HEMOPHILIA A PROJECT (1) .PPTX 3.10.2018

ESTIMATION OF FACTOR VIII INHIBITORS IN
HEMOPHILIA A PATIENTS
Project Proposal under
THE UNIVERSITY RESEARCH GRANT

Principal Investigator: Dr. P. Arumugam, M.D,
Co – Investigator:
Place of Study:
Department of Transfusion Medicine
The Tamil Nadu Dr MGR Medical University
Guindy, Chennai – 32.
Period of study: 1 year.

INTRODUCTION
• Hemophilia A is a common, X-linked, inherited congenital
bleeding disorder. It is caused by dysfunctional or deficient
production of coagulation Factor VIII (FVIII). 1
• According to World Federation of Hemophilia Survey the

number of Hemophilia patients worldwide is approximately
4, 00,000.
• In India ,the number of expected Patients with hemophilia
would be approximately 120000.
• In India, according to World Federation of Hemophilia Global
survey 2010 only 13993 patients were registered. 2
• This indicates the gross under diagnosis, early deaths and lack
of awareness to access treatment facilities
Classification of Hemophilia
• Classification of hemophilia is based on plasma procoagulant
Severe Hemophilia A : <1% of FVIII
Moderate Hemophilia A : 1-5% of FVIII
Mild Hemophilia A : >5% & less than 30% of FVIII
• In mild Hemophilia, the patients bleed excessively only after

trauma or surgery.
• Patients with Severe Hemophilia A have spontaneous

bleeding or excessive bleeding after minor trauma, particularly
into joint muscles.3
Treatment of Hemophilia A
Ø Administration of exogenous Factor VIII either in the form of
Fresh Frozen plasma/ cryoprecipitate.
Ø Plasma derived Factor VIII .
Ø Recombinant Factor VIII.4

COMPLICATIONS OF TREATMENT
Development of antibodies against the exogenous Factor VIII is

the major potential complication of the treatment of
Hemophilia A. These antibodies are known as inhibitors.
Inhibitors are classified according to their levels in plasma as

high titre, those with ≥5 Bethesda units/ml and low titre
inhibitors <5 Bethesda units/ml. 5
One Bethesda unit is defined as the inhibitory titre needed to
inactivate 50 percent of the Factor VIII present in normal

plasma within 2 hour incubation period at 37°C.6
AIM & OBJECTIVE
• To estimate Factor VIII level in Hemophilia A patients.

• To screen Factor VIII inhibitors by mixing study & inhibitor
screening assay.
• To quantify Factor VIII inhibitors by Bethesda assay.

• Study design: Prospective Study
• Place of Study: Department of Transfusion Medicine,
The Tamil Nadu Dr MGR Medical University,
Guindy, Chennai – 32.

• Inclusion Criteria:
Patients diagnosed as Hemophilia A refractory to Factor VIII

treatment.
• Exclusion Criteria:
Hemophilia A patients with known Factor VIII inhibitors.

Hemophilia B patients
Von willebrand Disease

• Sample size and Study Period:
Samples will be received from Hemophilia A patients not responding to
Factor VIII treatment (Purposive sampling) during the study period of 1
year.
• Statistics: Statistical analysis:
Data entry and analysis will be done using SPSS software version 21.0.
Statistical analysis will be done using “chi square test” and analysis of
variance for categorical variables and “Pearson correlation” to find
correlation. P <0.05 was considered significant.
PROCEDURE
aPTT (Prolonged )
Factor VIII assay ( Classify the Hemophilia A )
Mixing Study (Normal plasma fails to correct the

aPTT an inhibitor should be suspected)
Inhibitor Screening ( If inhibitor screen positive)
BETHESDA ASSAY
REQUIREMENTS
S.NO REQUIREMENTS TYPE OF
EXPENDITURES
1. Coagulometer Non –Recurring
2. Micropipettes Non-Recurring
3. APTT Reagent Recurring
4. FVIII deficient Recurring

Plasma
5 Recurring
Cuvette
6 Recurring
Vacutainer
FINANCIAL COMMITMENTS
S.No. Requirements Quantity Estimated Total amount
cost per unit requested
1 Coagulometer 01 90,000/ 90,000/
Heamostar I Channel
2. aPTT reagent 02 650x2 Rs. 1300

(25samples/vial)
3. Factor VIII Deficient 30 sample Rs. 5760x1 Rs.5760
Plasma (3x1 ml)
4 Cuvettes 30 sample Rs.1000x2 Rs.2000-/-
5 Vacutainers 50 sample Rs.500x1 Rs.500/-
FINAL ABSTRACT
S.NO ITEMS AMOUNT
1. Coagulometer 90000/-
Heamostar 1 Channel
2. aPTT reagent 1300/-
3. FVIII deficient Plasma 5760/-
4. Cuvettes 2000/-
5. Vacutainers 500/-
6. Grand Total 99,560/-
Total : Ninety Nine Thousand Five Hundred and Sixty only/-
CONCLUSION
• Inhibitor assays are performed in Hemophilia A patients as a
screening procedure when the presence of inhibitor is suspected in
the case of abnormal bleeding in spite of taking adequate Factor
VIII or poor response to Factor VIII replacement therapy
• Hence, the above proposal is to find out Presence of inhibitor in the

treatment of Hemophilia A to control bleeding manifestation,
maintain the haemostasis and to improve the overall quality of life.
REFERENCES :
1. Mannucci PM, Edward G.D, Tuddenham et al. The Hemophilia – From

Royal Genes to genes to gene therapy.NEJM 2001 June 7; 344(23):1773-
1779
2. Pinto P, Shelar T, Nawadkar V et al. The Epidemiology of FVIII Inhibitors
in Indian Hemophilia A Patients. Indian J Hematol Blood Transfus
2014 Oct- Dec ; 30(4) : 356-363
3. Srivastava A, Brewer A.K, Mauser-bunshoten E,P et al. Guidelines for the
management of hemophilia. Hemophilia 2012 June 6;1-47.
REFERENCES
5.. White G.C, Rosendal F, Aledort L.M et al. Recommendation of the
scientific subcommittee on Factor VIII and Factor IX of the scientific and
standardization Committee of the International Society on Thrombosis and
Haemostasis. Thromb Haemost 2001; 85: 560.
6.Lewis S M, Bain BJ, Bates I. Practical hematology. Churchil Livingston

;Elsievere ltd ;2006.ISBN: 0-433-06660-4.
THANK YOU

HEMOPHILIA A PROJECT (1) .PPTX 3.10.2018

Uploaded by

Copyright:

Available Formats

HEMOPHILIA A PROJECT (1) .PPTX 3.10.2018

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

HEMOPHILIA A PROJECT (1) .PPTX 3.10.2018

Uploaded by

Copyright:

Available Formats

ESTIMATION OF FACTOR VIII INHIBITORS IN

Project Proposal under

THE UNIVERSITY RESEARCH GRANT

Period of study: 1 year.

• According to World Federation of Hemophilia Survey the

• In India, according to World Federation of Hemophilia Global

survey 2010 only 13993 patients were registered. 2

Moderate Hemophilia A : 1-5% of FVIII

Mild Hemophilia A : >5% & less than 30% of FVIII

• In mild Hemophilia, the patients bleed excessively only after

• Patients with Severe Hemophilia A have spontaneous

Ø Plasma derived Factor VIII .

Ø Recombinant Factor VIII.4

Development of antibodies against the exogenous Factor VIII is

Inhibitors are classified according to their levels in plasma as

One Bethesda unit is defined as the inhibitory titre needed to

inactivate 50 percent of the Factor VIII present in normal

• To estimate Factor VIII level in Hemophilia A patients.

• To quantify Factor VIII inhibitors by Bethesda assay.

The Tamil Nadu Dr MGR Medical University,

Guindy, Chennai – 32.

Patients diagnosed as Hemophilia A refractory to Factor VIII

Hemophilia A patients with known Factor VIII inhibitors.

Von willebrand Disease

Factor VIII assay ( Classify the Hemophilia A )

Mixing Study (Normal plasma fails to correct the

Inhibitor Screening ( If inhibitor screen positive)

3. APTT Reagent Recurring

4. FVIII deficient Recurring

2. aPTT reagent 02 650x2 Rs. 1300

• Hence, the above proposal is to find out Presence of inhibitor in the

1. Mannucci PM, Edward G.D, Tuddenham et al. The Hemophilia – From

6.Lewis S M, Bain BJ, Bates I. Practical hematology. Churchil Livingston

You might also like

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.