Fibrinolytic Potential Assay for Pleural Fluid Dosing

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Solution Overview

Problem

Current intrapleural fibrinolytic therapy (IPFT) for empyema lacks predictive testing for dosing and outcome, leading to unpredictable efficacy and safety due to empiric approaches, with no clinically tractable methods to guide delivery or predict results.

Innovation Solution

The Fibrinolytic Potential Assay (FPA) measures a mammalian subject's fibrinolytic potential in pleural fluid by incubating labeled fibrin with a plasminogen activator, allowing for prediction of IPFT outcomes, optimal dosing, and selection of appropriate therapy, using a method that can be performed in community hospitals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If empiric dosing protocols are used for intrapleural fibrinolytic therapy, then treatment can be administered without predictive testing, but outcomes remain unpredictable and bleeding risk increases

Engineering Contradiction:

Improvepredictability of therapy outcomeVSAvoidcomplexity of dosing protocol

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The FPA is performed before administering intrapleural fibrinolytic therapy to predict the patient's response. The assay measures fibrinolytic potential in pleural fluid samples obtained prior to treatment, allowing clinicians to anticipate therapy outcomes and adjust dosing accordingly, rather than relying on empiric protocols

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The FPA provides quantitative feedback about a patient's fibrinolytic potential by measuring specific parameters (fibrinolytic activity, PAI-1 levels, plasminogen concentration) in pleural fluid. This feedback enables personalized dosing decisions and prediction of therapy response, transforming the empiric approach into a data-driven treatment strategy

Inventive Principle:

Principle #23Feedback

2Reliability

If higher doses of fibrinolysin are administered to ensure efficacy, then therapeutic effect may be improved, but bleeding risk increases

Engineering Contradiction:

Improveefficacy of therapyVSAvoidbleeding risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The FPA measures multiple parameters including fibrinolytic activity, PAI-1 levels, and plasminogen concentration to determine the optimal dose of fibrinolysin for each patient. By quantifying these parameters, the assay enables personalized dosing that achieves therapeutic efficacy while minimizing bleeding risk, replacing the one-size-fits-all empiric dosing approach

Inventive Principle:

Principle #35Parameter changes

3Object-affected harmful factors

If PAI-1 targeted IPFT is used to reduce fibrinolysin dosage, then bleeding risk decreases, but the need for predictive testing arises to identify suitable candidates

Engineering Contradiction:

Improvebleeding riskVSAvoiddifficulty of predicting therapy response

Core Design Contradiction:

Object-affected harmful factorsVSDifficulty of detecting and measuring

Solution Approach 1:

The FPA replaces the mechanical trial-and-error approach of empiric dosing with a biochemical measurement system. By measuring fibrinolytic potential, PAI-1 levels, and plasminogen concentration in pleural fluid, the assay provides a biochemical basis for predicting response to PAI-1 targeted therapy and guiding dosing decisions

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 FPA effectively predicts IPFT outcomes, optimizes dosing, and reduces bleeding risks by using lower, otherwise ineffective, doses of fibrinolysin, improving the safety and efficacy of IPFT in empyema treatment.

Implementation Method 1

measuring fibrinolysis of the labeled fibrin by measuring detectable label released from the labeled bound fibrin

Methodology Applied

Scientific EffectFibrinolysis: Enzyme

Data Source

PatentUS10175255B2Fibrinolytic potential: a test of pleural fluid to predict outcomes and guide dosing in fibrinolytic therapy

Publication Date: 2019.01.08 BOARD OF RGT THE UNIV OF TEXAS SYST

AI summary

An assay that informs precision-based intrapleural fibrinolytic therapy (IPFT) is disclosed. Provided is a simple assay based on measurement of the Fibrinolytic Potential (FP)—total fibrinolytic activity in pleural fluid when plasminogen activator inhibitors (PAIs) are neutralized and endogenous plasminogen (PLG) is activated. The assay is used to determine FP in baseline pleural fluids of patients undergoing IPFT with agents such as tPA or scuPA to determine the dose and dose intervals for the particular patient. Pleural fluids are also collected after IPFT to confirm that intrapleural fibrinolysis is inhibited and endogenous PLG accumulates in the pleural fluid. Inhibition of intrapleural fibrinolysis in combination with its increase after supplementation of pleural fluid with a plasminogen activator indicates whether or not the subject should be treated with more or higher doses of an IPFT drug.