Haematology Flashcards
Sources: InnovAiT 7:9 (September 2014); teaching from Phil!; GP notebook; OHCM
What is a porphyrias?
Disorders caused by defects in the synthesis of haemoglobin. Rare (1:30,000)
Precipitating factors for porphyria attacks?
Alcohol.Smoking.AnestheticsDrugs (barbiturates, chlordiazapoxide, rifampicin, carbemazepine, primidone, contraceptive pills, sulphanimides, phenobarbitones, ergots).Fluctuations in female sex hormones. (May be seen in pregnancy, premenstrually, and on contraceptive pills).Infections.Starvation
Clinical features of porphyria (during an acute attack)?
Neuropsychiatric - psychosis, confusion.Abdominal pain.Fever.Constipation or vomiting.Peripheral neuropathy.Seizures.Electrolyte disturbances (low Na, low K).May be tachycardia, hypertension, and shock, due to sympathetic overdrive.Some forms may have gallstones.May be splenomegallyMay be anaemia.Some forms have photosensitive blistering skin lesions.Rare but serious: respiratory and bulbar paralysis.
Treatment of porphyrias
-Avoidance/removal of ppt factors is best action-IVI to correct electrolyte disturbance.-High carbohydrate intake (by NG or IVI if necessary).-IV haematin may be used.-Prochlorperazine for N&V.-Diazepam for seizure.-Opiates for pain control.-Tachycardia and hot can be Rx with beta blocker.
Porphyrias can be caused by defects affecting which organs?
Liver or bone marrow.
What are the different forms of porphyria? Of these, which show photosensitive dermal features?
-Acute intermittent porphyria-Variagate porphyria (shows photosensitivity)-Hereditary coproporphyria (shows photosensitivity)
What is the mode of inheritance of the porphyrias?
They are all autosomal dominant. AIP is the most common, but still rare; it shows incomplete penetrance. Around 1/4 of AIP is due to a new spontaneous mutation.
In what age and sex are AIP attacks most common?
Women aged between 18-40.
What ethnic group is most at risk of which form of porphyria?
Afrikaners in South Africa are more prone to variegate porphyria.
What are the genetic inheritance patterns of the thalassaemias?
They are all autosomal recessive.
What are the 3 different forms of haemoglobin, what chains do they each consist of, and in what percentages are the found on average in most adults?
1) HbA - two alphas, two betas, 97%2) HbA2 - two alphas, two deltas, 2%3) HbF - two alphas, two gammas, less than 1%
Which globin chains are affected by the thalassaemias? Why does this cause a problem? What type of genetic error is at work?
If there is not a balanced 1:1 ratio of alpha and beta globins, the globins precipitate in the mature red cells or their precursors and results in lysis of the cell and ineffective erythropoesis, leading to anaemia.Alpha globulin gene deletions cause alpha thalassaemia, while beta globulin gene mutations result in beta thalassaemia.
What is the prevalence of thalassaemia? Where in the world are the thalassaemias most common?
Worldwide, the prevalence of carriers is around 5% for alpha, around 1.5% for beta.Alpha is most common in Southeast Asia, Africa, and India. Beta is most common in Central and Southern Asia, China, the Middle East, and the Mediterranean.
What globins are haemoglobin comprised of in thalassaemia?
HbH - 4 betas.HbBarts - 4 gammas
In a normal person, how many copies of the gene for the alpha globin do they have?What are the results of differing numbers of these copies being deleted, and what are they called?
1 deletion - alpha plus thalassaemia trait - silent carrier.2 deletions - alpha zero thalassaemia trait - usually a mild microcytosis, with or without anaemia. 3 deletions - thalassaemia intermedia- moderate anaemia, jaundice, splenomegally. HbH disease; HbH (4 betas), HbBarts, as well as HbA, and HbA2. Not usually transfusion dependent.4 deletions - incompatible with life - HbBarts (4 gamma chains) results, causing either stillbirth or death shortly after birth. The infant is pale and oedematous with hepatosplenomegally (hydrops fetalis).
Which forms of alpha thalassaemia can result in a child born of two carriers having thalassaemia alpha major (I.e., incompatible with life)?
Alpha zero thalassaemia; this will not happen if two people who are carriers as alpha zero thalassaemia trait.HbH disease (thalassaemia intmedia) will of course result in offspring who are invariably either carriers, HbH, or HbBarts.
What are the subtypes of beta thalassaemia and what are they caused by?
Beta thalassaemia trait - mutation of one copy of beta.Beta thalassaemia intermedia - mutation of both copies of beta, but less severe.Beta thalassaemia major - mutation of both copies, but more severe.Note that intermedia and major are essentially on a spectrum of severity, unlike the various forms of alpha thalassaemia, which are all discrete.
In beta thalassaemia trait, what is the clinical picture?
Mild microcytosis, with or without anaemia, but essentially symptomless.
What signs may be displayed by someone with beta thalassaemia intermedia or beta thalassaemia major? What determines the severity of the condition, I.e., what determines where on the spectrum they will fall?
The clinical picture is one of anaemia, jaundice, recurrent infections, bony deformities, microcytosis, hepatosplenomegally, and the effects of iron deposits throughout the body.The severity of having both beta genes mutated is influenced by the severity of those mutations, co-inheritance of alpha thalassaemia (which actually makes the picture less severe); hereditary persistence of HbF can also make the picture less severe.
What is thalassaemia beta major also known as? At what age does it usually present and why?
Also known as Cooley’s anaemia.Usually presents at 3-6/12, as this is when the production of HbF is switched off, gamma chains being switched off and the defective beta chains being switched on.
What problems can result from the increased iron absorption and deposition throughout the body in beta thalassaemia major?
Pituitary, thyroid, and adrenal abnormalities.Heart failure from iron deposits in the myocardium.Diabetes.Growth restriction.
What bony deformities may typically develop in beta thalassaemia?
Fontal bossing of the skull, dental malocclusion.
Why might pancytopaenia develop in beta thalassaemia?How is this problem addressed, and which problem does this treatment in turn bring about?
Ineffective erythropoesis results in increased numbers of fragile or damaged red blood cells; this forces the spleen to work overtime, causing it to become huge and overactive (hypersplenism), resulting in cells of many types pooling three and getting munched away to nothing.Splenectomy may ultimately be required, but this of course results in increased risk of infection.
In porphyria, what Ix?
In AIP, urine porphobilinogens are raised during acute attacks, and in 50% of people, they are raised at all times.Genetic analysis may be useful.
Why might patients with thalassaemia be at increased risk of gallstones and gout?
The high rates of haemolysis in these patients can precipitate both of these conditions.
There are many treatments for thalassaemia, but only one cure - what is it?
Stem cell transplant.
What is the life expectancy of someone with thalassaemia?
Thalassaemia HbBarts is incompatible with life.All other forms are compatible with life, but have varying life expectancies; additionally, prognosis for these patients does seem to be improving, due to better treatments and perhaps earlier diagnosis.Carriers of all types have normal life expectancy.HbH disease (alpha thalassaemia alpha intermedia) patients usually live into adulthood, though not always.Beta thalassaemia major - currently, around 80% of patients have a life expectancy exceeding 40yrs (in 1970, they had life expectancy of 17yrs!).
What would the FBC look like in someone with thalassaemia trait, as compared to someone with iron deficiency?What further blood tests would be useful to distinguish between these two possibilities?
In iron deficiency, the Hb would fall in tandem with the MCV and MCH. In thalassaemia trait, a near normal Hb can be expected with a significantly low MCV.Haematinics would be useful - could show if Fe and/or ferritin was low. Haemoglobin electrophoresis would show Hb subtypes and confirm thalassaemia.
A patient with a low MCH is tests for thalassaemia by looking at HbA2 percentages. What level of MCH would prompt his test, and what would the results indicate?
The test could be performed if the MCH is less than 27; if the HbA2 is 3.5% or higher this is suggestive of thalassaemia trait; if the HbA2 is <3.5, this would imply alpha-thalassaemia.
According to NICE, when should haemoglobin variant screening be performed to determine if someone has thalassaemia? If the screening is performed, what else should be done?
Carrier testing and preconception counselling should be performed if a patient comes from a high-prevalence area or if a family origin questionnaire suggests a high risk of thalassaemia carrier status. This is thus an example of a the GP having a role in opportunistically screening for thalassaemia preconception.
Antenatal screening for thalassaemia and sickle cell disease is split into high and low prevalence areas; what is done for each patient group?
High prevalence area - family origin questionnaire + tests for sickle cell! haemoglobin variants, proportion of haemoglobin subtypes, and FBC.Low prevalence area - only a family origin questionnaire and FBC are performed initially. If the father is from a high risk ethnic group, or the results suggest mother is high risk (either due to ethnicity or an MCH less than 27), tests for haemoglobin variants and subtype proportions are carried out.
Other than antenatal screening, what further screening may elicit sickle cell or thalassaemia?
Newborn blood spot test - although it does not routinely screen for thalassaemia, the majority of infants with beta thalassaemia major are identified as a result of sickle cell disease testing.If this test suggests thalassaemia, referral to paediatrician for confirmation is advised.
If a mother is identified as a thalassaemia trait carrier, the father should be tested. However, this may not happen as the father may be a scent or may refuse testing - what should be done then?
Consider chorionic villous sampling. This should also be considered if the father tests positive.
What is the role of antenatal services in thalassaemia?
-Can give counselling to parents-to-be about caring for a child with thalassaemia; the other option is termination if the fetus is +ive.-Can be informed about possibility of pre-implantation genetic testing for future pregnancies (embryo produced in vitro, cells removed for genetic testing, and an embryo which does not have thalassaemia is then selected for implantation).
What infectious organisms are more likely to be responsible for a bacteraemia in a patient with thalassaemia major? Why?What is usually done for these patients to minimise the risk of bacteraemia?
A patient with thalassaemia major may have undergone a splenectomy, making them more vulnerable to encapsulated organisms, e.g., strep. Pneumoniae, neisseria meningitides, or haemophillus influenzae. Also gram -ive organisms such as e-coli, salmonella, or klebsiella.Splenectomy patients thus usually receive pneumococcal, meningococcal, and haemophillus influenzae vaccinations, as well as annual influenza vaccinations, and lifelong prophylactic antibiotics (usually penicillins or macrolides).
Which organism is of especial concern in thalassaemia patients and why?What is the presentation of this infection?How is it treated?
Yersinea enterocolitica, because it thrives in high iron concentrations.Presentation is fever, D&V, abdo pain.Pain is secondary to messenger if adenitis; but can often be mistaken for appendicitis or peritonitis.Rx is usually started prior to culture results with empirical ciprofloxacin; desferrioxaimine should also be withheld until a week after the infection has resolved.
What is a potential explanation for a thalassaemia patient presenting acutely pale, tired, and breathless?
They may be having an aplastic crisis precipitated by parvovirus B19 - this is a transient red cell aplastic crisis; a red cell transfusion may be required with careful monitoring.Hb usually returns to normal after 2/52
In beta thalassaemia and HbH, what is the target Hb that should be aimed for?
Above 9.5
