Haem - general Flashcards
1
Q
Anaemia in men + women
A
Men Hb <130 g/lWomen Hb <120 g/l
Men: 135-180 g/l (180-135=45)
Women: 115-160 g/l (160-115=45)
2
Q
Alpha defect in thalassaemia on chromosome
A
Chr 16
3
Q
Beta defect in thalassaemia on chromosome
A
Chr 11
4
Q
Sickle cell anaemia inheritance
A
AR
point mutation β globin gene on Chr 11
5
Q
What kind of anaemia does hypothyroidism cause?
A
Macrocytic anaemia which is non-megaloblastic
6
Q
Causes of macrocytic anaemia
A
B12 deficiency deficiency
- Alcohol
- IBD + Coeliac
- Bariatric surgery
- Malnutrition (meat is the predominant source of vit B12)
- Pernicious anaemia (AI loss of parietal cells +/or IF )
Folate deficiency
- Alcohol
- IBD + Coeliac
- Anti-folate drugs
- Pregnancy
Myelodysplasia, hypothyroidism, liver disease, haemolysis, alcohol, B12 deficiency, folate deficiency
7
Q
Causes of HUS
A
- E coli strain EO157:H7
Organisms proliferate in undercooked red meat, unpasteurized milk or milk products, water, fruits, and vegetables.
Rarely - shigella, strep. pneumoniae, genetics
8
Q
Which Von Willebrand Factor cleaving protein (VWFCP) is mutated in thrombotic thrombocytic purpura?
A
ADAMTS-13
Deficiency of VWF cleaving enzyme (ADAMTS-13) –> unusually large VW multimers –> platelet aggregation –> thrombocytopenia + thrombi
9
Q
ITP definition
A
Primary ITP Immune thrombocytopenic purpura
• Autoimmune haematological disorder
• Isolated thrombocytopenia (<100x10^9/L) in the absence of an identifiable cause
• Antibody-mediated destruction of peripheral platelets, antibody-mediated inhibition of platelet production
10
Q
ITP in children
A
Happens following a viral infection or following immunisation (CMV, VZ, HCV, HIV)
11
Q
What is Hodgkin’s Lymphoma?
A
- Uncommon haematological malignancy arsing from mature B cells
- Malignant tumour of the lymphatic system
- Characterised by the presence of Hodgkin’s cells + multinucleated giant cells (Reed-Sternberg cells)*
Happens following an infection
RF • Epstein-Barr virus infection - implicated in around 50% of cases • HIV • Immunosuppression • Smoking • FHx
*Reed strenberg cells = giant cells derived from B lymphocytes containing >2 oval nuclei with eosinophilic nuclei resembling “owl eyes”
12
Q
Hodgkin’s lymphoma epidemiology
A
- Young adults
* Peak in 20-34, second peak in >70
13
Q
Non-Hodgkin’s lymphoma epidemiology
A
- > 50
- M>F
- More common than Hodgkin’s lymphoma
- The 2 most common types of NHL are diffuse large B cell lymphoma and follicular lymphomas
14
Q
Which species causes the most severe malaria?
How is it transmitted?
When do patients present?
A
Plasmodium falciparum
o Transmitted to humans through a bite by an infected female Anopheles mosquito
o Patients present within the 1st month or within the first 6 months of infection
15
Q
What is the myelodysplastic sydrome?
A
- Dysplastic changes in one or more cell lineages
- Ineffective + dysplastic haematopoiesis resulting in 1 or more cytopenias
- Blasts <20%
- Variable predilection to development of acute myeloid leukaemia (AML if blasts >20% (incl 20%))
• The bone marrow
Becomes hypercellular
With disordered growth
Maturation of a clonal proliferation of abnormal cells
16
Q
Extrinsic pathway of the clotting cascade
How is it measured
Normal value
Affected by
A
PT
14s
Warfarin, Liver disease
17
Q
Intrinsic pathway of the clotting cascade
How is it measured
Normal value
Affected by
A
APTT
34s
Heparin, Haemophilias, von Willebrand disease
18
Q
Platelet deficiency causes
A
petechial haemorrhages
Ecchymoses
19
Q
Clotting factor deficiency produces
A
haematomas + hemarthroses
20
Q
Which clotting factor is deficient in haemophilia A?
A
F VIII
21
Q
Which clotting factor is deficient in haemophilia B?
A
F IX
22
Q
How is haemophilia inherited?
A
X-linked recessive disorder
therefore it affects MALES born to carrier mothers
23
Q
Which is the most common haemophilia?Which is the most severe haemophilia?
A
Haemophilia A
24
Q
Pathophysiology of haemochromatosis
A
Deficiency of hepcidin
HFE gene mutations on the short arm of Chr 6
Known mutations of the HFE gene are C282Y and H63D (must be homozygous)
Increased intestnal absorption of iron causes accumulation in tissues , esp liver
This can lead to organ damage
normally hepcidin prevents enterocytes from allowing iron into the hepatic portal system, thereby reducing dietary iron absorption
25
RF for ALL
- Insulation from common infections in early life may predispose children to abnormal immune responses when they encounter them later, placing them at higher risk of developing ALL
26
RF for AML
Radiation
Benzene
Chemo
Constitutional karyotype abnormalities (T21, XXY, T13 (Patau's syndrome)T8:21, inverted 16)
27
RF for CLL
What conditions is it assosicated with?
What can it transform to?
FHx
* Can be associated with AI thrombocytopenia + anaemia
* Can transform to aggressive NHL – Richter’s syndrome
28
RF for CML
T9:22 transolcation --> shortened Chr22 --> Philadelphia chromosome (encodes for a protein with tyrosine kinase activity)
Transolaction places an oncogene (abl) from the long arm of Chr 9 to the long arm of Chr 22 in the BCR region
BCR-ABL - causes an abnormal expansion of the myeloid cells in the BM + peripheral blood
29
Most common leukaemia in children
ALL
| Acute lymphoblastic leukaemia
30
Multiple myeloma definition
Plasma cell disorder
Infiltration of the bone marrow by plasma cells
Presence of a monoclonal immunoglobulin in the serum +/or urine
Classified by the type of ab they produce
IgG myeloma is the most common type
Malignant proliferation of plasma cells that secrete monoclonal antibodies + light immunoglobulin chains
31
What causes renal impairement in multiple myeloma?
Light chains (Bence Jones’ proteins) precipitate out as casts in the distal tubule, causing tubular obstruction + tubulo-interstitial inflammation + AKI
Other causes of renal impairement in patients with myeloma
- Amyloid deposition
- Dehydration
- Hypercalcaemia
- Hyperviscosity
- Nephrotoxic drugs
32
Sickle cell disease pathophysiology
• AR
Amino acid glutamic acid (hydrophilic) is replaced by valine (hydrophobic) at position 6 in the beta globin chain
This causes the RBC to sickle in acidosis, hypoxia, dehydration
Sickling causes vasoocclusion + haemolysis (intravascular + extravascular)
33
On which chromosome are the genes that are mutated in Thalassaemia A?
Chr 16
| Two copies of α genes on each chromosome 16
34
On which chromosome are the genes that are mutated in Thalassaemia B?
Chr 11
| One copy of β gene on each chromosome 11
35
How is thalassaemia inherited and what is the pathophysiology?
AR inheritance
| Deceased/absent synthesis of one of the two polypeptide chains (α or β) that form HbA
36
Function of VWF
o Assists in platelet plug formation by attracting circulating platelets to the site of damage (exposed vascular subendothelium)
o Binds to coagulation factor VIII preventing its clearance from the plasma
37
Difference bn VWD + haemophilia
* VWD F>M (as opposed to haemophilias were Males are always affected)
* In VWD patients might present later in life, in haemophilia the defect is usually apparent in infancy
* VWD usually presents with mucocutaneous bleeding as opposed to haemophilias which present with musculoskeletal bleeding
38
Which are the different types of VWD
o Type 1 - quantitative defect AD, reduced VWF
60-80% of all cases
Normal lifespan
Occasionally easy bruising +/or menorrhagia
Bleeding after dental work, major surgery
o Type 2 - qualitative defect (multimers abnormal or subgroups absent) AD, defective VWF
20-30% of all cases
Bleeding tendency varies
o Type 3 - quantitative defect AR, complete absence of VWF, low FVIII
1-5% of cases
no vWF antigen, low F VIII
Severe mucosal bleeding
May have hemarthrosis (as in haemophilia)
```
I heterozygous (AD) for gene defect, reduced levels of vWF
II normal vWF levels but structurally abnormal
IIA abnormality in synthesis of vWF or with proteolysis
IIB increased function of vWF, leading to spontaneous platelet binding
III homozygous (AR) for gene defect resulting in severe bleeding tendencies
```
39
Classifications of polycythaemia
Primary Polycythaemia vera
Secondary
Appropriate (hypoxia in e.g. COPD, smoking)
Inappropriate (EPO secreting tumour e.g. kidney, hepatocellular carcinomas)
Fluid loss (dehydration, severe burns - decrease in plasma volume causes apparent increase in RBC mass)
40
Polycythaemia vera might evolve into
```
Myelofibrosis (spent phase of PV) (30%)
Secondary AML (5%)
```
41
Which are the 2 phases of PV
Blast phase
BM produces lots of RBC because of JAK2 V617F mutation that stimulates they haematopoietic cell to produce RBC
```
Spent phase
RBC start to die out + form scar tissue within the BM
BM can no longer produce RBC
Anaemia - decreased RBC levels
Thrombocytopenia - decreased plt levels
Leukopenia - decreased WBC levels
This is MYELOFIBROSIS
```
42
PV complications
```
Prone to blood clots
• Stroke
• Heart attack
• DVT
• Budd-Chiari syndrome – when it occurs, it raises suspicion of PV
```
43
Which muatted gene produces antiphospholipid ab?
HLA DR7
44
Antiphospholipid syndrome epidemiology
* Young females
* Venous Thrombosis most common in females – DVT, PE
* Arterial thrombosis most common in males – MI, stroke, limb ischaemia, libman sacks endocarditis (vegetations (mixture of immune cells + blood clots) form on the mitral valve)
* Typical history – young adults (<50) with ischaemic stroke, women with recurrent miscarriages, young patient presenting with arterial thrombosis in any vessel
45
Which factor initiates the clotting process
F VII initiates the clotting process due to tissue damage
46
How to reverse
a) warfarin
b) heparine
warfarin - vitamin K
| Heparin - protamine sulphate
47
Aplastic crisis cause
Parvovirus B19 infection
Sickle cell anaemia
Hereditary spherocytosis
48
Which are the 3 microangiopathic haemolytic anaemias
DIC
TTP
HUS
49
What is promyelocytic leukaemia
* Subtype of AML
* Very aggressive
* T(15;17)
* Associated with DIC
50
Difference bn CLL and CML
CLL
• Accumulation of mature incompetent lymphocytes (unable to undergo apoptosis)
CML
• Uncontrolled proliferation of granulocyte precursors in BM but in slower progression than AML
51
Describe the 3 phases of CML
o Chronic (<5% blasts) - responsive to treatment
o Accelerated – increased BM/peripheral blasts, increased BM/peripheral basophils + eosinophils, resistance to therapy, increased constitutional symptoms, progressive splenomegaly, leucocytosis, thrombocytosis/thrombocytopenia (10-19% blasts)
o Blast crisis/blastic phase – severe constitutional symptoms due to tumour burden (weight loss, fever, night sweats, bone pain) (>20% blasts) [disease progresses into an acute leukaemia usually AML]
52
What is Burkitt's lymphoma
```
Burkitt’s lymphoma
• Subtype of NHL (B cell)
• EBV
• African child
• Large lesion in the jaw (fast growing)
• Under microscopy – starry sky appearance
```
53
What is monoclonal gammopathy of unknown significance
Monoclonal gammopathy of unknown significance
• Pre-malignant condition – accumulation of some monoclonal plasma cells
• 1% acquire additional mutations – MM
• Absent CRAB features
54
What can precipitate DIC?
Sepsis (esp children with meningococcal septicaemia)
Trauma
Obstetric complications
Malignancy
Incompatible blood transfusion, transplant rejection
Severe liver disease, pancreatitis
55
• Anaemia with increased reticulocyte count
vs
• Anaemia with decreased reticulocyte count
• Anaemia with increased reticulocyte count
haemolytic crises
(ddx: haemorrhage) [response to breaking down RBC or losing them]
• Anaemia with decreased reticulocyte count
parovirus B19 infection
aplastic crisis in patients with sickle cell anaemia
blood transfusion
B12 deficiency
56
Dx for normocytic anaemia + reticlocytosis + spherocytosis + jaundice
Haemolytic anaemia due to
a) Hereditary spehrocytosis
b) Autoimmune haemolytic anaemia
(increased reticulocytes suggest haemolysis, spherocytes present in hereditary spherocytosis + autoimmune haemolytic anaemia)
carry out Coomb’s test to differentiate bn the 2 (Coomb’s test positive in autoimmune haemolytic anaemia, negative in spherocytosis)
57
What is aplastic anaemia?
pancytopenia (anaemia + leukocytopenia + thrombocytopenia)
Autoimmune destruction of the hematopoietic stem cells
HLA-DR2
(do not confuse with aplastic crisis that happens in sickle cell disease + hereditary spherocytosis as a result of parvovirus B19 infection – in this case aplastic crisis means BM failure to produce erythrocytes alone)
58
RF for aplastic anaemia
o Genetic disorders – Fanconi’s anaemia (pancytopenia, predisposition to malignancy, short stature, microcephaly, developmental delay, café au lait skin lesions, absent/hypoplastic thumbs)
```
o Environmental agents
-Drugs
chemotherapeutic agents
NSAIDs (indomethacin)
anti-seizure medications
antithyroid medications (propylthiouracil, methimazole)
antibiotics (chloramphenicol, sulphonamides))
-Hepatitis
-Infectious agents (EBV, HIV)
-Toxins (insecticides)
-Industrial agents that contain benzene
-Radiation
```
59
Causes of macrocytic megaloblastic anaemia
o Vitamin B12 deficiency
| o Folate
60
Causes of macrocytic non megaloblastic anaemia
```
(Alcoholics May Have Liver Failure)
o Alcohol
o Liver disease
o Hypothyroid
o Myelodysplasia
o Acute leukaemia
```
61
Tear drop shaped cells
```
Myelofibrosis
Pernicious anaemia
Thalassaemia
Polycythemia vera
ACD
```
62
Bleeding after an infection
Think ITP
Hallmark of ITP - isolated thrombocytopenia
1. FBC - isolated thrombocytopenia
2. Blood film
63
Difference between ITP + TTP
ITP - normal morphology of RBC
| TTP - fragmented RBC - schistocytes
64
A 35-yo man presents with multiple bruises on his arms. He is deeply jaundiced and has recently been found to have gallstones + a dilated biliary tree on US examination
Abnormalities of the following clotting factors are likely to be responsible for his bruising except
```
F II
F VII
F IX
F X
F V
```
F V
Vitamin K - fat soluble vitamin, requires bile salts for absorption
Necessary for the activity of PT, F 2, 7, 9, 10
Deficiency - impaired coagulation activity
65
Von Willebrand factor gene found on Chr
12
66
Relative polycythaemia
vs
Absolute polycythaemia
Relative polycythaemia – normal cell mass but reduced plasma volume
Absolute polycythaemia – increased red cell mass
67
Causes of Microcytic anaemia
```
Microcytic anaemia – TAILS
Thalassaemia
ACD
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
Sideroblastic anaemia – inability of haem synthesis resulting in the inability to incorporate iron in Hb
```
68
Causes of Macrocytic anaemia
```
Macrocytic anaemia
Myelodysplasia
Hypothyroidism
Liver disease
Haemolysis
Alcohol
B12 deficiency
Folate deficiency
```
69
Causes of normocytic anaemia
```
Normocytic anaemia
MR I CAALMM
Marrow failure
Renal failure
Iron deficiency (early)
ACD (early)
Aplastic anaemia
Acute blood loss
Leukaemia
Myelofibrosis
MM
Sickle cell
```
70
What type of anaemia do they cause
Myelodysplasia
Myelofibrosis
MM
Myelodysplasia - macrocytic
Myelofibrosis - normocytic
MM - normocytic
71
Schistocytes present in
Microangiopathy haemolytic anaemias (MAHA) - HUS, DIC, TTP
Macroangiopathic haemolytic anaemias - aortic stenosis, prosthetic heart valves, infections
72
What is the most appropriate investigation to determine iron store levels?
Serum ferritin as it originates from the storage pools in the BM, spleen, liver
Only accurate when CRP levels are normal since ferritin is an acute phase protein
73
Transfusion complications buzzwords
Tissue related lung injury
Immediate haemolytic transfusion reaction
Delayed haemolytic transfusion reaction
IgA deficiency
Febrile non-haemolytic transfusion reaction
Tissue related lung injury
2-6h after tranfusion
fever, hypotension, cyanosis, pulmonary oedema
Immediate haemolytic transfusion reaction
Hypotension, tachycardia, abdominal pain, loin pain, nausea, SOB, pain, fever
<24h (occurs within minutes of transfusion)
Delayed haemolytic transfusion reaction
similar as above
>24h
IgA deficiency
Anaphylactic type reaction
bronchospasm, laryngeal oedema, hypotension
Febrile non-haemolytic transfusion reaction
history of previous blood transfusions, pregnancy
74
How to differentiate between AML + ALL
Sudan black B preferentially stains myeloblasts against lymphoblasts - useful in differentiating between AML + ALL
Sudan black will stain cells in AML but not in ALL
Myeloperoxidase staining
ALL Lack staining for myeloperoxidase
ALL Will not have granules in the cytoplasm (compared to AML)
ALL stains with periodic acid achiff stain
Sudan black B + flow cytometry are the most appropriate ix
75
Leukocyte ALP raised in, low in
Raised in
PCV, myelofibrosis, essential thrombocytopenia
Low in
CML, paroxysmal nocturnal haemoglobinuria
76
EPO + RBC mass in
A. renal failure
B. BM failure
C. RCC
D. Polycythaemia vera
A Low erythropoietin and low red cell mass
B Raised erythropoietin and low red cell mass
C Raised erythropoietin and raised red cell mass
D Low erythropoietin and raised red cell mass
77
Difference bn Aplastic crisis and sequestration crisis
• Aplastic crisis has reduced reticulocytes, whereas sequestration crisis has increased reticulocytes
