Fetal anaemia and related disorders Flashcards
At what two points in pregnancy should women have their blood group and antibody status determined?
Booking
28/40
Collect 28/40 sample before Anti-D administration
If Rh -, at what gestations in pregnancy should women be offered Anti-D, and why?
28/40 and 34/40
625IU
To prevent iso-immunisation
Due to the risk of spontaneous sensitisation that can occur at this gestation
If Rh-, what care should women receive postnatally?
Cord blood for fetal rh status
Dose of Anti-D (routine prophylaxis, 625IU) within 72 hours if rh pos
Measurement of Kleihauer: quantification of fetal-maternal haemorrhage
What proportion of women are Rh negative
1 in 7
What proportion of women will have
- red cell antibodies
- clinically significant antibodies
detected in pregnancy?
Red cell antibodies = 1.2%
Clinically significant antibodies = 0.4%
What are 5 examples of sensitising events in the first trimester, that would be indications for Anti-D in a Rh negative woman
Miscarriage
MTOP or STOP
Ectopic pregnancy
CVS
There is insufficient evidence to suggest that a threatened miscarriage before 12/40 necssitates Anti-D (RANZCOG)
NZ Blood Bank advises to give Anti-D due to a small risk of anti-D isoimmunisation
250IU unless multiple pregnancy: 625IU
What are 5 examples of sensitising events in the second and third trimester, that would be indications for Anti-D in a Rh negative woman
Abdominal trauma TOP APH / Obstetric haemorrhage Amniocentesis ECV attempt
When is routine Anti-D prophylaxis not required in the Rh negative woman in pregnancy?
Women is already sensitised i.e. has Anti-D antibodies
Fetal genotyping confirms the fetus is Rh negative
Father is confirmed to be Rh negative
What is the pathophysiology of Haemolytic Disease of the Newborn?
Fetal RBCs enter maternal circulation and her immune system creates antibodies against these.
Trans-placental passage of maternal IgG antibodies into fetal circulation.
Antibodies cause fetal RBCs to be destroyed by their own immune system leading to HDFN.
What is different about Anti-K HDN compared to Anti-D and Anti-c?
Anti-K: erythroid suppression, immune destruction of early erythroid progenitor cells
Severe fetal anaemia can occur at low antibody titres
Therefore, refer at any titre level
What are the main three antibodies that can cause fetal anaemia, via HDN?
Anti-D
Anti-c
Anti-K
What are five less common antibodies that can cause fetal anaemia via HDN?
Anti-E Anti-Fy Anti-Jk Anti-C Anti-c+E
Which antibody potentiates the severity of fetal anaemia due to anti-c antibodies?
Anti-E
Therefore, if Anti-E present with anti-c, referral at lower titres is indicated
What are the titres for Anti-D for mild risk, moderate risk and severe risk
Mild <4
Refer to fetal medicine if >4
Moderate: 4-15
Severe > 15
IU/mL
What are the titres for Anti-c for mild risk, moderate risk and severe risk of fetal anaemia
Mild risk: < 7.5
Refer to fetal medicine if >7.5
Moderate risk: 7.5-20
Severe risk > 20
In the presence of antibodies that can cause HDN, how often should the titres be measured?
Every 4 weeks until 28/40, then every 2 weeks
Once titres reach level required for referral, subsequent measurements is of doubtful significance
In the presence of levels/titres of maternal antibodies associated with moderate / severe risk for HDN, what should the management be?
Weekly USS, specifically assessing for MCA PSV
MCA PSV
- predictive of moderate or severe fetal anaemia with 100% sensitivity and a false positive rate of 12%
- less sensitive after 36/40
Weekly USS can also assess for polyhydramnios, skin oedema, cardiomegaly
If the MCA PSV > 1.5MoM in the context of maternal antibodies implicated in HDN, what is the management?
FBS
- measure Hb, bilirubin, DAT
Intra-uterine transfusion
What did the Cochrane Review regarding Anti-D administration in pregnancy for preventing Rhesus alloimmunisation show?
Compared women given anti-D at 28/40 and 34/40 vs not
No clear difference in the risks of iso-immunisation
RANCOG Statement reads this as SHOWING a difference (but none were significant)
What is the Cochrane Review evidence regarding postnatal Anti-D
Anti-D, given within 72 hours after childbirth, reduces the risk of RhD alloimmunisation in Rh negative women who have given birth to a Rh positive infant
Within six months of the birth and in their next pregnancy
What is the Cochrane Review evidence regarding Anti-D administration after spontaneous miscarriage for preventing Rh alloimmunisation?
Insufficient data, small size
Until high quality evidence available, should follow local / national guidelines
What is the Cochrane evidence regarding IV vs IM Anti-D?
Findings suggest they are equally effective
Low numbers, insufficient data
What is mirror syndrome?
Rare complication of fetal hydrops
Association of fetal and placental hydrops
With maternal oedema and PET
“Triple oedema”
Oedema
Mild maternal hypoalbuminaemia
PET is unusual
What is a rare maternal complication of fetal hydrops?
Mirror Syndrome
What is the overall perinatal survival with red cell antibodies?
84%
Non-hydropic 94%
Hydropic 74%
Outline the causes of fetal anaemia:
Infection:
- Parovirus
- CMV
- Toxo
- Syphilis
Immune:
- RBC alloimmunisation: Rh and other antigens
Inherited: metabolic diseases e.g. pyruvate kinase deficiency, G6PD deficiency.
- thalassaemia
Obstetric:
- MC twins: TAPS
- Feto maternal haemorrhage
- Down syndrome: transient abnormal myelopoeisis
- Maternal acquired red cell aplasia
- Vascular tumour e.g. chorioangioma
- AVM
List the clinical implications of maternal red cell antibodies for mother and fetus
Fetus:
- Fetal, neonatal anaemia and thrombocytopaenia
- Fetal hydrops and perinatal death
- Preterm birth
- Late anaemia secondary to transfusion-mediated suppression of neonatal erythropoeisis.
- Hyperbilirubinaemia, jaundice, kernicterus and SNHL (toxicity 8th CN).
- Cholestasis: iron overload of liver from multiple transfusions.
Mother:
- Issues with timely provision of blood or blood components.
- Risk of alloimmunisation during FBS/IUT.
Antenatal administration of Anti-D particularly for routine prophylaxis reduces the risk of alloimmunisation by what %?
80%
What history would you want to know for a woman with clinically significant antibodies?
Cause of alloimmunisation:
- Blood transfusions
- Inadequate or omitted anti-D prophylaxis
Previous pregnancy outcomes:
- IUTs and gestation at which they were started.
- Gestation at delivery
- Neonatal anaemia
- Need for exchange transfusions or phototherapy
Relevant past history
What causes fetal/neonatal alloimmune thrombocytopaenia?
Maternal-paternal platelet type incompatibility leading to maternal immune system making platelet specific antibodies.
What is the incidence of FNAIT?
Rare 1 in 8000
What history would you want to know from a woman with platelet specific alloantibodies?
Previous pregnancies affected (fetus or neonate) including:
- Intracranial haemorrhage and timing.
- Cord/newborn Plt count
- Maternal antiplatelet antibody investigations
- Any maternal therapies.
What is the prognosis for FNAIT?
- 80% risk of recurrence if previous child affected and not treatment received.
- Tends to worsen with each pregnancy without treatment.
What investigations are part of work-up for FNAIT?
- Maternal platelet specific alloantibodies
- Ultrasound to identify fetal ICH
- Maternal and parternal platelet typing and compatibility of both parents
What test results would make you concerned this pregnancy is at risk of FNAIT?
Paternal platelet testing: heterozygous for particular antibody producing antigen. Tissue typing lab should be consulted for advice on invasive testing of pregnancy to tissue type the fetus.
If fetus is compatible with the mother, ongoing treatment and surveillance is not required.
What is the antenatal management of FNAIT
- Sibling without ICH: start weekly IVIG from 28 weeks, dose 0.5g/kg.
- Sibling WITH ICH: start weekly IVIG from 16 weeks, dose 1g/kg.
- Fetal ICH diagnosed but pregnancy continuing: weekly IVIG, dose 1g/kg.
- Consider steroids for high risk women however lack of evidence it improves Plt counts.
Fetal ICH diagnosed: for fetal brain MRI and MDM. Options to continue pregnancy or terminate.
What is the role of FBS and IUPT?
What is the issue with IUPT?
What are the risks?
Reserved for time of delivery planning.
Transfusion threshold Plt count <30 x <30 x 10^9/L.
Should be considered pre-CS if sibling had ICH.
Needs to be performed in setting where immediate CS can be performed.
Issue: tranfused platelets have short half-life 2-5 days unlikely RBCs.
Risk of fetal bleeding from puncture site.
What is the recommended timing and mode of delivery for FNAIT fetuses?
- Sibling without ICH: elective IOL at 37 weeks. Should avoid FSE, FBS and instrumental deliveries.
- Sibling with ICH: elective CS at 36 weeks. Consider pre-CS FBS and IUPT.
IOL considered if strong maternal wish. - This fetus diagnosed with ICH: elective CS at 34 weeks.
