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ANEMIA IN PREGNANCY
OBSTETRICS II 6th LONG EXAM
Dr. Ganzon
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HEMATOLOGIC CHANGES IN
PREGNANCY
Hypervolemic state
40-45% above non-pregnant blood volume
Occurs after 32-34 weeks AOG Also seen in hydatidiform moles (form of
pregnancy without fetus)
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HYPERVOLEMIA IN PREGNANCY
1. Meet metabolic demands of enlarged uterus
(hypertrophied blood vessels)
2. Provide abundant nutrients to rapidly
growing placenta and fetus
3. Protect mother and fetus from impaired
venous return in the supine and erect
positions
4. Protect mother from adverse effects of blood
loss during delivery
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BLOOD VOLUME INCREASE
12 weeks
- 15% increase
Much of the increase occurs in 2nd trimester
Slower rate in 3rd trimester then plateaus
Plasma & erythrocytes increase cause increased
volume
-Erythroid hyperplasia in bone marrow
-Elevated reticulocyte count
-Increased maternal erythropoeitin levels (peak during
early 3rd
trimester)
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HEMOGLOBIN & HEMATOCRIT
Hemoglobin & hematocrit decrease slightly
due to relative increase in plasma
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IRON METABOLISM
Total iron content = 2.0-2.5 g for normal adult women
Total iron stores = 300 mg
1000 mg of iron required for normal pregnancy
-300 mg actively transferred to fetus and placenta-200 mg lost, excreted via GIT
-500 mg stored in erythrocytes / red blood cells
Iron requirements 6-7 mg/day esp during midpregnancy
-iron supplements necessary during this time
-iron in diet & iron stores insufficient for metabolic needs
Around 5 months of gestation we give iron supplementation
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ANEMIAS IN PREGNANCY
Mostly occur or diagnosed during mid-
pregnancy
Most are relative decrease in hemoglobin and
hematocrit due to increased plasma volume
Influenced by economic status & dietary
customs
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CAUSES OF ANEMIA IN
PREGNANCYACQUIRED HEREDITARY
Iron deficiency anemia Thalassemias
Acute blood loss Sickle cell hemoglobinopathies
Due to inflammation or malignancy
sepsis, UTI
Other hemoglobinopathies
Megaloblastic anemia Hereditary hemolytic anemias
Acquired hemolytic anemia
Aplastic or hypoplastic anemia
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CONSEQUENCES OF ANEMIA IN
PREGNANCY
Increase risk of preterm birth
Low birthweight
Small for gestational age infants-related to degree of anemia
-influence on placental vascularization
-alteration in angiogenesis during earlypregnancy
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PARADOX OF INCREASED HEMOGLOBIN
CONCENTRATION IN PREGNANCY
Also increased risk for adverse perinatal
outcomes
Low plasma volume with increased red cell
mass
Also with increased preterm or growth
restricted infants (due to blood thickness)
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IRON DEFICIENCY ANEMIA
Seen as drop in hemoglobin concentration
3rd trimester; need for additional iron
-transport to fetus and augment maternal Hgb
-newborn of severely iron deficient mother does not
suffer iron deficiency anemia
-neonatal iron stores are related to maternal iron status
and timing of cord clampingMost common cause of anemia
During the 3rd trimester or 28th week of gestation there
is a need for more iron
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IRON DEFICIENCY ANEMIA
Hypochromic RBCs
Microcytosis
Serum ferritin lower than normal Due to expansion of plasma volume without
normal expansion of maternal Hgb mass
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DIAGNOSTICS
Hemoglobin/hematocrit
Red cell indices
Peripheral blood smear Sickle cell preparation (if African in origin)
very prone to sickle cell anemia
Serum iron / ferritin levels On CBC, if very low Hgb/Hct you may have IDA
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TREATMENT
Ferrous sulfate (oral)
Ferrous fumarate (oral) will not cause
vomiting compared to ferrous sulfate
Ferrous gluconate (oral)
-provide 200 mg of elemental iron per day
Ferrous sucrose safer than iron dextran(parenteral)
-continue treatment 3 months after anemia has
been resolved
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ACUTE BLOOD LOSS
Abortion, ectopic pregnancy, H.mole are
pregnancies that may also cause anemia due
to acute blood loss
Most common = obstetrical hemorrhage
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ASSOCIATED WITH CHRONIC
DISEASE Weakness
Weight loss
Pallor
Chronic renal failure (kidneys do not produce
erythropoeitin)
Cancer & chemotherapy
Human immunodeficiency virus infection Chronic inflammation (e.g. SLE)
-hypochromic & microcytic RBCs
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A. CHRONIC RENAL DISEASE
Erythropoeitin deficiency
Intensified during pregnancy
Ex: Acute pyelonephritis with sepsis -> anemia-acute red cell destruction from endotoxin
mediated sepsis. Treat with recombinant
erythropoeitin when hematocrit is 20% & lower
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MEGALOBLASTIC ANEMIA
Blood and bone marrow abnormalities
DNA synthesis is impaired
1. Folic acid deficiency2. Vitamin B12 deficiency
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FOLIC ACID DEFICIENCY
Pernicious anemia of pregnancydo not eat 3x a day
especially on charity patients
Neurologic abnormalities
Dietary insufficiency
-inadequate consumption of fresh green leafy vegetables,
legumes or animal protein
Consequently cause anorexia
Ethanol ingestion -> folic acid deficiency 400 ug/day is required
Hypersegmented neutrophilsmicroscopic examination
Newly formed erythrocytes
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Hypersegmented neutrophils
Newly-formed erythrocytes
Macrocytic RBCs Peripheral nucleated RBCs are also seen if folic
acid deficiency is severe
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Fetus & placenta extract folate from maternal
circulation
Folic acid, nutritious diet, & iron
1 mg folic acid per day for pregnant women
with folic acid deficiency
-4 mg if with previous baby with neural tube
defect
Prevents neural tube defects in fetus
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INCREASED FOLATE DEMANDS
DURING
Multifetal pregnancy
Hemolytic anemia
Crohns disease Alcoholism
Inflammatory skin disorders/problems
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VITAMIN B12 DEFICIENCY
Vitamin B12 = cyanocobalamin
megaloblastic anemia
Rare Addisonian pernicious anemia (lack of intrinsic
factor for absorption of vitamin B12)
May be due to partial or total gastric resection Associated with Crohn disease, ileal resection
& bacterial overgrowth in small bowel
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VITAMIN B12 DEFICIENCY
During pregnancy, cobalamin levels are low
-decreased binding proteins, haptocorrin &
transcobalamin II
Treatment would be 1000 ug vitamin B12 IM
monthly
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HEMOLYTIC ANEMIAS
Primary hemolytic anemias are of unknown causes
Most common are secondary types
1. Lymphomas
2. Leukemias
3. SLE
4. Connective tissue diseases
5. Infections
6. Drug induce antibodies (ketoconazole, cefuroxime)
7. Epstein barr virus
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AUTOIMMUNE HEMOLYTIC
ANEMIA COLD AGGLUTININ DISEASE
-Hemolysis
-Induced by infections (i.e. Mycoplasma pneumoniae or Epstein
Barr virus mononucleosis
Characteristics
-hemolysis
-positive antiglobulin test
-spherocytosis-reticulocytosis
Fetal red cells are not affected IgM does not cross placenta
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AUTOIMMUNE HEMOLYTIC
ANEMIA
Uncommon
Production of aberrant antibody
Positive Direct & Indirect Coombs test 80-90% caused by warm active autoantibodies
Primary AIHA have unknown causes
Secondary AIHA are due to:
-Lymphomas, leukemia, connective tissue
diseases, infections, chronic inflammatory
diseases & drug induced antibodies
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AUTOIMMUNE HEMOLYTIC
ANEMIA
Treatment:
Prednisone 1mg/kg per orem per daily
Blood transfusions should be at bodytemperature to prevent destruction by cold
agglutinins
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DRUG INDUCED HEMOLYTIC
ANEMIA
Mild resolves with withdrawal of the drug,
drug acts as hapten & it attaches to your RBC
& antibodies recognizes & destroys your RBC
Drug mediated immunological injury to red
cells
Probenecid, quinidine, rifampin, thiopental,
antibiotics and anti-fungals
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DRUG INDUCED HEMOLYTIC
ANEMIA
Mild to moderate chronic hemolysis
Also related to a congenital erythrocyte
enzymatic defect G6PD
G6PD deficiency undergoes hemolytic
anemia
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PREGNANCY INDUCED HEMOLYTIC
ANEMIA
Unexplained rare condition
Occurs during pregnancy
Immune mediated Intraerythrocytic or extraerythrocytic defects
Possibly an autoimmune disease
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PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA
Hemolytic stem cell disorder (Intermittenthappening)
Defective platelets, granulocytes anderythrocytes
Acquired
Arises from one abnormal clone of cells
X-linked gene PIG-A (phosphatidyl glycanprotein
A) = abnormal anchor proteins on RBCs andgranulocyte membrane make them susceptible tolysis by complement
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PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA
Chronic hemolytic anemia
Insiduous
Mild to lethal in form
Hemoglobinuria (red brown urine) at irregular
intervals
-initiated by blood transfusion, infection,surgery
- 40% have venous thrombosis, occurs in
legs/lower extremities
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PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA
Renal failure , hypertension
Budd chiari syndrome
May need thrombocytic therapy/ anticoagulation
Very fatal if it occurs after delivery
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PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA
Treatment
Bone marrow transplant
Eculizumab ( anti-body that inhibit complemnt
activation)
Have not been used in pregnant patient
Chemotherapy targeted agent
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PAROXYSMAL NOCTURNAL
HEMOGLOBINURIA
Fatal in 10-20% of pregnant women
Venous thrombosis in 50%of postpartum
women (ask if there is leg pain or difficulty of
breathing)
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SEVERE PREECLAMPSIA-
ECLAMPSIA
Fragmentation
Microangiopathis hemolysis with
thrombocytopenia
HELLP SYNDROME (hemolysis, elevated liver
enzymes, low platelet)
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BACTERIAL TOXINS
Most common pathogens;
Clostridium perfringens
Group A beta hemolytic streptococcus
Gram negative bacteria (lipopolysaccharide)
Cause hemolysis > mild to moderate anemia
Bacteremia from severe pyelonephritis
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HEMOLYTIC ANEMIA DUE TO
INHERITED ERYTHROCYTE DEFECTS
Mild to moderate anemia most common cause is
pyelonephritis, UTI not treated properly goes up to kidneys
Result in destabilization of membrane lipid layer of
erythrocytes
Surface area deficiency
Poorly deformable RBSs
Result in hemolysis
Hereditary spherocytosis
Pyropoikilocytosis
ovalocytosis
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HEREDITARY SPHEROCYTOSIS
Take out the spleen and patient is okay (but
dont do it in pregnancy)
Autosomal dominant -> spectrin
deficiency/ankyrin deficiency/ autosomal
recessive proteins in the membrane
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HEREDITARY SPHEROCYTOSIS
Autosomal dominant, variably penetrant
spectrin deficiency
Affect rbc membrane proteins
Autosomal recessoive or dde novo gene
mutations
Deficiency of ankyin, protein 4.2 moderate band 3
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HEREDITARY SPHEROCYTOSIS
Characteristics
Varying degrees of hemolysis
Jaundice
Spherocytosis on blood smear
Reticulocytosis
Inc. osmotic fragility
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CRISIS in H.S
Severe anemia
Accelarated RBC destruction
Spenic sequestration
Splenomegaly
Splenectomy is an option to reduce hemolysis,
anemia and jaundice Parvovius B19 known to cause hemolysis and
suppress bone marrow production
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HEREDITARY SPHEROCYTOSIS IN
PREGNANCY
Do well during pregnancy
Folic acid supplements are recommended
In new born who inherited HS, may exhibit
hyperbilirubinemia and anemia
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RED CELL ENZYME DEFICIENCIES
Permit anaerobic glucose may
Cause hereditary nonspherocytic anemia
Most are autosomal recessive
G6PD however is X-linked
Induced by drugs or infections
Variable hemolysis
Anemia is episodic
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RED CELL ENZYME DEFICIENCIES
Pyruvate kinase deficiency
Autosomal recessive
Variable anemia and hypertension
Iron overload common due to massive
transfusions
Hydrops fetalis is associated
Confirmed by venipuncture
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APLASTIC ANEMIA
Pancytopenia with hypoplastic bone marrow Grave coplication but rare
Linked with autoimmune disease
Induced by drug, infection, chemicals, radiation,leukemia, immunological disorders, fanconianemia, diamond blackfan syndrome
Marked decrease in committed marrow stem
cells Immune mediated
Difficult to manage
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APLASTIC ANEMIA
Hematopoietic stem cell transplantation
Treatment:
Immunosuppressive therapy + bone marrow transplant
75% with good response
Long term survival is seen withantithymocyte globulin
and cyclosporine
Antibiotic for infection and transfusion for anemia
20% HCT is ok for them Anemia caused by chemotherapy: patient may die
because of infection
If acquired in pregnancy, effects are hemorrhage and
infection and 50% is fatal
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APLASTIC ANEMIA IN PREGNANCY
Major risk: hemorrhage and infection
50% mortality rate
Treatment:
Antibiotics
Red cell transfusions
Maintain hct > 20 volume %
Platelet transfusion to control hemorrhage
Favor vaginal delivery section
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BONE MARROW TRANSPLANT
Can result in successful pregnancies
Risk of preterm delivery and hypertension
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CHRONIC AND ACUTE CHANGES IN
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CHRONIC AND ACUTE CHANGES IN
SICKLE CELL DISEASE Osteonecrosis of femoral and humeral head Renal medullary damage
Autosplenectomy in Hgb SS
Splenomegaly in other variants
Hepatomegaly
Ventricular hypertrophy
Pulmonary infarctions
Pulmonary hypertensions
Cerebrovascular accidents
Leg ulcers
Risk of infection and sepsis
RR for death = 4-11x
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SICKLE CELL IN PREGNANCY
Increased OR (odds ratio) for: Renal failure
Gestational hypertension/preeclampsia
Eclampsia
Placental abruption
Preterm delivery
Fetal growth restriction
Cerebrovascular vein thrombosis
Pneumonia
Deep vein thrombosis Pulmonary embolism
Cardiomyopathy
Pulmonary hypertension
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SICKLE CELL TREATMENT
Close observation! Prenatal folic acid 4mg/day
Pain is from intense sequestrationof sickled RBCs withinfarction of other organs
Treat Bacteriuria/ acute pyelonephritis If in pain, suspect crisis already
Advised to be vaccinated as they can get simpleinfections):
Pneumococcal
Flu vaccine Meningococcal vaccine
Acute chest syndrome Pleuritic chest pain, fever, cough, lung infiltrates, hypoxia
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LABOR AND DELIVERY
Similar to management of pregnant women
with cardiac problems (gravidocardiacs)
Comfortable but not heavily sedated
Epidural analgesia
Blood transfusion
Prophylactic red blood cell transfusion
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THALASSEMIAS
Impaired production of one or more of the
normal globin peptide chains
Abnormal synthesis, hemolysis -> anemia
Classified according to globin chain that is
deficient
Alpha or beta thalassemia, major types
Incidence 1 in 300-500 pregnancies
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GENOTYPES AND PHENOTYPES
genotype genotype phenotype
normal aa/aa -
Alpha thalassemia
(heterozygote)
-a/aa aa/-a Silent carrier
Alpha thalassemia
(heterozygote )
Alpha thalassemia
-a/-a
--/aa
Alpha thalassemia minor-
mild hypochromic
microcytic anemis
Compound heterozygousa/a
--/aa Hgb 4 with moderate tosevere hemolytic anemia
Homozygous a thalassemia --/-- Hydrops fetalis
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ALPHA THALASSEMIA
4 alpha globin chains
Severity depends on the combination of synthesis
impairement
Gene loci centered on chr.16 2 main groups:
Alpha deletion of both locci from one chr (--/aa)
Alpha single locus from one allele(-a/aa) or lossfrom each allele(-a/-a)
Hydrops fetalis happens when there is homozygous
alpha thalassemia
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BETA THALASSEMIA
Impaired production of beta globin chains or instabilityof alpha chains
Single nucleotide substitution
Transcription or translation defects
RNA splicing or modification
Frameshift-> unstable hemoglobins can be the cause
Gene cluster is on chr 11
Decrease beta chain production
Excess alpha chains precipitate ->membrane damage
Alpha chain instability
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