Haematology Flashcards
1
Q
Causes of microcytic anaemia
A
iron deficiency anaemia (most common cause of anaemia)
thalassemia
Sideroblastic anaemia
2
Q
Causes of normocytic anaemia
A
Anaemia of chronic disease Acute blood loss Haemolytic anaemia Chronic renal failure combined haematinic deficiency
3
Q
Causes of macrocytic anaemia
A
Vitamin B12 or folate deficiency (megaloblastic anaemia)
excess alcohol
Liver disease
Hypothyroidism
haemolytic anaemia (if presence of high RC)
Haematological diseases beginning with ‘M’: myeloproliferative, myelodysplastic, multiple myeloma
4
Q
Causes of neutrophilia
A
Bacterial infection
Tissue damage (inflammation, infarct, malignancy)
steroids
5
Q
Causes of neutropaenia
A
Viral infection
Chemo or radiotherapy
Carbimazole
Clozapine
6
Q
Causes of lymphocytosis
A
viral infection
Lymphoma
Chronic lymphocytic leukaemia
7
Q
Causes of thrombocytopaenia?
A
reduced production:
- infection (usually viral)
- drugs (esp. penicillamine (e.g. in rheumatoid arthritis treatment))
- myelodysplasia, myelofibrosis, myeloma
Increased destruction:
- heparin
- disseminated intravascular coagulation (DIC)
- idiopathic thrombocytopenic purpura (ITP)
- haemolytic uraemic syndrome/thrombotic thrombocytopenic purpura
8
Q
Causes of thrombocytosis?
A
reactive:
- bleeding
- tissue damage (inflammation, infection, malignancy)
- postsplenectomy
primary:
myeloploriferative disorders
9
Q
What differentiates Hodgkin’s lymphoma from Non-Hodgkin’s lymphoma?
A
Hodgkin lymphoma is marked by the presence of Reed-Sternberg cells. In non-Hodgkin lymphoma, these cells are absent.
10
Q
What are the 4 globin chains found in adult Hb
A
2 alpha globin and 2 beta globin chains
11
Q
What are the 4 globin chains found in fetal Hb
A
2 alpha globin and 2 gamma globin chains
12
Q
What are thalassemias?
A
The thalassaemias are genetic diseases of unbalanced Hb synthesis, with underproduction (or no production) of one globin chain. Unmatched globins precipitate, damaging rbc membranes, causing their haemolysis while still in the marrow. They are inherited in an autosomal recessive pattern.
13
Q
what is the relationship bw MCV and Hb lvls in thalassemias?
A
significant thalassemia causes microcytic anaemia. Usually in thalassemias, the MCV is ‘too low’ for their given Hb level and the red cell count is raised.
14
Q
What are the clinical phenotypes of B Thalassemia?
A
The genes defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in the beta-globin protein at all. Based on this, beta-thalassaemia can be split into three types:-
1. Beta thalassemia minor or trait
2. B thalassemia intermedia
3. B thalassemia major
the severity is not always associated with the genotype
15
Q
B thalassemia minor/trait
A
heterozygous state. carrier state. usually asymptomatic. sometimes mild well tolerated anaemia which may worsen in pregnancy. MCV <75. Hb >90.usually patients only require monitoring and no active treatment.
16
Q
B thalassemia intermedia
A
Thalassaemia intermedica causes a more significant microcytic anaemia and patients require monitoring and occasional blood transfusions. If they need more transfusions they may require iron chelation to prevent iron overload.
17
Q
B thalassemia major
A
Patients with beta thalassaemia major are homozygous for the deletion genes. They have no functioning beta-globin genes at all. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood (important to note doesn’t present immediately after birth though (then alpha thalassemia is more likely)).
it causes -
Severe microcytic anaemia
extramedullary heamatopoiesis (eg skull bossing, malar eminences
hepatosplenomegaly(this also occurs due to haemolysis)).
osteopaenia
Hb F (fetal haemoglobin) will be very high and ferritin will be normal.
18
Q
What is a big SE of lifelong blood transfusions? What is the treatment for this SE?
A
Iron overload. it can affect endocrine organs, liver and the heart. it can be mitigated by using iron chelators (eg desferrioxamine or deferiprone). large amounts of vit C can also help by increasing urinary excretion of Fe.
hormone replacements or other treatment for endocrine complications may be required.
19
Q
Treatment for B thalassemia major
A
lifelong blood transfusions required.
splenectomy (ideally after 5 yrs of age) if hypersplenism persists with increasing transfusion requirements.
histocompatible marrow transplant can offer the chance of a cure.
20
Q
anaemia?
A
reduced red cell mass. dehydration can mask anaemia
21
Q
red cell life span
A
apprx 120 days
22
Q
red cell production site
A
bone marrow
23
Q
red cell removal site
A
spleen
liver
bone marrow
24
Q
RC count relevance in telling whether anaemia is production or removal problem?
A
if RC goes up then removal problem and if RC low then production problem (like bone marrow problem).
25
types of anaemia?
microcytic, normocytic, macrocytic and haemolytic (may be normocytic or, if there are many young (hence larger) rbcs and reticulocytes, macrocytic)
26
general symptoms of anaemia?
fatigue, dyspnoea, faintness, palpitations, headache, anorexia—and angina if there is pre-existing coronary artery disease.
27
If heart failure arises in severe anaemia, what do u need to be careful about?
here, rapid blood transfusion can be fatal.In severe anaemia with heart failure, transfusion is vital to restore Hb to a safe level. Give it slowly with diuretic. Check for signs of worsening overload: rising jvp and basal crackles: in this eventuality, stop and treat.
28
ix for anaemia?
```
Hx and examination
FBC + film
RC count
U/Es, LFTs, TSH
B12, folate and ferritin
```
29
causes of iron deficiency anaemia?
• Blood loss, eg menorrhagia or gi bleeding.
• Poor diet or poverty may cause ida in babies or children.
• Malabsorption (eg coeliac disease) is a cause of refractory ida.
• In the tropics, hookworm (gi blood loss) is the most common cause.
Increased requirement — physiological iron requirements are three times higher in pregnancy
30
S&S of iron def anaemia?
in addition to s&s of anaemia,
```
Pallor
Intermittent claudication
Nail changes, e.g. koilonychia
Angular cheilitis
Atrophic glossitis
```
31
what investigations can confirm fe deficiency
Confirmed by ↓ferritin (also ↓serum iron with ↑tibc, but these are less reliable). Ferritin is an acute phase protein and ↑ with inflammation, eg infection, malignancy.
Blood film: microcytic, hypochromic anaemia with anisocytosis and poikilocytosis.
A serum ferritin level of less than 15 micrograms/L confirms iron deficiency
32
management of iron def anaemia?
New iron deficiency in an adult without a clear underlying cause should be investigated with suspicion. This involves doing a oesophago-gastroduodenoscopy (OGD) and a colonoscopy to look for cancer of the gastrointestinal tract.
Treat the cause.
3 ways to correct anaemia -
1. blood transfusion (will immediately correct the anaemia but not the underlying iron deficiency and also carries risks)
2. parenteral iron (very small risk of anaphylaxis but it quickly corrects the iron deficiency. It should be avoided during sepsis as iron “feeds” bacteria)
3. Oral iron, eg ferrous sulfate se: nausea, abdominal discomfort, constipation, black stools.
When correcting iron deficiency anaemia with iron you can expect the haemoglobin to rise by around 10 grams/litre per week.
33
complications of IDA
Heart failure
Adverse effects on immune status and morbidity from infection
Cognitive and behavioural impairment in children
Impaired muscular performance
34
sign of megaloblastic anaemia on blood films
hypersegmented neutrophils in macrocytic RBCs
35
ix for macrocytic anaemia?
lft, tft, serum b12 (cobalamin), and serum folate (or red cell folate—a more reliable indicator of folate status, as serum folate only reflects recent intake).
36
co-existing B12 and folate deficiency. what shd u do?
treat B12 before folate
37
folate sources
```
broccoli
brussels sprouts
leafy green vegetables, such as cabbage, kale, spring greens and spinach
peas
chickpeas and kidney beans
fortified breakfast cereal
```
38
tx for folate deficiency?
folic acid po for 4 months, NEVER without b12 unless the patient is known to have a normal b12 level!!
Any underlying cause - eg, coeliac disease - should be treated.
39
causes of folate deficiency
DIETARY DEFICIENCY -
1. Malabsorption (eg, coeliac disease, tropical sprue, jejunal resection, inflammatory bowel disease).
2. Poor intake (main cause of folate deficiency)
3. Old age.
4. Alcohol excess (also causes impaired utilisation).
5. Food fads.
EXCESSIVE REQUIREMENT -
1. Physiological (eg, pregnancy, lactation, prematurity and infancy).
2. Malignancy (eg, leukaemia, carcinoma, lymphoma).
3. Blood disorders (eg, haemolytic anaemias, sickle cell anaemia, thalassaemia major,etc).
4. Inflammation (eg, tuberculosis, Crohn's disease, malaria).
EXCESSIVE URINARY EXCRETION -
This includes, for example, congestive heart failure, acute liver damage and chronic dialysis.
ANTIFOLATE DRUGS -
1. With uncertain mechanism of action (eg, anticonvulsants and possibly alcohol and nitrofurantoin).
2. Causing malabsorption of folate (eg, colestyramine, sulfasalazine, methotrexate).
3. Trimethoprim may exacerbate pre-existing folate deficiency but does not cause megaloblastic anaemia.
40
prophylactic folate dose for women wanting to get pregnant?
400 micrograms daily. higher dose of 5mg daily recommended for -
- prev baby with NTD in either partner
- Fhx of NTD in mum
- NTD in either partner
- coeliac disease
- diabetes
- women with BMI>30
41
where is iron mainly absorbed?
duodenum and jejunum
42
what medications can interfere with iron absorption and why?
PPIs. iron requires the acid from the stomach to keep the iron in the soluble ferrous (Fe2+) form. When the acid drops it changes to the insoluble ferric (Fe3+) form. Therefore, medications that reduce the stomach acid such as proton pump inhibitors (lansoprazole and omeprazole) can interfere with iron absorption.
43
name some conditions that can cause inadequate iron absorption
Conditions that result in inflammation of the duodenum or jejunum such as coeliac disease or Crohn’s disease can also cause inadequate iron absorption.
44
what is pernicious anaemia?
Pernicious anaemia is an autoimmune condition where antibodies form against the parietal cells or intrinsic factor. A lack of intrinsic factor prevents the absorption of vitamin B12 and the patient becomes vitamin B12 deficient.
45
symptoms of vitamin B12 deficiency
- neurological symptoms:
Peripheral neuropathy with numbness or paraesthesia (pins and needles)
Loss of vibration sense or proprioception
Visual changes
Mood or cognitive changes
- symptoms of anaemia
- Neuropsychiatric features may include irritability, depression, psychosis and dementia.
46
ix used to test for pernicious anaemia?
Intrinsic factor antibody is the first line investigation
| Gastric parietal cell antibody can also be tested but is less helpful
47
management of pernicious anaemia
1mg of intramuscular hydroxycobalamin 3 times weekly for 2 weeks, then every 3 months. More intense regimens are used where there are neurological symptoms (e.g. 1mg every other day until the symptoms improve).
48
give some causes of vit B12 deficiency
1. insufficient intake
2. pernicious anaemia (most common cause)
3. malabsorption (eg due to coeliac's or IBD)
4. Drugs - eg, colchicine, metformin, anticonvulsants.
5. Long-term use of drugs that affect gastric acid production (eg, H2-receptor antagonists, proton pump inhibitors) can worsen deficiency because gastric acid is needed to release vitamin B12 bound to proteins in food.
49
complications of vitamin B12 deficiency
permanent neurological disability
Severe anaemia causing a risk of cardiopulmonary complications
Subacute combined degeneration of the spinal cord
Vitamin B12 deficiency predisposes to neural tube defects in the fetus.
ineffective production of any type of blood cells derived from bone marrow.
Vitamin B12 or folate deficiency may cause reversible sterility
People with pernicious anaemia are at increased risk of developing gastric cancer
50
causes of haemolytic anaemia
```
inherited -
sickle cell anaemia
thalassaemia
G6PD deficiency
hereditary spherocytosis
hereditary elliptocytosis
```
```
acquired -
autoimmune haemolytic anaemia
alloimune haemolytic anaemia (transfusion reactions and haemolytic disease of the newborn)
Paroxysmal nocturnal haemoglobinuria
Microangiopathic haemolytic anaemia
Prosthetic valve related haemolysis
```
51
common features of haemolytic anaemias
anaemia
splenomegaly
jaundice
52
investigations to test for haemolytic anaemias
Full blood count shows a normocytic anaemia
Blood film shows schistocytes (fragments of red blood cells)
Direct Coombs test is positive in autoimmune haemolytic anaemia
53
what is hereditary spherocytosis
It is an autosomal dominant condition. It causes sphere shaped red blood cells that are fragile and easily break down when passing through the spleen.
54
presentation of hereditary spherocytosis
It presents with jaundice, gallstones, splenomegaly and notably aplastic crisis in the presence of the parvovirus. It is diagnosed by family history and clinical features with spherocytes on the blood film. The mean corpuscular haemoglobin concentration (MCHC) is raised on a full blood count. Reticulocytes will be raised due to rapid turnover of red blood cells.
55
tx for hereditary spherocytosis
Treatment is with folate supplementation and splenectomy. Removal of the gallbladder (cholecystectomy) may be required if gallstones are a problem.
**Hereditary elliptocytosis is very similar to hereditary spherocytosis except that the red blood cells are ellipse shaped. It is also autosomal dominant. Presentation and management are the same.
56
what is G6PD deficiency?
G6PD deficiency is a condition where there is a defect in the red blood cell enzyme G6PD. It is more common in Mediterranean and African patients and is X linked recessive.
57
what can trigger haemolytic crisis in someone with G6PD deficiency
infections, certain medications or fava beans (broad beans).
Medications that trigger haemolysis include primaquine (an antimalarial), ciprofloxacin, sulfonylureas, sulfasalazine and other sulphonamide drugs.
58
presentation of g6pd deficiency
It presents with jaundice (usually in the neonatal period), gallstones, anaemia, splenomegaly and heinz bodies on blood film.
in exams may be smthing like jaundice and anaemia in a patient after eating broad beans, developing an infection or being treated with antimalarials. The underlying diagnosis might be G6PD deficiency.
59
what can be used to diagnose g6pd deficiency
Diagnosis can be made by doing a G6PD enzyme assay.
60
2 types of autoimmune haemolytic anaemia
There are two types based on the temperature at which the auto-antibodies function to cause the destruction of red blood cells.
1. Warm Type Autoimmune Haemolytic Anaemia - more common type. Haemolysis occurs at normal or above normal temperatures. It is usually idiopathic.
2. Cold Type Autoimmune Haemolytic Anaemia - aka cold agglutinin disease. At lower temperatures (e.g. less than 10ºC) the antibodies against red blood cells attach themselves to the red blood cells and cause them to clump together (agglutination). This agglutination results in the destruction of the red blood cells as the immune system is activated against them and they get filtered and destroyed in the spleen. Cold type AIHA is often secondary to other conditions.
61
Cold type AIHA is often secondary to other conditions such as?
```
lymphoma
leukaemia
systemic lupus erythematosus
mycoplasma infectn
EBV infectn
CMV infectn
HIV infectn
```
62
management of AIHA?
Blood transfusions
Prednisolone (steroids)
Rituximab (a monoclonal antibody against B cells)
Splenectomy
63
what is Paroxysmal Nocturnal Haemoglobinuria
rare condition that occurs when a specific genetic mutation in the haematopoietic stem cells in the bone barrow occurs during the patients lifetime. The specific mutation results in a loss of the proteins on the surface of red blood cells that inhibit the complement cascade. this results in activation of the complement cascade on the surface of red blood cells and destruction of the red blood cells.
64
characteristic presentation of paroxysmal nocturnal haemoglobinuria?
red urine in the morning containing haemoglobin and haemosiderin. The patient becomes anaemic due to the haemolysis.
They are also predisposed to thrombosis (e.g. DVT, PE and hepatic vein thrombosis) and smooth muscle dystonia (e.g. oesophageal spasm and erectile dysfunction).
65
Management of paroxysmal nocturnal haemoglobinuria
eculizumab or bone marrow transplantation.
Eculizumab is a monoclonal antibody that targets complement component 5 (C5) causing suppression of the complement system. Bone marrow transplantation can be curative.
66
what is microangiopathic haemolytic anaemia and what are its causes?
Microangiopathic haemolytic anaemia (MAHA) is where the small blood vessels have structural abnormalities that cause haemolysis of the blood cells travelling through them. it is usually 2ndary to an underlying condition such as -
- DIC
- HUS
- TTP
- SLE
- cancer
67
what is prosthetic valve haemolysis, what is the pathophysiology and in brief how is it managed?
Haemolytic anaemia is a key complication of prosthetic heart valves. It occurs in both bioprosthetic and metallic valve replacement.
It is caused by turbulence around the valve and collision of red blood cells with the implanted valve.
```
Management involves:
Monitoring
Oral iron
Blood transfusion if severe
Revision surgery may be required in severe cases
```
68
causes of anaemia of chronic disease?
- malignancy
- infection
- inflammatory disorders
- CKD
69
typically, what is the ferritin status in anaemia of chronic disease? esr status?
normal or raised ferritin
ESR is usually elevated in ACD
70
diagnosis of thalassemia?
Haemoglobin electrophoresis is used to diagnose globin abnormalities.
Full blood count shows a microcytic anaemia and DNA testing can be used to look for the genetic abnormality
Pregnant women in the UK are offered a screening test for thalasseamia at booking.
71
cause of iron overload in pts with thalassemia?
faulty creation of red blood cells, recurrent transfusions and increased absorption of iron in response to the anaemia.
72
complications of iron overload?
```
Fatigue
Liver cirrhosis
Infertility and impotence
Heart failure
Arthritis
Diabetes
Osteoporosis and joint pain
```
73
management of iron overload in pts with thalassemia
Patients with thalassaemia have serum ferritin levels monitored to check for iron overload. Management involves limiting transfusions, and, iron chelation.
74
alpha and beta thalassemia genetic defect is on which chromosome
alpha - chromosome 16
| beta - 11
74
alpha and beta thalassemia genetic defect is on which chromosome
alpha - chromosome 16
| beta - 11
75
what is Hb Barts?
Hb Barts or hydrops foetalis is the most severe form of alpha thalassemia with no functional alpha globin genes. either death in utero or death shortly afterwards.
76
what is sickle cell anaemia
Sickle cell anaemia is a genetic condition that causes sickle (crescent) shaped red blood cells. these are more easily destroyed leading to an haemolytic anaemia.
77
inheritance pattern of sickle cell anaemia
autosomal recessive
there is an abnormal gene for beta-globin on chromosome 11. One copy of the gene results in sickle-cell trait. Patients with sickle-cell trait they are usually asymptomatic. Two abnormal copies are required for sickle-cell disease.
78
what is the realtion bw the sickle cell inheritance and malaria
Sickle cell disease is more common in patients from areas traditionally affected by malaria such as Africa, India, the Middle East and the Caribbean. Having one copy of the gene (sickle-cell trait) reduces the severity of malaria. As a result, patients with sickle-cell trait are more likely to survive malaria and pass on their genes. Therefore, there is a selective advantage to having the sickle cell gene in areas of malaria. This leads to a high proportion of the population in these areas having the gene.
79
when is sickle cell diagnosed?
Sickle cell disease is tested for on the on the newborn screening heel prick test at 5 days of age.
Pregnant women at risk of being carriers of the sickle cell gene are offered testing during pregnancy.
80
complications of sickle cell disease
```
Anaemia
Increased risk of infection
Stroke
Avascular necrosis in large joints such as the hip
Pulmonary hypertension
Painful and persistent penile erection (priapism)
Chronic kidney disease
Sickle cell crises
Acute chest syndrome
```
81
what is the general management of sickle cell disease
Avoid dehydration and other triggers of crises
Ensure vaccines are up to date
Antibiotic prophylaxis to protect against infection with penicillin V (phenoxymethypenicillin)
Hydroxycarbamide can be used to stimulate production of fetal haemoglobin (HbF). Fetal haemoglobin does not lead to sickling of red blood cells. This has a protective effect against sickle cell crises and acute chest syndrome.
Blood transfusion for severe anaemia
Bone marrow transplant can be curative
82
what is sickle cell crises
Sickle cell crisis is an umbrella term for a spectrum of acute crises related to the condition. These range from mild to life threatening. They can occur spontaneously or be triggered by stresses such as infection, dehydration, cold or significant life events.
83
management of sickle cell crises
supportive management
Have a low threshold for admission to hospital
Treat any infection
Keep warm
Keep well hydrated (IV fluids may be required)
Simple analgesia such as paracetamol and ibuprofen
Penile aspiration in priapism
**NSAIDs such as ibuprofen should be avoided where there is renal impairment.
84
what is vaso-occlusive crisis? symptoms? emergency related to it?
Vaso-occlusive crisis is caused by the sickle shaped blood cells clogging capillaries causing distal ischaemia. It is associated with dehydration and raised haematocrit. triggered by cold, dehydration, infection, or hypoxia. Symptoms are typically severe pain, fever and those of the triggering infection. It can cause priapism in men by trapping blood in the penis causing a painful and persistent erection. This is a urological emergency and is treated with aspiration of blood from the penis.
85
what is Splenic Sequestration Crisis, symptoms, consequences and management?
Splenic sequestration crisis is caused by red blood cells blocking blood flow within the spleen. This causes an acutely enlarged and painful spleen. The pooling of blood in the spleen can lead to a severe anaemia and circulatory collapse (hypovolaemic shock). it mainly affects children.
Splenic sequestration crisis is considered an emergency. Management is supportive with blood transfusions and fluid resuscitation to treat anaemia and shock.
Splenectomy prevents sequestration crisis and is often used in cases of recurrent crises. Recurrent crises can lead to splenic infarction and therefore susceptibility to infections.
86
Aplastic Crisis in sickle cell disease?
Aplastic crisis describes a situation where there is a temporary loss of the creation of new blood cells. This is most commonly triggered by infection with parvovirus B19.
It leads to significant anaemia. Management is supportive with blood transfusions if necessary. It usually resolves spontaneously within a week.
87
what is acute chest syndrome in ppl with sickle cell disease?
A diagnosis of acute chest syndrome requires:
Fever or respiratory symptoms with
New infiltrates seen on a chest xray
This can be due to infection (e.g. pneumonia or bronchiolitis) or non-infective causes (e.g. pulmonary vaso-occlusion or fat emboli).
Is a medical emergency with a high mortality and requires prompt supportive management and treatment of the underlying cause:
Antibiotics or antivirals for infections
Blood transfusions for anaemia
Incentive spirometry using a machine that encourages effective and deep breathing
Artificial ventilation with NIV or intubation may be required
88
what is the most common inherited disease in england?
sickle cell disease
89
what is used to confirm the diagnosis of sickle cell disease
Hb electrophoresis
90
what are some causes of bone marrow failure?
Fanconi's anaemia
acute myeloid leukaemia
acute lymphoblastic leukaemia
chronic lymphocytic leukaemia
myelofibrosis
Antineoplastic agents (chemotherapy), and other pharmacological agents (eg, steroids, NSAIDs, allopurinol, anti-thyroid medication
multiple myeloma
Ionising radiation
Viruses (hepatitis B virus, Epstein-Barr virus, parvovirus B19)
Vitamin B12 or folate deficiency causing maturation defects of the cells.
91
presentation of bone marrow failure
Anaemia - tiredness, weakness, pallor, breathlessness, tachycardia.
Neutropenia - recurrent or severe bacterial infections.
Thrombocytopenia - easy bruising, petechiae, bleeding from the nose and/or gums.
92
starting investigations for bone marrow failure?
FBC, reticulocyte count and blood film
from there investigation will be guided by findings from history, examination and that report
93
what is bone marrow failure?
The term ‘bone marrow failure’ encompasses conditions in which there is a primary failure, at the haemopoietic precursor level, to produce one or more of the circulating blood cell lineages.
