Angelillo-Scherrer, Anne

Cotting, Jacques

Eggimann, Philippe

Perez, Marie-Hélène

Schneider, Antoine

Schoettker, Patrick

Tozzi, Piergiorgio

Voirol, Pierre

Von Segesser, Ludwig

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Antoine G. SchneiderMarie-He´le`ne PerezPiergiorgio TozziPierre VoirolPatrick SchoettkerAnne Angelillo-ScherrerJacques CottingLudwig Von SegesserPhilippe EggimannRecombinant factor VIIafor intractable life-threateningbleeding in patientswith circulatory assist devicesAccepted: 27 April 2010Published online: 3 June 2010 Copyright jointly held by Springer andESICM 2010Dear Editor,Circulatory assist devices requiretight anticoagulation therapy and maybe complicated by severe bleeding.Despite warnings related to potentiallethal thrombotic complications, off-label use of recombinant factor VIIa(rFVIIa) is increasingly reported forrefractory hemorrhage, includingafter cardiac surgery [1, 2]. However,its use in patients with circulatoryassist devices has seldom beenreported and its safety remains tobe established [3–5].We reviewed 12 consecutivepatients with surgically implanteddevices who received rFVIIa asrescue treatment for intractable life-threatening bleeding between March2004 and November 2009 (Table 1).According to strict and constringentlocal consensus guidelines, a sys-tematic cross-check for aggressivecorrection of hypothermia, acidosis,and coagulation factors with parallelsurgical control for bleeding orembolization was obtained beforerFVIIa administration in all cases.The median age of patientswas 45 years. The rFVIIa wasadministered in the operating room(3/12), in the intensive care unit(7/12), or both (2/12). Underlyingconditions were cardiovascularsurgery (11/12, including 4 hearttransplantations) and bipulmonarytransplantation (1/12). The devicewas an extracorporal membraneoxygenator (9/12) and a left ventric-ular assist device (3/12). Median doseof rFVIIa was 95 lg/kg (45–180),administered in one (3/12) or severaldoses (9/12).In these otherwise terminalpatients, the bleeding assessed by thenumber of ml/kg of packed red bloodcells and fresh frozen plasmarequirement within 12 h before andafter rFVIIa administration was sig-nificantly reduced. Six patients (50%)died within 30 days, including 2(18%) from persistent bleeding. Acareful analysis of coagulation andother physiological parameters didnot reveal significant differencebetween responders andnon-responders.Table 1 Patient characteristicsAge(years)Typeof deviceTotal doseof rFVIIa(lg/kg)Numberof dosesThrombo-emboliceventDeviceclottingPRBC requirements(ml/kg)FFP requirements(ml/kg)Outcome at30 days12 hbefore12 hafterD(%)12 hbefore12 hafterD(%)1 10 ECMO 180 2 No No 96.0 75.0 -22 26.8 35.7 33 Alive2 \1 ECMO 180 2 No No 270.0 77.0 -71 160 42 -74 Death day 7 frommultiple organfailure3 15 ECMO 45 1 No No 22.8 35.9 57 10.9 21.7 99 Alive4 \1 ECMO 180 2 Stroke No 130.0 37.0 -72 111 107 -4 Death day 2 fromhemorrhage5 55 ECMO 105 1 No No 182.6 6.5 -96 76.1 21.7 -71 Alive6 51 ECMO 90 3 No No 66.3 34.9 -47 52.3 34.9 -33 Death day 9 fromcardiogenicshock7 43 LVAD 100 2 No No 105.0 40.0 -62 75 20.8 -72 Alive8 47 ECMO 54 1 No No 31.4 45.3 44 34.9 49.4 42 Death day 1 fromhemorrhage9 49 LVAD 60 2 No No 33.8 11.3 -67 25 6.3 -75 Alive10 63 LVAD 76 3 No No 34.7 6.3 -82 34.2 5.3 -85 Death day 18 fromseptic shock11 46 ECMO 126 2 No No 88.4 18.9 -79 63.2 26.3 -58 Death day 7 fromseptic shock12 25 ECMO 47 2 No No 144.0 56.0 -61 100 43.3 -57 AliveECMO extracorporal membrane oxygenator; LVAD Thoratec IVAD as left ventricular assist device; PRBC packed red blood cells (300ml per unit), D p = 0.007 by Wilcoxon T test; FFP fresh frozen plasma (250 ml per unit), D p = 0.007 by Wilcoxon T testIntensive Care Med (2010) 36:1620–1621DOI 10.1007/s00134-010-1937-y CORRESPONDENCEIn all cases, adequate anticoagula-tion was further maintained and nocircuit thrombosis occurred; hence nodevice required replacement. Onethromboembolic complication occur-red (a stroke) in a neonate followingcardiac arrest after a Jatene switch.The relationship between this eventand the rFVIIa administrationremained unclear.We conclude that after meticulouscontrol for all other potential con-tributing factors, the careful use ofsmall and if necessary repeated dosesof rFVIIa (25–30 lg/kg), allowed oneto control life-threatening intractablebleeding in 9/12 patients with surgi-cally implanted circulatory assistancedevices without any clot of thedevices. As suggested by currentguidelines, these data confirm pre-liminary reports [3–5], but the safetyof rFVIIa in this context should nowbe confirmed by controlled trials inlarger groups of patients.References1. Karkouti K, Beattie WS, Arellano R,Aye T, Bussieres JS, Callum JL, ChengD, Heinrich L, Kent B, Lee TW,MacAdams C, Mazer CD, Muirhead B,Rochon AG, Rubens FD, Sawchuk C,Wang S, Waters T, Wong BI, Yau TM(2008) Comprehensive Canadian reviewof the off-label use of recombinantactivated factor VII in cardiac surgery.Circulation 118:331–3382. Dunning J, Versteegh M, Fabbri A, PavieA, Kolh P, Lockowandt U, Nashef SA(2008) Guideline on antiplatelet andanticoagulation management in cardiacsurgery. Eur J Cardiothorac Surg 34:73–923. Veldman A, Neuhaeuser C, Akintuerk H,Thul J, Gehron J, Schranz D, Michel-Behnke I (2007) rFVIIa in the treatmentof persistent hemorrhage in pediatricpatients on ECMO following surgery forcongenital heart disease. PaediatrAnaesth 17:1176–11814. Agarwal HS, Bennett JE, ChurchwellKB, Christian KG, Drinkwater DC Jr, HeY, Taylor MB (2007) Recombinantfactor seven therapy for postoperativebleeding in neonatal and pediatriccardiac surgery. Ann Thorac Surg84:161–1685. Gandhi MJ, Pierce RA, Zhang L, MoonMR, Despotis GJ, Moazami N (2007)Use of activated recombinant factor VIIfor severe coagulopathy post ventricularassist device or orthotopic hearttransplant. J Cardiothorac Surg 2:32A. G. Schneider ())  P. EggimannDivision of Adult Intensive Care Medicine,Centre Hospitalier Universitaire Vaudois(CHUV), Lausanne, Switzerlande-mail: antoine.schneider@chuv.chM.-H. Perez  J. CottingDivision of Pediatric Intensive Medicine,Centre Hospitalier Universitaire Vaudois(CHUV), Lausanne, SwitzerlandP. Tozzi  L. Von SegesserDivision of Cardiovascular Surgery, CentreHospitalier Universitaire Vaudois (CHUV),Lausanne, SwitzerlandP. VoirolDivision of Hospital Pharmacy,Centre Hospitalier Universitaire Vaudois(CHUV), Lausanne, SwitzerlandP. SchoettkerDivision of Anesthesiology,Centre Hospitalier Universitaire Vaudois(CHUV), Lausanne, SwitzerlandA. Angelillo-ScherrerDivision and Central Laboratoryof Hematology, Centre HospitalierUniversitaire Vaudois (CHUV),Lausanne, SwitzerlandA. G. Schneider  M.-H. Perez  P. Tozzi P. Voirol  P. Schoettker A. Angelillo-Scherrer  J. Cotting L. Von Segesser  P. EggimannFaculty of Biology and Medicine,University of Lausanne, Lausanne,Switzerland1621

Recombinant factor VIIa for intractable life-threatening bleeding in patients with circulatory assist devices

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Recombinant factor VIIa for intractable life-threatening bleeding in patients with circulatory assist devices

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