Anaemia & Thrombocytopenia in Pregnancy

Giselle Kidson-Gerber Haematology Registrar Prince of Wales Hospital

Anaemia in pregnancy

Physiological changes in normal pregnancy

RBC dilution with rise in blood volume and plasma volume Definition of anaemia in pregnancy

T1, T2

T3

Hb < 110g/L Hb < 105g/L

Return to normal within 1 week postpartum, if normal iron stores

Potential consequences of moderate to severe anaemia

Maternal
Fatigue,

dyspnoea, syncope, chest pain Mortality (esp < 50g/L)

Foetal

(esp < 60g/L) Impaired mental development if low iron stores Low birth weight Preterm labour Perinatal death Low amniotic fluid volume Spontaneous miscarriage Placental Hypertrophy

Common causes of anaemia in pregnancy

Low MCV
Iron deficiency

Normal MCV
Iron deficiency

High MCV

Thalassaemia

Folate deficiency Chronic disease B12 deficiency Sickle cell Haemolysis Bleeding

Infection

Preconception
Assess nutrition status Full blood count Investigate if anaemia present Correct anaemia prior to conception Haemoglobinopathy screening

Investigations
FBC, with MCV, blood film Fe studies: ferritin esp. Folate (RCF stores) & B12 levels Reticulocyte count UEC, LFT, Coagulation studies Haemoglobinopathy screening

Iron deficiency anaemia

Most common cause in Western countries Increased iron requirements during pregnancy, especially multiple pregnancies
Replace: Ferrous sulfate 325mg tds (105mg elemental Fe)

Anaemia corrects in 4 - 6 weeks Stores replaced in 4 - 6 months

Dietary advice

Once replete

Ongoing supplement: 30 - 60mg elemental iron daily Monitor, including whilst breastfeeding

Iron therapies
Formulation
Ferrous sulfate Fefol FGF

Elemental Fe (mg) 105

87.4 80

Folic Acid (mcg) 300 300

Elevit
Blackmores Pregnancy

60
5

800
200

Folic Acid deficiency

2nd most common cause of anaemia in pregnancy Increased requirements for mother and foetus Red cell folate: measure more reflective of tissue stores over past months Supplement all: 200 - 500mcg/d (greater if haemolysis) Replacement: 1000mcg/d

Haemoglobinopathies: Practical significance

Major haemoglobinopathy in mother

Rare Specialist

obstetric & haematology care

Haemoglobinopathy traits in mother

Silent risk: foetus

Transfusion-dependent anaemia or sickle cell disease Barts disease/hydrops foetalis: maternal & foetal morbidity

Dependent on maternal and paternal genotype Importance of appropriate & timely screening

Difficulties with detection of haemoglobinopathy traits

Patient asymptomatic Patient unaware of carrier status Difficult to detect in laboratory:

May have normal Hb or MCV Haemoglobinopathy screening does not detect all cases Iron deficiency can mask indicator of thalassaemia trait

Haemoglobinopathies
Genotype Thalassaemia
Trait Intermedia Major (2 genes) +,, +, + , (4 genes) , , , , , (2 genes) s, s, s s, /+

Anaemia

MCV
N/

Spleen

Transfusion

1 abnormal gene 2 mildly abnormal genes 2 abnormal genes

None-mild Mild-moderate Severe

+/+ +

No Sometimes Dependent

Thalassaemia
Trait 2-gene minus HbH disease Barts disease

1 missing gene 2 missing genes 3 missing genes 4 missing genes

None None-mild

N N/

+/-

No No Sometimes

Mod - severe + Incompatible with life death in utero

Sickle Cell
Trait Disease thal compound

1 abnormal gene 2 abnormal genes 2 abnormal genes

None Mod-severe Variable

N N/

+/-/ +/-/

No Variable Variable

Screening

Why?
Who?

- Detect foetus at risk of major haemoglobinopathy

- At risk ethnic groups, ? all - Mother + partner

(Southern Europe, Middle East, Africa, Asia, Indian subcontinent)

When? What?

- Ideally preconception - Limited timeframe for Ix & intervention - FBC: Hb, MCV - HbEPG (includes HPLC, HbH bodies)

Full blood count

1.

Simple Limitations: MCV may not detect

2.

- thalassaemia trait - sickle trait Hb may not detect - thalassaemia trait - thalassaemia trait - sickle trait Iron deficiency must be excluded as cause of low MCV

HbEPG: Hb Electrophoresis

Separates different haemoglobins according to charge Alkaline & acid gels Known position of haemoglobin bands
HbA2,C,E HbS
HbA
HbF

HbS trait Control

Normal HbE trait HbE disease thalassaemia trait

HPLC: High Performance Liquid Chromatography

Separate according to elution time Quantify % of different haemoglobins present Iron deficiency lowers HbA2

Normal

HbS trait

HbA predominant haemoglobin: 88%

HbS band: 39% HbA: 50%

When to refer or ask for help

Positive result Unexplained anaemia Uncertain what investigations to perform Uncertain how to interpret investigations

Complex area! Variation in conditions and test results Specialist services are available: DNA testing is readily available & should be accessed when there is doubt

DNA testing

Confirm results or clarify unclear results Test mother & partner Foetus
If

have a known mutation in both parents Usually gives definitive genotype, although not 100% predictive of phenotype

Formal genetic counselling prior Must be organised EARLY in pregnancy - ideally preconception. Option of prenatal genetic diagnosis with IVF

Take home message

Evaluate anaemia PRIOR to pregnancy Determine cause of low MCV Replace iron, if deficient Low threshold for haemoglobinopathy screening and referral

Thrombocytopenia in pregnancy

Thrombocytopenia
Physiological thrombocytopenia in normal pregnancy Average decrease in platelet count of 10% Occurs mostly in 3rd trimester Due to haemodilution or accelerated destruction Normalises 24 -72 hours post-partum
Complicated Thrombocytopenia Up to 10% of pregnancies Mild - 100 - 150 x 109/L Moderate - 50 - 100 x 109/L Severe - < 50 x 109/L

Causes of Thrombocytopenia in Pregnancy

Pregnancy-specific
Increased destruction: Gestational

Non-pregnancy-specific
Increased destruction: Idiopathic thrombocytopenic purpura (ITP)

Preeclampsia HELLP Acute Fatty Liver of Pregnancy Disseminated intravascular coagulopathy

Microangiopathies: TTP, HUS, DIC SLE, Antiphospholipid syndrome Drug-induced Viral infections: HIV, HCV, EBV, CMV Hypersplenism Decreased production: Bone Marrow Disease Nutritional deficiency Liver disease Congenital thrombocytopenia

Causes of Thrombocytopenia in Pregnancy

Pregnancy-specific
Increased destruction: Gestational

Non-pregnancy-specific
Increased destruction: Idiopathic thrombocytopenic purpura (ITP)

Preeclampsia HELLP Acute Fatty Liver of Pregnancy Disseminated intravascular coagulopathy

Microangiopathies: TTP, HUS, DIC SLE, Antiphospholipid syndrome Drug-induced Viral infections: HIV, HCV, EBV, CMV Hypersplenism Decreased production: Bone Marrow Disease Nutritional deficiency Liver disease Congenital thrombocytopenia

Causes of Thrombocytopenia in Pregnancy

Pregnancy-specific
Increased destruction: Gestational

Non-pregnancy-specific
Increased destruction: Idiopathic thrombocytopenic purpura (ITP)

Preeclampsia HELLP Acute Fatty Liver of Pregnancy Disseminated intravascular coagulopathy

Microangiopathies: TTP, HUS, DIC SLE, Antiphospholipid syndrome Drug-induced Viral infections: HIV, HCV, EBV, CMV Hypersplenism Decreased production: Bone Marrow Disease Nutritional deficiency Liver disease Congenital thrombocytopenia

Causes of Thrombocytopenia in Pregnancy

Pregnancy-specific
Increased destruction: Gestational

Non-pregnancy-specific
Increased destruction: Idiopathic thrombocytopenic purpura (ITP)

Preeclampsia HELLP Acute Fatty Liver of Pregnancy Disseminated intravascular coagulopathy

Microangiopathies: TTP, HUS, DIC SLE, Antiphospholipid syndrome Drug-induced Viral infections: HIV, HCV, EBV, CMV Hypersplenism Decreased production: Bone Marrow Disease Nutritional deficiency Liver disease Congenital thrombocytopenia

Clinical approach
Symptoms, bleeding history Prenatal platelet count Gestation Previous pregnancies Associated features Co-morbidities

Gestational Thrombocytopenia
Occurs in 5-8% of all pregnancies 75% of all pregnancy-associated thrombocytopenia ? Mechanism: haemodilution, accelerated plt turnover, trapping or

destruction at placenta

Maternal haemorrhage risk: not increased Foetal thrombocytopenia risk: not increased

Gestational Thrombocytopenia

Clinically

- asymptomatic - normal pre-natal platelet count - occurs in late T2 & in T3 - normalises post-partum

Mild thrombocytopenia:
Platelet

count > 70 x109/L (usually > 100)

Anti-platelet antibodies do not reliably distinguish from ITP Diagnosis of exclusion

Idiopathic Thrombocytopenic Purpura (ITP)

5% of pregnancy-associated thrombocytopenia, 0.1% of pregnancies Concern: maternal and foetal haemorrhage Clinically - any trimester - prenatal thrombocytopenia - bleeding history Especially likely to be ITP if
Platelet T1 History

count <50 x109/L of auto-immune disease

Idiopathic Thrombocytopenic Purpura (ITP)

Maternal haemorrhage risk increased, relates to platelet count

Platelet count < 20: risk of spontaneous bleeding Platelet count > 50: aim for NVD Platelet count > 70: for epidural (variable, anaesthetist preference)

Foetal thrombocytopenia due to trans-placental passage of maternal IgG:

10-20% platelet count < 50 x109/L 5% platelet count < 20 x109/L: 25-50% develop bleeding Best predictor: sibling Check cord platelet count at delivery, nadir day 2-3.

Therapeutic options: monitor only, IVIg, prednisone, (splenectomy)

Summary of approach to thrombocytopenia in pregnancy

Exclude pre-eclampsia syndromes

BP,

UA, symptoms, FBC, UEC, LFT, Uric Acid

Exclude non-pregnancy-related medical causes, usually have specialist involved already When to refer: Known history of ITP Unknown cause & platelet count is
x 109/L in T1 & T2 <100 x 109/L in T3
<130

Otherwise monitor FBC monthly

Thank-you