IRON DEFICIENCY ANAEMIA

Anemia is a public health problem, and still it is a major contributor to maternal mortality and morbidity.

1. NEW INSIGHTS INTO IRON DEFICIENCY ANEMIA AND ITS MANAGEMENT Presented by: DR KIRAN PANDEY MBBS MS FRCOG FIMSA FICMCH MAMS PROF & HOD, DEPT OF Obs & Gyne , GSVM MC PRESIDENT KANPUR OB&GYN SOCIETY 2016-18 DR PAVIKA LAL ASSISTANT PROFESSOR DEPT OF Obs & Gyne , GSVM MC

2. Name : DR KIRAN PANDEY MD, FICOG, FIMSA, FICMCH, MAMS Designation: Head of department , dept of OBG, GSVM medical college, kanpur . President 2016-18, kanpur obs & gynae society Secretary upsc agoi 2017-2019 Vice-president state chapter ( upcog ) 2018-u.P. CITY: kanpur Affiliations : GSVM medical college, kanpur Organizing secretary : AGOI surgical video workshop & UPSC annual CME – Dec 2018 Organizing secretary : WWWCON – 2018 Organizing chairperson : adolescent workshop, emergency obstetrics workshop – oct 2018 Organizing chairperson : National Adolescent Conference Youth Summit And C.M.E 2017 Organising Secretary ,National Conf of Obs &Gynae 2015. Organising Chairperson, Urogynaecology , NDVH, Pelvic Floor Repair Workshop, National Conference 2015 Awards : 11 National, 8 State level & 8 District level Awards & > 30 awards at IMA FOGSI facilitated with Nari Swasthya Award in AICOG(ODISHA) 2018. Awarded “ Certificate of Appreciation “ for excellent contribution in family welfare 2017-2018 Received “ President Appreciation Award ” from Adolescent Health Committee at AICOG. Received “ Matrashakti Samaan Award ” on International Women’s day 2019 Honoured by Mr.Satyadev Pachauri Minister of Khadi and Village Industries organised by Amar Ujjala Aprajita (100 million smiles). Received DR VC RASTOGI AWARD for Best women doctor in IMA UP State. Received WOMEN OF SUBSTANCE award on international women’s day 2009-10. Working towards a new Innovation for early diagnosis of cervical cancer with IIT kanpur – ‘GYTI’ AWARD from NIF India at RASHTRAPATI BHAWAN FOGSI AWARD for original research work ” Dr.Chitrathara and Dr.Gangadharan preventive & research oncology award” Publications: Published > 100 research Papers in National & International Journals Contributed chapters in various books- Fetus in-utero, Abnormal Uterine Bleeding, Amniotic fluid embolism, Gestational diabetes in “Current trends” , epilepsy in pregnancy, PCOS & auto immunity, maternal monitoring in pre eclampsia SPECIAL INTERESTS: Gynae- Oncology, Infertility, Adolescent health, Uro-gynaecology , High risk pregnancy

3. WHO. The global prevalence of anaemia in 2011. Geneva: World Health Organization; 2015. ANAEMIA AFFECTS AROUND 800 MILLION CHILDREN AND WOMEN GLOBALLY Level of public health significance: Severe Anemia: A Global Burden

4. National Family Health survey 4.Ministry of Health and Family welfare.2015-16 Anemia in Women: Declined in most states from NFHS-3 to NFHS-4,but still remains high Anaemia among Children and Adults NFHS 4 (2015-16) NFHS 3(2005-06) Urban (%) Rural (%) Total (%) Total (%) Non-pregnant women age 15-49 years (<12.0 g/dl) 51.0 54.3 53.1 55.2 Pregnant women age 15-49 years (<11.0 g/dl) 45.7 52.1 50.3 57.9 All women age 15-49 years 50.8 54.2 53.0 55.3 National Family Health Survey -4 (2015-16) data

5. Anemia During Pregnancy Hemoglobin (gm/dl) CDC <11 ( 1 st trimester) <10.5 (2 nd trimester) <11 (3 rd trimester) WHO <11 Postpartum Anemia Hemoglobin (gm/dl) WHO <10 WHO classification of severity of anemia in adult females [ Hemoglobin in gm/dl] Mild Moderate Severe Non pregnant women(age >15 years or above) 11–11.9 8–10.9 < 8 Pregnant women 10–10.9 7–9.9 < 7   Indian J Hematol Blood Transfus . 2018:1-2. Definitions

6. Milman N Ann Hematol 2006; 85(9):559-565 Iron requirement in pregnancy Anemia precedes pregnancy Pregnancy MAKES anemia VISIBLE Delivery WORSENS the ANAEMIA

7. Peripheral blood smear and red cell indices Fragmented cells , spherocytes,sickle cell Only red cells abnormal(next slide) Abnormalities of RBC alongwith abnormal WBC and platelet Abnormal cells on peripheral smear Leukemia Work up for hemolytic anemia Pancytopenia Megaloblastic anemia Aplastic anemia Bone marrow aspiration MYELOPROLIFERATIVE DISORDERS LYMPHOPROLIFERATIVE DISORDERS INVESTIGATIONS FOR ANEMIA

8. 11

9. 13 MANAGEMENT TREAT THE UNDERLYING CAUSE DIETARY OR NUTRITIONAL SUPPLEMENTATIONS IRON SUPPLEMENTATION TO CORRECT ANEMIA AND REPLENISH STORES

10. Guidelines For Management Of Maternal Anaemia Deworming with one 400 mg of tablet albendazole after meals at 14-16 weeks First Estimation Of Blood Haemoglobin at 14-16 weeks If Blood Hb < 7gm./dl If Blood Hb 7.1-10.9gm/dl If Blood Hb >11gm./dl Refer to Higher Institutions for blood transfusion Therapeutic dose of tablet 100 mg elemental iron 1 bd With 0.5 mg of folic acid. 1 Tab of vitamin b12 15mcg. And vitamin C 100 mg/ od Preventive dose of 100mg of elemental iron 1 od 0.5mg of folic acid 1 tab of vitamin b12 15mcg And vitamin C 100 mg/ od AT 14-16 WEEKS-

11. SECOND ESTIMATION OF BLOOD HEMOGLOBIN at 20-24 weeks of gestation after the consumption of preventive/therapeutic dose of iron If Blood Hb < 7gm./dl If Blood Hb 7.1-8.9gm./dl If Blood Hb 9-11gm./dl If Blood Hb >11gm./dl Refer to higher institutions for Blood transfusion Injection Iron Sucrose infusion intravenous- 4 doses of 100 mg. for 4 days over a period of 2 weeks with 2-4 days interval b/w each dose Continue with therapeutic dose Continue with preventive dose AT 20-24th WEEKS

12. III. AT 26-30 WEEKS OF GESTATION : Third Estimation Of Blood Hemoglobin after 1 month of the above 4doses (not later than 30 weeks ) If Blood Hb < 7gm./dl If Blood Hb 7.1-8.9gm./dl If Blood Hb 9-11gm./dl If Blood Hb >11gm./dl Refer to higher institutions for Blood Transfusion Counsel mother for further improvement Continue oral iron till delivery Continue with preventive dose Not Received earlier in current pregnancy Received earlier in current pregnancy Injection iron sucrose Inj. Iron Sucrose i /v infusion- 4 doses of 100 mg for 4 days over 2 weeks with 2-4 days interval 2 top up doses of inj. iron sucrose i /v infusion-100mg in 100 ml normal saline for 30 min (with 2-4 days interval)

13. Comfortable position to the mother. High flow oxygen. Encourage deep breathing b/w contractions. Strict asepsis should be maintained. MOST STRESSFUL(Cardiac failure can occur) A Tendency for Prolongation of the 2 nd stage can be curtailed by forceps. AMTSL, Avoid over loading of fluid like crystalloids etc. Replenish only if hypovolemic . In PRETERM LABOUR betamimetics and steroids should be given with caution to avoid pulmonary edema . 1st STAGE 2nd STAGE 3rd STAGE Iron & folate therapy should be continued for at least 3 months. Infection should be treated . DURING LABOUR DURING PUERPERIUM

14. How far we have come :- Iron deficiency anemia Oral iron therapy Parenteral iron therapy Intramuscular preparations Intravenous preparations Blood transfusions First generation preparations-ferric hydroxide,iron dextran Second generation preparations –ferric gluconate,iron sucrose Third generation drugs- FCM,iron isomaltose

15. Oral Iron Supplementation only 1–8% of iron is absorbed from the available oral iron preparations The absorption increases with increasing doses of oral iron only up to 160 mg/day Iron absorption is increased in iron deficient individuals take oral iron empty stomach or 1 h after meals for better absorption preferably with vitamin C Gastrointestinal side effects – major limitation ; upto 70% (especially Ferrous sulphate )   Indian J Hematol Blood Transfus . 2018:1-2.

16. Prevention Of Iron Deficiency IFA PROPHYLAXIS : Twelve by twelve initiative Weekly iron supplementation for adolescent girls Iron supplementation during pregnancy FOOD FORTIFICATION Food fortification was identified as the SECOND STRATEGY of four by the WHO and FAO to begin decreasing the incidence of nutrient deficiencies at the global level. E.g . cereals, milk, fats and oils, accessory food items,tea  & other beverages DIETARY DIVERSIFICATION :   change food consumption at the household level, such as increasing the consumption of ANIMAL SOURCE FOODS BIANNUAL DEWORMING

17. FACTORS AFFECTING ORAL IRON ABSORPTION

18. Ferrous bisglycinate

19. FERROUS ASCORBATE & FERROUS BISGLYCINATE showed significantly more rise in Hb as compared to others Maximum side effects were with FERROUS FUMARATE.

20. Intramuscular preparations Iron sorbitol citrate Iron dextran - 1 ml contain 50mg elemental iron Advantages Can be given in primary care setup Intramuscular route is not preferred now a days because of serious and long term side effects and availability of better iron preparations HMW LMW

21. Parenteral Iron Therapy Iron Oxyhydroxide core Carbohydrate shell – stabilizes the molecule and slows release of elemental iron Hemodial Int. 2017 Jun;21 Suppl 1:S83-S92 Intramuscular preparations Intravenous preparations

22. DOSE CALCULATION: Required iron dose (mg) = (2.4 × (target Hb -actual Hb ) × pre-pregnancy weight (kg)) + 1000mg for replenishment of stores Oral Iron should be stopped at least 24 hours prior to therapy to avoid toxic reaction RESTART 1 WEEK AFTER COMPLETION OF FULL DOSE OF PARENTERAL THERAPY.

23. Parenteral Iron Preparations Type Thermodynamic property Examples Type I complex Strong Ferric Carboxymaltose,Iron Isomaltoside, Ferumoxytol, Iron dextran Type II complex Moderately strong Iron sucrose Type III complex Weak Ferric hydroxide, Ferric gluconate Classification depending on type of complex: Under certain conditions, mixed complexes will be formed and such mixtures are classified as Type IV Arzneimittelforschung 2010;60(6a):345–353

24. Iron sucrose ( 2000) Advantages No tissue peroxidation Less oxidative and parenchymal tissue injury Higher availability of iron for erythropoiesis Minimal side effects Less anaphylaxis reactions Hb rise as early as 5 days Clinical use of intravenous iron: administration, efficacy, and safety. Auerbach M, Ballard H Hematology Am Soc Hematol Educ Program. 2010; 2010():338-47. [ PubMed ] [ Ref list ] Disadvantages multiple infusions Multiple visits & longer duration of therapy less but significant no of reactions So need of a setup where anaphylactic reactions can be handled

25. Newer intravenous iron formulations ferric carboxymaltose (FCM) iron isomaltose 1000 Ferumoxytol Unique strong complex structure releasing much lower levels of labile or free iron allowing large doses of iron be given over shorter time period

26. Ferric Carboxymaltose (FCM)

27. Method of administration-Bolus Injection Can be administered by intravenous injection using undiluted solution. The maximum single dose is 15 mg iron/kg body weight but should not exceed 1,000 mg iron Volume of FCM required Equivalent iron dose Administration time/minimum administration time 2 - 4 ml 100 – 200 mg No minimal prescribed time > 4 – 10 ml > 200 – 500 mg 100 mg iron/minute > 10 – 20 ml > 500 – 1000 mg 15 minutes

28. Method of administration -Infusion Must be diluted only in sterile 0.9% sodium chloride solution. The maximum single dose is 20 mg iron/kg body weight , but should not exceed 1,000 mg iron. Volume of FCM required Equivalent iron dose Maximum amount of sterile 0.9% m/V sodium chloride solution Administration time/minimum administration time 2 - 4 ml 100 – 200 mg 50 ml - > 4 – 10 ml > 200 – 500 mg 100 ml 6 minutes > 10 – 20 ml > 500 – 1000 mg 250 ml 15 minutes

29. FCM-closest to ideal iron preparations Property Ideal Iron dextran Iron sucrose Ferric carboxymaltose Antigenicity Low High Low Low Test dose No Yes yes No Time for injection Short 4 - 6 h for 20mg/kg 15 min for 100mg 15 min for 1000mg

30. Side effects of FCM Most commonly reported ADR’s include: Nausea Injection/infusion site reactions Headache,dizziness,flushing,hypertension Hypophosphataemia Most serious ADR is Anaphylactoid reactions (rare; frequency ≥ 1/10000 to <1/1000 subjects)

31. Contraindications

32. Ferric carboxymaltose - Clinical Experience Extensively studies across different indications including: Postpartum anemia IDA due to Abnormal uterine bleeding Chronic Kidney Disease Chronic Heart Failure Inflammatory bowel disease Pre- and post-operative anemia

33. Ferumoxytol   Approved by the FDA in 2009 in CKD patients with IDA Can be administrated as a relatively large dose (max 510 mg) in a rapid (< 20 seconds) session without test dose requirement. it is not currently approved in Europe and the FDA is continuing to evaluate Ferumoxytol due to reports of serious cardiac disorders (product information.feraheme ( ferumoxytol )” Alza pharmaceuticals,mountain view CA) 

34. Iron isomaltoside 1000   The newest IV iron agent Very low immunogenic potential Very low content of free iron Rapid high dose infusion of up to 2000 mg No need of a test dose Considerable dose flexibility Possibility of providing full iron repletion in a single infusion (one-dose iron repletion).

35. Evidence in postpartum anemia

36. 91.4% had an increase in Hb >3 g/ dL from baseline at any time with FCM, compared with 64.6% of subjects in the oral iron group ( P .0001). The percentage of subjects with Hb >12 g/ dL was significantly greater in the FCM group than in the oral iron group (91.4% vs 66.7%; P .0001)

37. Indications of blood Transfusion in anemia INTRAPARTUM PERIOD a. Hb <7 g/ dL POSTPARTUM PERIOD a . Anemia with signs of shock/acute hemorrhage / hemodynamic instability. . Hb <7g% Antepartum period PERIOD 1.POG <34 WEEKS: a. Hb <5 g/ dL with /without CHF b. Hb 5-7 g/ dL – in presence of CHF 2. POG >34 WEEKS: a. Hb <7 g/ dL even without CHF b. Severe anemia with decompensation 3. ACUTE HEMORRHAGE: II Intrapartum period Post partum period

38. FOGSI GCPR 2017 recommendations

39. FOGSI GCPR 2017 recommendations FOGSI General Clinical Practice Recommendations. Management of Iron Deficiency Anemia in Pregnancy.India;2017

40. FCM In Abnormal Uterine Bleeding Efficacy and safety of IV ferric carboxymaltose (FCM) in comparison with IV iron sucrose (ISC) in the treatment of anemia due to abnormal uterine bleeding (AUB). The primary outcome, increase in hemoglobin above baseline, was monitored over a 12-week period. International Journal of Gynecology and Obstetrics 2016; 133, 43–48 Increases in mean Hb levels from baseline were significantly higher in the FCM group at 6 weeks (P=0.005). The increase in serum ferritin levels were significantly higher in the FCM group (P b 0.001).

41.   50 It is a nervous disorder characterized by symptoms of dysesthesias in the lower extremities . Diagnosis is basically clinical , as there is no specific test . The five basic criteria for clinically diagnosing the disorder are: RESTLESS LEG SYNDROME URGE TO MOVE Associated with abnormal, unpleasant, or uncomfortable sensations. Get worse during rest or inactivity. Relieved by movements Aggravated in the evening or night. Not due to any other medical or behavioral condition .

42. 51 LIFESTYLE CHANGES IRON SUPPLEMENATATION ANTI SEIZURE DRUGS avoiding alcohol and tobacco regular sleep pattern moderate exercise massaging the legs warm bath heating pad or ice pack.  Trial of iron supplements is recommended as the first treatment The FDA has approved gabapentin enacarbil for the treatment of moderate to severe RLS RLS with iron deficiency without anemia can be cured by single dose of FCM therapy TREATMENT OPTIONS

43. Administration of large doses (15 mg/kg infusion) in a single infusion Rapid (15-minute) infusion No need of test dose Rapid replenishment of iron stores FCM - treats anemia in 15 mins ITS USE HAS BEEN EXPANDING AND INCREASING IN PREGNANCY AS WELL AS IN IRON DEFICIENCY GYNAECOLOGICAL PROBLEMS