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Correction of Severe Coagulopathy and Hyperfibrinolysis by Tranexamic Acid and Recombinant Factor VIIa in a Cirrhotic Patient After Trauma: A Case Report

Louro, Jack MD*; Andersen, Katherine MD; Dudaryk, Roman MD*

doi: 10.1213/XAA.0000000000000550
Case Reports: Case Report

Coagulopathy induced by trauma or cirrhosis is a well-recognized entity. Viscoelastic testing has been used in either condition for goal-directed transfusion and detection of fibrinolysis since conventional coagulation tests do not correlate with clinical risk of bleeding. Hemostatic resuscitation may not be adequate for a trauma patient with liver disease due to complex alterations in coagulation systems and occasionally require adjuvant therapy. We report a case of trauma-induced coagulopathy presenting as severe hyperfibrinolysis in a cirrhotic patient who was refractory to hemostatic resuscitation but was rapidly corrected by the administration of tranexamic acid and recombinant Factor VIIa.

From the *Department of Clinical Anesthesiology, University of Miami, Miami, Florida; and Anesthesiology Resident, University of Miami, Jackson Memorial Hospital, Miami, Florida.

Accepted for publication February 28, 2017.

Funding: None.

The authors declare no conflicts of interest.

Address correspondence to Roman Dudaryk, MD, Department of Anesthesiology, Perioperative Medicine, and Pain Management, University of Miami Miller School of Medicine, 1611 NW 12th Ave (T-215), Miami, FL 33136. Address e-mail to

Trauma and liver disease are well-known independent contributors to coagulopathy. Severe injury produces primary trauma-induced coagulopathy (TIC) and secondary coagulopathy due to pathophysiologic changes such as acidosis, hypothermia, hemodilution, and factor consumption.1 Cirrhosis produces coagulopathy due to hepatic synthetic dysfunction of factors and proteins involved in the hemostatic, coagulation, and fibrinolytic systems.2

Cirrhotic patients after trauma have worse outcomes than noncirrhotic patients. This effect is more pronounced in patients requiring laparotomies and is mostly due to persistent uncontrolled bleeding.3,4 Monitoring of coagulation parameters and correction of the coagulopathy of these patients can be challenging.5 We present the case of a cirrhotic patient after trauma with severe coagulopathy and hyperfibrinolysis as evidenced by a thromboelastogram (TEG) and clinical observation of diffuse microvascular bleeding that was resistant to conventional hemostatic resuscitation. Written informed consent for publication was obtained from the patient’s health care proxy.

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A 69-year-old man with an unclear medical history presented to the trauma resuscitation bay in stable condition after an isolated blunt abdominal injury due to a motor vehicle collision. The patient was disoriented but admitted to having a history of hypertension and liver disease from alcohol abuse of unknown severity. Laboratory studies obtained on arrival to the resuscitation bay demonstrated a prothrombin time (PT) of 18.7 seconds with international normalized ratio (INR) of 1.66 and a platelet count of 103, suggestive of liver disease. An abdominal computed tomography scan performed while the patient remained hemodynamically stable revealed contrast extravasation from the spleen and retroperitoneal injury. The patient’s Injury Severity Score was 17 without major injuries outside of the abdominal cavity. Shortly after imaging, the patient developed hemodynamic instability with mean arterial pressures dropping below 60 mm Hg and was taken to the operating room approximately 2.5 hours after arrival for an emergent exploratory laparotomy and splenectomy.

Intraoperatively, there was significant bleeding from the left upper quadrant, which was explored and packed, and a splenectomy was performed. Massive transfusion protocol (MTP) and hemostatic resuscitation with 1:1:1 ratio of packed red blood cells, fresh frozen plasma, and platelets was initiated at the time when the patient was scheduled for emergency laparotomy. Intraoperatively, we targeted a blood pressure goal of 90 mm Hg systolic and mean arterial pressure of 60 mm Hg. The patient was also observed to have a small, hard, and nodular-appearing liver consistent with advanced liver disease along with significant varices throughout the upper abdomen. The spleen was removed and colon, mesenteric and gastrosplenic ligament vessels were ligated, achieving control of anatomical sources of bleeding. Nevertheless, the patient became increasingly tachycardic and hypotensive. Diffuse persistent microvascular bleeding with little clotting was observed throughout the abdomen. At this juncture, the patient had received approximately 25 units of packed red blood cells, 20 units of fresh frozen plasma, 30 units of platelets, and 10 units of cryoprecipitate. The patient had been kept normothermic near 37°C and had improving lactic acidosis with most recent pH of 7.2. A Rapid TEG (Haemonetics, Braintree, MA) was performed and revealed profound derangements of coagulation manifested as prolongation of activated clotting time, decreased maximum amplitude and most notably severe hyperfibrinolysis (Figure 1). A multidisciplinary discussion among an experienced trauma surgeon, trauma anesthesiologist, critical care team, and a clinical pharmacist was done in an expedited fashion, and the decision to proceed with the administration of recombinant factor VIIa (FVIIa) in addition to a dose of tranexamic acid (TXA) was made. MTP was continued, along with administration of the bolus dose of 1 g of TXA and 1 mg of FVIIa. Of note, TXA was not given on admission because the patient was transferred to our center after more than 3 hours from the time of injury. Approximately 30 minutes after the administration of the loading dose of TXA and FVIIa, a repeat TEG showed almost complete correction of the coagulopathy (Figure 2). Clinically, the patient exhibited marked improvement in clot formation with a dry surgical field providing better visualization for the surgical team with timely completion of the damage control surgery.

Figure 1.

Figure 1.

Figure 2.

Figure 2.

After surgery, the patient remained intubated and mechanically ventilated and admitted to an intensive care unit (ICU). Postoperative laboratory values demonstrated correction of the PT and INR with values of 14 seconds and 1.2, respectively. In the immediate postoperative period, the patient did not show evidence of rebleeding or clot deterioration. Although the patient required 40 units of packed red blood cells intraoperatively, only 2 units of packed red blood cells were given in the ICU. The patient later went on to develop acute kidney injury and severe acute respiratory distress syndrome as the day progressed. With multisystem organ failure and his significant medical comorbidities, the family decided to withdraw life-sustaining care on the first postoperative day. This was based on the patient’s known wishes to avoid prolonged intubation and hospitalization. The patient died on the second postoperative day. From ICU arrival until the time of death, no signs of coagulopathy or bleeding were noted.

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Advanced liver disease frequently alters conventional tests of hemostasis. Abnormal values of PT, INR, and activated partial thromboplastin time may not reflect increased risk of bleeding during invasive procedure in patients with liver disease.6 Trauma patients with liver disease represent a particular challenge because such abnormalities of coagulation tests may represent either baseline liver dysfunction, acute TIC, or a combination of both. Hemostatic resuscitation using a conventional MTP may not be adequate in a trauma patient with liver disease due to complex alterations of both pro- and anticoagulant systems. In our case, the use of viscoelastic testing allowed the diagnosis of TIC and profound hyperfibrinolysis resistant to MTP, which was successfully corrected with TXA and off-label use of FVIIa.

TIC is a well-described phenomenon that is triggered by inflammatory pathways after acute tissue injury.1 Hyperfibrinolysis has been implicated as a part of the TIC. Hemostatic resuscitation has become the standard of care for trauma patients and encompasses the early use of plasma and platelets with a packed red blood cell:plasma:platelet ratio of 1:1:1 in the initial phase of resuscitation.7 Early use of TXA has been demonstrated to have a survival benefit after trauma.8

Patients with cirrhosis are at increased risk for coagulopathy. There is a decreased production of factors II, VII, IX, X that are procoagulant, along with an increase in tissue plasminogen activator that can destabilize clot. At the same time, patients with liver disease have reduced production of the anticoagulant factors: antithrombin, proteins C and S, resulting in so-called rebalanced hemostasis.5,6 Frequently, the net effect of these changes is adequate in vivo coagulation despite grossly abnormal conventional coagulation tests. Many cirrhotic patients also suffer from fibrinolysis further complicating their ability to achieve hemostasis.2 With the administration of fresh-frozen plasma containing both pro- and anticoagulant factors, conventional laboratory values of coagulation such as PT and INR may improve, without correction of the coagulation deficiency. In fact, some argue that fresh-frozen plasma monotherapy in a patient with liver disease may elevate both pro- and anticoagulant proteins without significant net effect on hemostasis.9 In general, abnormal PT and partial thromboplastin time values are of limited benefit in patients with advanced liver disease as many will have normal viscoelastic testing and lack clinical coagulopathy.6 These traditional measures such as activated partial thromboplastin time can be inaccurate due to elevated levels of FVIII in liver disease. In many instances, the traditional coagulation tests have been unable to predict the risk of bleeding during procedures in patients with liver disease and can be explained as these tests were designed to measure anticoagulant medication effect rather than in vivo coagulation in disease state.5,6 TEG, on the other hand, has some prognostic value for determining rebleeding from esophageal varices in cirrhotic patients despite normal traditional coagulation tests.2 The utility of viscoelastic testing in liver disease as well as its potential survival benefit when used to guide resuscitation in trauma make it a uniquely valuable tool for patients with pre-existing coagulopathies suffering from trauma.6,7

Blunt abdominal trauma in a cirrhotic patient has a high mortality and has been referred to as the “deadly duo.”4 Trauma patients with cirrhosis have a 20-fold increase in mortality compared to noncirrhotic trauma patients with the same injury severity even without undergoing surgery. If surgical intervention is required, the increase in mortality in the cirrhotic trauma patients is even higher.4

FVIIa is mainly used as replacement therapy in hemophilia. Off-label administration has been described for correction of coagulopathy stemming from liver failure, trauma, and intracranial hemorrhage.2,6 As early as the 1990s, there are reports of using FVIIa for successful treatment of traumatic bleeding. One retrospective study demonstrated decreased mortality when FVIIa was used during massive transfusion after combat trauma.10 However, later randomized controlled trials have shown that the use of FVIIa reduces the amount of blood product required in trauma without demonstrating any mortality benefit11 and raised questions about the increased risk of thrombotic complications.12 Despite mixed data with FVIIa for off-label use in trauma, recent studies seem to indicate that although there is no mortality difference with the use of FVIIa, there is also no significant increase in the rate of thromboembolism. One potential benefit exists in the reduction of acute respiratory distress syndrome, which could be related to the reduced number of blood products used in resuscitation.13,14 Although at this point, the use of FVIIa is not supported as a standard therapy in trauma patients due to its high cost and limited evidence for outcomes benefit, it is still reserved for select cases of extreme coagulopathy resistant to conventional hemostatic resuscitation.7,13

In our case, despite massive 1:1:1 transfusion ratio of packed red blood cells, fresh-frozen plasma, and platelets along with cryoprecipitate, severe derangement of all values was evident on TEG and the patient continued to bleed diffusely. While there is evidence for the use of TXA for fibrinolysis in trauma patients, we felt the severe hyperfibrinolysis superimposed on advanced liver disease and profound TIC in this case would not respond to a single agent. A recent study looking at TEG patterns of hyperfibrinolysis identified a subgroup with the TEG pattern seen in our patient described as the “death diamond” with a steep rise to early maximal amplitude and severe hyperfibrinolysis returning to baseline. In this study, mortality in the patients with the “death diamond” pattern was 100% even though many received antifibrinolytics.15 In our case, we decided to add FVIIa to overcome the clot initiation deficiency, as FVIIa combines with tissue factor to initiate the coagulation cascade, and it is commonly deficient in cirrhotic patients due to its short half-life compared to other coagulation factors.2 After administration of TXA and FVIIa, the TEG values normalized, and the patient showed clinical improvement in clot formation. The changes in the TEG and clinically evident hemostasis were noted just 30 minutes after the administration of FVIIa and TXA. Although FVIIa is not indicated for the routine use in trauma patients, it is occasionally used as a last resort drug. It is unclear if the rapid correction of the TEG would have been achieved with either agent in isolation, but the concurrent administration of FVIIa and TXA created a procoagulant milieu that corrected the TEG and stopped the bleeding rapidly.

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Name: Jack Louro, MD.

Contribution: This author helped write the case report, and analyze the literature.

Name: Katherine Andersen, MD.

Contribution: This author helped write the case report, analyze the literature, and acquire the data.

Name: Roman Dudaryk, MD.

Contribution: This author helped care for the patient, revise the case report, and analyze the literature.

This manuscript was handled by: Richard P. Dutton, MD.

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