Haemoglobinopathies Flashcards
Thalassaemia indices but normal hba2- need to exclude what
Look at HBF- raised in delta-beta,
Hb E and Lenore
If none of these then it’s alpha or gamma delta beta thalassaemia
PCV complicated by Fe def-
Will have inc rdw compared w thal
Zinc protoporphyrin
Raised in alpha and beta so not helpful to distinguish alpha/beta
Reasons for normal HbA2 in beta thal
Fe or folate def
HbH and beta thal hetero
Presence of A2 variant causing split in A2 band
Neonate prior to 6 months
Genetics of hb lepore
Cross over during meiosis of he beta and delta producing fusion gene
Hblepore detection
Hplc- 5-15%
Moves hbs on alk ph, he A on acid
Hb lepore clinical/lab
Imp to dx because of final interaction w hbs and beta thal
Film etc like beta trait
Sometimes inc hbf
If homo- like beta thal major
Inc hba2
Hyperthyroidism
Vit b12/folate
Treatment of infection by hiv
Dec hba2
Fe def ACD Sideroblastic anaemia Lead poisoning Juvenile mml Acquired HBH dx Erythroleukaemia Aplastic anaemia Hypothyroid Chemo induced hb f inc
Raise hbf neonate
Premmy SGA Chronic intrauterine hypoxia Diabetic mum Smoking
Raised hbf adults
Pgy stress erythropoiesis
Aplasti anaemia
Pernicious anemia
Mds, PNh, m6’ dm, starvation, thyrotoxic drugs
McHale red in fe def or thalassaemia?
Iron deficiency
Which genes in mum indicate neonatal testing in haemoglobinopathies
Hb S, C, DPunjab, E, OArab, Lepore or β or δβ thalassaemia trait).
Babies dx with what should be retested in 6 weeks
Hbs SS, SC, SDPunjab, SOArab or Sβ thalassaemia
Heel price- use hplc or ief
Can do gel w cord
Detection of an unstable haemoglobin
Heat stability test
Isopropanol test
The unstable haemoglobins are frequently silent using electrophoretic or chromatographic techniques and tests for haemoglobin instability are essential in the detection or exclusion of an unstable haemoglobin.
Sickling syndromes
SS SS-a/aa, SS-a/-a SB thal SDelta beta thal S Lepore SD Punjab SO Arab SC
What does the strip test detect?
Hb barts- of which there is normally amount of in any alpha thal
Guide to sickle transfusion to prevent Stroke
Regular transfusion to maintain HbS <30% should be offered as initial
treatment to children with SS or S/βo thalassaemia aged 2-16 years judged to
be at high risk for a first stroke on the basis of Transcranial Doppler
ultrasonography
Transfusion of sickle in pgy
Women on long-term transfusions for stroke prevention or for amelioration of
severe sickle complications should continue with regular transfusions
throughout pregnancy
Transfusion should be considered in women with worsening anaemia or those
with acute SCD complications
Prophylactic transfusion is not routinely required for sickle pregnancy, but
should be considered for women with:
• previous or current medical, obstetric or fetal problems related to SCD
• women previously on hydroxycarbamide because of severe disease
• multiple pregnancy (
De scribe hplc
Separates by cation exchange chromatography
§Identifies variant Hbs by change in electrical charge
§Change in gradient of buffer means Hb attached to column will elute at different times
Sickle solubility test
Packed red cells reconstitute to a haematocrit of 50%.
§+ PO4 buffer containing reducing and lysis agents
§Sickle Hb is induced to sickle by the reducing agent and gets trapped in red cells
§Normal Hb is lysed
§Centrifuge and read
§Any sickle Hb results in turbidity
False positive sickle solubiliy test
Hyperlipidaemia
§Paraprotein
§Heinz body haemolytic anaemia
§Very high white count or nucleated red cell count
Ind for non rhd genotyping
Serological antigen typing/phenotyping cannot be determined due to chronic transfusion requirement (e.g. Thalassemia major, Blackfan Diamond anemia).
- Serologically complex patients - with multiple or unidentified antibodies who require ongoing transfusion support.
- Patients with autoimmune hemolytic anemia and/or with a positive DAT (in spite of chemical treatment), and circulating autoantibody.
- Patients with a suspected alloantibody against an antigen for which no commercial antisera is available (e.g. Possible anti-Doa).
- Select patients with variable or null reactivity using serological methods when a variant allele is suspected (e.g.Sickle cell anemia).
Ind for rhd genotyping
Prenatal patients with discrepant, weak or inconclusive serological RhD testing results where RHD genotyping may modify their blood product or Rh Immune Globulin (RhIG) requirements. For example: prenatal patients with weak or discrepant RhD serology may be Weak D type 1, 2 or 3 and would not require RhIG.
- Patients likely to require chronic transfusion, or with complex transfusion needs, where RHD genotyping may modify their blood product requirements.
- Patients who likely require transfusion with an anti-D who appear serologically D positive.
Genotyping may be useful in a variety of situations where a phenotype cannot be determined
Transfusion indicators thal beta inter
failure to thrive in childhood in the presence of significant anaemia;
emergence of bone deformities;
increasing anaemia not attributable to rectifiable factors;
evidence of a clinically relevant tendency to thrombosis;
presence of leg ulcers;
development of pulmonary hypertension;
delayed or poor pubertal growth spurt and
progressive splenic enlargement.
