hematological
disorders tony tagacay ii
dra. mae mullet-panaligan
ANEMIA DIAGNOSIS
st rd
• 11g/dL – 1 and 3 trimester • Erythrocyte hypochromia and microcytosis
nd
• 10.5g/dL – 2 trimester o Classic morphological evidence of IDA
th
• Cut off – 5 percentile o Less prominent in pregnant
• Caused by a relatively greater expansion of plasma o Moderate IDA in pregnancy à usually not
volume compared with the increase in red cell accompanied by obvious morphological
volume change in erythrocyte
o However, serum ferritin level is lower than
CAUSES OF ANEMIA normal
• Geography • IDA in pregnancy
• Ethnicity o Consequence of expansion of plasma
• Nutritional status volume without normal expansion of
• Preexisting iron status maternal hemoglobin mass
• Prenatal iron supplementation • Initial evaluation includes:
• Socioeconomic o Hemoglobin
o Hematocrit
o Red cell indices
o Peripheral blood smear
o Sickle cell preparation – African origin
o Serum iron
o Serum ferritin à normally declines during
pregnancy
§ Levels <10-15 mg/L à confirm IDA
TREATMENT
• 30-60 mg – elemental iron
• 400 microgram folic acid
• Simple iron stores – ferrous sulfate, fumarate,
gluconate – provides 200 mg daily of elemental iron
• Iron sucrose (IV)
o Preferred over iron dextran
EFFECTS ON PREGANCY OUTCOMES B. ANEMIA FROM ACUTE BLOOD LOSS
• Low birthweight • Early pregnancy blood loss
• Preterm birth o Abortion
• SGA o Ectopic
• Lower mental development o H-mole
• Fetal growth restriction • Anemia is much more common postpartum
o Hemorrhage
A. IRON DEFICIENCY ANEMIA • Massive hemorrhage demands immediate treatment
• Iron deficiency & acute blood loss à two most • MODERATE ANEMIA
common cause of anemia o Hemoglobin: 7g/dL
• Maternal need for iron (singleton): 1000 mg o Not septic, ambulatory, no other symptoms,
o 300 à fetus and placenta Blood transfusion is not indicated
o 500 à maternal hemoglobin mass o Iron therapy is given for 3 months
expansion o IV ferric carboxymaltose
o 200 à shed normally through gut, urine & § Given weekly
skin § Was as effective as 3x-2x a day oral
• Drop in hemoglobin concentration ferrous sulfate
•
rd
3 trimester
o Additional iron is needed to augment
maternal hemoglobin and for transfer of
fetus
C. ANEMIA ASSOCIATED WITH CHRONIC DISEASE TREATMENT
• Chronic disease • Folic acid is given along with iron, together with
o Weakness nutritious diet
o Weight loss • After 7 days of folic acid, reticulocyte count increases
o Pallor
• Second most common form of anemia worldwide PREVENTION
• In non-pregnant with chronic inflammatory disease • Folic acid
o Hemoglobin concentration is rarely <7g/dL o Prevents megaloblastic anemia
o Bone marrow cellular morphology is not • Requirements increase
altered o Crohn’s disease
o Serum iron concentrations are decreased o Multifetal pregnancy
o However, serum ferritin is elevated o Alcoholism
• HEPCIDIN o Inflammatory skin disorders
o Polypeptide produced in the liver that • 4 mg daily – with previous neural tube defects
participates in iron balance and transport (NTDs)
PREGNANCY VITAMIN B12
• In pregnant with preexisting anemia, it may be • Decrease during pregnancy because of decreased
intensified as plasma volume expands levels of binding proteins that include haptocorrin–
disproportionately to red cell mass expansion transcobalamins I & III–and transcobalamin II
• CAUSES OF CHRONIC DISEASES: • During pregnancy
o Chronic renal failure o Megaloblastic anemia is rare from
o Inflammatory bowel disease (IBD) deficiency of B12 (cyanocobalamin)
o Connective tissue disorders • ADDISONIAN PERNICIOUS ANEMIA
o Granulomatous infections o Results from absent intrinsic factor, which is
o Malignant neoplasm requisite for Vit B12
o Rheumatoid arthritis o Autoimmune
o Chronic suppurative conditions o Onset is at age 40 years
• CHRONIC RENAL FAILURE • Total gastrectomy
o Most common disorder during pregnancy o Requires 1000 ug B12 (IM) each month
• Some cases are accompanied by erythropoietin • Partial gastrectomy
deficiency o Does not need supplementation
• The degree of red cell mass expansion ins inversely • Other causes of megaloblastic anemia from B12
related to renal impairment include:
• At the same time, plasma volume expansion is o Crohn’s Disease
usually normal and this anemia is intensified o Ileal resection
o Bacterial overgrowth in small bowel
TREATMENT
• Recombinant EPO for hematocrit of 20% E. HEMOLYTIC ANEMIA
AUTOIMMUNE HEMOLYSIS
D. MEGALOBLASTIC ANEMIA • Cause of aberrant antibody production is unknown
• Characterized by blood and bone marrow • Both direct and indirect antiglobulin (Coombs) tests
abnormalities from impaired DNA synthesis are positive
• Anemias caused by these factors may be due to
FOLIC ACID DEFICIENCY warm active autoantibodies (80-90%), cold
• In US, megaloblastic anemia beginning during antibodies, or a combination
pregnancy almost always result from folic acid • Treatment: Glucocorticoid
deficiency (Pernicious Anemia of Pregnancy)
• Found in woman who do not consume fresh green DRUG-INDUCED HEMOLYSIS
leafy vegetables, legumes or animal protein • Hemolysis is mild and resolves with drug withdrawal
• Excessive ethanol ingestion • Example: G6PD deficiency
o Contributes to folate deficiency
• Non-pregnant folic acid requirement: 50-100 ug/day PREGNANCY-INDUCED HEMOLYSIS
• Pregnancy: 400 ug daily • Immunological cause is accepted
• Early morphological change
o Hypersegmented neutrophils and
macrocytic newly-formed erythrocytes
• PBS: demonstrate macrocytes
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA • Major risk to pregnant woman with hypoplastic
• Acquired; arise from abnormal clone of cells, like anemia à hemorrhage & infection
neoplasm • Management depends on gestational age, disease
• THROMBOSIS severity and whether treatment is given
o Most serious complication in pregnancy • Supportive care includes continuous infection
• Unpredictable surveillance and microbial treatment
• Maternal mortality is high • Granulocyte transfusions
• Red cell transfusion
SEVERE PREECLAMPSIA & ECLAMPSIA • Platelet transfusion à to prevent hemorrhage
• Fragmentation or microangiopathic hemolysis with
thrombocytopenia PREGNANCY AFTER BONE MARROW TRANSPLANT
• HELLP syndrome • Successful pregnancies
• However, complicated by preterm delivery and
ACUTE FATTY LIVER OF PREGNANCY hypertension
• Associated with severe hemolytic anemia
POLYCYTHEMIA
BACTERIAL TOXINS • SECONDARY POLYCYTHEMIA
• Clostridium perfringens and group A beta-hemolytic o Excessive erythrocytosis during pregnancy
streptococcus à most fulminant o Related to chronic hypoxia from congenital
cardiac disease or chronic pulmonary
HEREDITARY SPHEROCYTOSIS disorder
• Most common identified in pregnancy • POLYCYTHEMIA VERA
• Autosomal dominant o Myeloproliferative hemopoietic stem cell
• Diagnosis is confirmed by identification of disorder characterized by excessive
spherocytes proliferation of erythroid, myeloid, and
• Crises – characterized by severe anemia, from megakaryotic precursors
accelerated hemolysis o Uncommon; likely acquired genetic disorder
• Develops in patients with large spleen of stem cell
• Parvovirus B19
HEMOGLOBINOPATHIES
F. APLASTIC & HYPOPLASTIC ANEMIA SICKLE CELL HEMOGLOBINOPATHIES
• Rare in pregnancy • HEMOGLOBIN A
• Pancytopenia and hypocellular bone marrow o Most common hemoglobin tetramer
• Multiple etiologies, some linked to autoimmune o Consists of two alpha and two beta chains
• SICKLE HEMOGLOBIN (HEMOGLOBIN S)
PREGNANCY o Originate from a single beta chain
• Diagnosis precedes conception or develops during substitution of glutamic acid by valine
pregnancy as a chance of occurrence o Stems from an A fro T substitution at codon
• DIAMOND BLACK FAN ANEMIA 6 of beta globin gene
o Rare form of pure red cell aplasia • Associated with increased maternal and perinatal
o 40 % familial morbidity and mortality
o Autosomal dominant
o Good response to glucocorticoid PATHOPHYSIOLOGY
o Complications: • Red cells with hemoglobin S undergo sickling when
§ Miscarriage deoxygenated and the hemoglobin aggravates
§ Preeclampsia • Constant sickling and unsickling cause membrane
§ Preterm birth damage
§ Still birth • Irreversibly sickled
§ FGR • Hallmarks:
• GAUCHER DISEASE o When there is ischemia and infarction in
o Autosomal recessive lysosomal enzyme various organs
deficiency • Pain – predominant symptom – sickle cell crises
o Deficient acid beta glucosidase activity o There may be aplastic, megaloblastic,
o Affects multiple system including bone sequestration and hemolytic crises
marrow
o Patients have anemia and
thrombocytopenia affecting pregnancy
PREGNANCY & SICKLE CELL SYNDROMES o Minimal to moderate hypochromic,
• Serious burden – especially hemoglobin SS microcytic anemia
• Increased risk for renal failure, gestational • Fetus
hypertension and fetal growth restriction o Hemoglobin Bart at birth
• MATERNAL MORBIDITY
o Ischemic necrosis of multiple organs, esp B. BETA THALASSEMIA
bone marrow – causing pain • Consequence of impaired b-globin chain production
o Pyelonephritis or alpha chain instability
o Pneumonia • Homozygous B-thalassemia
o Other pulmonary complications o Beta Thalassemia Major (Cooley anemia)
• ACUTE CHEST SYNDROME o Serious and fatal disorder
o Pulmonary infiltrates and respiratory
symptoms PREGNANCY
§ Infection • Folate and Iron supplements
§ Narrow emboli • Pregnancy is advisable if there is normal cardiac
§ Thromboembolism function
§ Atelectasis
PRENATAL DIAGNOSIS
MANAGEMENT DURING PREGNANCY • Targeted mutation analysis is done
• Requires close prenatal observation • Identify familial mutation
• These women maintain hemoglobin mass by intense • Non-invasive testing of circulating fetal nucleic acids
hemopoiesis to compensate for markedly shortened in maternal plasma
erythrocyte life span
• Prenatal folic acid 4mg daily- for support to rapid red PLATELET DISORDERS
cell turnover A. THROMBOCYTOPENIA
• IV fluids • Inherited
• Opioids for pain • Idiopathic, acute or chronic
• Prophylactic transfusions • <150,000/microliter
• FETAL ASSESSMENT
• LABOR & DELIVERY 1. GESTATIONAL THROMBOCYTOPENIA
o Identical to cardiac patients • Due to hemodilution
o Epidural anesthesia • Splenic mass characteristic of pregnancy is
o Blood contributory
o Cesarean delivery • Platelet life span – unchanged in pregnancy
§ Reserved fro OB complications
2. INHERITED THROMBOCYTOPENIA
CONTRACEPTION & STERILIZATION • BERNARD-SOULIER SYNDROME
• IUD o Lack of platelet membrane glycoprotein
• Progestin only (POP) methods (GPIb/IX)
o Causes severe dysfunction
THALASSEMIA SYNDROMES • Maternal antibodies against fetal GPIb/IX antigen
• Classified according to globin chain that is deficient can cause alloimmune fetal thrombocytopenia
• 2 major forms involve, impaired production or
instability of alpha peptide chains – causing alpha 3. IMMUNE THROMBOCYTOPENIC PURPURA (ITP)
thalassemia or of beta chains – causing beta • Primary form (ITP)
thalassemia o Formed by cluster of IgG antibodies
• May involve point mutations, deletions or directed against one or more platelet
translocations involving the alpha or non alpha glycoproteins
globin gene o Antibody coated platelets are destroyed
prematurely in the reticuloendothelial
A. ALPHA THALASSEMIA system (RES), esp. spleen
• Inheritance is more complicated than beta because • Secondary form
there are four alpha globin genes o Appear in association with systemic lupus
erythematosus (SLE), lymphomas,
PREGNANCY leukemias & several systemic diseases
• Depend on number of gene deletions
• Deletions of two genes
o Thalassemia Minor
DIAGNOSIS & MANAGEMENT
• No irrefutable evidence that pregnancy increases the
relapse in women with previous ITP or worsens
thrombocytopenia during pregnancy
• Considered if platelet is <30,000-50,000
• IVIG
• Prednisone 1mg/kg/day
• In pregnant: may do open or laparoscopic
splenectomy
o CS may be necessary for exposure
FETAL & NEONATAL EFFECTS
• Platelet associated IgG cross the placenta & may
cause fetal/neonatal thrombocytopenia
• Fetal death à from hemorrhage
• Intracranial hemorrhage with labor and delivery
B. THROMBOCYTOSIS
• Persistent platelet counts of >450,000
• Thrombocythemia
• Common causes of secondary or reactive
thrombocytosis
o IDA
o Infection
o Inflammatory diseases
o Malignant tumors
• Asymptomatic
o But arterial and venous thrombosis may
occur
INHERITED COAGULATION DEFECTS
A. HEMOPHILIA A & B
• Dependent on plasma factor levels
• Bleeding in pregnancy is related to factor VIII or
factor IX levels
B. VON WILLEBRAND DISEASES
• Most common inherited bleeding disorder
• Pregnancy outcome is generally good but
postpartum hemorrhage is encountered
