1
Q
Amyloidosis Investigations
A
Biopsy of rectum, abdominal fat, or affected organ.
Congo red staining: Apple-green birefringence under polarised light confirms amyloid.
2
Q
AL (Primary) Amyloidosis: causes
A
Caused by plasma cell dyscrasias.
Multiple myeloma
MGUS (Monoclonal gammopathy of undetermined significance)
Waldenström’s macroglobulinaemia
3
Q
Cardiac Complications and Clinical Features
Primary Amyloidosis
A
Restrictive cardiomyopathy
Right heart failure: raised JVP, peripheral oedema
ECG: Low voltage QRS complexes
Echo: Thickened walls with ‘sparkling’ myocardium
4
Q
Thickened walls with ‘sparkling’ myocardium
A
Restrictive cardiomyopathy? In primary amyloidosis
5
Q
Complications and Clinical Features AL (Primary) Amyloidosis
A
Restrictive cardiomyopathy
Peripheral neuropathy:
Nephrotic syndrome:
6
Q
AA (Secondary) Amyloidosis Caused by
A
chronic inflammation or infection
Chronic Infections
Tuberculosis
Bronchiectasis
Autoimmune Diseases
Rheumatoid arthritis
SLE
IBD (Crohn’s disease, ulcerative colitis)
7
Q
low-voltage ECG + sparkling myocardium on echo.
A
AL cardiac involvement: l
8
Q
B12 is absorbed in
A
distal ileum with intrinsic factor
9
Q
folate is absorbed in
A
proximal small bowel.
10
Q
macrocytic RBCs (MCV > 100) with immature nuclei.
A
megaloblastic anaemia
11
Q
Pernicious anaemia
Investigations
A
Anti-parietal cell antibodies (sensitive), Anti-IF antibodies (specific)
12
Q
Drugs causing Pernicious anaemia
A
Metformin, PPIs
13
Q
Crohn’s disease, gastrectomy, giardiasis can cause wat anemia
A
Pernicious anaemia
14
Q
Folate Deficiency Causes
A
Dietary deficiency or excess alcohol
Malabsorption: Coeliac disease, IBD
Drugs: Alcohol, antiepileptics, methotrexate, trimethoprim
15
Q
Drugs causing Folate Deficiency
A
Alcohol, antiepileptics, methotrexate, trimethoprim
16
Q
Angular cheilitis Glossitis
A
Megaloblastic Anaemia
17
Q
Blood film: Hypersegmented neutrophils
A
Folate Deficiency
18
Q
Serum B12: <
A
200 ng/L
If low: check anti-intrinsic factor antibodies
19
Q
Folate: <
A
3 mcg/L
If low: screen for coeliac disease (anti-TTG or EMA antibodies)
20
Q
Management
B12 Deficiency Anaemia
Neurological involvement
A
Specialist input required
Alternate-day IM hydroxocobalamin (1 mg)
21
Q
Management
B12 Deficiency Anaemia
No neurological involvement
A
If loading required: IM hydroxocobalamin 1 mg, three times a week for 2 weeks
Maintenance:
Diet-related: PO cyanocobalamin 50–150 mcg daily
Non-diet-related: IM hydroxocobalamin 1 mg every 2–3 months
22
Q
Folate Deficiency Anaemia mx
A
Oral folic acid 5 mg once daily (usually for 4 months)
Continue longer if cause persists (e.g. alcohol excess, poor diet)
⚠️ Always correct B12 before folate → prevents subacute combined degeneration of the cord
23
Q
avoid precipitating SADC
A
Correct B12 before folate
24
Q
Microcytic (< 80 fL) examples
A
Iron deficiency anaemia
Thalassaemia
Sideroblastic anaemia
Lead poisoning
25
Normocytic (80–100 fL) examples
Anaemia of chronic disease
Acute blood loss
Aplastic anaemia
Red blood cell membrane disorders (hereditary spherocytosis, sickle cell disease)
Haemolytic anaemia
26
Macrocytic (> 100 fL) examples
B12 deficiency (including pernicious anaemia)
Folate deficiency
Alcohol misuse
Liver disease
27
Sideroblastic Anaemia
⚡ Causes
Congenital
delta-aminolevulinate synthase 2 deficiency
28
Sideroblastic Anaemia
⚡ Causes
Acquired
Lead poisoning
Myelodysplastic syndromes
Alcohol use
TB medications (e.g. isoniazid)
29
Reticulocyte count: low
Aplastic Anaemia
30
Bone marrow biopsy: Aplastic Anaemia
<30% cellularity, replaced by fat
31
Investigations anaphylaxixs
Serum tryptase (1–2 hours post-onset): Confirms mast cell activation
Allergy testing: Delayed investigation to identify the specific trigger
32
Adrenaline Dosing (IM 1:1000)
Adults and children > 12 years: 500 micrograms (0.5 mL)
Children 6–12 years: 300 micrograms (0.3 mL)
Children < 6 years: 150 micrograms (0.15 mL)
33
APTT depents on
intrinsic pathway: Factors VIII, IX, XI
34
Investigations Haemophilia
Prolonged APTT (intrinsic pathway: Factors VIII, IX, XI)
Mixing test (1:1 patient:donor plasma) corrects APTT
Normal bleeding time
Normal PT/INR
35
Diagnosis and severity hemophilia a
Factor VIII clotting activity:
Severe: <1%
Moderate: 1–5%
Mild: 6–40%
36
Dx and severity hemophilia b
Factor IX clotting activity:
Severe: <1%
Moderate: 1–5%
Mild: 6–40%
37
Haemophilia C
🧬 Inheritance and Pathophysiology
Autosomal recessive
Factor XI deficiency
38
Acquired Haemophilia
🧬 Pathophysiology
IgG autoantibodies against Factor VIII
Autoimmune conditions (e.g. rheumatoid arthritis, IBD)
Drugs (e.g. phenytoin)
39
Acquired Haemophilia mx
Low antibody titre: Factor VIII replacement
High antibody titre: Immunosuppression (e.g. corticosteroids)
40
most common inherited bleeding disorder.
Von Willebrand's Disease (VWD)
41
🧬 Von Willebrand's Disease (VWD)
🧬 Pathophysiology
Autosomal dominant
Deficiency or dysfunction of von Willebrand Factor (VWF)
VWF mediates platelet adhesion during primary haemostasis, and carries Factor VIII, protecting it from degradation
42
Investigations
🧬 Von Willebrand's Disease (VWD)
Prolonged bleeding time
Mildly prolonged APTT
Reduced Factor VIII activity
Diagnosis: PFA-100 test (platelet function analysis) > 95% sensitivity
43
Von Willebrand's Disease (VWD) mx
Mild bleeding: Tranexamic acid
Procedural prophylaxis: desmopressin (releases stored VWF)
Severe: Factor VIII concentrate
44
Dic Investigations
Prolonged APTT, PT/INR, and bleeding time
Thrombocytopenia (consumption)
Low fibrinogen (consumption)
Blood film: Schistocytes (fragmented RBCs)
45
clotting times prolonged + low fibrinogen + schistocytes
Dic
46
Cisplatin Electrolyte abnormalities:
hypomagnesaemia, hypokalaemia, hypocalcaemia
47
dry cough and exertional dyspnoea in a patient post chemo
Bleomycin
Pulmonary fibrosis
48
Cyclophosphamide
Haemorrhagic cystitis
Caused by
toxic metabolite acrolein
49
Mesna
binds and detoxifies acrolein in urine)
For Cyclophosphamide cysyitis
50
Puffy face + hyperglycaemia
dexamethasone
51
If DVT Likely (Wells score ≥2)
Offer proximal leg vein ultrasound within 4 hours
If not available within 4 hours:
Check D-dimer
Start interim anticoagulation
Arrange scan within 24 hours
52
DVT Unlikely (Wells score ≤1)
Offer D-dimer
If not available within 4 hours:
Offer interim anticoagulation
53
Interim Anticoagulation If DOACs not suitable
LMWH for at least 5 days
Transition to longer-term anticoagulation (e.g. warfarin, or continue LMWH)
Continue LMWH until INR >2
Pregnancy: LMWH is anticoagulant of choice
End-stage renal failure (ESRF): Warfarin preferred
54
End-stage renal failure (ESRF): Interim Anticoagulation
warfarin
55
🩸 Sickle Cell Disease
🧬 Genetics and Pathophysiology
Autosomal recessive
Mutation in the β-globin gene on chromosome 11
Glutamate is replaced by valine at codon 6 → HbS
HbS polymerises when deoxygenated → sickling of RBCs
56
Investigations 🩸 Sickle Cell Disease
Newborn screening (UK)
FBC: Normocytic, normochromic anaemia
Blood film: Howell-Jolly bodies, target cells (hyposplenism)
Reticulocytosis
Haemoglobin electrophoresis
57
Gold standard diagnostic investigation 🩸 Sickle Cell Disease
Haemoglobin electrophoresis
58
Management 🩸 Sickle Cell Disease
Hydroxycarbamide: increases HbF, reduces crises
Prophylactic penicillin V
Pneumococcal vaccine every 5 years
59
Most common cause of death 🩸 Sickle Cell Disease
Acute chest syndrome
60
Sudden anaemia with low reticulocyte count
Often triggered by parvovirus B19
Aplastic crisis
61
Hyposplenism mx
lifelong prophylactic penicillin
62
Thalassaemia
🧬 Pathophysiology
Inheritance: Autosomal recessive
Defective globin chain synthesis → imbalance → ineffective erythropoiesis and haemolysis
63
), 2 alpha + 2 gamma
(HbF)
64
Alpha-Thalassaemia
🧬 Genetics
Mutation/deletion in alpha-globin genes (chromosome 16)
65
the phenotype/disease of alpha thalassaemia is determined by the number of defective alpha genes:
1 gene deletion: Silent carrier
2 gene deletion: Alpha-thalassaemia trait → microcytosis
3 gene deletion: HbH disease → microcytic anaemia, splenomegaly
4 gene deletion: Hydrops fetalis (Hb Barts) → usually fatal in utero
66
Beta-Thalassaemia
🧬 Genetics
Mutation in β-globin gene (chromosome 11)
67
significant microcytosis, which is disproportionate to the level of anaemia.
Beta-thalassaemia minor (trait)
One normal β-globin gene
68
May develop anaemia during stress or pregnancy
Beta-thalassaemia intermedia
69
Cooley’s anaemia)
Beta-thalassaemia major (Cooley’s anaemia)
No functional β-globin production
Presents age 6–24 months: failure to thrive, pallor, hepatosplenomegaly
Signs: severe microcytic anaemia, skull bossing, jaundice, extramedullary haematopoiesis
70
Management thalassemia
Regular blood transfusions
Iron overload management with chelation therapy (e.g. subcutaneous desferrioxamine)
71
Skull bossing
beta-thalassaemia major (due to bone marrow expansion)
72
Acute anaemia + low reticulocytes
parvovirus-induced aplastic crisis
73
Microcytic anaemia + normal iron
think thalassaemia
74
Heinz bodies + bite cells
G6PD deficiency
75
Jaundice + splenomegaly + family history =
hereditary spherocytosis
76
Morning haemoglobinuria + thrombosis =
think PNH
77
Gallstones may develop with chronic
haemolysis
78
Investigating Haemolytic Anaemia
Low haemoglobin + elevated bilirubin
Raised LDH
Reticulocytosis → raised MCV
Direct Coombs Test (DCT):
Indirect Coombs Test:
Schumm Test: measures methemalbumin → increased in intravascular haemolysis
79
Schumm Test:
measures methemalbumin → increased in intravascular haemolysis
80
Intravascular Haemolysis Findings
Elevated bilirubin
Schumm test positive
81
Intravascular Haemolysis
Causes
Cold autoimmune haemolytic anaemia (IgM)
Acute haemolytic transfusion reaction
Paroxysmal nocturnal haemoglobinuria (PNH)
G6PD deficiency
Mechanical trauma: prosthetic valves, haemolytic uraemic syndrome
82
Extravascular Haemolysis
Findings
Normal methemalbumin (Schumm test negative)
83
Causes Extravascular Haemolysis
Sickle cell disease
Thalassaemia
Hereditary spherocytosis
Haemolytic disease of the newborn
Warm autoimmune haemolytic anaemia (IgG
84
IgG-mediated autoimmune haemolytic anaemia
Warm AIHA
85
Warm AIHA Blood film
spherocytes
86
Warm AIHACauses
SLE, lymphoma, drugs (penicillin, cephalosporins, methyldopa)
Exam clue: splenomegaly
87
Cold AIHA Causes
Often associated with Raynaud’s, acrocyanosis
Causes: EBV, Mycoplasma pneumoniae, lymphoma
88
➡️ G6PD Deficiency
🧬 Pathophysiology
X-linked recessive
G6PD deficiency → glutathione deficiency → RBC susceptible to oxidative stress → intravascular haemolysis
89
➡️ G6PD Deficiency triggered by
Fava beans
Antimalarials
Ciprofloxacin
Sulfonamides (e.g. co-trimoxazole)
90
➡️ G6PD Deficiency blood film
Heinz bodies, bite cells, spherocytes
91
➡️ G6PD Deficiency gold std
G6PD enzyme assay
92
Hereditary Spherocytosis
🧬 Pathophysiology
Autosomal dominant
RBC cytoskeletal defect → RBC as sphere shaped (spherocytes) → splenic destruction (extravascular haemolysis)
93
investigation of choice if uncertain diagnosis/atypical in Hereditary Spherocytosis
Hb electrophoresis
94
Management Hereditary Spherocytosis
Folic acid
Splenectomy to reduce haemolysis
95
Paroxysmal Nocturnal Haemoglobinuria (PNH)
🧬 Pathophysiology
An acquired disorder, PIG A mutation - causes reduced GPI (a cell surface protein anchor)
RBCs lack CD55/CD59 → unregulated complement-mediated lysis
Affects RBCs → anaemia; WBCs → infection ; platelets → risk of thrombosis
96
Dark morning urine (haemoglobinuria)
Thrombosis: DVT, Budd-Chiari syndrome
Pnh
97
Pnh dct schumm
Positive
98
Investigations pnh
DCT positive - autoimmune
Schumm positive - intravascular
Pancytopenia
Gold standard: Flow cytometry for CD59/CD55
Ham’s test: acid-induced haemolysis (older method)
99
Gold standard: pnh
Flow cytometry for CD59/CD55
100
Pnh mx
Anticoagulation
Blood transfusions as needed
Stem cell transplant
101
IgM, acrocyanosis, infection-linked
Cold aiha
102
IgG, splenomegaly, drug/SLE-related
Warm aiha
103
Hereditary Haemochromatosis
Pathophysiology
Autosomal recessive disorder caused by mutations in the HFE gene, chromosome 6.
Mutation leads to increased intestinal absorption of iron
104
Endocrine features in Hereditary Haemochromatosis
Erectile dysfunction
Loss of libido
Diabetes mellitus (due to pancreatic iron deposition)
105
Cardiac features in Hereditary Haemochromatosis
Dilated cardiomyopathy
Heart failure
106
Investigations Hereditary Haemochromatosis
General Screening: 1st-line investigation is to measure transferrin saturation.
Genetic Testing
If family history or elevated transferrin saturation → test for HFE gene mutations:
C282Y homozygous is most common and pathogenic
X-ray chondrocalcinosis
Lft
107
Transferrin saturation Hereditary Haemochromatosisl
55% in men
50% in women
108
Middle-aged man with fatigue, diabetes, joint pain, skin darkening →
consider haemochromatosis
109
Management Hereditary Haemochromatosis
1st line: Venesection
2nd line: Iron chelation
Desferrioxamine (Alternative chelators: deferasirox, deferiprone
110
Function
Protein C
Vitamin K–dependent zymogen activated to activated protein C (APC)
Inactivates clotting factors Va and VIIIa
111
Function
Protein s
Cofactor to protein C, enhancing APC’s anticoagulant function
112
Deficiency of protein C or S →
failure to inactivate Va and VIIIa
Pro-coagulant state → increased risk of thrombosis
113
Most common inherited thrombophilia
Factor V Leiden
114
Factor V Leiden Pathophysiology
Gain-of-function mutation in Factor V
Results in resistance to activated protein C → factor Va is not broken down → hypercoagulable state
115
Clinical Features Factor V Leiden
VTE (esp. DVT/PE) age <50
Recurrent DVT/PE
Family history of VTE
Cerebral venous sinus thrombosis (CVST) in young adult
116
Antithrombin III Deficiency
Pathophysiology
Inheritance: Autosomal dominant
ATIII inhibits thrombin (IIa) and Factor Xa, with additional effects on IXa, XIa, XIIa
Deficiency leads to uninhibited coagulation and risk of thrombosis
117
Young adult with recurrent unprovoked VTE or family history of DVT/PE
Factor V Leiden is the most common
118
microcytic, hypochromic anaemia with low ferritin.
Ida
119
Blood Results IDA
Microcytic anaemia (low MCV)
Hypochromic red cells (low MCH)
Low serum ferritin, low transferrin saturation (TSAT)
Ferritin <30 µg/L confirms iron deficiency (NICE), or <100 µg/L in chronic kidney disease
120
For ALL patient with confirmed IDA Investigations
Screen for coeliac disease: anti-TTG antibodies + total IgA
Urine dipstick: to exclude haematuria
Consider FIT test according to guidelines (e.g. aged ≥60 with unexplained IDA)
Post-menopausal bleeding aged ≥55 (consider if <55)
121
Treatment IDA
First-line: Oral iron (e.g. ferrous fumarate or sulfate), once daily
Continue for 3 months after normalisation of Hb to replenish iron stores
Recheck: Hb within 4 weeks
122
1st-line investigation:ida
FBC and serum ferritin
123
Auer rods
Acute Myeloid Leukaemia (AML)
eosinophilic needle inclusions visible within the myeloblast cytoplasm - pathognomonic of AML
124
Bone marrow biopsy: >30% myeloblasts
Aml
125
Acute Promyelocytic Leukaemia (APML)
Pathophysiology
An important subtype of AML
t(15;17) → PML-RARα fusion gene
126
Apml mx
ATRA (all-trans retinoic acid) + chemotherapy
127
ATRA
Apml
128
chronic → accelerated → blast phase
Chronic Myeloid Leukaemia (CML)
129
Philadelphia chromosome
t(9;22) long arms - results in the formation of BCR:ABL proto-oncogene fusion protein which stimulates abnormal proliferation of cells.
t(9;22) Philadelphia chromosome
BCR-ABL fusion gene (tyrosine kinase)
Cml
130
Diagnosis cml
PCR/FISH - Philadelphia chromosome
BM biopsy: Increased myeloid:erythroid ratio
131
Cml mx
1st line: Imatinib (TK inhibitor)
Others: Hydroxyurea, IFN-α, bone marrow transplant
132
Monoclonal B-cell proliferation
Indolent
Chronic Lymphocytic Leukaemia (CLL)
133
Smudge cells
Cml
134
Investigations cll
FBC: Lymphocytosis, anaemia, thrombocytopenia
Blood film: Smudge cells
Flow cytometry: CD19+, CD5+, CD23+
135
Indications for chemotherapy in cll
Conservative if asymptomatic
Indications for chemotherapy: BM failure, massive lymphadenopathy/splenomegaly, rapid lymphocyte rise, systemic symptoms
136
Common regimen cll
FCR (fludarabine, cyclophosphamide, rituximab)
137
ALL Most common in
children aged 2–5
138
Elderly with bruising, fatigue, infections
AML
Cll
139
Bleeding + DIC in AML picture
APML
140
Weight loss, splenomegaly, very high WCC
CML
141
Elderly with lymphocytosis and smudge cells
CLL
142
1st line investigation: aml
Blood film (Auer rods)
143
CLL 1st line investigation
Flow cytometry
144
Most common adult leukaemia,
Cll
145
Splenomegaly lecocytosis(granulocytes
Chronic Myeloid Leukaemia (CML)
146
Reed–Sternberg cells and a bimodal age distribution.
Hodgkin’s
Bimodal age peaks: 30s and 70s
147
Reed–Sternberg cells
large, binucleated lymphocytes with "owl-eye" inclusions
(HL)
148
Painful lymph nodes after alcohol
Hl
149
B symptoms
Weight loss >10% in 6 months
Fever >38.3°C
Drenching night sweats
150
Ann Arbor System
Staging lymphoma
Stage I: Single LN region
Stage II: Multiple regions, same side of diaphragm
Stage III: LN regions on both sides of diaphragm
Stage IV: Organ involvement
Add "A" (no B symptoms) or "B" (B symptoms present)
151
Management hodgkims
Chemotherapy + radiotherapy
Lifelong irradiated blood products if transfusion required
152
Hepatosplenomegaly
Extranodal involvement whivh lymphoma
153
Burkitt’s Lymphoma types
Endemic (African):EBV-associated Maxillary or mandibular mass
Sporadic (Non-endemic):Ileocecal or abdominal tumour Often HIV-associated
154
Management Burkitt’s Lymphoma
Chemotherapy
Rasburicase prophylaxis to prevent tumour lysis syndrome
155
Rasburicase
prophylaxis to prevent tumour lysis syndrome
156
Bloods Tumour Lysis Syndrome
Hyperkalaemia
Hyperphosphataemia
Raised uric acid
Hypocalcaemia
Elevated creatinine
157
Prevention Tumour Lysis Syndrome
IV fluids for hydration
Rasburicase (urate oxidase)
Allopurinol (xanthine oxidase inhibitor) if rasburicase unavailable
158
30M with painless cervical lymphadenopathy night sweats and weight loss
Hl first?
159
After chemotherapy, patient with arrhythmia and AKI
Tumour Lysis Syndrome
160
Hypercellular marrow with dysplastic features
Myelodysplasia (Myelodysplastic Syndrome)
161
massive splenomegaly, fatigue and tear drop cells
Myelofibrosis
162
Tear drop. Cells
myelofibrosis
163
risk of progression to AML.
Myelodysplasia (MDS)
164
Investigations Myelofibrosis
FBC: Pancytopenia,
LDH and urate: Raised (↑ cell turnover)
Blood film:Tear drop cells (dacrocytes)
Bone marrow biopsy: Collagen fibrosis, megakaryocyte proliferation
165
Management Myelofibrosis
1st line: Ruxolitinib (JAK2 inhibitor)
Other options: Chemotherapy, splenectomy
Only curative treatment: Allogeneic stem cell transplant
166
Ruxolitinib
JAK2 inhibitor)
Myelofibrosis
167
Elderly patient with progressive pancytopenia
Myelodysplasia
168
CRAB features
Calcium, Renal, Anaemia, Bone
169
AutoImmune CRAB
Myeloma Clinical Features – Mnemonic:
A – Amyloidosis (AL type)
I – Infections:
C – Calcium: hypercalcaemia →
R – Renal: renal failure
A – Anaemia: marrow infiltration →
B – Bone: osteolytic lesions →
170
Initial Investigations Myeloma
FBC
Calcium
ESR or plasma viscosit
For patients >60 with bone pain or unexplained fractures:
171
High Risk for myeloma
Age > 60 with hypercalcaemia, leukopenia and symptoms suggestive of myeloma
Patients with abnormal ESR/plasma viscosity or incidental blood tests and presentation suggestive of myeloma
172
High risk patients, perform the following tests very urgently (< 48hrs)
Myeloma
Serum protein electrophoresis
Serum free light-chain assay
Urine protein electrophoresis (Bence Jones protein)
If serum/urine electrophoresis suggests myeloma, refer urgently via 2WW to haematology
MRI whole body - Gold standard to assess skeletal involvement
173
Management myeloma
Chemotherapy (e.g. cyclophosphamide, doxorubicin)
Steroids (e.g. dexamethasone)
Bisphosphonates
Autologous stem cell transplant
Transfusions if cytopenia present
174
Monoclonal Gammopathy of Undetermined Significance (MGUS)
Pathophysiology
Asymptomatic clonal plasma cell proliferation
Monoclonal paraprotein with no clinical features
Precursor to myeloma → 1% per year progression risk
Normal β2 microglobulin
175
Waldenström's Macroglobulinaemia
Pathophysiology
Lymphoplasmacytic lymphoma producing monoclonal IgM
Often preceded by IgM-MGUS
176
Hyperviscosity symptoms:
Headache
Blurred vision
Tinnitus
Waldenström's, prv
177
Management Waldenström's
Rituximab
Chemotherapy
Steroids
Plasmapheresis if hyperviscosity
178
60+ with bone pain, anaemia, renal failure, hypercalcaemia
Myeloma
179
Asymptomatic older adult with isolated paraproteinaemia
MGUS
180
70-year-old man with fatigue, blurred vision, anaemia, IgM paraproteinaemia
Waldenström's
181
JAK2-positive
Polycythaemia Rubra Vera (PRV)90%
Essential thrombocythemia 50%
182
Relative Polycythaemia causes
dehydration, diuretics, alcohol misuse
183
Secondary Polycythaemia causes
Chronic hypoxia: COPD, obstructive sleep apnoea
Increased production of EPO: cerebellar haemangioma, renal cell carcinoma (hypernephroma), high-altitude living
184
Pruritus after warm showers
Prv
185
Erythromelalgia
painful, red extremities
Prv
Essential thrombocythemia
186
distinguishes PRV from secondary polycythaemia
Low EPO (
187
PRV mx
1st line: Venesection to maintain haematocrit <0.45
Aspirin for thrombosis prevention and erythromelalgia
Hydroxycarbamide in high-risk patients (age >60 or history of thrombosis)
Alternatives: Interferon-α or ruxolitinib if hydroxycarbamide contraindicated or not tolerated
188
Complications prv
Thrombosis (stroke, DVT, PE)
Myelofibrosis (~10%): bone marrow scarring → cytopenias
Acute myeloid leukaemia (~10%)
189
60-year-old man with pruritus after hot shower, headache, splenomegaly
Prv
190
Darier’s sign
urticarial/wheal after rubbing the skin.
Systemic Mastocytosis
191
Investigations Systemic Mastocytosis
Blood film: May show monocytosis
Serum tryptase: Elevated (>20 ng/mL suggests systemic involvement)
Urinary histamine: Increased excretion
Bone marrow biopsy: Diagnostic — shows dense mast cell infiltrates with abnormal morphology
192
Diagnostic InvestigationsSystemic Mastocytosis
Bone marrow biopsy: Diagnostic — shows dense mast cell infiltrates with abnormal morphology
193
Management Systemic Mastocytosis
H1 antihistamines (e.g. cetirizine) for flushing, urticaria
Cytoreductive therapy (e.g. interferon-α) in aggressive forms
194
Recurrent flushing and abdominal pain with positive Darier’s sign
1st line investigation:
Serum tryptase level
195
Consumptive Thrombocytopenia
TTP, DIC, HUS
196
Drug-induced Thrombocytopenia
Heparin (HIT), quinine, valproate, carbamazepine, chemotherapy
197
Idiopathic Thrombocytopenic Purpura (ITP)
Pathophysiology
IgG autoantibodies target GP2b/3a receptors on platelets
Leads to premature destruction of platelets in the spleen
198
Commonest cause of death itp
intracranial haemorrhage
199
Acute ITP:
Most common in children post-infection
Self-limiting within 2–3 weeks
200
Chronic ITP:
More common in adults
Relapsing/remitting course - may require splenectomy
201
Idiopathic Thrombocytopenic Purpura (ITP)
Mx
1st line: Oral prednisolone - steroids are 1st line management.
2nd line: IV immunoglobulins (IVIG)
3rd line: Splenectomy
202
Thrombotic Thrombocytopenic Purpura (TTP)Causes
Idiopathic, infections, pregnancy, drugs, HIV, SLE, malignancy
Deficiency of ADAMTS13 enzyme
Unregulated vWF activity
Platelet consumption
203
Classic pentad ttp
Petechiae, purpura
Fluctuating neurological signs: confusion, seizures, headache
Fever
AKI
Thrombocytopenia
204
differentiates TTP from ITP
he fluctuating neurological signs / renal failure
205
Management ttp
1st line: Urgent plasma exchange
206
Heparin-Induced Thrombocytopenia (HIT) Pathogenesis
5-14 days after starting heparin (e.g. LMWH - enoxaparin)
IgG antibodies form against heparin-PF4 complex on platelet surface
207
Investigations HIT
HIT antibody assay
208
Management HIT
Stop heparin immediately
Start fondaparinux or argatroban
209
Young child post-viral illness with petechiae
1st line investigation:
ITP
FBC
210
Patient with fever, renal failure, confusion, and petechiae
Ttp
211
Ttp investigations
Blood film and ADAMTS13 assay
212
Thrombocytosis causes
Reactive thrombocytosis:
Malignancy
Essential thrombocythaemia (a myeloproliferative neoplasm)
213
Essential Thrombocythaemia mutation
JAK2 (50%)
214
Management Essential Thrombocythaemia
Low risk (age <60, no history of thrombosis): Aspirin monotherapy
Intermediate–high risk (age >60 or previous thrombosis): Hydroxycarbamide
History of thrombosis:
Venous: hydroxyurea + anticoagulation
Arterial: hydroxyurea + aspirin twice daily
215
Middle-aged woman with platelets >600, burning red hands admitted with chest pain.
Essential Thrombocythaemia
216
Minor Allergic Reaction Transfusion Reactions mx
Antihistamines (e.g. chlorphenamine)
Continue transfusion cautiously if symptoms resolve
217
Anaphylaxis Transfusion Reactions common in
IgA-deficient patients with anti-IgA antibodies
218
Acute Haemolytic Transfusion Reaction (AHTR)Pathophysiology
ABO mismatch
IgM-mediated complement activation → intravascular haemolysis
219
Investigations Acute Haemolytic Transfusion Reaction (AHTR)
Positive direct Coombs test
Remember: Coombs detects antibodies/complement on surface of RBCs
positive = autoimmune process
↓ Haptoglobin
↑ LDH, ↑ bilirubin
220
Acute Haemolytic Transfusion Reaction (AHTR) mx
Immediate cessation of transfusion
IV fluids + diuretics
Monitor renal function and electrolytes
221
Transfusion Associated Circulatory Overload (TACO)Management
Slow or stop transfusion
IV diuretics - furosemide
222
Transfusion Related Acute Lung Injury (TRALI) Pathophysiology
Donor anti-leukocyte antibodies react with recipient WBCs → Inflammatory lung injury and non-cardiogenic pulmonary oedema
223
Taco vs trali
TACO HYPERTENSION
TRALI HYPOTENSION
224
Delayed Haemolytic Transfusion Reaction
Pathophysiology
IgG-mediated extravascular haemolysis
Occurs 5–7 days post-transfusion
225
InvestigationsDelayed Haemolytic Transfusion Reaction
Positive direct Coombs test
226
ManagementDelayed Haemolytic Transfusion Reaction
Monitor Hb
Supportive care
Repeat transfusion if clinically indicated
227
SOB + Hypotension <6hr post-transfusion
TRALI
228
SOB + Hypertension in pt with HF/elderly blood transfusion
TACO
229
IgA-deficient patient with shock after transfusion →
Anaphylaxis
230
Jaundice and low Hb 5 days after transfusion
Delayed haemolysis
231
Bronze diabetes
Hereditary hemochromatosis
232
Tear drop poikilocytes dacrocytes
Myelofibrosis
233
Rucolitinib
Jak2i
Myelofibrosis
234
Smudge cells are
Fragile lymphocytes that crush diring slide prep
Cll
235
Tumor lysis biochemical abnormalities
Hyperk
Hyperphosphat
Hypoca
236
Hereditary spherocytosis extra or intravascular hemolysis
Extra
237
G60d intra or extravascular hemolysis
Intra
Schum positive
238
Mantle cell lymphoma stains positive for
Cyclin d1 t11:14
239
Cd15 cd30
Hodgkins
240
Cd20 cd79
Diffuse large b cell
241
releases stored VWF)
desmopressin
242
Ferritin <..... confirms iron deficiency (NICE), or <... in chronic kidney disease
30ug/l
100 µg/L
MSRA
flashcards
Decks in class (27)
# Cards
-
MEDICINE228
-
Antibiotics31
-
Ent149
-
Psychiatry59
-
Contraception49
-
Gynae95
-
Ortho1
-
Cardio304
-
Resp120
-
Derma278
-
Ophthal180
-
Endocrine322
-
Metabolic58
-
Gastro343
-
Surgery168
-
Infectious Diseases269
-
Hematology242
-
Rheumat + Musculoskeletal497
-
Rheumat + Musculoskeletal 264
-
Pediatrics389
-
Pharma254
-
Psychiatry168
-
Respiratory247
-
Uro101
-
Renal175
-
Obgyn340
-
Neuro269
