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 % - Developed51% - Developing countries65-75% - India80 % leading to maternal deaths

DEFINITIONReduction in circulating Hb mass < 12g/dl in non-pregnant women<10 g/dl in pregnant womenCDCAnaemia in iron supplemented preg. WomanHct 33% & Hb 11g/dl – 1st & 3rd trimesterHct 32% & Hb 10.5 g / dl - 2nd trimester

WHO grading of anemia

Mild 10g/dlModerate 7- 10 g/dlSevere < 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 pregnancyPlasma volume s 40-50%RBC mass s 30 %As a result Hb concentration decreases by 2g/dlDecreased Hb concn. Is due to haemodilution

Criteria of Physiological Anemia1) Hb 10 gm %2)RBC 3.2 million cells / cu mm3)PCV 32%4)Peripheral Smear – Normal morphology

Classification of Anaemia

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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. anemiaIron Deficiency Anemia – 3 stagesa)Depletion of Iron storesb)Iron deficient erythropoiesisc)Frank Iron deficiency Anemia

Symptoms of IRON DEFICIENCY ANEMIAFatigueWeaknessHeadacheLoss of appetiteDysphagiaPalpitationsDyspnea on exertionAnkle swellingParesthesiasLeukoplakia

Physical examinationPallor of varying degrees (Mucous membranes

, nail beds – Koilonychia or PlatynychiaGlossitisStomatitisHeart murmursIncreased JVPTachycardiaTachypneaPostural hypotension Crepitations- due to lung congestion

Depletion of Iron storesFerritin <20 ng/mlHb / Hct. NormalRBC INDICES normal

Iron deficient erythropoiesisFerritin <20 ng/mlTransferrin saturation<25%Hb –NormalSerum Iron < 60mg/dl

c)Frank Iron deficiency Anemiaferritin <20 ng/mlTransferrin saturation<25 %Serum iron <60 mg/dlHb <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 response1.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

3 .Epithelial changes (esp tongue & nail ) revert to normal

Hb concn. Is normal after 6 wks of therapy

PARENTERAL ADMINISTRATIONINDICATIONS1.Intolerance to oral iron2.Non compliance pt.3.Inflammatory bowel disease4.Pt. unable to absorb iron orally5.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 DefciencyPathophysiologyPreg. 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/ml2.Erythrocyte Folate levels - <20 ng/ml3.Peripheral smear – Hypersegmented

neutrophils,Oval macrocytes,Pancytopenia

TreatmentPregnancy induced megaloblastic anaemia- Folic acid, nutritious diet & Iron .Supplementation of 1mg of folic acid daily can

improve MA by 7 to 10 daysFolic acid should be given with ironAscorbic acid 100mg Tid enhances actionIn other conditionsRecommended folic acid dose – 5mg /day

orally dailyProphylaxisWHO – 400 micrograms folic acid daily to

prevent neural tube defects

Vit – B12 Deficiency

PathophysiologyVit B12 absorption is unaltered during pregnancyTissue uptake is increased Decreased serum

B12Recommended B12 intake – 3 microgram /day.

CAUSES of Vit B12 def.Strict Veg. dietUse of proton pump inhibitorsMetformin.GastritisGastrectomyIleal bypass Crohn’sH. Pylori infection

Gastric juice IF Antibody

Pathogenisis of

PERNICIOUS

ANEMIA

Clinical manifestations

Macrocytic Megaloblastic AnemiaGlossitisPeripheral neuropathySubacute combined degeneration of the

Spinal cord

DIAGNOSISSer.Vit B12 levels ,100 pg /mlRadio active Vit B12 absorption test .

( Schilling Test )

Treatment1000 microgram parenteral

cyanocobalamin every wk * 6 weeksPernicious Anaemia – Oral Vit B12Total Gastrectomy – 1000 microgram Vit

B12 im every month.Partial gastrectomy – Ser. Vit B12 levels

measured.

ANAEMIA ASSOC. WITH CHRONIC INFECTIONS / DISEASE

Common in developing countriesPoor response to Haematinics unless primary

cause is treatedWorm infestations is common ( Diagnosed by

stool examination )Urinary tract inf, & asymptomatic bacteriuria

in preg. Is assoc. with refractory anaemiaChronic renal disorders = due to

erythropoietin def.Treated with recombinant Erythropoitin

Anaemia from acute blood lossIn 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 anemiaAUTOIMMUNE HEMOLYTIC ANEMIAAUTOANTI-BODIES OF iGg OR WARM

ANTIBODIES AGAINST Red cell antigens, causes premature destruction of RBC”s

ETIOLOGYLymphomas,Leukemias , Connective tissue

diseases, Infections , Chronic. Inflammatory diseases & drug induced antibodies

DiagnosisDirect Coomb’s TestBlood smear – Spherocytosis &

Reticulocytosis

TREATMENT Prednisone 1mg / kg / day

orally Azathioprine Splenectomy

2)Preg. Induced hemolytic anemiaUnexplained hemolytic anemia uring pregnancy is rareSevere hemolysis occurs early in pregnancy & resolves

within months after deliveryNo evidence of immune mechanism or defects in RBCsPrednisone given untill delivery

3) Paroxysmal Nocturnal HemoglobinuriaAcquired hemolytic anemiaArises from one abnormal clone of cells like neoplasmAnemia 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 requiredBone marrow transplantation – Definitive

treatment

Effect on pregnancySerious & unpredictableMaternal mortality 10 – 20%Venous thrombosis occurs during post partum

APLASTIC ANAEMIARarely seen in preg.Marked decrease in marrow stem cels

ETIOLOGYInfectionsIrradiationLeukemiaImmunological disorders

May be Immunological mediated or autosomal recessive inheritance

30% cases Anaemia improves once pregnancy is terminated.

ComplicationsInfectionHaemorrhage

DiagnosisBlood Values – Anemia Leucopenia Thrombocytopenia

Bone Marrow - Hypocellular

ManagementSupportive care – Cont. Infection surveillance

& anti microbial therapyRed cell transfusions to maintain Hct. > 20Granulocyte transfusion given only during

InfectionsPlatelet transfusion to control haemorrhage.Glucocorticoid therapy may be helpful

IN SEVERE casesBone marrow or Stem Cell TransplantationVaginal delivery is preferred

Effect of anaemia in preg.

In MOTHERDuring 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

FetusAmount of iron transferred to fetus is

unaffected even if mother is in iron deficient state

PrematurityLow birth weight babiesIntra 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

DIAGNOSIS OF ANEMIA

DURING PREGNANCY

PLATELET DISORDERSThrombocytopenia - Gestational - Immune mediated Mild – 1,50,000 – 1,00,000 Moderate – 1,00,000 – 50,000 Severe - < 50,000Abnormalities of Platelet function

Causes of Thrombocytopenia during PregnancyCOMMON CAUSES1.Gestational Thrombocytopenia2.Severe Pre-eclampsia3.HELLP syndrome4.Immune thrombocytopenic Purpura5.Disseminated Intravascular coagulation

RARE CAUSES1.Lupus anticoagulant/APA syndrome2.SLE3.Hemolytic Uremic Syndrome4.Type 2b Von- Willebrand’s syndrome5.Folic acid def.6.HIV infections7.Hemotoligical malignancies8.May – Hegglin syndrome – Congenital

Thrombocytopenia

Gestational ThrombocytopeniaBenign Common disorderAppears in 8% of all preg.Unknown causeRarely drops < 70,000 /mm3

FEATURESDiagnosis of Exclusion – No specific test availableMild Thrombocytopenia , Count > 70,000 – 1 lakhNo maternal bleedingNo past history of thrombocytopeniaOccurs in 3rd trimester No assoc. fetal thrombocytopeniaSpont. Resolution after deliveryMay reccur in subsequent pregnancies

ManagementMajority cases treated as normalIn 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 takenSamples taken on day 1 & 4CS reseved for obstetric indications

Immune ThrombocytopeniaChronic condition , Incidence 1 in 1000 to 1

in 10000 pregnanciesCharecterised by autoantibody mediated

destruction of maternal platelets

MECHANISMAutoanti bodies react with platelet

Glycoprotein complex & antibody coated platelets are phagocytosed by Macrophages

SYMPTOMSUsually asymptomatic , sometimes

Bleeding , Petechiae

DIAGNOSISPlat count < 50,000 / cu mm with

past h/o bleeding disordersNo specific diagnostic test

Prepregnancy counselling for ITP ( RCOG 2009 )May relapse or worsenIf treatment reqd, it will carry for both

maternal & fetal risksIncreased risk of Hemorrhage at deliveryEpidural Anaesthesia is not possibleRisk prediction in neonate is not possible.

High risk if sibling has thrombocytopenia or mother has undergone splenectomy

Maternal deaths / serious outcome – RARERisk of Intracranial Haemorrhage in fetus

is very low.

ManagementAdequate Plat. Count should be maintainedCounts monitored throughout pregnancyIf > 30,000 – No treatmentIf< 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 deliveryPlatelet > 50,000 / cu mm – Vaginal or

operative deliveryPlatelet 50,000 Platelets standbyCS not routinely recommendeMeasures should be taken to avoid trauma

to baby headCord sample taken, If low confirmed by

capillary sampleIf count low, further day 1 & 4 is collectedInj im Vit K avoided till count is known

Fetal & Neonatal EffectsPA IgG antibodies crosss placenta causes

fetal & neonatal ThrombocytopeniaMaternal treatment do not have effect o fetal

countRole of Intracaranial hemorrhage < 1 %

MICROANGIOPATHIESThrombotic thrombocytopenic purpuraRare – life threateningSigns & symptoms ( PENTAD )1.Microangiopathic hemolytic anemia2.Thrombocytopenia3.Neurological symptoms4.Renal dysfunction5.Fever

ETIOLOGYSevere def. of VON WILLIBRAND FACTOR

( cleaving protein ( ADAM TS13)Acqd autoantibodyCongenital Genetic defect

Incidence 1 in 25000 pregnanciesTime of onset of TTP is variable 1st trimester to several wks post partumMaternal mortality is high

MANAGEMENTACQUIREDPlasma Exchange Fresh frozen Plasma infused daily until

Platelets turn to NormalRituximab, Monoclonal antibodies against

CD20

CONGENITALFFPPlatelet transfusion contraindicated

HEMOLYTIC UREMIC SYNDROMEMicroangiopathic hemolytic anaemia &

thrombocytopenia with predominant Renal involvement

Due to endothelial damage by bacterial or viral infections

In Preg. Response is poor for plasma exchange

THROMBOCYTOSISDefined as persistant Platelet count >4.5 lakhs /

cummCAUSES1 )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 & SYMPTOMSUsually asymptomaticArterial & venous ThrombosisHepatomegalyBone marrow – Hyperplastic with gross

increase in megakaryocytesBlood picture ->1 million Leucocytosis Anemia or mild

polycythemia Anisocytosis &

Poikilocytosis

In Pregnancy – Spont. Abortion , fetal demise & preeclampsia.

TREATMENTAspirin , Dipyramidole, Heparin,

Plateletpheresis

PROGNOSIS depends on underlying diseaseDeath due to either thrombosis /

hemorrhage / comp of Myeloproliferative disorders/ marrow failure.