
White A, etal. The inuence of smoking status on the pharmacokinetics and pharmacodynamics of Clopidogrel and Prasugrel: the
PARADOX study. J Am Coll Cardiol. 2013;62(6):505–12.
147. Holmberg MT, Tornio A, Neuvonen M, Neuvonen PJ, Backman
JT, Niemi M.Grapefruit juice inhibits the metabolic activation of
Clopidogrel. Clin Pharmacol Ther. 2014;95(3):307–13.
148. Delaney JA, Opatrny L, Brophy JM, Suissa S.Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ. 2007;177(4):347–51.
149. Cattaneo M, Lecchi A.Inhibition of the platelet P2Y
receptor
12
for adenosine diphosphate potentiates the antiplatelet effect of
prostacyclin. J Thromb Haemost. 2007;5(3):577–82.
150. Danielak D, Karaźniewicz-Łada M, Główka F.Assessment of the
risk of Rhabdomyolysis and myopathy during concomitant treatment with Ticagrelor and statins. Drugs. 2018;78(11):1105–12.
151. Bennett JS.Structure and function of the platelet integrin alphaIIbbeta3. J Clin Invest. 2005;115(12):3363–9.
152. McFadyen JD, Schaff M, Peter K.Current and future antiplatelet
therapies: emphasis on preserving haemostasis. Nat Rev Cardiol.
2018;15(3):181–91.
153. Michelson AD.Antiplatelet therapies for the treatment of cardiovascular disease. Nat Rev Drug Discov. 2010;9(2):154–69.
154. Mukherjee D, Rof M.Glycoprotein IIb/IIIa receptor inhibitors in
2008: do they still have a role? J Interv Cardiol. 2008;21(2):118–21.
155. Serebruany VL, Malinin AI, Eisert RM, Sane DC.Risk of bleeding complications with antiplatelet agents: meta-analysis of
338,191 patients enrolled in 50 randomized controlled trials. Am J
Hematol. 2004;75(1):40–7.
156. PLETAL. (PLAY-tal) (cilostazol) (sil-OS-tah-zol) Tablets.
157. Mader TJ. Adenosine: adverse interactions. Ann Emerg Med.
1992;21(4):453.
158. Huang W, Xin G, Wei Z, Ji C, Zheng H, Gu J, etal. Metformin
uniquely prevents thrombosis by inhibiting platelet activation and
mtDNA release. Sci Rep. 2016;6:36222.
159. Li XL, Steiner M.Fish oil: a potent inhibitor of platelet adhesiveness. Blood. 1990;76(5):938–45.
160. Morriss R.Antidepressants are associated with hospital admitted
intracranial bleeds in people taking other medication associated
with bleeding. Evid Based Ment Health. 2016;19(1):24.
161. Dehmer SP, Maciosek MV, Flottemesch TJ.Aspirin use to prevent cardiovascular disease and colorectal cancer. Aspirin use to
prevent cardiovascular disease and colorectal cancer: a decision
analysis: technical report. 2015.
162. Pratt LA, Brody DJ, Gu Q. Antidepressant use among persons
aged 12 and over:United States,2011–2014. NCHS Data Brief.
2017;283:1–8.
163. Antibrinolytic Drugs. In: Encyclopedia of molecular Pharmacology. Springer; 2008. p. 130. https://doi.
org/10.1007/978-3-540-38918-7.
164. Ker K, Roberts I, Shakur H, Coats T.Antibrinolytic drugs for
acute traumatic injury. Sao Paulo Med J. 2015;129(5):CD004896.
165. Hobbs JC, Welsby IJ, Green CL, Dhakal IB, Wellman SS.Epsilon
aminocaproic acid to reduce blood loss and transfusion after total
hip and total knee arthroplasty. J Arthroplast. 2018;33(1):55–60.
166. Furuta T, Sugimoto M, Kodaira C, Nishino M, Yamade M, Uotani
T, Sahara S, et al. Inuence of low-dose proton pump inhibitors on anti-platelet function of clopidogrel. Gastroenterology.
2012;142:S215.
167. Ponomaryov T, Payne H, Fabritz L, Wagner DD, Brill A. Mast
cells granular contents are crucial for deep vein thrombosis in
mice. Circ Res. 2017;121(8):941–50.
Blood Transfusion in the Severe Trauma
https://t.me/medicina_free
Patient
Jose C. Humanez, Oladapo Oshikoya, Albert Hsu, and
Amie
L. Hoefnagel
20
Initial Trauma Bay Management
A systematic and organized approach is required for the
immediate management of any trauma patient irrespective of
the injury’s severity. The Advanced Trauma Life Support®
(ATLS®) program developed by the American College of
Surgeons (ACS) teaches a standardized approach for the
treatment of the trauma patient. It has been adopted at trauma
centers in the United States and worldwide and is recognized
as the standard of care in the treatment of multiply injured
patients. The underlying foundation of the ATLS program is
that life-threatening conditions should be treated expeditiously. Furthermore, a detailed and accurate history is not
essential to begin the initial evaluation of a patient with acute
injuries [2].
The initial assessment and management of injured patients
begins with the primary survey. The purpose of the primary
survey is to rapidly assess and initiate treatment of lifethreatening conditions in a prioritized sequence so that the
greatest threat to life is treated rst. The following ABCDE
algorithm constitutes the sequential steps of the primary
survey.
• Airway maintenance with cervical spine protection
• Breathing and ventilation
• Circulation with bleeding control
J. C. Humanez · O. Oshikoya · A. L. Hoefnagel (*)
University of Florida– Jacksonville, Department of
Anesthesiology, Jacksonville, FL, USA
e-mail: Jose.humanez@jax.u.edu; oladapo.oshikoya@jax.u.edu;
amie.hoefnagel@jax.u.edu
A. Hsu
University of Florida – Jacksonville, Department of Surgery,
Jacksonville, FL, USA
e-mail:
albert.hsu@jax.u.edu
• Disability/neurologic assessment
• Exposure and environmental control
Performing the primary survey is a coordinated effort
among all members of the medical team. The steps are frequently performed simultaneously when medical providers
are well experienced with treating trauma patients. The airway is assessed rst for patency. The airway may need to be
suctioned, and any foreign bodies should be removed. The
chin lift and jaw thrust maneuvers can help maintain airway
patency. A prompt decision is made to secure a denitive airway if it is required. The presence of a tension pneumothorax, massive hemothorax, rib fractures with ail chest and
pulmonary contusion, or open pneumothorax is rapidly identied and treated as those conditions can severely impair
ventilation and oxygenation.
Hemorrhage is the leading cause of preventable death in
trauma patients. Hemorrhagic shock has to be recognized
promptly and the source of bleeding identied and addressed
as soon as possible. External bleeding should be controlled
with direct pressure or a tourniquet. Resuscitation begins
with obtaining adequate intravenous access in the form of
two large bore peripheral lines or a large bore central line,
preferably above the diaphragm. The massive transfusion
protocol may need to be activated and the use of hemostatic
adjuncts such as tranexamic acid should be considered. A
sample of blood is obtained from the patient and sent to the
blood bank so that cross-matched blood may be administered when feasible. The decision to transfer the patient to
the operating room to address the source of hemorrhage also
needs to be made expediently.
At the end of the survey, a rapid and basic neurologic
evaluation is performed to determine the level of consciousness and the presence of any focal neurologic decits. The
primary survey concludes with completely undressing the
patient to facilitate a thorough assessment and then covering
the patient in warm blankets to prevent hypothermia.
© Springer Nature Switzerland AG 2021
C. S. Scher et al. (eds.), Essentials of Blood Product Management in Anesthesia Practice,
https://doi.org/10.1007/978-3-030-59295-0_20
191
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Transfusion Strategies
The strategy of damage control resuscitation of a trauma
patient in hemorrhagic shock involves preserving endorgan perfusion and preventing any further progression of
the lethal triad of death. The triad of death in the setting of
trauma describes the combination of hypothermia, acidosis, and coagulopathy that is commonly associated with
hemorrhagic shock [1]. Patients with severe hypothermia
despite warming maneuvers, persistent metabolic acidosis
despite massive resuscitation, and coagulopathy with
bleeding not amenable to surgical control have a high mortality rate of 20–50% [3]. Packed red blood cells should be
transfused to maintain oxygen-carrying capacity and other
blood components transfused to optimize hemostasis.
Administration of crystalloids should be minimized as its
use is associated with increased morbidity as demonstrated
by a multi-institutional analysis from Duchesne etal. [4]
Infusion of large volumes of crystalloid can also worsen
coagulopathy by diluting coagulation factors. In this setting, the trauma surgeon may elect to perform a damage
control operation to limit the surgical intervention, to control only hemorrhage and contamination, and to minimize
the amount of time spent in the operating room. The patient
is then further resuscitated in the ICU setting prior to
returning to the OR.
For a patient in hemorrhagic shock requiring large volume resuscitation, a massive transfusion protocol (MTP)
that was developed and implemented by the institution
should be followed. The benets of a massive transfusion
protocol in improving mortality and reducing the usage of
blood products are discussed separately in this text (Chap.
8). The protocol denes the target ratio of blood products
that should be transfused during the initial phase of resuscitation. Many centers have adopted the practice of administering plasma, platelets, and red blood cells in a balanced
1:1:1 transfusion ratio. This was largely the result of the
publication of the landmark Pragmatic, Randomized
Optimal Platelet and Plasma Ratios (PROPPR) trial. The
multicenter randomized controlled PROPPR trial, published in 2015, was designed to determine the safety and
efcacy of a balanced 1:1:1 transfusion ratio in patients
predicted to require massive transfusion. The study compared a 1:1:1 transfusion ratio with a 1:1:2 ratio [5].
Though the study found no difference in all cause 24h or
30day mortality comparing the 1:1:1 with the 1:1:2 ratio,
there was a signicant decrease in 24h mortality due to
exsanguination in the 1:1:1 group. The physiology supporting a balanced transfusion strategy is that the 1:1:1
transfusion ratio mimics the composition of whole blood.
Furthermore, an unbalanced transfusion ratio where more
of one blood component is administered will serve to
dilute the other two components and may lead to inade-
quate hemostasis [6]. The practice of a 1:1:1 transfusion
ratio in the initial phase of resuscitation was also incorporated into a recently published clinical practice guideline
on damage control resuscitation [7].
More recently, whole blood transfusion in trauma patients
has been gaining in popularity. Our institution has recently
made whole blood available for use in the Trauma
Resuscitation Unit. The benets of whole blood transfusion
are that the blood components are more concentrated, and it
is simpler to administer compared to blood component therapy. The indications, interactions, and adverse effects of
whole blood transfusion are discussed separately. Further
research, however, is needed before it can be determined that
whole blood should be included as part of the standard practice for damage control resuscitation.
Tranexamic Acid
Tranexamic acid (TXA) is an antibrinolytic lysine analog
used to prevent the enzymatic breakdown of brin blood
clots. TXA has a structural similarity to lysine, which allows
TXA to competitively inhibit plasminogen conversion to
plasmin and reduces the rate of brin degradation [8]. TXA
also partially prevents brinogenolysis induced by tissue
factor [9]. The administration of TXA has been shown to
decrease the amount of intraoperative blood loss and associated blood transfusion for patients undergoing either elective
or emergency surgery [8]. TXA has been shown to decrease
blood loss by one-third, regardless of surgery type or amount
of expected blood loss, when given intraoperatively to surgical patients just prior to incision [10, 11].
When given within 3h of trauma to a bleeding trauma
patient, TXA reduces the risk of death from bleeding. TXA
actually increases mortality risk when given longer than 3h
post-traumatic incident so its administration should be as
close to the traumatic event as possible, potentially suggesting prehospital administration [12]. For all of its antibrinolytic properties and ability to reduce blood loss, TXA
has not been shown to increase the risk of thrombosis and
has actually shown reduced odds of fatal and non-fatal vascular occlusive events [13, 14].
Administration of TXA in trauma patients is typically a
1g loading dose over 10min, followed by an infusion of 1g
over 8h [12]. Alternative dosing regimens exist, including
bolus injection of 10mg/kg over 30min followed by an infusion of 1mg/kg/h. TXA is a pregnancy category B medication, with no harm found in animal models, so its use in
parturients involved in bleeding trauma should be considered. A dose reduction is required in mild to moderate renal
impairment and contraindicated in severe renal impairment
due to 95% renal excretion. No such dose reduction exists
for liver impairment [15].
20 Blood Transfusion in the Severe Trauma Patient
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193
Cell Saver and Autologous Blood Transfusion
Trauma patients utilize large amounts of hospital resources,
including the use of approximately 70% of all blood transfused at a trauma center, [16] which can have a nancial and
resource burden for the institution. Transfusion protocols
from donated cross-matched blood and the use of MTP
remain the standard treatment for the patient in hemorrhagic
shock due to trauma. Transfusion of donated blood does not
come without risks; the potential for citrate toxicity, hyperkalemia, disease transmission, hypothermia, acidosis, hypomagnesemia, sepsis, acute respiratory failure (TRALI,
TACO, ARDS), and thrombotic side effects pose a signicant risk [17–20]. Auto-transfusion has been widely used as
an alternative or adjunct to transfusion of donated blood to
reduce or avoid the number of transfusions and the associated risks and costs, with fewer side effects.
Autotransfusion was rst documented in 1818 by Dr. James
Blundell. He experimented with auto-transfusion in canine
models and later tried on humans, but with signicant mortality [21]. In 1874, Dr. William Highmore at the Yeatman
Hospital in the United Kingdom proposed the idea of reinfusing shed blood. He described a case of a woman that suffered
a postpartum hemorrhage. The patient died with “several
pounds of blood in a vessel and in the bed, which, could have
been used to save her life had he been able to transfuse it back
into her veins” [22]. In 1883, at the Roosevelt Hospital in
NewYork, William Halsted described a technique for “reinfusion blood” to treat carbon monoxide poisoning. His method
included debrination and straining of blood removed from
the patient prior to reinfusion [23]. Other successful cases of
autotransfusion were reported by Duncan and Miller in 1885
at the Royal Inrmary in Edinburgh, Scotland, where a patient
with crush injury was retransfused his own blood after it had
been treated with phosphate of soda [24]. In 1914, the German
gynecologist H. J. Thies treated removed blood with citrate
and strained it through gauze before returning it to his patients
[25]. In 1943, Griswold and Ortner published 100 patients in
the rst case series [26]. However, autotransfusion fell out of
favor in the 1940s and 1950s with progress in blood donation,
blood storage, and advances in blood banking that simplied
and increased the safety of allogeneic transfusion. In the 1960s
and 1970s, there was renewed interest in autotransfusion when
Dyer, Klebanof, and Pathak developed techniques and new
devices for the reinfusion of salvaged unwashed blood. Their
research provided data on hemolysis reduction, contaminant
ltration, and most importantclinical outcomes. Klebanoff’s
device consisted of a cardiotomy reservoir and a roller pump,
which was known as the Bentley autotransfuser [27]; its use
decreased after the report of several cases of air embolism. In
1968, Wilson and Taswell from the Mayo Clinic developed a
prototype machine that collected and washed the salvaged
blood. Technological advances in the 1970s resulted in the
availability of several commercial devices [28]. In 1974,
Haemonetics (Braintree, MA) developed a device that could
collect, wash, and concentrate autologous red blood cells and
make them available for reinfusion. They called it the “cell
saver” device. Subsequently, the term “cell saver” refers
generically any blood salvage device used perioperatively.
Indications and Contraindications
Cell saver or autologous blood transfusion should be considered in every trauma patient with active bleeding. In order to
make it worthwhile, there should be a blood loss of at least
1000mL [14]. Other reported indications include the need
for immediate blood, inability to obtain or provide crossmatched blood, and if the patient is unwilling to receive
cross-matched blood [30]. The American Association of
Blood Banks recommends the use of cell saver if the expected
surgical blood loss is either 20% of the patient’s estimated
blood volume, or greater than 1000 mL, or if the average
transfusion for the procedure is greater than 1 unit of blood.
Further indications are patient refusal of allogenic transfusion or lack of availability of cross-matched blood [32].
More than the indication, one important question is the
consideration of contraindications for the use of cell saver.
One contraindication is if the blood has suffered contamination either by an infectious or non-infectious source. An
example of an infectious source is the mix of blood with gastrointestinal contents or purulent material. Non-infectious
sources involve the mixing of blood with solutions such as
iodine, sterile water, alcohol, chlorhexidine, irrigation solutions, or hemostatic agents such as thrombin [31, 32].
Other contraindications for autologous blood transfusion
include sickle cell disease, presence of malignancy (risk of
reinfusion of cancer cells and development of metastasis),
and cesarean delivery (theoretical risk of amniotic uid
embolism) Table20.1 summarizes the indication and contraindication for the use of a cell saver device.
Table 20.1 Indications and relative contraindications to autologous
blood salvage
Indications for cell salvage
Surgery with ≥1000ml (or 20% of total blood volume)
anticipated blood loss
To reduce or avoid exposure to allogeneic blood
When crossmatch compatible blood is difcult to nd
Patients with red cell alloantibodies
Patients who do not accept allogeneic blood
Low preoperative red cell mass and high bleeding risk
Contraindications to cell salvage
Sickle cell disease
Drug and other contaminants (betadine, alcohol, prep solutions)
Thrombin, brin and other hemostatic agents
Bone cement (methyl methacrylate)
Relative contraindications to cell salvage
Caesarean section (amniotic uid contamination)
Cancer surgery
Bacterial contamination
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https://t.me/medicina_free
J. C. Humanez et al.
The Cell Saver Equipment and Process
The cell saver process has three phases: cell salvage or collection, washing, and reinfusion. The nal product has a
hematocrit that varies between 50% and 80%, has a storage
time of less than 6h, and requires the use of a lter to provide
leukocyte reduction.
Blood is collected via suction from the surgical eld and
transferred into a canister where it is mixed with an anticoagulant. The process involves centrifugation of the blood and
then removal of the supernatant. To remove residual harmful
contaminants, copious amounts of normal saline and further
centrifugation are used to wash the blood. The red cells are
then resuspended in normal saline for infusion. Figure20.1
depicts the different components that are part of the autotransfusion device.
The composition of the salvaged blood has physiologic
differences from circulating blood due to chemical and physical contaminants from the surgical eld and cellular breakdown products from the operative eld and blood contact
with the articial surfaces in the cell saver device. Finally,
washing of the salvaged blood removes the contaminants and
plasma proteins that would not be removed by simple
ltration.
Once blood is collected, it must be anticoagulated. There
are two primary anticoagulants used for this purpose: heparin and citrate. Heparin anticoagulated salvaged blood leads
to lower levels of free hemoglobin, improved osmotic fragility, and oxidative reserve capacity [33]; however, for patients
with heparin-induced thrombocytopenia, citrate is the anticoagulant of choice.
Once the nal product is obtained, it is passed through a
leukoreduction lter resulting in 99.6–100% removal of bac-
teria. Though not routinely practiced, the addition of antibiotics may reduce bacterial load even further [33].
The use of cell saver and autotransfusion does not come
without risk or development of complications. The most
common complication of autotransfusion is loss of ability to
return blood if the setup is not properly connected. The more
serious complication includes blood contamination, resulting in infection and development of sepsis [29] which can be
prevented by following sterile guidelines. Other less common complications include hemodilution, hemolysis due to
suction or degradation, air embolism, contamination of activated leukocytes, and thrombocytopenia [29]. Overall complications are avoidable with the use of sterile technique and
if less than 3000mL of blood is reinfused.
In conclusion, cell saver and autotransfusion should be
considered in trauma patients without contraindications in
whom signicant blood loss is anticipated. It can be used in
addition to cross-matched blood or can be used as a temporizing measure while waiting for the arrival of cross-matched
blood. The use of cell saver can reduce the risk of transfusion
reactions for the patient as may provide cost-saving benets
compared with allogeneic blood transfusion.
Thromboelastography (TEG) in Trauma
Resuscitation
Thromboelastography (TEG) is a test of whole blood coagulation. There is an entire chapter in this text dedicated to this
subject, so we will touch on it only briey here. The test results
are available within an hour; however, there is computer software that will allow clinicians to watch the tracing form in real
time. This tracing is frequently displayed within the trauma
Fig. 20.1 Components of the
autotransfusion device
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