HAEMOTOLOGICAL DISORDERS IN PREGNANCY

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HAEMOTOLOGICAL DISORDERS IN PREGNANCY

• Dr. RAMYA
• MODERATOR Dr.PALLAVEE

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HAEMOTOLOGICAL DISORDERS IN PREGNANCY ANAEMIA PL
ATELET DISORDERS HAEMOGLOBINOPATHIES INHERITED
COAGULATION DEFECTS
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ANAEMIA Commonest haematological disorder occur
in preg. Prevalance in pregnant women 14 -
Developed 51 - Developing
countries 65-75 - India 80 leading to maternal
deaths
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DEFINITION Reduction in circulating Hb mass
lt 12g/dl in non-pregnant women lt10 g/dl in
pregnant women CDC Anaemia in iron supplemented
preg. Woman Hct 33 Hb 11g/dl 1st 3rd
trimester Hct 32 Hb 10.5 g / dl - 2nd trimester
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• WHO grading of anemia
• Mild 10g/dl
• Moderate 7- 10 g/dl
• Severe lt 7 g/dl

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ICMR GRADING
Range in g/dl
MILD 10 10.9
MODERATE 7 9.9
SEVERE lt 7
VERY SEVERE lt 4
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Hemotological Changes in preg.
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Physiological Anemia of pregnancy

• Plasma volume s 40-50
• RBC mass s 30
• As a result Hb concentration decreases by 2g/dl
• Decreased Hb concn. Is due to haemodilution
• Criteria of Physiological Anemia
• 1) Hb 10 gm
• 2)RBC 3.2 million cells / cu mm
• 3)PCV 32
• 4)Peripheral Smear Normal morphology

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Classification of Anaemia
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Classification .
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Classification .
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Classification .
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Classification .
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ERYTHROPOISES
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IRON METABOLISM
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• IRON Requirements during Pregnancy
• Maternal req. Of total Iron -1000mg
• 500 mg ? Mat. Hb. Mass expansion
• 300 mg ? Fetus Placenta
• 200mg ? Shed through gut urine, skin

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DEVELOPMENT OF Iron def. anemia

• Iron Deficiency Anemia 3 stages
• a)Depletion of Iron stores
• b)Iron deficient erythropoiesis
• c)Frank Iron deficiency Anemia

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• Symptoms of IRON DEFICIENCY ANEMIA
• Fatigue
• Weakness
• Headache
• Loss of appetite
• Dysphagia
• Palpitations
• Dyspnea on exertion
• Ankle swelling
• Paresthesias
• Leukoplakia

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• Physical examination
• Pallor of varying degrees (Mucous membranes ,
  nail beds Koilonychia or Platynychia
• Glossitis
• Stomatitis
• Heart murmurs
• Increased JVP
• Tachycardia
• Tachypnea
• Postural hypotension
• Crepitations- due to lung congestion

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• Depletion of Iron stores
• Ferritin lt20 ng/ml
• Hb / Hct. Normal
• RBC INDICES normal
• Iron deficient erythropoiesis
• Ferritin lt20 ng/ml
• Transferrin saturationlt25
• Hb Normal
• Serum Iron lt 60mg/dl

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• c)Frank Iron deficiency Anemia
• ferritin lt20 ng/ml
• Transferrin saturationlt25
• Serum iron lt60 mg/dl
• Hb lt10g/dl, Hct.lt28

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Microcytic Hypochromic
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PROPHYLAXIX

• WHO - 60 mg Elemental iron 400 micro gram
  Folic acid / day 6 months 3 months postpartum
• National Nutritional Anemia Control Programme of
  India
• - 60 mg elemental Iron 500 mcg Folic acid
  Prophylactic supplementation 100 days in 2nd
  trimester

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Iron Supplements
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• Ferrous sulphate 300mg Tid orally daily after
  meals
• To be contd for 12 months after anemia is
  corrected
• Indicators of iron therapy response
• Increase in Reticulocyte count (Increases 3-5
  days after initiation of therapy )
• Increase in Hb levels. Hb increases 0.3 to 1 g/
  week
• 3 .Epithelial changes (esp tongue nail ) revert
  to normal
• Hb concn. Is normal after 6 wks of therapy
  

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PARENTERAL ADMINISTRATION

• INDICATIONS
• Intolerance to oral iron
• Non compliance pt.
• Inflammatory bowel disease
• Pt. unable to absorb iron orally
• Patients near term

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• TDI Total Dose Infusion
• Amount of iron needed to restore Hb conc
  to normal additional allowance to provide
  adequate replenishment of iron stores
• Formulae
• 1 Total Dose ( mg )
• ( normal Hb Pts Hb
  ) (body wt. in
• 
  kg ) 2.21
• 2 Total Iron Dose (mg )
• 2.3 wt. kg before
  preg D (Target Hb) 500 mg for
  body store

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MEGALOBLASTIC ANAEMIA

• Incidence 0.2 5
• Caused by folic acid deficiency Vit B12
  deficiency

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• Folic Acid Defciency
• Pathophysiology
• Preg. Causes 20 -30 fold increase in Folate
  requirement (150-450 microgram / day ) to meet
  needs of fetus placenta.
• Placenta transports folate actively to fetus even
  if the mother is deficient.
• This cause decreased plasma folate levels.

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• Causes of Folic acid deficiency
• 1.Diet- Poor intake, prolonged cooking.
• 2. Malabsorption Coeliac disease.
• 3.Increased demand Pregnancy, cell
  proliferation (hemolysis )
• 4.Drugs anticonvulsants, contraceptive pill,
  cytotoxic drugs (Methotrexate )
• 5.Diminished storage Hepatic disorders Vit C
  deficiency

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• Diagnostic features of Folic acid deficiency
• 1.Serum Folate levels Low lt3 ng/ml
• 2.Erythrocyte Folate levels - lt20 ng/ml
• 3.Peripheral smear Hypersegmented
  neutrophils,Oval macrocytes,Pancytopenia

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• Treatment
• Pregnancy induced megaloblastic anaemia-
• Folic acid, nutritious diet
  Iron .
• Supplementation of 1mg of folic acid daily can
  improve MA by 7 to 10 days
• Folic acid should be given with iron
• Ascorbic acid 100mg Tid ?enhances action
• In other conditions
• Recommended folic acid dose 5mg /day orally
  daily
• Prophylaxis
• WHO 400 micrograms folic acid daily to prevent
  neural tube defects

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Vit B12 Deficiency
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Pathophysiology

• Vit B12 absorption is unaltered during pregnancy
• Tissue uptake is increased ? Decreased serum
  B12
• Recommended B12 intake 3 microgram /day.
• CAUSES of Vit B12 def.
• Strict Veg. diet
• Use of proton pump inhibitors
• Metformin.
• Gastritis
• Gastrectomy
• Ileal bypass
• Crohns
• H. Pylori infection

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Pathogenisis of PERNICIOUS ANEMIA ?
Gastric juice IF Antibody
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Clinical manifestations

• Macrocytic Megaloblastic Anemia
• Glossitis
• Peripheral neuropathy
• Subacute combined degeneration of the Spinal cord

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• DIAGNOSIS
• Ser.Vit B12 levels ,100 pg /ml
• Radio active Vit B12 absorption test . (
  Schilling Test )
• Treatment
• 1000 microgram parenteral cyanocobalamin every wk
  6 weeks
• Pernicious Anaemia Oral Vit B12
• Total Gastrectomy 1000 microgram Vit B12 im
  every month.
• Partial gastrectomy Ser. Vit B12 levels
  measured.

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ANAEMIA ASSOC. WITH CHRONIC INFECTIONS / DISEASE

• Common in developing countries
• Poor response to Haematinics unless primary cause
  is treated
• Worm infestations is common ( Diagnosed by stool
  examination )
• Urinary tract inf, asymptomatic bacteriuria in
  preg. Is assoc. with refractory anaemia
• Chronic renal disorders due to erythropoietin
  def.
• Treated with recombinant Erythropoitin

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Anaemia from acute blood loss

• In preg. Abortion , ectopic preg, hydatidform
  mole, PPH
• Treatment.
• Blood transfusion
• Indicated patient symptomatic
• Not indicated If hemodynamically stable, Hb lt 7
  g/dl, able to ambulate without adverse symptoms
  not septic.

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Acquired hemolytic anemia

• AUTOIMMUNE HEMOLYTIC ANEMIA
• AUTOANTI-BODIES OF iGg OR WARM ANTIBODIES AGAINST
  Red cell antigens, causes premature destruction
  of RBCs
• ETIOLOGY
• Lymphomas,Leukemias , Connective tissue diseases,
  Infections , Chronic. Inflammatory diseases
  drug induced antibodies

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• Diagnosis
• Direct Coombs Test
• Blood smear Spherocytosis Reticulocytosis
• TREATMENT
• Prednisone 1mg / kg / day
  orally
• Azathioprine
• Splenectomy

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2)Preg. Induced hemolytic anemia

• Unexplained hemolytic anemia uring pregnancy is
  rare
• Severe hemolysis occurs early in pregnancy
  resolves within months after delivery
• No evidence of immune mechanism or defects in
  RBCs
• Prednisone given untill delivery
• 3) Paroxysmal Nocturnal Hemoglobinuria
• Acquired hemolytic anemia
• Arises from one abnormal clone of cells like
  neoplasm
• Anemia is insiduous in onset hemoglobinuria
  develoes at irregular intervals

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• Hemolysis may be initiated by transfusion ,
  infections or surgery
• 40 suffer venous thrombosis, renal failure , HTN
  Budd Chiari syndrome.
• Prophylactic anticoagulation is required
• Bone marrow transplantation Definitive
  treatment
• Effect on pregnancy
• Serious unpredictable
• Maternal mortality 10 20
• Venous thrombosis occurs during post partum

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APLASTIC ANAEMIA

• Rarely seen in preg.
• Marked decrease in marrow stem cels
• ETIOLOGY
• Infections
• Irradiation
• Leukemia
• Immunological disorders

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• May be Immunological mediated or autosomal
  recessive inheritance
• 30 cases Anaemia improves once pregnancy is
  terminated.
• Complications
• Infection
• Haemorrhage

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Diagnosis

• Blood Values
• Anemia
• Leucopenia
• Thrombocytopenia
• Bone Marrow - Hypocellular

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Management

• Supportive care Cont. Infection surveillance
  anti microbial therapy
• Red cell transfusions to maintain Hct. gt 20
• Granulocyte transfusion given only during
  Infections
• Platelet transfusion to control haemorrhage.
• Glucocorticoid therapy may be helpful
• IN SEVERE cases
• Bone marrow or Stem Cell Transplantation
• Vaginal delivery is preferred

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• Effect of anaemia in preg.
• In MOTHER
• During preg.
• Pre eclampsia
• Infectuion
• Heart failure
• Pretem labour
• Labour
• Uterine inertia
• Postpartum Haemorrhage
• Cardiac failure
• Shock
• Puerperium
• Puerperal sepsis
• Subinovulation
• Failure of lactation
• Puerperal venous thrombosis

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• Fetus
• Amount of iron transferred to fetus is unaffected
  even if mother is in iron deficient state
• Prematurity
• Low birth weight babies
• Intra uterine deaths due to severe maternal
  anoxemia

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• Effect of pregnancy in anaemia
• Pt. Mildly anemic progresses to marked Anaemia
• Pt. Who is severely anemic becomes symptomatic by
  the end of 2nd trimester

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DIAGNOSIS OF ANEMIA DURING PREGNANCY
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PLATELET DISORDERS

• Thrombocytopenia - Gestational
• - Immune
  mediated
• Mild 1,50,000 1,00,000
• Moderate 1,00,000 50,000
• Severe - lt 50,000
• Abnormalities of Platelet function

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Causes of Thrombocytopenia during Pregnancy

• COMMON CAUSES
• Gestational Thrombocytopenia
• Severe Pre-eclampsia
• HELLP syndrome
• Immune thrombocytopenic Purpura
• Disseminated Intravascular coagulation
• RARE CAUSES
• Lupus anticoagulant/APA syndrome
• SLE
• Hemolytic Uremic Syndrome
• Type 2b Von- Willebrands syndrome
• Folic acid def.
• HIV infections
• Hemotoligical malignancies
• May Hegglin syndrome Congenital
  Thrombocytopenia

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Gestational Thrombocytopenia

• Benign Common disorder
• Appears in 8 of all preg.
• Unknown cause
• Rarely drops lt 70,000 /mm3
• FEATURES
• Diagnosis of Exclusion No specific test
  available
• Mild Thrombocytopenia , Count gt 70,000 1 lakh
• No maternal bleeding
• No past history of thrombocytopenia
• Occurs in 3rd trimester
• No assoc. fetal thrombocytopenia
• Spont. Resolution after delivery
• May reccur in subsequent pregnancies

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Management

• Majority cases treated as normal
• In mod. To severe cases Reluctance of
  Anaesthesiologists to give spinal or epidural if
  Platelets lt 80,000 /cu mm
• Treatment with steroids IgG or platelet
  transfusion before delivery
• Cord sample should be taken
• Samples taken on day 1 4
• CS reseved for obstetric indications

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Immune Thrombocytopenia

• Chronic condition , Incidence 1 in 1000 to 1 in
  10000 pregnancies
• Charecterised by autoantibody mediated
  destruction of maternal platelets
• MECHANISM
• Autoanti bodies react with platelet Glycoprotein
  complex antibody coated platelets are
  phagocytosed by Macrophages

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• SYMPTOMS
• Usually asymptomatic , sometimes Bleeding ,
  Petechiae
• DIAGNOSIS
• Plat count lt 50,000 / cu mm with past h/o
  bleeding disorders
• No specific diagnostic test

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Prepregnancy counselling for ITP ( RCOG 2009 )

• May relapse or worsen
• If treatment reqd, it will carry for both
  maternal fetal risks
• Increased risk of Hemorrhage at delivery
• Epidural Anaesthesia is not possible
• Risk prediction in neonate is not possible. High
  risk if sibling has thrombocytopenia or mother
  has undergone splenectomy
• Maternal deaths / serious outcome RARE
• Risk of Intracranial Haemorrhage in fetus is very
  low.

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Management

• Adequate Plat. Count should be maintained
• Counts monitored throughout pregnancy
• If gt 30,000 No treatment
• Iflt 30,000 - 1 ) Prednisolone 1 -2 mg / kg oral
  daily,
• 2) IV IG 2g/kg over 2
  to 5 days , If no response then
• 3) Splenectomy
• 4) Immunosuppressive
  drugs like
• a)
  azathioprine
• b)
  Cyclophosphamide , Cyclosporine

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Management Of delivery

• Platelet gt 50,000 / cu mm Vaginal or operative
  delivery
• Platelet 50,000 ? Platelets standby
• CS not routinely recommende
• Measures should be taken to avoid trauma to baby
  head
• Cord sample taken, If low ? confirmed by
  capillary sample
• If count low, further day 1 4 is collected
• Inj im Vit K avoided till count is known

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Fetal Neonatal Effects

• PA IgG antibodies crosss placenta ? causes fetal
  neonatal Thrombocytopenia
• Maternal treatment do not have effect o fetal
  count
• Role of Intracaranial hemorrhage lt 1

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MICROANGIOPATHIES

• Thrombotic thrombocytopenic purpura
• Rare life threatening
• Signs symptoms ( PENTAD )
• Microangiopathic hemolytic anemia
• Thrombocytopenia
• Neurological symptoms
• Renal dysfunction
• Fever

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• ETIOLOGY
• Severe def. of VON WILLIBRAND FACTOR ( cleaving
  protein ( ADAM TS13)
• Acqd ? autoantibody
• Congenital ? Genetic defect
• Incidence
• 1 in 25000 pregnancies
• Time of onset of TTP is variable
• 1st trimester to several wks post partum
• Maternal mortality is high

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MANAGEMENT

• ACQUIRED
• Plasma Exchange
• Fresh frozen Plasma infused daily until Platelets
  turn to Normal
• Rituximab, Monoclonal antibodies against CD20
• CONGENITAL
• FFP
• Platelet transfusion contraindicated

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HEMOLYTIC UREMIC SYNDROME

• Microangiopathic hemolytic anaemia
  thrombocytopenia with predominant Renal
  involvement
• Due to endothelial damage by bacterial or viral
  infections
• In Preg. Response is poor for plasma exchange

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THROMBOCYTOSIS

• Defined as persistant Platelet count gt4.5 lakhs /
  cumm
• CAUSES
• 1 )Secondary or Reactive ( gt 80000)
• a)Iron def.
• b) Infections
• c) Splenectomy
• d) Surgery Trauma ( bone fractures )
• e) Malignancy
• 2) Essential Thrombocytosis gt I million
• a) Idiopathic
• b) Myelodysplastic syndromes

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• SIGNS SYMPTOMS
• Usually asymptomatic
• Arterial venous Thrombosis
• Hepatomegaly
• Bone marrow Hyperplastic with gross increase in
  megakaryocytes
• Blood picture -gt1 million
• Leucocytosis
• Anemia or mild
  polycythemia
• Anisocytosis
  Poikilocytosis

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• In Pregnancy Spont. Abortion , fetal demise
  preeclampsia.
• TREATMENT
• Aspirin , Dipyramidole, Heparin, Plateletpheresis
• PROGNOSIS depends on underlying disease
• Death due to either thrombosis / hemorrhage /
  comp of Myeloproliferative disorders/ marrow
  failure.