Factor VIIa for Intracerebral Hemorrhage Subpopulation

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Solution Overview

Problem

Current treatments for intracerebral hemorrhage (ICH) are inadequate in preventing hemorrhage growth and oedema generation, particularly in a defined subpopulation of patients with specific characteristics, such as age ≤70, baseline ICH volume ≤60 mL, baseline IVH volume ≤5 mL, and elapsed time since onset of symptoms less than 2.5 hours, leading to significant morbidity and mortality.

Innovation Solution

The use of Factor VIIa or its equivalent as a medicament to prevent or attenuate hemorrhage growth, oedema generation, and complications in selected ICH patients, administered within 2.5 hours of symptom onset, either alone or in combination with other coagulation agents, to enhance haemostatic control and reduce hospitalization and mortality risks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for intracerebral hemorrhage, then general patient care is maintained, but hemorrhage growth and oedema generation are not effectively prevented in selected subpopulations

Engineering Contradiction:
Improveprevention of hemorrhage growthVSAvoidapplicability to selected subpopulation
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies local quality by identifying and targeting a specific subpopulation of ICH patients based on precise criteria (age ≤70, baseline ICH volume ≤60 mL, baseline IVH volume ≤5 mL, elapsed time <2.5 hours). This allows the treatment to be optimized for the specific characteristics of this subgroup, improving prevention effectiveness for hemorrhage growth and oedema generation in this defined population.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent utilizes parameter changes by establishing specific threshold values for patient selection (age, volume, time parameters) and by defining precise dosage parameters for Factor VIIa administration. These parameter specifications enable the treatment to achieve optimal effectiveness in preventing hemorrhage expansion and oedema in the selected subpopulation.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If Factor VIIa is administered to all ICH patients, then hemorrhage growth prevention is maximized, but patient safety and suitability assessment becomes more complex

Engineering Contradiction:
Improveprevention of hemorrhage growthVSAvoidpatient selection and assessment process
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by establishing patient selection criteria and suitability assessment protocols before administering Factor VIIa. The predefined parameters (age, baseline volume, time elapsed) are evaluated in advance to identify suitable candidates, ensuring safe and effective treatment while avoiding unnecessary administration to inappropriate patients.

Inventive Principle:
Principle #10Preliminary action

3Productivity

If treatment is delayed beyond 2.5 hours, then more patients can be treated, but hemorrhage growth prevention effectiveness is reduced

Engineering Contradiction:
Improvenumber of patients treatedVSAvoidprevention of hemorrhage growth
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent emphasizes the importance of early intervention by setting a 2.5-hour time window for Factor VIIa administration. This preliminary time constraint ensures that treatment is administered during the critical phase when hemorrhage growth and oedema generation are most active, maximizing prevention effectiveness while allowing treatment of a substantial number of patients within this timeframe.

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

The administration of Factor VIIa or its equivalent significantly reduces hemorrhage growth, oedema, and complications in the targeted subpopulation, improving survival rates and reducing hospitalization days, with a notable effect when administered within the specified time frame and dosage.

Implementation Method 1

Haemostasis is a complex physiological process which ultimately results in the arrest of bleeding. This is dependent on the proper function of three main components: blood vessels (especially the endothelial lining), coagulation factors, and platelets.

Methodology Applied
Scientific EffectCoagulation: Coagulation

Implementation Method 2

Endogenous FVIIa becomes proteolytically active only after forming a complex with TF. This ensures a highly localized activation of coagulation and prevents disseminated coagulation.

Methodology Applied
Scientific EffectProteolytic activation: Enzyme

Implementation Method 3

Once a haemostatic plug is formed, the timely activation of the fibrinolytic system is equally important to prevent further unnecessary haemostatic activation. Any malfunction of this system (due to a reduced number, or molecular dysfunction, of the haemostatic components or increased activation of the fibrinolytic components) may lead to clinical bleeding

Methodology Applied
Scientific EffectFibrinolytic inhibition:

Data Source

PatentUS8354377B2Use of factor VIIa or factor VIIa equivalents for preventing or attenuating haemorrhage growth, and/or oedema generation following intracerebral haemorrhage (ICH) in a selected subpopulation of ICH patients
Publication Date: 2013.01.15 NOVO NORDISK HEALTH CARE AG

AI summary

The invention relates to a method for preventing or attenuating one or more complications of intracerebral haemorrhage (ICH), the method comprising: (i) selecting an ICH patient who exhibits one or more of the following characteristics: age≦70, baseline ICH volume≦60 mL, baseline IVH volume≦5 mL, and elapsed time since onset of symptoms of less than about 2.5 hours; and (ii) administering to said patient in need thereof an effective amount of a first coagulation agent comprising Factor VIIa or a Factor VIIa equivalent.