This document summarizes key haematological changes during pregnancy. Physiological changes include anaemia due to plasma volume expansion, increased white blood cell counts dominated by neutrophils, and lower platelet counts. Common causes of anaemia are iron deficiency and folate deficiency. Thrombocytopenia is usually due to gestational thrombocytopenia, but may also result from preeclampsia or immune thrombocytopenic purpura. Pregnancy induces a hypercoagulable state through increased clotting factors and reduced inhibitors. Low molecular weight heparin is the anticoagulant of choice for treating thromboembolic disorders during pregnancy.

1. HAEMATOLOGY OF
PREGNANCY
Dr Ibrahim Khider
Assistant professor of Haematology
OCTOBER 2017

2. Introduction
• The changes in haematological
parameters during pregnancy and the
puerperium are driven by changes in
hormones (oestrogen)
• Range from subtle to substantial
• A thorough understanding of these
changes is important to avoid both over
and under-diagnosing abnormalities

3. Physiological Haematology
Changes
1. Red blood cells – Anaemia
2. White Blood Cells – Changes in counts
3. Platelets – Lower counts
4. Coagulation factors

4. Red cell changes
 Physiological anaemia is the term often used to
describe the fall in haemoglobin (Hb) concentration
that occurs during normal pregnancy.
 During pregnancy, the total blood volume increases
by about 1.5 , mainly to supply the needs of the
new vascular bed.
 Almost 1 liter of blood is contained within the uterus
and maternal blood spaces of the placenta.

5. Red cell changes
 Red cell mass also increases by 10%–20% but the
net result is that hemoglobin (Hb) concentration falls.
 Typically, this is by 1–2 g/dL by the late second
trimester and stabilizes thereafter.
 Women who take iron supplements have less
pronounced Hb changes, as they increase their red
cell mass proportionately more than those without
dietary supplements

6. Red cell changes
• Hb 10.4 g/dL suggests anemia.
• Hb 13.5 g/dL is unusual and suggests
inadequate plasma volume expansion .
-which can be associated with pregnancy
problems including pre-eclampsia and
poor fetal growth

7. ANAEMIA
1. Anaemia
- Normal Hb (12-15g/dl)
- WHO defines anaemia in pregnancy as
(Hb<11g/dl)

8. ANAEMIA cont/
NB an Hb > 13.5g/dl is unusual – suggests
inadequate plasma volume expansion
which can be associated with pregnancy
problems including preeclampsia and poor
foetal growth

9. Iron deficiency anaemia
• Up to 600 mg iron is required for the increase in
red cell mass and a further 300 mg for the fetus.
• Despite an increase in iron absorption, few
women avoid depletion of iron reserves by the
end of pregnancy.
• In uncomplicated pregnancy, the mean MCV
typically rises by approximately 4 fL
• A fall in red cell MCV is the earliest sign of iron
deficiency.
• Later, the MCH falls and finally anaemia results.

10. ANAEMIA CONT/
Figure 1. Peripheral Blood Film - Iron deficiency anaemia
Figure 1a. Normal RBCs

11. Iron deficiency anaemia
• Early iron deficiency is likely if the serum ferritin
is below 15 IJ,g/L together with serum iron <10
µmol/L and should be treated with oral iron
supplements.
• The use of routine iron supplementation in
pregnancy is debated but iron is probably better
avoided until the Hb falls below 10 g/dL or MCV
below 82 fL in the third trimester.

12. ANAEMIA cont/
- In treatment if iron deficiency expect a Hb
rise of 2g/dl over 3-4 weeks
- Continue for 3 months after Hb normalizes
to replenish iron stores

13. Folate deficiency
• Folate requirements are increased
approximately twofold in pregnancy
• Serum folate levels fall to approximately
half the normal range with a less dramatic
fall in red cell folate
• In some parts of the world, megaloblastic
anaemia during pregnancy is common
because of a combination of poor diet and
exaggerated folate requirements.

14. Folate deficiency
• Given the protective effect of folate against
neural tube defects, folic acid 400 µg/day should
be taken periconceptually and throughout
pregnancy
• Food fortification with folate is now being
practised in many countries.

15. Vitamin B12 deficiency
• Vitamin B12 deficiency is rare during
pregnancy
• Although serum vitamin B12 levels fall to
below normal in 20-30% of pregnancies
and low values are sometimes the cause
of diagnostic confusion.

16. ANAEMIA cont/
Figure 2. Peripheral Blood Film - Megaloblastic Anaemia

17. CHANGES IN WCC
2. Changes in WCC (elevated)
- Mainly increase in neutrophils
Figure 3. Neutrophil Leucocytosis

18. CHANGES IN WCC cont/
• WCC normal reference range (4-10
x10^9/l)
• In pregnancy (6-16 x10^9/l)
• In the hours post partum (9-25 x10^9/l)
• Return to normal at about 4 weeks post
partum

19. CHANGES IN WCC cont/
- Left shift in granulocytes and toxic
granulation
Figure 6. Left shift (bands) in granulocytes- Peripheral Blood

20. CHANGES IN WCC cont/
- Lymphocyte count increases slightly
during 3rd
trimester only
Figure 7. Lymphocytosis in Peripheral Blood

21. CHANGES IN WCC cont/
- Monocyte count is higher (esp. 1st
trimester)
Figure 8. Monocytosis – Peripheral blood

22. CHANGES IN WCC cont/
• Eosinophil and Basophil counts do not
change
Figure 9. Eosinophil Figure 10. Basophil

23. 3. Platelet Count
- Decreases by 10%
(Normal PLT count = 150-400x10^9/l)
i) Left Shift Of The Whole Distribution Of
Platelet Counts At Term
ii) Haemodilution
CHANGES IN PLT COUNT

24. CHANGES IN PLT COUNT
cont/
iii) Increased platelet consumption driven by
increased levels of thromboxane A2
iv) In multiple pregnancies owing to
increased thrombin generation

25. CHANGES IN PLT COUNTS
cont/
• Thrombocytopenia in pregnancy is the 2nd
most common haematological finding after
anaemia
• Can be physiological or pathological
• Affects 7-10% of all pregnant women
• Thrombocytopenia is a drop in platelet
count < 150 x10^9/L
• Platelets 120-150 x10^9/l are frequent in
the 3rd
trimester

26. • Thrombocytopenia in pregnancy is a
common reason for a haematologist
consultation
• The role of the haematologist is :
1. Determine the cause
2. Advise in the management of
thrombocytopenia
3. Help estimate the risk to the mother and
foetus
CHANGES IN PLT COUNTS
cont/

27. Bleeding complications
• Pregnant women with thrombocytopenia
have fewer bleeding complications
compared to non pregnant women due to
pro-coagulant state induced by increased
levels of: 1. Fibrinogen
2. Factor VIII
3. von Willebrand factor
4. Suppressed fibrinolysis
5. Reduced protein S activity

28. Pregnancy- specific Not pregnancy-specific
Isolated thrombocytopenia Gestational thrombocytopenia
(70-80%)
Primary ITP (1-4%)
Secondary ITP (<1%)*
Drug induced thrombocytopenia**
Type IIB von Willebrand disease**
Congenital thrombocytopenia**
Thrombocytopenia
associated with systemic
disorders
Severe pre-eclampsia (15-20%)
HELLP syndrome (<1%)
Acute fatty liver of pregnancy
(<1%)
TTP/HUS**
SLE**
Antiphospholipid syndrome**
Viral infections**
Nutritional deficiency**
Splenic sequestration(liver diseases, portal
vein thrombosis, storage disease, etc)**
Thyroid disorders**
Table 1. Differential diagnosis of
Thrombocytopenia in Pregnancy
*Secondary ITP – includes isolated thrombocytopenia secondary to some infections (HIV, HCV, H.pylori) and
to other autoimmune disorders such as SLE.
**Rare (probably <1%)
Reference – American Society of Haematology. 2013 Clinical Practice Guide on Thrombocytopenia in
Pregnancy.

29. Gestational Thrombocytopenia
• Occurs in 5-9% of healthy women
• Mild-moderate thrombocytopenia (70-80x10^9/L)
• With about two-thirds being 130-150x10^9/L

30. Gestational Thrombocytopenia
cont/
• Commonly occurs
mid 2nd
- 3rd
trimester
• No maternal bleeding risk
• No foetal or neonatal thrombocytopenia or
bleeding risk
• Normal platelet count outside of pregnancy and
return to normal within 1- 2 months post partum

31. Gestational Thrombocytopenia
cont/
• Is a diagnosis of exclusion
• The main competing diagnosis is ITP-
considered if the degree of
thrombocytopenia is more severe

32. Gestational Thrombocytopenia
cont/
• Gestational thrombocytopenia VS ITP?
- No laboratory testing to differentiate the
two
- Existence of pre-pregnancy
thrombocytopenia should rule out GTP
- History of past pregnancies complicated
by thrombocytopenia should favour
gestational thrombocytopenia

33. Gestational Thrombocytopenia
cont/
• Also response to immune modulation with
steroids or immunoglobulins would favour
ITP.

34. Gestational Thrombocytopenia
cont/
• Treatment and Management:
- Not necessary if asymptomatic
- Platelet count monitoring recommended
periodically, depending on the degree of
thrombocytopenia
- Patients with platelet counts of 30-
50x10^9/L should be able to deliver safely
via NVD or surgically

35. Laboratory Investigations
Recommended tests Full blood count
Reticulocyte count
Peripheral blood smear
Liver function tests
Viral screening (HIV, HCV,HBV)
Tests to consider in clinically indicated Antiphospholipid antibodies
Antinuclear antibody (ANA)
Thyroid function tests
H.pylori testing
DIC testing
VWB type IIB testing*
Coombs test^
Quantitative immunoglobulins^^
Tests that are not recommended Antiplatelet antibody testing
Bone marrow biopsy
Thrombopoietin (TPO) levels
*Consider if history of bleeding, family history of thrombocytopenia, or unresponsive to ITP therapy
^ Appropriate to rule out autoimmune thrombocytopenia (Evans syndrome) if anaemia and reticulocytosis is present
^^In the setting of recurrent infections, low immunoglobulins may reveal a previously undiagnosed immunodeficiency
disorder (e.g. common variable immune deficiency)
Reference – American Society of Haematology. 2013 Clinical Practice Guide on Thrombocytopenia in
Pregnancy.

36. ITP In Pregnancy
• The incidence is <1%
accounting for 3% of all thrombocytopenic
pregnancies
• Onset any trimester
• Thrombocytopenia outside of pregnancy
• Moderate thrombocytopenia <100x10^9/L but may be
lower
• May have signs of bleeding, bruising, or petechiae

37. ITP in Pregnancy cont/
• +/- large platelets on peripheral blood
smear
• Normal bone marrow
biopsy

38. ITP in Pregnancy cont/
• Pathophysiology :
- Antibodies against platelet glycoproteins
(GPIIb/IIIa and GPIb/IX leading to
destruction in the RES)

39. ITP in Pregnancy cont/
• Is a diagnosis of exclusion
• May be associated with foetal
thrombocytopenia – IgG antibodies cross
the placenta
• However 90% of
these neonates will
not have significant
thrombocytopenia

40. ITP in Pregnancy cont/
• Similarly to gestational thrombocytopenia
there should be no additional
haematological abnormalities, no
microangiopathy, or evidence of DIC and
liver dysfunction

41. Haemostasis In Normal Pregnancy
• --

42. HAEMOSTASIS cont/
• PREGNANCY = HYPERCOAGULABLE
STATE INCLUDING PUERPERIUM
1. Protection from haemorrhage during
delivery
2. Predisposes to
thromboembolism

43. Effect Of pregnancy On The
Coagulation System
1. Increase of Clotting Factors
▪ FVIII, FVII, FX, Fibrinogen, von Willebrand factor
2. Reduction of Coagulation Inhibitors
▪ Protein S, Antithrombin
▪ Protein C remains stable
3. Reduction Of Fibrinolysis Inhibition
(hypofibrinolysis)
▪ Due to increase in Plasminogen Activator
Inhibitor-1 (PAI-1)

44. Antithrombotic Agents
1. Vitamin K antagonists (Warfarin) contraindicated
(relative CI)
▪ Crosses the placenta
▪ Risk of bleeding
▪ Teratogenic (6-12 weeks)
2. Low Molecular Weight Heparin>>UFH
▪ Anticoagulants of choice
▪ Does not cross the placenta
▪Excellent bioavailability and predictable
effect
▪ Short half-life
▪Well-tolerated (rare thrombocytopenia,osteoporosis)

45. End Of Presentation
• THANK YOU FOR YOUR ATTENTION