Trauma
Trauma-Induced Coagulopathy ELIZABETH D. KATRANCHA, RN, DNP, CNS, CNE LUIS S. GONZALEZ III, PharmD, BCPS
Coagulopathy is the inability of blood to coagulate normally; in trauma patients, it is a multifactorial and complex process. Seriously injured trauma patients experience coagulopathies during the acute injury phase. Risk factors for trauma-induced coagulopathy include hypothermia, metabolic acidosis, hypoperfusion, hemodilution, and fluid replacement. In addition to the coagulopathy induced by trauma, many patients may also be taking medications that interfere with hemostasis. Therefore, medication-induced coagulopathy also is a concern. Traditional laboratory-based methods of assessing coagulation are being supported or even replaced by point-of-care tests. The evidence-based management of trauma-induced coagulopathy should address hypothermia, fluid resuscitation, blood components administration, and, if needed, medications to reverse identified coagulation disorders. (Critical Care Nurse. 2014;34[4]:54-63)
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trauma patient’s greatest risk of death after the first 24 hours of injury stems from a combination of 3 conditions: hypothermia, acidosis, and coagulopathy.1,2 Nurses caring for trauma patients must be aware of these factors and how to manage them in an evidence-based manner. This article is focused on seriously injured trauma patients and the coagulopathies that they experience in the acute phase of injury. It provides an overview of coagulation and explores risk factors for trauma-induced coagulopathy. In addition to the coagulopathy induced by trauma, many patients may also be taking medications that interfere with hemostasis. Therefore, medication-induced coagulopathy is reviewed. We briefly review current evidence-based guidelines for blood component and fluid management and the role of thromboelastography (TEG or ROTEM) point-of-care diagnostic tools in the assessment and management of trauma-induced coagulopathies (TIC).
Normal Physiological Mechanisms of Coagulation A large body of research has resulted in better defining how coagulation takes place. This cell-based model of coagulation has replaced the traditional version of the intrinsic and extrinsic coagulation cascade system. This cell-based model consists of 3 phases that overlap one another: initiation, amplification, and propagation3,4 (Figure 1). The initiation phase begins when the blood vessel wall is injured, exposing tissue factor. When plasma containing factor VIIa comes in contact with cells bearing tissue factor, the 2 factors form a complex.3,4 This complex then activates factors IX and X. Factor Xa complexes with factor Va to form thrombin (factor IIa) in small amounts. ©2014 American Association of Critical-Care Nurses doi: http://dx.doi.org/10.4037/ccn2014133
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II
X
Initiation TF
VIIa
Xa
Propagation
IIa
Va
Tissue factor–bearing cell TF VIIa
Tissue factor–bearing cell
IX
TF VIIa
IXa
II
VIIIa + free vWF XI
VIII/vWF
TFPI Xa TF VIIa
Xa
Va
Tissue factor–bearing cell
XIa
VIIIa
IIa
XIa
Platelet
V
V
XIa
Va
II
X
IXa
Amplification
IX
IXa
Xa
VIIIa
Va
IIa
Activated platelet
IX
Va
Activated platelet
Figure 1 Cell-based model of coagulation. Abbreviations: TF, tissue factor; TFPI, tissue factor pathway inhibitor; vWF, von Willebrand factor. Reproduced from Davidson,5 with permission.
The amplification stage begins with thrombin binding to and activating platelets that have adhered to the site of injury.3,4 The activated platelets secrete partially activated factor V, which becomes fully activated by the action of thrombin. Thrombin activates factor IX and cleaves the factor VIII/von Willebrand complex, releasing factor VIII. At this point, activated platelets bind factors Va, VIIIa, and Xa.4 The propagation step starts with factor IXa diffusing from its site of activation on the tissue factor–bearing Authors Elizabeth D. Katrancha is an instructor of nursing in the baccalaureate nursing program at the University of Pittsburgh at Johnstown. Luis S. Gonzalez III is a clinical pharmacist at Conemaugh Memorial Medical Center in Johnstown, Pennsylvania. Corresponding author: Elizabeth D. Katrancha, RN, MSN, CNS, CNE, University of Pittsburgh at Johnstown, 216 Nursing and Health Sciences, 450 Schoolhouse Road, Johnstown, PA 15904 (e-mail: [email protected]). To purchase electronic or print reprints, contact the American Association of CriticalCare Nurses, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 899-1712 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, [email protected].
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cell and attaching to the surface of activated platelets. Factors IXa and VIIIa form a complex, which then activates platelet-bound factor X. Finally, factor Xa binds to factor Va on the platelet surface, resulting in a burst of thrombin formation that results in the generation of a clot.3 There are also naturally occurring anticoagulants that regulate coagulation, including antithrombin, protein C, protein S, and plasmin.
Etiology Coagulopathy is simply the inability of blood to coagulate normally; however, in trauma patients, it is a multifactorial and complex process. Abnormal coagulation can result from depletion, dilution, or inactivation of normal clotting factors.6 TIC is precipitated by massive tissue injury and is a multifactorial problem, currently thought to be confounded by hypothermia, acidosis, hypoperfusion, and hemodilution. The triad of hypothermia, acidosis, and hypotension occurring together cause the greatest risk of mortality.2 CriticalCareNurse
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Pathophysiology Protein C has been implicated in several studies in the development of TIC. As hypoperfusion occurs, protein C is converted to activated protein C (APC).7-9 APC inhibits cofactors V and VIII, reducing thrombin generation.7,9 Tissue plasminogen activator also plays a role in fibrinolysis; APC reduces inhibition of tissue plasminogen activator, which in turn accelerates the conversion of plasminogen to plasmin.7 Fibrinolysis The cell-based model of coagulation con- is imporsists of 3 overlapping phases: initiation, tant in amplification, and propagation. maintaining homeostasis by localizing clot formation to damaged endothelium.10 In TIC, a hyperfibrinolysis restricts coagulation and allows the trauma patient to bleed excessively.
Risk Factors Hypothermia Patients involved in trauma face exposure to the environment beginning at the moment of the incident. Prehospital personnel often remove clothing in order to assess the patient thoroughly. Intravenous fluids are administered and may be at room temperature or below. Upon arrival in the emergency department, patients are again exposed in order for diagnostic testing such as focused assessment with sonography for trauma examination, radiography, and a secondary survey to be performed. Some drugs such as muscle relaxants, sedatives, anesthetics, and opioids also can reduce a patient’s body temperature. Metabolic Acidosis Hypoperfusion of tissues results in decreased oxygen delivery and the conversion to anaerobic metabolism via the citric acid cycle, resulting in lactic acid accumulation. Resuscitation with fluids containing large amounts of chloride combined with hypothermia contributes to the metabolic acidosis through the development of a nonanion gap acidosis. Laboratory values of pH less than 7.4, elevated serum level of lactate, and base deficits reaching 10 mmol/L reduce the activity of various coagulation factors by up to 40%.4,11 Base deficit is the amount of base required by a liter of whole arterial blood to normalize the pH to 7.4 and as such is an indicator
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of the severity of the acidosis. This metabolic acidosis results in coagulation system disorders such as prolonged clotting times and reduced clot strength.6,12 Hypoperfusion, Hemodilution, and Fluid Resuscitation Recent studies have indicated that despite injury severity, patients who are hypoperfused experience coagulopathies.8,10,12 Wafaisade et al12 report that a systolic blood pressure less than 90 mm Hg correlated with a 3 times greater risk of coagulopathy developing. Brohi et al7 hypothesize that hypoperfusion of tissues leads to increased levels of soluble thrombomodulin. Thrombomodulin combines with and inhibits thrombin, and this complex activates protein C. APC impairs clot formation and increases existing clot dissolution.7,9 Hypoperfusion should not be confused with permissive hypotension, which may be a strategy employed in damage-control resuscitation. Bleeding trauma patients are often volume resuscitated with crystalloids, colloids, packed red blood cells, and fresh frozen plasma. These volume-resuscitating efforts may result in a dilutional coagulopathy. Researchers have reported an association between coagulopathy and receiving 3000 mL or more of intravenous fluids before arriving at the hospital. The long-accepted approach of immediate delivery of 2 L of isotonic crystalloids after trauma may exacerbate coagulopathy.11,13 Medications A large segment of the population is taking prescribed and even over-the-counter antithrombotic medications. Although the contribution of antithrombotic medications to the development of TIC is unknown at this time, being aware of these medications and their effect on hemostasis may facilitate resuscitation efforts. Antithrombotic therapy is indicated for the treatment and prevention of many common diseases. The most common are atrial fibrillation, coronary artery disease, and deep vein thrombosis.14 Four categories of medications prevent normal clotting: antiplatelets, anticoagulants, fibrinolytics (not routinely used in outpatients), and herbals. The common coagulation studies of activated partial thromboplastin time (aPTT), prothrombin time/international normalized ratio (PT/INR), platelet count, and fibrinogen levels evaluate only certain points in the coagulation process and take time to be measured in the laboratory. In addition, the presence of many medications affecting hemostasis would not be detected by routine coagulation studies.
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100 80
Amplitude (firmness), mm
60 40
MCF
ML
A10 20
alpha
LI30
0
CT CFT alpha A10 MCF LI30 ML
CFT CT 0
10
20
30
Clotting time Clot formation time Alpha-angle Amplitude 10 min after CT Maximum clot firmness Lysis index 30 min after CT Maximum lysis
40
50
60
Time, min
Figure 2 ROTEM parameters. Reprinted from ROTEM website,19 with permission. Copyright TEM International GmbH.
Methods of Assessing Coagulation in TIC The coagulation profile (PT, aPTT, fibrinogen concentration, and platelet count) can take up to 30 minutes to process in the laboratory and measures only clot initiation.15 Thrombelastograph hemostasis analyzer system (TEG, Haemonetics Corp) and rotational thromboelastometry (ROTEM, Tem International Gmbh) are devices that are used by trauma teams to detect and monitor coagulation disarray in a real-time environment.10,16,17 TEG and ROTEM are both used to assess elastic changes in clotting whole blood. Whole blood is placed in a heated cup that contains a pin connected to a detector system. The cup and pin oscillate relative to one another and at an angle. Fibrin forms between the cup and the pin, and a tracing is generated. The tracing is divided into parts that reflect the various stages of coagulation over time. These parameters assist the trauma team in deciding which drugs and blood components to administer. Commonly reported ROTEM results are reaction time (R), clotting time (CT), clot formation time (K, CFT), alpha angle (), maximum amplitude (MA), maximum clot firmness (MCF), and lysis (ly).18 Test parameters commonly reported are EXTEM, INTEM, FIBTEM, and APTEM. EXTEM is an extrinsic screening test in which CT is not sensitive for heparin. The INTEM is an intrinsic screening test in which CT is sensitive for heparin. In
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both EXTEM and INTEM, amplitude and CFT are influenced by fibrinogen and platelets. FIBTEM reports activation the same as EXTEM but platelet inhibition reagent is added. In APTEM, the activation is the same as in EXTEM; however, fibrinolysis inhibition is induced with aprotinin.19 HEPTEM is specific to heparin effect on coagulation.19 The analysis, printed in graph form, provides information from the beginning of clot formation until dissolution, concentration activity of coagulation factors, effects of anticoagulants, fibrin generation, and platelet count and function. Figure 2 illustrates the parameters measured in a ROTEM tracing, and Figure 3 illustrates interpretations of ROTEM results. It is helpful to note the areas on the report that correspond to the various stages of clot forma- Commonly reported ROTEM results are reaction. The tion time, clotting time, clot formation time, results of alpha angle, maximum amplitude, maximum this point- clot firmness, and lysis. of-care coagulation test guide the trauma team’s fluid and blood component resuscitation strategies, providing real-time information on which to base decisions to administer fresh frozen plasma, platelets, cryoprecipitate, tranexamic acid (TXA), or other coagulation factor concentrates.16
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Normal patient:
EXTEM
INTEM
CT:
67s
CFR:
CFT:
54mm MCF:
87s : 57mm ML:
73º -%
CT: CFR:
FIBTEM CT:
CFT:
54mm MCF:
67s
:
61mm ML:
77º -%
APTEM 66s
CFR:
200s
CFT:
9mm MCF:
-s : 10mm ML:
57º
CT:
-%
CFR:
74s
CFT:
53mm MCF:
89s
:
61mm ML:
72º -%
Platelet deficiency:
EXTEM CT: A10:
INTEM :
57s
CFT:
444s
23mm
MCF:
35mm ML:
80º
CT:
200s
CFT:
-%
A10:
23mm
MCF:
-º
CT:
-%
A10:
FIBTEM CT: A10:
449s
:
32mm ML:
72º -%
APTEM 67s
CFT:
15mm
MCF:
-s : 16mm ML:
52s
CFT:
398s
25mm
MCF:
35mm ML:
:
80º -% Continued
Figure 3 ROTEM result interpretations. The assessment of the ROTEM analysis is carried out along the time axis (from left to right). A disturbed activation of coagulation is indicated by a prolonged clotting time (CT). As causes, a factor deficiency or heparin effects have to be considered. The comparison of INTEM and HEPTEM allows specific detection of a heparin effect. An abnormal clot formation is indicated by a prolonged clot formation time (CFT) and/or a reduced maximum clot firmness (MCF). The CFT is thereby influenced more strongly by a clot polymerization disorder than the MCF. A prolonged CFT, with at the same time a normal MCF, indicates therefore a polymerization disorder, whereas a reduced MCF with a normal CFT rather indicates a deficiency of clottable substrate (fibrinogen and/or platelets). Fibrinolysis is detected by the lysis of the clot (maximum lysis [ML] >15%) or by the finding of a better clot formation (shorter CFT, greater MCF) in APTEM as compared with EXTEM. Several centers already use, in massive bleeding, a shortening of the CT in APTEM, as compared with EXTEM, as a trigger for administration of an antifibrinolytic drug. Parameters EXTEM, INTEM, FIBTEM, APTEM, and HEPTEM are explained in text. Reprinted from ROTEM website,19 with permission. Copyright TEM International GmbH.
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Fibrinogen deficiency:
EXTEM
INTEM
CT:
109s
CFT:
A10:
31mm
MCF:
263s
:
38mm ML:
48º
CT:
-%
A10:
-º
CT:
-%
A10:
FIBTEM
236s
CFT:
33mm
MCF:
220s
:
42mm ML:
55º -%
APTEM
CT:
185s
CFT:
A10:
3mm
MCF:
-s
:
3mm ML:
98s
CFT:
31mm
MCF:
276s
:
40mm ML:
46º -%
Hyperfibrinolysis:
EXTEM CT: A10:
INTEM 59s
CFT:
130s
44mm
MCF:
48mm ML:
:
65º 100%
CT:
200s
CFT:
A10:
46mm
MCF:
FIBTEM CT: A10:
88s
:
48mm ML:
74º 100%
APTEM 51s
CFT:
7mm
MCF:
-s : 7mm ML:
-º
CT:
94%
A10:
62s
CFT:
132s
44mm
MCF:
55mm ML:
:
64º 0% Continued
Figure 3 Continued
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Heparin influence:
INTEM
EXTEM CT: A10:
67s
CFT:
50mm
MCF:
104s
:
57mm ML:
68º 0%
CT: A10:
FIBTEM
852s
CFT:
41mm
MCF:
198s
:
48mm ML:
51º 0%
HEPTEM
CT:
63s
CFT:
A10:
6mm
MCF:
-s
:
8mm ML:
-º
CT:
202s
CFT:
0%
A10:
52mm
MCF:
75s
:
58mm ML:
76º 0%
Figure 3 Continued
Management of TIC Hypothermia Hypothermia affects all body systems and is generally classified as mild (32°C-36.5°C), moderate (28°C-32°C), or severe (20°C-28°C). The effects of moderate and severe hypothermia include but are not limited to increases in heart rate, blood pressure, cardiac output, respiratory rate, hematocrit, PT, PTT, and level of D-dimer.6 Moderate to severe hypothermia may cause some forms of coagulopathy, but because it is standard practice to prewarm blood samples to 37°C before testing, this contribution to coagulopathy is rarely picked up by standard laboratory coagulation studies.6,12 Nurses must accurately monitor trauma patients’ core temperature and remember basic hypothermia precautions. They should ensure that the fluid warmer is on and stocked and make every attempt to instill only warmed intravenous fluids. Keep the ambient temperature in the emergency department reasonable (at least 26°C), keep the patient covered, and replace any wet or bloody clothing. Consider using a forced-air warming device or a polymer blanket. Severely hypothermic patients may require pleural or peritoneal lavage or in
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extreme cases cardiopulmonary bypass, hemodialysis, or continuous arteriovenous rewarming, with a goal of a core temperature greater than 36.5°C.1,6,12 Metabolic Acidosis Assess patients for signs of metabolic acidosis such as decreased level of consciousness and tachypnea and monitor laboratory data. Prevention of metabolic acidosis includes prevention and treatment of hypothermia, maintaining hemodynamic stability, avoiding overresuscitation with large amounts of chloride-containing fluids and blood products, and ensuring adequate oxygenation.1 Assess end-organ perfusion parameters including vital signs, level of consciousness, and hourly urinary output. Astute nurses often can identify hypoperfusion before vital signs change markedly. Fluid Resuscitation Nurses must be aware of the type and amount of fluids given in the prehospital setting to help guide the team toward the best options in fluid resuscitation. Avoiding hemodilution from crystalloid fluids and platelet impairment from colloidal fluids demands the attention of the
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trauma team. Rotational thromboelastometry (ROTEM) or the thrombelastograph hemostasis analyzer system (TEG) are valuable point-of-care guides in this process. The American College of Surgeons 2008 Advanced Trauma Life Support for Doctors course11 advises that 2 L of crystalloid fluid be administered to all trauma patients. This practice has been questioned by numerous research studies, and the updated American College of Surgeons 2013 Advanced Trauma Life Support for Doctors course advises administration of 1 L of crystalloid and early use of blood products.20 Current military guidelines restrict fluid resuscitation for patients in shock, are limited for volume, and have specific end points.21,22 Although these guidelines are not an exact parallel of guidelines for civilian trauma, the approach can be considered. Cherkas22 recommends that the current approach to trauma resuscitation be based on the principles of damage control resuscitation. They should include “permissive hypotension, minimization of crystalloid resuscitation, control of hypothermia, prevention of acidosis, and the use of TXA and fixed-ratio blood product transfusion to minimize coagulopathy.”22 TXA is an antifibrinolytic agent that inhibits both plasminogen activation and plasmin activity. In a large high-quality study, those patients receiving TXA had lower mortality and risk of death from bleeding than did patients in the control group.22,23 In the study,23 14.5% of those receiving TXA died, and 16% of those receiving placebo died, this difference was clinically and statistically significant (relative risk, 0.91 and P = .004). Evidence supports the use of intravenous TXA 1g administered in 10 minutes followed by a 1-g intravenous infusion administered in 8 hours in all bleeding trauma patients.21 If definitive bleeding control is established, the patient can be transferred to the intensive care unit, and if not, to the operating room or angiography suite for bleeding control measures.22 The evidence-based clinical pathway for resuscitation in hemorrhagic shock follows the damage control resuscitation pathway. Prehospital interventions should be minimized and the patient rapidly transported to definitive care. The goal of resuscitation in patients with penetrating trauma but no head injuries is a systolic blood pressure of 70-90 mm Hg or normal mentation and peripheral pulses.22 In patients with a traumatic brain injury, an important principle to follow is the avoidance of hypotension.11 Other experts believe it is too soon to adopt a delayed fluid resuscitation strategy, pending
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completion of further prospective studies. It is imperative to monitor all trauma patients’ response to fluid administration, with the goal of end-organ perfusion in mind. Each facility should develop a massive transfusion protocol based on current evidence that applies to the population that they serve. The protocol should include a descriptor of the ratio of fresh frozen plasma (FFP) to packed red blood cells (PRBCs). Holcomb et al24 recommend a FFP:PRBC ratio of 1:1, reporting in a retrospective multicenter trial of 467 patients that the 30-day survival rate was increased with high FFP:PRBC ratios and high platelet:PRBC ratios. They also reported that the combination of high plasma and high platelet to PRBC ratios decreased hemorrhage and increased survival.24 Kaschuk and colleagues18 reviewed 133 trauma patients who received 10 units or more of PRBCs and concluded that those receiving FFP:PRBC at a rate of 1:1 had Trauma teams can use TEG and ROTEM to reduced detect and monitor coagulation problems in coagulopareal time. thy, but the reduced coagulopathy did not necessarily translate into improved survival. In another retrospective study25 in 2010 of 331 patients receiving 5 units of PRBCs or more, researchers concluded that a FFP:RBC ratio of 1:1 had no association with mortality after the first 24 hours, but a lower than 1:1 ratio in the first 4 hours of resuscitation was associated with higher mortality. Further randomized controlled trials must be done to determine the best FFP:PRBC ratio in civilian trauma. It is possible that the point-of-care testing systems of ROTEM or TEG can help guide the component resuscitation therapy to best suit the individual patient. Review Medications Last, take into consideration medications that the patient may be prescribed and how they affect hemostasis. Medications affecting hemostasis, their mechanism of action, and possible reversal agent(s) are listed in the Table.
Conclusion Trauma patients have the potential to experience TIC beginning immediately after injury. Currently, the most appropriate resuscitation strategies are a field of active investigation. Treating and preventing hypothermia, acidosis, hypoperfusion, and excessive hemodilution are important interventions to assist the team in the
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Table
Medications that may interfere with clottinga
Medication
Mechanism
Antiplatelet medicines Aspirin
Reversal
Prevents platelets from aggregating; lasts 7-10 days
Platelets
Clopidogrel Prasugrel Ticagrelor
Inhibits platelet surface receptor for up to 7 days
Platelets
Dipyridamole
Increases adenosine levels
Platelets
Nonsteroidal anti-inflammatory drugs
Prevents platelets form aggregating; lasts ≥2 days
Platelets
Abciximab Eptifibatide
Inhibits platelet binding via glycoprotein IIb/IIIa
Platelets
Inhibits vitamin K–dependent clotting factors
Vitamin K Plasma Prothrombin Complex concentrate
Heparin
Combines with antithrombin to inhibit clotting factors
Protamine Plasma
Enoxaparin
Combines with antithrombin to inhibit clotting factors (Xa and IIa)
Protamine Plasma
Argatroban Lepirudin Bivalrudin Dabigatran
Directly inhibits thrombin
No real antidote, plasma?
Fondaparinux Rivaroxaban Apixiban
Inhibits clotting factor Xa
No real antidote, plasma?, prothrombin complex concentrate?
Converts plasminogen to plasmin, which degrades fibrin
Cryoprecipitate
May cause a decrease in platelet count or platelet dysfunction
None
Anticoagulant medicines Warfarin
Fibrinolytic medicines Alteplase Herbal medicines Anise, garlic, ginger, ginseng, Ginkgo biloba, feverfew a Information
compiled by using data obtained from Barron et al,26 The Food and Drug Administration website,27 and the National Center for Complementary and Alternative Medicine website.28
management of TIC. Medications that interfere with coagulation may be present in severely injured trauma patients, and such patients may require specific therapies to limit ongoing bleeding. Testing with bedside point-of-care tests such as ROTEM and TEG have the potential to limit the morbidity and mortality of TIC because they provide real-time information about the entire coagulation process. Nurses must be aware of the emerging evidence while continuing to employ nursing care activities that prevent, evaluate, and treat TIC. CCN Acknowledgment The authors acknowledge Tom Causer, RN, trauma coordinator at Conemaugh Memorial Medical Center, for his thoughtful suggestions.
Financial Disclosures None reported.
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Now that you’ve read the article, create or contribute to an online discussion about this topic using eLetters. Just visit www.ccnonline.org and select the article you want to comment on. In the full-text or PDF view of the article, click “Responses” in the middle column and then “Submit a response.”
To learn more about trauma care, read “Demographic Differences in Systemic Inflammatory Response Syndrome Score After Trauma” by NeSmith et al in the American Journal of Critical Care, January 2012;21:35-41. Available at www.ajcconline.org. References 1. Lewis AM. Trauma triad of death. Nursing2000. 2000;30(3):62-64. 2. Maegele M, Paffrath T, Bouillon B. Acute traumatic coagulopathy in severe injury: incidence, risk stratification and treatment options. Dtsch Arztebl Int. 2011;108(49):827-835. http://www.ncbi.nlm.nih.gov/pmc /articles/PMC3254043/. Accessed May 12, 2014. 3. Hoffman M, Monroe DM III. A cell-based model of hemostasis. Thromb Haemost. 2001;85:958-965.
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4. Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol. 2002;22:1381-1389. 5. Davidson SJ. Inflammation and acute phase proteins in haemostasis. In: Janciauskiene S, ed. Acute Phase Proteins. 2013. http://www.intechopen .com/books/acute-phase-proteins/inflammation-and-acute-phase -proteins-in-haemostasis. Accessed May 11, 2014. 6. LaPointe LA, Von Rueden KT. Coagulopathies in trauma patients. AACN Clin Issues. 2002;13(2):192-203. 7. Brohi K, Cohen MJ, Ganter MT, Matthay WA, Mackersie RC, Pitter JF. Acute traumatic coagulopathy: initiated by hypoperfusion modulated through the protein C pathway? Ann Surg. 2007;245(5):812-818. doi: 0.1097/01.sla.0000256862.79374.31. 8. Chesebro BB, Rahn P, Carles M, et al. Increase in activated protein C mediates acute traumatic coagulopathy in mice. Shock. 2009;32(6):659665. doi: 10.1097/SHK.0b013d3181a5a632. 9. Jansen JO, Scarpelini S, Pinto R, Tien HC, Callum J, Rizoli SB. Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity. J Trauma. 2011;71(5):S435-S440. doi: 10.1097/TA.0b013e318232e5cb. 10. Theusinger OM, Wanner GA, Emmert MY, et al. Hyperfibrinolysis diagnosed by rotational thromboelastometry (ROTEM) is associated with higher mortality in patients with severe trauma. Anesth Analg. 2011; 113(5):1003-1012. doi: 10.1213/ANE.0b013e31822e183f. 11. Advanced Trauma Life Support for Doctors. Chicago, IL: American College of Surgeons; 2008. 12. Wafaisade A, Wutzler S, Lefering R, et al. Drivers of acute coagulopathy after severe trauma: a multivariate analysis of 1987 patients. J Emerg Med. 2010;27:934-939. doi: 10.1136/emj.2009.088484. 13. Sorensen B, Fries D. Emerging treatment strategies for trauma-induced coagulopathy. Br J Surg. 2012;99(suppl 1):40-50. doi: 10.1002/bjs.7770. 14. Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013; 368:2113-2124. 15. Plotkin AJ, Wade CE, Jenkins DH, et al. A reduction in clot formation rate and strength assessed by thrombelastography is indicative of transfusion requirements in patients with penetrating injuries. J Trauma. 2008;64(2):S64-S67. doi: 10.1097/TA.0b013e318160772d. 16. Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Trans Med Rev. 2012;26(1):1-13. doi: 10.1016/j.tmrv.2011.07.005. 17. Johansson PI. Coagulation monitoring of the bleeding traumatized patient. Curr Opin Anesthesiol. 2012;25:235-241. doi: 10.1097/ACO .0b013e32834fab76. 18. Kaschuk JL, Moore EE, Johnson JL, et al. Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer? J Trauma. 2008;65(2):261-270. doi: 0b012e31817de3e1 19. ROTEM. The bleeding management system website. http://www .rotem.de/site/. Accessed May 12, 2014. 20. Advanced Trauma Life Support for Doctors. Chicago, IL: American College of Surgeons; 2013. 21. Butler F. Fluid resuscitation in tactical combat casualty care: brief history and current status. J Trauma. 2011;79(5):S11-S12. doi: 10.1097/TA .0b013e31821a4b90. 22. Cherkas D. Traumatic hemorrhagic shock: advances in fluid management. Emerg Med Pract. 2011;13(11):1-20. http://www.ebmedicine.net /media_library/marketingLandingPages/Issues/EMP/11.11 /1111%20Store.pdf. Accessed May 12, 2014. 23. Shakur H, Roberts I, Bautista R. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH -2): a randomized, placebo-controlled trial. Lancet. 2010;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. 24. Holcomb JB, Wade CE, Michalek JE. Increased plasma and platelet to red blood cell ratios improves outcomes in 466 massively transfused civilian trauma patients. Ann Surg. 2008;248(3):447-458. doi: 10.1097 /SLA.0b013e318185a9ad. 25. Mitra B, Mori A, Cameron PA, Fitzgerald M, Paul E, Street A. Fresh frozen plasma (FFP) use during massive blood transfusion in trauma resuscitation. Injury. 2010;41(1):35-39. 26. Barron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013; 368:2113-2124. doi: 10.1056/NEJMra1206531. 27. US Food and Drug Administration website. Drugs. http://www.fda.gov /drugs. Accessed May 12, 2014. 28. US Department of Health and Human Services. National Center for Complementary and Alternative Medicine (NCCAM) website. http:// www.nccam.nih.gov. Accessed May 12, 2014.
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Trauma-Induced Coagulopathy Elizabeth D. Katrancha and Luis S. Gonzalez III Crit Care Nurse 2014, 34:54-63. doi: 10.4037/ccn2014133 © 2014 American Association of Critical-Care Nurses Published online http://www.cconline.org
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Critical Care Nurse is the official peer-reviewed clinical journal of the American Association ofCritical-Care Nurses, published bi-monthly by The InnoVision Group 101 Columbia, Aliso Viejo, CA 92656. Telephone: (800) 899-1712, (949) 362-2050, ext. 532. Fax: (949) 362-2049. Copyright © 2011 by AACN. All rights reserved. Downloaded from http://ccn.aacnjournals.org/ at UNIVERSITY OF IOWA on June 1, 2015
Trauma-Induced Coagulopathy ELIZABETH D. KATRANCHA, RN, DNP, CNS, CNE LUIS S. GONZALEZ III, PharmD, BCPS
Coagulopathy is the inability of blood to coagulate normally; in trauma patients, it is a multifactorial and complex process. Seriously injured trauma patients experience coagulopathies during the acute injury phase. Risk factors for trauma-induced coagulopathy include hypothermia, metabolic acidosis, hypoperfusion, hemodilution, and fluid replacement. In addition to the coagulopathy induced by trauma, many patients may also be taking medications that interfere with hemostasis. Therefore, medication-induced coagulopathy also is a concern. Traditional laboratory-based methods of assessing coagulation are being supported or even replaced by point-of-care tests. The evidence-based management of trauma-induced coagulopathy should address hypothermia, fluid resuscitation, blood components administration, and, if needed, medications to reverse identified coagulation disorders. (Critical Care Nurse. 2014;34[4]:54-63)
A
trauma patient’s greatest risk of death after the first 24 hours of injury stems from a combination of 3 conditions: hypothermia, acidosis, and coagulopathy.1,2 Nurses caring for trauma patients must be aware of these factors and how to manage them in an evidence-based manner. This article is focused on seriously injured trauma patients and the coagulopathies that they experience in the acute phase of injury. It provides an overview of coagulation and explores risk factors for trauma-induced coagulopathy. In addition to the coagulopathy induced by trauma, many patients may also be taking medications that interfere with hemostasis. Therefore, medication-induced coagulopathy is reviewed. We briefly review current evidence-based guidelines for blood component and fluid management and the role of thromboelastography (TEG or ROTEM) point-of-care diagnostic tools in the assessment and management of trauma-induced coagulopathies (TIC).
Normal Physiological Mechanisms of Coagulation A large body of research has resulted in better defining how coagulation takes place. This cell-based model of coagulation has replaced the traditional version of the intrinsic and extrinsic coagulation cascade system. This cell-based model consists of 3 phases that overlap one another: initiation, amplification, and propagation3,4 (Figure 1). The initiation phase begins when the blood vessel wall is injured, exposing tissue factor. When plasma containing factor VIIa comes in contact with cells bearing tissue factor, the 2 factors form a complex.3,4 This complex then activates factors IX and X. Factor Xa complexes with factor Va to form thrombin (factor IIa) in small amounts. ©2014 American Association of Critical-Care Nurses doi: http://dx.doi.org/10.4037/ccn2014133
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II
X
Initiation TF
VIIa
Xa
Propagation
IIa
Va
Tissue factor–bearing cell TF VIIa
Tissue factor–bearing cell
IX
TF VIIa
IXa
II
VIIIa + free vWF XI
VIII/vWF
TFPI Xa TF VIIa
Xa
Va
Tissue factor–bearing cell
XIa
VIIIa
IIa
XIa
Platelet
V
V
XIa
Va
II
X
IXa
Amplification
IX
IXa
Xa
VIIIa
Va
IIa
Activated platelet
IX
Va
Activated platelet
Figure 1 Cell-based model of coagulation. Abbreviations: TF, tissue factor; TFPI, tissue factor pathway inhibitor; vWF, von Willebrand factor. Reproduced from Davidson,5 with permission.
The amplification stage begins with thrombin binding to and activating platelets that have adhered to the site of injury.3,4 The activated platelets secrete partially activated factor V, which becomes fully activated by the action of thrombin. Thrombin activates factor IX and cleaves the factor VIII/von Willebrand complex, releasing factor VIII. At this point, activated platelets bind factors Va, VIIIa, and Xa.4 The propagation step starts with factor IXa diffusing from its site of activation on the tissue factor–bearing Authors Elizabeth D. Katrancha is an instructor of nursing in the baccalaureate nursing program at the University of Pittsburgh at Johnstown. Luis S. Gonzalez III is a clinical pharmacist at Conemaugh Memorial Medical Center in Johnstown, Pennsylvania. Corresponding author: Elizabeth D. Katrancha, RN, MSN, CNS, CNE, University of Pittsburgh at Johnstown, 216 Nursing and Health Sciences, 450 Schoolhouse Road, Johnstown, PA 15904 (e-mail: [email protected]). To purchase electronic or print reprints, contact the American Association of CriticalCare Nurses, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 899-1712 or (949) 362-2050 (ext 532); fax, (949) 362-2049; e-mail, [email protected].
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cell and attaching to the surface of activated platelets. Factors IXa and VIIIa form a complex, which then activates platelet-bound factor X. Finally, factor Xa binds to factor Va on the platelet surface, resulting in a burst of thrombin formation that results in the generation of a clot.3 There are also naturally occurring anticoagulants that regulate coagulation, including antithrombin, protein C, protein S, and plasmin.
Etiology Coagulopathy is simply the inability of blood to coagulate normally; however, in trauma patients, it is a multifactorial and complex process. Abnormal coagulation can result from depletion, dilution, or inactivation of normal clotting factors.6 TIC is precipitated by massive tissue injury and is a multifactorial problem, currently thought to be confounded by hypothermia, acidosis, hypoperfusion, and hemodilution. The triad of hypothermia, acidosis, and hypotension occurring together cause the greatest risk of mortality.2 CriticalCareNurse
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Pathophysiology Protein C has been implicated in several studies in the development of TIC. As hypoperfusion occurs, protein C is converted to activated protein C (APC).7-9 APC inhibits cofactors V and VIII, reducing thrombin generation.7,9 Tissue plasminogen activator also plays a role in fibrinolysis; APC reduces inhibition of tissue plasminogen activator, which in turn accelerates the conversion of plasminogen to plasmin.7 Fibrinolysis The cell-based model of coagulation con- is imporsists of 3 overlapping phases: initiation, tant in amplification, and propagation. maintaining homeostasis by localizing clot formation to damaged endothelium.10 In TIC, a hyperfibrinolysis restricts coagulation and allows the trauma patient to bleed excessively.
Risk Factors Hypothermia Patients involved in trauma face exposure to the environment beginning at the moment of the incident. Prehospital personnel often remove clothing in order to assess the patient thoroughly. Intravenous fluids are administered and may be at room temperature or below. Upon arrival in the emergency department, patients are again exposed in order for diagnostic testing such as focused assessment with sonography for trauma examination, radiography, and a secondary survey to be performed. Some drugs such as muscle relaxants, sedatives, anesthetics, and opioids also can reduce a patient’s body temperature. Metabolic Acidosis Hypoperfusion of tissues results in decreased oxygen delivery and the conversion to anaerobic metabolism via the citric acid cycle, resulting in lactic acid accumulation. Resuscitation with fluids containing large amounts of chloride combined with hypothermia contributes to the metabolic acidosis through the development of a nonanion gap acidosis. Laboratory values of pH less than 7.4, elevated serum level of lactate, and base deficits reaching 10 mmol/L reduce the activity of various coagulation factors by up to 40%.4,11 Base deficit is the amount of base required by a liter of whole arterial blood to normalize the pH to 7.4 and as such is an indicator
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of the severity of the acidosis. This metabolic acidosis results in coagulation system disorders such as prolonged clotting times and reduced clot strength.6,12 Hypoperfusion, Hemodilution, and Fluid Resuscitation Recent studies have indicated that despite injury severity, patients who are hypoperfused experience coagulopathies.8,10,12 Wafaisade et al12 report that a systolic blood pressure less than 90 mm Hg correlated with a 3 times greater risk of coagulopathy developing. Brohi et al7 hypothesize that hypoperfusion of tissues leads to increased levels of soluble thrombomodulin. Thrombomodulin combines with and inhibits thrombin, and this complex activates protein C. APC impairs clot formation and increases existing clot dissolution.7,9 Hypoperfusion should not be confused with permissive hypotension, which may be a strategy employed in damage-control resuscitation. Bleeding trauma patients are often volume resuscitated with crystalloids, colloids, packed red blood cells, and fresh frozen plasma. These volume-resuscitating efforts may result in a dilutional coagulopathy. Researchers have reported an association between coagulopathy and receiving 3000 mL or more of intravenous fluids before arriving at the hospital. The long-accepted approach of immediate delivery of 2 L of isotonic crystalloids after trauma may exacerbate coagulopathy.11,13 Medications A large segment of the population is taking prescribed and even over-the-counter antithrombotic medications. Although the contribution of antithrombotic medications to the development of TIC is unknown at this time, being aware of these medications and their effect on hemostasis may facilitate resuscitation efforts. Antithrombotic therapy is indicated for the treatment and prevention of many common diseases. The most common are atrial fibrillation, coronary artery disease, and deep vein thrombosis.14 Four categories of medications prevent normal clotting: antiplatelets, anticoagulants, fibrinolytics (not routinely used in outpatients), and herbals. The common coagulation studies of activated partial thromboplastin time (aPTT), prothrombin time/international normalized ratio (PT/INR), platelet count, and fibrinogen levels evaluate only certain points in the coagulation process and take time to be measured in the laboratory. In addition, the presence of many medications affecting hemostasis would not be detected by routine coagulation studies.
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100 80
Amplitude (firmness), mm
60 40
MCF
ML
A10 20
alpha
LI30
0
CT CFT alpha A10 MCF LI30 ML
CFT CT 0
10
20
30
Clotting time Clot formation time Alpha-angle Amplitude 10 min after CT Maximum clot firmness Lysis index 30 min after CT Maximum lysis
40
50
60
Time, min
Figure 2 ROTEM parameters. Reprinted from ROTEM website,19 with permission. Copyright TEM International GmbH.
Methods of Assessing Coagulation in TIC The coagulation profile (PT, aPTT, fibrinogen concentration, and platelet count) can take up to 30 minutes to process in the laboratory and measures only clot initiation.15 Thrombelastograph hemostasis analyzer system (TEG, Haemonetics Corp) and rotational thromboelastometry (ROTEM, Tem International Gmbh) are devices that are used by trauma teams to detect and monitor coagulation disarray in a real-time environment.10,16,17 TEG and ROTEM are both used to assess elastic changes in clotting whole blood. Whole blood is placed in a heated cup that contains a pin connected to a detector system. The cup and pin oscillate relative to one another and at an angle. Fibrin forms between the cup and the pin, and a tracing is generated. The tracing is divided into parts that reflect the various stages of coagulation over time. These parameters assist the trauma team in deciding which drugs and blood components to administer. Commonly reported ROTEM results are reaction time (R), clotting time (CT), clot formation time (K, CFT), alpha angle (), maximum amplitude (MA), maximum clot firmness (MCF), and lysis (ly).18 Test parameters commonly reported are EXTEM, INTEM, FIBTEM, and APTEM. EXTEM is an extrinsic screening test in which CT is not sensitive for heparin. The INTEM is an intrinsic screening test in which CT is sensitive for heparin. In
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both EXTEM and INTEM, amplitude and CFT are influenced by fibrinogen and platelets. FIBTEM reports activation the same as EXTEM but platelet inhibition reagent is added. In APTEM, the activation is the same as in EXTEM; however, fibrinolysis inhibition is induced with aprotinin.19 HEPTEM is specific to heparin effect on coagulation.19 The analysis, printed in graph form, provides information from the beginning of clot formation until dissolution, concentration activity of coagulation factors, effects of anticoagulants, fibrin generation, and platelet count and function. Figure 2 illustrates the parameters measured in a ROTEM tracing, and Figure 3 illustrates interpretations of ROTEM results. It is helpful to note the areas on the report that correspond to the various stages of clot forma- Commonly reported ROTEM results are reaction. The tion time, clotting time, clot formation time, results of alpha angle, maximum amplitude, maximum this point- clot firmness, and lysis. of-care coagulation test guide the trauma team’s fluid and blood component resuscitation strategies, providing real-time information on which to base decisions to administer fresh frozen plasma, platelets, cryoprecipitate, tranexamic acid (TXA), or other coagulation factor concentrates.16
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Normal patient:
EXTEM
INTEM
CT:
67s
CFR:
CFT:
54mm MCF:
87s : 57mm ML:
73º -%
CT: CFR:
FIBTEM CT:
CFT:
54mm MCF:
67s
:
61mm ML:
77º -%
APTEM 66s
CFR:
200s
CFT:
9mm MCF:
-s : 10mm ML:
57º
CT:
-%
CFR:
74s
CFT:
53mm MCF:
89s
:
61mm ML:
72º -%
Platelet deficiency:
EXTEM CT: A10:
INTEM :
57s
CFT:
444s
23mm
MCF:
35mm ML:
80º
CT:
200s
CFT:
-%
A10:
23mm
MCF:
-º
CT:
-%
A10:
FIBTEM CT: A10:
449s
:
32mm ML:
72º -%
APTEM 67s
CFT:
15mm
MCF:
-s : 16mm ML:
52s
CFT:
398s
25mm
MCF:
35mm ML:
:
80º -% Continued
Figure 3 ROTEM result interpretations. The assessment of the ROTEM analysis is carried out along the time axis (from left to right). A disturbed activation of coagulation is indicated by a prolonged clotting time (CT). As causes, a factor deficiency or heparin effects have to be considered. The comparison of INTEM and HEPTEM allows specific detection of a heparin effect. An abnormal clot formation is indicated by a prolonged clot formation time (CFT) and/or a reduced maximum clot firmness (MCF). The CFT is thereby influenced more strongly by a clot polymerization disorder than the MCF. A prolonged CFT, with at the same time a normal MCF, indicates therefore a polymerization disorder, whereas a reduced MCF with a normal CFT rather indicates a deficiency of clottable substrate (fibrinogen and/or platelets). Fibrinolysis is detected by the lysis of the clot (maximum lysis [ML] >15%) or by the finding of a better clot formation (shorter CFT, greater MCF) in APTEM as compared with EXTEM. Several centers already use, in massive bleeding, a shortening of the CT in APTEM, as compared with EXTEM, as a trigger for administration of an antifibrinolytic drug. Parameters EXTEM, INTEM, FIBTEM, APTEM, and HEPTEM are explained in text. Reprinted from ROTEM website,19 with permission. Copyright TEM International GmbH.
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Fibrinogen deficiency:
EXTEM
INTEM
CT:
109s
CFT:
A10:
31mm
MCF:
263s
:
38mm ML:
48º
CT:
-%
A10:
-º
CT:
-%
A10:
FIBTEM
236s
CFT:
33mm
MCF:
220s
:
42mm ML:
55º -%
APTEM
CT:
185s
CFT:
A10:
3mm
MCF:
-s
:
3mm ML:
98s
CFT:
31mm
MCF:
276s
:
40mm ML:
46º -%
Hyperfibrinolysis:
EXTEM CT: A10:
INTEM 59s
CFT:
130s
44mm
MCF:
48mm ML:
:
65º 100%
CT:
200s
CFT:
A10:
46mm
MCF:
FIBTEM CT: A10:
88s
:
48mm ML:
74º 100%
APTEM 51s
CFT:
7mm
MCF:
-s : 7mm ML:
-º
CT:
94%
A10:
62s
CFT:
132s
44mm
MCF:
55mm ML:
:
64º 0% Continued
Figure 3 Continued
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Heparin influence:
INTEM
EXTEM CT: A10:
67s
CFT:
50mm
MCF:
104s
:
57mm ML:
68º 0%
CT: A10:
FIBTEM
852s
CFT:
41mm
MCF:
198s
:
48mm ML:
51º 0%
HEPTEM
CT:
63s
CFT:
A10:
6mm
MCF:
-s
:
8mm ML:
-º
CT:
202s
CFT:
0%
A10:
52mm
MCF:
75s
:
58mm ML:
76º 0%
Figure 3 Continued
Management of TIC Hypothermia Hypothermia affects all body systems and is generally classified as mild (32°C-36.5°C), moderate (28°C-32°C), or severe (20°C-28°C). The effects of moderate and severe hypothermia include but are not limited to increases in heart rate, blood pressure, cardiac output, respiratory rate, hematocrit, PT, PTT, and level of D-dimer.6 Moderate to severe hypothermia may cause some forms of coagulopathy, but because it is standard practice to prewarm blood samples to 37°C before testing, this contribution to coagulopathy is rarely picked up by standard laboratory coagulation studies.6,12 Nurses must accurately monitor trauma patients’ core temperature and remember basic hypothermia precautions. They should ensure that the fluid warmer is on and stocked and make every attempt to instill only warmed intravenous fluids. Keep the ambient temperature in the emergency department reasonable (at least 26°C), keep the patient covered, and replace any wet or bloody clothing. Consider using a forced-air warming device or a polymer blanket. Severely hypothermic patients may require pleural or peritoneal lavage or in
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extreme cases cardiopulmonary bypass, hemodialysis, or continuous arteriovenous rewarming, with a goal of a core temperature greater than 36.5°C.1,6,12 Metabolic Acidosis Assess patients for signs of metabolic acidosis such as decreased level of consciousness and tachypnea and monitor laboratory data. Prevention of metabolic acidosis includes prevention and treatment of hypothermia, maintaining hemodynamic stability, avoiding overresuscitation with large amounts of chloride-containing fluids and blood products, and ensuring adequate oxygenation.1 Assess end-organ perfusion parameters including vital signs, level of consciousness, and hourly urinary output. Astute nurses often can identify hypoperfusion before vital signs change markedly. Fluid Resuscitation Nurses must be aware of the type and amount of fluids given in the prehospital setting to help guide the team toward the best options in fluid resuscitation. Avoiding hemodilution from crystalloid fluids and platelet impairment from colloidal fluids demands the attention of the
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trauma team. Rotational thromboelastometry (ROTEM) or the thrombelastograph hemostasis analyzer system (TEG) are valuable point-of-care guides in this process. The American College of Surgeons 2008 Advanced Trauma Life Support for Doctors course11 advises that 2 L of crystalloid fluid be administered to all trauma patients. This practice has been questioned by numerous research studies, and the updated American College of Surgeons 2013 Advanced Trauma Life Support for Doctors course advises administration of 1 L of crystalloid and early use of blood products.20 Current military guidelines restrict fluid resuscitation for patients in shock, are limited for volume, and have specific end points.21,22 Although these guidelines are not an exact parallel of guidelines for civilian trauma, the approach can be considered. Cherkas22 recommends that the current approach to trauma resuscitation be based on the principles of damage control resuscitation. They should include “permissive hypotension, minimization of crystalloid resuscitation, control of hypothermia, prevention of acidosis, and the use of TXA and fixed-ratio blood product transfusion to minimize coagulopathy.”22 TXA is an antifibrinolytic agent that inhibits both plasminogen activation and plasmin activity. In a large high-quality study, those patients receiving TXA had lower mortality and risk of death from bleeding than did patients in the control group.22,23 In the study,23 14.5% of those receiving TXA died, and 16% of those receiving placebo died, this difference was clinically and statistically significant (relative risk, 0.91 and P = .004). Evidence supports the use of intravenous TXA 1g administered in 10 minutes followed by a 1-g intravenous infusion administered in 8 hours in all bleeding trauma patients.21 If definitive bleeding control is established, the patient can be transferred to the intensive care unit, and if not, to the operating room or angiography suite for bleeding control measures.22 The evidence-based clinical pathway for resuscitation in hemorrhagic shock follows the damage control resuscitation pathway. Prehospital interventions should be minimized and the patient rapidly transported to definitive care. The goal of resuscitation in patients with penetrating trauma but no head injuries is a systolic blood pressure of 70-90 mm Hg or normal mentation and peripheral pulses.22 In patients with a traumatic brain injury, an important principle to follow is the avoidance of hypotension.11 Other experts believe it is too soon to adopt a delayed fluid resuscitation strategy, pending
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completion of further prospective studies. It is imperative to monitor all trauma patients’ response to fluid administration, with the goal of end-organ perfusion in mind. Each facility should develop a massive transfusion protocol based on current evidence that applies to the population that they serve. The protocol should include a descriptor of the ratio of fresh frozen plasma (FFP) to packed red blood cells (PRBCs). Holcomb et al24 recommend a FFP:PRBC ratio of 1:1, reporting in a retrospective multicenter trial of 467 patients that the 30-day survival rate was increased with high FFP:PRBC ratios and high platelet:PRBC ratios. They also reported that the combination of high plasma and high platelet to PRBC ratios decreased hemorrhage and increased survival.24 Kaschuk and colleagues18 reviewed 133 trauma patients who received 10 units or more of PRBCs and concluded that those receiving FFP:PRBC at a rate of 1:1 had Trauma teams can use TEG and ROTEM to reduced detect and monitor coagulation problems in coagulopareal time. thy, but the reduced coagulopathy did not necessarily translate into improved survival. In another retrospective study25 in 2010 of 331 patients receiving 5 units of PRBCs or more, researchers concluded that a FFP:RBC ratio of 1:1 had no association with mortality after the first 24 hours, but a lower than 1:1 ratio in the first 4 hours of resuscitation was associated with higher mortality. Further randomized controlled trials must be done to determine the best FFP:PRBC ratio in civilian trauma. It is possible that the point-of-care testing systems of ROTEM or TEG can help guide the component resuscitation therapy to best suit the individual patient. Review Medications Last, take into consideration medications that the patient may be prescribed and how they affect hemostasis. Medications affecting hemostasis, their mechanism of action, and possible reversal agent(s) are listed in the Table.
Conclusion Trauma patients have the potential to experience TIC beginning immediately after injury. Currently, the most appropriate resuscitation strategies are a field of active investigation. Treating and preventing hypothermia, acidosis, hypoperfusion, and excessive hemodilution are important interventions to assist the team in the
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Table
Medications that may interfere with clottinga
Medication
Mechanism
Antiplatelet medicines Aspirin
Reversal
Prevents platelets from aggregating; lasts 7-10 days
Platelets
Clopidogrel Prasugrel Ticagrelor
Inhibits platelet surface receptor for up to 7 days
Platelets
Dipyridamole
Increases adenosine levels
Platelets
Nonsteroidal anti-inflammatory drugs
Prevents platelets form aggregating; lasts ≥2 days
Platelets
Abciximab Eptifibatide
Inhibits platelet binding via glycoprotein IIb/IIIa
Platelets
Inhibits vitamin K–dependent clotting factors
Vitamin K Plasma Prothrombin Complex concentrate
Heparin
Combines with antithrombin to inhibit clotting factors
Protamine Plasma
Enoxaparin
Combines with antithrombin to inhibit clotting factors (Xa and IIa)
Protamine Plasma
Argatroban Lepirudin Bivalrudin Dabigatran
Directly inhibits thrombin
No real antidote, plasma?
Fondaparinux Rivaroxaban Apixiban
Inhibits clotting factor Xa
No real antidote, plasma?, prothrombin complex concentrate?
Converts plasminogen to plasmin, which degrades fibrin
Cryoprecipitate
May cause a decrease in platelet count or platelet dysfunction
None
Anticoagulant medicines Warfarin
Fibrinolytic medicines Alteplase Herbal medicines Anise, garlic, ginger, ginseng, Ginkgo biloba, feverfew a Information
compiled by using data obtained from Barron et al,26 The Food and Drug Administration website,27 and the National Center for Complementary and Alternative Medicine website.28
management of TIC. Medications that interfere with coagulation may be present in severely injured trauma patients, and such patients may require specific therapies to limit ongoing bleeding. Testing with bedside point-of-care tests such as ROTEM and TEG have the potential to limit the morbidity and mortality of TIC because they provide real-time information about the entire coagulation process. Nurses must be aware of the emerging evidence while continuing to employ nursing care activities that prevent, evaluate, and treat TIC. CCN Acknowledgment The authors acknowledge Tom Causer, RN, trauma coordinator at Conemaugh Memorial Medical Center, for his thoughtful suggestions.
Financial Disclosures None reported.
62
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To learn more about trauma care, read “Demographic Differences in Systemic Inflammatory Response Syndrome Score After Trauma” by NeSmith et al in the American Journal of Critical Care, January 2012;21:35-41. Available at www.ajcconline.org. References 1. Lewis AM. Trauma triad of death. Nursing2000. 2000;30(3):62-64. 2. Maegele M, Paffrath T, Bouillon B. Acute traumatic coagulopathy in severe injury: incidence, risk stratification and treatment options. Dtsch Arztebl Int. 2011;108(49):827-835. http://www.ncbi.nlm.nih.gov/pmc /articles/PMC3254043/. Accessed May 12, 2014. 3. Hoffman M, Monroe DM III. A cell-based model of hemostasis. Thromb Haemost. 2001;85:958-965.
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4. Monroe DM, Hoffman M, Roberts HR. Platelets and thrombin generation. Arterioscler Thromb Vasc Biol. 2002;22:1381-1389. 5. Davidson SJ. Inflammation and acute phase proteins in haemostasis. In: Janciauskiene S, ed. Acute Phase Proteins. 2013. http://www.intechopen .com/books/acute-phase-proteins/inflammation-and-acute-phase -proteins-in-haemostasis. Accessed May 11, 2014. 6. LaPointe LA, Von Rueden KT. Coagulopathies in trauma patients. AACN Clin Issues. 2002;13(2):192-203. 7. Brohi K, Cohen MJ, Ganter MT, Matthay WA, Mackersie RC, Pitter JF. Acute traumatic coagulopathy: initiated by hypoperfusion modulated through the protein C pathway? Ann Surg. 2007;245(5):812-818. doi: 0.1097/01.sla.0000256862.79374.31. 8. Chesebro BB, Rahn P, Carles M, et al. Increase in activated protein C mediates acute traumatic coagulopathy in mice. Shock. 2009;32(6):659665. doi: 10.1097/SHK.0b013d3181a5a632. 9. Jansen JO, Scarpelini S, Pinto R, Tien HC, Callum J, Rizoli SB. Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity. J Trauma. 2011;71(5):S435-S440. doi: 10.1097/TA.0b013e318232e5cb. 10. Theusinger OM, Wanner GA, Emmert MY, et al. Hyperfibrinolysis diagnosed by rotational thromboelastometry (ROTEM) is associated with higher mortality in patients with severe trauma. Anesth Analg. 2011; 113(5):1003-1012. doi: 10.1213/ANE.0b013e31822e183f. 11. Advanced Trauma Life Support for Doctors. Chicago, IL: American College of Surgeons; 2008. 12. Wafaisade A, Wutzler S, Lefering R, et al. Drivers of acute coagulopathy after severe trauma: a multivariate analysis of 1987 patients. J Emerg Med. 2010;27:934-939. doi: 10.1136/emj.2009.088484. 13. Sorensen B, Fries D. Emerging treatment strategies for trauma-induced coagulopathy. Br J Surg. 2012;99(suppl 1):40-50. doi: 10.1002/bjs.7770. 14. Baron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013; 368:2113-2124. 15. Plotkin AJ, Wade CE, Jenkins DH, et al. A reduction in clot formation rate and strength assessed by thrombelastography is indicative of transfusion requirements in patients with penetrating injuries. J Trauma. 2008;64(2):S64-S67. doi: 10.1097/TA.0b013e318160772d. 16. Bolliger D, Seeberger MD, Tanaka KA. Principles and practice of thromboelastography in clinical coagulation management and transfusion practice. Trans Med Rev. 2012;26(1):1-13. doi: 10.1016/j.tmrv.2011.07.005. 17. Johansson PI. Coagulation monitoring of the bleeding traumatized patient. Curr Opin Anesthesiol. 2012;25:235-241. doi: 10.1097/ACO .0b013e32834fab76. 18. Kaschuk JL, Moore EE, Johnson JL, et al. Postinjury life threatening coagulopathy: is 1:1 fresh frozen plasma:packed red blood cells the answer? J Trauma. 2008;65(2):261-270. doi: 0b012e31817de3e1 19. ROTEM. The bleeding management system website. http://www .rotem.de/site/. Accessed May 12, 2014. 20. Advanced Trauma Life Support for Doctors. Chicago, IL: American College of Surgeons; 2013. 21. Butler F. Fluid resuscitation in tactical combat casualty care: brief history and current status. J Trauma. 2011;79(5):S11-S12. doi: 10.1097/TA .0b013e31821a4b90. 22. Cherkas D. Traumatic hemorrhagic shock: advances in fluid management. Emerg Med Pract. 2011;13(11):1-20. http://www.ebmedicine.net /media_library/marketingLandingPages/Issues/EMP/11.11 /1111%20Store.pdf. Accessed May 12, 2014. 23. Shakur H, Roberts I, Bautista R. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH -2): a randomized, placebo-controlled trial. Lancet. 2010;376(9734):23-32. doi: 10.1016/S0140-6736(10)60835-5. 24. Holcomb JB, Wade CE, Michalek JE. Increased plasma and platelet to red blood cell ratios improves outcomes in 466 massively transfused civilian trauma patients. Ann Surg. 2008;248(3):447-458. doi: 10.1097 /SLA.0b013e318185a9ad. 25. Mitra B, Mori A, Cameron PA, Fitzgerald M, Paul E, Street A. Fresh frozen plasma (FFP) use during massive blood transfusion in trauma resuscitation. Injury. 2010;41(1):35-39. 26. Barron TH, Kamath PS, McBane RD. Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med. 2013; 368:2113-2124. doi: 10.1056/NEJMra1206531. 27. US Food and Drug Administration website. Drugs. http://www.fda.gov /drugs. Accessed May 12, 2014. 28. US Department of Health and Human Services. National Center for Complementary and Alternative Medicine (NCCAM) website. http:// www.nccam.nih.gov. Accessed May 12, 2014.
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Trauma-Induced Coagulopathy Elizabeth D. Katrancha and Luis S. Gonzalez III Crit Care Nurse 2014, 34:54-63. doi: 10.4037/ccn2014133 © 2014 American Association of Critical-Care Nurses Published online http://www.cconline.org
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