Low Molecular Weight Heparin in an ECMO Patient − Case Study
Extracorporeal membrane oxygenation (ECMO) has an irreplaceable role in intensive care medicine. In the context of preventing complications caused by blood clot formation, unfractionated heparin is most commonly used in patients on extracorporeal circulation. However, its administration can lead to complex coagulopathies, which may result in increased bleeding or, perhaps surprisingly, a higher frequency of blood clot formation. A unique case study recently presented by authors from Motol University Hospital in Prague demonstrates the safety and effectiveness of using low molecular weight heparin (LMWH) enoxaparin in this indication for a patient connected to ECMO for a very long duration (3 months), with several days even on two devices simultaneously.
Case Description
A 43-year-old man was hospitalized in a small hospital for covid pneumonia requiring mechanical ventilation. Due to the worsening of his condition caused by bacterial superinfection, he was transferred to a higher-level facility. He was urgently connected via the right femoral and jugular vein to venovenous (V-V) ECMO. This was preceded by a bolus intravenous administration of 6000 IU enoxaparin, followed by its continuous administration aiming to achieve prophylactic anti-Xa levels of 0.4−0.6 IU/ml. Blood gas values improved shortly thereafter.
On the 5th day of hospitalization, the patient developed a spontaneous pneumothorax requiring drainage. Due to minor bleeding into the airways, platelet function was examined using the PFA 200 device with COL/EPI and COL/ADP cartridges, both showing significant closure time disorders − indicating significant primary hemostasis disorder. Secondary hemostasis was normal according to the ROTEM analysis. The bleeding was successfully treated with von Willebrand factor and recombinant activated factor VII.
Due to gradual reduction in patient sedation, technical problems with ECMO emerged; therefore, on the 8th day of hospitalization, a change to VV-V ECMO (a cannula was added via the left femoral vein) was made, achieving sufficient oxygenation. On the 10th day, a tracheostomy was performed under continuous anticoagulation therapy without bleeding complications.
Due to slight improvement in lung function and patient cooperation, on the 44th day, a decision was made to revert to the original V-V ECMO. On the 51st day of hospitalization, a bicaval cannula was inserted via the left jugular vein, and the original right-sided cannulas were removed. However, the patient's condition was again complicated by lung infection and right-sided heart failure, and on the 57th day, venoarterial (V-A) ECMO was added via the left femoral vessels. The patient was on two ECMO devices simultaneously. Anticoagulation therapy remained unchanged.
Over the following days, the patient recovered from heart failure, allowing the disconnection of V-A ECMO on the 65th day and V-V ECMO on the 94th day. Consequently, continuous intravenous enoxaparin treatment was replaced with standard subcutaneous administration at a dose of 2x 40 mg/12 hours. Continuous improvement also allowed for the removal of the tracheostomy cannula on the 112th day.
During the hospitalization, there were no significant or life-threatening bleeding or thrombotic complications.
Low Molecular Weight Heparin or Unfractionated Heparin?
LMWH does not inhibit thrombin formation. Thus, if bleeding occurs in the patient, procoagulant therapy may be more effective. Unfractionated heparin can paradoxically have an activating effect on platelet aggregation, which might explain the frequent thrombotic complications observed with its use. The disadvantage of LMWH is its relatively long half-life and the absence of a highly effective antidote, although protamine can be used. To ensure good effect and safety, maintaining anti-Xa levels within the range of 0.4−0.6 IU/ml is crucial, as this level appears to be safe for bleeding prevention.
Safe Indication of LMWH
In conclusion, this case demonstrates the possibility of safe anticoagulant therapy using enoxaparin as an alternative to unfractionated heparin in patients requiring ECMO support.
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Source: Durila M., Beroušek J., Vlasáková V., Vymazal T. Intravenous enoxaparin as alternative ECMO anticoagulation over a period of 94 days: a case report. J Cardiothorac Surg 2023 Apr 11; 18 (1): 137, doi: 10.1186/s13019-023-02226-0.
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