1. HAEMOTOLOGICAL DISORDERS IN PREGNANCY
Dr. RAMYA
MODERATOR : Dr.PALLAVEE

2. HAEMOTOLOGICAL DISORDERS IN PREGNANCY
ANAEMIA
PLATELET DISORDERS
HAEMOGLOBINOPATHIES
INHERITED COAGULATION DEFECTS

3. ANAEMIA Commonest haematological disorder occur in preg.
Prevalance in pregnant women –
14 % Developed
51% Developing countries
65-75% - India
80 % leading to maternal deaths

4. 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

5. WHO grading of anemia
Mild g/dl
Moderate g/dl
Severe < 7 g/dl

6. ICMR GRADING MILD 10 – 10.9 MODERATE 7 – 9.9 SEVERE < 7 VERY SEVERE
Range in g/dl
MILD
10 – 10.9
MODERATE
7 – 9.9
SEVERE
< 7
VERY SEVERE
< 4

7. Hemotological Changes in preg.

8. 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

9. Classification of Anaemia

10. Classification …….

11. Classification …….

12. Classification …….

13. Classification …….

14. ERYTHROPOISES

15. IRON METABOLISM

16. 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

17. DEVELOPMENT OF Iron def. anemia
Iron Deficiency Anemia – 3 stages
a)Depletion of Iron stores
b)Iron deficient erythropoiesis
c)Frank Iron deficiency Anemia

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

19. 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

20. Depletion of Iron stores
Ferritin <20 ng/ml
Hb / Hct. Normal
RBC INDICES normal
Iron deficient erythropoiesis
Transferrin saturation<25%
Hb –Normal
Serum Iron < 60mg/dl

21. c)Frank Iron deficiency Anemia
ferritin <20 ng/ml
Transferrin saturation<25 %
Serum iron <60 mg/dl
Hb <10g/dl, Hct.<28%

22. Microcytic Hypochromic

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

24. Iron Supplements

25. 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

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

27. Formulae 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) mg for body store

28. MEGALOBLASTIC ANAEMIA
Incidence – 0.2 – 5 %
Caused by folic acid deficiency & Vit B12 deficiency

32. Folic Acid Defciency
Pathophysiology
Preg. Causes fold increase in Folate requirement ( 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.

33. 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

34. 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

35. Treatment In other conditions Prophylaxis
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

36. Vit – B12 Deficiency

37. Pathophysiology CAUSES of Vit B12 def.
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

38. Pathogenisis of PERNICIOUS ANEMIA 
GASTRIC ATROPHY ? autoimmune
Reduced IF secretion
Failure of absorption of dietary Vit B12
Deficiency of Vit B12
Pathogenisis of PERNICIOUS ANEMIA 
Gastric juice IF Antibody

39. Clinical manifestations
Macrocytic Megaloblastic Anemia
Glossitis
Peripheral neuropathy
Subacute combined degeneration of the Spinal cord

40. Treatment 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.

41. 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

42. 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.

43. 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

44. Diagnosis
Direct Coomb’s Test
Blood smear – Spherocytosis & Reticulocytosis
TREATMENT
Prednisone 1mg / kg / day orally
Azathioprine
Splenectomy

45. 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

46. 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

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

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

49. Diagnosis Blood Values – Anemia Leucopenia Thrombocytopenia
Bone Marrow - Hypocellular

50. 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

51. 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

52. 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

53. 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

54. DIAGNOSIS OF ANEMIA DURING PREGNANCY
Pt. with Anemia Hb<11, Hct <0.33
Investigations- MCV, PS ,Retic count
MCV <80 Low
PS –Microcytic
Serum Iron studies
Serum Iron reduced TIBC-Increased Ser. Ferritin – reduced
IRON DEF ANEMIA TREATMRNT WITH ORAL / PARENTERAL IRON
MCV 80 – 90
PS – Normal
RETIC COUNT INCREASED
-Hemolytic Hemoglobin opathies Autoimmune Cases Drug induced
RETIC – NORMAL / DECREASED
Drugs Bone marrow path Chronic diseases
MCV >99
PS-Macrocytic
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
DIAGNOSIS OF ANEMIA DURING PREGNANCY

55. 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

56. 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- Willebrand’s syndrome
Folic acid def.
HIV infections
Hemotoligical malignancies
May – Hegglin syndrome – Congenital Thrombocytopenia

57. 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

58. 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

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

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

61. 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.

62. Management Adequate Plat. Count should be maintained
Counts monitored throughout pregnancy
If > 30,000 – No treatment
If< 30, ) 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

63. 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

64. 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 %

65. MICROANGIOPATHIES Thrombotic thrombocytopenic purpura
Rare – life threatening
Signs & symptoms ( PENTAD )
Microangiopathic hemolytic anemia
Thrombocytopenia
Neurological symptoms
Renal dysfunction
Fever

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

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

68. 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

69. 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

70. 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

71. 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.