haematology Flashcards
(142 cards)
1
Q
types of crises in sickle cell disease
A
1) thrombotic crisis (painful crisis)
2) aplastic crisis - no production of rbcs by bone marrow so low reticulocytes
3) acute chest syndrome - chest pain
4) sequestration crisis - rbcs sequestrated in spleen so increased reticulocytes since increased production to compensate for seq.
and more but these are some main
2
Q
what is the pathophysiology and genetics of sickle cell anaemia
A
one HbS allele instead of two HbA alleles so its a autosomal recessive condition (when people only carry it they can develop symptoms but only in severe hypoxia)
3
Q
what population is sickle cell trait more common in
A
in poeple of african descent since it protects against malaria
4
Q
when to sickle cell symptoms develop in life
A
usually at 4-6 months since foetal haemoglobin is replaced by regular haemoglobin in this case with sickle cell deformity
5
Q
diagnostic tool of sickle cell anaemia
A
haemoglobin electrophoresis
usually picked up in newborn blood screen in some countries
6
Q
treatment of sickle cell anaemia
A
pain management (opioids)
antibiotics for stuff like underlying infection in ACS
transfusions
7
Q
what medication should patients be started on to reduce the incidence of complications and acute crises in SCA
A
hydroxycarbamide
8
Q
which is the most common leukemia seen in adults (and rank the rest IN ADULTS)
A
CLL
AML
ALL
CML
9
Q
which is the most common malignancy in children
A
Acute lymphoblastic leukaemia
10
Q
What is the pathology of CLL
A
monoclonal proliferation of well differenciated lymphocytes almost always B cells (99%).
11
Q
features of CLL
A
often none: may be picked up by an incidental finding of lymphocytosis
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than chronic myeloid leukaemia
12
Q
key investigation for CLL
A
mmunophenotyping is the key investigation
most cases can be identified using a panel of antibodies specific for CD5, CD19, CD20 and CD23
13
Q
IMPOrtant investigations for CLL
A
FBC
blood film
immunophenotyping
14
Q
blood film CLL findings
A
smudge cells (also known as smear cells)
15
Q
FBC cll FINDINGS
A
lymphocytosis
anaemia: may occur either due to bone marrow replacement or autoimmune hemolytic anaemia (AIHA)
thrombocytopenia: may occur either due to bone marrow replacement or immune thrombocytopenia (ITP)
16
Q
AML presenting features
A
Features are largely related to bone marrow failure: (often pancytopenia):
anaemia: pallor, lethargy, weakness
neutropenia: whilst white cell counts may be very high, functioning neutrophil levels may be low leading to frequent infections etc
thrombocytopenia: bleeding
splenomegaly
bone pain
17
Q
poor prognostic features of AML
A
> 60 years
20% blasts after first course of chemo
cytogenetics: deletions of chromosome 5 or 7
18
Q
wha is the peak incidence of ALL
A
2-5 YEARS of age
19
Q
features of ALL
A
Features may be divided into those predictable by bone marrow failure:
- anaemia: lethargy and pallor
- neutropenia: frequent or severe infections
- thrombocytopenia: easy bruising, petechiae
And other features
- bone pain (secondary to bone marrow infiltration)
- splenomegaly
- hepatomegaly
- fever is present in up to 50% of new cases (representing infection or constitutional symptom)
- testicular swelling
20
Q
TYPES of ALL and most common one
A
common ALL (75%), CD10 present, pre-B phenotype
T-cell ALL (20%)
B-cell ALL (5%)
21
Q
poor prognostic factors oF ALL
A
age < 2 years or > 10 years
WBC > 20 * 109/l at diagnosis
T or B cell surface markers
non-white ethnicity
male sex
22
Q
investigations in ALL and which confirms diagnosis
A
- full blood count: often shows leucocytosis or sometimes even normal/low WBC, anaemia, thrombocytopenia
- bone marrow biopsy: confirms diagnosis and allows immunophenotyping
- lumbar puncture: assesses for CNS involvement
- additional tests (e.g. imaging) may be used to evaluate extramedullary disease
23
Q
main management of Acute lymphoblastic leukemia and some other aspects
A
chemotherapy
supportive care (e.g. blood product support, infection prophylaxis)
haematopoietic stem cell transplantation in selected high-risk cases
24
Q
CML cause
A
The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML). It is due to a translocation between the long arm of chromosome 9 and 22
The resulting BCR-ABL gene codes for a fusion protein that has tyrosine kinase activity in excess of normal.
25
presentation of CML and age group
anaemia: lethargy
weight loss and sweating are common
splenomegaly may be marked → abdo discomfort
an increase in granulocytes at different stages of maturation +/- thrombocytosis
decreased leukocyte alkaline phosphatase
may undergo blast transformation (AML in 80%, ALL in 20%)
26
what is the management of CML
imatinib is now considered first-line treatment
inhibitor of the tyrosine kinase associated with the BCR-ABL defect
very high response rate in chronic phase CML
hydroxyurea
interferon-alpha
allogenic bone marrow transplant
27
how to classify all lymphomas
hodgkins and non hodgkins
non hodgkins further subclassified into: High grade and low grade (aka aggressive and non aggressive)
AND also if its B cell or T cell lymphoma
28
what is a lymphoma and a hodgkins lymphoma
Lymphoma is the malignant proliferation of lymphocytes which accumulate in lymph nodes or other organs.
Hodgkin's lymphoma is characterized by the presence of Reed-Sternberg cells
29
risk factors of non hodgkins lymphoma
Elderly
Caucasians
History of viral infection (specifically Epstein-Barr virus)
Family history
Certain chemical agents (pesticides, solvents)
History of chemotherapy or radiotherapy
Immunodeficiency (transplant, HIV, diabetes mellitus)
Autoimmune disease (SLE, Sjogren's, coeliac disease)
30
what is the presentation of non hodgin's lymphoma
symptoms;
Painless lymphadenopathy (non-tender, rubbery, asymmetrical)
Constitutional/B symptoms (fever, weight loss, night sweats, lethargy)
Extranodal Disease - gastric (dyspepsia, dysphagia, weight loss, abdominal pain), bone marrow (pancytopenia, bone pain), lungs, skin, central nervous system (nerve palsies)
signs:
Palpable abdominal mass - hepatomegaly, splenomegaly, lymph nodes
Testicular mass
31
what are "B symptoms"
they are constitutional symptoms:fever, weight loss, night sweats, lethargy highly indicative of a lymphoma
and they are called that because if they are present the lymphoma is termed as a "B" lymphoma (meaning higher grade) as opposed to "A"
32
what are symptoms that can differenciate a hodgkins form a non Hodgkins lymphoma clinically
Lymphadenopathy in Hodgkin's lymphoma can experience alcohol-induced pain in the node
'B' symptoms typically occur earlier in Hodgkin's lymphoma and later in non-Hodgkin's lymphoma
Extra-nodal disease is much more common in non-Hodgkin's lymphoma than in Hodgkin's lymphoma
33
what is the diagnostic investigation of choice for a lymphoma
Excisional node biopsy is the diagnostic investigation of choice- this also determines the type
34
what is the investigation of choice to assess the staging of a lymphoma?
ct chest abdo pelvis
35
other invesitgations important for non hodgkins lymphoma
HIV test (often performed as this is a risk factor for non-Hodgkin's lymphoma)
FBC and blood film (patient may have a normocytic anaemia and can help rule out other haematological malignancy such as leukaemia)
ESR (useful as a prognostic indicator)
LDH (a marker of cell turnover, useful as a prognostic indicator)
Other investigations can be ordered as the clinical picture indicates
36
what is the name of the staging tool used in all lymphomas
Lugano staging
37
explain the lugano staging
Stage I: Involvement of a single lymph node region (I) or a single extralymphatic organ or site (IE).
Stage II: Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of an extralymphatic organ or site and one or more lymph node regions on the same side of the diaphragm (IIE).
Stage III: Involvement of lymph node regions on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an extralymphatic organ or site (IIIE), involvement of the spleen (IIIS), or both (IIIE+S).
Stage IV: Diffuse or disseminated involvement of one or more extralymphatic organs, with or without associated lymph node involvement.
In addition to these stages, the classification includes the following:
A/B Symptom Designation: The absence of significant symptoms is designated as 'A', while the presence of fever, night sweats, or weight loss is designated as 'B'.
X: Bulky disease (large tumor mass) is denoted by the letter 'X'.
38
general management principles of non Hodgkins lymphoma
Management is dependent on the specific sub-type of non-Hodgkin's lymphoma and will typically take the form of watchful waiting, chemotherapy or radiotherapy.
Rituximab is used in combination with conventional chemotherapy regimes (e.g. CHOP) for a variety of types of NHL
39
what should patients be screened for before taking rituximab
All patients should be screened for hepatitis B (HBV) before treatment with rituximab as it can cause reactivation of HBV in patients with prior exposure
40
what should patients be monitored for during treatment for non hodgins lymphoma
Patients should also be monitored for cytopenias during treatment
All patients will receive flu/pneumococcal vaccines
Patients with neutropenia may require antibiotic prophylaxis
41
complications of non hodkins lymphoma treatment
Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia
Superior vena cava obstruction
Metastasis
Spinal cord compression
Complications related to treatment e.g. Side effects of chemotherapy
42
prognosis of low and high grade non hodginks lymphoma
Low-grade non-Hodgkin's lymphoma has a better prognosis
High-grade non-Hodgkin's lymphoma has a worse prognosis but a higher cure rate
43
what is the age distribution of Hodgkn's Lymphoma
bimodal age distribution most commonin third and seventh decades
44
risk factors for hodgkins lymphoma
HIV
Epstein-Barr virus
45
presentation of hodginks lymphoma
lymphadenopathy (75%)
most commonly in the neck (cervical/supraclavicular) > axillary > inguinal
usually painless, non-tender, asymmetrical
alcohol-induced lymph node pain is characteristic of Hodgkin's lymphoma but is seen in less than 10% of patients
systemic - 'B symptoms' (25%)
weight loss
pruritus
night sweats
fever (Pel-Ebstein)
other possible presentations include a mediastinal mass
may be symptomatic (e.g. cough) or found incidentally on a chest x-ray
46
incestigations for hodgins lymphoma
normocytic anaemia
may be multifactorial e.g. hypersplenism, bone marrow replacement by HL, Coombs-positive haemolytic anaemia etc
eosinophilia
caused by the production of cytokines e.g. IL-5
LDH raised
lymph node biopsy
Reed-Sternberg cells are diagnostic: these are large cells that are either multinucleated or have a bilobed nucleus with prominent eosinophilic inclusion-like nucleoli (thus giving an 'owl's eye' appearance)
47
management of hodgins lymphoma
chemotherapy is the mainstay of treatment. Two combinations may be used
ABVD considered the standard regime
BEACOPP alternative regime with better remission rates but higher toxicity
radiotherapy
combined modality therapy (CMT):
chemotherapy followed by radiotherapy
hematopoietic cell transplantation:
may be used for relapsed or refractory classic Hodgkin lymphoma
Complications of treatment:
most patients now achieve long-term survival free of Hodgkin's lymphoma with modern therapy
complications of treatment are therefore more of an issue for these patients
secondary malignancies are a risk, in particular solid tumours: breast and lung
48
what is burkitts lymphoma
Burkitt's lymphoma is a high-grade B-cell neoplasm.
49
types of burkitts lymphoma
endemic (African) form: typically involves maxilla or mandible-- epstein barr virus strongly implicated in the development of this form
sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV
50
lymph node excisional biopsy specific finding of burkitt's lymphoma
'starry sky' appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells
51
management of burkit's lymphoma and complcation
Management is with chemotherapy. This tends to produce a rapid response which may cause 'tumour lysis syndrome'
52
complcations of tumour lysis syndrome
hyperkalaemia
hyperphosphataemia
hypocalcaemia
hyperuricaemia
acute renal failure
53
what is gastric malt lymphoma associated with
associated with H. pylori infection in 95% of cases
54
gastric malt lymphoma prognosis
good
not usually very aggressive
55
features of Gastric MALT lymphoma
paraproteinaemia may be present
presence of abnormal monoclonal proteins (immunoglobulins) in the serum
56
what are plasma cells
they are the mature form of b cells
57
what is multiple myeloma
Multiple myeloma (MM) is a haematological malignancy characterised by plasma cell proliferation.
It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells.
58
median age of presentation of MM
70 years old
59
presentation of MM
CRABBI
hypercalcaemia
renal
anaemia
bleeding
bones - pain and increased risk of pathological fractures
infection -
60
other features of multiple myeloma
amyloidosis e.g. macroglossia
carpal tunnel syndrome
neuropathy
hyperviscosity
61
investigations done for MM
BLOODS: FBC anaemia
peripheral blood film: rouleaux formation
u+e: renal failure
bone profile: hypercalcaemia
protein electrophoresis: raised concentrations of monoclonal IgA/IgG proteins will be present in the serum
in the urine, they are known as Bence Jones proteins
Bone marrow aspiration
confirms the diagnosis if the number of plasma cells is significantly raised
IMAGING:
whole body MRI
XRAYS: rain drop skull
62
MAJOR diagnostic criteria for MM
Plasmacytoma (as demonstrated on evaluation of biopsy specimen)
30% plasma cells in a bone marrow sample
Elevated levels of M protein in the blood or urine
63
minor diagnostic criteria for MM
10% to 30% plasma cells in a bone marrow sample.
Minor elevations in the level of M protein in the blood or urine.
Osteolytic lesions (as demonstrated on imaging studies).
Low levels of antibodies (not produced by the cancer cells) in the blood.
64
what combination of major/ minor critdo you need for MM diagnosis
one major and one minor criteria
or three minor criteria
in an individual who has signs or symptoms of multiple myeloma.
65
what is haemophilia + cause
Haemophilia is an X-linked recessive disorder of coagulation.
66
how common is it for haemophilia patients not to have family history of the condition
Up to 30% of patients have no family history of the condition.
67
what are the two types of haemophilia and the difference
Haemophilia A is due to a deficiency of factor VIII whilst in haemophilia B (Christmas disease) there is a lack of factor IX
68
features of haemophilia
haemoarthroses
haematomas
prolonged bleeding after surgery or trauma
69
blood test findings of haemophilia
prolonged APTT
bleeding time, thrombin time, prothrombin time normal
70
what percentage of patients wiht haemophilia develop ab to factor VIII treatment?
Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment.
71
main causes of normocytic anaemia
RECENT bleeding (acute situation) (NOT menorrhagia related- that is microcytic bc its iron def.)
anaemia of chronic disease
72
signs and symptoms of anemia in general
Shortness of breath
Fatigue
Pallor of the conjunctiva
Cold extremities
Increased cardiac output, palpitations, heart murmurs and cardiac failure
Severe anaemia can lead to chest pain and cognitive impairment
73
which test is key in identifying haemoglobinopathies
Haemoglobin Electrophoresis
74
test good at differentiating iron def anemia from other types
peripheral blood smear A blood smear examination allows a closer look at the size, shape, and color of red blood cells. It can provide valuable clues, such as the presence of abnormal cell shapes (spherocytes, schistocytes) or specific inclusions (Heinz bodies).
Iron Studies: Measuring serum iron, ferritin, total iron-binding capacity (TIBC), and transferrin saturation helps diagnose iron-deficiency anaemia and differentiate it from other forms.
75
what are morphological features of macrocytic anaemia on peripheral blood smear
large RBCs due to abnormal RBC development
, giant metamyelocytes
and hypersegmented neutrophils (in the peripheral circulation).
76
causes of megaloblastic anemia
B12 deficiency:
reduced intake (eg. dietary)
reduced absorption (eg. pernicious anaemia,
inflammatory bowel disease, gastrectomy)
Folate deficiency
Drugs
77
drug causing folate def and thus megaloblastic anemia
methotrexate
78
drugs causing megaloblastic anemia
hydroxycarbamide (previously called hydroxyurea)
azathioprine
cytosine arabinoside
azidothymidine
79
Causes of non-megaloblastic/normoblastic macrocytic anaemia
Liver disease
Alcohol
Hypothyroidism
Myelodysplastic syndrome
Pregnancy (usually a mild macrocytosis)
80
symptoms specific to megaloblastic anemia
Glossitis and "Beefy Tongue": , glossitis, is the inflammation of the tongue, giving it a swollen and reddened appearance,
Severe vitamin B12 deficiency can affect the nervous system, leading to neurological symptoms such as paresthesias (tingling and numbness), ataxia (impaired coordination), and cognitive impairment.
81
specific investigations for macrocytic anemia
Haematinics: Serum vitamin B12 and folate levels should be assessed to identify deficiencies.
Blood Film: A peripheral blood smear can show macrocytosis and the presence of hypersegmented neutrophils.
Specific tests to investigate for underlying causes include:
TFTs to look for hypothyroidism
LFTs to assess liver function
Antibodies to intrinsic factor +/- gastric parietal cells, seen in pernicious anaemia
Markers of haemolysis - bilirubin, DAT testing, LDH
82
should vit b12 def or folate def be adressed first and why
address vitamin B12 deficiency before folate replacement (if both are deficient) to avoid exacerbating neurological symptoms and precipitating subacute degeneration of the spinal cord (SACD).
83
iron def anemia specific symptoms
Nail changes such as koilonychia (spoon-shaped nails)
Atrophic glossitis
Angular stomatitis
Pica: Iron-deficiency anaemia may manifest as pica, with cravings for non-food substances like ice (pagophagia) or clay (geophagia).
84
how long do people with iron defeciency anemia take iron for
usually 3 month course
85
side effects of oral iron supplementation
Side effects - diarrhoea, constipation, black stools, abdominal pain, nausea
86
how should iron tablets be taken
Iron supplements should be taken on an empty stomach (preferably one hour before a meal) with a drink containing vitamin C, such as a glass of orange juice or another juice drink with added vitamin C. This aids absorption.
87
which medications absorption is reduced by oral iron
Levothyroxine. Therefore if both are prescribed, advise patients to take at least 4 hours apart.
88
DEFinition of polycythemia
Polycythaemia is characterised by an increase in haematocrit, red cell count, and haemoglobin concentration.
It can be relative, due to low plasma volume, or absolute, where the red cell mass is genuinely increased.
89
median age of presentation of polycythaemia
The median age for presentation is 55–60 years, but polycythaemia can occur at any age.
90
relative polycythaemia causes
Dehydration
Chronic alcohol intake
Excess diuretic use
Pyrexia
Diarrhoea and vomiting
'Stress polycythaemia' refers to relative polycythaemia that is found predominantly in middle-aged men with stressful occupations and chronically reduced plasma volumes of uncertain cause
91
how to tell if polycythemia is absolute and subtypes
If the plasma volume is normal, the polycythaemia is an absolute polycythaemia (red cell mass will be raised).
Absolute polycythaemia is classified into primary and secondary causes.
92
what is primary polycythemia usually caused by
In the majority of cases, it is due to the myeloproliferative condition polycythaemia rubra vera (PRV), which is also known as 'primary proliferative polycythaemia', although there are also some rare familial causes.
93
primary polycythemia pathophysiology
excess and uncontrolled erythrocytosis that is independent of erythropoietin (EPO) levels.
Most cases of PV are associated with mutations in the JAK2 gene, leading to uncontrolled production of blood cells, especially RBCs.
94
pathophysiology in secondary polycythemia
In secondary polycythaemia, the excess RBC production is driven by excess EPO.
95
causes of secondary polycythaemia
- An appropriate rise in EPO, as seen in conditions of chronic hypoxia (e.g. COPD or spending time at high altitude)
- Anabolic steroid use
- Inappropriate secretion of EPO, which may be seen:
- In renal neoplasms as a paraneoplastic effect
- In CKD - impaired renal function can lead to reduced erythropoietin clearance, causing an increase in RBC production
- In cyanotic heart disease (e.g. tetralogy of Fallot)
- In high-affinity haemoglobinopathies (e.g. haemoglobin M)
96
polycythaemia signs and symptoms
Fatigue
Headache
Visual disturbances (secondary to hyperviscosity)
Pruritus (typically after a hot bath)
Erythromelalgia (a painful burning sensation in the fingers and toes)
Arterial thrombosis (eg. myocardial infarction or stroke)
Venous thrombosis (eg. pulmonary embolus or deep vein thrombosis)
Haemorrhage (intracranial or gastrointestinal)- paradoxical increased bleeding risk (due to impaired platelet function)
Increased risk of gout (caused by hyperuricaemia secondary to increased cell turnover).
Facial redness on examination (plethora)
Splenomegaly
Hypertension
Peptic ulceration
97
Specific clinical features of primary polycythaemia:
- Hyperviscosity symptoms: Chest pain, myalgia, weakness, headache, blurred vision, loss of concentration
- 'Ruddy complexion'
- Splenomegaly
98
main findings of polycythemia on FBC
Raised haematocrit
Raised haemoglobin
Raised red cell mass with low/low–normal plasma volume (ie. true polycythaemia)
Raised leukocytes and platelet counts – seen in half of patients
--- In contrast, the neutrophil count and platelet count are usually normal in secondary polycythaemia
99
WHAT other things from bloods may be found in polycythaemia
urate high (thing causing crystals)
vit b12 often high in myeloprolif disease
JAK-2 mutation
hypercellular bone marrow on biopsy
abnormal ultrasound in kidneys liver and spleen
100
what condition is it important to rule out when investigating for polycythemia and how to do so
It is important to exclude chronic myeloid leukaemia, which is done by cytogenetic testing.
101
what is the goal hematocrit for primary and secondary polycythemia
Haematocrit <45% in primary polycythaemia
Haematocrit <55% in secondary polycythaemia
102
polycythemia ruba vera essential management
Regular venesection as above
Aspirin 75mg daily
103
when to offer cytoreductive therapy in polycythemia ruba vera
to suppress erythropoeisis in those where venesection isn't sufficient, or those at high risk of thrombosis (most older patients):
104
Cytoreductive therapy 1st 2nd and 3rd line
1st line: hydroxycarbamide – suppresses erythrocytosis and causes a macrocytosis
2nd line: - Interferon, JAK-2 inhibitors (eg. ruxolitinib)
3rd line: Busulfan can be used but is leukaemogenic.
In younger patients, interferon is first line with hydroxycarbamide second line
105
other potential interventions in polycythemia
Allopurinol (for gout/hyperuricaemia)
Antihistamines, selective serotonin reuptake inhibitors, or interferon (for pruritus)
106
what is myelofibrosis
Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by the gradual replacement of normal bone marrow tissue with fibrous tissue.
This condition results in bone marrow scarring, peripheral blood abnormalities, and enlarged spleen (splenomegaly).
107
how common is myelofibrosis and age
Myelofibrosis is a rare disorder with an estimated annual incidence of 1 to 2 cases per 100,000 individuals.
It typically affects older adults (>65), and there is no significant geographical variation.
108
cause of myelofibrosis
The development of myelofibrosis is closely associated with genetic mutations, including the Janus kinase 2 (JAK2), calreticulin (CALR), and myeloproliferative leukaemia virus oncogene (MPL) mutations.
109
symptoms of myelofibrosis
Constitutional symptoms – weight loss, fever, night sweats
Marrow failure – anaemia, recurrent infection, and abnormal bleeding/bruising
Bone pain
Haemorrhage and thrombosis (less common in myelofibrosis than in other myeloproliferative disorders)
110
signs of myelofibrosis
Splenomegaly (can be massive and painful) – abdominal discomfort, early satiety
Hepatomegaly (seen in 50% of patients)
111
main investigations and findings in myelofibrosis
Blood film typically shows tear-shaped poikilocytes and a leucoerythroblastic blood film
Owing to the marrow fibrosis, it is difficult to aspirate the bone marrow, often resulting in a 'dry tap'
JAK-2 V617F is positive in 50% of cases
112
myelofibrosis management
Myelofibrosis is generally an incurable condition
Allogeneic stem cell transplantation is the one exception – reserved for patients aged <70 years with good performance status and high-risk disease
JAK-2 inhibitors (ruxolitinib) can have a good effect particularly in reducing splenomegaly and treating B symptoms
Cytotoxic agents, immunomodulatory drugs (eg. thalidomide), splenic irradiation and splenectomy can be used as treatments to lessen the need for transfusion and improve symptom control
113
pancytopenia most common pathophysiology + others
decreased marrow haematopoetic function
Inherited causes of marrow failure:
Increased destruction/sequestration of blood cells peripherally: (liver)
Immune destruction of blood cells:
(drugs - eg sulphonamide or rifampicin)
114
Causes of decreased marrow haematopoetic function:
Common causes include chemotherapy and radiotherapy (the pancytopenia may be transient).
Vitamin B12 and folate deficiency.
Marrow infiltration by haematological malignancies (leukaemias or lymphomas).
Myelofibrosis, in which there is progressive marrow fibrosis.
Multiple myeloma (a plasma cell dyscrasia).
Parvovirus infection in haemolytic disease (such as sickle cell anaemia).
115
causes of Increased destruction/sequestration of blood cells peripherally:
This is seen in conditions affecting the liver (such as hepatitis B/C, autoimmune hepatitis, and cirrhosis).
116
what is thalassaemia give a little intro
Thalassaemia is a group of inherited disorders characterised by abnormal haemoglobin production.
Defects in the four genes for α-globin result in α-thalassaemia in the two genes for β-globin result in β-thalassaemia
The clinical severity of the syndrome is proportional to the number of absent or abnormal genes
117
epidemiology of thalassaemia
Mediterranean Europe, Central Africa, the Middle East, the Indian subcontinent and Southeast Asia – having thalassaemia trait is believed to confer some protection against falciparum malaria.
118
inheritance pattern of thalassaemia
autosomal recessive
119
describe the different alpha thalassaemias
If 1 or 2 alpha globulin alleles are affected then the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal
If are 3 alpha globulin alleles are affected results in a hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease
If all 4 alpha globulin alleles are affected (i.e. homozygote) then death in utero (hydrops fetalis, Bart's hydrops)
120
management of alpha thalassaemia
Blood transfusions
Stem cell transplantation
A splenectomy is an option, particularly in patients with HbH disease.
Regular folic acid can also be given, especially in those who are pregnant.
121
types of beta thalassaemia
minor - only one of the two copies of the relevant gene affected - typically asymptomatic
major both gene copies affected
122
features of beta tha;assaemia trait
mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia
HbA2 raised (> 3.5%)
123
which chromosome is alpha globin chains in and which is beta chains
alpha- 16
beta -11
124
beta thalassaemia major presentation
presents in the first year of life
(because levels of HbF, which does not contain β-globin, fall and should be replaced by HbA (made up of two α- and two β-globin chains), which is lacking in β-thalassaemia major)
with failure to thrive and hepatosplenomegaly
microcytic anaemia
HbA2 & HbF raised
HbA absent
125
Management of β-thalassaemia major
Treatment is with regular blood transfusions
The most important long-term consideration in these patients is to reduce the risk of iron overload toxicity
Iron overload can be prevented with iron chelating agents (eg. desferrioxamine/deferiprone/deferasirox)
126
Acute complications of blood transfusions
allergies,
acute haemolytic transfusion reactions,
febrile non-haemolytic transfusion reactions,
transfusion-related acute lung injury,
and transfusion-associated circulatory overload.
127
Late complications to blood transfusion
delayed haemolytic transfusion reaction,
transfusion-associated graft-versus-host disease and
iron overload.
128
Allergy
transfusion reaction
Presentation ranges from urticaria to angioedema and anaphylaxis
Management – stop the transfusion, give saline, adrenaline (in case of anaphylaxis), chlorphenamine, and hydrocortisone
129
Acute haemolytic transfusion reaction
Caused by giving an incompatible blood bag to a patient
Early signs include fever, hypotension and anxiety
Late complications include generalised bleeding secondary to DIC
Management – stop the transfusion, give saline, treat DIC
130
Febrile nonhaemolytic transfusion reaction
Presents with fever, rigors/chills, but patients are otherwise well
Management – Slow the transfusion, give paracetamol
131
Transfusion-related acute lung injury
Presents with pulmonary oedema and can cause acute respiratory distress syndrome (ARDS)
Management – stop the transfusion, give saline, treat ARDS
132
Transfusion-associated circulatory overload
Presents with fluid overload
Management – Slow the transfusion, give furosemide
133
Delayed haemolytic transfusion reaction
Caused by an exaggerated response to a foreign red cell antigen that the patient has been exposed to before
Patients present with jaundice, anaemia, and fever, usually on day 5 post-transfusion
134
Transfusion-associated graft-versus-host disease
Caused by donor blood lymphocytes attacking the recipient's body
Rare but carries a high risk of mortality
135
Iron Overload
transfusion complication
Iron overload usually becomes an issue after 20 units have been given or if serum ferritin rises above 1000 µg/l
Subcutaneous desferrioxamine is required regularly to lower iron levels
136
what disease can give you functional hyposplenism and how commonly
coeliac disease (30%)
137
features of functional hyposplenism
target cells
Howell-Jolly bodies
Pappenheimer bodies
siderotic granules
acanthocytes
138
Iron-deficiency anaemia blood film findings
target cells
'pencil' poikilocytes
if combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells
139
myelofibrosis blood film finding
'tear-drop' poikilocytes
140
Intravascular haemolysis
blood film finding
schistocytes
141
megaloblastic anaemia
hypersegmented neutrophils
142
what medication class are: glimepiride, gliclazide
sulfonylurias
