Alpha-1 Antitrypsin for Cardiopulmonary Bypass Bleeding

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Cardiopulmonary bypass (CPB) during cardiac surgery leads to excessive bleeding and multi-organ failure, with existing anti-inflammatory agents like Aprotinin posing risks and being withdrawn from use, necessitating a new treatment to reduce post-operative blood loss and organ damage.

Innovation Solution

Administration of a therapeutically effective amount of alpha-1 antitrypsin (AAT-1) or its functional variants to prevent or treat injuries associated with cardiac surgery, particularly through compositions comprising AAT-1 administered before, during, or after surgery, to mitigate excessive bleeding and organ injury.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of substance

If Aprotinin is used to reduce postoperative bleeding, then blood loss is reduced, but the risk of myocardial infarction and death increases

Engineering Contradiction:
Improvepostoperative blood lossVSAvoidpatient safety
Core Design Contradiction:
Loss of substanceVSReliability

Solution Approach 1:

The patent replaces Aprotinin (a long-standing, widely used agent) with Alpha-1 Antitrypsin, a newer agent that acts as a safe, effective alternative. The invention introduces a substitute that achieves the same hemostatic benefit without the harmful side effects, effectively treating Aprotinin as a 'disposable' solution to be replaced by a safer option.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent changes the pharmacological parameter from Aprotinin (a kallikrein inhibitor) to Alpha-1 Antitrypsin (a serine protease inhibitor). This parameter change in the type of protease inhibitor used allows achieving hemostasis through a different mechanism that does not carry the same risk of myocardial infarction, thus resolving the contradiction between bleeding control and patient safety.

Inventive Principle:
Principle #35Parameter changes

2Adaptability or versatility

If cardiopulmonary bypass is used during cardiac surgery, then complex heart procedures can be performed, but excessive bleeding and multi-organ failure occur

Engineering Contradiction:
Improvesurgical capabilityVSAvoidbleeding and organ damage
Core Design Contradiction:
Adaptability or versatilityVSObject-generated harmful factors

Solution Approach 1:

The patent introduces Alpha-1 Antitrypsin as an intermediary substance that mediates between the cardiopulmonary bypass machine and the patient's blood system. This intermediary agent protects the blood components from activation and damage during bypass, reducing bleeding and organ injury while allowing the bypass procedure to continue.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies Alpha-1 Antitrypsin before and during cardiopulmonary bypass to provide preemptive protection against bleeding and organ damage. By administering the agent beforehand, the system cushions against the harmful effects that would otherwise occur during the bypass procedure, allowing safe performance of complex heart surgeries.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

3Object-affected harmful factors

If re-operation is performed for postoperative bleeding, then bleeding can be controlled, but hospital mortality increases and hospital stay is extended

Engineering Contradiction:
Improveexcessive bleeding controlVSAvoidhospital stay
Core Design Contradiction:
Object-affected harmful factorsVSLoss of time

Solution Approach 1:

The patent applies Alpha-1 Antitrypsin during the initial surgery to prevent excessive bleeding before it occurs. This preliminary action eliminates the need for re-operation, thereby preventing the extension of hospital stay and reducing mortality risks associated with repeat surgeries.

Inventive Principle:
Principle #10Preliminary action

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

AAT-1 significantly reduces post-operative bleeding and organ damage, attenuates inflammatory responses, and decreases the need for blood products, thereby improving patient outcomes and reducing hospital stay.

Implementation Method 1

alpha-1 antitrypsin (AAT-1)...inhibiting serine proteases...protecting various cell types from cell death

Methodology Applied
Scientific EffectProtease inhibition: Enzyme

Data Source

PatentUS10617745B2Methods for preventing post-operative complications of cardiopulmonary surgery
Publication Date: 2020.04.14 ABRAHAMOV DAN

AI summary

A method for preventing bleeding, blood-brain barrier disruption, brain injury, or a combination thereof in a subject destined for cardiac surgery is disclosed. The method involves administering to the subject prior to cardiac surgery a therapeutically effective amount of alpha-1 antitrypsin (AAT-1), or functional variant thereof. The result is that it prevents bleeding, blood-brain barrier disruption, or a combination thereof in a subject destined for cardiac surgery.