Perioperative Management of Hemophilia A Patients Undergoing Cardiac Surgery: A Literature Review of Published Cases

      Objective: To investigate the perioperative management of patients with hemophilia A (HA) who undergo cardiac surgery.


      Retrospective analysis of the published literature.


      University hospital.


      HA patients undergoing cardiac surgery.


      The PubMed, Embase, Web of Science Core Collection, CNKI, VIP, and WANFANG databases were searched with the terms “hemophilia A,” “cardiac surgery,” “cardiopulmonary bypass,” “coronary artery bypass graft,” “valve disease,” and “congenital heart disease” to identify relevant articles. Data regarding patient characteristics, perioperative management protocols, and clinical outcomes were extracted and analyzed.

      Measurements and Main Results

      Fifty articles, with 72 patients aging from 12 days to 80 years, were included. The analyzed population consisted of 36 (50%) mild HA, 10 (14%) moderate HA, and 25 (35%) severe HA patients. Factor VIII inhibitors were detected in 7 cases. Surgical procedures included 27 coronary artery bypass grafting procedures, 15 valve surgeries, 8 combined coronary artery bypass grafting with valve surgery procedures (1 with left ventricular assist device), 1 ventricular aneurysm resection with valve surgery, 11 corrections of congenital heart disease, 7 adult aortic surgeries, 3 heart transplantations, and 1 repair of heart injury. Factor VIII concentrates were used as a substitution therapy to ensure normalization of perioperative coagulation function. Although an uneventful clinical outcome was achieved in the majority of cases, 20% of patients developed complications with different severities.


      Execution of a perioperative management strategy with a multidisciplinary approach, a thorough factor replacement protocol, and careful monitoring of factor levels facilitate an optimal outcome for HA patients undergoing cardiac surgery.

      Key Words

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        • Srivastava A
        • Brewer AK
        • Mauser-Bunschoten EP
        • et al.
        Guidelines for the management of hemophilia.
        Haemophilia. 2013; 19: e1-e47
        • Xu H
        • Henry D
        • Li C
        • et al.
        Peri-cardiac surgery coagulation management in a severe hemophilia A patient: A case report.
        Medicine (Baltimore). 2019; 98: e15897
        • Sahin F
        • Atilla FD
        • Demirci Z
        • et al.
        Coronary artery bypass surgery in three patients with haemophilia.
        Haemophilia. 2019; 25: 85
        • Topaloğlu US
        • Özmen R
        • Yüksel RC
        • et al.
        A successful coronary artery bypass operation with intermittent factor VIII administration in a hemophilia A patient who was admitted due to acute myocardial infarction: A rare and difficult case.
        Turk J Haematol. 2019; 36: 135-137
        • Bezaire J
        • Thomson D
        • McNair E
        Recombinant factor VIII measurement in a hemophilia A patient undergoing cardiopulmonary bypass-supported cardiac surgery.
        J Extra Corpor Technol. 2018; 50: 170-177
        • Li M
        • Chou G
        • Bai Y
        • et al.
        Perioperative nursing of a hemophilia infant with congenital heart disease.
        West Chin Med. 2017; 32: 1829-1830
        • Ramaprabhu K
        • Sahu D
        • Cherian V
        • et al.
        David's procedure in a patient with haemophilia.
        Indian J Thorac Cardiovasc Surg. 2017; 33: 247-248
        • Odonkor P
        • Srinivas A
        • Strauss E
        • et al.
        Perioperative coagulation management of a hemophilia A patient during cardiac surgery.
        Semin Cardiothorac Vasc Anesth. 2017; 21: 312-320
        • Misgav M
        • Mandelbaum T
        • Kassif Y
        • et al.
        Thromboelastography during coronary artery bypass grafting surgery of severe hemophilia A patient - the effect of heparin and protamine on factor VIII activity.
        Blood Coagul Fibrinolysis. 2017; 28: 329-333
        • Furukawa S
        • Nogami K
        • Yoshizawa H
        • et al.
        Successful perioperative haemostatic management of aortic coarctation in a 5-week-old infant with severe haemophilia A.
        Haemophilia. 2017; 23: e243-e246
        • Croteau SE
        • Abajas YL
        • Wolberg AS
        • et al.
        Recombinant porcine factor VIII for high-risk surgery in peadiatric congenital heamophilia A with high-titre inhibitor.
        Haemophilia. 2017; 23: e93-e98
        • Chamos C
        • Yates M
        • Austin S
        • et al.
        Minimally invasive aortic valve replacement in a patient with severe hemophilia A.
        J Cardiothorac Vasc Anesth. 2017; 31: 1378-1380
        • Yildirim F
        • Ozbakkaloglu A
        • Ozturk T
        • et al.
        Bentall operation in a patient with severe hemophilia A and Marfan syndrome by use of a biologic composite graft.
        Ann Thorac Surg. 2016; 101: e69-e70
        • Menard CE
        • Zawadski D
        • Singal RK
        • et al.
        Coronary artery bypass surgery in a patient with haemophilia A: A case report.
        Haemophilia. 2016; 22: e76-e79
        • Tran DQ
        • Moss E
        • Murphy DA
        • et al.
        Mitral valve repair in a Jehovah's witness with haemophilia A with high-titre inhibitor.
        Haemophilia. 2015; 21: e523-e525
        • Mohammadzadeh A
        • Babapoursaatlou B
        Coronary surgery in an old patient with hemophilia A.
        Aging Clin Exp Res. 2015; 27: 83-84
        • German M
        • Minuk L
        • Adams C
        • et al.
        Robotic coronary artery bypass surgery in a patient with haemophilia A.
        Haemophilia. 2015; 21: 128-130
        • Bhave P
        • McGiffin D
        • Shaw J
        • et al.
        Guide to performing cardiac surgery in patients with hereditary bleeding disorders.
        J Card Surg. 2015; 30: 61-69
        • Damodar S
        • Bhat P
        • Kumar P
        • et al.
        Successful aortic valve replacement surgery in a patient with severe haemophilia a with low titre inhibitor.
        Indian J Hematol Blood Transfus. 2014; 30: 64-66
        • Quader M
        • Rusina Z
        • Lewis NP
        • et al.
        Left ventricular assist device and heart transplantation in hemophilia a patient.
        Ann Thorac Surg. 2013; 96: 2245-2247
        • Fitzsimons MG
        • Walton K
        • Makar R
        • et al.
        Redo aortic valve replacement in a patient with immunoglobulin A deficiency and hemophilia A.
        Ann Thorac Surg. 2013; 96: 311-313
        • Zatorska K
        • Orłowska-Baranowska E
        • Abramczuk E
        • et al.
        Short and long-term management of haemophilia A patient requiring heart valve surgery.
        Haemophilia. 2012; 18: e352-e354
        • Wermes C
        • Köditz H
        • Wieland I
        • et al.
        Factor VIII replacement therapy during heart surgery under cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) in an infant with severe haemophilia A.
        Hamostaseologie. 2012; 32: A49
        • Sprunck A
        • Maechel AL
        • Levy F
        • et al.
        Off-pump myocardial revascularization in a patient with haemophilia A: A case report and operative strategies.
        Haemophilia. 2012; 18: e20-e22
        • Kypson AP
        • Rodriguez E
        • Anderson CA
        Coronary surgery in a hemophiliac with continuous factor VIII replacement.
        Asian Cardiovasc Thorac Ann. 2012; 20: 191-192
        • Furutachi A
        • Furukawa K
        • Oda Y
        • et al.
        Total arch replacement for acute aortic dissection (Stanford A) in a patient with hemophilia A.
        Ann Thorac Surg. 2012; 93: e61-e62
        • Diplaris KT
        • Karfis EA
        • Ampatzidou F
        • et al.
        Acute type-A dissection in a patient with severe hemophilia A.
        J Cardiothorac Vasc Anesth. 2012; 26: 660-663
        • Barillari G
        • Pasca S
        • Erice F
        • et al.
        Successful double bypass in a patient with severe hemophilia A: A case report.
        J Thromb Thrombolysis. 2012; 33: 193-196
        • Han B
        Nursing care in tricuspid plasty of a patient with hemophilia A and infective endocarditis under cardiopulmonary bypass.
        Chin J Ethnomed Ethnopharm. 2011; 11: 122-124
        • Lison S
        • Spannagl M
        • Dietrich W
        (Working Group of Perioperative Hemostasis). Hemophilia A in cardiac operations: A model of reduced thrombin generation.
        Ann Thorac Surg. 2011; 91: 1606-1608
        • Kuzmanovic M
        • Stajevic M
        • Vukomanovic V
        • et al.
        FVIII replacement in 12-day-old newborn with haemophilia A requiring surgical repair of D transposition of great arteries.
        Haemophilia. 2011; 17: 821-822
        • Rodriguez V
        • Burkhart HM
        • Schmidt KA
        • et al.
        Hemostatic management of an infant with severe hemophilia A and tetralogy of Fallot for cardiac bypass surgery.
        Pediatr Blood Cancer. 2010; 55: 1399-1401
        • Elezovic I
        • Antic D
        • Matic D
        • et al.
        Carotid endarterectomy and triple aorto-coronary bypass grafting in a patient with haemophilia A.
        Haemophilia. 2010; 16: 90
        • Tang M
        • Wierup P
        • Terp K
        • et al.
        Cardiac surgery in patients with haemophilia.
        Haemophilia. 2009; 15: 101-107
        • Gasparović H
        • Zupancic-Salek S
        • Brida V
        • et al.
        Aortic valve replacement in a patient with severe hemophilia.
        Coll Antropol. 2007; 31: 355-357
        • Stine KC
        • Becton DL
        Use of factor VIII replacement during open heart surgery in a patient with haemophilia A.
        Haemophilia. 2006; 12: 435-436
        • Eren A
        • Friedl R
        • Hannekum A
        • et al.
        Cardiac surgery in a patient with haemophilia A.
        Thorac Cardiovasc Surg. 2006; 54: 212-214
        • Murugan SJ
        • Viswanathan S
        • Thomson J
        • et al.
        Heart surgery in infants with hemophilia.
        Ann Thorac Surg. 2006; 81: 336-339
        • De Bels D
        • Demeere JL
        • Dugauquier J
        • et al.
        Continuous infusion of factor VIIIc during heart surgery in a patient with haemophilia A.
        Eur J Anaesthesiol. 2004; 21: 984-986
        • Barnes C
        • Hogan C
        • Antippa P
        • et al.
        Penetrating injury to the heart in a patient with haemophilia.
        Haemophilia. 2004; 10: 101
        • Thiagarajan RR
        • Roth SJ
        • Margossian S
        • et al.
        Extracorporeal membrane oxygenation as a bridge to cardiac transplantation in a patient with cardiomyopathy and hemophilia A.
        Intensive Care Med. 2003; 29: 985-988
        • Kaminishi Y
        • Aizawa K
        • Saito T
        • et al.
        Modified Bentall operation in a patient with hemophilia A.
        Jpn J Thorac Cardiovasc Surg. 2003; 51: 68-70
        • Sheth S
        • Dimichele D
        • Lee M
        • et al.
        Heart transplant in a factor VIII-deficient patient with a high-titre inhibitor: Perioperative management using high-dose continuous infusion factor VIII and recombinant factor VIIa.
        Haemophilia. 2001; 7: 227-232
        • MacKinlay N
        • Taper J
        • Renisson F
        • et al.
        Cardiac surgery and catheterization in patients with haemophilia.
        Haemophilia. 2000; 6: 84-88
        • Rupert E
        • Muralidhar K
        • Shetty DP
        Tetralogy of Fallot and hemophilia A: Successful management of intracardiac repair.
        Asian Cardiovasc Thorac Ann. 1999; 7: 132-134
        • Nahas C
        • Jones JW
        • Beall Jr, AC
        • et al.
        Myocardial revascularization in a hemophiliac.
        Cardiovasc Surg. 1996; 4: 557-558
        • Leggett PL
        • Doyle D
        • Smith WB
        • et al.
        Elective cardiac operation in a patient with severe hemophilia and acquired factor VIII antibodies.
        J Thorac Cardiovasc Surg. 1984; 87: 556-560
        • Meagher PD
        • Rickard KA
        • Richards JG
        • et al.
        Aortic and mitral valve replacement in a patient with severe haemophilia A.
        Aust N Z J Med. 1981; 11: 76-79
        • Holub DA
        • Norman JC
        • Cooley DA
        Successful aortocoronary bypass surgery in a patient with classical hemophilia A.
        Cardiovasc Dis. 1978; 5: 229-234
        • Lusher JM
        • Ravindranath Y
        • Arciniegas E
        • et al.
        Open heart surgery in a hemophiliac patient. Hematologic management.
        Am J Dis Child. 1974; 127: 708-711
        • Brockman SK
        • Aprill SN
        • Rabiner FS
        Aortic valve replacement in hemophilia.
        Report of a case. JAMA. 1972; 22: 660-661
        • Kanellopoulou T
        • Nomikou E
        Replacement therapy for coronary artery bypass surgery in patients with hemophilia A and B.
        J Card Surg. 2018; 33: 76-82
        • Rossi M
        • Jayaram R
        • Sayeed R
        Do patients with haemophilia undergoing cardiac surgery have good surgical outcomes?.
        Interact Cardiovasc Thorac Surg. 2011; 13: 320-331
        • Ferraris VA
        • Boral LI
        • Cohen AJ
        • et al.
        Consensus review of the treatment of cardiovascular disease in people with hemophilia A and B.
        Cardiol Rev. 2015; 23: 53-68
        • Krakow EF
        • Walker I
        • Lamy A
        • et al.
        Cardiac surgery in patients with haemophilia B: A case report and review of the literature.
        Haemophilia. 2008; 15: 108-113
        • Karkouti K
        • Mccluskey SA
        • Syed S
        • et al.
        The influence of perioperative coagulation status on postoperative blood loss in complex cardiac surgery: A prospective observational study.
        Anesth Analg. 2010; 110: 1533-1540
        • Cormier M
        • Batty P
        • Tarrant J
        • et al.
        Advances in knowledge of inhibitor formation in severe haemophilia A.
        Br J Haematol. 2020; 189: 39-53
        • Garagiola I
        • Palla R
        • Peyvandi F
        Risk factors for inhibitor development in severe hemophilia A.
        Thromb Res. 2018; 168: 20-27
        • Krudysz-Amblo J
        • Parhami-Seren B
        • Butenas S
        • et al.
        Quantitation of anti-factor VIII antibodies in human plasma.
        Blood. 2009; 113: 2587-2594
        • Teitel JM
        Treatment and prevention of bleeding in congenital hemophilia A patients with inhibitors.
        Transfus Apheresis Sci. 2018; 57: 466-471
        • Mannucci PM
        • Mauser-Bunschoten EP
        Cardiovascular disease in haemophilia patients: A contemporary issue.
        Haemophilia. 2010; 16: 58-66
        • Mannucci PM
        • Schutgens RE
        • Santagostino E
        • et al.
        How I treat age-related morbidities in elderly persons with hemophilia.
        Blood. 2009; 114: 5256-5263