The paper describe the use of rFVIIa in the management of massive bleeding in a patient with polytrauma involving
liver injury. An 18-year-old girl with severe polytrauma sustained during a bus–car collision. She had multiple musculoskeletal
injuries, severe concussion of the liver with amputation of the left liver lobe, disruption of the left hepatic
vein from the inferior vena cava, and impaired hemostasis. Acute bleeding (>5 L) was not improved by conservative
methods and a single dose of rFVIIa 90 g/kg was administered. Infusion of rFVIIa resulted in an immediate clinical effect
with rapid improvements in blood laboratory measurements and coagulation parameters. rFVIIa should be considered
as an adjunctive treatment for the control of hemorrhage in severely injured patients with uncontrolled bleeding
and impaired hemostasis

Branka Maldini

Ivan Zvonimir Lubina

Senka Baranović

Tatjana Nikolić

English

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Coll. Antropol. 35 (2011) 1: 193–196Case reportSuccessful Use of Recombinant Factor VIIain Traumatic Liver Injury – A Case ReportSenka Baranovi}1, Ivan Zvonimir Lubina2, Tatjana Nikoli}3 and Branka Maldini41 University of Zagreb, University Hospital of Traumatology, Department of Anesthesiology and Intensive Care Unit, Zagreb,Croatia2 University of Zagreb, University Hospital of Traumatology, Department of Radiology, Zagreb, Croatia3 University of Zagreb, University Hospital of Traumatology, Department of Physical Medicine and Rehabilitation, Zagreb,Croatia4 University of Zagreb, »Sveti Duh« University Hospital, Department of Anesthesiology and Intensive Care Unit, Zagreb, CroatiaA B S T R A C TThe paper describe the use of rFVIIa in the management of massive bleeding in a patient with polytrauma involvingliver injury. An 18-year-old girl with severe polytrauma sustained during a bus–car collision. She had multiple mus-culoskeletal injuries, severe concussion of the liver with amputation of the left liver lobe, disruption of the left hepaticvein from the inferior vena cava, and impaired hemostasis. Acute bleeding (>5 L) was not improved by conservativemethods and a single dose of rFVIIa 90 g/kg was administered. Infusion of rFVIIa resulted in an immediate clinical ef-fect with rapid improvements in blood laboratory measurements and coagulation parameters. rFVIIa should be consid-ered as an adjunctive treatment for the control of hemorrhage in severely injured patients with uncontrolled bleedingand impaired hemostasis.Key words: recombinant FVIIa, polytrauma, liver, coagulopathy, hemorrhage, hemostasisIntroductionPolytrauma is a life-threatening condition character-ized by severe blunt trauma with injuries to multiple or-gan systems, generally including musculoskeletal andabdominal organ injuries, and extensive soft tissue in-jury. Individuals with polytrauma are at a high risk ofsystemic soft tissue inflammation, contusions and ede-ma1, and most require massive blood volume replace-ment together with implementation of treatment strate-gies for adequate and safe bleeding control2,3.Surgery followed by blood-product transfusion suc-cessfully manages hemorrhage and hemostatic instabil-ity in many polytrauma patients, but some patients con-tinue to bleed uncontrollably. Persistent blood loss is amajor cause of trauma-related deaths and the mortalityrisk is further increased by the inevitable consequencesof hemodilution, hypothermia, acidosis and coagulopa-thy4. Initial treatment for intractable hemorrhage in-volves blood-component therapy (e.g. packed red bloodcells PRBC, fresh frozen plasma FFP). Massive bloodtransfusion may be required in the most severe cases,but this is associated with serious complications such asinfection and multiple organ failure4–8. In recent years, anumber of pharmacotherapies have become available(e.g. desmopressin, tranexamic acid, aprotinin) to beused when surgery is insufficient to curb the bleedingand also to reduce transfusion requirements9.Recombinant factor VIIa (rFVIIa, Novo Nordisk, Bag-svaerd, Denmark) is a hemostatic agent that is approvedin over 50 countries worldwide for the management ofspontaneous or surgical hemorrhage in patients withbleeding disorders. Evidence from investigational researchhas indicated that rFVIIa may also be effective in intrac-table bleeding episodes of varying etiology in non-hemo-philia patients10. Indeed, effective use of rFVIIa in atrauma situation was first reported in 1999 when bleed-ing was stopped in a patient with a serious rifle injuryfollowing unsuccessful surgical intervention and blood--product transfusion11. Successful hemorrhage controlwith adjunctive rFVIIa in patients with severe traumahas since been demonstrated in a number of case re-193Received for publication July 18, 2010ports12–20, as well as two randomized, placebo-controlled,double-blind clinical trials21. The present case report de-scribes the use of rFVIIa in the management of massivebleeding in a female patient with polytrauma involvingliver injury.Case ReportAn 18-year-old girl sustained severe polytrauma as apassenger on a bus involved in a bus–car collision, andwas transferred by ambulance to the University Hospitalof Traumatology in Zagreb. On admission, the patientwas somnolent and amnestic of the event, with a Glas-gow Coma Score (GCS) of 13, Trauma Score (TS) of 12,and she was hemodynamically unstable (tachycardia,120 beats/min; blood pressure, 90/60 mmHg). She com-plained of pain in the abdomen, back and right he-mithorax. Clinical examination revealed right thorax de-formity and, on auscultation, there was shallow breathingon the right side with subcutaneous emphysema. Neuro-logical status was normal with preserved motoricity of allfour extremities. Peripheral venous lines were insertedfor volume replacement with crystalloid and colloid infu-sions and analgesia was administered with morphine at adose of 0.1 mg/kg. Emergency diagnostic assessmentswere conducted, including x-ray, ultrasonography andcomputed tomography (CT).The patient was found to have multiple musculo-skeletal injuries. Intrathoracic x-ray revealed fractureand cranial dislocation of the seventh and eighth ribs onthe right, along with pleural effusion.The right side ofthe thorax was distorted, with a visible gap of approxi-mately 10 cm between the inferior ribs. X-ray of the spineshowed T6 fracture without fracture fragment migrationto the spinal canal.The patient remained free from neu-rological deficit and brain CT was normal but had a se-verely painful, tight and distended abdomen. After ad-mission to the intensive care unit, abdominal ultraso-nography and CT scan revealed a large amount of freeintraperitoneal fluid on the right, along the lateral livermargin and left liver lobe. Extensive free fluid was alsoobserved in the pelvis minor, close to the bladder. Labora-tory test results of slightly lower hemoglobin (98 g/L;normal range, 115–165 g/L) and hematocrit level (0.31;normal range, 0.36–0.47), normal prothrombin time (PT14.6 s; normal range is usually within the range of 10–15seconds), metabolic acidosis (with base excess of –8mmol/L) and increased lactate levels (3.0 mmol/L; nor-mal range, 0.5–2.2 mmol/L, Table 1).Emergency laparotomy revealed severe concussion ofthe liver with amputation of the left liver lobe and dis-ruption of the left hepatic vein from the inferior venacava. Acute blood loss was estimated to be approximately5 L, so replacement therapy with 4.5 L of crystalloids and1 L of colloids plus 7.5% NaCl (4 mL/kg) was adminis-tered. The patient’s marked hemodynamic instabilitycontinued, indicated by a second laboratory assessment(reduced hemoglobin 35 g/L, hematocrit 0.11 and plate-lets 117 x 109/L, prolonged PT 18.9 s and aPTT 38.2 s,low fibrinogen 0.7 g/L, Table 1) as well as systolic bloodpressure of approximately 60 mmHg and tachycardia of140 beats/min. Consequently, inotropic support with no-repinephrine (0.02–0.04 g/kg/min) was introduced in-traoperatively and, prior to ligature of the blood vessels,a single dose of rFVIIa 90 g/kg was administered. Animmediate clinical effect of the rFVIIa was observed, andresection of the left liver lobe and suture of the inferiorvena cava were performed. During the 3-hour surgicalprocedure, blood loss exceeded one circulating blood vol-ume so massive blood transfusion was required (15 unitsof PRBC; 8 units of FFP, 15 mL/kg and 8 units of plate-lets).Laboratory assessment 6 hours after surgery showedthat blood counts had near-normalized following the ad-ministration of rFVIIa: hemoglobin increased to 110 g/Land hematocrit to 0.32 (Table 1). Similarly, improve-ments in coagulation parameters meant that they wereclose to or within the reference ranges (PT of 12.6 s;aPTT of 24 s; fibrinogen of 2 g/L). Metabolic acidosis wascorrected, while the level of lactate decreased from 3mmol/L to 1.2 mmol/L within 24 hours of trauma.Postoperatively, the patient was connected to a me-chanical respiratory device, extubated within 24 hours ofthe injury and the right hemithorax was drained. Coagu-lation factors were found to be within or close to theirreference ranges 4 days after rFVIIa administration (Ta-ble 2). Posterior spondylosis of the thoracic spine wasidentified 12 days after the injury and corrected with sur-gical intervention. The patient was discharged from hos-pital in good general condition 20 days after admission.A CT scan of the abdomen was performed on the eightpostoperative day after liver resection. It shows the con-dition after resection of the left liver lobe with signs ofpancreatic contusion and low level of ascites.S. Baranovi} et al.: Use of Recombinant Factor VIIa in Traumatic Liver Injury, Coll. Antropol. 35 (2011) 1: 193–196194TABLE 1LABORATORY PARAMETERS BEFORE AND AFTER rFVIIa ADMINISTRATIONHemoglobin (g/L) Hematocrit Platelets (x109/L) PT (s) aPTT (s) Fibrinogen (g/L)D-dimers(mg/mL)On admissionBefore rFVIIaAfter rFVIIaAt discharge9835110790.310.110.320.2427711711818914.618.912.614.422.738.224.027.81.90.72.03.0No data1.20.60.3aPTT – activated partial thromboplastin time, PT – prothrombin timeDiscussionIn this case study, adjunctive treatment with a singledose of rFVIIa (90 g/kg) proved useful in the control ofsevere hemorrhage due to polytrauma and involvingblunt liver injury. The liver plays a crucial role in the reg-ulation of coagulation factors and injury may impairhemostasis resulting in massive bleeding, as seen in thispatient6,22. Blunt liver trauma is a major cause of deathin patients with abdominal injury, with reported mortal-ity rates of 11–21% potentially increasing to 50–67% insevere cases; most deaths are attributed to exsanguina-tions13,23–28. As blood loss is usually severe in patientswith polytrauma involving the liver, frequently exceed-ing one circulating blood volume, replacement therapywith high volumes of crystalloids and colloids, as well astransfusion of multiple blood products, is generally nec-essary in order to maintain normovolemia and to preventhypoxemia29. However, such treatment causes dilution ofcoagulation factors and platelets, and ultimately leads toconsumption coagulopathy.The present case illustrates the typical clinical pic-ture of polytrauma with liver injury. Despite the severityof the situation, treatment with rFVIIa in conjunctionwith surgical intervention led to hemorrhage controlwith rapid improvements in blood laboratory measure-ments and coagulation parameters.The mechanism of action of rFVIIa in non-hemophiliapatients is yet to be established; pharmacological dosesdirectly activate factor IX on the surfaces of activatedplatelets, in the absence of tissue factor, leading to forma-tion of additional tenase complexes, and improved throm-bin generation, clot structure and clot stability at the siteof injury30.The effectiveness of rFVIIa in our case patient adds tothe evidence of its beneficial effects in blunt trauma inju-ries shown in clinical trials21 and case reports13,14,17–20.ConclusionThis report indicates that rFVIIa may be useful as anadjunctive treatment for the control of hemorrhage intraumatized patients and may reduce the need to admin-ister blood products; in many cases, coagulation parame-ters are normalized. Although associated with additionalcosts, early hemorrhage control through rFVIIa adminis-tration can reduce the risk of infection transmission andcosts associated with blood product transfusion. Investi-gations to determine the optimal therapeutic use of rFVIIain non-hemophilia patients with uncontrolled bleedingare warranted.R E F E R E N C E S1. PEPE PE, BMJ, 327 (2003) 1119. — 2. GOWERS CJD, PARR MJA,Anaesth Intensive Care, 33 (2005) 96. — 3. DUTTON RP, HESS JR, SCA-LEA TM, J Clin Anesth, 15 (2003) 184. — 4. SPAHN DR, ROSSAINT R,Br J Anaesthesia, 95 (2005) 130. — 5. ARMAND R, HESS JR, TransfusMed Rev, 17 (2003) 223. — 6. GROUNDS M, Blood Rev, 17 (2003) S11. —7. HARDY JF, Can J Anaesth, 49 (2002) S4. — 8. HOYT DB, Semin He-matol, 41 (2004) 40. — 9. CHIU J, KETCHUM LH, REID TJ, Curr OpinHematol, 9 (2002) 544. — 10. ERHARDTSEN E, Intensive Care Med, 28(2002) S248. — 11. KENET G, WALDEN R, ELDAD A, MARTINOWITZU, Lancet, 354 (1999) 1897. — 12. 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GIRGIN S, GEDIK E, TACYIL-DIZ IH, Ulus Travma Acil Cerrahi Derg, 12 (2006) 35. — 24. GAO J, DUD, ZHAO X, LIU G, YANG J, ZHAO S, LIN X, Chin J Traumatol, 5 (2002)346. — 25. GAO JM, DU DY, ZHAO XJ, World J Surg, 27 (2003) 703. —26. GUR S, ORSEL A, ATAHAN K, HOKMEZ A, TARCAN E, Hepato-gastroenterology, 50 (2003) 2109. — 27. COLOMBO F, SANSONNA F,BATICCI F, CORSO R, SCANDROGLIO I, MAGGIONI D, Di LERNIA S,FERRARI GC, MAGISTRO C, COSTANZI A, PUGLIESE R, Chir Ital, 57(2005) 695. — 28. DUANE TM, COMO JJ, BOCHICCHIO GV, SCALEATM, J Trauma, 57 (2004) 494. — 29. STEIN DM, DUTTON RP, Curr OpinCrit Care, 10 (2004) 520. — 30. GABRIEL DA, LI X, MONROE DM, ROB-ERTS HR, J Thromb Haemost, 10 (2004) 1816.S. Baranovi}University of Zagreb, University Hospital of Traumatology, Department of Anesthesiology and Intensive Care Unit,Dra{kovi}eva 19, 10 000 Zagreb, Croatiae-mail: senka.baranovic1@zg.t-com.hrS. Baranovi} et al.: Use of Recombinant Factor VIIa in Traumatic Liver Injury, Coll. Antropol. 35 (2011) 1: 193–196195TABLE 2COAGULATION FACTORS 4 DAYS AFTER rFVIIaADMINISTRATIONCoagulationfactorDay 4 after rFVIIaReference value(kIU/L)Factor IIFactor VFactor VII0.781.270.690.75–1.200.75–1.200.70–1.20USPIJE[NA PRIMJENA AKTIVIRANOG REKOMBINANTNOG FAKTORA VIIa KOD TRAUMATSKEOZLIJEDE JETRE: PRIKAZ SLU^AJAS A @ E T A KAktivirani rFVIIa je dobro hemostatsko sredstvo u zbrinjavanju krvarenja kod bolesnika sa hemofilijom i inhibi-torima faktora VIII ili IX. Tako|er se uspje{no upotrebljava u kontroli krvarenja u kirur{kih bolesnika u traumi i»non-hemophilia« koagulopatija kod kojih je ugro`en `ivot zbog nekontrolibilnog krvarenja. Politrauma u okviru te{kihozljeda lokomotornog sustava sa pridru`enim o{te}enjem abdominalnih organa je za `ivot opasno stanje, koje zahtjevaveliku nadoknadu volumena i krvnih pripravaka, te adekvatnu i sigurnu kontrolu krvarenja. Donosimo vam prikazslu~aja primjene rFVIIa u zbrinjavanju masivnog krvarenja kod politraumatizirane bolesnice sa dominantnom ozlije-dom jetre.S. Baranovi} et al.: Use of Recombinant Factor VIIa in Traumatic Liver Injury, Coll. Antropol. 35 (2011) 1: 193–196196

Successful Use of Recombinant Factor VIIa in Traumatic Liver Injury – A Case Report

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