1. We know that during pregnancy, women have a five- fold  risk of VTE as compared to non-pregnant women. Absolute risk of group VTE during pregnancy is between 0.5-3/100 women, based on studies using Radiographic documentation. As we know that PE is one of leading cause of maternal death in U.S. The prevalence and severity of this condition warrant consideration of anticoagulant therapy in pregnancy for women at risk for VTE.

2. Numerous changes in the coagulation system account for the hypercoagulation state associated with pregnancy.  Virchow ’ s triad  factor (Fibrinogen, we will brand, Ristocetin co-factor activity)  anticoagulant (AI, UI, S,C) marked mean term and post delivery. Recently, it has been recognized that up to ½ of women who have thrombotic events during pregnancy possess an underlying congenital or acquired thrombophilia.

3. Most common thrombophilias in occasion: –FSLM – prevalence of 5% of this population. –PGM – 2% of 5% of this population. In approximately 50% of patient with hereditary thrombophilia, the initial thrombotic event occurs in the presence of an additional risk factor e.g. pregnancy ocp orthopedic trauma, and major surgery. Traditionally, it was believed that the risk of VI was greatest in the 3 rd trimester and immediately postpartum.

4. Most recent studies have found that antepartum DVT is at least as common as postpartum and occurs with equal frequency in all 3 trimester. However, PE is a common postpartum. Recurrence: Women with history of TE have an  risk of recurrence when they become pregnant. The estimate recurrence 7.5 – 12% were based only on 2 random secondary trials. But no studies differentiated between the risk of recurrence based on underlying risk factor (but most of the estimate of recurrence are based on women who had their initial event day OCP use).

5. ? Other familial hypercoagulation state

6. These are some of the clinical consideration and recommendation that might assure some of these question which we needed in our clinical practice. How should be tested? 1.Hx of thrombosis esp. if it will affect man. 2.Family hx of thrombosis without personal but strong family hx of thrombosis. History of thrombosis  control, e.g. first degree relative with AT deficiency homozygous factor 5LM or PGM. May benefit from testing, e.g. – antepartum prophylaxis. – They are more likely to have multiple inherited risk factors with  risk of thrombosis (4-40%), e.g. 15% C + 39% S  positive FSLM with markedly  risk of thrombosis.

7. APS  (pt with history of T, RDL, early or severe PET or unexplained IUGR)  prophylactic anticoagulation may improve the pregnancy outcome. Hereditary thrombophilia  C, S, AT, FSL, PGM, Meth. THFR. Severe early PET, unexplained fetal loss or still birth Abruption  No RCT supporting the efficacy of anticoagulation Rx in preventing these conditions. So, it is important to discuss with the patient the implication of Positive test and to determine whether the patient management would be altered during pregnancy or not.

8. 3.Also test AT, PC&S with extensive ____, Warfarin and Heparin use – may result in falsely low valves. 4.DNA test for FSLM, PGM, THFR are reliable in pregnancy.

9. So after we identified our patient candidate for Rx, what are the type of anticoagulation.

10. What test should we order? These are the test that we order to evaluate the risk of thromboembotic events in female with history of thrombosis FHx 1 st degree relative with specific mutation. 1.Given the law prevalence of AT-III and consideration should variable pathogenicity of Protein C & S) be given to test only when all other studies have yielded with negative results. Normal physiological changes in pregnancy result in marked alteration. 2.In Prot S & C, so the test should be deferred until after pregnancy, e.g. Prot S  by 40% in pregnancy.

11. HEPARIN –  in pregnancy   p. volume  R. clearance  in Heparin binding Protein  Heparin deg. by the placenta  Bioavailability of Hep. No prospective trials that have determined adequate prophylactic doses in pregnancy.

12. Still the major concerns with use of Heparin during pregnancy are not fetal but maternal  include OST, Bleeding, skin necrosis - 2 P.T. of pregnant women exposed to Heparin confirmed a mean bone loss of 5%, complete reversability of this process has not been clearly established nor the dose response relationship. - Some found that selected patient with FHx of osteoporosis, smoker – p. evaluation of bone density may have therapeutic implication.

13. HIT IT BNIT IT Common - Less common Reversible - >severe Less severe - D 5-14 of full dose Occur in 1 st few days of Rx of Heparin Not require cessation of Rx - 3% of patient may have wide spread thrombosis

14. DVT and PE are the most frequent presentation Rx should discontinue It is recommended to measure Platelets on Day 5 and periodically for the 1 st 2 weeks of treatment.

15. LMWH 1. Advantages over standard Heparin –It may reduces the 3 complications associated with standard Heparin – (Bleeding, Osteoporosis, HIT). –It crosses the placenta into fetal circulation. –It has better bio-availability over the standard Heparin because of  H binding process. –It can be restricted to once or twice daily dosing.

16. 2.Dose   same reason  R. clearance and p. volume. 3.No need for laboratory monitoring but peak antifactor – Q4-6 weeks should be utilized especially in patient receiving twice daily dose.

17. Relatively C.I. in pregnancy, because it crosses the placenta into fetal circulation. It is use mainly pp and antipartum should be restricted to selected patient – RhD, vulv. HD, AF – those with prolonged high dose Heparin Rx is contraindicated.

18. After we knew the type of anticoagulant, what do we use for them?

19. Adjusted dose not frequently used mainly used in selected patient those with vulvular heart disease and AF. Certain high risk condition that require dosage adjustment to achieve higher therapeutic level.

20. Because of the absence of adequate prospective trials, number of different prophylactic regimen was offered by various consensus panel. One study determined that during pregnancy, a doubling of the dose of Heparin was required to achieve same anticoagulant response of non- pregnant patient – Taley 5u 2t/d. Pregnant ladies who require adjusted dose prophylactic, may benefit from higher bio- availability of LMWH. REGIMEN

21. ACUTE THROMBOSIS After 3 months of therapeutic heparinization, experts differ as to what should be done for rest of the pregnancy. Some recommend using L.D. of S.C. Heparin and others in continuing therapeutic anticoagulant for the rest of prgnancy. LMWH may be an alternative Rx for acute event but actual dose is not clear yet.

22. INTRAPARTUM & POSTPARTUM Intrapartum care is complicated, and Rx approaches vary. It is helpful to consult with personnel who have expertise in the intrapartum management of such patient. Low dose – varies widely, although all agree that the postpartum period is one of high risk.

23. ANALGESIA The use of spinal or epidural in patient may receiving thromboembolic prophylaxis is controlled. Safety of LMW, or oral anticoagulant – before the procedure is unclear (because no studies addressing anticoagulant in pregnancy relative to use of conduction anesthesia). Although, FDA – reported cases of Finally, the American Society of _______ anesthesia has recommended.

24. MAJOR CONCERN 6-12 Wks. Mid Trimester - Skeletal embryopathy- optic atrophy - Stippled epiphysis- microcephaly - Nasal & limb hypoplasia - developmental delay Bleeding and fetal loss may occur at anytime.