Haematology

Question 1

What is a porphyrias?

Answer 1

Disorders caused by defects in the synthesis of haemoglobin. Rare (1:30,000)

Question 2

Precipitating factors for porphyria attacks?

Answer 2

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

Question 3

Clinical features of porphyria (during an acute attack)?

Answer 3

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.

Question 4

Treatment of porphyrias

Answer 4

-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.

Question 5

Porphyrias can be caused by defects affecting which organs?

Answer 5

Liver or bone marrow.

Question 6

What are the different forms of porphyria? Of these, which show photosensitive dermal features?

Answer 6

-Acute intermittent porphyria-Variagate porphyria (shows photosensitivity)-Hereditary coproporphyria (shows photosensitivity)

Question 7

What is the mode of inheritance of the porphyrias?

Answer 7

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.

Question 8

In what age and sex are AIP attacks most common?

Answer 8

Women aged between 18-40.

Question 9

What ethnic group is most at risk of which form of porphyria?

Answer 9

Afrikaners in South Africa are more prone to variegate porphyria.

Question 10

What are the genetic inheritance patterns of the thalassaemias?

Answer 10

They are all autosomal recessive.

Question 11

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?

Answer 11

1) HbA - two alphas, two betas, 97%2) HbA2 - two alphas, two deltas, 2%3) HbF - two alphas, two gammas, less than 1%

Question 12

Which globin chains are affected by the thalassaemias? Why does this cause a problem? What type of genetic error is at work?

Answer 12

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.

Question 13

What is the prevalence of thalassaemia? Where in the world are the thalassaemias most common?

Answer 13

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.

Question 14

What globins are haemoglobin comprised of in thalassaemia?

Answer 14

HbH - 4 betas.HbBarts - 4 gammas

Question 15

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?

Answer 15

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).

Question 16

Which forms of alpha thalassaemia can result in a child born of two carriers having thalassaemia alpha major (I.e., incompatible with life)?

Answer 16

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.

Question 17

What are the subtypes of beta thalassaemia and what are they caused by?

Answer 17

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.

Question 18

In beta thalassaemia trait, what is the clinical picture?

Answer 18

Mild microcytosis, with or without anaemia, but essentially symptomless.

Question 19

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?

Answer 19

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.

Question 20

What is thalassaemia beta major also known as? At what age does it usually present and why?

Answer 20

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.

Question 21

What problems can result from the increased iron absorption and deposition throughout the body in beta thalassaemia major?

Answer 21

Pituitary, thyroid, and adrenal abnormalities.Heart failure from iron deposits in the myocardium.Diabetes.Growth restriction.

Question 22

What bony deformities may typically develop in beta thalassaemia?

Answer 22

Fontal bossing of the skull, dental malocclusion.

Question 23

Why might pancytopaenia develop in beta thalassaemia?How is this problem addressed, and which problem does this treatment in turn bring about?

Answer 23

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.

Question 24

In porphyria, what Ix?

Answer 24

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.

Question 25

Why might patients with thalassaemia be at increased risk of gallstones and gout?

Answer 25

The high rates of haemolysis in these patients can precipitate both of these conditions.

Question 26

There are many treatments for thalassaemia, but only one cure - what is it?

Answer 26

Stem cell transplant.

Question 27

What is the life expectancy of someone with thalassaemia?

Answer 27

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!).

Question 28

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?

Answer 28

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.

Question 29

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?

Answer 29

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.

Question 30

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?

Answer 30

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.

Question 31

Antenatal screening for thalassaemia and sickle cell disease is split into high and low prevalence areas; what is done for each patient group?

Answer 31

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.

Question 32

Other than antenatal screening, what further screening may elicit sickle cell or thalassaemia?

Answer 32

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.

Question 33

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?

Answer 33

Consider chorionic villous sampling. This should also be considered if the father tests positive.

Question 34

What is the role of antenatal services in thalassaemia?

Answer 34

-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).

Question 35

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?

Answer 35

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).

Question 36

Which organism is of especial concern in thalassaemia patients and why?What is the presentation of this infection?How is it treated?

Answer 36

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.

Question 37

What is a potential explanation for a thalassaemia patient presenting acutely pale, tired, and breathless?

Answer 37

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

Question 38

In beta thalassaemia and HbH, what is the target Hb that should be aimed for?

Answer 38

Above 9.5

Question 39

How is iron overload prevented in patients with thalassaemia?What are the side effects of the first line Rx?How is the effectiveness of these measures monitored?

Answer 39

Iron chealating agents.First line agent is injections of desferrioxamine. Side effects (e.g., local injection reactions, hearing loss, colour blindness) may lead to oral alternatives being used.Effectiveness monitored by CT/MRI scanning.

Question 40

What is the difference between primary and secondary haemostasis?

Answer 40

Primary - activation of platelets exposed to damaged vessel walls, mediated by Von Willenbrand factor (activated by tissue factor and binds to collagen, then binds to platelets also).Secondary - tissue factor initiates the coagulation cascade, resulting in activation of thrombin, which in turn activated fibrin (as well as activating more platelets), the fibrin forming a deme network of intercellular bridges.

Question 41

What happens to platelets when they are activated by binding to Avon Willenbrand Factor?

Answer 41

They undergo morphological change to maximise surface area.They release cytoplasmic granules, which activated more platelets and also release growth factors which results in repair of the damaged vessel.They up-regulate membrane receptors that augment clot development.

Question 42

In clotting, which tests are used to look at the effectiveness of the various pathways involved?

Answer 42

The extrinsic pathway - PT - prothrombin time.The intrinsic pathway - aPTT - activated partial thromboplastin time.The common pathway - TT - thrombin time.

Question 43

What is the initial event that activates the extrinsic and intrinsic pathways in clotting? Describe these pathways?

Answer 43

Extrinsic pathway - activated by tissue damage, which leads to exposure of tissue factor (VIIa). This then acts on X in the common pathway, converting it to Xa.Intrinsic pathway - surface contact, which converts XII to XIIa. XIIa converts XI to XIa; XIa converts IX to IXa; IXa works via factor XIII, platelet membrane phospholipid, and calcium ions to activate X to Xa in the common pathway.

Question 44

Describe the events of the common pathway in clotting?

Answer 44

Initial event is production of Xa from X, which can occur by either the intrinsic or extrinsic pathway.Xa in the presence of V, platelet membrane phospholipid, and calcium ions promotes the conversion of prothrombin to thrombin.Thrombin converts fibrinogen to fibrin.Thrombin also promotes formation of XIII.XIII acts on fibrin to form a stable clot.

Question 45

What are the factors that can affect the coagulation cascade? What is the coagulation cascade also known as?

Answer 45

AKA secondary haemostasis.Congenital factors: low factor IX (haemophilia B) or low factor VIII (haemophilia A).Acquired factors: warfarin, LMWH, new anticoagulants (e.g., dabigatran), DIC, vitamin K deficiency, liver disease.

Question 46

What is the role of factor VIII?

Answer 46

In conjunction with platelet phospholipid receptor and calcium ion, allows activated IX (IXa) to convert X to Xa.

Question 47

What is the role of factor IX?

Answer 47

When activated to factor IXa, it acts in the presence of factor VIII, calcium ions, and platelet membrane phospholipid to convert X to Xa

Question 48

What factors can result in problems in primary haemostasis?

Answer 48

1) Platelet affected. | 2 )Von Willenbrand Factor affected. Vessel wall affected.

Question 49

In what ways can platelets be affected resulting in a bleeding disorder?

Answer 49

Thrombocytopenia (e.g., immune thrombocytopenia, bone marrow infiltration (e.g., leukaemia, metastatic malignancy), aplastic anaemia, drug induced thrombocytopenia.Qualitative defect (e.g., anti platelet therapy with aspirin or clopidogrel; renal failure; platelet disorders such as Glanzmann's thrombasthenia).

Question 50

What are the different forms of Von Willenbrand disease?

Answer 50

Type 1 and type 3 are both quantitative disorders (1 is mild and 3 is severe); while type 2 is a qualitative disease.

Question 51

What problems with vessel walls can result in bleeding disorders?

Answer 51

Marian's syndrome.Vasculitis.Hereditary hemorrhagic telangectasia.Senile purpura.

Question 52

What is the inheritance mode of haemophilia A and B?

Answer 52

Both are X-linked recessive; thus they tend to occur almost exclusively in males, and present early in childhood

Question 53

What are the typical symptoms of disorders of platelet function and disorders of Von Willenbrand factors?

Answer 53

Bleeding observed immediately post surgery (failure of platelet plug formation).Primary mucocutanious bleeding, purpura, menorrhagia, recurrent epistaxis, prolonged bleeding following superficial cuts.

Question 54

What are the typical symptoms of disorders of clotting factors?

Answer 54

Delayed bleeding post surgery (platelet plug forms but is not reinforced by fibrin clot).Haemarthrosis.Muscle/soft tissue haematomas.

Question 55

What are the typical bleeding symptoms of a vessel wall disorder?

Answer 55

Mild bleeding symptoms. Predominated by presence of petechiae and bruises. If a vessel wall disorder is suspected, patient should be assessed for other clinical signs associated with connective tissue disorder.

Question 56

What drugs can result in secondary immune thrombocytopenia? (5)

Answer 56

1) Trimethoprim 2) Carbamazepine 3) Sodium valproate 4) Quinine 5) Some homeopathic agents, e.g., omega-3 oils and garlic preparations (especially in patients wig pre-existing mild platelet function disorder).

Question 57

When suspecting a bleeding disorder, what should the examination include?

Answer 57

Mucous membranes.Joints.Stigmata of liver disease.Signs of malignancy (if bone marrow failure suspected).When assessing large bruises, palpate for presence of underlying haematoma.

Question 58

What are the five laboratory tests typically used to look into bleeding disorders?

Answer 58

Platelet count.PT (prothrombin time)aPTT (activated partial thromboplastin time)TT (thrombin time)PFA-100

Question 59

What is PFA-100?What will give falsely high results?

Answer 59

Platelet function analyser; not routinely requested by GPs in the UK. Can be used to look for platelet and Von Willenbrand disorders.Works by subjecting blood to conditions that simulate platelet aggregation and measuring the time taken for a clot to form.Although very sensitive to these disorders, prolonged times (ie, false positives) can result from drugs (aspirin, NSAIDS, clopidogrel), thrombocytopenia, and anaemia.

Question 60

What blood test will be altered in haemophilia?

Answer 60

aPTT will be prolonged.

Question 61

What tests for clotting will be altered in liver disease?

Answer 61

PT, aPTT, and TT are all prolonged.The platelet count can be normal or reduced.The PFA-100 may be prolonged secondary to thrombocytopenia.

Question 62

What tests (other than INR) will be affected by warfarin? (Or by vitamin K deficiency).

Answer 62

PT always prolonged. aPTT and TT may be either normal or prolonged.

Question 63

What tests for clotting will heparin affect?

Answer 63

PT not affected except at high doses (cf warfarin). aPTT and TT both prolonged.

Question 64

Which haematology tests does dabigatran affect?

Answer 64

The aPTT and TT are prolonged, with the PT being less effected.

Question 65

If a severe pancytopaenia is found on FBC in a patient with a suspected bleeding disorder, what follow up test is mandatory and why?

Answer 65

Ix for bone marrow failure, to look for metastatic deposits or for evidence of leukaemia.

Question 66

When a blood film is described as leukoerythroblastic, what does this suggest?

Answer 66

It means that immature blood cells are present in the peripheral blood; they are usually only present in the marrow, and though this picture may be the result of stress such as infection or severe blood loss, it is more likely to represent bone marrow infiltration.Occasionally, peripheral blast cells are seen, and this is highly suggestive of underlying acute leukaemia.

Question 67

What condition are the haemophilias often mistakenly investigated for before the correct diagnosis is reached? Why?

Answer 67

Non-accidental injury. This is because the presentation is often that of a young child (e.g., 15 month old) who has a lot of bruises and prolonged bleeding.

Question 68

What is the median age of onset of symptoms with haemophilia?

Answer 68

Around 9 months, as this coincides with when the child begins to become more mobile and has minor injuries which would not normally result in bruises or bleeds,but do in this child. Haematomas and haemathroses also occur.

Question 69

What proportion of haemophilia A is due to a new spontaneous mutation (in which case, of course, no Fx of the disease will be present)?

Answer 69

25% are due to a new spontaneous mutation.

Question 70

What level of factor VIII represents severe haemophilia A? How are patients with haemophilia A Rx?

Answer 70

<1% factor VIII represents severe disease.Patients are treated with a prophylactic factor VIII regime, patients and cares being taught to administer it IV, usually three times a week, sometimes adapted so that levels are highest before playing sports.

Question 71

How can a patient with haemophilia A self-treat during a minor bleeding episode?

Answer 71

Administration of extra doe of factor VIII and also transexemic acid (an anti-fibrinolytic agent).

Question 72

What is the mode of inheritance of Von Willenbrand disease? What is the difference between type 1 and type 3?

Answer 72

Type 1 is autosomal dominant, and results in a mild reduction in Von Willenbrand factor, with symptoms of a mild bleeding disorder. It has a prevalence of 1% in the general population.Type 3 is autosomal recessive, and is very rare. It results in a total lack of Von Willenbrand factor, and is clinically indistinguishable from haemophilia.

Question 73

How are patients with Von willenbrand's disease Rx?

Answer 73

If mild, then treatment may centre around tranexemic acid when required, and prophylactic measures before surgery or labour.if menorrhagia present, hormonal contraceptives can help.If severe, then replacement with both Von Willenbrand factor and factor VIII may be required.

Question 74

If a viral illness precedes the occurrence of bruises and petechia, especially in children, what should be suspected? What might the FBC show?What questions should be asked to rule out a different condition?

Answer 74

ITP, an immune-mediated destruction of platelets precipitated by a viral infection that results in production of autoantibodies against a patient's own platelets.FBC will likely show a low platelet count.Questions should be asked to establish a definite lack of constitutional symptoms,me.g., bone pain, weight loss, or night sweats, and to check for no lymphadenopathy or splenomegally, as differentials to consider would in such a case would include malignancy.

Question 75

How long will paediatric ITP last? How common is it? What treatment is required?

Answer 75

In children, ITP is quite common and usually lasts around 6 months before resolving spontaneously.If the platelet count is especially low, treatment may be required, though often it is not.Treatment goal is to achieve a platelet count associated with adequate haemostasis.Current guidelines are that if the child has no bleeding or only minor bleeding, observation only.If there is heavier bleeding, a short course of corticosteroids or a single dose of IV immunoglobulins may be used.

Question 76

How are adults with ITP different from children with the condition?

Answer 76

In adults, the condition is much more likely to persist, guidelines suggest Rx be commenced if platelets reach 30 or lower.Longer courses of corticosteroids are preferred over shorter courses or IV immunoglobulin as 1st line,However, IV immunoglobulins should be used in conjunction with corticosteroids when a more rapid increase in platelet count is required.

Question 77

What is the most dangerous subtype of acute myeloid leukaemia and why? How is it Rx?

Answer 77

Acute Promylocytic leukaemia - these patient are at risk of developing DIC rapidly, resulting in consumption of all clotting factors, fibrinogen, and platelets. Patients often suffer intracranial bleeds.It is a medical emergency and urgent initiation of chemotherapy is the only treatment.

Question 78

Are the haemophilias always inherited disorders?

Answer 78

No. Haemophilia A may occasionally develop as an acquired condition due to the formation of antibodies against factor VIII. Usually seen in people over 60; 50% of cases are idiopathic! the remainder are associated with malignancy, autoimmune conditions, and pregnancy. Presentation is often with severe/life threatening bleed.The test for acquired haemophilia A is a prolonged aPTT that does not improve with mixing studies, signalling the presence of an inhibitor.Haematology should be involved early and immunosuppressive Rx commenced.

Question 79

What is the life expectancy of people with haemophilia?

Answer 79

Today, the life expectancy of people with haemophilia is about ten years less than their 'normal' counterparts. This is when considering patient with 'serious' disorders, e.g., Von Willenbrand 3 and haemophilia A. However, as treatments improve over the coming years, this will likely improve for those born today.Mild bleeding disorders should not impact on patients life expectancy.

Question 80

Does HbF or HbA have a greater affinity for oxygen?

Answer 80

foetal - so the mum can offload oxygen to the baby.

Question 81

Which glob in chain does sickle cell affect?

Answer 81

Beta globin. Sickle cell Hb is alpha 2x2 and sickle x2 Sickle globin is a 1 amino acid substitution in the beta glob in gene. If one copy is affected - trait, carrier. If both copies affected - sickle cell disease.

Question 82

Which very common test used in primary care can identify sickle cell carriers or sickle cell patients?

Answer 82

HbA1C --> If it comes up on the electrophoresis as having some level of HBS, then the patient is automatically invited to genetic counselling sessions, to a nurse led clinic. (Note that the GP is notified that this has been found, but the referral happens anyway). Note the ethical dilemma of this! A study in Leicester, however, showed that people were overwhelmingly glad that this testing method is done. Not that it is much more common now that HbA1c is the diagnostic test for diabetes.

Question 83

What is the main problem for sickle cell HB I i.e., HbSS?

Answer 83

Under stressful conditions (e.g., cold, physical stress, dehydration, alcohol, perhaps some medications), the RBC will "sickle" and polymerise and become insoluble. They can then clump together and block up microvasculature --> ischaemia. This is the most common type of a sickle cell crisis - a vasoocclusive crisis.

Question 84

How do you treat a faso-occulisve sickle cell crisis?

Answer 84

1) Warm them up! 2) Haematology referral. 3) Hydration. 4) Examine chest (why?) 5) Patients often carry treatment cards as this condition can be so painful - pethidine, s/c morphine are often used. (Note that there is a lot of problems with opiate addiction and opiate toxicity in sickle cell patients!)

Question 85

What happens to the spleens of most children with sickle cell disease by the age of five? What should they be treated with?

Answer 85

Hyposplenism - not due to splenectomy, but because of multiple splenic infarcts. These patients should receive the annual influenza vaccine, and also vaccinations against encapsulated organisms (H. influenza, N. Meningitidis, and Pneumococcal). They should also be given lifelong prophylactic antibiotics (Pen V unless allergic).

Question 86

Why is it so important to examine the chest and neurology of someone with a sickle cell crisis, and how to treat what you find?

Answer 86

Chest - could be a simple chest infection, but could also be a chest crisis (infiltrates in the chest - parenchymal infiltrates with sickle cells in clumps); they may need critical care - it is a similar condition to ARDS. In this case it is very important t measure sats on and off oxygen. Neurologically - it can cause strokes.

Question 87

Why are people reluctant to transfuse in sickle cell disease (4).

Answer 87

People are very reluctant to transfuse in sickle cell, because: 1) They can tolerate low Hb much better because of a right shift on the disassociation curve of the Hb. 2) Chronic transfusion can lead to Fe overload. 3) They can also have rare antibodies to the blood due to multiple transfusions, giving host and donor transfusion reactions. 4) However, in some severe cases transfusion is unavoidable - and in some crisis situations, and exchange transfusion is performed (redress balance of sickling cells with normal cells).

Question 88

What is an aplastic crisis in sickle cell disease? | What can provoke it?

Answer 88

Can be provoked by parvovirus. In this, the reticulocyte count will go right down as well as the Hb (reticulocytes are usually high in sickle cell disease).

Question 89

What is a sequisation crisis in sickle cell disease?

Answer 89

Blood pools in the spleen - Hb drops by about 2 units (20) as it is all munched up by the spleen.

Question 90

What chronic Rx should sickle cell patients be on?

Answer 90

Folic acid (as the bone marrow is under stress).

Question 91

What is hydroxycarbimide? | Side effects?

Answer 91

A chemotherapy agent - brings down cell counts - in sickle cell, it promotes HbF (rather than HbS; these patients can't have HbA). Also, it has an anti-inflammatory action that can help prevent vasoocclusive crisis. BUT has side effects - cytopanias, neutropaenias, infections - also some people have more need of it than others, have less crises than others.

Question 92

How many main types of leukaemia are there, and what are they called?

Answer 92

Four: 1) Acute Lymphoblastic Leukaemia (ALL) 2) Acute Myeloid Leukaemia (AML) 3) Chronic myeloid Leukaemia (CML) 4) Chronic Lymphocytic Leukaemia (CLL)

Question 93

What cells does acute lymphoblastic leukaemia affect?

Answer 93

It is a malignancy of the lymphoid cells - either B or T lymphocytes - arresting maturation, and promoting uncontrolled proliferation of immature blast cells, with bone marrow failure and tissue infiltration.

Question 94

How does acute lymphoblastic leukaemia develop? What age range is most effected?

Answer 94

It is thought to develop from a combination of genetic susceptibility (e.g., with translocations and gains and losses of whole chromosomes) + an environmental trigger. Important associations are ionising radiation (e.g., X-rays) during pregnancy and Down's syndrome. It is the commonest cancer of childhood and it is rare in adults.

Question 95

What are the signs and symptoms of acute lymphoblastic anaemia?

Answer 95

Bone marrow failure and tissue infiltration lead to anaemia, bruising, bleeding, infection, low true white cell count (though a high count of immature blast cells may be present); also hepato- and splenomegaly, lymphadenopathy, and sometimes CNS involvement - e.g., cranial nerve palsies, meningism.

Question 96

What infections are common in acute lymphoblastic leukaemia?

Answer 96

Chest, mouth, peri-anal, and skin. Bacterial septicaemia can occur, as can herpes zoster, CMV, measles, candidiasis, and pneumocystis pneumonia.

Question 97

What tests for acute lymphoblastic leukaemia?

Answer 97

1) Blood film/bone marrow - characteristics blast cells. 2) FBC - WCC usually high. 3) CXR/CT - mediastinal and abdominal lymphadenopathy. 4) LP - to look for CNS involvement.