BACKGROUND: Thrombocytopenia is a recognized risk factor for bleeding during extracorporeal membrane oxygenation (ECMO). This study determines the incidence, risk factors, and clinical relevance of thrombocytopenia and platelet transfusions during venovenous (VV) ECMO. METHODS: The multicenter, prospective observational PROTECMO study included 652 adult patients who received VV ECMO for respiratory failure. Thrombocytopenia was classified as mild (100-149·109/L), moderate (50-99·109/L), or severe (< 50·109/L). Bleeding events were evaluated using a modified Bleeding Academy Research Consortium score. Cox proportional hazards and logistic regression analyses were done to identify predictors, and quantify the association between platelet counts and bleeding risk. RESULTS: A total of 182 patients (27.9%) had thrombocytopenia at baseline (mild in 14.7%, moderate in 8.7%, and severe in 4.4%). Thrombocytopenia during ECMO, at least once in 80.2% of patients, was mild in 21.3% of cases, moderate in 32.2%, and severe in 26.7%. A 10·109/L decrease in platelet count was associated with a 3.7% (95% CI: 2.4-5.0%) increase in risk of bleeding. There was no strong evidence of nonlinear relationship within the platelet count range between 25,000 and 300,000. This relation remained consistent across all ECMO weeks. Mild thrombocytopenia increased the risk of experiencing a bleeding event by 61% (hazard ratio (HR) 1.611, 95% CI 1.230-2.109, p = 0.0005), while moderate and severe thrombocytopenia increased the risk by roughly 90% (moderate: HR 1.944 (CI 1.484-2.545), p < 0.0001; severe: HR 1.876 (CI 1.275-2.7680), p = 0.0014). The risk for thrombocytopenia < 100·109/L during ECMO significantly increased with ICU days prior to ECMO start, postoperative admission, immunocompromised state, renal replacement therapy, septic shock, low hemoglobin, and circuit exchange. CONCLUSIONS: Thrombocytopenia is highly prevalent in VV ECMO, and associated with a significant increase in the risk of bleeding, and a reduction in 6-month survival, particularly at platelet counts below 100·109/L. Further research is needed to better define the outcomes associated with specific thresholds for transfusion of platelets.

• Klíčová slova
• Anticoagulation, Bleeding, Intensive care, Platelet kinetics, Predictors, Thrombocytopenia, VV ECMO,
• MeSH
• dospělí MeSH
• incidence MeSH
• krvácení etiologie   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace * škodlivé účinky   metody   MeSH
• počet trombocytů metody   MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• transfuze trombocytů MeSH
• trombocytopenie * epidemiologie   etiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Unfractionated heparin has long been considered the standard anticoagulation in ECMO, despite some pitfalls such as heparin resistance, heparin induced thrombocytopenia (HIT), etc Recently, some centres started to increasingly use argatroban for this purpose, typically using activated partial thromboplastin time (aPTT) for its monitoring. Direct monitoring of the efficacy of argatroban using Anti-IIa is not yet an established method, although it might be more appropriate as it targets the same pathway.An observational study was performed in adult veno-venous ECMO patients hospitalized with SARS-CoV-2 infection anticoagulated with argatroban to an aPTT target of 40-60 s and Anti-IIa target of 0.4-0.6 µg/mL. Bleeding and thrombotic complications were monitored.Forty-four VV ECMO patients were included, with an overall hospital mortality of approx. 50%. No life-threatening thrombotic events were recorded. The risk of bleeding complications significantly increased with aPTT above 52.7 s and with Anti-IIa values over 0.78 µg/mL. Using the above cut-offs for both the aPTT and Anti-IIa and their combination, the negative predictive value for bleeding was approximately 90%.It seems that the generally recommended limits for Anti-IIa of 1.5 µg/mL may be high. However, further data are needed to confirm lower limits.Trial Registration:retrospectively registered in ClinicalTrials.gov, NCT06038682.

• Klíčová slova
• Anti-IIa, activated partial thromboplastin time (aPTT), anticoagulation, argatroban, extracorporeal oxygenation (ECMO), monitoring,
• MeSH
• antikoagulancia * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• arginin analogy a deriváty   MeSH
• COVID-19 * krev   terapie   mortalita   komplikace   MeSH
• dospělí MeSH
• farmakoterapie COVID-19 * MeSH
• krvácení chemicky indukované   MeSH
• kyseliny pipekolové * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace * metody   MeSH
• monitorování léčiv metody   MeSH
• parciální tromboplastinový čas MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• sulfonamidy MeSH
• trombóza prevence a kontrola   etiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• antikoagulancia * MeSH
• argatroban MeSH Prohlížeč
• arginin MeSH
• kyseliny pipekolové * MeSH
• sulfonamidy MeSH

BACKGROUND: Anticoagulation during extracorporeal membrane oxygenation (ECMO) might still lead to severe bleeding complications. Heparin is the most frequently used anticoagulant, but novel drugs could be promising. Argatroban is a new alternative to heparin. To date, no robust studies have confirmed the clear superiority of argatroban (AG) over heparin, although it has some advantages and may be safer. STUDY DESIGN AND METHODS: An observational study was conducted in all adult veno-venous ECMO patients with COVID-19-associated acute respiratory distress syndrome admitted to the University Hospital Ostrava (n = 63). They were anticoagulated with heparin in the first period and with AG in the second period, targeting the same activated partial thromboplastin time (aPTT; 45-60 s). Bleeding complications requiring transfusion and life-threatening bleeding events were evaluated. The primary objective was to compare heparin and AG in terms of bleeding, transfusion requirements and mortality-related bleeding. RESULTS: The total time on ECMO per patient was 16 days with an in-hospital mortality of 55.6%. The red blood cell consumption in the AG group (median 2.7 transfusions/week) was significantly lower than in the heparin group (median 4.2 transfusions/week, p = 0.011). Life-threatening bleeding complications were higher in the heparin group compared to the AG group (35.7% vs. 10.2%, p = 0.035), and mortality-related bleeding complications were also higher in the heparin group (21.4% vs. 2.0%, p = 0.032). DISCUSSION: Argatroban is an interesting alternative to heparin with less bleeding, less need for red blood cell transfusions and improved safety of ECMO with less mortality-related bleeding.

• Klíčová slova
• anticoagulation, argatroban, bleeding, extracorporeal membrane oxygenation (ECMO), heparin,
• MeSH
• antikoagulancia * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• arginin analogy a deriváty   škodlivé účinky   aplikace a dávkování   analogy a deriváty   MeSH
• COVID-19 * terapie   krev   mortalita   MeSH
• dospělí MeSH
• heparin * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• krvácení * chemicky indukované   epidemiologie   prevence a kontrola   MeSH
• kyseliny pipekolové * škodlivé účinky   aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace * škodlivé účinky   mortalita   MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• sulfonamidy * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH
• Názvy látek
• antikoagulancia * MeSH
• argatroban MeSH Prohlížeč
• arginin MeSH
• heparin * MeSH
• kyseliny pipekolové * MeSH
• sulfonamidy * MeSH

Extracorporeal membrane oxygenation (ECMO) has been established as a life-saving technique for patients with the most severe forms of respiratory or cardiac failure. It can, however, be associated with severe complications. Anticoagulation therapy is required to prevent ECMO circuit thrombosis. It is, however, associated with an increased risk of hemocoagulation disorders. Thus, safe anticoagulation is a cornerstone of ECMO therapy. The most frequently used anticoagulant is unfractionated heparin, which can, however, cause significant adverse effects. Novel drugs (e.g., argatroban and bivalirudin) may be superior to heparin in the better predictability of their effects, functioning independently of antithrombin, inhibiting thrombin bound to fibrin, and eliminating heparin-induced thrombocytopenia. It is also necessary to keep in mind that hemocoagulation tests are not specific, and their results, used for setting up the dosage, can be biased by many factors. The knowledge of the advantages and disadvantages of particular drugs, limitations of particular tests, and individualization are cornerstones of prevention against critical events, such as life-threatening bleeding or acute oxygenator failure followed by life-threatening hypoxemia and hemodynamic deterioration. This paper describes the effects of anticoagulant drugs used in ECMO and their monitoring, highlighting specific conditions and factors that might influence coagulation and anticoagulation measurements.

• Klíčová slova
• aPTT, antiIIa, antiXa, anticoagulation, argatroban, bivalirudin, extracorporeal membrane oxygenation, heparin,
• MeSH
• antikoagulancia škodlivé účinky   MeSH
• antitrombiny terapeutické užití   MeSH
• hemokoagulace MeSH
• heparin * škodlivé účinky   MeSH
• lidé MeSH
• mimotělní membránová oxygenace * škodlivé účinky   metody   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antikoagulancia MeSH
• antitrombiny MeSH
• heparin * MeSH