haemotological disorders in pregnancy
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Transcript haemotological disorders in pregnancy
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.