Hemophilia is an X-linked, recessive bleeding disorder. Improvements in factor replacement
therapy and overall approach to hemophilia management have increased the lifespan
and quality of life for patients with hemophilia. Thus, they are presenting for cardiac
surgery related to age-related atherosclerosis, vascular disorders, and degenerative
valvular disease. Although challenging, cardiac surgery can be performed safely with
appropriate planning, using a multidisciplinary approach. This article provides a
narrative review and framework for the perioperative management of patients with hemophilia
A and B undergoing cardiac surgery.
Key Words
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References
- Guidelines for the management of hemophilia.Haemophilia. 2013; 19: e1-47
- The World Federation of Hemophilia annual global survey 1999-2018.Haemophilia. 2020; 26: 591-600
- Global assays in hemophilia.Semin Hematol. 2016; 53: 40-45
- Factor VIII: Long-established role in haemophilia A and emerging evidence beyond haemostasis.Blood Rev. 2019; 35: 43-50
- WFH guidelines for the management of hemophilia, 3rd edition.Haemophilia. 2020; 26: 1-158
National Hemophilia Foundation. Hemophilia A. Available at: https://www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Hemophilia-A. Accessed July 16, 2020.
- Haemophilia B: Where are we now and what does the future hold?.Blood Rev. 2018; 32: 52-60
- Hemophilia A in the third millennium.Blood Rev. 2013; 27: 179-184
- Risk factors for inhibitor development in severe hemophilia A.Thromb Res. 2018; 168: 20-27
- Hemophilia: In review.Pediatr Rev. 2013; 34 (quiz 295): 289-294
- Treatment regimens with bypassing agents in patients with hemophilia A and inhibitors: A survey from the Italian Association of Hemophilia Centers (AICE).Semin Thromb Hemost. 2018; 44: 551-560
- Hemophilia and inhibitors: Current treatment options and potential new therapeutic approaches.Hematology Am Soc Hematol Educ Program. 2016; 2016: 657-662
- Diagnosis and treatment of hemophilia.Clin Adv Hematol Oncol. 2019; 17: 344-351
- Inhibitors in hemophilia B.Semin Thromb Hemost. 2018; 44: 578-589
- Recombinant factor VIII measurement in a hemophilia A patient undergoing cardiopulmonary bypass-supported cardiac surgery.J Extra Corpor Technol. 2018; 50: 170-177
- Guide to performing cardiac surgery in patients with hereditary bleeding disorders.J Card Surg. 2015; 30: 61-69
- Off-pump technique and replacement therapy for coronary artery bypass surgery in a patient with hemophilia B.J Thromb Thrombolysis. 2019; 48: 299-302
- Perioperative management of mild hemophilia B during and after coronary artery bypass grafting: Challenges and solutions.J Cardiothorac Vasc Anesth. 2019; 33: 549-555
- Consensus review of the treatment of cardiovascular disease in people with hemophilia A and B.Cardiol Rev. 2015; 23: 53-68
- Hemophilia A in cardiac operations: A model of reduced thrombin generation.Ann Thorac Surg. 2011; 91: 1606-1608
- Coronary artery bypass surgery in a patient with Haemophilia A: A case report.Haemophilia. 2016; 22: e76-e79
- Robotic mitral valve repair in a type B hemophiliac.J Card Surg. 2020; 35: 1129-1131
- Perioperative coagulation management of a hemophilia A patient during cardiac surgery.Semin Cardiothorac Vasc Anesth. 2017; 21: 312-320
- Revascularization strategies and in-hospital management in acute coronary syndromes complicated by hemophilia A or hemophilia B.Blood Coagul Fibrinolysis. 2017; 28: 650-657
- Do patients with haemophilia undergoing cardiac surgery have good surgical outcomes?.Interact Cardiovasc Thorac Surg. 2011; 13: 320-331
- Cardiac surgery in patients with Hemophilia: Is it safe?.J Cardiothorac Surg. 2020; 15: 76
- Coronary artery bypass grafting in a patient with hemophilia B: Continuous recombinant factor IX infusion as per the Japanese guidelines for replacement therapy.Gen Thorac Cardiovasc Surg. 2016; 64: 481-483
- Cardiac surgery in patients with haemophilia.Haemophilia. 2009; 15: 101-107
- Peri-cardiac surgery coagulation management in a severe hemophilia A patient: A case report.Medicine (Baltimore). 2019; 98: e15897
- Successful haemostatic management of replacement of the ascending aorta for type A acute aortic dissection in a patient with mild haemophilia B.Haemophilia. 2016; 22: e109-e111
- Perioperative management of hemophilia A patients undergoing cardiac surgery: A literature review of published cases [e-pub ahead of print].J Cardiothorac Vasc Anesth. 2020; (doi: https://doi.org/Accessed July 12, 2020)https://doi.org/10.1053/j.jvca.2020.06.074
- How full-length FVIII benefits from its heterogeneity - insights into the role of the B-domain.Pharm Res. 2019; 36: 77
- Recombinant factor VIII concentrates.Semin Thromb Hemost. 2010; 36: 493-497
- Physicochemical characterisation of rVIII-SingleChain, a novel recombinant single-chain factor VIII.Thromb Res. 2015; 136: 388-395
- Intermittent injections vs. continuous infusion of factor VIII in haemophilia patients undergoing major surgery.Br J Haematol. 2000; 110: 715-720
- Pharmacokinetic-guided dosing of factor VIII concentrate in a patient with haemophilia during renal transplantation.BMJ Case Rep. 2016; 2016
- Population pharmacokinetics of factor IX in hemophilia B patients undergoing surgery.J Thromb Haemost. 2018; 16: 2196-2207
- Cardiac surgery and catheterization in patients with haemophilia.Haemophilia. 2000; 6: 84-88
- Continuous infusion of factor VIIIc during heart surgery in a patient with haemophilia A.Eur J Anaesthesiol. 2004; 21: 984-986
- Total arch replacement for acute aortic dissection (Stanford A) in a patient with hemophilia A.Ann Thorac Surg. 2012; 93: e61-e62
- Acute type-a dissection in a patient with severe hemophilia A.J Cardiothorac Vasc Anesth. 2012; 26: 660-663
- Stress-induced alterations in coagulation: Assessment of a new hemoconcentration correction technique.Psychosom Med. 2012; 74: 288-295
- Pathophysiological mechanisms of endogenous FVIII release following strenuous exercise in non-severe haemophilia: A review.Thromb Haemost. 2017; 117: 2237-2242
- Activated coagulation time of whole blood.JAMA. 1966; 196: 436-440
- The activated coagulation time of whole blood as a routine pre-operative sceening test.Calif Med. 1971; 114: 15-18
- 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
- One-stage vs. chromogenic assays in haemophilia A.Eur J Haematol. 2015; 94: 38-44
- Development of a sensitive and rapid chromogenic factor IX assay for clinical use.Haemostasis. 1990; 20: 276-288
- Thromboelastography-based transfusion algorithm reduces blood product use after elective CABG: A prospective randomized study.J Card Surg. 2009; 24: 404-410
- Principles and practice of thromboelastography in clinical coagulation management and transfusion practice.Transfus Med Rev. 2012; 26: 1-13
- Activated coagulation time vs. intrinsically activated modified rotational thromboelastometry in assessment of hemostatic disturbances and blood loss after protamine administration in elective cardiac surgery: Analysis from the clinical trial (NCT01281397).J Cardiothorac Surg. 2014; 9: 129
Tanaka K.A., Henderson R.A., Strauss E.R. Evolution of viscoelastic coagulation testing. Expert Rev Hematol 2020:1-11.
- The utility of thromboelastography in inherited and acquired bleeding disorders.Br J Haematol. 2016; 174: 503-514
- Clinical utility of viscoelastic testing (TEG and ROTEM analyzers) in the management of old and new therapies for hemophilia.Am J Hematol. 2019; 94: 249-256
- Systematic monitoring of hemostatic management in hemophilia A patients with inhibitor in the perioperative period using rotational thromboelastometry.J Thromb Haemost. 2015; 13: 1279-1284
- Recommendations for performing thromboelastography/thromboelastometry in hemophilia: communication from the SSC of the ISTH.J Thromb Haemost. 2014; 12: 103-106
- The mild phenotype in severe hemophilia A with Arg1781His mutation is associated with enhanced binding affinity of factor VIII for factor X.Thromb Haemost. 2013; 109: 1007-1015
- Surgery in patients with hemophilia and inhibitors: A review of the Norwegian experience with FEIBA.Semin Hematol. 2006; 43: S18-S21
- History of lysosomal storage diseases: An overview.in: Mehta A. Beck M. Sunder-Plassmann G. Fabry Disease: Perspectives from 5 Years of FOS. Oxford PharmaGenesis, Oxford2006 (Available from) (Accessed July 12, 2020)
- The efficacy of bypassing agents in surgery of hemophilia patients with inhibitors.Blood Res. 2015; 50: 173-178
- Management of perioperative hemostasis in a severe hemophilia A patient with inhibitors on emicizumab using global hemostasis assays.Ther Adv Hematol. 2019; 102040620719860025
- Evaluating and monitoring the efficacy of recombinant activated factor VIIa in patients with haemophilia and inhibitors.Blood Coagul Fibrinolysis. 2014; 25: 754-760
- Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: Current state of art and future perspectives.Blood. 2013; 121: 1944-1950
- Safety analysis of rFVIIa with emicizumab dosing in congenital hemophilia A with inhibitors: Experience from the HAVEN clinical program.J Thromb Haemost. 2019; 17: 1470-1477
- Emicizumab prophylaxis in patients who have hemophilia A without inhibitors.N Engl J Med. 2018; 379: 811-822
- The effect of emicizumab prophylaxis on health-related outcomes in persons with haemophilia A with inhibitors: HAVEN 1 Study.Haemophilia. 2019; 25: 33-44
- Emicizumab prophylaxis in hemophilia A with inhibitors.N Engl J Med. 2017; 377: 809-818
- Efficacy, safety, and pharmacokinetics of emicizumab prophylaxis given every 4 weeks in people with haemophilia A (HAVEN 4): A multicentre, open-label, non-randomised phase 3 study.Lancet Haematol. 2019; 6: e295-e305
- Efficacy of emicizumab prophylaxis versus factor VIII prophylaxis for treatment of hemophilia A without inhibitors: Network meta-analysis and sub-group analyses of the intra-patient comparison of the HAVEN 3 trial.Curr Med Res Opin. 2019; 35: 2079-2087
- A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model.Nat Med. 2012; 18: 1570-1574
- Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra®): Proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP).Haemophilia. 2019; 25: 731-737
- Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee.Haemophilia. 2018; 24: 344-347
- Routine measurements of factor VIII activity and inhibitor titer in the presence of emicizumab utilizing anti-idiotype monoclonal antibodies.J Thromb Haemost. 2018; 16: 1383-1390
- Global coagulation function assessed by rotational thromboelastometry predicts coagulation-steady state in individual hemophilia A patients receiving emicizumab prophylaxis.Int J Hematol. 2019; 110: 419-430
- Inhibition of tissue factor pathway inhibitor (TFPI) as a treatment for haemophilia: Rationale with focus on concizumab.Drugs. 2018; 78: 881-890
- Concizumab, an anti-tissue factor pathway inhibitor antibody, induces increased thrombin generation in plasma from haemophilia patients and healthy subjects measured by the thrombin generation assay.Haemophilia. 2017; 23: 769-776
- Current and emerging biologics for the treatment of hemophilia.Expert Opin Biol Ther. 2019; 19: 801-810
- An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B.J Blood Med. 2018; 9: 135-140
- New therapies using nonfactor products for patients with hemophilia and inhibitors.Blood. 2019; 133: 399-406
- BIVV001, a new class of factor VIII replacement for hemophilia A that is independent of von Willebrand factor in primates and mice.Blood. 2020; 135: 1484-1496
- Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer.Blood. 2012; 119: 3038-3041
- AAV-mediated factor IX gene transfer to skeletal muscle in patients with severe hemophilia B.Blood. 2003; 101: 2963-2972
- Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response.Nat Med. 2006; 12: 342-347
- Gene therapy for hemophilia.Hematology Am Soc Hematol Educ Program. 2019; 2019: 1-8
- Enhanced factor IX activity following administration of AAV5-R338L "Padua" factor IX versus AAV5 WT human factor IX in NHPs.Mol Ther Methods Clin Dev. 2019; 15: 221-231
- Etranacogene dezaparvovec (AMT-061 phase 2b): Normal/near normal FIX activity and bleed cessation in hemophilia B.Blood Adv. 2019; 3: 3241-3247
- Multiyear follow-up of AAV5-hFVIII-sq gene therapy for hemophilia A.N Engl J Med. 2020; 382: 29-40
- AAV5-factor VIII gene transfer in severe hemophilia A.N Engl J Med. 2017; 377: 2519-2530
- The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical practice guidelines-anticoagulation during cardiopulmonary bypass.Ann Thorac Surg. 2018; 105: 650-662
- The impact of heparin concentration and activated clotting time monitoring on blood conservation. A prospective, randomized evaluation in patients undergoing cardiac operation.J Thorac Cardiovasc Surg. 1995; 110: 46-54
- More effective suppression of hemostatic system activation in patients undergoing cardiac surgery by heparin dosing based on heparin blood concentrations rather than ACT.Thromb Haemost. 1996; 76: 902-908
- Perioperative blood transfusion and blood conservation in cardiac surgery: The Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline.Ann Thorac Surg. 2007; 83: S27-S86
- Management of severe perioperative bleeding: Guidelines from the European Society of Anaesthesiology.Eur J Anaesthesiol. 2013; 30: 270-382
- Prevention and treatment of major blood loss.N Engl J Med. 2007; 356: 2301-2311
- Tranexamic acid in patients undergoing coronary-artery surgery.N Engl J Med. 2017; 376: 136-148
- Tranexamic acid in coronary artery surgery: One-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial.J Thorac Cardiovasc Surg. 2019; 157 (644-52.e649)
- A randomized, double-blinded trial comparing the effectiveness of tranexamic acid and epsilon-aminocaproic acid in reducing bleeding and transfusion in cardiac surgery.Ann Card Anaesth. 2019; 22: 265-272
- Tranexamic acid-associated seizures: Causes and treatment.Ann Neurol. 2016; 79: 18-26
- The influence of perioperative coagulation status on postoperative blood loss in complex cardiac surgery: A prospective observational study.Anesth Analg. 2010; 110: 1533-1540
- Activation of the hemostatic system during cardiopulmonary bypass.Anesth Analg. 2011; 113: 1319-1333
- Cell salvage as part of a blood conservation strategy in anaesthesia.Br J Anaesth. 2010; 105: 401-416
- A randomized controlled trial of cell salvage in routine cardiac surgery.Anesth Analg. 2008; 107: 1487-1495
- Specific and global coagulation tests in patients with mild haemophilia A with a double mutation (Glu113Asp, Arg593Cys).Blood Transfus. 2015; 13: 622-630
- Coagulation assessment with thromboelastography during abdominal endovascular aneurysm repair in a patient with hemophilia A.JA Clin Rep. 2020; 6: 7
- In-vitro evaluation of anti-factor IXa aptamer on thrombin generation, clotting time, and viscoelastometry.Thromb Haemost. 2017; 101: 827-833
- Society of Cardiovascular Anesthesiologists clinical practice improvement advisory for management of perioperative bleeding and hemostasis in cardiac surgery patients.J Cardiothorac Vasc Anesth. 2019; 33: 2887-2899
- Perioperative use of coagulation factor concentrates in patients undergoing cardiac surgery.J Cardiothorac Vasc Anesth. 2017; 31: 1810-1819
- Platelets and hemophilia: A review of the literature.Thromb Res. 2017; 155: 131-139
- Desmopressin in treatment of haematological disorders and in prevention of surgical bleeding.Blood Rev. 2014; 28: 95-102
- Response of patients with mild and moderate hemophilia A and von Willebrand's disease to treatment with desmopressin.Ann Intern Med. 1985; 103: 6-14
- Intranasal desmopressin (DDAVP) by spray in mild hemophilia A and von Willebrand's disease type I.Blut. 1990; 60: 187-191
Circular of information for the use of human blood and blood components. Available at: http://www.aabb.org/tm/coi/Documents/coi1017.pdf. Accessed September 15, 2020.
- Cryoprecipitate therapy.Br J Anaesth. 2014; 113: 922-934
- Cardiac catheterization and intervention in haemophilia patients: Prospective evaluation of the 2009 institutional guideline.Haemophilia. 2013; 19: 370-377
- Presentation and management of acute coronary syndromes among adult persons with haemophilia: Results of an international, retrospective, 10-year survey.Haemophilia. 2015; 21: 589-597
- How I treat patients with inherited bleeding disorders who need anticoagulant therapy.Blood. 2016; 128: 178-184
- Surgery in patients with hemophilia: is thromboprophylaxis mandatory?.Thromb Res. 2012; 130: S23-S26
- Diagnosis and treatment of factor VIII and IX inhibitors in congenital haemophilia: (4th edition). UK Haemophilia Centre Doctors Organization.Br J Haematol. 2013; 160: 153-170
National Hemophilia Foundation Medical and Scientific Advisory Council. Recommendation on the use and management of emicizuzmab-kxwh (Hemlibra) for hemophilia A with and without inhibitors. Available at: https://www.hemophilia.org/Researchers-Healthcare-Providers/Medical-and-Scientific-Advisory-Council-MASAC/MASAC-Recommendations/Recommendation-on-the-Use-and-Management-of-Emicizumab-kxwh-Hemlibra-for-Hemophilia-A-with-and-without-Inhibitors. Accessed July 15, 2020.
- Minimally invasive aortic valve replacement in a patient with severe hemophilia A.J Cardiothorac Vasc Anesth. 2017; 31: 1378-1380
- Transcatheter aortic valve implantation in a person with haemophilia.Haemophilia. 2015; 21: e323-e325
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Published online: October 18, 2020
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