Haematology Flashcards
1
Q
Anaemia
Definition (2)
A
Low haemoglobin concentration, due to either a low red cell mass or increased plasma volume (eg. in pregnancy)
<135g/l for men, <115g/l for women
2
Q
Anaemia
Signs + symptoms (7)
A
Fatigue Faintness Dyspnoea Palpitations Headache Pallor In severe anaemia, there may be signs of hyperdynamic circulation, eg. tachycardia, flow murmurs (ejection systolic-loudest over apex)
3
Q
Anaemia
Types (4)
A
Low MCV (microcytic): iron deficiency, thalassaemia Normal MCV (normocytic): acute blood loss, anaemia of chronic disease, bone marrow failure, pregnancy, hypothyroidism High MCV (macrocytic): B12 deficiency, folate deficiency, alcohol, myelodysplastic, hypothyroid Haemolytic: normo/macrocytic, suspect if reticulocytosis and increased bilirubin, mild jaundice but no bilirubin in urine as it causes pre hepatic jaundice
4
Q
Iron Deficiency Anaemia
Aetiology (3)
A
Blood loss (menorrhagia, GI bleeding)
Malabsorption (coeliac)
Hookworm most common cause in the Tropics
5
Q
Iron Deficiency Anaemia
Signs + symptoms (3)
A
Koilonychia (spoon shaped nails)
Atrophic glossitis
Angular cheiolosis (ulceration at side of mouth)
6
Q
Iron Deficiency Anaemia
Investigations (3)
A
Microcytic, hypochromic anaemia
Reduced ferritin
Reduced serum iron with increased total iron inding capacity
7
Q
Iron Deficiency Anaemia
Treatment (4)
A
Treat cause
Oral iron, eg. ferrous sulfate (SE: nausea, abdo discomfort, constipation, black stool)
Continue treatment until Hb is normal and for at least 3 months to restore stores
IV iron almost never needed unless oral route is impossible or ineffective, eg. chronic renal failure with erythropoietin therapy
8
Q
Anaemia of Chronic Disease
Aetiology (5)
A
Chronic infection Vasculitis Rheumatoid Malignancy Renal failure
9
Q
Anaemia of Chronic Disease
Pathology (3)
A
Poor use of iron in erythropoiesis
Cytokine-induced shortening of RBC survival
Reduced production of and response to erythropoietin
10
Q
Anaemia of Chronic Disease
Investigations (3)
A
Mild normocytic anaemia
Normal/increased ferritin
Do blood film, B12, folate, TSH and tests for haemolysis
11
Q
Anaemia of Chronic Disease
Treatment (2)
A
More vigorous treatment of underlying disease
Erythropoietin is effective in raising the haemoglobin level (SE: flu like symptoms, hypertension)
12
Q
Macrocytic Anaemia
Aetiology (3)
A
Megaloblastic: B12 deficiency, folate deficiency, cytotoxic drugs
Non-megaloblastic: alcohol (most common cause of macrocytosis but not often anaemia), reticulocytosis (eg. haemolysis), liver disease, hypothyroidism, pregnancy
Other haematological disease: myelodysplasia, myeloma, myeloproliferative disorders
13
Q
Macrocytic Anaemia
Investigations (5)
A
Blood film: hypersegmented polymorphs in B12 and folate deficiency
LFT
TFT
Serum B12 and serum folate
Bone marrow biopsy: megaloblastic, normoblastic marrow (eg. in liver disease, hypothyroidism), abnormal erythropoiesis (eg. leukaemia), increased erythropoiesis (eg. haemolysis)
14
Q
Macrocytic Anaemia Folate deficiency (3)
A
Found in green vegetables, nuts and yeast
Causes: poor diet, increased demand (pregnancy, haemlysis, malignancy), malabsorption (coeliac disease), drugs (alcohol, anti-epileptics, methotrexate)
Treatment: folic acid for 4 months, never without B12 unless they have normal levels
15
Q
Macrocytic Anaemia B12 deficiency (4)
A
Found in meat, fish and dairy
B12 binds to intrinsic factor in the stomach and then is absorbed in the terminal ileum
Causes: dietary (eg. vegan), malabsorption (lack of intrinsic factor = pernicious anaemia, often post gastrectomy or ileal restriction)
Can lead to subacute combined degeneration of the spinal cord with peripheral neuropathy
16
Q
Macrocytic Anaemia Pernicious anaemia (4)
A
Caused by an autoimmune atrophic gastritis, leading to lack of intrinsic factor secretion
Associated with other autoimmune disease: thyroid disease, Addison’s disease, hypoparathyroidism, stomach cancer (so have low threshold for doing upper GI endoscopy)
Investigations: low Hb, high MCV, low serum B12, megaloblastic marrow, intrinsic factor antibodies
Treatment: treat cause, may need B12 injections
17
Q
Haemolytic Anaemia
Pathology (3)
A
Haemolysis = premature breakdown of RBCs
Occurs in the circulation (intravascular) or in the reticuloendothelial system, ie. macrophages of liver, spleen and bone marrow (extravascular)
Haemolysis may be asymptomatic but if the bone marrow doesn’t compensate sufficiently, a haemolytic anaemia results
18
Q
Haemolytic Anaemia
Signs + symptoms (5)
A
Jaundice Dark urine Hepatosplenomegaly (when extravascular) Gallstones (pigmenteed, due to increased bilirubin from haemolysis) Leg ulcers (due to poor blood flow)
19
Q
Haemolytic Anaemia
Investigations (7)
A
FBC Reticulocytes Bilirubin LDH Urinary urobilinogen Blood film: macrocytes Direct antiglobulin (Coombs) test identifies red cells coated with antibody or complement, a +ve result indicates an immune cause of the haemolysis)
20
Q
Haemolytic Anaemia
Causes (6)
A
Drug induced: causing formation of RBC autoantibodies binding to RBC membranes (eg. penicillin) or production of immune complexes (eg. quinine), Coombs +ve
Autoimmune: autoantibodies cause extravascular haemolysis, Coombs +ve
Hep B + C: Coombs -ve, autoimmune haemolytic anaemia
Enzyme defects: G6PD deficiency is chief one, most asymptomatic but can cause oxidative crisis –> rapid anaemia + jaundice
Membrane defects: Coombs -ve and need folate, eg. hereditary spherocytosis
Haemoglobinopathy: sickle, thalassaemia
21
Q
Sickle Cell Anaemia
Definition (1)
A
Autosomal recessive disorder causing production of abnormal B-globin chains (mostly in those of African descent)
22
Q
Sickle Cell Anaemia
Pathology (2)
A
An amino acid substitution in the gene coding for the B chain results in the production of HbS rather than HbA
HbS polymerises when deoxygenated causing RBCs to deform, producing sickle cells, which are fragile and haemolyse and also block small vessels
23
Q
Sickle Cell Anaemia
Signs + symptoms (7)
A
Usually well tolerated unless in crisis (due to microvascular occlusion)
Often affects marrow, causing severe pain; triggered by cold, dehydration, infection, hypoxia
Occlusion may occur, causing mesenteric ischaemia, mimicking acute abdo
CNS infarction: stroke, seizures, cognitive defects
Dactylitis
Avascular necrosis
Leg ulcers
24
Q
Sickle Cell Anaemia
Investigations (6)
A
May have haemolysis Hb 60-90g/L Increased reticulocytes Increased bilirubin Blood film shows sickle cells Hb electrophoresis to confirm diagnosis
25
Sickle Cell Anaemia
| Treatment of chronic disease (2)
Hydroxycarbamide if frequent crises
| Splenic infarction leads to hyposplenism so give prophylactic antibiotics and immunisation
26
Sickle Cell Anaemia
| Treatment of crises (4)
Analgesia
Crossmatch blood
Antibiotics if fever, unwell or chest signs
Give blood transfusion if Hb or reticulocytes fall sharply
27
Thalassaemia
| Definition (2)
Genetic disease of unbalanced Hb synthesis, with under or no production of one globin chain
Unmatched globins precipitate damaging RBC membranes, causing their haemolysis while still in the marrow
28
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Thalassaemia
alpha thalassaemia (6)
```
There are 4 alpha genes
Alpha thalassaemias are caused by gene deletions
If 4 genes are deleted, death in utero
If 3 genes are deleted, there may be moderate anaemia and features of haemolysis: hepatosplenomegaly, leg ulcers and jaundice
If 2 genes are deleted, there is asymptomatic carrier state with reduced MCV
If 1 gene deleted, clinical state is normal
29
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Thalassaemia
beta thalassaemia (4)
```
Usually caused by point mutations in B-globin genes leading to reduced B chain production or absence
B thalassaemia minor: carrier state and usually asymptomatic or mild, well tolerated anaemia (often confused with iron deficiency)
B thalassaemia intermedia: moderate anaemia but not requiring trasnfusions
B thalassaemia major: abnormalities in both B-globin genes, presents in 1st year with severe anaemia and failure to thrive, extramedullary heamopoiesis in response to anaemia causing weird head shape + hepatosplenomegaly
30
Thalassaemia
| Investigations (5)
```
FBC
MCV
Blood film
Iron
Hb electrophoresis
```
31
Thalassaemia
| Treatment (5)
Regular lifelong transfusions to suppress extramedullary haematopoiesis and allow normal growth
Iron-chelatores to prevent iron overload
Ascorbic acid to increase urinary excretion of iron
Splenectomy if hypersplenism persists
Marrow transplant may cure
32
Differential White Cell Count
| Neutrophils (3)
Ingest and kill bacteria, fungi and damaged cells
Neutrophilia: bacterial infections, inflammation, myeloproliferative disorders, drugs (steroids), stress (trauma, haemorrhage), malignancy
Neutropenia: viruses, drugs (post chemo), severe sepsis, hypersplenism, bone marrow failure
33
Differential White Cell Count
| Lymphocytes (4)
Divided into T and B
Important for cell-mediated immunity and antibody production
Lymphocytosis: acute viral infections, chronic infection (eg. TB, syphilis, hepatitis), leukaemia, lymphoma
Lymphopenia: steroid therapy, SLE, HIV, post chemo, radio
34
Differential White Cell Count
| Eosinophils (2)
Mediate allergic reactions and defend against parasites
| Eosinophilia: drug reactions eg. erythema multiforme, allergies, parasites, skin disease
35
Differential White Cell Count
| Monocytes (2)
Precursors of tissue macrophages
| Monocytosis: post chemo/radio, chronic infections, malignancy
36
Differential White Cell Count
| Basophils (2)
Contain histamine, which is released on binding IgE
Basophilia: myeloproliferative disease, viral infections, IgE mediated hypersensitivity reactions (eg. urticaria), inflammatory disorders (eg. UC, RA)
37
Haemophilia
| Definition (3)
Haemophilia A- factor VIII
Haemophilia B- factor IX deficiency
X-linked recessive
38
Haemophilia
| Signs + symptoms (2)
Bleeds into joints leading to crippling arthropathy
| Bleeds into muscles causing haematomas (increased pressure can lead to nerve palsies and compartment syndrome)
39
Haemophilia
| Investigations (2)
Reduced factor VIII/IX assay
| High APTT
40
Haemophilia
| Treatment (4)
Avoid NSAIDs + IM injections
Minor bleeds: pressure and elevation, desmopressin works to increase factor VIII
Major bleeds eg. haemarthrosis: increases factor VIII levels to 50% of normal
Life threatening bleeds: need factor VIII levels of 100% eg. with recombinant factor VIII
41
von Willebrand's Disease
| Role of vWF (3)
Bring platelets into contact with exposed subendothelium
Make platelets bind to each other
Bind to factor VIII, protecting it from destruction in the circulation
42
von Willebrand's Disease
| Types (3)
Type I: most common, autosomal dominant, reduced levels of vWF, mild
Type II: autosomal dominant, abnormal vwF, bleeding tendency varies
Type III: least common, autosomal recessive, undetectable vWF so less factor VIII, severe
43
von Willebrand's Disease
| Signs + symptoms (4)
Bruising
Epistaxis
Menorrhagia
Increased bleeding post tooth extraction
44
von Willebrand's Disease
| Investigations (4)
Increased APTT
Increased bleeding time
Reduced factor VIIIC (clotting activity)
INR + platelets normal
45
von Willebrand's Disease
| Treatment (2)
Desmopressin for mild bleeding
| vWF-containing factor VIII concentrate for surgery or major bleeds
46
Acute Lymphoblastic Leukaemia
| Definition (2)
Malignancy of lymphoid cells, affecting T/B cells, arresting maturation and promoting uncontrolled proliferation of immature blast cells, with marrow failure and tissue infiltration
Commonest cancer in childhood
47
Acute Lymphoblastic Leukaemia
| Classification (3)
Morphological (microscopic appearance)
Immunological (surface markers- precursor/T/B cells)
Cytogenetic (chromosomal analysis, useful for prognosis- poor with Philadelphia chromosome, 9:22 translocation)
48
Acute Lymphoblastic Leukaemia
| Signs + symptoms (2)
Marrow failure: anaemia (low Hb), infection (low WCC), bleeding (low platelets)
Infiltration: hepatomegaly, splenomegaly, lymphadenopathy, CNS involvement (CN palsies, meningism)
49
Acute Lymphoblastic Leukaemia
| Investigations (4)
Blood film: characteristic blast cells
Bone marrow: characteristic blast cells
High WCC
CXR: CT for mediastinal or abdominal lymphadenopathy
50
Acute Lymphoblastic Leukaemia
| Treatment (7)
Platelet/blood transfusion
IV fluids
Allopurinol (prevents TLS)
Immediate antibiotics for infection
Start neutropenic regimen: prophylactic antivirals, antifungals, antibiotics
Chemo
Matched related allogeneic marrow transplant once in 1st remission (no evidence of leukaemia in blood)
51
Acute Lymphoblastic Leukaemia
| Prognosis (2)
Cure rates 70-90% for kids
| 40% cure rate in adults
52
Acute Myeloid Leukaemia
| Definition (2)
Neoplastic proliferation of blast cells that is derived from marrow myeloid elements
Commonest acute leukaemia of adults, progresses rapidly (death in 2 months if untreated)
53
Acute Myeloid Leukaemia
| Aetiology (3)
Age
Long term complication of chemo
Myelodysplastic syndromes
54
Acute Myeloid Leukaemia
| Signs + symptoms (2)
Marrow failure: anaemia, infection, bleeding
| Infiltration: hepatomegaly, splenomegaly, gum hypertrophy, skin involvement
55
Acute Myeloid Leukaemia
| Investigations (5)
```
WCC high/normal/low
Blood film: blast cells may be few
Bone marrow biopsy: multiple blasts
Immunophenotyping
Cytogenetic analysis effects treatment recommendations and guides prognosis
```
56
Acute Myeloid Leukaemia
| Treatment (5)
Blood/platelet transfusions
IV fluids
Allopurinol (prevents TLS)
V. intensive chemo for marrow suppression
Bone marrow transplant (+ ciclosporin +/- methotrexate to reduce graft vs host disease- new marrow attacking patient's body)
57
Acute Myeloid Leukaemia
| Complications (2)
Infection is major problem
| Chemo causes increased urate levels (from TLS)
58
Chronic Myeloid Leukaemia
| Definition (2)
Uncontrolled clonal proliferation of myeloid cells
| Myeloproliferative disorder
59
Chronic Myeloid Leukaemia
| Aetiology (2)
40-60
| Philadelphia chromosome present in >80% (those without it have a worse prognosis)
60
Chronic Myeloid Leukaemia
| Signs + symptoms (12)
```
Mostly chronic and insidious
Weight loss
Fatigue
Fever
Sweats
Features of gout (purine breakdown)
Bleeding (platelet dysfunction)
Splenomegaly (>75%), often massive
Hepatomegaly
Anaemia
Bruising
Abdo discomfort (organomegaly)
```
61
Chronic Myeloid Leukaemia
| Investigations (5)
Really high WCC (especially myeloid cells- neutrophils, myelocytes, basophils, eosinophils)
Low/normal Hb
High urate
High B12
Ph chromosome found on cytogenetic analysis or bone marrow
62
Chronic Myeloid Leukaemia
| Phases (4)
Median survival 5-6 years
Chronic phase: lasting months/years, no symptoms
Accelerated phase: increased symptoms, increased splenomegaly
Blast transformation phase: acute leukaemia +/- death
63
Chronic Myeloid Leukaemia
| Treatment (2)
Tyrosine kinase inhibitor
| Stem cell transplant (offers only cure but significant morbidity + mortality, may be 1st line for young patients)
64
Chronic Lymphocytic Leukaemia
| Definition (2)
Accumulation of mature B cells that have escaped programmed cell death
Commonest leukaemia
65
Chronic Lymphocytic Leukaemia
| Signs + symptoms (6)
```
Often asymptomatic and found on a routine FBC
Anaemia
Prone to infections
Enlarged, rubbery non-tender nodes
Splenomegaly
Hepatomegaly
```
66
Chronic Lymphocytic Leukaemia
| Investigations (2)
Increased lymphocytes
| Later, marrow infiltration: low Hb, low neutrophils, low platelets
67
Chronic Lymphocytic Leukaemia
| Complications (3)
Autoimmune haemolysis
Increased rate of infection due to hypogammaglobulinaemia (low IgG)- often the cause of death
Marrow failure
68
Chronic Lymphocytic Leukaemia
| Treatment (4)
Consider drugs if symptomatic, immunoglobulin genes are unmutated
Rituximab
Radiotherapy for lymphadenopathy and splenomegaly
Supportive: transfusions, IV human immunoglobulin if recurrent infection
69
Chronic Lymphocytic Leukaemia
| Prognosis (3)
1/3 never progress
1/3 progress slowly
1/3 progress actively
70
Hodgkin's Lymphoma
| Definition (2)
Lymphomas are disorders caused by malignant proliferations of lymphocytes (accumulate in lymph nodes causing lymphadenopathy)
In Hodgkin's, characteristic cells are found (with mirror-image nuclei) called Reed-Sternberg cells
71
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Hodgkin's Lymphoma
Risk factors (7)
```
```
2 peaks: young adults and elderly
Male
Affected sibling
EBV
SLE
Post-transplant
Obesity
```
72
Hodgkin's Lymphoma
| Signs + symptoms (5)
Often presents with enlarged, painless, non-tender superficial lymph node, typically cervical (size may increase and decrease in size spontaneously)
Constitutional upset: fever, weight loss, night sweats, pruritus and lethargy
Mediastinal lymph node involvement can cause features due to mass effect, eg. bronchial/sVT obstruction
Anaemia
Spleno-or hepatomegaly
73
Hodgkin's Lymphoma
| Investigations (5)
Tissue diagnosis: lymph node excision biopsy
FBC
Blood film
High ESR or low Hb indicates a worse prognosis
LDH is raised as it is released during cell turnover
74
Hodgkin's Lymphoma
| Staging (5)
I- confined to single lymph node region
II- involvement of 2+ nodal areas on same side of diaphragm
III- involvement of nodes on both sides of diaphragm
IV- spread beyond lymph nodes, eg. liver/bone marrow
Each stage is either A (no systemic symptoms) or B (presence of B symptoms- weight loss, >10% in 6 month, unexplained fever >38, night sweats)
75
Hodgkin's Lymphoma
| Treatment (2)
Radiotherapy +/- short courses of chemo for stages IA+IIA
| Longer courses of chemo for more advanced disease
76
Hodgkin's Lymphoma
| Prognosis (2)
>95% in IA
| <40% with IVB
77
Non-Hodgkin's Lymphoma
| Definition (2)
All lymphomas without Reed-Sternberg cells
| Most are derived from B cells
78
Non-Hodgkin's Lymphoma
| Signs + symptoms (3)
Superficial lymphadenopathy (75% at presentation)
Possible sites: skin, oropharynx, stomach, small bowel, bone, CNS, lung
Pancytopenia from marrow involvement: anaemia, infection, bleeding
79
Non-Hodgkin's Lymphoma
| Investigations (2)
Blood: FBC, U&E, LFT, high LDH (worse prognosis, reflecting high cell turnover)
Marrow and node biopsy for classification
80
Non-Hodgkin's Lymphoma
| Treatment (3)
May need no treatment if no symptoms
Radiotherapy may be curative in localised disease
Rituximab
81
Non-Hodgkin's Lymphoma
| Prognosis (2)
Very variable
| 30% for high grade + >50% for low grade (5 year survival)
82
Bleeding
| Physiological processes of stopping bleeding (3)
Vasoconstriction
Gap-plugging by platelets
Coagulation cascade
83
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Bleeding
Vascular defects (3)
```
Lead to prolonged bleeding from cuts, bleeding into skin (bruising, purpura) and bleeding from mucus membranes (epistaxis, menorrhagia)
Congenital: Ehlers-Danlos
Acquired: seile purpura, steroids, Henoch-Schonlein purpura
84
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Bleeding
Platelet disorders (4)
```
Leads to prolonged bleeding from cuts, bleeding into skin and bleeding from mucous membranes
Decreased marrow production: marrow infiltration (leukaemia, ,yeloma), marrow suppression (cytotoxic drugs, radiotherapy)
Excess destruction: immune thrombocytopenic purpura (acute in children following infection or chronic in women), TTP or HUS
Poorly functioning platelets: myeloproliferative diseae, NSAIDs
85
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Bleeding
Coagulation disorders (3)
```
Cause delayed bleeding into joints and muscle
Congenital: haemophilia, von Willebrand's
Acquired: anticoagulatns, liver disease, DIC
86
Bleeding
| Investigations (5)
FBC, film + coagulation tests
Prothrombin time: thromboplastin is added to test the extrinsic system (coagulation), tests for abnormalities in factor I, II, V, VII, X, prolonged by warfarin, vit K deficiency, liver disease (shown as INR)
Activated partial thromboplastin time (APTT): kaolin added to test intrinsic system (coagulation) tests for abnormalities in factor I, II, V, VIII, IX, X, XI, XII, prolonged by heparin, haemophilia, DIC, liver disease
Thrombin time: prolonged by heparin, DIC
D-dimers: fibrin degradation product, occurs in DIC or in presence of venous thromboembolism
87
Bleeding
| Treatment (2)
If bleeding continues in presence of clotting disorder or massive transfusion, may need FFP + platelets
In ITP, steroids +/- IV immunoglobulin may be used
88
Blood Transfusion
| Packed red cells (3)
Used in transfusion for chronic anaemia
Used for acute haemorrhage
Usually over 2h but in an emergency stat
89
Blood Transfusion
| Platelets (3)
Highest risk of bacterial infection as stored at room temp.
Used for bleeding in thrombocytopenia
Used pre-op in thrombocytopenia to prevent bleeding
90
Blood Transfusion
| Fresh frozen plasma (4)
Contains clotting factors, albumin and immunoglobulin
Risk severe allergic reactions
Prophylaxis in major surgery, where risk of significant bleeding
Plasma replacement in massive transfusion
91
Blood Transfusion
| Acute haemolytic transfusion reaction (4)
Caused by ABO incompatibility
Red cells react with patients anti-A or anti-B antibodies causing rapid intravascular haemolysis of transfused cells and release of inflammatory cytokines leading to shock, AKI, DIC
Agitation, pyrexia, hypotension, abdo/chest pain, AKI, DIC
Stop transfusion, check identity and name on unit and inspect pack, inform haematologist, send samples to lab
92
Blood Transfusion
| Anaphylaxis (2)
More likely with platelets/FFP
| Bronchospasm, cyanosis, hypotension, angioedem
93
Blood Transfusion
| Transfusion associated lung injury (TRALI) (3)
Happens when donor blood antibodies react with patient neutrophils/monocytes/pulmonary endothelium causing leakage of plasma into alveolar spaces + ARDS
SOB, pyrexia, hypotension, cough
Stop transfusion, give O2, manage as ARDS, donor removed from panel
94
Blood Transfusion
| Transfusion Associated Circulatory Overload (TACO) (4)
Circulatory overload from red cell or high dose FFP transfusions
Within 6h of transfusion
SOB, hypoxia, tachycardia, elevated JVP, basal crackles, HTN
Stop transfusion, give O2, give furosemide
95
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Bone Marrow Failure
Marrow physiology (3)
```
Responsible for haemopoiesis
Normally takes place in central skeleton (vertebrae, sternum, ribs, skull) and proximal long bones
In some anaemias (eg. thalassaemia), increased demand induces haematopoiesis beyond the marrow, eg. in liver, spleen, causing organomegaly
96
Bone Marrow Failure
| Pancytopenia (3)
Reduction in all the major cell lines
| Due to reduced marrow production: aplastic anaemia, infiltration (eg. acute leukaemia, myelodysplasia, myeloma)
97
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Bone Marrow Failure
Aplastic anaemia (4)
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Rare stem cell disorder leading to pancytopenia and hypoplastic marrow (it stops making cells)
Presents with features of anaemia (low Hb), infection (low WCC) or bleeding (reduced platelets)
Most cases are autoimmune
Do allogeneic marrow transplant
98
Myeloproliferative Disorders
| Pathology (6)
Proliferation of a clone of haematopoietic myeloid stem cells in the marrow
Classification by cell type which is proliferating
RBC --> polycythaemia rubra vera
WBC --> chronic myeloid leukaemia
Platelets --> essential thrombocythaemia
Fibroblasts --> myelofibrosis
99
Myeloproliferative Disorders
| Polycythaemia rubra vera (4)
Cause: JAK2 mutation
Pathology: myeloproliferative disorder of red cells casing hyperviscosity and thrombosis
Signs + symptoms: hyperviscosity- headache, visual disturbance, dizziness, thrombosis, gout (high urate from RBC turnover)
Treatment: venesection in young or hydroxycarbamide if >60
100
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Myeloproliferative Disorders
Essential thrombocytopenia (2)
```
Pathology: myeloproliferative disorder of megakaryocytes causing increased platelets leading to bleeding, thrombosis and microvascular occlusion
Treatment: aspirin or hydroxycarbamide
101
Myeloproliferative Disorders
| Myelofibrosis (4)
Epidemiology: elderly
Pathology: myeloproliferative disorder with hyperplasia of megakaryocytes which produce platelet-derived growth factor, leading to intense marrow fibrosis and myeloid metaplasia (haemopoiesis in spleen and liver) --> massive hepatosplenomegaly
Signs + symptoms: night sweats, fever, weight loss, organomegaly, bone marrow failure (low Hb, infections, bleeding)
Median survival 4-5 years
102
Myeloma
| Aetiology (1)
Neoplastic disorder of plasma cells result in the excessive production of a single immunoglobulin (paraprotein)
103
Myeloma
| Pathology (5)
Plasma cells cause osteolytic bone lesions + bone marrow failure
Paraproteins deposited in kidney causing cast nephropathy and AKI
Hyperviscosity leads to microvascular congestion and bleeding
Hypogammaglobinaemia leads to imunoparesis (infections)
Hypercalcaemia occurs due to increased osteoclastic bone resorption caused by local cytokines released by myeloma cells
104
Myeloma
| Signs + symptoms (4)
```
Calcium increased (due to increased osteoclast activation by signalling myeloma cells)
Renal failure (amyloidosis, hyperviscosity, light chain deposition, monoclonal immunoglobulins cause glomerular changes)
Anaemia (or neutropenia/thrombocytopenia from marrow infiltration by plasma cells)
Bony lesions (causing back ache, pathological fractures and vertebral collapse)
```
105
Myeloma
| Investigations (8)
FBC: normocytic normochromic anaemia
Blood film: rouleaux formation
ESR: persistently elevated
Increased urea and creatinine
Increased calcium
Bone marrow biopsy: plasma cells increased
Screening test: serum and urine electrophoresis (monoclonal protein band)
X-rays: lytic lesions ('punched out' appearance)
106
Myeloma
| Treatment (8)
Analgesia for bone pain
Bisphosphonates
Transfusion + erythropoietin for anaemia
Renal failure: fluid intake increase, may need dialysis
Treat infections
Chemotherapy
Autologous stem cell transplant
Allogeneic transplant can be curative in younger people but carries high risk of mortality
107
Myeloma
| Prognosis (1)
Median survival 3 years
108
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Amyloidosis
Aetiology (2)
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Primary (AL amyloid): myeloma, lymphoma
| Secondary (AA amyloid): reflects chronic inflammation in RA, UC, Crohn's
109
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Amyloidosis
Prognosis (1)
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Median survival 1-2 years
110
Thrombophilia
| Definition (1)
An inherited or acquired coagulopathy predisposing to thrombosis
111
Thrombophilia
| Inherited (2)
Factor V Leiden: main cause, mutation in factor V Leiden stops it being broken down by APC (activated protein C)
Prothrombin gene mutation: high prothrombin levels due to down-regulation of fibrinolysis
112
Thrombophilia
| Acquired (2)
COCP
| Antiphospholipid syndrome
113
Thrombophilia
| Investigations (2)
FBC + film
| Clotting profile: PT, thrombin time, APTT, fibrinogen
114
Thrombophilia
| Treatment (2)
Standard VTE treatment
| Recurrence: consider lifelong warfarin
