Heparin is the principal anticoagulant for ECMO despite its shortcomings

Despite improvements in anticoagulation monitoring, the majority of complications in extracorporeal membrane oxygenation (ECMO) continue to involve patient bleeding and circuit clotting.

The technology leading to the development of ECMO grew out of the experience with cardiopulmonary bypass, and unfractionated heparin (UNFH) has long been the anticoagulant of choice for both of these methods of support. Heparin was first used clinically in 1937 for the prevention of pulmonary embolisms in post-operative and postpartum patients. [1] UNFH continues to be widely used, widely available, and relatively inexpensive. As an intravenous infusion, it has a relatively short half-life, and it can be easily reversed with protamine.

Most of the anticoagulant effect of UNFH is due to its binding with antithrombin. The UNFH-antithrombin complex is approximately 1000-fold more effective than antithrombin alone. [2] The remaining anticoagulant effect comes from the increased release of tissue factor pathway inhibitor (TFPI) with UNFH administration. [3] As the effect of UNFH is largely dependent on antithrombin, it is difficult to achieve therapeutic anticoagulation with UNFH in patients with congenital or acquired antithrombin deficiency. Antithrombin can be replaced with commercially available concentrate or with fresh frozen plasma (FFP). However, antithrombin concentrate is very costly, and replacement of antithrombin with FFP exposes the patient to a large volume of blood product replacement. One milliliter of FFP contains approximately one unit of antithrombin. [4] Studies on the use of antithrombin concentrates for patients on ECMO have failed to demonstrate meaningful improvement in clinical outcomes. [5,6]

Another complication of UNFH is the potential of heparin-induced thrombocytopenia (HIT). The incidence of HIT is 0.9 to 4.9% in adult patients treated with heparin [7] and carries a mortality of 17% to 30%. [8] HIT is less commonly seen in pediatric patients. [9]


[1] Verstraete M. Heparin and thrombosis: a seventy year long story. Haemostasis 1990

[2] Pratt CW, Church FC. Antithrombin: structure and function. Semin Hematol 1991

[3] Sandset PM, Bendz B, Hansen JB. Physiological function of tissue factor pathway inhibitor and interaction with heparins. Haemostasis 2000

[4] Mintz PD, Blatt PM, Kuhns WJ, Roberts HR. Antithrombin III in fresh frozen plasma, cryoprecipitate, and cryoprecipitate-depleted plasma. Transfusion 1979

[5] Niebler RA, Christensen M, Berens R, Wellner H, Mikhailov T, Tweddell JS. Antithrombin replacement during extracorporeal membrane oxygenation. Artificial Organs 2011

[6] Byrnes JW, Swearingen CJ, Prodhan P, Fiser R, Dyamenahalli U. Antithrombin III supplementation on extracorporeal membrane oxygenation: impact on heparin dose and circuit life. ASAIO J 2014

[7] Warkentin TE, Sheppard JA, Horsewood P, Simpson PJ, Moore JC, Kelton JG. Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood 2000

[8] Jang IK, Hursting MJ. When heparins promote thrombosis: review of heparin-induced thrombocytopenia. Circulation 2005

[9] Avila ML, Shah V, Brandao LR. Systematic review on heparin-induced thrombocytopenia in children: a call to action. J Thromb Haemost 2013