Heritable thrombophiliastog oct11.4 All major her. Throm.

Have een found to be associated with increased risk of VTW , but absolute risk remains low. Testing for throm. Only if it affects management. Ideally testing should be performed after the acute event when the woman is not receiving anti coag. And is not pregnant.

Ethical Issues: Ideally testing in an expert centre, supported by effective cunselling and explanation of the implications of positive and negative results. Detailed and sensitive disc. Reg. her. Throm. And adverse pregnancy outcomes. Defn; In1990 the British Committee for Standards in Hematology (BCSH) defined thrombo. as familial OR acquired disorders of the hemostatic mech. Which are likely to predispose to thrombosis.

Hereditary Thrombopiias Due to deficiencies of the aturally occurring anticoagulents:Antithrombin, ProteinC, Protei S OR Abnormalitiesof coagulant factors:Factor five leiden, prithrombin gene mutation\ All lead to gan in pocoagulent function. Approx. 11% of normal population have one these heritable throm. Which can be detected by lab. Tests. Other risk factors: High conc. Ofprocoagulent factors : VIII, IX, XI and Fibrinogen Homozygosty for methylene tetrahydro folate reductaseC677T can cause hyper homocysteinemia which can cause inc. risk of vascular events. But recent review calculated no inc. risk in pregnant women. Her. Throm. And risk of VTE All major Her. Throm. Associated with inc. risk of VTE in and out of preg.

Major heritable thrombophilias and relative risk for venous thromboembolism in pregnancy10 Thrombophilia Prevalence in normal Relative population % relativerisk

FactorVLeiden heterozygosity 27 FactorVLeiden homozygosity Prothrombin mutation heterozygosity 2 Prothrombin mutation homozygosity Protein S deficiency 0.030.13 Protein C deficiency 0.200.33 Antithrombin deficiency 0.250.55

9.32 34.4 6.8 26.4 3.19 4.76 4.69

The most prothrombotic condn. Is antithrombin def. where absol. Risk for preg. related vte is 31% if no anticoag. Prophylaxis, 495 with previous h/o vte. Her. Thromb. Act in synergy with acd. Risk factors: obesity, immobility, med. Cond. To give a resulting risk greater than would be expected for the sum of the individual factors.

Lab. Inv.: Detection of thrombophilia does not affect the initial management of vte but may affect decisions reg. duration of anticoagulation. DEtecion may be beneficial for f irst- deg family members who are carriers of the defect but who are still asymptomatic. May be accorded a lower threshold for primary preventive strategy. testing also identifies individuals with combined or homozygous defects who are at higher risk of vte or likely to develop it earlier in life. WHO TO TEST FOR THROMBOPHILIA: guidelines from RCOG and BCSH suggest testing for women in the presence of: 1. h/o unprovoked vte 2. thrombosis in preg or occp 3. previous event due to minor provoking factor, sucfh as travel 4. first deg. Family h/o idiopathic thrombosis; or vte related to preg.;use of comb. Cont. pill, minor risk factor. I f the family

member has a known risk fctor tests can be selective. 5. In the first two groups of women tsting does not influence the need for antenatal prophylaxis but may affect decision reg. dosage and duration of trt. And isbeneficial for first-deg relatives. 6. Where testing is performed on asymptomatic person as part of family studies the risks , benefits and limitations of the tests should be carefully explained and considered. Testing not indicated: 1. Arterial thrombosis 2. Assisted conception or OHSS, in the absence of VTE 3. significant provoking factors to a thrombotic event 4. family h/o provoked thrombosis when to test: 1. Factor five leiden and ptm are detected by genetic analysis and tests can be performed at any time.

2. Plasma levels of protein C, protein S and antithrombin should be tested at least 4 wks. After the acute event because of the initial consumption of factors durng the thrombotic process. 3. Free (biologically active) protein s levels fall in pre. Because of the rise in pr.s binding globulin so test 3 months postpartum. 4. Tests not reliable during anti coag. As heparin reduces levels of antithrombin,warfarin affects pr.c and s which are both vit. K dependent factors. Preferable to postpone testing until 4 wks . after discontinuation of trt. SUMMARY: OF TESTING Away from the acute event When anticoag. Is discontinued When the woman is not preg. or on ccp

Venous thromboembolism prevention strategies 1. All women should be assessed for risk of thrombosis either early in preg. or nonpreg. And repea if circumstances change or hospital admission is reqd. 2. Pregnant women should be advised reg. general antithrombotic measures: weight control, leg care., hydration, mobility. 3. Women with previous DVT should also be advised to wear antiembolic stockings, or classII compression stockings if still wthin 2 yrs. Of thrombotic event. 4. Women with known thrombophilia will require AN LMWH if they have a personal h/o thrombosis. 5. Women with thrombophilia but no h/o thrombosis:t he need for AN LMWH will depend on nature of thromvbophilia, family history , presence of acqd. Factors such as obesity.

6. Antithrombin def.- high risk of vte in preg.justifies prophylaxis even in asymp.cases with no additional factors. Labor and delivery: hydration,, antiembolic stockings, early mobilization. Women with thrombophlia will need lmwh in the postpartum period for atleast 7 days Extend to 6 wks . if positive family history or other risk factors. Those previously receiving warfarin will need to retur to this regimen in the postpartum period,overlapping with lmwh for the first few days and until the INR(PT) is withn normal limits. Both warfarin and heparin are safe during breastfeeding.

HERITABLE THROMBOPHILIAS AND PREGNANCY COMPLICATIONS

1. Preg. loss nd thrombophilias- conclusion from various studies absolute risks are low and screening s not indicated. Recommendations for women with thrombophilia and adverse preg. outcome 1. Unselected testing in preg. not recommended:positive tests have a poor predictive value. Current national and internat. Guidelines advocate testing only for antiphospholipid synd.antibodies and not for her. Thromb., in view of the weak associations of most comp. with thromb. As some adverse outcomes have been assocated with Hyperhomocysteinaemia: pet,a pragmatic approach would be to advise women with a relevant clinical histo 5mg folic acid for the duration of preg 2. Pre-eclampsia and Thrombophilia:no significant association 3. FGR, SGA and Thromb: no association 4. Placental abruption and thromb.

Significant association only with factorVleiden mutation 5.conception and thromb. No results in studies Outcomes for prophylaxis and thrombophilias The results of ALIFE and SPIN studies examining the effect of antithrombotic trt.on pregnancies f women with at least two miscarriages were published in 2010. Neither demonstrated benefit with LMWH, no benefit from either study for thromb. Subgroup also.