Extracorporeal Membrane Oxygenation Anticoagulation

Anatomy and Physiology

The ECMO circuit temporarily assumes the function of the heart, lungs, or both by withdrawing deoxygenated blood from the venous system, directing it through a membrane oxygenator for gas exchange, and returning oxygenated blood to the patient. Standard components include drainage and return cannulas, a centrifugal or roller pump, a membrane oxygenator, a heat exchanger, a sweep gas source, and integrated monitoring sensors.

Venovenous Extracorporeal Membrane Oxygenation Configurations

VV-ECMO is most commonly used in cases of isolated respiratory failure. Several configuration options are available, depending on patient anatomy and institutional preference.

The femoral-internal jugular (fem-IJ) approach involves drainage through the femoral vein and return via the internal jugular vein. The fem-IJ setup is one of the most frequently used. The femoral-femoral (fem-fem) configuration places both cannulas in the femoral veins bilaterally. Although technically easier to insert, the fem-fem setup may limit patient ambulation.

A dual-lumen cannula, typically inserted through the internal jugular vein, contains separate ports for drainage and return within a single device. When positioned to direct oxygenated blood toward the tricuspid valve, the cannula reduces bleeding risk and supports ambulation and extubation. This configuration is especially well-suited for patients being bridged to lung transplantation or rehabilitation. Individuals with fem-IJ or fem-fem cannulation may also be extubated and participate in physical therapy when clinically appropriate.

VV-ECMO provides pulmonary support only. Gas exchange occurs within the oxygenator, allowing for lung-protective ventilator settings and facilitating lung rest.

Venoarterial Extracorporeal Membrane Oxygenation Configurations

VA-ECMO supports both cardiac and pulmonary function, making it appropriate for patients in cardiogenic shock or cardiac arrest. Venous drainage is typically achieved through the femoral or internal jugular vein, while oxygenated blood is returned via the femoral, axillary, or carotid artery.

Femoral arterial return results in retrograde aortic perfusion, which can compromise coronary or cerebral blood flow if native cardiac function recovers unevenly, producing a watershed phenomenon. Axillary artery cannulation provides antegrade flow that more closely approximates physiologic conditions and lowers the risk of limb ischemia, although it requires a surgical cutdown and graft placement. Carotid artery cannulation is generally reserved for neonates and infants weighing less than 15 kg.

VA-ECMO fully bypasses both heart and lung function. The circuit maintains cardiac output, while the oxygenator performs gas exchange.[3]

Central Extracorporeal Membrane Oxygenation

Central cannulation is used in select cases, such as postcardiotomy support or when peripheral access is inadequate. The technique involves direct cannulation of the right atrium and ascending aorta through a sternotomy. Although more invasive, central ECMO offers superior venous drainage, antegrade arterial perfusion, and effective left ventricular decompression. This approach carries increased risks of bleeding and infection but can be lifesaving in severe cardiac dysfunction.

Circuit Components and Thrombogenicity

The ECMO circuit includes a drainage cannula for venous blood removal, a centrifugal pump to propel blood with minimal shear stress, an oxygenator for gas exchange, a heat exchanger to maintain normothermia, and a return cannula to deliver oxygenated blood to the patient. Blood contact with artificial surfaces activates platelets and triggers inflammatory cytokine release, contributing to a prothrombotic state. Older roller pumps, associated with higher shear stress and hemolysis, have been largely replaced by centrifugal pumps due to improved biocompatibility and flow regulation. The oxygenator is particularly susceptible to thrombus formation and requires regular inspection by perfusionists or ECMO specialists.[4]

Indications

ECMO is indicated when conventional therapies fail to maintain adequate gas exchange or hemodynamic support. Proper patient selection is crucial to optimize outcomes, as ECMO is resource-intensive and carries significant risk. Indications may be broadly categorized into respiratory failure, cardiac failure, and extracorporeal cardiopulmonary resuscitation. The choice between VV-ECMO and VA-ECMO depends on whether the primary failure involves the lungs or the heart, respectively.

Venovenous Extracorporeal Membrane Oxygenation Indications

VV-ECMO is primarily used in cases of severe respiratory failure with preserved cardiac function. Common adult indications include severe hypoxemia, typically defined by an arterial oxygen partial pressure-to-inspired oxygen fraction (PaO2/FiO2) ratio below 100 mm Hg despite maximal ventilatory support and prone positioning. This threshold is associated with high mortality and often prompts ECMO consideration.

Refractory hypercapnia with persistent respiratory acidosis despite escalated mechanical ventilation is another indication. Acute respiratory collapse, such as in status asthmaticus, massive aspiration, or near-drowning, may also necessitate VV-ECMO when oxygenation or ventilation cannot be supported conventionally. Severe acute respiratory distress syndrome due to pneumonia, trauma, or inhalation injury is a frequent indication, as is bridging to lung transplantation for patients with progressive respiratory failure. Posttransplant primary graft dysfunction is another recognized indication, particularly in specialized transplant centers.

In pediatric populations, VV-ECMO initiation is often guided by the oxygenation index rather than the PaO2/FiO2 ratio. Values above 16 are generally used to define severe pediatric acute respiratory distress syndrome, as outlined by the Pediatric Acute Lung Injury Consensus Conference. Although no absolute threshold exists, worsening oxygenation index trends are closely monitored to guide the timing of support initiation.[5]

Venoarterial Extracorporeal Membrane Oxygenation Indications

VA-ECMO provides both cardiac and pulmonary support. This modality is warranted when the heart cannot generate adequate output.

Common indications include cardiogenic shock due to acute myocardial infarction, fulminant myocarditis, decompensated heart failure, and postcardiotomy low cardiac output syndrome. VA-ECMO is also used during cardiac arrest requiring extracorporeal cardiopulmonary resuscitation, particularly in witnessed in-hospital events with short low-flow duration. Failure to wean from cardiopulmonary bypass following cardiac surgery may warrant VA-ECMO as a bridge to recovery or further intervention. Additional indications include bridging to durable mechanical circulatory support, such as ventricular assist devices or cardiac transplantation.

In patients with massive pulmonary embolism and hemodynamic collapse, VA-ECMO can stabilize circulation during thrombolysis or surgical embolectomy. Severe cardiac suppression from drug overdose or poisoning may also necessitate support with VA-ECMO.[6] In select cases of sepsis-induced cardiomyopathy, VA-ECMO may be considered when hypotension and end-organ hypoperfusion persist despite maximal vasopressor and inotropic therapy.

General Considerations

When evaluating a patient for ECMO, clinicians must assess the reversibility of the underlying condition or its potential to serve as a bridge to definitive therapy. The duration of mechanical ventilation before ECMO initiation is a critical factor, as outcomes deteriorate with prolonged intubation beyond 7 days. Comorbidities such as chronic organ dysfunction or immunosuppression may also limit the likelihood of recovery. Resource availability and institutional expertise significantly influence outcomes and must be considered in the decision-making process.

In clinical practice, ECMO is most effective when initiated early in the course of potentially reversible cardiopulmonary failure, before the onset of multiorgan dysfunction. The decision to proceed with ECMO should be individualized and made by an experienced interprofessional team based on a careful assessment of risks and anticipated benefits.

Contraindications

Although ECMO can be life-saving, it is an invasive, resource-intensive therapy associated with substantial risk. No universally accepted absolute contraindications exist. However, several conditions are considered relative contraindications due to their association with poor outcomes or elevated procedural risk. The decision to initiate ECMO should be individualized and guided by input from an experienced interprofessional team.

Relative Contraindications

Several conditions are considered relative contraindications to ECMO due to limited benefit or elevated procedural risk. Irreversible neurologic injury, such as massive intracranial hemorrhage or global anoxic brain injury without the potential for meaningful recovery, generally precludes ECMO, as the intervention does not alter neurologic outcome. Severe immunosuppression or terminal malignancy also limits the appropriateness of ECMO, particularly in patients with poor healing capacity or shortened life expectancy due to progressive disease or susceptibility to overwhelming infection.

Advanced age, particularly beyond 75 years, is associated with reduced physiologic reserve and poorer outcomes. Although not an absolute contraindication, ECMO decisions in this population should consider frailty, preillness functional status, and stated goals of care. Prolonged mechanical ventilation exceeding 7 to 10 days prior to ECMO initiation is linked to worse outcomes, especially in the presence of high ventilator pressures and inspired oxygen fractions. In such cases, irreversible lung injury may have already occurred.

Severe multiorgan failure, including irreversible renal, hepatic, or neurologic dysfunction in the setting of refractory shock, may also limit the potential benefit of ECMO, particularly in the absence of a viable bridge to recovery. Morbid obesity introduces additional technical challenges, such as cannulation difficulty, reduced ECMO flow relative to body surface area, and increased risk of complications, including bleeding and thrombosis. Despite these risks, morbid obesity is not a strict contraindication, and favorable outcomes remain possible in selected patients.

Poor baseline quality of life or a lack of potential for meaningful recovery further limits the utility of ECMO. Patients with end-stage organ disease, progressive neurodegenerative disorders, or other conditions incompatible with functional independence may not derive benefit, particularly when aligned with individual goals of care.

Challenges with Anticoagulation

A key consideration is the inability to safely administer anticoagulation, such as in the setting of active bleeding, recent surgery, or elevated risk of intracranial hemorrhage. Anticoagulation is critical for preventing thrombosis within the ECMO circuit. In select cases, such as postoperative bleeding or intracranial pathology, centers may adopt low-dose or anticoagulant-free protocols under close monitoring. These patients face heightened risk for both thrombosis and bleeding, requiring continuous interprofessional coordination.

Patients with known heparin-induced thrombocytopenia present an additional challenge. Although not a contraindication to ECMO, these patients require alternative anticoagulants such as direct thrombin inhibitors, including bivalirudin or argatroban. These agents can be more difficult to titrate and are not easily reversible.

Ethical and Logistical Considerations

Ethical concerns such as lack of social support, incarceration, or unwillingness to pursue future therapies, including transplant refusal, may influence decisions regarding ECMO. Logistical barriers such as the absence of ECMO-trained personnel, limited perfusion support, or unavailable intensive care unit beds may also preclude timely initiation.

ECMO candidacy must be determined through collaborative evaluation of physiologic risk, anticipated benefit, institutional resources, and patient-centered goals of care. Shared decision-making with the patient or surrogate remains essential.

Technique or Treatment

The technique of ECMO includes both vascular cannulation and anticoagulation. Each component must be tailored to the patient's condition and aligned with institutional protocols.

Cannulation

Peripheral cannulation is the most common approach and may be performed using the Seldinger technique, surgical cutdown, or graft anastomosis. In VV-ECMO, venous drainage typically occurs through the femoral or internal jugular vein, and return is directed to the right atrium using either dual-lumen catheters or separate cannulas. VA-ECMO involves venous drainage from the femoral or internal jugular vein with arterial return through the femoral or axillary artery. Axillary cannulation permits antegrade arterial flow and reduces the risk of limb ischemia.

Central ECMO requires surgical access via sternotomy and involves direct cannulation of the right atrium and ascending aorta. This method offers improved drainage and antegrade perfusion but carries greater risks of bleeding and infection. This approach is generally reserved for postcardiotomy or other surgical cases.

Following cannulation, blood flows through a circuit composed of tubing, a centrifugal pump, and a membrane oxygenator. Exposure to these nonendothelial surfaces activates platelets, neutrophils, and coagulation cascades. Proinflammatory cytokines further amplify the response, producing a highly thrombogenic environment that necessitates continuous anticoagulation.

Anticoagulation

Unfractionated heparin (UFH) is the most widely used anticoagulant during ECMO. Antithrombin activity is enhanced, leading to inhibition of thrombin and factor Xa and reduction in clot formation.[7] Most institutions administer a bolus at the time of cannulation, followed by continuous infusion. Titration is guided by 1 or more monitoring strategies. Activated clotting time is rapid and readily available but may overestimate anticoagulation, especially in pediatric patients. Activated partial thromboplastin time is commonly targeted within a range of 60 to 90 seconds. Anti-factor Xa, considered the gold standard, typically targets 0.25 to 0.7 IU/mL.[8]

Heparin resistance may occur in the setting of antithrombin III deficiency, particularly in neonates, patients with nephrotic syndrome, or individuals requiring high doses of UFH. Supplementation with antithrombin III concentrates may restore therapeutic response. Institutional protocols usually define thresholds and monitoring frequency.

Direct thrombin inhibitors such as bivalirudin and argatroban are preferred in patients with heparin-induced thrombocytopenia or persistent heparin resistance. Bivalirudin is dosed as a 0.5 mg/kg bolus followed by infusion at 0.5 to 2.5 mcg/kg/min, while argatroban is given as a 350 mcg/kg bolus with infusion at 25 mcg/kg/min. Both agents are titrated using activated partial thromboplastin time.[9][10][11] Direct thrombin inhibitors provide more predictable anticoagulation because they do not rely on antithrombin, but their use is limited by cost and the lack of specific reversal agents in the event of bleeding.

Daily Anticoagulation Targets

Target parameters for anticoagulation during ECMO often include a UFH level of 0.25 to 0.5 IU/mL, with some protocols allowing up to 0.7 IU/mL. Antithrombin III activity should exceed 50%. Hematocrit is typically maintained above 35%, and platelet counts above 100,000/μL, although lower thresholds may be accepted in the setting of active bleeding. Prothrombin time or international normalized ratio should remain below 2, depending on the monitoring method used. Fibrinogen levels should remain above 100 mg/dL.

Viscoelastic assays such as thromboelastography or rotational thromboelastometry provide additional insight into clot formation and fibrinolysis, particularly in complex bleeding or thrombotic states.[12] Optimal ECMO management requires continuous reassessment of anticoagulation intensity in response to hemorrhage, thrombosis, surgical intervention, or hemodynamic instability. Achieving therapeutic goals while minimizing complications depends on close collaboration among intensivists, pharmacists, nurses, perfusionists, and laboratory personnel.

Complications

Complications Arising from Venovenous Extracorporeal Membrane Oxygenation

In VV-ECMO, complications frequently result from inadequate circuit flow relative to elevated native cardiac output, as seen in sepsis. When cardiac output surpasses ECMO flow, incomplete mixing of oxygenated and deoxygenated blood may lead to persistent hypoxemia despite optimal ventilator settings and functional circuit performance.

Complications Resulting from Venoarterial Extracorporeal Membrane Oxygenation

VA-ECMO presents unique challenges related to retrograde arterial flow. Femoral artery cannulation may impair distal limb perfusion and increase the risk of ischemia. This complication may be reduced by placing selective reperfusion catheters or by using axillary artery access. Retrograde flow also increases left ventricular afterload, which may lead to ventricular distension, pulmonary edema, and reduced coronary perfusion.[13] Clinical indicators include diminished arterial pulsatility, elevated left ventricular end-diastolic pressure, and ventricular arrhythmias. Management strategies to decompress the left ventricle include placement of an Impella device, surgical venting, or atrial septostomy to facilitate forward flow.

Thrombosis and Heparin-Induced Thrombocytopenia

Thromboembolic events remain a concern during both VV-ECMO and VA-ECMO, particularly in regions of low flow, stagnant zones, and within the oxygenator. Hemolysis from mechanical shear stress further increases thrombogenic risk. Pump head thrombosis may present with elevated plasma-free hemoglobin levels exceeding 500 mg/dL and a platelet count reduction greater than 50%, often necessitating urgent circuit replacement.

Heparin-induced thrombocytopenia is a potentially life-threatening, immune-mediated complication of heparin therapy. Suspicion should arise with a platelet decline of 50% or more occurring within 5 to 14 days of heparin initiation.[14] Diagnosis requires laboratory confirmation, such as enzyme-linked immunosorbent assay or serotonin release assay. Once confirmed, heparin must be discontinued and replaced with a direct thrombin inhibitor.

Other Complications

Additional risks include bleeding at cannulation sites or inside the body, particularly within the gastrointestinal tract or intracranial space. Infection, air embolism, circuit component failure, and progressive hemolysis also pose significant risks. Early recognition and structured, protocol-driven management by an interprofessional team are essential to reduce morbidity and improve patient outcomes.

Clinical Significance

The complexity of anticoagulation management continues to grow as ECMO becomes more widely utilized. Rigorous monitoring is essential to reduce the dual risks of thrombosis and bleeding. A clear understanding of circuit pathophysiology, anticoagulant pharmacology, and appropriate monitoring strategies enables clinicians to intervene early and tailor care to individual patient needs. Team-based assessment and effective communication across disciplines, particularly between intensivists, nurses, perfusionists, and pharmacists, are critical for identifying circuit complications, adjusting therapy, and improving patient outcomes. Timely recognition of clinical deterioration and circuit-related issues directly influences survival and recovery.

Enhancing Healthcare Team Outcomes

The safe and effective use of ECMO depends on continuous interprofessional collaboration. From initiation through weaning, successful management requires coordinated efforts among surgical, critical care, nursing, perfusion, and pharmacy teams.

A cardiothoracic surgeon typically performs cannulation and initiates support. Perfusionists operate the ECMO circuit at the bedside, adjusting parameters in real time and monitoring for complications such as oxygenator failure, hemolysis, and thrombus formation to ensure uninterrupted function.

Intensive care physicians, physician assistants, and nurse practitioners oversee daily management, including hemodynamic support, ventilator adjustments, anticoagulation titration, and multisystem care. Pharmacists assist with anticoagulant dosing, heparin resistance, and drug-drug interaction management. Nurses provide one-to-one bedside care, conduct frequent neurologic assessments, inspect cannula sites, and monitor circuit alarms and patient responses.

Anticoagulation oversight, hourly monitoring, and arterial blood gas interpretation are shared responsibilities. When clinical deterioration occurs, early recognition and rapid response by any team member can lead to lifesaving intervention.

Structured communication tools, standardized handoffs, and mutual respect across disciplines enhance team function and reduce complications. Flattened hierarchy and shared accountability strengthen interprofessional collaboration and improve both the safety and outcomes of ECMO therapy.

Nursing, Allied Health, and Interprofessional Team Interventions

Responsibilities of Bedside Staff to the Patient

Caring for patients on ECMO typically requires a staffing model that approximates 1:1 care for both the individual and the ECMO circuit. The circuit is treated as a second patient, demanding continuous monitoring and immediate intervention when complications arise.

Patient Monitoring and Intervention

Patient movement during imaging or repositioning should be coordinated with multiple team members to reduce the risk of complications. Daily chest radiographs must be obtained to assess lung fields and confirm the position of cannulas, endotracheal tubes, chest tubes, and central lines. Cannula sites should be inspected frequently for signs of bleeding, infection, or mechanical issues such as kinking or dislodgement.

Neurologic examinations must be performed every 1 to 2 hours due to the elevated risk of intracranial hemorrhage, stroke, and seizures. These assessments should include evaluation of pupillary reflexes, spontaneous respirations, pain responses, and, in pediatric patients, fontanelle size and autonomic signs such as episodic tachycardia or hypertension, which may indicate subclinical seizures or intracranial bleeding.

Ventilator settings should be adjusted based on ECMO circuit performance. Since ventilation is often significantly reduced while on ECMO, declining gas exchange may indicate thrombus formation within the oxygenator. Arterial blood gases are typically monitored every 30 to 60 minutes during initiation, then every 2 to 4 hours once stable. Endotracheal suctioning is performed as needed. The presence of bright red blood in the endotracheal tube may suggest pulmonary hemorrhage, which may respond to increased positive end-expiratory pressure.

Renal function and hemolysis should be continuously monitored. Urine output and color must be documented regularly. Gross hematuria may result from anticoagulation. Plasma-free hemoglobin levels exceeding 500 mg/dL, accompanied by a decline in platelet count, raise suspicion for pump head thrombosis.[15] Levels above 53 mg/dL have been associated with increased risk for renal replacement therapy and mortality.[16]

Responsibilities of Bedside Staff to the Extracorporeal Membrane Oxygenation Circuit

The ECMO circuit should be inspected regularly for signs of clot formation, tubing discoloration, or structural abnormalities. Circuit performance must be evaluated by trending transmembrane pressures, bladder pressures, fraction of inspired oxygen, and sweep gas flow. Audible circuit "chatter" should be recognized as a potential indicator of hypovolemia or low venous return, which may result from inadequate preload, pneumothorax, or cardiac tamponade.

System alarms must be addressed without delay. These alerts may be triggered by patient agitation, volume depletion, or cannula kinking. Rapid evaluation is required to prevent circuit compromise and ensure uninterrupted support.