Patients with Antiphospholipid Syndrome (APS) undergoing cardiopulmonary bypass (CPB) surgery are at increased risk for thrombotic and hemorrhagic complications. Anticoagulation during CPB is typically monitored with activated clotting time (ACT) which may be falsely prolonged in patients with APS. The Hepcon Hemostasis Management System quantitatively determines the whole blood heparin concentration through heparin/protamine titration.
Methods
This was a retrospective study of APS patients who underwent cardiac surgery requiring CPB at the Cleveland Clinic between April 2013, and July 2020. The primary endpoint was the composite rate of hemorrhagic or thromboembolic complications per surgical case in patients monitored by Hepcon versus patients monitored by ACT. Secondary endpoints were median volume of chest tube output and packed red blood cell (PRBC) transfusion within the first three post-operative days.
Results
43 patients were included. 20 (47%) patients were monitored using Hepcon while 23 (53%) were monitored using ACT. For the primary endpoint of rate of thromboembolic or hemorrhagic complications per surgical case, there was no statistically significant difference between the Hepcon and ACT groups (HMS, 6/20 [30%]; ACT, 7/23 [30%]; p = >0.99). For the secondary endpoints, there was no statistically significant difference in median post-operative chest tube output (780 mL vs. 850 mL; p = 0.88) and median post-operative PRBC transfusion (1 unit vs. 0 unit; p = 0.28) between the Hepcon and ACT groups, respectively.
Conclusion
There was no difference in the composite outcome of thrombotic or hemorrhagic complications in patients monitored by Hepcon versus those monitored by ACT.
XourgiaETektonidouMG. An update on antiphospholipid syndrome. Curr Rheumatol Rep2022; 23: 84.
2.
TektonidouMG. Cardiovascular disease risk in antiphospholipid syndrome: thrombo-inflammation and atherothrombosis. J Autoimmun2022; 128: 102813.
3.
LeeESNarasimhanUKofidisT, et al.Difficulties with the use of thromboelastometry in a patient with antiphospholipid syndrome undergoing cardiac Surgery. J Cardiothorac Vasc Anesth2015; 29: 1016–1020.
4.
MøllerCHSteinbrüchelDA. Platelet function after coronary artery bypass grafting: is there a procoagulant activity after off-pump compared with on-pump surgery?Scand Cardiovasc J2003; 37: 149–153.
5.
BerkunYElamiAMeirK, et al.Increased morbidity and mortality in patients with antiphospholipid syndrome undergoing valve replacement surgery. J Thorac Cardiovasc Surg2004; 127: 414–420.
6.
ColliAMestresCAEspinosaG, et al.Heart valve surgery in patients with the antiphospholipid syndrome: analysis of a series of nine cases. Eur J Cardiothorac Surg2010; 37: 154–158.
7.
MassoudyPCetinSMThielmannM, et al.Antiphospholipid syndrome in cardiac surgery-an underestimated coagulation disorder?Eur J Cardiothorac Surg2005; 28: 133–137.
8.
HegdeVAVivasYShahH, et al.Cardiovascular surgical outcomes in patients with the antiphospholipid syndrome--a case-series. Heart Lung Circ2007; 16: 423–427.
9.
UralKOwenC. Pro: the Hepcon HMS should be used instead of traditional Activated Clotting Time (ACT) to dose heparin and protamine for cardiac surgery requiring cardiopulmonary bypass. J Cardiothorac Vasc Anesth2016; 30: 1727–1729.
10.
HortonSAugustinS. Activated Clotting Time (ACT). In: MonagleP (ed). Haemostasis: Methods and Protocols. Totowa, NJ: Humana Press, 2013, pp. 155–167.
11.
GorkiHMalinovskiVStanbridgeRD. The antiphospholipid syndrome and heart valve surgery. Eur J Cardiothorac Surg2008; 33: 168–181.
12.
SekiTShinguYSugikiH, et al.Anticoagulation management during cardiopulmonary bypass in patients with antiphospholipid syndrome. J Artif Organs2018; 21: 363–366.
13.
MehtaTPSmytheMAMattsonJC. Strategies for managing heparin therapy in patients with antiphospholipid antibody syndrome. Pharmacotherapy2011; 31: 1221–1231.
14.
WangJMaHPZhengH. Blood loss after cardiopulmonary bypass, standard vs titrated protamine: a meta-analysis. Neth J Med2013; 71: 123–127.
15.
LaxMPesonenEHiippalaS, et al.Heparin dose and point-of-care measurements of hemostasis in cardiac surgery-results of a randomized controlled trial. J Cardiothorac Vasc Anesth2020; 34: 2362–2368.
16.
RaymondPDRayMJCallenSN, et al.Heparin monitoring during cardiac surgery. Part 1: validation of whole-blood heparin concentration and activated clotting time. Perfusion2003; 18: 269–276.
17.
BrownsteinLBartholomewTPSilverDG, et al.A case report of mitral valve replacement in a patient with lupus antibody syndrome. Perfusion2003; 18: 373–376.
18.
JervisKSenthilnathanVLernerAB. Management of a patient with lupus anticoagulant and antiphospholipid syndrome for off-pump coronary artery bypass grafting using the Hepcon system. Anesth Analg2009; 108: 1116–1119.
19.
SamejimaYKodakaMIchikawaJ, et al.Management of a patient with antiphospholipid syndrome undergoing aortic valve replacement using the hepcon hemostasis management system plus and rotational thromboelastometry: a case report. A A Case Rep2017; 8: 100–104.
20.
UralKEdelsonJ. Antiphospholipid syndrome and cardiac bypass: the careful balance between clotting and bleeding. J Extra Corpor Technol2021; 53: 46–49.
21.
MiyakisSLockshinMDAtsumiT, et al.International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome. Journal of Thrombosis and Haemostasis2006; 4: 295–306.
22.
KaatzSAhmadDSpyropoulosAC, et al.Definition of clinically relevant non-major bleeding in studies of anticoagulants in atrial fibrillation and venous thromboembolic disease in non-surgical patients: communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis2015; 13: 2119–2126.
23.
NuttallGASmithMMSmithBB, et al.A blinded randomized trial comparing standard activated clotting time heparin management to high target active clotting time and individualized Hepcon HMS heparin management in cardiopulmonary bypass cardiac surgical patients. Ann Thorac Cardiovasc Surg2022; 28: 204–213.
24.
RadulovicVLaffinAHanssonKM, et al.Heparin and protamine titration coes not improve haemostasis after cardiac surgery: a prospective randomized study. PLoS One2015; 10: e0130271.
25.
SlightRDBuellRNzewiOC, et al.A comparison of activated coagulation time-based techniques for anticoagulation during cardiac surgery with cardiopulmonary bypass. J Cardiothorac Vasc Anesth2008; 22: 47–52.
26.
O'Carroll-KuehnBUMeeranH. Management of coagulation during cardiopulmonary bypass. Continuing Education in Anaesthesia Critical Care and Pain2007; 7: 195–198.
27.
NoordermeerTMolhoekJESchutgensREG, et al.Anti-β2-glycoprotein I and anti-prothrombin antibodies cause lupus anticoagulant through different mechanisms of action. J Thromb Haemost2021; 19: 1018.
28.
SimmelinkMJHorbachDADerksenRH, et al.Complexes of anti-prothrombin antibodies and prothrombin cause lupus anticoagulant activity by competing with the binding of clotting factors for catalytic phospholipid surfaces. Br J Haematol2001; 113: 621–629.
29.
EastCJClementsFMathewJ, et al.Antiphospholipid syndrome and cardiac surgery: management of anticoagulation in two patients. Anesth Analg2000; 90: 1098–1101.
30.
LennonMJThackrayNMGibbsNM. Anti-factor Xa monitoring of anticoagulation during cardiopulmonary bypass in a patient with antiphospholipid syndrome. Anaesth Intensive Care2003; 31: 95–98.
31.
SheikhFLechowiczASetlurR, et al.Recognition and management of patients with antiphospholipid antibody syndrome undergoing cardiac surgery. J Cardiothorac Vasc Anesth1997; 11: 764–766.
32.
DespotisGJJoistJHHogueCWJr., et al.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 Surg1995; 110: 46–54.
33.
KhuriSFWolfeJAJosaM, et al.Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and nonsurgical blood loss. J Thorac Cardiovasc Surg1992; 104: 94–107.
34.
BeerkensFJClaessenBEMahanM, et al.Contemporary coronary artery bypass graft surgery and subsequent percutaneous revascularization. Nat Rev Cardiol2022; 19: 195–208.
35.
SpadaccioCAlkhameesKAl-AttarN. Recent advances in aortic valve replacement. F1000 Res2019; 8.
36.
GeorgeTJBeatyCAEwaldGA, et al.Reoperative sternotomy is associated with increased mortality after heart transplantation. Ann Thorac Surg2012; 94: 2025–2032.
37.
SabikJF3rdBlackstoneEHHoughtalingPL, et al.Is reoperation still a risk factor in coronary artery bypass surgery?Ann Thorac Surg2005; 80: 1719–1727.
38.
YapCHSposatoLAkowuahE, et al.Contemporary results show repeat coronary artery bypass grafting remains a risk factor for operative mortality. Ann Thorac Surg2009; 87: 1386–1391.
39.
ChaturvediSMcCraeKR. Diagnosis and management of the antiphospholipid syndrome. Blood Rev2017; 31: 406–417.
40.
DykeCAronsonSDietrichW, et al.Universal definition of perioperative bleeding in adult cardiac surgery. J Thorac Cardiovasc Surg2014; 147: 1458–1463.e1.
41.
HoKMBhamEPaveyW. Incidence of venous thromboembolism and benefits and risks of thromboprophylaxis after cardiac surgery: a systematic review and meta-analysis. J Am Heart Assoc2015; 4: e002652.
42.
KhouryHLyonsRSanaihaY, et al.Deep venous thrombosis and pulmonary embolism in cardiac surgical patients. Ann Thorac Surg2020; 109: 1804–1810.
43.
Al-AttarNJohnstonSJamousN, et al.Impact of bleeding complications on length of stay and critical care utilization in cardiac surgery patients in England. J Cardiothorac Surg2019; 14: 64.
