Inherited thrombophilias are genetic conditions -its il effects on Pregancy

Inherited thrombophilias are genetic conditions that increase the risk of thromboembolic disease.

  Point 1:-Thromboembolic disease in pregnancy is seen in 0.2-0.3% of pregnancies. During pregnancy the thrombogenic potential of these inherited disorders is enhanced

Part I:-Normal coagulatory factors increase in pregancy period :--Why so ?? Because of pregnancy associated changes in several coagulation factors: Point 1 :-Which factors increase in normal pregancy ?? :-. 1) Fibrinogen and 2 ) factors II, 3) VII, 4) VIII 5) X besides thete is increased levels and  6) activity of the fibrinolytic inhibitors, 7)  thrombin Activatable fibrinolytic inhibitor PAI-1 and PAI-2 .The net effect of these pregnancy induced changes is to produce a hypercaoguable state in normal women.

Part II:---Inherited disorders is enhanced:: The inherited thrombophilias can compound this increase in hypercoaguability and thus increase risk of thromboembolic complications during pregnancy.

. Point 2:--Resistance to activated protein C increases in the second and third trimesters.

Point 3:- protein S activity decreases due to estrogen induced decrease in total protein S and Point 4:-  increases in the complement 4B binding protein which binds protein S

TYPES OF THROMBOPHILIAS

Type II :àInherited Thrombophilias

1)   Abnormalities of pro-coagulant factors 2) .Factor V Leiden mutation causing activated protein C resistance(APCR) 3)

. Prothrombin gene mutation (prothrombin G 20210A)

. 4) Plasminogen activator inhibitor-1(PAI-1) gene mutation

5) Deficiencies of Endogenous Proteins in the Coagulation Cascade like . Protein C ,. Protein S ,. Anti thrombin& Factor V Leiden

Factor V Leiden occurs as result of a single point mutation in the factor V gene at the cleavage site (position 506) where protein C acts. FVL is the most common cause of activated proen C resistance . The most cost efficient way of screening for FVL is to check for the abnormal phenotype.

Heterozygostiy for the FVL mutation is present in 20 to 40 % of nonpregnant individuals with venous thromboembolism .

Homozygosity for the FVL mutation carries an 80 fold risk of VTE .

Incidence of  Inherited Thrombophilias

A)Inherited  A)  Factor V  ledine Mutation  : This Occurs in 5 to 15 % of ethnic European populations .Rarely found in Asian or African populations .Associated Risks..Given the low prevalence of VTE in pregnancy the risk of VTE in asymptomatic FVL carriers is only 0.2% . Second and third trimester fetal loss.

. Severe intrauterine growth restriction

. Abruption

. Severe early onset pre-eclampsia

. Preterm delivery

. When compared with non- carriers , FVL carriers demonstrate an increased proportion of pathological Doppler measurements including bilateral uterine artery notches.

Inherited  B)  Prothrombin Gene Mutation: A mutation at nucleotide 20210 occurs in the gene encoding prothrombin resulting in higher circulating levels of prothrombin the precursor of thrombin . Incidence: Prevalence of the gene in the general populations is 2 to 5 % more prevalent in Casucasian women. Associated Risks,. Threefold increased risk of venous thrombosis .. Controversy remains about whether prothrombin gene mutation is associated with pre- eclampsia

. Intrauterine growth restriction;. Placental abruption

Laboratory investigations: Evaluation for the prothrombin gene mutation is best performed through direct genetic analysis to identify the G20210A transition.

Inherited  C)   Protein C deficiency:-It can result from protean mutations producing two primary phenotypes:Type I: Both immunoreactive protein levels and protein C activity are reduced Type I: Immunoreactive levels are normal but activity is reduced . Protein C is highly sensitive to consumption as may be caused by systemic thrombosis or surgery. Protein C levels are reduced in women with disseminated intravascular coagulation liver disease and women that use vitamin K antagonists.