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Good morning chairman , cochairman and the audience. My name is

Patamaporn Muenpitak. The third year resident of Phramongkutklao
hospital.
Today I proudly present my research Appropriate mean corpuscular
volume (MCV) cut off values for screening of -thalassemia 1
and -thalassemia genes in pregnant women

Thalassemia is the most common form of hereditary hematologic

disease in Thailand. The prevalence of -thalassemia 1, -thalassemia
and Hemoglobin E among Thais is 14%, 3.9%, 13%, respectively
The types of disease are several degrees, mild, moderate and severe
form. As you can see homozygous -thalassemia, - thalassemia/
Hemoglobin E disease (-thal/Hb E) are moderate form and
Hemoglobin Barts disease (Hb Barts) is most severity.
The affected people of the first condition have a low quality of life,
need blood transfusions, have higher risks of gall stones, and they also
have an estimated average life expectancy of only 10 years. Fetuses
with Hb Barts hydrops have never survived because of the diseases
high chance to cause pregnancy complications including preeclampsia,
shoulder dystocia, postpartum hemorrhage due to megaloplacenta and
maternal depression.

The severe type of Thalassemia need to make prenatal Thalassemia

screening test.
For example, such as Mean corpuscular volume (MCV), Mean
corpuscular hemoglobin (MCH), Osmotic fragility test (OFT),
Dichlorophenol indophenol precipitation test (DCIP), KKU-DCIP or CMUHbE.
MCV
It is a simple process and available on an automated machine

determining Complete blood count!!! in routine first antenatal care lab.

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Although some studies have shown that this might be effective in

screening a thalassemia carrier, using the cut-off point of <75-80
femtolitre(fl), it has never been evaluated for the appropriate MCV cutoff level to discriminate between normal and abnormal tests.
And, the standard cut-off level (MCV <75-80 fl) was considered positive
or abnormal, and patients were tested for hemoglobin typing and
polymerase chain reaction (PCR) for the -thalassemia 1 gene (SEA,
THAI type). This method is highly inefficient, making the process a
waste of time and increasing maternal anxiety.

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So, The objective of this study is to study the appropriate mean

corpuscular volume (MCV) cut off values for screening of -thalassemia
1 and -thalassemia genes in pregnant women.

The study is the retrospective study, a diagnostic test.

Pregnant women attending the antenatal care (ANC) clinic at
Phramongkutklao hospital between 1 January 2014 - 31 January 2016
were recruited into the study.

Statistic analysis was performed by using the SPSS statistical software

(version 17) included
1. demographic data or obstetric background were presented as
percentages , means and standard deviation etc.
2. Accuracy of the screening test was presented as ROC curve,
sensitivity and specificity with 95% confidence interval (95% CI) in
detecting thalassemia carrier status.

Sample size

This study included all pregnant women at their first visit, regardless
of gestational age, MCV < 80 fl and no known Thalassemia carrier
status (history of previous child with the disease or screening in the
previous pregnancy). Exclusion criteria comprised subjects whose

follow-up data on final outcome could not be obtained and those with
complicated anemia secondary to any cause such as chronic kidney
disease etc.
The 250 pregnant women were enrolled to study
250 blood samples were sent to evaluated MCV by an automated
nematology analyzer and all blood samples that had MCV below 80 fl
were also sent to detect -thalassemia trait by Hb typing and thalassemia 1 trait by PCR for -thalassemia 1 gene (SEA, THAI type).
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The results

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The data is show mean of hemoglobin concentration was 11.35 g/dl,

and hematocrit was 34.54 Vol%. The mean of MCV was 73.21 fl.

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Hemoglobin typing showing normal typing was 30%, and abnormal

typing was 70%.
The -thalassemia trait was 16(6.4%), thal/HbE was 2(0.8%) and PCR for -thalassemia 1 trait that showed
positive was 24(9.6%).

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ROC curve of MCV in predicting -thalassemia 1 and

thalassemia trait (area under curve 0.852)

This area is good cut off MCV

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As picture

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In the table, the effective cut-off level of MCV in predicting thalassemia

carriers was 72.55 fl. The positive MCV (<72.55 fl) gave a sensitivity of
92.9% and specificity of 74.0% in screening -thalassemia 1 and thalassemia genes. The positive predictive value was 41.94% and the
negative predictive value was 98.09%.

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And, The positive MCV (<75.05fl) gave a sensitivity of 97.62% and

specificity of 56.73% in screening -thalassemia 1 and -thalassemia
genes. The positive predictive value was 31.30% and the negative

predictive value was 99.16%.

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Discussion

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The efficient screening using the MCV test cut-off level of <80 fl has a
sensitivity and specificity equal to 92.9% and 83.9%, respectively. The
result of false positive screening -thalassemia 1 and -thalassemia
genes may be too high. Other conditions such as -thalassemia 2 and
iron deficiency anemia were included.

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This study shows that MCV at the cut-off level of <72.55 fl is an

effective screening test for both -thalassemia 1 and -thalassemia
gene among asymptomatic pregnant woman giving a sensitivity of
92.86%, specificity of 74.04% and negative predictive valve of 98.09%.
However, the positive predictive value was rather low (PPV=41.94%)
leading to the need for a confirmatory diagnostic test among a
relatively large number of women.

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The strength of this study is that the MCV cut-off level used to
differentiate normal from abnormal test results was derived from the
ROC curve unlike previous reports where the cut-off level was based on
traditional practice.
Additionally, previous studies have suggested the cut-off level of MCV
is high. The appropriate cut-off should also depend on nature of test,
just not only on ROC curve.
The effective cut-off based on ROC curve may not be the effective in
terms of clinical use. Phramongkutklao Hospital used a screening test
with a sensitivity 95%. Thus, from this study, we have found that
MCV value at the cut-off level of <75.05 fl is appropriate because the
sensitivity increased to 97.62%, negative predictive valve increased to
99.16%.
This test is simple and cheap we may need high sensitivity with
additional little load work for Hb typing and PCR to prevent even a

small of missed cases of serious disease if the added burden is

acceptable, but specificity and positive predictive value decreased
leading to the need for a confirmatory diagnostic test if positive case.
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In conclusion, MCV at the cut-off level of <75.05 fl is appropriate

because the sensitivity of 97.62% for screening -thalassemia 1 and thalassemia genes among pregnant women decreased over
investigation, reduced processed time, reduced patient anxiety and
was highly efficient.
Therefore, this cut-off level for MCV is recommended for routine
primary screening tests of thalassemia.

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We should use the others study is prospective.

And, the population in this study were enrolled in Phramongkutklao
Hospital.

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I would like to express my sincere thanks to my research advisor, Dr.

Nutthaphon Imsom Somboon for their favor and encouragement
throughout the course of this research.
And Dr. Suthee Panichkul,
Statistician,
In addition, I am grateful for my teachers and all of patients in
Phramongkutklao hospital to fulfill my knowledge and experience.

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Thank you for you attention