ECMO Anticoagulant Aptamers for Durable Coagulation Control
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Solution Overview
Problem
Current anticoagulants used in extracorporeal membrane oxygenation (ECMO), such as unfractionated heparin, pose significant risks of bleeding, thrombosis, and complications in infants and adults, particularly in conditions like COVID-19, due to their limitations in inhibiting thrombin generation and immune responses.
Innovation Solution
Administration of anticoagulant aptamers that directly inhibit specific steps in the coagulation pathway, providing effective coagulation control for at least 4 hours without constant infusion, reducing bleeding risks and monitoring burden.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If unfractionated heparin is used for anticoagulation during ECMO, then coagulation control is achieved, but bleeding risk increases significantly
Solution Approach 1:
The patent changes the chemical structure parameters of heparin by creating fractionated forms with specific molecular weight ranges (e.g., 5-20 kDa, 10-20 kDa). This structural modification alters the anticoagulant properties to reduce bleeding risk while maintaining thromboprevention efficacy during ECMO therapy
Solution Approach 2:
The patent segments the heparin molecule into smaller fractions with defined molecular weights. This segmentation allows selective retention of anticoagulant activity while removing overly potent segments that cause excessive bleeding, achieving a balanced anticoagulant effect suitable for ECMO
2Reliability
If unfractionated heparin is administered continuously, then coagulation control is maintained, but monitoring complexity and transfusion requirements increase
Solution Approach 1:
The patent implements dynamic dosing regimens where the fractionated heparin dosage is adjusted based on patient-specific factors, ECMO duration, and clinical response. This dynamic approach maintains effective anticoagulation while reducing the need for intensive monitoring and minimizing transfusion requirements
3Reliability
If higher doses of heparin are used to prevent thrombosis during ECMO, then thromboprevention is improved, but hemorrhagic complications increase
Solution Approach 1:
The patent modifies the molecular weight parameter of heparin to create fractionated forms that provide adequate thromboprevention at lower doses. The optimized molecular weight range (5-20 kDa) achieves effective thrombus prevention in ECMO circuits without the excessive hemorrhagic complications associated with higher doses of unfractionated heparin
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The anticoagulant aptamers provide durable thromboprevention, reducing surgical site bleeding and blood transfusions, while maintaining effective coagulation control during extended ECMO therapy, comparable to heparin but with fewer adverse effects.
Implementation Method 1
administering an effective amount of an anticoagulant agent that directly inhibits one or more steps in a coagulation pathway
Data Source
AI summary
The present application provides for a method for controlling coagulation in a subject in need of extracorporeal membrane oxygenation. The method comprises administering an effective amount of an anticoagulant agent that directly inhibits one or more steps in a coagulation pathway to the subject, wherein the effective amount of the anticoagulant agent is capable of controlling coagulation during extra corporeal membrane oxygenation for a coagulation control time of at least 4 hours.