haematology hell Flashcards
ddx low platelets in pregnancy
Ddx Gestation thrombocytopenia HTN related disease of pregnancy Infection DIC TTP Acute fatty liver Antiphospholioid syndrome / SLE ITP
Ix
Peripheral blood film
Urea and electrolytes + urate
LFT
If haemolysis suspected reticulocytes, LDH, direct coombs test
Coagulation screen
Lupus anticoagulant, anticardiolipin antibodies and ANA
Virology screen – TORCH EBV HIV Malaria
If blood count otherwise normal then bone marrow biopsy not needed in pregnancy
Sickle cell
Risks to pregnancy Maternal 2.5% mortality in pregnancy PET Acute painful crises in pregnancy Increased by dehydration, cold, hypoxia, overexertion, stress N+V of pregnancy can result in dehydration Worsening of anaemia and this leads to ACS and increased infection risk Antenatal hospitalisation LSCS VTE Infection APH
Fetal Perinatal mortality PTL FGR, FD in labour, LSCS Miscarriage
Pregnancy risk on disease
Painful vaso occlusive crisis is a frequent complication with 30-50% of woman having a painful crises during pregnancy
Look for causes – infection, dehydration, acute chest syndrome, anaemia, splenic enlargement and thrombotic events
Ix FBC, HbS percentage, reticulocytes, urea, electrolytes Blood cultures, throat swab, MSU and sputum CTG CXR NSAIDS can be used between 12-28 weeks Work up the pain ladder Adequate fluid intake
If admitted needs clexane
Acute chest syndrome presents in 7-20% of woman
non infectious vaso-occlusive crisis of the pulmonary vasculature
Often precipitated by a LRTI – inflammation and loss of oxygen tension makes further sickling occur
Rare but life threatening complication
Pyrexia, decreased oxygen sats, abnormal CXR with pulmonary infiltrates
Ddx is PE and LRTI
Spiral CT is best
Tx
Needs ICU care
Need urgent transfusion / exchange transfusion
Oxygen
Antibiotics to cover mycoplasma and S pneumoniae
Pain control
Consider VTE prophylaxis
Management
Prepregnancy
Education for the woman on pregnancy risks – it should be discussed at each consultation from adolescence
Contraception advice so pregnancy can be planned
Genetic screening for the partner
If the partner has a trait or affected by a haemoglobinopathy then the couple should receive appropriate counselling
Discussions around preimplantation genetic diagnosis, prenatal diagnosis and TOP
High dose folic acid pre conception and throughout pregnancy
SCD are on folic acid 1mg daily usually
Stop any teratogenic treatments – may need to wean them down
Hydroxycarbamide (hydroxyurea) should be stopped 3 months pre conception
ACEi stopped (often on as renal protective)
Screen for rubella, Hep B, HIV, Varicella,
Recommend vaccinations if not up to date and immune
H Influenza type b
Conjugated meningococcal C
Pneumococcal every 5 years
Hep B if not immune
Influenzas (should get annually)
Screen for chronic disease complications
ECHO for pulmonary hypertension (associated with an increase in mortality)
BP + Urinalysis – PET + renal disease
Retinal screening for proloferative retinopathy
Iron overload from multiple transfusions – aggressive chelation is recommended
Screen for red cell antibodies
Pregnancy
First visit
All of the above if not performed pre pregnancy .. including genetic screening
MDT approach including obstetrician and haematologist experienced in SCD
Advice about avoiding precipitators to crises (cold, hypoxia, dehydration)
High dose folic acid throughout T1
Aspirin for PET prophylaxis from 12 weeks
Penicillin prophylaxis
SCD pts are hyposplenic and at risk of infections from encapsulated organisms eg Neisseria meningitides, streptococcus pneumonia, Haemophilis influenzae
Woman should have a viability scan at 7-9 weeks
Ongoing management Routine nuchal scan Detailed anatomy Monitor anaemia – Hb each visit Urine dip for protein and BP each visit for monitoring for PET MSU for culture monthly
LMWH if admitted and throughout pregnancy on consideration of other risk factors
Monitor for complications eg sickle cell crisis, acute chest syndrome, and treat with analgesia and fl
Growth scans 2-4 weekly from 24 weeks with umbilical artery doppler if FGR is diagnosed
Routine Blood transfusion is not recommended
If required for management of a sickle cell complication blood should have extended phenotype testing, Rh C,D,E and Kell – blood should be CMV negative
Anaesthetic review in pregnancy
Intrapartum Del 38-40 weeks Deliver in hospital LSCS for obstetric indications Recommend epidural Avoid pethidine – increases the risk of seizures Avoid sepsis and dehydration and hypothermia CEFM Cross match if atypical antibodies
Post natal
If the baby is high risk, capillary samples should be sent for testing an an experienced lab
Maintain maternal 02 above 94% and keep warm and hydrated
LMWH 7/7 post NVD and 6/62 post LSCS
Progesterone only contraceptives are better and preferred then oestrogen containing agents
major thalassamia B in the mum
B thalassemia
Epidemiology
Autosomal recessive
80% India Pakistan and Blangladesh50% die from cardiac failure
Thalassaemia - the basic defect in the thalassaemia syndromes is reduced globin chain synthesis with the resultant red cells having inadequate haemoglobin content. There is an excess of non functioning alpha globin chains
Extravascular haemolysis due to the release of damaged red cells
Ineffective erythropoiesis
Splenectomy use to be the mainstay of treatment but not any more – but a lot of patients will have had a splenectomy
Treatment now is blood transfusion and iron chelation
Improvement in this has improved qoL for thalassaemia patients
Reduced mortality from iron overload since developed MRI monitoring for iron overload
Blood film
Codocyte – target cells, typically seen in iron deficiency but may be seen in thalassaemia
Limited oxygen carrying capacity and cannot be destroyed in the liver
If hyposplenic then these abnomral cells are not removed from the population and target cells increase
Anisocytosis – abnormal size
Poikilocytosis – abnormal shapes >10%
Elliptocytosis
Hypochromic anemia
Schistocytes
Iron overload
Hepatic cardiac and endocrine dysfunction
Cardiac failure is the primary cause of death for 50 % of people
Anterior pituitary is very sensitive to iron overload and dysfunction is common
Puberty delayed and incomplete resulting in low bone mass
Subfertility and require ovulation induction
Major
Intermedia / trait
require more then 7 transfusions per year
Homozygous B
Present in first 2 years of life
Most at 3 months when Hb F switches to adult Hb
Bone marrow transfusion can be curative
Extramedullary haematopoesis – causing frontal bossing
7 or fewer transfusions per year
Heterozygous
Mild to moderate microcytic anaemia
No significant detrimental affect to the overall health
Dx from 2-6 years old, growth and development are impaired
Others are completely asymptomatic / splenomegaly / mild anaemia /
As below
Aggressive pre pregnancy chelation
Ovulation induction
Folic acid 5 mg / day
Cardiology assessment for iron deposition + EF monitoring
Test partners and consider PND
Avoid iron
Tranfuse as needed
Monitor growth
Assess for alloantibodies
Often anaemic – folic acid 5mg / day. Iron only if low
Pregnancy risks
Maternal risk
Fetal risk
Cardiomyopathy due to iron overload
Development of new endocrinopathies due to no chelation – T2DM, hypothyroid, hypoparathyroidism due to increasing iron burden
Miscarriage (especially thalassaemia + diabetes)
IUGR
Pre pregnancy
Ongoing discussions around pregnancy intentions
Contraception if not desired
COCP ok
Screen for end organ damage
Assess burden of iron overload
Review of transfusion requirements
Optimise iron stores
Compliance with chelation – aggressive pre pregnancy chelation can reduce and optimise body iron burden and reduce end organ damage
All chelation therapy is teratogenic in T1
Desferrioxamine can be used in T2 and T3
Optimising iron burden pre pregnancy is critical as ongoing iron accumulation from transfusion exposes her to disease progression
Screen for complications
Screen for and treat diabetes
Common in adults with thalassaemia
Multifactorial
Iron induced islet cell insufficiency
Genetic factors
Autoimmunity
Insulin resistance
Aim HbA1c below 43 as this reduces the risk of congential malformations
HbA1c not reliable as a marker of glycaemic control as it is diluted by transfused blood and results in underestimation
Serum fructosamine is preferred for monitoring
Thyroid – ensure normal function
Hypothyroid is associated with maternal morbidity and perinatal morbidity and mortality
Screen for hypothyroid
Liver
Iron load assessed with Ferriscan or liver T2
Should be <7 mg/g
If over 15mg/g the risk of myocardial load increases so chelation is indicated from 20 weeks
If high iron burden then should have aggressive chelation pre pregnancy
If iron load very high then cardiac load will be present, and therefore may need chelation in pregnancy 20-28 weeks
USS liver and gall bladder for cholelithiasis and liver cirrhosis or transfusion related viral hepatitis
Risk of cholecystitis in pregnancy
Liver cirrhosis and hep C make increase pregnancy risk and should have lvier team involved
Heart
ECHO and ECG
T2 cardiac MRI to assess for iron overload
Aim is no cardiac iron but this can take years to achieve – so maybe aim for minimal iron
Level of iron on T2 weighted MRI dictates chelation
High iron related to increased risk of cardiac failure
Iron causes myocyte apoptosis and fibrosis
Reduced EF is a relative contraindication to pregnancy
MDT input
Bone density scanning
Pre existing OP should be documented
Pathology complex – maybe chelation of calcium, hypogonadism, Vit D deficiency and thalassaemia itself
Serum Vit D optimised with supplements as needed
Deficiency common
Red cell antibodies
ABO and full group genotype and antibody titres should be measures
Alloimmunity occurs in 16.5% of woman with thalassaemia
Limit blood for transfusion
Medication review
Iron chelators should be reviewed
Deferasirox and deferiprone ideally discontinued 3 months before conception
Desferrioxamine has a short half life and can be used during ovulation induction but then avoided in T1
Safe at low dose after 20 weeks
Bisphosphonates are contraindicated in pregnancyand should be discontinued 3 months pre preg
Ovarian stimulation may be needed
MDT counselling pre pregnancy
Genetic screening
Partner testing
Genetic counselling
Options for testing
IVF / ICSI with PGD should be considered in the presence of haemoglobinopathies
Egg and sperm donors considering IVF should be screened for haemoglobinopathies
Immunisation
Hep B vaccination if not already
If prev splenectomy should have vaccination for pneumococcus (every 5 years) and haemophilus influenza and meningococcal
Annual influenza
Infections
If previous splenectomy then should have penicillin prophylaxis (erythromycin if allergic)
Hep C status should be assessed
Supplements
5 mg folic acid
High demand for folic acid
Antenatal
MDT
High risk obstetrician, haematologist, high risk MW, other specialties as indicated
Individualised
Specific to thalassaemia
Receive blood transfusions on a regular basis aiming for pretransfusion Hb of 100
For intermedia
Clinical decision when to start transfusions
If worsening anaemia, FGR then consider regular transfusions
Same target – pretransfusion 100
Initially a 2-3 unit then top up the next week – until Hb 120
Hb checked in 2 weeks
Hb of 80 is about the threshold for transfusion but this is a clinical multifactorial decision
Reviewed monthly until 28 weeks and fortnightly thereafter
If diabetic – monthly fructosamine concentrations
28 week cardiac assessment(thalassaemia major)
Monitoring iron load
Myocardial iron load should have close cardio follow up with careful monitoring of EF – cardiac decompensation is a primary indication for chelation
Severe hepatic iron loading should be reviewed and consideration given to chelation
VTE prophylaxis
Splenectomy or platelets over 600 – aspirin
Splenectomy and platelets over 600 – aspirin and heparin
At least if admitted
Monitor TFTs
Fetal monitoring
Early dating scan
Routine T1 scan 11-14 weeks
Anatomy 18-20
Serial biometry 4 weeks from 24 weeks
Intrapartum
MDT
If there are antibodies, cross match blood
If Hb below 100 – then cross match 2 untis
Peripartum chelation
If transfusion dependant and not being chelated then will have a toxic iron species called non transferrin bound iron. This causes free radical damage and cardiac dysrhythmia when the woman is in the active stress of labour
If major – IV desferrioxamine 2 g over 24 hours should be administered for the duration of the labour
CEFM
Increased risk fetal hypoxia and possible operative delivery
Active management of third stage to minimise blood loss
No specific evidence for timing or MOD
Postpartum
High risk for VTE
LMWH while in hospital
6 weeks post lscs
7 days post NVD
Breast feeding is safe and should be encouraged
If breastfeeding can start desferrioxamine – not harmful to baby
If not breastfeeding – IV or sc desferrioxamine is continued until discharge and resumption of previous chelation
Cord blood
For couples with an affected child, cord transplantation from a subsequent non affected pregnancy can be curative
Gestational thrombocytopenia
60% of thrombocytopenia in pregnancy
5-10%of woman
Benign self limiting condition Can present in T1 but more commonly as the pregnancy progresses
No increase in bruising or bleeding
If below 100 000 then unlikely to be GT
Resolved PP - can take 6 weeks
A normal pre pregnancy patelet count is helpful
Risk of GT is 14X higher if previous GT
No tx required, no change to care
Uncertain mechanis,. Physiological adaptation from increased plasma volume, pooling or consuption in the placenta
ITP
11% of low platelets in pregnancy
1-3 : 10,000 pregnancies
GT is 100X more common
In the general population it is 3 : 100,000 adults
Can occur in any trimester
Plt decrease at the same rate in pregnancy and are 15-20% lower at delivery
Autoimmune condition where antiplatelet antibodies interfere with platelet production and cause destruction of circulating platelets
GT and ITP cannot be distinguished in pregnancy
Antiplatelet maternal IgG can cross the placenta and casue fetal thrombocytopenia
Risk of the fetus of severe low platelets in about 5-10%
Very low risk of fetal ICH best predictor is a previously affected child
Management
Exclude APS or SLE (often associated conditions)
Plt count monthly then more frequently in the third trimester
Tx - T1/2
Plt <20
Maternal bleeding
Pre procedure eg CVS
T3 – Plt <80 likely warrant Tx
Corticosteriods are first line 20-30 mg prednisolone
IVIG delayed clearance of IgG covered platelets – more rapid but $ and only helps with short term
Anti D Ig therapy can be given as a decoy nd helps raise platelets
Splenoectomy should be avoided in pregnancy if possible
Platelet transfusion are a last result as then antibodies are increased and imrpovement is only short term
Fetal considerations
LSCS for obstetric indication – no evidence it reduces the risk of ICH
IgG crosses the placenta towards term so baby is not as risk before labour and delivery
Cord sampling is not justified as the risk of ICH is about equivalent to cordiocenesis
Neonatal platelet count reaches a nadar 2-5 days PN once splenic circulation is established
Can give IVIG to babies when bleeding or low platelets
avoid IM Vit K to neonatal
VWD
VWF levels increase in pregnancy and this can be protective
Levels drop quickly in the post partum At or within hours of delivery and again 5-15 days later – increased primary and secondary PPH
Prepregnancy Assess type and response to DDVAP (desmopressin) Genetic counselling Pre natal dx for type 3 disease Risks of rpegnancy and delviery
Antenatal
Prenatal testing with haemostatic cover if required
VWF activity and factor VIII level >50 is advisable before invasive testing
MDT care
VW screen T1 or T3
Anesthetic review
Intrapartum
T1 vWD with normal levels regional is safe
Avoid FSE FBS vetnouse, rotational forceps if not normalsed / severe disease
LSCS for noral obs indication
Primary and second PPH so FBC G+H
Avoid IM injections – can give subcut immunisations
Post partum
Active management third stage
Factor support / TXA / DDAVP as needed – if given continue for 3 days
Type 3 can be dx from cord blood- small risk to fetus, just paeds referral
