Low Dose Aspirin Obstetrics Gestosis

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Low dose aspirin is a wonderful drug in the management of cerebrovascular and cardiovascular disease.However ther is lot of controversies about its use in obstetrics largely due to conclusions drawn on trials with flawed methodology, a reader must always view the evidence critically especially when the not harmful interventions are likely to benefit the patient....

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Low Dose Aspirin Obstetrics Gestosis

  1. 1. Obstetric indications for Low dose aspirin<br />Dr. Veerendrakumar C.M.<br />Associate professor<br /> Dept of OBG,VIMS, <br /> Bellary, Karnataka<br />
  2. 2. Inadequate trophoblastic invasion…<br />Normal <br />abnormal<br />
  3. 3. Preeclampsia -Imbalance in favor of vasoconstrictor profile <br />PGI2<br />TXA2<br />
  4. 4. ? The wonder drug aspirin (C9H8O4)<br />
  5. 5. Mechanism of action<br />Aspirin is a cyclooxygenase inhibitor…<br />It inhibits production of both PGI2 and TXA2-<br />theoretically no effect must be seen.<br />TXA2 - PlateletsPGI2 - Endothelium<br />
  6. 6. Selective inhibition by aspirin<br />Irreversible inhibition of PLT cyclooxygenase.<br />Endothelial cyclooxygenase is quickly regenerated <br /> In low doses less aspirin reaches peripheral vessels compared to platelets.<br />Also stimulates production of cytokines which are important for implantation.. <br />Am J ObstetGynecol 157: 123, 1987<br />
  7. 7. Net effect on microcirculation-dilatation and no thrombosis<br />TXA2 < PGI2 and no aggregation of PLT<br />No placental infarcts - No ‘factor X’ releasedgood placental flow<br /> improved function <br /> normal fetal growth- No IUGR<br />
  8. 8. For prevention of preeclampsia - 1970’s and 1980’s……<br />Prof .Wallenberg and RothmansAm J ObstetGynecol 157:123, 1987<br />Everette and Macdonald J ClinEndocrinolMetab 45:1007,1978<br />
  9. 9. CAUGHT BETWEEN EVIDENCE & EXPERIENCE<br />
  10. 10. CLASP TRIAL- routine prophylactic administration not recommended<br />213 centres, 9364 patients <br />-Non significant 12% reduction in proteinuric HTN -significant reduction in PT delivery<br /> - no effect on IUGR, stillbirth and NNDLancet. 1994 Mar 12;343(8898):619-29.<br />
  11. 11. Cochrane systematic review2000 and 2007<br />WITHDRAWN: Antiplatelet agents for preventing and treating pre-eclampsia.<br />Knight M, Duley L, Henderson-Smart DJ, King JF. low dose aspirin, have small-moderate benefits when used for prevention of pre-eclampsia. Further information is required to assess which women are most likely to benefit, when treatment should be started, and at what dose.<br />
  12. 12. High risk women..<br />low-dose aspirin is mildly beneficial in terms of reducing the incidence of preeclampsia in women at high risk of developing preeclampsia.Clinics (Sao Paulo).  2005; 60(5):407-14 <br />
  13. 13. EBM - integrating individual skill with the best available evidence from systematic research <br />J Emeagi criticized L Duley for drawing conclusions on flawed methodologyletter - BMJ.,319,1999<br />Many large trials in her review did not address timing of starting LDA and trials with low risk women were also included<br />
  14. 14. Adopt evidence with pinch of salt<br />
  15. 15. Women with abnormal uterine doppler findings<br />ASA treatment initiated early in pregnancy is an efficient method of reducing the incidence of preeclampsia and its consequences.<br /> J ObstetGynecol Can. 2009 Sep;31(9):818-26.<br />
  16. 16. Women with abnormal uterine doppler findings<br />Low-dose aspirin administered as early as 14-16 weeks of gestation to pregnant women may reduce or modify the course of severe preeclampsia. Its effects on the prevention of IUGR need further evaluation.<br />Croat Med J. 2005 Oct;46(5):826-31.<br />
  17. 17. Lancet. Published online May 17, 2007.<br />meta-analysis suggests that antiplatelet therapy …… moderate effect in reducing the risks for preeclampsia …………… Antiplatelet therapy was not associated with significant adverse events.<br />
  18. 18. No evidence of harm- Coomarasamy et al ObstetGynecol. 2003 <br />Aspirin reduces the risk of perinatal death and preeclampsia in women with historical risk factors. <br />aspirin therapy should be considered in women with historical risk factors.<br />No increase inplacental abruptionantenatal admissionintraventricular hemorrhage<br />
  19. 19. Latest….Obstet Gynecol. August 2010 ;116<br />Low-dose aspirin initiated in early pregnancy (16 weeks or earlier) is an efficient method of reducing the incidence of preeclampsia and IUGR<br />Preeclampsia 9.3% v/s 21.3%IUGR 7% v/s 16.3%<br /> PT birth 3.5% v/s 16.9%<br />Bujold E et al<br />
  20. 20. FOGSI experience of 1216 pts in 9 centers<br />3 groups recruitedTherapeutic prophylacticprimigravidae<br />Significant reduction in need for induction<br />IUGR and PT delivery reduced<br />Primigravidae significant difference not seen <br /> FLASP (FOGSI Low Dose Aspirin study) <br />
  21. 21. Anti phospholipid antibody syndrome ..<br />Heparin and aspirin therapy improves live birth rate by 54%Empson M et al ObstetGynecol 2002;99<br />LDA as soon as preg test is positive and LMWH after 7 weeks..<br />
  22. 22. No effect on unexplained RPL..<br />LDA does not increase the live birth rate in women with unexplained recurrent miscarriage51st annual meeting of the American Society of Hematology in New Orleans.Dec 2007<br />
  23. 23. Thrombophilia…<br />Combined treatment with LMWH (dalteparin) and low-dose ASA in women with inherited thrombophilia.<br />decreases the risk of preeclampsia by 20%<br /> fetal growth restriction by 30% J ObstetGynaecol Can 2007;29(10):787–793<br />
  24. 24. Effects of low-dose aspirin in in-vitro fertilization.<br /> It is hypothesized that improve blood flow to a woman's implantation site will improve success rates.<br />Conflicting results leave the question of the effects of LDA in IVF unanswered.<br /> no need to overturn the current clinical practice for those using LDA in efforts aimed at achieving success with IVF.<br />CurrOpinObstet Gynecol. 2009 Jun;21(3):275-8<br />
  25. 25. Thromboprophylaxis- For pts with mechanical heart valves..<br />A daily low dose aspirin is recommended for patients for pts with high risk for TED.Bonow et al Circulation, 1998;98<br />
  26. 26. No adverse effect on infants..<br /> No significant relationship between LDA and any long-term adverse outcome. <br />Furthermore, they reported an association of LDA with a decrease in behavioral difficulties.<br />VinodBhutani et alPediatrics. Published online December 21, 2009.<br />
  27. 27. Adverse effects..<br />Aspirin- an increased risk of vascular disruptions, particularly gastroschisis and possibly premature closure of the ductusarteriosus.<br /> large trials demonstrate low-dose aspirin's relative safety and generally positive effects on reproductive outcomes.ObstetGynecolSurv. 2008 Jan;63(1):49-57<br />
  28. 28. Dose …<br />Most trials - 50-75 mg / day<br />Greater effect among women treated with doses > 75mg / dayRR 0.49<br />Villar et al SeminNephrol 2004; 24:607-615<br />

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