1499Vol. 11 | No. 02 | March- April 2014 |U R O LO G Y J O U R N A L Non Invasive Management of Refractory Hemorrhage after Renal Surgery with Factor VIIa: Report of 3 Cases Wadah Ceifo,1 Adel Al Tawheed,2 Aischa Fakeir3 Corresponding Author: Wadah Ceifo, MD Departments of Surgery, Urology Unit, Al-Jahra Hospital, Ministry of health, P.O. Box: 40206, Al-Jahra, Kuwait. Tel: +965 9739 0065 Fax: +965 4570 858 E-mail: wceifo@yahoo.de Received June 2012 Accepted January 2013 Departments of Surgery and Urology1,2 and Hematology Units,3 Al Jahra Hospital, Al- Qasr, Al-Jahra, Kuwait. CASE REPORT Keywords:‎blood‎loss;‎surgical;‎prevention;‎control;‎urologic‎surgical‎procedures,‎adverse‎ef- fects;‎intraoperative‎complications;‎kidney;‎surgery. IINTRODUCTION Recombinant‎activated‎factor‎VII‎(rFVIIa)‎is‎a‎vitamin‎K-dependent‎glycoprotein‎consisting‎of‎406‎amino‎acid‎residues‎(molecular‎weight‎50‎K‎Dalton).(1) It is struc-turally‎similar‎ to‎human‎plasma-derived‎factor‎VIIa.(2)‎Over‎the‎last‎few‎years,‎ rFVIIa‎has‎been‎used‎“off-label”‎in‎patients‎with‎uncontrolled‎bleeding‎due‎to‎occult‎he- mostatic‎abnormality‎caused‎by‎trauma‎and/or‎massive‎blood‎loss,(3,4)‎ thrombocytopenia,‎ platelet‎dysfunction‎or‎liver‎dysfunction‎‎and‎many‎other‎situations‎characterized‎by‎critical‎ bleeding.(5)‎We‎present‎our‎experience‎of‎the‎successful‎use‎of‎‎rFVIIa‎to‎treat‎life‎threaten- ing‎hemorrhage‎in‎3‎patients‎who‎had‎refractory‎hemorrhage‎following‎surgical‎procedures‎ on‎the‎kidney.‎ CASE REPORT Three‎previously‎healthy‎males,‎without‎pre-existing‎coagulopathy,‎presented‎with‎staghorn‎ calculus‎(n‎=‎2)‎and‎a‎large‎renal‎pelvic‎calculus‎(n‎=‎1).‎Two‎patients‎were‎subjected‎to‎per- 1500 | cutaneous‎nephrolithotomy‎(PCNL)‎and‎one‎had‎open‎py- elolithotomy.‎In‎one‎case‎during‎PCNL,‎there‎was‎pneumo- hemothorax‎and‎retroperitoneal‎bleeding‎up‎to‎day‎5‎after‎ the‎ procedure.‎ In‎ the‎ other‎ case‎ of‎ PCNL,‎ uncontrollable‎ hemorrhage‎occurred‎on‎day‎13‎following‎removal‎of‎PCNL‎ tube.‎Profuse‎bleeding‎started‎on‎day‎5‎in‎the‎patient‎with‎py- elolithotomy.‎All‎3‎patients‎were‎initially‎managed‎by‎blood‎ transfusions.‎ When‎ hemorrhage‎ persisted‎ despite‎ blood‎ transfusions‎and‎the‎patients‎became‎hemodynamically‎un- stable,‎intravenous‎rFVIIa‎was‎given‎at‎a‎dose‎of‎60-90‎µg/ kg.‎The‎clinical‎characteristics‎and‎treatment‎response‎of‎all‎ the‎3‎cases‎are‎shown‎in‎Table‎1.‎Blood‎products‎usage‎and‎ change‎in‎coagulation‎profile‎before‎and‎24‎hours‎after‎ad- ministration‎of‎rFVIIa‎is‎summarized‎in‎Table‎2. DISCUSSION The‎Tissue‎‎Factor‎‎is‎exposed‎‎and‎‎forms‎‎a‎complex‎‎with‎‎ rFVIIa‎‎following‎‎injury‎‎to‎the‎vessel‎‎wall.(6)‎This‎complex‎ activates‎factor‎X‎which‎leads‎to‎‎conversion‎‎of‎‎prothrombin‎‎ to‎thrombin,‎‎and‎‎activation‎‎of‎platelets,‎greatly‎enhanced‎ thrombin‎ generation,‎ and‎ activation‎ of‎ thrombin‎ activated‎ fibrinolysis‎ ‎ inhibitor‎ ‎ (TAFI).(6)‎ rFVIIa‎ ‎ is‎used‎ ‎ to‎ treat‎ patients‎with‎hemophilia‎A‎and‎B,(7)‎also‎‎for‎the‎treatment‎‎ of‎life‎threatening‎‎hemorrhage‎in‎the‎setting‎of‎coagulopa- thy disorders,(8,9)‎blunt‎and‎penetrating‎trauma‎and‎surgical‎ bleeding.(10)‎rFVIIa,‎can‎‎minimize‎‎blood‎‎loss‎‎and‎‎need‎‎ for‎blood‎‎transfusion‎prior‎to‎retropubic‎‎prostatectomy(11)‎ or in patients on platelet aggregation inhibitors, prior to renal transplantation.(12,13) As‎shown‎on‎Table‎1,‎our‎study‎demonstrated‎the‎effective- ness‎of‎intravenous‎(IV)‎administration‎of‎rFVIIa‎in‎late‎on- set‎bleeding‎after‎renal‎surgery.‎In‎all‎3‎cases,‎hemorrhage‎ subsided‎after‎rFVIIa‎administration.‎It‎is‎possible‎for‎bleed- ing to occur again in a patient that has shown response to initial‎administration‎of‎ rFVIIa.‎ From‎ our‎ third‎patient,‎ it‎ would‎appear‎that‎future‎responses‎to‎IV‎administration‎of‎ rFVIIa‎can‎be‎expected‎with‎repeated‎dosing.‎Table‎2‎shows‎ the‎possible‎mechanism‎of‎action‎of‎IV‎rFVIIa‎usage.‎‎In‎all‎ 3‎patients‎the‎hemoglobin‎remained‎stable‎and‎there‎was‎an‎ improvement‎in‎prothrombin‎time‎(PT),‎partial‎thromboplas- tin‎time‎(PTT)‎and‎international‎normalized‎ratio‎(INR)‎after‎ IV‎rFVIIa‎administration.‎Angiography‎with‎embolization‎of‎ any‎bleeding‎vessels‎is‎the‎standard‎method‎of‎dealing‎with‎ significant‎hemorrhage‎from‎the‎kidney‎after‎renal‎surgery. (13)‎However,‎in‎some‎cases,‎the‎bleeding‎vessels‎may‎be‎dif- ficult‎to‎identify.‎What‎is‎more,‎when‎bleeding‎is‎from‎other‎ sources‎like‎lumbar‎vessels‎and‎etc.,‎as‎an‎adjuvant‎prior‎to‎ embolization,‎IV‎administration‎of‎rFVIIa‎is‎worth‎a‎trial.‎ The‎advantage‎of‎IV‎rFVIIa‎administration‎over‎angiogra- phy‎and‎embolism‎is‎that,‎it‎does‎not‎require‎any‎expertise‎ to‎administer‎and‎it‎is‎easier‎and‎quicker‎to‎use‎than‎angio- embolization.‎Furthermore,‎in‎patients‎in‎extremis,‎IV‎rFVIIa‎ can‎be‎used‎easily.‎None‎of‎our‎patients‎experienced‎any‎fur- ther‎episodes‎of‎bleeding‎after‎a‎mean‎follow‎up‎of‎about‎6‎ months.‎Similarly,‎there‎was‎no‎loss‎of‎renal‎function‎from‎ the‎affected‎kidneys.‎When‎there‎is‎any‎clinical‎or‎laboratory‎ signs‎of‎presence‎of‎thrombosis,(14)‎the‎rFVIIa‎dosage‎should‎ be‎reduced‎or‎stopped,‎depending‎on‎the‎patient’s‎symptoms.‎ CONCLUSION This‎study‎revealed‎that‎administration‎of‎rFVIIa‎is‎a‎prom- ising‎treatment‎option‎for‎patients‎undergoing‎renal‎surgery‎ Table 1. Clinical and imaging features of the series. Case Age, years/sex Primary Diagnosis Coagulopathy Dosage (µg/kg) Clinical Efficacy* Complications Death 1 43/Male Partial right stage horn stone No 90 Yes None No 2 39/Male Right renal pelvic stone No 60 Yes None No 3 51/Male Left lower calyceal stone No 60a Yes None No Key: rFVIIa, recombinant activated factor VII. a Multiple doses administered. * Defined as marked reduction or cessation of post-operative hemorrhage. Case Report 1501Vol. 11 | No. 02 | March- April 2014 |U R O LO G Y J O U R N A L Management of Refractory Hemorrhage after Renal Surgery | Ceifo et al complicated‎with‎life-threatening‎hemorrhage.‎It‎seems‎to‎be‎ both‎effective‎and‎safe.‎However,‎further‎research‎is‎required‎ to‎extend‎the‎approval‎of‎this‎product‎in‎urologic‎procedures‎ while‎assessing‎potential‎complications. CONFLICT OF INTEREST None declared. Table 2. Study parameters in patients who received four rFVIIa replacement therapies before and 24 hours after treatment. Case PRBC (U) FFP (U) Platelets (U) Hb PT PTT INR PRBC (U) FFP (U) Platelets (U) Hb PT PTT INR 1 3 0 0 8.8 11.6 34.4 0.0913 0 0 0 10.1 10.2 28.7 0.0767 2 2 0 0 9.6 11.0 35.1 0.0912 0 0 0 10.6 10.7 27.8 0.0765 3a 2 0 0 9.2 11.2 34.3 0.0911 0 0 0 10.1 10.3 27.8 0.0870 3b 2 0 0 9.1 11.7 34.2 0.0913 0 0 0 10.2 10.1 27.7 0.0760 Keys: rFVIIa, recombinant activated factor VII; PRBC, packed red blood cells; FFP, fresh frozen plasma; U, units; Hb, hemoglobin; PT, prothrombin time; PTT, partial thromboplastin time; INR, international normalized ratio. Hb in g/dL. a, first administration of rFVIIa in case 3. b, second administration of rFVIIa in case 3. REFERENCES 1. Hedner U. Recombinant coagulation factor VIIa: from the concept to clinical application in haemophilia treatment in 2000. Semin Thromb Hemost. 2000;26:363-6. 2. Lisman T, Mosnier LO, Lambert T, et al. 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