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.
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.
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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