Your SlideShare is downloading. ×
Am 10.40 deloughery
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×

Introducing the official SlideShare app

Stunning, full-screen experience for iPhone and Android

Text the download link to your phone

Standard text messaging rates apply

Am 10.40 deloughery

423
views

Published on

Published in: Business, Economy & Finance

0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
423
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
14
Comments
0
Likes
2
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. The Woman at Risk for Blood Clots: Guidelines for Screening & ManagementTom DeLoughery, MD FACP FAWMOregon Health and Sciences University
  • 2. DISCLOSURERelevant Financial Relationship(s)Speaker Bureau - NoneConsultant – AmgenGrants - Alexion
  • 3. Estrogen and Thrombosis• Key principles – Estrogen in any dose causes thrombosis – Drugs that act like or oppose estrogen causes thrombosis – Hypercoagulable states synergize with estrogen effect – Age is a hypercoagulable state – The past predicts the future
  • 4. Women’s Deaths from VTE vs Age Age Death/Million 15-24 0.3 24-34 3.4 35-44 9.9
  • 5. Estrogen Containing Contraception• Most common medication in young woman – 12 million users• First associated with DVT in 1961• Despite reduction in estrogen, risk remains
  • 6. Overall Risk• Overall risk of thrombosis is increase 3 fold with use of oral contraception – 1-3:10,000 to 3-6:10,000• Risk higher with 1st and 3rd generation pills – 1st – huge estrogen doses – 3rd- progestin component
  • 7. Overall RiskLewis MA Human Reproduction 1999
  • 8. Overall Risk 2nd vs 3rdKemmeren, et al BMJ 2001
  • 9. 3 Generation Pills rd• Desogestrel, gestodene, and norgestimate• Reduced androgenic side effects• RR over 2nd generation pills 1.7-2.6 – 1-2 extra DVT/10,000 users
  • 10. Drospirenone• Progestin with antimineralocorticoid and antiandrogen effect• Risk varies in studies but appears double of 2nd generation pills – FDA ~ 1.5
  • 11. Progestin Only• Pills (northethisterone, desogestrel) – No increased risk• Injectable – 2.2-3.6 increase risk – Patient selection?
  • 12. Levonorgestrel IUD• No increase risk of thrombosis• Decrease menstruation can be an advantage in women on anticoagulation
  • 13. Modifiers of Risk• Timing: increased in first three months of use – RR as high as 12 reported• Risk does persist throughout time of use• With stopping OCP, risk disappears after three months
  • 14. Age of Patient• Risk higher in older patients – Additive effect with thrombophilia of aging
  • 15. Risk of DVT vs AgeBMJ 2011:343:d6423
  • 16. Hypercoagulable States• Dramatic interactions with hypercoagulable states• RR range from 10-99!• Highest in OCP that contain desogestrel or gestodene (3rd generation)• ABSOLUTE risk is still 28-50/10,000
  • 17. FVL and OCPFVL OCP RR CI - - 1 - + 3.7 2-6 + - 6.9 2-28 + + 34.7 7-224Lancet. 1995 Dec 16;346(8990):1593-6
  • 18. Should Woman be Screened for Hypercoagulable States?• No utility in screening!• Will deny contraception to > 60 women to prevent one DVT
  • 19. OCP Recommendations: Hypercoagulable State• No general screening• + Hypercoagulable state but NO thrombosis – Controversial – If strong need for OCP - ok – If strong family history - no
  • 20. OCP Recommendations: History of Thrombosis• If not anticoagulated - no estrogen containing OCP – Progesterone ok – LNG IUS ok• If anticoagulated estrogen containing OCP ok – Unclear if any increase thrombotic risk – Unplanned pregnancy while anticoagulated difficult
  • 21. Rings and Patches• Patches have same to higher risk as pills• Rings unknown but probably similar to patches/pills• Same precautions apply as OCP
  • 22. HRT• Overall risk with combined therapy is RR of 2• However baseline risk is 1:1000 – Absolute risk is 1:500• Estrogen only replacement RR is 1.33
  • 23. Hypercoagulable States• Marked synergy with HRT and hypercoagulable states• RR 6.7-17• Absolute risk is higher due to age effect
  • 24. FVL and HRTFVL HRT RR CI - - 1 - + 3.2 2-6 + - 3.9 1.3-11.2 + + 15.5 3-76Br J Haematol. 2002 Mar;116(4):851-4
  • 25. RCT: HRT and Prior Thrombosis• 71 vs 60 women with history of DVT randomized to HRT• HRT: 10% DVT (3 PE, 1 CVT) – 8.5%/year• Placebo: 2.2% – 1%/year• Trial terminated early
  • 26. HRT Patch• Unlike contraceptive patch, the risk of thrombosis appears to be lower with HRT patch• Several studies show no activation of coagulation• Needs to be prospective studied
  • 27. Recommendations: HRT• History of DVT: no HRT unless anticoagulated• + Hypercoagulable state: No – Patch - ???• On anticoagulation: Yes
  • 28. Estrogen Related Thrombosisand Risk of Future Thrombosis• “Estrogen” is most common risk factor for provoked DVT in woman• Increasing data on risk of future DVT
  • 29. JAMA. 2005 May 18;293(19):2352-61
  • 30. Estrogen Related Thrombosis and Risk of Future Thrombosis• Data from Prevent trial – With non-hormone-related thrombosis • Recurrence rate 15.0% – With hormone-related thrombosis • Recurrence rate 5.0% – With hormone-related thrombosis • 58% lower risk than men (HR 0.42) – With hormone-related thrombosis • 46% lower recurrence risk than other women (HR 0.54)
  • 31. Estrogen Related Thrombosisand Risk of Future Thrombosis• Women who have a DVT due to “estrogen” have very low rates of recurrence• Not influenced by most genetic hypercoagulable states
  • 32. Estrogen like Drugs• All drugs that interfere with estrogen appear to be prothrombotic• Tamoxifen raised DVT rates 3 fold• Raloxifene doubles risk• Aromatase inhibitors also slightly increase risk
  • 33. Assisted Reproduction• Increasing reports of DVT with ART – Mainly upper extremity – Appears to be associated with hyperstimulation syndrome• Should treat for at least 6 weeks – Longer if pregnancy successful• Unclear prophylaxis is useful in at risk women
  • 34. Pregnancy• Multiple factors lead to hypercoagulable state – Estrogens – Venous stasis due to anatomical changes – Bed rest
  • 35. Pregnancy• Multiple issues – Risk of DVT – Use of anticoagulants – Hypercoagulable states and adverse pregnancy outcomes
  • 36. Modifiers of Risk: Age• Overall risk is 1:1000 – 50% post-partum• Risk rises with age• Major concern as women are having children at older age
  • 37. Rates of VTE by Age (DVT/1000 Pregnancies) 3 2.752.5 2.13 2 1.67 1.731.5 1.58 1.47 10.5 0 <20 20-24 25-29 30-34 35-39 >40
  • 38. Age and Death from VTEAge Death/Million No-OCP OCP Pregnancy15-24 0.3 6.0 5.024-34 3.4 7.9 7.735-44 9.9 13.4 19.2
  • 39. Risk Modifiers: History of DVT• Women with history if DVT at higher risk of recurrence – Risk is 2-8%• Higher if idiopathic DVT
  • 40. Risk Modifiers: Bed rest• > 3 days of bed rest increase rate from 0.8/1000 to 15.6/1000• Venous stasis vs hypercoagulable state• Prophylaxis?
  • 41. Hypercoagulable States• Again a profound influence• RR 57 in meta-analysis• Most women with DVT during pregnancy have hypercoagulable state
  • 42. Therapy• Warfarin: No!• New drugs: No!• Heparin• Low molecular weight heparin• (Fondaparinux)
  • 43. Warfarin• Teratogenic – Bone development – Increased incidence of CNS defects? – Highest risk 9-12 weeks – Greatest with dose > 5 mg/day
  • 44. Standard Heparin in Pregnancy• aPTT unreliable in pregnancy• Must use “heparin levels” (anti-Xa) even with prophylaxis – PK of UFH changed in pregnancy• Leads to osteoporosis in 36% of women – Not dose dependent!• Inconvenient dosing
  • 45. Low Molecular Weight Heparin• Safe and effective in pregnancy – Abundant use• Does not cross placenta• Predicable dosing• Lesser risk of osteoporosis
  • 46. LMWH in Pregnancy• Prophylaxis – Enoxaparin 40mg/day – Dalteparin 7500q day or 5000 q12 – No need to check levels• Therapy – Usual dose • Enoxaparin 1mg/kg q12hours – Check levels qmonth • 4 hours after dose • 0.7-1.1 anti-Xa units
  • 47. Duration of Therapy• 3 months or 6 weeks after delivery for first thrombosis• 2 DVTs: life long• “Strong” hypercoagulable state: lifelong – True APLA, MPS, PNH, cancer• “Weak” hypercoagulable state: does not effect duration• Note: warfarin is NOT a contraindication to breast feeding
  • 48. History of DVT• Women with history of DVT needs prophylaxis• LMWH--->warfarin/LMWH for 6 weeks – Provoked DVT just post-partum• Hypercoagulable state but no DVT history – Controversial! – 1-10% rate with factor V Leiden – Post-partum prophylaxis
  • 49. Hypercoagulable States• Controversial if all women with thrombosis during pregnancy need evaluation – Establish duration of therapy – Establish type of therapy – Family studies and interventions• Etiologies may be found in up to 60% of women
  • 50. What to Evaluate• Antithrombin III• Protein C• Protein S• Factor V Leiden• Prothrombin gene mutation• Antiphospholipid antibodies – Lupus inhibitor – Anticardiolipin antibodies• MTHFR – NO!
  • 51. When to Evaluate• During pregnancy – Antiphospholipid assays – Antithrombin levels – Factor V Leiden – Prothrombin gene defect• 3 month post-partum – Protein C – Protein S • Note: Protein S can drop to very low levels during pregnancy
  • 52. Patient on Warfarin Planning Pregnancy• Frequent pregnancy checks• Change to LMWH when test is positive• Alternative is to change to LMWH
  • 53. Are Pregnancy Complications Thrombotic?• Placental ischemia results in: – Decreased fetal growth – Fetal death – Pregnancy induced hypertension
  • 54. Frequent Miscarriages• Placenta becomes blood supply to fetus 8-9 weeks• Early losses due to many factors• Strong association with hypercoagulable states if miscarriage after 10 weeks.
  • 55. Overall Risk• Miscarriages 16:100 – 2-3 trimester 1-2:100• Preeclampsia 2-4:1000• How dose hypercoagulable states influence this risk?
  • 56. Risk of Pregnancy Loss with Thrombophilia Disorder OR for Preg Loss Factor V Leiden 2-5 Prothrombin Gene 2-9 Mutation Protein C Deficiency 2-3 Protein S Deficiency 2-40 Combined 5-14Am J Obstet Gynecol. 2004 Aug;191(2):412-24.
  • 57. Who Should Be Evaluated?• No use in screening• + Family history• + Thrombosis• Pregnancy complications (HELLP,PIH,....)• 1 or more fetal death after 10 weeks• 1 or more premature birth due to PIH or FUGR• 3 or more miscarriages before week 10
  • 58. LMWH Prophylaxis• Antiphospholipid syndrome – Yes• Unselected women with 2 or more losses – 2 RCT say No• Definite Thrombophilia - ?• Multiple last losses - ?
  • 59. Recommendations: Therapy• Consider prophylaxis with one or more unexplained loss and hypercoagulable state• Difficulty is in woman with no identifiable hypercoagulable state – Consider therapy if multiple early losses, late losses, or evidence of placental thrombosis
  • 60. Summary• Risk of thrombosis with estrogen is dependent on – Age – Thrombophilia – History of thrombosis