24-03-23 - Haematology in Pregnancy Flashcards
Learning outcomes
- Understand physiological changes in pregnancy relating to both cellular and plasma blood components
- Understand how haematological complications of pregnancy present and are managed
- Understand the process of antenatal screening for thalassaemia and haemoglobinopathy as an example of the principles of disease screening
- Understand immunological changes in pregnancy.
Physiological changes in pregnancy. What are 5 haematological changes seen in pregnancy?
- 5 haematological changes seen in pregnancy:
1) Hb declines to 110 to 105 to 100 g/l as lower limit during pregnancy. Increase in red cells but bigger increase in plasma volume
2) Rise in white blood cell numbers- neutrophils mainly
3) Fall in platelets eg to lower limit of 80-100 x10^9/l “gestational thrombocytopenia”
4) Rise in mean cell volume (MCV) by 4fl e.g 84 to 88
5) Rise in fibrinogen and factors VIII, IX, X so hypercoagulable state
Why does anaemia occur in pregnancy?
How can we check this?
What is a solution to this?
- Increased demands of foetus leads to iron deficiency anaemia
- To check this, we check ferritin (MCV may be “normal” as it rises by about 4fl during pregnancy)
- Common to supplement iron in pregnancy but constipation/abdominal pain/nausea common - IV iron e.g Ferinject is an option
How much folic acid should be given pre-conception?
Why is this?
When should it be continued?
How rare is true B12 deficiency?
- Folic acid 400mcg/day given pre-conception- reduce neural tube defects (neural tube formed 2-4 weeks from conception)
- This is continued in pregnancy due to increased demands of foetus
- True B12 deficiency very rare but drop in reference range for B12 in pregnancy can cause diagnostic difficulty
What is Immune thrombocytopenic purpura (ITP)?
What are 3 ways ITP can be triggered?
What occurs in this condition?
What are 5 ways ITP can be treated?
Why might treatment be required?
Why is there a risk of neonatal thrombocytopenia?
- Immune thrombocytopenic purpura (ITP) is an autoimmune disease of children or adults
- 3 ways ITP can be triggered:
1) Infection
2) Drugs
3) Pregnancy - In this condition, auto antibodies to platelets (marrow normal
- 5 ways ITP can be treated:
1) Watch and wait
2) Steroids
3) Immunoglobulins
4) Splenectomy
5) Drugs to mimic thrombopoietin - Patient’s may ay need treatment to achieve platelets of 50+ for labour
- There is some risk of neonatal thrombocytopenia due to IgG antibodies crossing placenta
What is Thrombotic thrombocytopenic purpura (TTP).
What is TTP caused by?
What are 3 ways TTP can present? How can we screen for TTP?
What can TTP be associated with?
How is it treated?
- Thrombotic thrombocytopenic purpura (TTP) is a rare but life-threatening “thrombotic microangiopathy”
- TTP is caused by Enzyme (ADAMS13), which prevents large Von Willebrands polymers - this becomes deficient and platelets aggregate
- 3 ways TTP can present:
1) Fever
2) Neurological and renal disease
3) Low platelets and fragmented red cells - A coagulation screen can be used to detect TTP
- TTP can be associated with auto-immune disease/HIV/pregnancy
- It is treated by plasma exchange (to replace enzyme)
Thromboembolic disease.
What is the UK maternal death rate.
What is the leading direct cause?
When is a high-risk, hypercoagulable state in women?
What are 6 additional risk factors for Thromboembolic disease?
- Thromboembolic disease
- UK maternal death rate is 10.9 per 100,000 (during pregnancy and up to 6 weeks after)
- Pulmonary embolism is leading “direct” cause
- Pregnancy and 6 weeks post-partum is high-risk, hypercoagulable state.
- 6 Additional risk factors for Thromboembolic disease:
1) Age
2) Previous clot
3) Smoking
4) Twins
5) Obesity
6) Thrombophilia eg antithrombin deficiency
Thromboembolic disease.
What can occur in late pregnancy?
What could be signs of DVT?
What tests should be conducted at this point?
What is a D-dimer?
Why is looking for D-dimers not useful?
- Thromboembolic disease
- In late pregnancy, pelvic veins can be compressed, which can lead to leg swelling
- Progressive pain, tenderness, unilateral swelling- could be signs of DVT
- A Doppler exam of leg should be conducted, along with a chest x-ray
- If the chest x-ray is abnormal, then CT pulmonary angiogram (higher radiation dose) more reliable than ventilation/perfusion scan
- D-dimer is a protein fragment (small piece) that’s made when a blood clot dissolves in the body.
- Looking for d-dimers won’t be useful, as these will be raised in pregnancy
What is the treatment of choice for Thromboembolic disease?
When might be have to alter the dose of (LMWH)?
What is required to ensure effective dosing?
What medication will be required in future pregnancy?
- Low molecular weight heparin (LMWH) is treatment of choice for Thromboembolic disease
- Monitoring of anti Xa levels (3-4 hours post dose) is required to show effective dosing
- Prophylactic anticoagulation will be required for future pregnancy
What are 5 signs of Preeclampsia (PET)?
How is PET linked to HELLP?
What are 6 signs of HELLP syndrome?
What is the treatment for HELLP?
- 5 signs of Preeclampsia (PET):
1) Hypertension,
2) Fluid retention
3) Proteinuria
4) Headache
5) Urate high - A minority of patients with PET will develop HELLP
- 6 signs of HELLP syndrome:
1) Evidence of haemolysis
2) Anaemia
3) Red cell fragments
4) Raised LDH
5) Raised liver enzymes (ALT/AST)
6) Low platelets - The treatment for HELLP is prompt delivery of baby and supportive care
What is the cause of Disseminated intravascular coagulation (DIC).
What are 6 signs of DIC?
What are 3 treatments for DIC?
- Disseminated intravascular coagulation (DIC) can be an acute and serious complication typically following:
1) Placental abruption
2) Amniotic fluid embolism
3) Dead foetus - 6 Signs of DIC:
1) Typically, haemorrhagic
2) Very unwell
3) Organ failures
4) Depletion of coagulation factors
5) Low platelets
6) Red cell fragments - 3 treatments for DIC:
1) Treating the cause
2) Coagulation factors
3) Platelets
When can major haemorrhage occur?
How common is it in maternal death?
What are 4 risk factors for major haemorrhage?
How is it treated?
- Major haemorrhage can be ante- or post- partum
- It is the 2nd or 3rdcommonest direct cause of maternal death
- 4 risk factors for major haemorrhage:
1) Placenta previa (over cervix)
2) Placental abruption
3) Retained products of conception
4) Poor uterine contraction after - We have to treat the cause and replace red cell/platelets/coagulation factors
How can Haemolytic disease of the new born be found?
How can this occur?
- Haemolytic disease of the new born can be found through blood group and antibody screen at booking of pregnancy
- This can occur when foetal red cells carrying antigens from the father transferring to maternal circulation from week 12 onwards - more in later pregnancy
- The mother can produce IgG antibodies to eg A or B antigens, Rhesus D, c, E, or Kell etc.
- Antibodies cross the placenta causing anaemia, jaundice, brain damage or foetal death
What globin chains do we need in haemoglobin?
What chromosomes do they come from?
What changes in the globin chains do we see from the foetus to birth?
Describe the globin chains we see in:
1) Hb A (adult)
2) Hb A2
3) Hb F (foetal)
When might we see HBA2?
- Haemoglobin needs:
1) 2 alpha-like chains (chromosome 16)
* Starts off as zeta (early foetal) then alpha
2) 2 beta-like chains (chromosome 11)
* Starts off as epsilon then gamma then delta then beta
- Globin chains we see in:
1) Hb A (adult) = 2 alpha, 2 beta
2) Hb A2 (normal variant of haemoglobin) = 2 alpha, 2 delta
* May be see in beta thalassemia or in people who are heterozygous for the beta thalassemia gene
3) Hb F (foetal)= 2 alpha, 2 gamma
What is the Wilson and Jungner screening criteria?
What are 7 signs/tests in the detection of haemoglobinopathy/thalassaemia carriers?
Describe the haemoglobinopathy world distribution (in photo)
- 7 signs/tests in the detection of haemoglobinopathy/thalassaemia carriers:
1) Ethnic origin
* Traits for thalassemia are more common in people from Mediterranean countries, like Greece and Turkey, and in people from Asia, Africa, and the Middle East.
2) Most will be microcytic e.g mean cell volume (MCV) <27
3) Blood film- target cells in thalassaemia heterozygous, sickle slide test
4) Cellulose acetate or agarose gel Hb electrophoresis
5) High performance Liquid Chromatography (HPLC)
6) Gene copy number
7) Gene sequencing
- Haemoglobinopathy world distribution (in photo)
What are the 2 steps in Haemoglobin electrophoresis?
- 2 steps in Haemoglobin electrophoresis:
1) Make lysate of red cells
2) Pass current thro’ paper/gel and stain
What are 2 steps in High performance Liquid Chromatography (HPLC)?
- 2 steps in High performance Liquid Chromatography (HPLC):
1) Red cell lysate added to column
2) Compare optical density trace to control and expected positions (beware Hb A1c)
What tests will Abnormal haemoglobins show on?
How will Beta thalassaemia heterozygous appear?
How will alpha thalasaaemiawith 1 and 2 deletions appear differently?
What other procedure might be needed for alpha thalassaemia?
- Abnormal haemoglobins will show on electrophoresis/HPLC
- Beta thalassaemia heterozygous will have Alpha globin genes low MCV and MCH and Hb A2 >3.5%
- Alpha thalassaemia with one gene deletion - no change, 2 deletions- low MCV
- Gene copy number or sequencing may be needed – important to know which deletions occur on what chromosomes to see how many deletions can be inherited
Where are thalassaemia/Haemoglobinopathy of low prevalence?
What are 5 parts of pre-natal haemoglobin screening in low prevalence areas?
Describe the questionnaire for of pre-natal haemoglobin screening (in photo)
- Thalassaemia/Haemoglobinopathy are of low prevalence in Scotland
- 5 parts of pre-natal haemoglobin screening in low prevalence areas:
1) Full blood count (FBC) at booking (approximately 12 weeks) – is MCH <27pg?
2) Fill in “family origin questionnaire” for both partners
3) If either is “positive” then HPLC to look for thalassaemia/Haemoglobinopathy
4) May need confirmatory tests
5) May need to check partner’s FBC etc (beware non-paternity)
- Questionnaire for of pre-natal haemoglobin screening (in photo)
