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Table of Contents
Year : 2011  |  Volume : 14  |  Issue : 2  |  Page : 146-149
Antiphospholipid syndrome, cardiac surgery and cardiopulmonary bypass

Department of Anaesthesiology and Critical Care, Armed Forces Medical College, Pune, India

Click here for correspondence address and email

Date of Web Publication25-May-2011

How to cite this article:
Sharma VK, Chaturvedi R, Manoj Luthra V. Antiphospholipid syndrome, cardiac surgery and cardiopulmonary bypass. Ann Card Anaesth 2011;14:146-9

How to cite this URL:
Sharma VK, Chaturvedi R, Manoj Luthra V. Antiphospholipid syndrome, cardiac surgery and cardiopulmonary bypass. Ann Card Anaesth [serial online] 2011 [cited 2022 Dec 8];14:146-9. Available from:

Antiphospholipid syndrome (APLS) is a multi-system disorder of autoimmune etiology. The diagnostic criterion of APLS is arterial and/or venous thrombosis or recurrent fetal loss associated with persistent antiphospholipid (APL) antibodies. [1] The presence of moderate or high blood levels of anticardiolipin IgG or IgM antibodies or lupus anticoagulant antibodies on two or more occasions at least 6 weeks apart is necessary to establish the diagnosis. [2] APL antibodies are a heterogenous group of antibodies that interact with anionic phospholipid cardiolipin (diphosphatidylglycerol) and other phospholipid-binding protein cofactors, the major one being the serum protein b2 -glycoprotein I (also known as apolipoprotein H). [3] Although, APLS occurs in about 2% of the general population, its prevalence increases with age, especially in elderly patients with coexistent chronic diseases. [4],[5],[6] Among patients with systemic lupus erythematosus (SLE), the prevalence of antiphospholipid antibodies is much higher, ranging from 12% to 30% for anticardiolipin antibodies [7],[8] and 15% to 34% for lupus anticoagulant antibodies. [8],[9]

The clinical manifestations of APLS are protean. Cardiac involvement includes valvular heart disease (Libman-Sachs endocarditis), coronary artery disease, intracardiac thrombi, pulmonary embolism, pulmonary hypertension and cardiomyopathy. Cardiac valvular involvement has a predilection for mitral valve disease; aortic valve is less often affected. [10],[11],[12],[13] In patients with APLS-associated mitral valve disease, the incidence of arterial embolization is 77%. [14] Central nervous system (CNS) manifestations of APLS are cerebrovascular accident, transient ischemic attack, seizures, chorea, migraine, pseudotumor cerebri, visual disturbances and dementia. Cutaneous features include livedo reticularis, ulcers, infarcts and superficial thrombophlebitis. These patients may develop renal arterial or venous thrombosis, acute or chronic renal failure, hemolytic anemia or thrombocytopenia. [15],[16],[17] Catastrophic APLS is a distinct entity that results in simultaneous multiple small vessel thromboses. Factors precipitating this 'thrombotic storm' include surgical trauma, infection, any change in anticoagulation therapy, or oral contraceptives. It is associated with nearly 50% mortality. [18],[19],[20]

Patients with APLS present for cardiac surgery under cardiopulmonary bypass (CPB) requiring valve replacement or repair and coronary revascularization. Occasionally, they may present for right atrial and pulmonary artery thrombectomy under CPB and deep hypothermic circulatory arrest (DHCA). [21] They exhibit an abnormal coagulation profile with prolonged activated partial thromboplastin time (aPTT). Paradoxically, they are at an increased risk of thrombotic complications, especially in the perioperative period. [3] Preoperatively, these patients may be on anticoagulation therapy with aspirin, warfarin and heparin. Discontinuation of anticoagulation before surgery; as well as inadequate anticoagulation intraoperatively and before reinstitution of anticoagulation postoperatively, exposes them to risk of vaso-occlusive complications, viz., cerebrovascular accident, myocardial infarction and venocaval thrombosis. [22],[23]

The perioperative management of patients with APLS undergoing CPB is especially challenging. Perioperative risks include thrombosis and/or bleeding secondary to excessive anticoagulation; and APL-associated clotting factor deficiencies (especially factor II). [22],[23] In patients with lupus anticoagulant antibodies, there is prolongation of aPTT, and of other coagulation assays like Russell viper venom time, dilute thromboplastin inhibition time, kaolin coagulation time and individual coagulation factor assays (IX and occasionally XI and VIII). However, in vivo function of these proteins is not affected and the risk of thrombosis persists. [3] Monitoring the effects of warfarin, heparin and other anticoagulants is complex. [24] As APLS is associated with both thrombocytopenia and clotting factor deficiencies, clotting factor assays should be performed in addition to routine tests to delineate which part of the coagulation cascade is affected, viz., intrinsic, extrinsic or common pathway. The intrinsic coagulation pathway is assessed by the activated partial-thromboplastin time (APTT), colloidal-silica clotting time (CSCT) and kaolin clotting time (KCT), thereby assessing factors IX, XI and XII. The extrinsic coagulation pathway is initiated by the formation of a complex between tissue factor (TF) and factor VIIa. The dilute prothrombin time (dPT) assay assesses the extrinsic pathway (factor VIIa). Both the intrinsic and extrinsic pathways result in the conversion of factor X to activated factor X (factor Xa). Finally, both intrinsic and extrinsic pathways converge on the final common pathway, the activation of prothrombin to thrombin followed by the conversion of fibrinogen to fibrin. Russell's viper venom directly activates factor X. Taipan, Textarin and Ecarin snake-venoms extract directly activate prothrombin but have different cofactor requirements. Taipan venom activation of prothrombin requires phospholipid and calcium but not factor Va. Textarin venom activation of prothrombin requires phospholipid, calcium and factor Va, whereas Ecarin venom activation of prothrombin is independent of cofactors and does not require phospholipid, calcium or factor Va. The activation of prothrombin to thrombin, like several other reactions in the coagulation cascade, requires the presence of phospholipid and calcium. These phospholipid-dependent reactions are believed to be targeted by lupus anticoagulant antibodies in vitro.[15] Specific assays, as elaborated here, would define the exact nature of coagulopathy.

Periods without anticoagulation should be kept to a minimum. While no consensus exists on the optimal perioperative management of anticoagulation in patients undergoing CPB, an attempt is made here to formulate a strategy. Heparin for anticoagulation during CPB is the safest and the most widely used anticoagulant. As kaolin-activated clotting time (ACT) is affected by APL antibodies, celite ACT is recommended for monitoring coagulation, and a higher target ACT is recommended. Heparin concentration considered therapeutic for CPB should be ≥ 3 U/mL, but individual dose response varies considerably. Alternative methods of monitoring anticoagulation include empirically doubling baseline ACT, obtaining heparin concentrations by protamine titration (Hepcon; Medtronic, Minneapolis, MN, USA), [25] performing anti-factor Xa assays, or plotting heparin/ACT titration curves preoperatively to determine patient-specific target ACT levels. Anti-factor Xa levels of 1.5 ± 2.0 U/mL are considered therapeutic for CPB; and postoperatively, levels greater than 1.0 U/mL may be associated with excess blood loss. [26] However, the turnaround time for anti-factor Xa estimation is currently incompatible with the time constraints of CPB. The in vitro heparin/ACT titration curve is a test of an individual patient's responsiveness to heparin. In the normal patient, a heparin concentration of 3 U/mL typically produces an ACT of more than 450 seconds. In patients with APLS, preoperatively, anti-Xa factor activity assays can be correlated with the patient-specific preoperative in vitro heparin ACT titration curve. [5] Although thromboelastography (TEG) is yet to be validated to enable making coagulation-related decisions in APLS patients receiving heparin, it may be a useful adjunct in this complex situation. APLS may be associated with heparin-induced thrombocytopenia (HIT), in which case, direct thrombin inhibitor bivaluridin has been used. [27],[28],[29] Varying reports of heparin reversal with half dose (partial reversal of residual heparin as assessed by Hepcon using half of the calculated dose of protamine) or restricted dose of protamine, or of no reversal of heparin exist, with no prevailing consensus. Antifibrinolytic drugs, viz., epsilon-amino-caproic acid (EACA), tranexemic acid and aprotinin, have been avoided commonly; however, Rand et al. report the use of EACA without any untoward prothrombotic episode. [24] Perioperative morbidity of thrombosis associated with cardiac surgery and APLS precludes the use of antifibrinolytic drugs, at least for the time being, pending the availability of more data. There seems to be a place for preoperative plasmapheresis and corticosteroids as extrapolation from therapy of catastrophic APLS. [29] Additional measures like antiembolic stockings, intermittent venous compression devices and adequate hydration are advisable. Tourniquets are to be avoided.

The reported incidence of postoperative thrombosis or bleeding is 84.2%; and mortality, 63.2%. [22] While Rawat et al. have reported an uncomplicated postoperative course in an APLS patient who underwent right atrial and pulmonary artery thrombectomy under CPB and DHCA with 1:1 reversal of heparin with protamine [21] ; early graft occlusion, hemothorax, pulmonary emboli and limb ischemia are known postoperative complications. [5] Postoperative early institution of anticoagulation with heparin and warfarin is recommended. The recommended target International normalized ratio (INR) favors moderate-intensity warfarin therapy (INR, 2.0-3.0) over high-intensity therapy (INR, 3.1-4.0). [30] Statins may be added to suppress inflammatory response in APLS. Other adjuvants mentioned are antiplatelet drugs, antimalarials, interleukin-3, complement inhibitors, peptide competitors, monoclonal antibodies, immunoabsorption procedures, and vaccinations; however, superiority over warfarin is not established. [31] Acute fulminant myocarditis is another dreaded complication, which can be managed by plasmapharesis, antithrombotic therapy, immunosuppressants or fresh frozen plasma replacement. [5],[32],[33]

Considering the virulent valvular tissue destruction with significant thickening and verrucous vegetations, repair of the native valve is not usually an option. Since these patients are younger and anticoagulation is mandatory, mechanical valves score over bioprosthetic valves as a choice for valve replacement. [34]

The authors' recommendations for management of APLS for cardiac surgery are as follows: multidisciplinary approach, minimized periods of "no anticoagulation," premeditated anticoagulation, coagulation factor assays, partial reversal of residual heparin dictated by Hepcon, use of TEG to guide coagulation-related decisions, close monitoring for complications and institution of postoperative anticoagulant therapy to a targeted INR of 2.0 to 3.0.

   References Top

1.Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: Report of an international workshop. Arthritis Rheum 1999;42:1309-11.  Back to cited text no. 1
2.Brandt JT, Triplett DA, Alving B, Scharrer I. Criteria for the diagnosis of lupus anticoagulants: An update. Thromb Haemost 1995;74:1185-90.  Back to cited text no. 2
3.Weiss S, Nyzio JB, Cines D, Detre J, Milas BL, Narula N, et al. Antiphospholipid syndrome: Intraoperative and postoperative anticoagulation in cardiac surgery. J Cardiothorac Vasc Anesth 2008;22:735-9.  Back to cited text no. 3
4.Shapiro SS, Thiagarajan P. Lupus anticoagulants. Prog Hemost Thromb 1982;6:263-85  Back to cited text no. 4
5.Dornan RI. Acute postoperative biventricular failure associated with antiphospholipid antibody syndrome. Br J Anaesth 2004;92:748-54.  Back to cited text no. 5
6.Petri M. Epidemiology of the antiphospholipid antibody syndrome. J Autoimmun 2000;15:145-51.  Back to cited text no. 6
7.Merkel PA, Chang YC, Pierangeli SS, Convery K, Harris EN, Polisson RP. The prevalence and clinical associations of anticardiolipin antibodies in a large inception cohort of patients with connective tissue diseases. Am J Med 1996;101:576-83.  Back to cited text no. 7
8.Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, et al. Systemic lupus erythematosus: Clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. Medicine (Baltimore) 1993;72:113-24.  Back to cited text no. 8
9.Love PE, Santoro SA. Antiphospholipid antibodies: Anticardiolipin and the lupus anticoagulant in systemic lupus erythematosus (SLE) and in non-SLE disorders: Prevalence and clinical significance. Ann Intern Med 1990;112:682-98.  Back to cited text no. 9
10.Nesher G, Ilany J, Rosenmann D, Abraham AS. Valvular dysfunction in antiphospholipid syndrome: Prevalence, clinical features, and treatment. Semin Arthritis Rheum 1997;27:27-35.  Back to cited text no. 10
11.Cervera R. Recent advances in antiphospholipid antibody-related valvulopathies. J Autoimmun 2000;15:123-5.  Back to cited text no. 11
12.Kaplan SD, Chartash EK, Pizzarello RA, Furie RA. Cardiac manifestations of the antiphospholipid syndrome. Am Heart J 1992;124:1331-8.  Back to cited text no. 12
13.Hojnik M, George J, Ziporen L, Shoenfeld Y. Heart valve Involvement (Libman-Sacks endocarditis) in the antiphospholipid syndrome. Circulation 1996;93:1579-87.  Back to cited text no. 13
14.Erdogan D, Goren MT, Diz-Kucukkaya R, Inanc M. Assessment of cardiac structure and left atrial appendage functions in primary antiphospholipid syndrome: A transesophageal echocardiographic study. Stroke 2005;36:592-6.  Back to cited text no. 14
15.Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med 2002;346:752-63.  Back to cited text no. 15
16.Asherson RA, Khamashta MA, Ordi-Ros J, Derksen RH, Machin SJ, Barquinero J, et al. The "primary" antiphospholipid syndrome: Major clinical and serological features. Medicine (Baltimore) 1989;68:366-74.  Back to cited text no. 16
17.Espínola-Zavaleta N, Vargas-Barrón J, Colmenares-Galvis T, Cruz-Cruz F, Romero-Cárdenas A, Keirns C, et al. Echocardiographic evaluation of patients with primary antiphospholipid syndrome. Am Heart J 1999;137:973-8.  Back to cited text no. 17
18.Asherson RA, Piette JC. The catastrophic antiphospholipid syndrome: Acute multiorgan failure associated with antiphospholipid antibodies: A review of 31 patients. Lupus 1996;5:414-74.  Back to cited text no. 18
19.Rojas-Rodriguez J, Garcia-Carrasco M, Ramos-Casals M, Enriquez-Coronel G, Colchero C, Cervera R, et al. Catastrophic antiphospholipid syndrome: Clinical description and triggering factors in 8 patients. J Rheumatol 2000;27:238-40.  Back to cited text no. 19
20.Asherson RA. The catastrophic antiphospholipid syndrome. J Rheumatol 1992;19:508-12.  Back to cited text no. 20
21.Rawat SK, Mehta Y, Vats M, Mishra Y, Khurana P, Threhan N. Anaesthetic management of right atrial mass removal and pulmonary artery thrombectomy in a patient with primary antiphospholipid antibody syndrome. Ann Card Anaesth 2010;13:39-43.  Back to cited text no. 21
[PUBMED]  Medknow Journal  
22.Ciocca RG, Choi J, Graham AM. Antiphospholipid antibodies lead to increased risk in cardiovascular surgery. Am J Surg 1995;170:198-200.  Back to cited text no. 22
23.Hegde VA, Vivas Y, Shah H, Haybron D, Srinivasan V, Dua A, et al. Cardiovascular surgical outcomes in patients with the antiphospholipid syndrome-a case series. Heart Lung Circ 2007;16:423-7.  Back to cited text no. 23
24.Rand JH, Wu XX, Andree HA, Ross JB, Rusinova E, Gascon-Lema MG, et al. Antiphospholipid antibodies accelerate plasma coagulation by inhibiting annexin-V binding to phospholipids: A "lupus procoagulant" phenomenon. Blood 1998;92:1652-60.  Back to cited text no. 24
25.Hogan WJ, McBane RD, Santrach PJ, Plumhoff EA, Oliver WC Jr, Schaff HV, et al. Antiphospholipid syndrome and perioperative haemostatic management of cardiac valvular surgery. Mayo Clin Proc 2000;75:971-6.  Back to cited text no. 25
26.East CJ, Clements F, Mathew J, Slaughter TF. Antiphospholipid syndrome and cardiac surgery: Management of anticoagulation in two patients. Anesth Analg 2000;90:1098-101.  Back to cited text no. 26
27.Leissner KB, Ketchedjian A, Crowley R, Ortega R, Hesselvik JF, Shemin RJ. Deep hypothermic circulatory arrest and bivalirudin use in a patient with heparininduced thrombocytopenia and antiphospholipid syndrome. J Card Surg 2007;22:78-82.  Back to cited text no. 27
28.Alpert D, Mandl LA, Erkan D, Yin W, Peerschke EI, Salmon JE. Anti-heparin platelet factor 4 antibodies in systemic lupus erythematosus are associated with IgM antiphospholipid antibodies and the antiphospholipid syndrome. Ann Rheum Dis 2008;67:395-401.  Back to cited text no. 28
29.Salmi L, Elalamy I, Leroy-Matheron C, Houel R, Thébert D, Duvaldestin P. Thrombosis of a cardiopulmonary bypass circuit despite recommended hypocoagulation with danaparoid during the acute phase of type II heparin-induced thrombocytopenia. Ann Fr Anesth Reanim 2006;25:1144-8.  Back to cited text no. 29
30.Crowther MA, Ginsberg JS, Julian J, Denburg J, Hirsh J, Douketis J, et al. A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003;349:1133-8.  Back to cited text no. 30
31.Lockshin MD, Erkan D. Treatment of the antiphospholipid syndrome. N Engl J Med 2003;349:1177-9.  Back to cited text no. 31
32.Asherson RA, Cervera R, Piette JC, Font J, Lie JT, Burcoglu A, et al. Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients. Medicine (Baltimore) 1998;77:195-207  Back to cited text no. 32
33.Nagappan R, Lodge RS. Acute autoimmune cardiomyopathy in primary antiphospholipid antibody syndrome. Anaesth Intens Care 2002;30:226-9.  Back to cited text no. 33
34.Berkun Y, Elami A, Meir K, Mevorach D, Naperstek Y. Increased morbidity and mortality in patients with antiphospholipid syndrome undergoing valve replacement surgery. J Thorac Cardiovasc Surg 2004;127:414-20.  Back to cited text no. 34

Correspondence Address:
Vipul Krishen Sharma
Department of Anaesthesiology and Critical Care, Armed Forces Medical College, Sholapur Road, Pune - 411 040
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-9784.81571

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