Anticoagulation Therapy in Patients on ECMO During the COVID-19 Pandemic
In the past 2 years, the use of extracorporeal membrane oxygenation (ECMO) in intensive care units (ICU) has increased in connection with the treatment of severe COVID-19 pneumonia. Dr. Pilar Marcos Neira from the ICU at Germans Trias i Pujol Hospital in Barcelona has compiled a summary of updated knowledge on anticoagulation therapy in these patients.
Recommended anticoagulation therapy in patients on ECMO
The goal of anticoagulation therapy in patients requiring ECMO is to prevent thrombotic events. However, anticoagulation therapy increases the risk of bleeding, which also rises with the use of ECMO alone due to artificially induced coagulation and consumption of clotting factors.
According to the Extracorporeal Life Support Organization (ELSO) recommendations, systemic anticoagulation therapy is suitable for all patients on ECMO. For patients with active bleeding or high risk of bleeding, ECMO devices with heparin-coated circuits are used. ELSO's recommendations for anticoagulation in COVID-19 patients on ECMO do not differ from non-COVID patients. It is always necessary to individually assess the risk of thrombosis and bleeding.
Anticoagulants
The most commonly available anticoagulant is the indirect thrombin inhibitor, unfractionated heparin (UFH), administered with an initial dose of 70–100 IU/kg followed by a maintenance dose of 18–20 IU/kg/hr. Its available antidote is protamine. The most common complications of UFH administration are bleeding, heparin-induced thrombocytopenia (HIT), and heparin resistance. All these complications worsen anticoagulation effects.
Thus, direct thrombin inhibitors (DTIs) – bivalirudin, indicated for percutaneous coronary intervention, and argatroban, indicated for HIT, are increasingly appreciated alternatives. (However, these medications are not registered in Czechia.) The reason being that UFH acts indirectly through the inhibition of thrombin. It does not block thrombin formation but inhibits thrombin released into circulation. On the contrary, bivalirudin directly inhibits thrombin, not only in circulation but also in already formed thrombi, and thus can mitigate the pro-thrombotic nature of acute respiratory distress syndrome (ARDS) in COVID-19. When administering bivalirudin and argatroban, the activated partial thromboplastin time (APTT) ratio (APTTr) and activated coagulation time (ACT) need to be monitored.
Studies comparing direct and indirect thrombin inhibitors in ECMO
In a cohort study involving 33 patients on ECMO due to ARDS from COVID-19 infection, initial bivalirudin dose was most commonly 0.2 mg/kg/hr. Therapeutic range (activated partial thromboplastin time [APTT] 40–80 s; APTTr 1.5–2; ACT 160–200 s; anti-Xa 0.3–0.7 IU/ml) was achieved on average in 20 hours. The incidence of bleeding was 15.1% and thrombosis 6.1%.
In another retrospective study, UFH and bivalirudin anticoagulation were compared in 295 patients with venovenous ECMO. The risk of thrombosis in the UFH group was 2.31 times higher than in the bivalirudin group. Besides, lower incidence of bleeding and reduced transfusion needs were observed with bivalirudin use.
A retrospective cohort study comparing UFH and bivalirudin in 424 patients with venoarterial ECMO showed lower mortality with bivalirudin in adults (odds ratio [OR] 0.39; p < 0.01) and fewer infusion needs in the first 24 hours for children (OR 0.28; p = 0.02).
In a retrospective study with 144 ECMO patients, 14 received bivalirudin due to HIT or heparin resistance. The authors did not observe any differences in the incidence of bleeding or thrombotic complications between UFH and bivalirudin patients, but the transfusion need was lower with bivalirudin.
ECMO without anticoagulation therapy
A systematic review including 34 studies with 201 ECMO patients did not show significant differences in the incidence of thrombosis on days when no anticoagulation was administered (average 4.75 days). An observational study showed thrombosis incidence of 6.5% for patients on ECMO without anticoagulation (average 7 days), all after the 5th day of treatment. Transfusion needs were one-third compared to published data.
Complications of anticoagulation therapy
Complications of anticoagulation therapy during ECMO include major bleeding, both related to invasive procedures and spontaneous. In life-threatening bleeding, it is recommended to rely on viscoelastic tests (TEG or ROTEM) when administering transfusions. Another well-known complication is heparin thrombocytopenia. The causes are multifactorial, and it is often difficult to distinguish between heparin-associated thrombocytopenia (HAT − a mild and transient decrease in platelet count at the beginning of therapy) and heparin-induced thrombocytopenia (HIT − moderate to severe thrombocytopenia, usually occurring 5–14 days after therapy start, with progressive or rapid onset). In patients on ECMO due to ARDS associated with COVID-19, no increased incidence of HIT was observed.
(zza)
Source: Neira P. M. Monograph III: Anticoagulation and risk of bleeding during extracorporeal membrane oxygenation therapy. Bleeding News, 2021 Oct.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
