The Relationship between Factor V Leiden Mutation and Recurrent Abortion Among

Palestinian Pregnant Women In The West Bank

Ayman HusseinAn-Najah National University

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Recurrent Pregnancy loss

Defined as 3 or more spontaneous fetal losses before the 20th week of pregnancy .

A major health problem affecting 0.5%-1.0% of pregnant women

occurring in about 20 % of all pregnancies, fewer than 50% of these cases have definitive causes .

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Thrombophilia• It is a predisposition to thrombosis.

• It is a multigenic disorder caused by inherited and acquired factors

• it contributes to the increasing incidence of poor pregnancy outcomes including recurrent abortion .

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Factor V Factor V protein 330 k Da made

chiefly by cells in the liver ,circulates in plasma as a single-chain molecule with a plasma half-life of about 12 hours1984).

In contrast to most other coagulation factors, it is not enzymatically active but functions as a cofactor

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Pregnant women have 2–5-fold higher risk for venous thromboembolism (VTE )compared to non-pregnant women.

The FVL variant allele increases the risk for (VTE) during pregnancy 8–10

times, compared to non-pregnant women with the wild-type genotype .

Factor VProcoagulant and Anticoagulant Actions of Factor V.

Procoagulant : , factor Va enhances the activation of prothrombin (factor II) by factor Xa.

Anticoagulant :Factor V can serve (with protein S) as a cofactor in the inactivation of factor VIIIa by activated protein C (APC)

GroupTotal No

NO

Of

women

%

OF

mutatio

n

%  Mutation genotypeComparison with the

control group

 homohetroP valueOdds

ratio95% CI

Control

group

50

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(22 %)0%22%0.5942.787(2.1575,

3.4165)

Primary

abortion

32/548(25.0

%)6.30%18.70%

 

 

 

 

 

 

Seconda

ry

abortion

22/54

7

31.8%0%31.80%

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Factor V Leiden mutationInheritance is autosomal dominant. Heterozygous :4.5-14.5% Homozygous : 1:5000Present in 4 to 10% of people of Caucasian

origin (Bertina et al 1994; Rees 1996).The most common cause of inherited

thrombophilia, accounting for 20% to 50% of cases (Bertina et al 1994).

Both homo. and heterozygous individuals with the mutation can develop thrombosis. Homo have 91 times increase in thrombosis .

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ObjectiveThe main objective of our study was :

To investigate if there is a significant association between factor V Leiden mutation and Recurrent Abortion among Palestinian Pregnant Women In the West Bank.

 

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Methodology Case Control Study Design

Data collection : Uniformed questionnaire & direct contact . ( Specific Inclusion & exclusion criteria's ).

Research Place: the Medical Centres in West Bank

Ethical consideration: approved by the Research and Ethical Committee in An-Najah University and Alquds University.

Sample processing: 1-Blood sample collection ( Three medical centers ) 2-Genomic DNA Purification (Master Pure TM

Genomic DNA Purification Kit) .

3-Genomic DNA Qualification (Agarose gel electrophoresis )

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Genomic DNA Qualification (Agarose

gel .electrophoresis

Lanes 1-6 contain separate DNA samples (1 ul)

Lane 7 contains 100 Base Pair DNA Ladder as size marker.

 *

Figure 2.1 Agarose gel electrophoresis For Genomic

DNA

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Identification of Mutation PCR & ARMS Test

ARMS Test :One of the basic methods of DNA assaysIt is an accurate, rapid and simple method (amplification +diagnostic steps are combines). . ***

The use of allele-specific primers for PCR amplification

RES

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Gel electrophoresis for Leiden mutation PCR product analysis

Ula Abu Hilal. 13

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

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ResultsObstetric History Case group: 191 women (at least 3 RA ).Control group: 205 women (gave normal birth

for at least two babies). Data indicates that both groups show basically

similar distribution according to Age , BMI values & usage of OCPs.

The prevalence of Thromboembolic events among relatives of the case group (18.5 %) was higher than. that among relatives of the control group (2 %) ( P= (0.006

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Characteristics of study participants. Cases

Controls No % No

%Age (y) 32.0 - 31.9 -Marriage age (y) 19.3 - 18.8 -Regional Camp 115.0 60.0 141.0 69.0

City 47.0 24.7 40.0 19.4 Village 29.0 15.3 24.0 11.6Smokers 19.0 10.0 19.0 10.0Education level Low 153.0 79.5 166.0 81.3 High 38.0 20.5 39.0 18.7BMI*

Normal 55.0 29.2 61.0 30.0 Overweight 76.0 40.1 63.0 30.7 Obese 57.0 30.7 70.0 34.2Abortion 78.0 43.0 0.0 0.0

Leiden Mutation Prevalence among participants.

Mutation

1st trimester aborters

(n=66)

Controls(n=155)

Odd RatioP-value

Leiden mutation

14( 21.2%)13( 8.4%)2.941.012

Mutation

2d trimester aborters

(n=25)

Controls(n=155)

Odd RatioP-value

Leiden mutation

12( 48%)13( 8.4%)10.083.000

MutationIUFD

(n=26)Controls

(n=155)Odd RatioP-value

Leiden mutation

8( 30.8)% 13( 8.4%)4.855.001

MutationPIH

(n=20)Controls

(n=155)Odd RatioP-value

Leiden mutation

1( 5%)13( 8.4%).5751