Anemia na gravidez

Question 1

Fisiologia

Answer 1

• Physiological adaptations in pregnancy are aimed to accommodate the needs of the Fetal-Placental unit

- Haemathologic changes during pregnancy
o Physiological Anemia 
o Leukocytosis and Neutrophilia 
o Mild thrombocytopenia
o Rise in procoagulant factors 
o Decreased fibrinolysis

• ESTADO HIPERVOLEMICO
  o Expansion of plasma volume : 10-15% at 6-12 weeks; 30-50% at 34 weeks (max. peak)
  o Nulliparous: increases 1200 ml
  o Multiparous: increases 1500 ml > em gravidezes multiplas
• Maternal blood volume at term: 100ml/kg -> Returns to normal in puerperium, between 6th and 8th week

Question 2

Eritropoiese na gravidez

Answer 2

• Increase in erythropoiesis
  o devido a HLP, PRG e PRL
• EPO aum 50% na gravidez normal
• aum 30% in erythrocyte mass vs non-pregnant, if supplemented with iron
• Aum 18% in erythrocyte mass vs non-pregnant, if NOT supplemented with iron
• Launching into circulation of new erythrocytes: Reticulocytes
• Aum VGM e CHGM (concentração hb globular media)

Question 3

Volume plasmático e anemia na gravidez

Answer 3

• Plasmic volume > erythrocyte mass (3:1)
• Aum iron requirements (1000 mg)
  o erythrocyte expansion (500mg)
  o Fetus (250mg)
  o Placenta (100mg)
  o Daily losses (150mg)
• ANEMIA FISIOLOGICA
• Pico nas 34 sem -> near term there is an increase in haemoglobin concentration
  o plateau de expansão plasmática
  o massa eritrocitaria continua a subir

Question 4

Anemia e gravidez

Answer 4

• Number of Erythrocytes, amount of Hb or Hct lower than in healthy adults of the same sex, age group and environment
• Hb < 11g/dl / Hct < 33% in 1st and 3rd T
• Hb < 10,5g/dl / Hct< 32% in 2nd T
• Afro-americanos: dim cut off 0,8 g/dl

- WHO:
o Hb < 11g/dl / Hct < 33% 
o Severe: Hb < 7g/dl
o Medical emergency: Hb < 4g/dl (risk DIC) 
o Post delivery: Hb < 10 g/dl

Question 5

Complicações

Answer 5

- fetais (Hb <9g/dl) :
o Preterm delivery (60%, in iron-deficiency anemia if iron deficiency 1st Q) 
o Fetal growth restriction (2x) 
o Miscarriage and fetal death (3x) 
o Low weight at birth
o Developmental disorder

• Obstetricas:
  o Descolamento
  o PE
• Hb ideal para previnir PPT e Restrição crescimento: 9,5-11,5 g/dl

Question 6

DX

Answer 6

- Anamnese:
o Ethnicity and country of origin 
o Occupation
o Socioeconomic status
o Type of diet (vegetarian?) 
o Drugs 
o Travels  
o Infections 
o Exposure to toxics and food items (beans,..) 
o Medical history (thyroid disease, infectious, liver disease, autoimmune...) 
o Family history (Hemoglobinopathy?)

• LAB:
  o Hemograma
  o Esfregaço sangue periferico
  o Reticulocitos (increase in peripheral destruction vs decrease in spinal cord production)
  o Estudo ferro (serum iron, transferrin, ferritin, CTFF)
  o Electrophoresis of Hb

Question 7

Anemia microcitica

Answer 7

- Dx diff:
o Iron-deficiency anemia 
o Thalassemia 
o Chronic bleeding 
o Chronic disease 
o Sideroblastic anemia

• HC (hx familiar talassémias, …)
• LAB (hemo, ferro, eletroforese Hb)
• Def ferro: ferro baixo, ferritina baixa, CTFF alto, eletro Hb normal
• Talassemia: ferro N/alto, ferritina N/baixa, CTFF N, eletro Hb anormal
• Doença crónica: ferro baixo, ferritina baixa, CTFF N/alto, eletro Hb normal
• Sideroblastica: ferro N/alto, ferritina N, CTFF N, eletro Hb normal
• If untreated, anemia will worsen during pregnancy and blood loss at delivery can be catastrophic, specially when there are risk factors (multipara, previous PPH)

Question 8

Anemia ferropenia

Answer 8

• Main cause of anemia in pregnancy (75-85%)
• Aum necessidade ferro durante gravidez
• dieta inapropriada
• Chronic depletion of iron reservoirs
  o menorrhagia, multiparous short inter-pregnancy interval, multiple pregnancies, teen pregnancy, low socioeconomic status
• Iron distributed over 3 compartments
  o Linked to Heme (Hb, myoglobin)
  o Stored: ferritin and hemosiderin
  o Transport: transferrin

- 1g of Fe required daily:
▪ 500 mg for erythrocyte expansion 
▪ 250 mg for the fetus
▪ 100 mg for the placenta 
▪ remaining to make up for daily losses

Gravidez -> feto e placenta

• Diet alone does not fulfill these needs and even women beginning pregnancy with intact storage are at risk of iron-deficiency -> PREVENTION: 30-60mg/day iron, fasting, > 20w (> 2 trim)
• Fetal anemia is rare (even when the maternal deficiency is severe)
• No relation to congenital malformations
• Increased risk of PPTermo, FGRestriction, and fetal death (severe anemia)

- TX: 
o 100-200mg/day iron per os for 2 weeks 
- Queremos:
o ↑ Hb 1-2g/dl in 2 weeks 
o ↑ reticulocytes in 3-7 days
- Melhora? -> mantain therapy for 4-6 months 
- Não melhora -> exclude poor adhesion and other causes of anemia
- EA:  nausea, vomiting, constipation
o Vitamina C em jejum (aum absorção)

• Tx alternativa:
  o Ferro IV- Venofer® (ferric oxide saccharate) - 2% associated risks (anaphylaxis, DIC, renal toxicity, bronchospasm)
  . Ferinject® (ferric carboxymaltose) - better tolerance, low toxicity, low immunogenic potential, administration in 15 min
• INDICAÇÕES:
  ✓ Intolerance or absence of response with oral therapy
  ✓ Malabsortion syndromes
  ✓ Post-partum if Hb ≥7 e ≤9g/dl
  ✓ Contraindications: active infection or 1st trimester
  ✓ Stop oral iron for at least 5 days after administration of ev iron

o transfusão sangue:
. Hb < 7g/dL if post-partum, symptoms or hemodynamic compromise
. Chronic disease with risk of decompensation
. Severe/active blood loss

Question 9

talassémia

Answer 9

• Changes in the synthesis of globin chains of the hemoglobin molecule -> Faulty hemoglobin synthesis - globin chains
• Autosomal recessive disorders
• Tipos:
  oA lpha α- Decrease or absence in the production of α chains
  o Beta β- Decrease or absence in the production of β chains
  o Gamma Υ
  o Delta δ
  o Epsilon ε
  o Zeta ζ
• > Mediterranean, India, Pakistan, Africa, and Southwest Asia
• Pgx depende do tipo genético
• TX:
  o Not necessary in the minor forms
  o Prevention with 1mg/day folate
  o Supplementation with iron – only when there is iron deficiency

Question 10

Beta talassemia

Answer 10

• Genotipos:
  o Talassemia minor: 1 gene affected - Disease levels, depending on the production rate of β chains -> Mild asymptomatic microcytic anemia
  . ++ HbA2 - 4-6%
  . Well tolerated pregnancy
  . No consequences for fetus if partner not affected
  . EVALUATE PARTNER and PRENATAL DIAGNOSIS if both parents are affected

o Thalassemia major: deletion of 2 genes (homozygotes); microcytic anemia - Variable severity (depending on whether synthesis of β-globin is reduced or absent)
. Hemolysis and ineffective erythropoiesis -> anemia grave -> transfusões freq
. Usually causes infertility but success cases have been described
. Fetus is sheltered from serious disease by the production of F Hb -> diminui apos parto -> anemia nos 3-6 meses
. EVALUATE PARTNER and PRENATAL DIAGNOSIS if both parents are affected

Question 11

alfa talassemia

Answer 11

• Genotipos:
  ▪ (αα,αα) Normal
  ▪ (αα,α-) Asymptomatic carrier: deletion of 1 gene, without anemia

▪ Thalassemic trait: deletion of 2 genes; microcytic anemia -> Microcytic anemia and slight to moderate hypochromia and increase in red cells, normal electrophoresis of Hb
. Usually pregnancy without complications.
o (α-,α-) Trans configuration o (αα,–) Cis configuration
o Fetus of parents with trace in cis configuration are at greater risk of homozygosity (HbBart)
. EVALUATE PARTNER and PRENATAL DIAGNOSIS If both parents affected

▪ (α-,–) Disease of Hb H: deletion of 3 genes -> Excess of β chains -> Tetramers of β chains -> HbH (5-30%)
o Greater affinity for oxygen
o Greater susceptibility to oxidative stress
o corpos de Heinz -> dano parede celular
o Variable chronic hemolytic anemia with exacerbations when under stress, splenomegaly, skeletal changes by augmented erythropoiesis
o Pregnancy: Anemia may be severe and require transfusion.
o Fetus: Fetal anemia with hydropsia may take place.
. EVALUATE PARTNER and PRENATAL DIAGNOSIS If both parents affected

▪ (–,–) HbBart disease: deletion of 4 genes -> There are no α chains -> fetus cannot produce F Hb
o Tetramers of gamma chains: Bart Hb
. High affinity for oxygen which is released for tissues
. Non-immune hydrops fetalis with death in uterus
. In case of survival (rare) – generalized edema, anemia and severe ICC, hepatomegaly. Need for frequent transfusions. Developmental disorders
. Possibility of termination of pregnancy

Question 12

Anemia normocitica

Answer 12

• Structural hemoglobinopathies
• Anemia falciforme
  o Substitution of valine for glutamic acid in position 6th of β chain -> HbS
  o Substitution of lysine for glutamic acid -> HbC
• > Beja, Faro, Santarém, and Setúbal; > África
• Major modifications: SS Hb, CS Hb, S Hb beta-tal
• Minor modifications: AS Hb, AC Hb
• Heterozigotos -> traço falciforme
  o Usually pregnancy well tolerated
  o > risk of urinary tract infection and PE
  o > risk of prematurity and low birth weight
  o > fetal death risk ?
  oEVALUATE PARTNER and PRENATAL DIAGNOSIS If both parents affected
• Homozigotico -> Anemia falciforme (HbSS)
  o Good fetal prognostic, if maternal oxygenation is sustained
  o >abortion risk, prematurity, FGR, and perinatal mortality
  o >Risk of hypertension complications, infections, stroke, pulmonary oedema
  o maternal mortality 6x greater
  o Crises vaso-oclusivas, infeção
  o Follow-up at specialized centers with differentiated Perinatal support
  o EVALUATE PARTNER and PRENATAL DIAGNOSIS
• HbSC - doença severa
• Hb S/ beta talassemia- sem afeção geral

Question 13

Anemia macrocitica

Answer 13

• Megaloblastica- Changes in DNA synthesis -> Affects cells with quick turnover like GI and blood cells (erythropoiesis more affected). More serious cases, also leukopenia and thrombocytopenia

- Causas:
✓Deficiency of folic acid ✓Deficiency of vitamin B12 ✓Toxicity ( : AZT) 
✓Liver disease 
✓Alcoholism 
✓Hypotiroidism

• Suplementação com Ácido fólico (400 micras/dia) -> 5 mg /dia

Question 14

Quando investigar anemia

Answer 14

- Durante gravidez se
o Family history
o Native of region with high prevalence 
o Microcytosis or anemia 
o Parent with known hemoglobinopathy

• Investigate the partner if the pregnant woman shows hemoglobinopathy
• Genetic counseling
• Prenatal Diagnosis: CVBiopsy/amniocentesis if both parents are affected