Haematology Flashcards
1
Q
Hb Value Anaemia - Men and women?
A
Men: <13.5
Women: <11.5
2
Q
Symptoms anaemia?
A
Fatigue Dyspneoa Faintness Palpitations Headache Tinnitus
3
Q
Signs anaemia?
A
May be absent even in severe.
Pallor
Hyperdynamic circulation: Tachycardia, flow murmur (apical ESM), cardiac enlargement
4
Q
Causes microcytic anaemia?
A
Iron-deficiency anaemia = the most common cause:
Thalassaemia (suspect if the mcv is ‘too low’ for the Hb level and the red cell count is raised, though definitive diagnosis needs dna analysis)
Sideroblastic anaemia
NB. Thal and sideroblastic both have increased serum iron and ferritin, with low TIBC (iron accumulation)
5
Q
Would would this suggest?:
microcytic anaemia
increased serum iron and ferritin
low total iron-binding capacity
A
Thalassaemia or Sideroblastic anaemia (iron accumulation)
6
Q
Causes of normocytic anaemia?
A
1 Acute blood loss. 2 Anaemia of chronic disease (or ↓mcv). 3 Bone marrow failure. 4 Renal failure. 5 Hypothyroidism (or ↑mcv). 6 Haemolysis (or ↑mcv) e.g. hereditary spherocytosis 7 Pregnancy.
7
Q
What would this suggest?
Normocytic anaemia
↓wcc or ↓platelets
A
Marrow failure
8
Q
Causes macrocytic anaemia?
A
1 B12 or folate deficiency. 2 Alcohol excess—or liver disease. 3 Reticulocytosis (eg with haemolysis). 4 Cytotoxics, eg hydroxycarbamide. 5 Myelodysplastic syndromes. 6 Marrow infiltration. 7 Hypothyroidism. 8 Antifolate drugs (e.g. phenytoin, methotrexate).
9
Q
What is haemolytic anaemia?
A
Increased RBC breakdown
10
Q
What is reticulocytosis?
A
Anaemia with increased MCV and polychromasia
11
Q
Signs of haemolytic anaemia?
A
Reticulocytosis Mild macrocytosis ↑bilirubin ↑ldh ↑urobilinogen Bile pigment stones Mild jaundice (pre-hepatic) so no bili in urine
12
Q
How would you give a transfusion in severe anaemia with heart failure?
A
SLOWLY
+ 10-40mg furosemide IV/PO with alternate units
Reassess for fluid overload regularly - JVP, basal crackles
13
Q
Causes iron-deficiency anaemia?
A
Blood loss, eg menorrhagia or GI bleeding
Poor diet or poverty in babies or children (but rarely in adults).
Malabsorption (eg coeliac disease) is a cause of refractory ida.
In the tropics, hookworm (gi blood loss) is the most common cause.
14
Q
Signs chronic iron deficiency anaemia?
A
- Koilonychia (spoon-shaped)
- Atrophic glossitis (smooth, painful tongue)
- Angular cheilosis/stomatitis
15
Q
Ix iron deficiency anaemia? + Their results
A
- Blood film: Microcytic, hypochromic. Poikilocytosis (various abnormal shapes RBC). Anisocytosis (variety in RBC sizes)
- Coeliac screen
- Haem studies: ↓ferritin, ↓transferrin saturation, ↑TIBC
NB. Ferritin is acute phase protein so ↑ c infection etc. - Urgent gastroscopy and colonoscopy
16
Q
Mx iron deficiency anaemia? SE of treatment?
A
Ferrous sulphate 200mg PO TDS
SE: GI upset - nausea, diarrhoea/constipation, black stool
Continue for at least three months after Hb normal.
17
Q
What is sideroblastic anaemia?
A
Ineffective erythropoiesis, leading to ↑iron absorption, iron loading in marrow (ringed sideroblasts) ± haemosiderosis (endocrine, liver, and heart damage due to iron deposition).
18
Q
Causes sideroblastic anaemia?
A
- Congenital (rare, x-linked)
- Acquired:
myelo-dysplastic/myeloproliferative diseases
drugs: chemotherapy, anti-TB drugs, irradiation, alcohol or lead excess.
19
Q
Ix sideroblastic anaemia? And results?
A
Blood film: Microcytic hypochromic, ringed sideroblasts in marrow
Plasma: ↑ferritin, ↑iron, ↔ TIBC
20
Q
Mx sideroblastic anaemia?
A
Remove cause
Pyridoxine ± repeated transfusions for severe anaemia
21
Q
What could cause macrocytosis without anaemia?
A
Alcohol
Myeloma (paraproteins)
Hyperglycaemia
22
Q
Causes macrocytosis?
A
Megaloblastic (Impaired DNA synth): B12 and folate deficiency. Cytotoxic drugs: Methotrexate, Phenytoin
Non-megaloblastic: Fatty deposits RBC - EtOH or liver disease, hypothyroidism, pregnancy
23
Q
Causes folate deficiency?
How long do body stores last?
A
- Poor dietary intake
- Increased demand: pregnancy, haemolytic, malignancy
- Malabsorption: Coeliac, Crohns
- Drugs: EtOH, Phenytoin, Valporate, Trimethoprim, Methotrexate
Around 4 months
24
Q
Treatment folate deficiency?
A
Assess underlying cause
Folic acid 5mg/day for 4 months, with B12 unless known normal
25
Why don't you give folate without B12?
In low B12 states can precipitate/worsen subacute combined degeneration cord
26
Causes B12 deficiency?
- Dietary (e.g. vegans - in meat, fish and dairy)
- Malabsorption:
lack of intrinsic factor (IF) - binds B12 in the stomach, enabling it to be absorbed in the terminal ileum.
or problems terminal ileum (ileal resection, Crohn’s disease, bacterial overgrowth, tropical sprue, tapeworms).
- Congenital metabolic errors
27
Features B12 deficiency?
Symptoms anaemia
‘Lemon tinge’ to skin - pallor (anaemia) and mild jaundice (due to haemolysis)
Glossitis (beefy-red sore tongue_
Angular cheilosis
```
Neuro:
Irritability, depression, psychosis, dementia
Peripheral neuropathy
Paraesthesia
Sub-acute combined degeneration cord
```
28
What are the features of subacute combined degeneration of the cord?
Peripheral sensory neuropathy, with both UMN and LMN signs due to ↓B12.
Classic triad:
• extensor plantars (UMN)
• absent knee jerks (LMN)
• absent ankle jerks (LMN).
Symmetrical signs
Insidious onset
Pain and temperature intact (spinothalamic)
Joint-position and vibration sense are often affected first leading to ataxia, followed by stiffness and weakness if untreated.
29
What is pernicious anaemia?
Autoimmune condition, autoAbs to parietal cells. Atrophic gastritis (loss of glandular cells) leads to a lack of IF secretion. Dietary B12 therefore remains unbound and conseqeuently cannot be absorbed by the terminal ileum.
30
Why have a low threshold for upper GI endoscopy in pernicious anaemia?
Stomach carcinoma 3x more common
31
What are the two types of autoimmune haemolytic anaemia?
Warm
Cold
= Optimum binding temperature to RBC
32
```
What class of autoantibody is responsible for warm autoimmune haemolytic anaemia?
What is the optimum temperature?
```
IgG
| Body temperature, 37 degrees
33
```
What class of autoantibody is responsible for cold autoimmune haemolytic anaemia?
What is the optimum temperature?
```
IgM
| <4 degrees
34
Causes warm autoimmune haemolytic anaemia?
Idiopathic
SLE
RA
35
Causes cold autoimmune haemolytic anaemia?
Idiopathic
| Following infection
36
Ix and Mx warm autoimmune haemolytic anaemia?
DAT +ve
Steroids/immunosuppressants
+/- splenectomy
37
Ix and Mx cold autoimmune haemolytic anaemia?
DAT +ve complement only
Keep warm
Cholarmbucil
38
What is paroxysmal cold haemoglobinuria?
| Cause?
Rare. Associated with viruses, esp. measles, mumps, chickenpox
Donath-Landsteiner antibodies stick to RBCs in cold, causing self-limiting haemolysis on rewarming
39
What is paroxysmal nocturnal haemoglobinuria?
Rare, acquired stem cell disorder with haemolysis (esp at night), marrow failure and thrombophilia
40
What is the inheritance of G6PD deficiency? How would you test for it? How long would you need to wait after a crisis to get results?
X-linked
Enzyme assay
>8 weeks as young RBCs may have enough enzyme - normal result
41
What happens in G6PD deficiency attacks? - Why?
What would you see on a film?
What may precipitate an attack?
Oxidative crisis - rapid anaemia and jaundice. Due to ↓glutathione production
Precipitated by: drugs (eg primaquine, sulfonamides, aspirin), exposure to Vicia faba (broad beans/favism), or illness. Henna
Film: Bite and blister cells
42
What is the inheritance of pyruvate kinase deficiency?
| Mechanism?
Autosomal recessive
↓ATP production causes ↓RBC survival. Rigid RBC phagocytosed in spleen.
43
Signs/symptoms pyruvate kinase deficiency?
Homozygotes have neonatal jaundice; later, haemolysis - anaemia with splenomegaly ± jaundice.
44
Ix and Mx pyruvate kinase deficiency?
Ix: Pyruvate kinase assay
Mx: Often not needed. Transfusion or splenectomy
45
What is the inheritance of hereditary spherocytosis?
| Pathophysiology?
Autosomal dominant. Commonest inherited haemolytic anaemia N europe
Path: defect in RBC membrane, less deformable, spherical so get trapped in spleen and haemolysed
46
Signs, Ix and Mx hereditary spherocytosis?
Signs: Splenomegaly, jaundice
Ix: Blood film, DAT (-ve)
Mx: Folate, splenectomy after childhood
47
Inheritance sickle-cell anaemia?
Autosomal recessive
48
What is the mutation in sickle-cell anaemia?
Glu-> Val at position 6 on B chain Hb. Produces HbS instead of HbA
49
What are the different phenotypes sickle-cell anaemia?
| Which are significant?
HbSS - Homozygote
HbAS - Sickle-cell trait. No disability, protective from malaria. - May have symptomatic sickle if hypoxic - unpressurised aircraft or anaesthetic
50
What is the pathogenesis sickle-cell anaemia?
HbS polymerises when deoxygenated - deforms RBC to sickle shape - fragile and haemolyse. Also block small vessels.
51
What Ix in sickle-cell anaemia?
| How would you distinguish between SS and AS?
Blood film: Sickle cells and target cells
Sickle solubility test +ve in both
Hb electrophoresis: confirms diagnosis and distinguishes
52
What is the Mx of a sickle-cell crisis?
```
General:
- Analgesia
- Rehydrate
- O2 as required
- Keep warm
- Abx if raised temp or chest signs
- Crossmatch
Ix:
- Septic screen
- FBC and reticulocyte count
```
Mx:
- Transfuse if required
- Exchange transfusion if severe
53
What would be the indications for exchange transfusion in sickle crisis?
Rapidly worsening
- Severe chest crisis
- Suspected CNS event
- Multiorgan failure
54
What are the triggers of vaso-occulsive crisis in sickle-cell anaemia?
- Infection
- Cold
- Hypoxia
- Dehydration
55
What are the features of vaso-occulsive crisis in sickle-cell anaemia?
```
S splenomegaly
I Infarction: stroke, spleen, AVN, leg ulcers, avascular necrosis fem head, BM
C crises: pulmonary, mesenteric, pain
K kidney disease
L liver, lung disease
E erection
D dactylitis (in young children)
```
56
What is an aplastic crisis in sickle cell?
| Cause?
Sudden reduction in marrow production, due to parvovirus B19.
Usually self-limiting, transfusion PRN
57
Complications of sickle cell?
```
Splenic infarction (<2 years age). Increases infection susceptibility
Poor growth
Chronic renal failure
Gallstones
Retinal disease
Iron overload (transfusions)
Lung disease
```
58
Mx chronic sickle cell?
Hydroxycarbamide if frequent crises (inc HbF)
Pencillin V BD and immunisations - splenic infarction
Folate
59
Causes increased APTT?
Lupus anti-coagulant
| Haemophilia
60
What is a thalassaemia? How does this cause problems?
Underproduction/no production of one globin chain.
| Unmatched globins precipitate, damage RBC membranes leading to haemolytic
61
What is B thalassaemia minor/trait?
| Consequences?
Heterozygous, carrier state.
| Usually asymptomatic - mild, well tolerated anaemia that may worsen in pregnancy
62
What is B thalassaemia intermedia?
| Consequences?
Intermediate state with moderate anaemia, not requiring transfusions.
May be splenomegaly.
- Mild homozygous B mutations
- Co-inheritance of B thal trait with other Hb-opathy e.g. HbC, HbB+ or sickle - B+
63
What is B thalassaemia major?
| Consequences?
Homozygous state. Significant abnormalities both B-globin genes
Presents in 1st year with severe anaemia and failure to thrive.
- Skull bossing
- Hepatosplenomegaly
- Osteopenia
64
Why do you get skull bossing in B thalassaemia major?
Extra-medullary haematopoeisis
65
Mx B thalassaemia major?
```
Regular (2-4 weekly) transfusions
Iron-chelators
Splenectomy as required
Hormone replacement
Marrow transplant is only cure
```
66
What causes the alpha thalassaemias?
Mainly gene deletions
| N: aa/aa
67
In a thalassaemia, what is HbH disease? Consequences?
--/-a - Three alpha gene deletion
Named because of the formation of B tetramers (HbH) on blood film (excess B chains)
Moderate anaemia
Features of haemolysis: hepatosplenomegaly, leg ulcers, jaundice
68
In a thalassaemia, what is the consequence of 1 or 2 gene deletion?
2 gene deletion: --/aa or -a/-a is an asymptomatic carrier state with decreased MCV
Single gene deletion gives a normal clinical state
69
What is the deficiency in Haemophilia A?
| How is it inherited?
Factor VIII
| X-linked recessive
70
How is Haemophilia A diagnosed?
| When and how does it present?
Diagnosis: ↑APTT and ↓factor VIII assay. Normal PT
Presentation variable depending on severity - often early in life or after trauma - bleeds into joints cause crippling arthropathy, bleeds into muscles cause haemotomas
71
Mx Haemophilia A? Major/minor bleeds?
Avoid NSAIDs and IM injections
Minor bleeds: Pressure, elevation. Desmopressin + tranexamic acid
Major: Recombinant factor VIII
72
What is the deficiency in Haemophilia B?
| How is it inherited?
Factor IX deficiency
| X-linked recessive
73
Presentation and Mx Haemophilia B?
Clinically behaves like Haemophilia A.
| Mx: Recombinant factor IX
74
What is acquired haemophilia?
Rare autoimmune bleeding disorder.
| Autoantibodies are most frequently against factor VIII
75
Ix and Mx acquired haemophilia?
↑APPT; ↑VIII autoantibody; FVIII activity <50%
Mx: Steroids
76
What is the impact of liver disease on bleeding?
↓synthesis of clotting factors, ↓absorption of vitamin k, and abnormalities of platelet function.
Increased INR.
77
```
Which of these causes an increase in INR?
Heparin
DIC
Liver disease
Platelet defect
Vit K deficiency
Haemophilia
von Willebrand's
```
Heparin (+)
DIC (++)
Liver disease (+)
Vit K deficiency (++)
78
```
Which of these causes an increase in APTT?
Heparin
DIC
Liver disease
Platelet defect
Vit K deficiency
Haemophilia
von Willebrand's
```
```
Heparin (++)
DIC (++)
Liver disease (+)
Vit K deficiency (+)
Haemophilia (++)
von Willebrands (++)
```
79
```
Which of these causes an increase in thrombin time?
Heparin
DIC
Liver disease
Platelet defect
Vit K deficiency
Haemophilia
von Willebrand's
```
Heparin (++)
DIC (++)
Liver disease (N/+)
80
```
Which of these causes an decrease in platelets?
Heparin
DIC
Liver disease
Platelet defect
Vit K deficiency
Haemophilia
von Willebrand's
```
```
DIC (-)
Liver disease (N/-)
```
81
What are the features of an acute haemolytic reaction to transfusion?
Why might this happen?
What do you do?
ABO incompatibility
Agitation, increased temp, decreased BP, flushing, abdo/chest pain, oozing venepuncture sites, DIC
STOP transfusion. Refer to haem. Send unit and FBC, U&E, cultures, urine to lab. Keep line open with saline.
82
What are the features of an anaphylactic reaction to transfusion?
What do you do?
Bronchospasm
Cyanosis
Reduced BP
Soft tissue swelling
STOP transfusion. Maintain airway and give oxygen.
Get anaesthetist.
83
What is ALL?
What cells does it affect? Pathogenesis?
Who does it affect?
Acute lymphoblastic leukaemia
B (80%) or T (20%) lymphocyte cell lineages - arrests development and promotes uncontrolled proliferation of immature blast cells, with marrow failure and tissue infiltration.
Children, normally 2-5. Rare in adults
84
Give two important associations (causes) ALL?
Ionizing radiation during pregnancy
| Down's syndrome
85
Signs/symptoms of ALL?
Bone marrow failure: anaemia (↓Hb), infection (↓wcc), and bleeding (↓platelets)
Infiltration: hepatosplenomegaly, lymphadenopathy—superficial or mediastinal, orchidomegaly, CNS involvement—eg cranial nerve palsies, meningism.
86
Ix in ALL?
Blood film/bone marrow: blast cells.
Bloods: WCC unusually high, ↓RBC, ↓Platelets
CXR and CT scan - lymphadenopathy
LP - ?CNS involvement
87
Mx ALL?
Supportive: Blood, Allopurinol (prevent tumour lysis syndrome), Hickman line (IV access)
Chemotherapy
Give immediate IV antibiotics and start neutropenic regimen if infection.
88
Prognosis ALL?
| Predictors of poor prognosis?
Cure rates children 70-90%
Adults: 40%
Bone marrow transplants are best option.
Poor prognosis: Adult, male, philadelphia chromosome (t 9-22), presentation with CNS signs, B cell ALL.
89
What is AML? What cells does it affect?
Neoplastic proliferation of blast cells derived from marrow myeloid elements
90
What is the commonest acute leukaemia in adults?
AML
91
What is the prognosis like for AML?
Rapid progression, death in about 2 months if untreated.
| 20% 3 year survival after treatment.
92
Signs and symptoms of AML?
Marrow failure: Anaemia, infection, or bleeding. DIC occurs in acute promyelocytic leukaemia, a subtype of AML.
• Infiltration: Hepatomegaly, splenomegaly, gum hypertrophy, skin involvement. CNS involvement at presentation is rare.
93
How do you differentiate AML from ALL?
On bone marrow biopsy
| AML have auer rods (crystals of coalesced granules) in myeloblast cells
94
What is CML?
| When does it present?
Uncontrolled clonal proliferation of myeloid cells.
| 40-60 years, slightly more commonly in males. Rare in childhood
95
What is the philedelphia chromosome?
| What type of leukaemia is it associated with?
Reciprocal translocation between chromosome 9 and 22.
Present in >80% of those with CML.
NB. CML without Ph has a worse prognosis.
96
Symptoms CML?
Mostly chronic and insidious: ↓weight, tiredness, fever, sweats. There may be features of gout (due to purine breakdown), bleeding (platelet dysfunction), and abdominal discomfort (splenic enlargement). ~30% are detected by chance.
97
Signs CML?
>75% have splenomegaly, often massive.
| Hepatomegaly, anaemia, bruising
98
Treatment of CML?
Imatinib (BCR-ABL tyrosine kinase inhibitor). There are newer -tinibs
99
What is the commonest leukaemia overall?
CLL
100
Signs and symptoms of CLL?
Often no symptoms, found on routine FBC.
May be anaemic or prone to infection, or have ↓weight, sweats, anorexia if severe.
Signs: Enlarged, rubbery, non-tender nodes. Splenomegaly, hepatomegaly.
101
How would you diagnose CML?
| What's wrong with the cells themselves?
↑Lymphocytes—may be marked
Later: autoimmune haemolysis, marrow infiltration: ↓Hb, ↓neutrophils, ↓platelets.
Abnormal lymphocytes accumulate in the blood, bone marrow, spleen, lymph nodes and liver.
Morphologically these lymphocytes have a normal appearance but are immature and nonreactive, resulting in immunological compromise.
102
What is the first line treatment for CML?
Fludarabine + rituximab ± cyclophos-phamide
103
What is the prognosis of CML?
What indicates a worse prognosis?
What usually causes death?
⅓ never progress (or even regress), ⅓ progress slowly, and ⅓ progress actively.
CD23 and β2 microglobulin correlate with bulk of disease and rates of progression.
Death is often due to infection or transformation to aggressive lymphoma (Richter’s syndrome).
104
What cells are seen in Hodgkin's lymphoma?
Reed-sternberg cells (cells with two mirror-image nuclei)
105
What are the incidence and RF for Hodgkin's lymphoma?
Two peaks of incidence, young adults (commonest malignancy in 15–24yr olds) and elderly. ♂:♀ ≈ 2:1.
RF: An affected sibling; EBV; SLE; post-transplantation.
106
Symptoms Hodgkin's lymphoma?
Enlarged, non-tender, ‘rubbery’ superficial lymph nodes (60–70% cervical, also axillary or inguinal). Node size may fluctuate, and they can become matted.
25% have constitutional upset, eg fever, weight loss, night sweats, pruritus, and lethargy.
There may be alcohol-induced lymph node pain.
Mediastinal lymph node involvement can cause mass effect, e.g bronchial or SVC obstruction.
107
Signs of Hodgkins?
Lymphadenopathy.
| Cachexia, anaemia, spleno- or hepatomegaly
108
What investigations would you do in suspected Hodgkin's?
Lymph node excision biopsy.
Bloods: FBC, film, ESR, LDH, urate, Ca2+.
↑ESR or ↓Hb indicate a worse prognosis. LDH is ↑ as it is released during cell turnover.
Imaging: CXR, CT/PET thorax, abdo and pelvis
109
What is the staging system used in Hodgkin's and Non-Hodgkin's?
What are the stages?
Ann Arbour.
I: Confined to single lymph node region.
II: Involvement of two or more nodal areas on the same side of the diaphragm.
III: Involvement of nodes on both sides of the diaphragm.
IV: Spread beyond the lymph nodes, eg liver or bone marrow.
110
What are the 'A' and 'B' symptoms in Hodgkin's? What does this mean?
‘A’—no systemic symptoms other than pruritus
‘B’—presence of B symptoms:
- weight loss >10% in last 6 months
- unexplained fever >38°C
- night sweats (needing change of clothes).
‘B’ indicates worse disease.
111
How is Hodgkin's treated?
| What is the regimen?
Radiotherapy with short courses of chemo for stages I-A and II-A
Longer courses for II-A with >3 areas involved through to IV-B.
ABVD: Adriamycin (doxorubicin), Bleomycin, Vinblastine, Dacarbazine - cures ~80% of patients.
112
SVC obstruction is an emergency. How would it present?
↑JVP, sensation of fullness in the head, dyspnoea, blackouts, facial oedema
113
What is non-Hodgkin's lymphoma?
| What is the most common type?
All lymphomas without Reed-Sternberg cells.
Most are B-cell lines.
Most common: Diffuse large B-cell lymphoma (DLBCL)
114
Causes NH lymphoma?
Immunodeficiency—drugs; HIV (usually high-grade lymphoma from EBV transformed cells; HTLV-1 (Human t-lymphotropic virus); H. pylori; toxins; congenital.
115
Signs/symptoms NH lymphoma?
75% have superficial lymphadenopathy.
50% have extra nodal disease. Gut is commonest site.
Systemic features: fever, night sweats, weight loss (less common than in Hodgkin’s lymphoma, and indicates disseminated disease).
Pancytopenia from marrow involvement—anaemia, infection, bleeding (↓platelets).
116
What tests would you do in NH lymphoma?
Bloods: FBC, U&E, LFT.
↑LDH ≈ worse prognosis, reflecting ↑cell turnover. Marrow and node biopsy for classification.
Imaging: CT ± PET of chest, abdomen, pelvis (for staging).
Send cytology of any effusion; LP for CSF cytology if CNS signs.
117
What are the characteristics of low-grade lymphomas?
Indolent, often incurable and widely disseminated.
118
What are the characteristics of high-grade lymphomas?
Aggressive, but often curable. There is often rapidly enlarging lymphadenopathy with systemic symptoms.
119
What are the poor prognostic signs in NH lymphoma?
| What is the typical prognosis?
```
If at presentation:
- Age >60yrs.
- Systemic symptoms.
- Bulky disease (abdominal mass >10cm).
- ↑LDH
- Disseminated disease.
Typical 5yr survival for treated patients: ~30% for high-grade and >50% for low-grade lymphomas, but the picture is very variable.
```
120
What is pancytopaenia?
Reduction in all the major cell lines: red cells, white cells and platelets.
121
Causes of pancytopenia?
↓Marrow production: Aplastic anaemia, infiltration (eg acute leukaemia, myelodysplasia, myeloma, lymphoma, solid tumours, TB), megaloblastic anaemia, myelofibrosis.
↑Peripheral destruction: Hypersplenism.
122
What is aplastic anaemia?
| What are the causes?
This is a rare (~5 cases per million/year) stem cell disorder in which bone marrow stops making cells, leading to pancytopenia. Presents with features of anaemia (↓Hb), infection (↓wcc), or bleeding (↓platelets).
Causes:
Most cases are autoimmune, triggered by drugs, viruses (eg parvovirus, hepatitis), or irradiation. May also be inherited, eg Fanconi anaemia.
123
How is aplastic anaemia treated?
Mainly supportive in asymptomatic patient.
Blood transfusions as required.
Neutropenic regimen if count <0.5×109/L.
Ideal treatment in young patients with severe disease is allogenic marrow transplant, which can be curative.
Immunosupression with ciclosporin and antithymocyte globulin may be effective, although it is not curative in most.
124
What is agranulocytosis?
| What are the drug causes?
Granulocytes: WBCs with neutrophil, basophil, or eosinophil granules have stopped being made
Drug causes: carbimazole, procainamide, sulfonamides, gold, clozapine, dapsone.
125
What are myeloproliferative disorders?
Clonal proliferation of haematopoietic myeloid stem cells in the bone marrow. These cells retain the ability to differentiate into RBCs, WBCs, or platelets, causing an excess of one or more of these cell types.
126
```
What is the myeloproliferative disorder for each of these cell types?
RBCs
WBCs
Platelets
Fibroblasts
```
RBCs - Polycythaemia rubra vera
WBCs - CML
Platelets - Essential thrombocythaemia
Fibroblasts - Myelofibrosis
127
What is relative polycythaemia?
| What are the causes?
An increased Hb concentration in the blood, due to ↓plasma volume with normal RBC mass.
Acute: Dehydration
Chronic: Obesity, HTN, high alcohol and tobacco intake.
128
What is absolute polycythaemia?
| what and the primary and secondary causes?
An increased Hb concentration in the blood, due to ↑ RBC mass.
Primary: Polycythaemia (rubra) vera
Secondary: Hypoxia (altitude, CLD, cyanotic congenital HD, heavy smoking) or inappropriately ↑erythropoietin secretion (eg in renal carcinoma, hepatocellular carcinoma).
129
What is polycathaemia vera?
| What is the mutation present in most patients?
Excess proliferation of rbcs, wbcs, and platelets, leading to hyperviscosity and thrombosis.
Mutation in JAK2 (JAK2 v617F) present in >95%
130
What is the typical presentation of PRV?
May be asymptomatic and detected on routine FBC.
Or vague symptoms due to hyperviscosity: headaches, dizziness, tinnitus, visual disturbance. Itching after a hot bath, and erythromelalgia (a burning sensation in fingers and toes) are characteristic.
Signs: facial plethora and splenomegaly (in 60%). Gout may occur due to ↑urate from RBC turnover. Features of arterial (cardiac, cerebral, peripheral) or venous (dvt, cerebral, hepatic) thrombosis may be present.
131
What investigations and results would you do in PRV?
FBC: ↑RCC, ↑Hb, ↑HCT, ↑PCV, often also ↑WBC and ↑platelets.
• ↑B12.
• Marrow shows hypercellularity with erythroid hyperplasia.
• Cytogenetics as required to differentiate from CML.
• ↓Serum erythropoietin.
• Raised red cell mass on 51Cr studies and splenomegaly, with normal PaO2, is diagnostic.
132
What is the treatment for PRV?
Keep HCT <0.45 to ↓risk of thrombosis.
- In younger patients at low risk, this is done by venesection. I
- If higher risk (age >60yrs, previous thrombosis), hydroxycarbamide (=hydroxyurea) is used. α-interferon is preferred in women of childbearing age.
Aspirin 75mg daily is also given.
133
What is thrombocytosis?
| What are the causes?
```
Increased platelets ↑ >450 × 109/L. May be reactive:
• Bleeding
• Infection
• Chronic inflammation, eg collagen disorders.
• Malignancy
• Trauma
• Post-surgery
• Iron deficiency
```
134
What are the features of multiple myeloma?
CRAB
- hyperCalcaemia
- Renal failure
- Anaemia (and thrombocytopenia)
- Bone fractures/lytic lesions
135
How is multiple myeloma diagnosed?
Serum or urine electrophoresis - monoclonal band/paraprotein of Ig.
Abnormal proliferation of a single clone of plasma or lymphoplasmacytic cells leads to secretion of Ig or an Ig fragment
136
What test should you always do in >50 with new back pain?
Serum electrophoresis - In case it's caused by multiple myeloma lytic lesions.
137
What Ig products are most common in multiple myeloma?
| How does this make the patient susceptible to infection?
Igg in ~ ⅔; Iga in ~ ⅓; a very few are Igm or Igd.
Other Ig levels are low- ‘immunoparesis’, causing ↑susceptibility to infection.
138
What proteins might you see in the urine in multiple myeloma?
Bence Jones proteins (in ⅔) = free Ig light chains, filtered by the kidney
139
What neutrophil count would indicate neutropenic sepsis? What is this a complication of?
What are the the other signs?
< 0.5 * 10^9
Complication of cancer therapy, particularly chemo.
- Temp higher than 38
140
What would be given as prophylaxis if anticipated that patient is likely to have a neutrophil count of < 0.5 * 10^9??
Fluoroquinolone
141
What is the initial Mx of suspected neutropenic sepsis?
Empirical antibiotic therapy: piperacillin with tazobactam (Tazocin) immediately
142
What drugs can precipitate renal failure in patients with multiple myeloma?
NSAIDs - Ibuprofen, naproxen
143
What would an isolated rise in y-GT indicate?
Alcohol excess
144
If patient is deficient in both B12 and folic acid how do you treat them?
Why?
Give IM B12 and then start oral folic acid when B12 levels are normal.
To prevent subacute combined degeneration of the cord.
145
What is tumour lysis syndrome?
| What is often given before chemotherapy to prevent this occurring?
Rapid response to chemo/spontaneously in those with cancer. Excessive cell lysis ->
- hyperkalaemia
- hyperphosphataemia
- hypocalcaemia
- hyperuricaemia
- acute renal failure
Rasburicase (enzyme catalysing BD uric acid)
146
What are the two forms of Burkitt's lymphoma?
| Which is more common in general, or in patients with HIV?
Two major forms:
- Endemic (African) form: typically involves maxilla or mandible
- Sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV.
147
What gene translocation and virus are associated with Burkitts?
c-myc gene translocation, usually t(8:14)
EBV strongly implicated in development of endemic form, but also to a lesser extent the sporadic.
148
What is transfusion associated lung injury (TRALI)?
Acute onset of non-cardiogenic, bilateral pulmonary oedema and hypoxia - during or within 6 hours of transfusion. Neutrophilic mediated.
PCWP high (N = 7mm systolic, 10mm diastolic).
Patients have antibodies to donor leukocytes.
Will not respond to treatment for pulmonary oedema, i.e. diuretics.
149
What is graft vs. host disease? What would the picture be in blood transfusion?
Associated with transfusion of unirradiated blood in immunosupressed patients. Transfusion associated GVHD can occur 4-30 days after a transfusion, with temperature, erythroderma and desquamation. May also have diarrhoea and abnormal LFTs.
150
What is waldenstrom's macroglobulinaemia?
Uncommon condition generally in older men.
| Lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein.
151
What are the features of waldenstrom's macroglobulinaemia?
Features:
- monoclonal IgM paraproteinaemia
- systemic upset: weight loss, lethargy
- hyperviscosity syndrome e.g. visual disturbance
- hepatosplenomegaly
- lymphadenopathy
- cryoglobulinaemia e.g. Raynaud's
152
What would Howell-Joly bodies suggest?
Hyposplenism - which can occur in sickle cell disease due to splenic infarction
153
What are the 4 types of sickle crisis?
- Thrombotic 'painful crisis'
- Sequestration
- Aplastic
- Haemolytic
154
What is a thrombotic sickle crisis? What might precipitate?
Also known as painful crises or vaso-occlusive crises
Precipitated by:
- infection
- dehydration
- deoxygenation
Infarcts occur in various organs including the bones (e.g. avascular necrosis of hip, hand-foot syndrome in children, lungs, spleen and brain
155
What is a sequestration sickle crisis? What might precipitate?
Sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia.
Acute chest syndrome: dyspnoea, chest pain, pulmonary infiltrates, low pO2 - the most common cause of death after childhood
156
What is an aplastic sickle crisis? What might precipitate?
Aplastic crises = sudden fall in haemoglobin
| Caused by infection with parvovirus
157
What is the threshold for RBC transfusion? What about in acute coronary syndrome?
Without ACS: 70g/dL
| With: 80g/dL
158
In ongoing bleeding, at what platelet value would you give a plt transfusion?
< 30 * 10^9/L
159
Which types of Hodgkin's lymphoma have the best and worse prognoses?
Best: Lymphocyte predominant
Worst: Lymphocyte depleted
160
What drugs can cause haemolysis in G6PD deficiency?
- Anti-malarials: primaquine
- Ciprofloxacin
- Sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
161
What is cryoprecipitate?
| When would you use it?
Factor VIII:C, von Willebrand factor, fibrinogen, Factor XIII and fibronectin.
Clinically it is most commonly used to replace fibrinogen, when 'clinically significant' but not 'major haemorrhage' when <1.5g/L
162
When would you give fresh frozen plasma (FFP)?
'Clinically significant' but not 'major haemorrhage' in patients with a prothrombin time (PT) ratio or activated partial thromboplastin time (APTT) ratio > 1.5
163
What are the causes of massive splenomegaly?
- Myelofibrosis
- Chronic myeloid leukaemia
- Visceral leishmaniasis (kala-azar)
- Malaria
- Gaucher's syndrome
164
What is the treatment once a DVT has been diagnosed?
| How long should this be continued for?
LMWH or fondaparinux initially, continued for 5 days or until INR 2.0 (whichever is longer)
Start warfarin within 24 hours - give concurrently with LMWH. Continue for 3 months if provoked, 6 months if not.
165
What investigations would you do in an unprovoked DVT? Why?
Investigate for cancer.
Examine, routine bloods (FBC, Calcium, LFT), antiphospholipid antibodies, urinalysis, CXR.
If over 40 then CT abdo and pelvis.
Do hereditary thrombophilia screen if there is a significant family history of venous thromboembolisms.
166
What would a 'pepper-pot' skull on skull x-ray suggest?
Multiple myeloma
167
What might you see on a skull x-ray in Paget's disease?
```
Thickened vault
Osteoporosis circumscripta (well defined radiolucent area of lytic lesion)
```
168
What is used in the emergency reversal of (warfarin) anticoagulation in patients with severe bleeding/head injury?
Vitamin K
| PCC (Beriplex)
169
Give 5 causes of microcytic anaemia?
```
Iron Deficiency
Beta-thalassaemia trait
Lead poisoning
Hereditary spherocytosis
Hereditary ellipsocytosis
```
170
Give 5 causes of macrocytic anaemia?
```
B12 deficiency
Folate deficiency
Hypothyroidism
Alcoholism
Haemolytic anaemia (need blood film to presence of schistocytes; has various causes)
```
171
6 causes of eosinophilia?
```
Atopy/allergy
Vasculitis (Churg-Strauss)
Parasitic infection
Hypereosinophilic syndrome
Pregnancy
Myelodysplastic Syndrome
```
172
4 causes of reactive thrombophilia? (inc platelets)
| What causes primary?
Reactive thrombophilia:
- Post operatively
- Infection
- Inflammation
- Infection
Primary thrombophilia: Myelodysplastic Syndrome
173
Differentials neutrophilia?
- Infection
- Vasculitis
- Inflammation
- Malignancy
174
Differentials neutropenia?
- Malignancy (with bone marrow infiltration)
- Iatrogenic
- Overwhelming infection
175
Differentials lymphocytosis?
- Acute viral infection
- Chronic Lymphocytic Leukaemia
- Acute Lymphocytic Leukaemia
- Some lymphomas with very poorly differentiated cells
176
Differentials lymphopenia?
- Iatrogenic causes: corticosteroid use and other medications; chemotherapy
- Infection - viral (common cold, HIV)
- Autoimmune disease - SLE, rheumatoid arthritis
177
Most common inherited thrombophilia?
Factor V leiden (=activated protein C resistance)
178
What is post-thrombotic syndrome?
| What are the features?
Venous outflow obstruction and venous insufficiency resulting in chronic venous hypertension.
- painful, heavy calves
- pruritus
- swelling
- varicose veins
- venous ulceration
179
Triggers of haemolysis in G6PD deficiency?
- anti-malarials: primaquine
- ciprofloxacin
- sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas
180
What is the most common inherited coagulopathy?
Von Willebrand's
181
Features of thrombotic thrombocytopenic purpora?
| Think purple mnemonic.
```
Purple FANTA:
Fever
Anaemia
Neurological (CNS defects)
Thrombocytopenia
AKI
```
Purpura
182
How is hereditary spherocytosis diagnosed?
Osmotic fragility test
183
What are megaloblasts?
Any cell where nuclear maturation is delayed compared with cytoplasm -> hypersegmented. Folate and B12 deficiency.
184
What would enlarged lymph nodes, becoming painful on EtOH ingestion suggest?
Hodgkin's lymphoma.
| Pain occurs in 10%.
185
What is the most common cause of adult death in sickle?
Acute chest syndrome
