haemotological disorders in pregnancy

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Dr. RAMYA
MODERATOR : Dr.PALLAVEE
HAEMOTOLOGICAL DISORDERS IN
PREGNANCY
ANAEMIA
PLATELET DISORDERS
HAEMOGLOBINOPATHIES
INHERITED COAGULATION DEFECTS
ANAEMIA
Commonest haematological disorder occur
in preg.
Prevalance in pregnant women –
14 % - Developed
51% Developing countries
65-75% - India
80 % leading to maternal deaths
DEFINITION
Reduction in circulating Hb mass
< 12g/dl in non-pregnant women
<10 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
WHO grading of anemia
Mild
10g/dl
Moderate 7- 10 g/dl
Severe
< 7 g/dl
ICMR GRADING
Range in g/dl
MILD
10 – 10.9
MODERATE
7 – 9.9
SEVERE
<7
VERY SEVERE
<4
Hemotological Changes in preg.
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
Classification of Anaemia
Classification …….
Classification …….
Classification …….
Classification …….
ERYTHROPOISES
IRON METABOLISM
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
DEVELOPMENT OF Iron def. anemia
Iron Deficiency Anemia – 3 stages
 a)Depletion of Iron stores
 b)Iron deficient erythropoiesis
 c)Frank Iron deficiency Anemia
Symptoms of IRON DEFICIENCY ANEMIA
 Fatigue
 Weakness
 Headache
 Loss of appetite
 Dysphagia
 Palpitations
 Dyspnea on exertion
 Ankle swelling
 Paresthesias
 Leukoplakia
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
Depletion of Iron stores
 Ferritin <20 ng/ml
 Hb / Hct. Normal
 RBC INDICES normal
Iron deficient erythropoiesis
 Ferritin <20 ng/ml
 Transferrin saturation<25%
 Hb –Normal
 Serum Iron < 60mg/dl
c)Frank Iron deficiency Anemia
 ferritin <20 ng/ml
 Transferrin saturation<25 %
 Serum iron <60 mg/dl
 Hb <10g/dl, Hct.<28%
Microcytic Hypochromic
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
Iron Supplements
 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 )
2. Increase in Hb levels. Hb increases 0.3 to 1 g/ week
1.
3 .Epithelial changes (esp tongue & nail ) revert to normal
 Hb concn. Is normal after 6 wks of therapy
PARENTERAL ADMINISTRATION
 INDICATIONS
1.
2.
3.
4.
5.
Intolerance to oral iron
Non compliance pt.
Inflammatory bowel disease
Pt. unable to absorb iron orally
Patients near term
 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
MEGALOBLASTIC ANAEMIA
Incidence – 0.2 – 5 %
Caused by folic acid deficiency &
Vit B12 deficiency
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.
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
Diagnostic features of Folic acid deficiency
 1.Serum Folate levels – Low <3 ng/ml
 2.Erythrocyte Folate levels - <20 ng/ml
 3.Peripheral smear – Hypersegmented
neutrophils,Oval macrocytes,Pancytopenia
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
Vit – B12 Deficiency
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
Crohn’s
H. Pylori infection
GASTRIC
ATROPHY ?
autoimmune
Pathogenisis
of
PERNICIOUS
ANEMIA 
Reduced IF
secretion
Gastric juice IF
Antibody
Failure of
absorption of
dietary Vit B12
Deficiency of
Vit B12
Clinical manifestations
 Macrocytic Megaloblastic Anemia
 Glossitis
 Peripheral neuropathy
 Subacute combined degeneration of the Spinal cord
 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.
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
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 < 7 g/dl,
able to ambulate without adverse symptoms & not
septic.
Acquired hemolytic anemia
 AUTOIMMUNE HEMOLYTIC ANEMIA
 AUTOANTI-BODIES OF iGg OR WARM
ANTIBODIES AGAINST Red cell antigens, causes
premature destruction of RBC”s
 ETIOLOGY
 Lymphomas,Leukemias , Connective tissue diseases,
Infections , Chronic. Inflammatory diseases & drug
induced antibodies
Diagnosis
 Direct Coomb’s Test
 Blood smear – Spherocytosis & Reticulocytosis
TREATMENT



Prednisone 1mg / kg / day orally
Azathioprine
Splenectomy
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
 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
APLASTIC ANAEMIA
 Rarely seen in preg.
 Marked decrease in marrow stem cels
ETIOLOGY
 Infections
 Irradiation
 Leukemia
 Immunological disorders
 May be Immunological mediated or
autosomal recessive inheritance
 30% cases Anaemia improves once pregnancy
is terminated.
Complications
 Infection
 Haemorrhage
Diagnosis
 Blood Values –



Anemia
Leucopenia
Thrombocytopenia
 Bone Marrow - Hypocellular
Management
 Supportive care – Cont. Infection surveillance & anti




microbial therapy
Red cell transfusions to maintain Hct. > 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
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
Pulmonary embolism
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
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
Pt. with
Anemia
Hb<11, Hct
DIAGNOSIS OF
ANEMIA
DURING
PREGNANCY
<0.33
InvestigationsMCV, PS ,Retic
count
MCV <80 Low
MCV 80 – 90
MCV >99
PS –Microcytic
PS – Normal
PS-Macrocytic
Serum
Iron
studies
Serum Iron reduced
TIBC-Increased Ser.
Ferritin – reduced
IRON DEF ANEMIA
TREATMRNT WITH
ORAL /
PARENTERAL IRON
RETIC
COUNT
INCREASED
-Hemolytic
-Hemoglobin
opathies
-Autoimmune
Cases
- Drug induced
RETIC –
NORMAL /
DECREASED
Drugs
Bone marrow
path.
Chronic
diseases
Ser.B12 &
Folic acid levels
Folate < 3ng/ml
Vit B12 <80pg/ml
Therapy with
1 mg/day – Folate
1000ug im B12 every wk *
6 wks foll by every month
PLATELET DISORDERS
 Thrombocytopenia - Gestational
- Immune mediated
Mild – 1,50,000 – 1,00,000
Moderate – 1,00,000 – 50,000
Severe - < 50,000
 Abnormalities of Platelet function
Causes of Thrombocytopenia during Pregnancy
 COMMON CAUSES
1. Gestational Thrombocytopenia
2. Severe Pre-eclampsia
3. HELLP syndrome
4. Immune thrombocytopenic Purpura
5. Disseminated Intravascular coagulation

1.
2.
3.
4.
5.
6.
7.
8.
RARE CAUSES
Lupus anticoagulant/APA syndrome
SLE
Hemolytic Uremic Syndrome
Type 2b Von- Willebrand’s syndrome
Folic acid def.
HIV infections
Hemotoligical malignancies
May – Hegglin syndrome – Congenital Thrombocytopenia
Gestational Thrombocytopenia




Benign Common disorder
Appears in 8% of all preg.
Unknown cause
Rarely drops < 70,000 /mm3
FEATURES
 Diagnosis of Exclusion – No specific test available
 Mild Thrombocytopenia , Count > 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
Management
 Majority cases treated as normal
 In mod. To severe cases – Reluctance of
Anaesthesiologists to give spinal or epidural if Platelets
= < 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
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
 SYMPTOMS
 Usually asymptomatic , sometimes Bleeding
, Petechiae
 DIAGNOSIS
 Plat count < 50,000 / cu mm with past h/o
bleeding disorders
 No specific diagnostic test
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.
Management
 Adequate Plat. Count should be maintained
 Counts monitored throughout pregnancy
 If > 30,000 – No treatment
 If< 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
Management Of delivery
 Platelet > 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
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 < 1 %
MICROANGIOPATHIES
Thrombotic thrombocytopenic purpura
 Rare – life threatening
 Signs & symptoms ( PENTAD )
1. Microangiopathic hemolytic anemia
2. Thrombocytopenia
3. Neurological symptoms
4. Renal dysfunction
5. Fever
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
MANAGEMENT
 ACQUIRED
 Plasma Exchange
 Fresh frozen Plasma infused daily until Platelets turn
to Normal
 Rituximab, Monoclonal antibodies against CD20
 CONGENITAL
 FFP
 Platelet transfusion contraindicated
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
THROMBOCYTOSIS
 Defined as persistant Platelet count >4.5 lakhs / cumm
 CAUSES
 1 )Secondary or Reactive ( > 80000)
a)Iron def.
b) Infections
c) Splenectomy
d) Surgery & Trauma ( bone fractures )
e) Malignancy
 2) Essential Thrombocytosis > I million
a) Idiopathic
b) Myelodysplastic syndromes
SIGNS & SYMPTOMS
 Usually asymptomatic
 Arterial & venous Thrombosis
 Hepatomegaly
 Bone marrow – Hyperplastic with gross increase in
megakaryocytes
 Blood picture ->1 million
Leucocytosis
Anemia or mild polycythemia
Anisocytosis & Poikilocytosis
 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.
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