Immunology & Haematology Small Conditions Flashcards
A type of macrocytic anaemia in which the bone marrow produces unusually large, structurally abnormal, immature red blood cells
Causes, presentation, diagnosis, management
Megaloblastic anaemia
Causes: B12 deficiency (pernicious anaemia*/GI disease) Folate deficiency (dietary/GI)
Presentation: “lemon yellow” tinge, pancytopenia (B12)
Diagnosis: macrocytic, ↓B12/folate
Management:
B12 i/m injection (loading dose, then 3 monthly)
Oral folate replacement
((*pernicious anaemia = autoimmune against intrinsic factor –> malabsorption))
Commonest cause of anaemia worldwide
causes, presentation, diagnosis, management
Iron deficiency anaemia
Causes: bleeding, diet, malabsorption, pregnancy
Presentation: koilonychia, atrophic tongue, angular stomatitis, general features of anaemia
Diagnosis: hypochromic microcytic, ↓ serum ferritin
Management: correct cause!, oral iron (IV if intolerant), blood transfusion (if chest pain at rest - risk of MI)
Anaemia due to defective iron utilisation
causes, diagnosis
Secondary anaemia/ anaemia of chronic disease
Causes: identifiable underlying disease
- infection
- inflammation
- malignancy
Diagnosis:
normochromic normocytic, normal reticulocyte count
OR hypochromic microcytic, normal serum ferritin
Anaemia due to accelerated red cell destruction and compensation by bone marrow
causes, diagnosis, management
Haemolytic anaemia
Causes:
congenital anaemias,
extravascular haemolysis = autoimmune haemolytic anaemia
intravascular haemolysis = non immune causes (severe infection, DIC, mechanical e.g. artificial valve, HUS, transfusion reaction)
Diagnosis: normochromic normocytic, ↑reticulocyte count*
direct antiglobulin test (+ve if immune mediated)
Management: folic acid (supports marrow function)
correct cause: steroids if autoimmune, splenectomy (remove site of destruction)…
Consider transfusion
*due to bone marrow compensation
Congenital anaemia caused by defects in structural proteins –> spherical RBCs that are removed by the reticuloendothelial system
Inheritance, presentation, treatment
Hereditary Spherocytosis
Inheritance: autosomal dominant
Presentation: anaemia, neonatal jaundice, splenomegaly, pigment gallstones
Treatment: folic acid, transfusion, splenectomy if severe
3 categories of causes of congenital anemia
Defects in red cell membrane
(e.g. hereditary spherocytosis)
Defects in metabolic pathways
(e.g. G6PD deficiency, pyruvate kinase deficiency)
Defects in haemoglobin (haemoglobinopathies)
(e.g. sickle cell disease, thalassaemias)
Congenital anaemia caused by a metabolic pathway deficiency leaving cells vulnerable to oxidative damage
Inheritance and presentation
G6PD (glucose 6 phosphate dehydrogenase) Deficiency
inheritance: X-linked
Presentation: anaemia, neonatal jaundice, splenomegaly, pigment gallstones
Haemolytic crisis triggered by infection/acute illness, foods (fava beans), drugs (antimalarials, aspirin, vitK)
((confers protection against malaria))
Congenital anaemia caused by a metabolic pathway deficiency leaving cells rigid
presentation
presentation
Pyruvate kinase deficiency
Presentation: anaemia, jaundice, gallstones
A group of congenital anaemias characterised by mutations or deletions in globin chain production –> chronic haemolysis and anaemia
Thalassaemias
A type of thalassaemia caused by absence of beta chains in the globin protein
inheritance, presentation, diagnosis, management
Beta Thalassaemia Major
Inheritance: autosomal recessive (carriers = thalassaemia trait)
Presentation: severe anaemia (present at 3-6 months old), bone deformities, growth retardation, splenomegaly
Diagnosis: “hair on end” appearance of skull on x-ray (expansion of ineffective bone marrow)
Management:
chronic transfusion support (4-6 weekly)
+ Iron chelation therapy (prevents death from iron loading)
or bone marrow transplantation = curative
((life expectancy <10yrs if untreated/irregular transfusions))
A type of clot usually secondary to atherosclerosis
composition, risk factors, presentation, management
Arterial thrombus
Composition: mainly platelets “white clot”
Risk factors:
age, obesity, smoking, sedentary lifestyle, hypertension, DM, hypercholesterolaemia
Presentation:
Coronary thrombus = MI/unstable angina
Cerebral TE = stroke/TIA
Peripheral TE = limb ischaemia
Management:
lifestyle modification + management of risk factors
Acute presentation = thrombolysis, antiplatelet/anticoagulant drugs
Secondary prevention = aspirin + antiplatelets (e.g. rivaroxaban)
A type of clot usually due to stasis and hypercoagulability
composition, consequences, risk factors, presentation, diagnosis, management
Venous thrombosis
composition: fibrin + some red cells “red thrombus”
Consequences: clot –> backpressure + valvular insufficiency –> post thrombotic syndrome
Risk factors:
obesity, age, high oestrogen (pregnancy, OCP, HRT), tissue trauma, surgery, immobility, systemic disease (cancer, autoimmune disease), FH
Presentation: Limb DVT, PE,
post thrombotic syndrome (hyperpigmentation, redness, swelling, pain - risk for up to 2 yrs)
Diagnosis:
Pre-test probability scoring: Wells/Geneva
If probability low: D-dimer
Then/if probability high: imaging
- Doppler USS*
- V/Q scan
- CT pulmonary angiogram (gold standard in PE)
Management: (aim to prevent clot extension, embolisation, recurrence)
- anticoagulants (LMWH, warfarin, DOACs)
- thrombolysis (in massive PE)
*Thrombosed vein = large + non compressible +/- echogenic material
An inherited predisposition to venous thrombosis
examples
Heritable Thrombophilia
e.g. Factor V Leiden Prothrombin G20210A Antithrombin deficiency Protein C/S deficiency
((Screening of family members is possible but not recommended as there is no intervention taken on diagnosis and it may negatively affect their insurance etc.
Majority of diagnoses are nor predictive of recurrent events ))
Mixed thrombi formed of platelets and/or fibrin, principally occurring in DIC
presentation
Microvascular Thrombus
Presentation: diffuse ischaemia
DIC stands for…
pathophysiology, occurs in…, management
Disseminated Intravascular Coagulation
path:
Systemic activation of coagulation cascade AND fibrinolysis pathway –> microvascular thrombi –> tissue ischaemia –> organ failure + gangrene
Eventually clotting factors become exhausted –> bleeding
Occurs in: septicaemia, malignancy, eclampsia
Management: Cautious use of very low dose anticoagulants (leads to correction in the long term)
Bleeding disorder caused by abnormalities in vWF
inheritance, presentation, management
Von Willebrand Disease
inheritance: autosomal dominant
Presentation: platelet type pattern of bleeding
Management: vWF concentrate / DDAVP Tranexamic acid Topical applications OCP etc... for menorrhagia
Pattern of bleeding caused by defects in primary haemostasis
(platelet/ mucosal type)
involves…
Mucosal bleeding Epistaxis Purpura Menorrhagia GI Post surgery bleeding
Pattern of bleeding caused by defects in secondary haemostasis
(coagulation factor type)
involves…
Articular bleeding
Muscle haematoma
CNS bleeding
An autoimmune condition causing a platelet-type pattern of bleeding
causes, management
Immune Thrombocytopenic Purpura (ITP)
Causes: infection (EBV, HIV), lymphoma, drug induced
Management: steroids, IVIg, splenectomy, thrombopoietin analogues
Bleeding/clotting caused by liver failure
Presentation, diagnosis, management
((liver produces fibrin and clotting factors so liver failure = Increased risk of venous thrombosis AND bleeding))
Presentation: bleeding from varices
Diagnosis: ↑PTT, ↓fibrinogen
Management: Vitamin K, replacement FFP
Management of haemorrhagic disease of the newborm
Completely preventable by I/M vitamin K at birth
((newborns have immature coagulation systems so fatal haemorrhage is possible))
((different to HAEMOLYTIC disease of the newborn))
Definitive diagnosis of haematological malignancy
BIOPSY
of lymph node/bone marrow
Typical presentation of a leukaemia
Triad of bone marrow failure:
1. ↓Hb = symptomatic anaemia (fatigue, SOB, angina, HF) 2. Thrompocytopenia = platelet pattern of bleeding 3. neutropenia/leukopenia = infections
Liver and spleen enlargement
Difference btw leukaemia and lymphoma
2 possible distributions of haematological cancers:
Leukaemia = usually presents with bone marrow failure + hepatosplenomegaly
Lymphoma = usually presents with lymphadenopathy, systemic (B) features + hepatosplenomegaly
But either could present atypically, the different diseases are defined by the malignant cell characteristics so diagnosis is ONLY MADE BY BIOPSY
Acute vs Chronic leukaemia
Cells retain the ability to differentiate in chronic (but not acute)
Acute is more rapidly fatal if untreated
Acute is more easily curable
A haematological malignancy characterised by a block to differentiation of myeloid progenitor cells causing malignant, rapidly dividing, non-differentiating blast cells, common in old age
presentation, diagnosis, management
Acute Myeloid Leukaemia (AML)
Presentation: triad of bone marrow failure
Diagnosis:
FBC: pancytopaenia, ↑WCC (due to blasts)
Bone marrow biopsy: >20% myeloblasts*
Management:
Anti-leukaemic chemotherapy (reduces blast cell no.)
Stem cell transplant
Biologics
*>20% = AML, 5-20%=myelodysplastic syndrome, <5% = remission
A haematological malignancy characterised by ineffective, malignant cells in the bone marrow which divide rapidly and only partially mature
Cause, presentation, diagnosis, management
Chronic Myeloid Leukaemia (CML)
Cause: Philadelphia chromosome
Presentation: Hepatosplenomegaly, bone marrow failure, hyperleukostasis
Diagnosis:
FBC: ↑↑neutrophils, ↑platelets*
Blood film/ bone marrow biopsy: hypercellular, all stages of WBC differentiation
Genetic testing: philadephia chromosome
Management:
Tyrosine kinase inhibitors
Bone marrow transplant (in TKI failure)
((*still bone marrow failure as low HEALTHY platelets + WBCs)
A haematological malignancy characterised by a block to differentiation of lymphoid progenitor cells causing malignant, rapidly dividing, non-differentiating blast cells, common in children
presentation, diagnosis, management
Acute Lymphoblastic Leukaemia (ALL)
Presentation: bone marrow failure, bone/joint pain (usually 2-3 week history)
Diagnosis:
FBC: ↓Hb, ↓platelets, ↑WCC
Bone marrow biopsy: 90% B lymphoblasts
Management:
Multiagent intensive chemotherapy (+maintenance treatment for 18 months as high relapse rate)
Stem cell transplant if high risk
CAR T-cells
((90% cure rate in children))
A haematological malignancy caused by mutations in lymphoid cells, commonly occurring in the lymph node germinal centre
presentation, diagnosis, staging, management
Chronic Lymphocytic Leukaemia (CLL)
Presentation: often asymptomatic at presentation, bone marrow failure, lymphadenopathy, hepatosplenomegaly
Diagnosis: lymphocyte count >5
Binet staging:
A: <3 lymph node areas = no change life expectancy
B: 3+ lymph node areas = 8yrs life expectancy
C: B + anaemia/thrombocytopenia = 6yrs life expectancy
Management: “watch and wait”
cytotoxic chemotherapy, monoclonal antibodies
A group of haematological malignancies characterised by overproduction of mature cells (mostly red cells + platelets)
examples
Myeloproliferative Neoplasms (MPN)
e.g.
polycythemia vera (PV)
essential thrombocythaemia
Idiopathic myelofibrosis
A myeloproliferative neoplasm characterised by overproduction of RBCs
presentation, diagnosis, management
Polycythaemia Vera (PV)
Presentation: headaches, thrombosis, splenomegaly
Diagnosis:
FBC: ↑↑Hb, ↑↑RCC, ↑WCC ↑platelets
↑uric acid
Management:
- aspirin
- venesection (bleeding)
- hydroxycarbamide (suppresses WCC + platelet count)
((may progress to myelofibrosis/AML))
A myeloproliferative neoplasm characterised by overproduction of platelets
presentation, management
Essential Thrombocythaemia (ET)
Presentation: arterial, venous + micro-thrombi, gout, headache
Management: aspirin, hydroxycarbamide (suppresses WCC + platelet count)
((may progress to myelofibrosis/AML))
Extensive scarring of the bone marrow caused by overproduction of cells
presentation
Idiopathic Myelofibrosis
presentation:
massive splenomegaly, bone marrow failure
Asymptomatic finding of elevated IgA/IgG paraproteins
management
Monoclonal Gammopathy of Uncertain Significance (MGUS)
management: monitor regularly, no treatment
((present in 3-4% of the population over 75%))
Any fever in a neutropenic patient
Febrile Neutropenia
(if chemo in last 14 days, likely neutropenic)
Lymphoma (general)
presentation, diagnosis + staging
Presentation: lymphadenopathy, hepatosplenomegaly,
Systemic (B) symptoms (weight loss >10% in 6 months, fever, drenching sweats…)
Diagnosis:
Lymph node biopsy, bone marrow biopsy
Staging:
I: 1 lymph node
II: ≥2 lymph nodes on ONE side of diaphragm
III: ≥2 lymph nodes on BOTH sides of the diaphragm +/- involvement of a nearby organ
IV: Multiple organ/tissue involvement
+
a: absence of B symptoms
b: B symptoms (weight loss, fever, night sweats)
Non-hodgkin lymphoma (B-cell or T-cell)
types + examples, management
Low grade NHL: often asymptomatic, incurable, e.g. follicular lymphoma
High grade NHL: aggressive fast growing, curable, e.g. diffuse large B-cell lymphoma
Management:
“watch and wait” if low-grade and asymptomatic
combination chemo
monoclonal antibodies
((70% of all lymphoma))
Hodgkin lymphoma
Aetiology + management
Aetiology: bimodal age curve
- 1st peak = 15-35yrs
- 2nd peak = later in life (EBV associated)
Management:
combination chemo +/- radiotherapy
monoclonal antibodies
immunotherapy
((30% of all lymphoma))
