Haematology Flashcards
1
Q
Anaemia
- Physiological effect
- What is it
- Classic symptoms
- Classic sign
A
Decreased oxygen transport, Tissue hypoxia, compensatory changes (inc RBC prod.)
low Hb (low red cell mass or inc plasma vol e.g. preg)
FDF
Fatigue, dyspnoea, faint
(may also worsen any symptoms related to hypoxia e.g. IC/angina)
Conjunctival pallor
2
Q
Normal Hb
A
Men: 13.5-17.5 g/dL (135-175g/L)
Women: 12.0-15.5 g/dL
3
Q
What is severe anaemia?
Feature
A
less than 80g/L
Tachycardia, inc CO, flow murmur, Cardiac enlargement
4
Q
Microcytic anaemia causes
A
TICS Thalassaemia Iron deficiency Chronic disease (20%) Sideroblastic
5
Q
Normocytic anaemia causes
A
Haemolytic anaemia
Pregnancy (increased plasma volume)
Bleeding (e.g. menses) Renal failure (decreased erythropoietin, may give recombinant)
Chronic disease (80%)
Primary marrow problem (Red cell aplasia, Myelodysplasia MM, infiltration)
6
Q
Macrocytic anaemia causes
A
B12
Folate
Drugs/alcohol
7
Q
Anaemia seen in Chronic disease
A
Microcytic in 20%
Normocytic in 80%
8
Q
What does reticulocyte level tell you in normocytic anaemia
A
Reticulocytes high (haemolytic or bleed)
If low:
Evidence of renal or endocrine failure or chronic inflammation (chronic disease)?
If No consider Primary marrow problem (Red cell aplasia, Myelodysplasia MM, infiltration)
9
Q
Where are Iron, Folate and B12 absorbed?
A
IRON = DUODENUM/JEJUNUM FOLATE = JEJUNUM B12 = ILEUM
10
Q
Iron transported by
Iron stored by (where is this)
A
Transferrin
Ferritin (intracellular)
11
Q
Iron deficiency anaemia:
- Causes
- Presentation
A
Inadequate intake
Poor absorption
Excessive loss
Excessive iron requirement
FPFD
Fatigue, Pallor, Faint, dyspnoea, Nail changes (Koilonychia - spoon, brittle), Mouth changes (Angular stomatitis, atrophic glossitis)
12
Q
Iron deficiency anaemia:
Inadequate intake
Poor absorption
Excessive loss
Excessive iron requirement
A
Diet
Surgery, Coeliac
GI bleed, Peptic ulcer (NSAID), surgery, Diverticulosis, Neoplasm, Menorrhagia.
Infancy, Pregnancy
13
Q
Iron deficiency: Hb MCV MCHC Iron studies (Serum iron, Ferritin, Transferrin, TIBC)
A
Hb
Less than 130g/L m, 120g/L f
MCV
Low - Microcytic
MCHC
Low - Hypochromic (Low Hb conc per cell)
Serum Fe: low
Ferritin: low
Transferrin Saturation: low
TIBC: increased
14
Q
What happens to ferritin in infection
A
This is an acute phase protein so inc in inflammation, infection, malignancy
15
Q
Iron deficiency anaemia Tx
SE
A
Oral Iron supplementation
(Ferrous sulphate
Continue for 3-6 months post Hb correction)
SE: constipation, black stools, vomiting
16
Q
When to transfuse in iron def anaemia
A
Transfusion if symptomatic at rest, dyspnoea, chest pain
17
Q
Sideroblastic anaemia
What is it
A
Ineffective erythropoiesis where iron can not be incorporated into Hb
18
Q
What is a Sideroblast
A
Abnormal erythroblast with perinuclear iron accumulation (Cant incorporate)
Microcytic anaemia resistant to iron supps
19
Q
Causes of Sideroblastic anaemia
A
Congenital (X-linked)
Acquired: Myeloma, B6 deficiency
20
Q
Sideroblastic anaemia
Hb
MCV
MCHC
Blood smear
Serum iron
Ferritin
TIBC
Marrow aspirate
A
Low Hb
MCV and MCHC low (Microcytic and hypo chromic)
Mix of normal and hypo chromic blood cells
Serum iron and ferritin high, TIBC low (not a problem with iron levels)
21
Q
Sideroblastic anaemia Tx
A
Mainly supportive
Iron chelation (removal) with Desferrioxamine - there is inc absorption or iron in Sideroblastic anaemia
22
Q
Chains seen in Hb:
HbA (normal adult)
HbF
A
2 x ⍺ + 2 x β
2 x ⍺ + 2 x ɣ (gamma)
23
Q
Beta-Thalassemia
- Pathophys
- Type of anaemia
- Mutation
- Genetics
A
Decreased (β+) Or Absent (β0) beta globulins. Alpha overprod to compensate = membrane damage/cell destruction
Microcytic
Chr 11 (β-glob gene)
Autosomal recessive
24
Q
Effect of Beta-Thalassemia
A
Cells can’t survive
Anaemia
-Microcytic
Erythroid hyperplasia
- Skull bossing/bony changes
- Hepatosplenomegaly (extra medullary hematopoiesis)
25
Types of Beta-Thalassemia + effect
Silent (Carrier)
Minor
Intermediate
Major
Normal Haem, These are carriers (Autosomal recessive disease)
Minor
- Mild anaemia
Intermediate
- Progressive pallor, abdo distension, skull bossing
Major
β0/β0
- Failure to thrive
26
Beta thalassaemia
FBC
Blood smear
Hb analysis
Other investigations
Microcytic
Target cells, Reticulocytes (nucleated RBC - haemolytic)
No HbA in Major, some HbA in others. HbF elevated in all
LFT (haemolysis = inc total and unconjugated bilirubin), Skull XR, Abdo USS hepatosplenomegaly.
27
Beta thalassaemia Tx
Genetic counselling, Transfusion if symptomatic/Surgry/Infection, Chelation (desferrioxamine)
28
Beta thalassaemia complications
Thrombotic
Iron overload (arthropathy, arythmias + contractile dysfunction)
Transfusion reactions/infections (HIV, HBV/HCV)
Splenectomy
29
Why splenectomy in Beta thalassaemia
Extramedullary erythropoiesis and multiple transfusion leads to hypersplenism
= inc transfusion requirement, leukopenia + thrombocytopenia
30
Alpha thalassemia
- Pathophys
- Type of anaemia
- Mutation
- Genetics
microcytic anaemia caused by mutation in alpha-globin genes. Dec alpha glob leads to excess beta prod.
Chr 16
Autosomal recessive
31
Alpha thalassaemia Pathophsy
Ineffective erythropoiesis (Alpha chain), microcytic anaemia and haemolysis
32
Genetics in Alpha thalassemia
There are two genes coding for alpha globulin from each parent (4 total)
HbA can be see with some Beta tetramers after 3 deletions ( less than this is mild anaemia)
4 deletions (mutations) leads to death in utero
33
Haemolytic anaemia:
- What is it
- Where can it happen
- Typical anaemia pattern
Premature destruction of RBC
1) intravascular (trauma e.g. mechanical heart valve, complement mediated/Autoimmune)
2) reticuloendothelial system (macrophages of liver, spleen, destruction due to immune tagging/opsonization)
Normocytic
34
Haemolytic Anaemia: Hereditary Vs Acquired Causes
Hereditary
- Enzyme defect (G6PD deficiency)
- Membrane defect (Spherocytosis)
- Abnormal Hb (Sickle cell)
Acquired
- Immune or non-immune mediated
35
Immune mediated haemolytic anaemia
- Cause
- Test + result
- Subtypes
Autoantibodies
Coombs antiglobulin +ve
Warm: IgG (Tx steroids)
Cold: IgM (Tx keep warm)
36
Non immune haemolytic anaemia
- Test and result
- Causes
Coombs negative
Infection (e.g. malaria), trauma, microangiopathic haemolytic anaemia (DIC, TTP, HUS, HELLP), hypersplenism, liver disease
37
Haemolytic anaemia presentation
RFs
Anaemia symptoms (Pallor, fatigue, dyspnoea, faintness)
Jaundice (inc bili due to haemolysis)
Autoimmune disease, Prosthetic valve, FH RBC defect, from Africa (malaria protection), Fava beans
38
Haemolytic anaemia
FBC
MCHC
Blood film
Other
Low Hb with reticulocytes
Inc MCHC suggests spherocytosis
sickle cells, spherocytes, heinz bodies (G6PDD)
Coombs test (+ve if immune), unconjugated bili mild elevation
39
Haemolytic anaemia
Differentiating between inc breakdown and increased production
Increased breakdown?
Increased bilirubin, increased urobilinogen, increased LDH
Increased production?
Increased MCV by increased reticulocytes, marrow hyperplasia
40
Haemolytic anaemia findings in
| Extravascular Vs Intravascular
Intravascular:
- inc free plasma Hb and haemoglobinuria
Extravascular:
- Splenomegaly
41
G6PDD
- pres
- investigate
FPFD+Jaundice, dark urine (intravasc), AKI (Hb precip)
FBC (low Hb, normal MCV, MCHC), Blood film (heinz bodies)
42
G6PDD
- Genetics
- Protective of what
- role of enzyme
- What precipitation haemolysis
x-linked,
malaria protective
protects from oxidative stress
Things that cause oxidation
Drug(cephalosporins)/fava bean, infection.
43
G6PDD Tx
Avoid precipitants
- Maintain fluid intake
- Folic acid 5mg orally (for RBC production)
- Blood transfusion if severe anaemia (<7g/dL)
- Renal support if renal impairment by haemoglobinuria (EPO)
44
Anaemia of chronic disease
- Description
- Mechanism
- types of disease assoc
Anaemia + evidence of immune system activation
Inflam (IL1/6)= decreased RBC prod and survival
Infection (acute and chronic), Neoplasm, autoimmune (RA, SLE), trauma, endocrine (DM), degenerative (CKD, CHF)
45
```
Anaemia of chronic disease blood results
RBC/MCHC
Reticulocytes
Iron
TIBC
Transferrin saturation
Ferritin
```
```
Normocytic normochromic/microcytic hypochromic
Low reticulocyte count
Low serum iron
High or normal TIBC (elevated ferritin)
Low transferrin saturation
Elevated ferritin
```
46
Anaemia of chronic disease
FBC
MCV + MCHC
Reticulocytes
Other investigations
Hb low, WCC/Pt may be raised
MCV/MCHC
Low or normal (Can be microcytic or normocytic)
Low Reticulocytes (Low prod.)
ESR/CRP
47
Anaemia of chronic disease Tx
Underlying cause
48
Aplastic anaemia
| triad
1) Pancytopenia
Neutropenia: infections
Anaemia: fatigue, pallor, dyspnoea, faintness
Thrombocytopenia: bleeding bruising
2) BM biopsy has hypocellularity,
3) No abnormal cells: no dysplasia or blasts
49
Caused of Aplastic anaemia
Acquired:
idiopathic, post drug/virus
Inherited: Fanconi anaemia, Shwachman-Diamond syndrome
50
Aplastic anaemia Tx (if severe)
Allogenic BM transplant if severe
RBC + Pt transfusion (in the meantime)
Abx (Prophylactic)
51
Causes of Neutropenia
what at risk of
```
Apalstic anaemia
Immunosuppression
Chemo
HIV
BM infiltration (MM)
```
Fatal infection (may also present atypically)
52
BM responsibility
| Which bones?
Haematopoiesis
Axial skeleton (vertebrae, sternum, ribs, skull)
Long bones
53
Sickle cell
- Autosomal ...
- effect of genetic mutation
Autosomal Recessive
Amino acid Glutamine replaced by Valine in beta chain of HbA resulting in sickling/cresent shape = HbS
54
Effect of RBC sickling
Disrupts blood flow/obstruction of small capillaries (shape)
Anaemia (varying degree) due to reduced RBC life and inc haemolysis
55
Effect of small vessel obstruction in SC
Painful crises
Organ damage
Increased vulnerability to infection
56
Sickle cell crisis precipitants
CHIDS
```
Cold
Hypoxia (extreme exercise)
Infection
Dehydration
Stress
```
57
Sickle cell epidemiology
Sub-Saharan africa (Malaria can live in sickled cells)
58
Sickle cell symptoms and signs
Anaemia + haemolysis (Fatigue, pallor, Faint, dyspnoea + Jaundice)
Vaso-occlusion: Dacytlitis, skeletal pain, chest/abdo pain, renal failure, CNS infarct, Priaprism
59
Sickle Cell Crisis
- Chest
- Bone
- Abdo
Acute chest: sickling in pulm vasc = pneumonia like syndrome)
Bone infarct and avast necrosis (e.g. femoral head). Osteomyelitis with salmonella
Acute abdo: mesenteric ischaemia, Splenic sequestration (stops blood leaving = engorgement) inc susceptibility to encapsulated bact (S.Pneuonia, H.Inf)
60
Sickle cell diagnosis
Guthrie 5 day heel prick test
61
Sickle cell infection prophylaxis
Give pneumococcal vaccine and penicillin prophylactically for pneumococcus
62
Sickle cell crisis Tx
Cross-match blood
Analgesia - paracetamol, ibuprofen, codeine phosphate or morphine (IV) (+antihistamine for pruritus with opiates)
Supportive care
- O2 (nasal cannula 2L/min) + treat cause e.g. correction of acidosis
- IV fluids (correct dehydration)
- Warmth
Antibiotics according to local guidelines
Give blood if Hb or reticulocytes fall quickly
63
Sickle cell chronic management
Manage chronic daily pain
Pneumococcal vaccination and penicillin prophylaxis
Trigger avoidance
Folic acid if severe haemolysis
Hydroxyurea (with monthly blood tests)
- Increases production of fetal haemoglobin - reduces painful crises
Repeat blood transfusion to maintain HbS below 30%
64
Sickle cell complications
Anaemia
Liver complications - jaundice, hepatomegaly and gallstones
Iron overload from chronic transfusion
Dactylitis
Leg ulcers
Priapism - requires urgent urological aspiration if >4 hours
CV - cardiomegaly
65
Causes of megaloblastic anaemia
B12/Folate deficiency
Alcohol
Drugs (hydroxyurea)
66
Causes of folate deficiency
Poor diet (in green veg, nuts, liver)
Inc demand (preg, renal disease)
Malabsorption (coeliac)
Drugs (Alcohol and anti-metabolites e.g. MTX)
67
Megaloblastic anaemia
Hb
MCV & MCHC
Blood smear
Other tests
Low Hb (may also have thrombocytopenia/neutropenia)
Elevated MCV/MCHC
Blood smear has macocytic RBS
Serum levels of B12/Folate will indicate the cause
IF antibody if pernicious anaem suspect
Other Alc related tests if suspect: Carbohydrate deficient transferrin
68
Folate deficiency Tx
ORal folic acid, Treat cause, packed red cell transfusion if severe/pancytopenia
69
B12
- use
- food
- deficiency due to ...
DNA synthesis (cofactor), nerves and red blood cells
Meat fish dairy
poor diet (Veg, vegan), old, surgery, Malabsorption (PPI/ H2 antagonists = acid needed to release B12 from food, pernicious anaemia = low intrinsic factor from parietal cells, coeliac, crohn's)
70
What binds B12
Intrinsic factor
71
B12 deficiency symptoms
Anaemia (Fatigue, Pallor, Faint, Dyspnoea)
Neurological - Posterior column degenerative = Paresthesia, Ataxia, loss of vibration
Mouth - glossitis
72
B12 def Tx
IM hydroxycobalamin (for 3 months, may be needed life long) - this is Vit B12a
73
Pernicious anaemia
- what is
- Assoc
- Complications
autoimmune disease with antibodies against IF or Parietal cells
Othe AI disease
Gastric cancer
74
Origins of haematological malignancy
BM: Myeloid
Lymphatic: Lymphoid (Can be B or T cell)
75
Haematological malignancy Tissue types
Leukaemia
Lymphoma
Myeloproliferative disorders
Leukaemia: Excess abnormal white cells (myeloid/from BM or lymphoid/lymphatic origin)
Lymphoma: Tumour presentation with lumps in lymphatic system
Myeloproliferative disorders: involve BM, liver and spleen
76
Haematological malignancy Clinical course types
Acute: rapid progression from onset. Life-threatening in weeks/months (AML = myeloid from BM, ALL = from lymphatics)
Chronic: slowly progressive, years between pres and clinical intervention
77
AML
- what is it
- Diagnostic feature
- Epidemiology
Clonal expansion of myeloid blasts in BM. Unable to diffrentiate into neutrophils
Bone marrow blasts over 20% OR blasts in peripheral blood
Most common Leukaemia in adults
78
AML associated diseases
Myelodysplastic syndrome,
Down’s syndrome,
Bone marrow failure syndromes (e.g. Fanconi, Diamon-Blackfan, aplastic anaemia),
79
What can cause AML
AML is a complication of Chemotherapy
80
AML prognosis
5 year survival 25%
81
AML investigations:
FBC + blood film
- Leukocytosis (inc WCC)
- neutropenia, thrombocytopenia, anaemia
Coagulation panel
- PT & PTT prolonged (thrombocytopenia)
BM biopsy (Diagnostic)
- Hypercellularity, over 20% blast cells
- Auer rods (needles of granular material in cytoplasm of blast cells)
CXR
- Pulmonary infiltrates
82
AML pres
Older person
Tiredness
Bruising/PEtechiae
Aching in bones (and boney tenderness)
Fever
83
AML Tx
Chemo: Cytarabine and Daunorubicin (watch for tumour lysis syndrome
Allogenic (donor match) stem cell transplant
84
Tumour lysis syndrome
Efflux of K+ = Hyperkalaemia (ECG)
Nucleic acid release -> purine catabolism -> high Uric acid = Uric acid crystals (AKI)
Phosphate (PO4) also released from intracellular. Causes HYPOCALCAEMIA (CATS) by binding to make calcium phosphate = stones = AKI
85
ALL Presentation
```
Younger child
Lethargy
Dyspnoea
Fever
Bruising
```
Hepatosplenomegaly
CXR: Mediastinal mass, pleural effusion
86
ALL
- What is it
- Diagnosis
- Epidemiology
- What has poor prognosis
Malignancy of lymphoid cells (B&T cells). Uncontrolled proliferation.
Lymphoid cells replace haemopoetic cells in BM
BM blasts voer 20%
Blood smear with leukaemic lymphoblasts
Most common childhood leukaemia (75% under 6yrs)
Philedelphia Chr (BCR-ABL fusion oncogene) = Poor prognosis
87
Symptoms of ALL CNS infiltration
Papilloedema
Nuchal rigidity
Meningism
Focal neurology: CN 3,4,6,7
88
ALL Investigations
FBC
- Leukopeia, thrombocytopenia, anaemia
Blood smear: Leukaemic blasts
BM biopsy (diagnostic)
- Hypercellularity
- Lymphoblasts (over 0-25%)
CXR: Mediastinal widening
LP and Pleural tap also give leukaemic lymphoblasts
89
ALL management
Chemo:
- Prednisolone + Vincristine + Daunorubicin (anthracycline) + TKinhib (imatinib)
If CNS disease: intrathecal MTX
```
Maintainence chemo (years):
- Mercaptopurine (daily) + MTX (weekly) + vincristine&prednisalone (monthly)
```
90
CML
- What is it
- Pres/symptoms
Uncontrolled proliferation of myeloid cells in bone marrow
1/3 asymptomatic
Malaise, Fever, Wt loss, splenomegaly (elevated WBC), night sweats, Arthralgia (inc uric acid from inc cell turnover)
91
What confirms Diagnosis of CML
Presence of Philadelphia chromosome/ BCR-ABL fusion gene confirms Dx
92
CML pathophys
Philedelphia chromosome oncogene causes active TK on myeloid cell surface = unregulated cell division
93
Complication of CML
May transform to accelerated (symptomatic) or blast phase (AML)
94
CML Investigation
Bloods: Leukocytosis (inc WCC), Anaemia
BM biopsy: Granulocytic hyperplasia
95
CML Tx
TK inhibitor: Imatinib
| Allogenic haemopoeitic stem cell transplant + Chemo cytarabine + daunorubicin
96
Philedelphia chromosome and prognosis
In CML = GOOD
in ALL = BAD
Philedelphia not good for kids...
97
What is a blast cell crisis
Seen in AML and CML
Leads to pancytopenia
98
CLL
- What is it
- What can trigger and in who
Malignancy of B lymphocytes that escape apoptosis. Involves BM, peripheral blood + haemopoietic organs (hepatosplenomegaly)
Pneumonia can trigger.
Risk increases with age. This is most common type of leukaemia.
99
AML
ALL
CML
CLL
Adults, myeloid cant make neutrophils
Kids, Philly = bad, years of chemo, malignant B&T from lymph replace haemopoietic in BM (pancytopenia)
Same as AML but slower rate, can switch to AML picture. Seen with Philadelphia chr
Most common leukaemia. B-cell apoptotic loss, hepatosplenomegaly (infiltration)
100
CLL symptoms
of anaemia
of infiltration
Other (remember the cell mainly involved)
SOB, fatigue
Hepatosplenomegaly,
Lymphadenopathy (painless + rubbery)
```
B-symptoms:
Fever/Chills
Night sweats
Weight loss
Fatigue
```
101
CLL investigation
FBC: MARKED lymphocytosis, low Hb, low pt
Blood film: smudge and smear cells (lymphocyte damage in slide prep
CT: hepatosplenomegaly, mediastinal lymph nodes
102
DDX CLL
Leukaemic phase of lymphoma
103
CLL Tx
Watch and wait if Hb and Pt normal (monitor FBC)
if anaemia/thrombocytopenia/lymphadenopathy
Chemo: Rituximab (B-CELL!) + cyclophosphamide + fludarabide + stem cell transplant (50% remission but high relapse)
104
CLL complications
Inc infection risk: lymphocytes cant produce antibodies (hypogammaglobulinaenia in IgA, IgG, IgM) - monthly IVIg
Autoimmune haemolytic anaemia: give prednisolone
105
Difference between leukaemia and lymphoma
Lymphoma is solid, leukaemia is circulating
106
Non-Hodgkin lymphoma name 4 types
```
Diffuse large B-cell (commonest - mainly B-cell lines)
Follicular
Burkitt's
Primary CNS
MALT
T-cell
```
107
What Lymphoma most common
Non-Hodgkin lymphoma 5X more common than Hodgkin
108
Non-Hodgkin lymphoma assoc disease
Associated with autoimmune disorders (Sjogren's RA, SLE, Coeliac, Pernicious anemia)
Assoc with immunodeficiency
109
Non-Hodgkin lymphoma presentation
Nodal: rapid lymphadenopathy
Extra-nodal: Pancytopenia, hepatosplenomegaly, dry cough (mediastinal mass)
Skin (t-cell)
```
B-symptoms:
Night sweats
Fever
Weight loss (over 10%)
Fatigue
```
110
Non-Hodgkin lymphoma Investigations
FBC: Pancytopenia (BM affected)
Lymph node core biopsy/BM biopsy
- Cytogenetics and tumour surface markers (diff in diff types)
Lactate raised
CXR: mediastinal nodes
111
What is used to stage Non-Hodgkin lymphoma
What does staging look at
What carries bad prognosis?
An Arbor
Lymph node involvement
B-symptoms = worse prognosis
112
Non-Hodgkin lymphoma Tx
Stage 1/2 = Radiotherapy
Chemo or stage 3/4
R-CHOP-21
rituximab, cyclophosphamide, hydroxy-duanorubicin, vincristine (oncovin) Prednisolone
21 days
113
Non-Hodgkin lymphoma chemo SE
Haematological (BM suppression) Infection (neutropenia) Cardiac (doxorubicin) Alopecia, chills, fever, hypotension (rituximab cd20 mAb)
114
Diffuse large B-cell lymphoma
80% cure
115
Hodgkin's lymphoma
- Cell type
- Common presentation
- Assoc cell
B-cells
Cervical or supraclavicular lymphadenopathy (painless)
30% have B-symptoms
Reed-Sternberg cells (multinucleate B-cells)
116
Hodgkin Lymphoma Causes&RFs
Immunodeficiency
- Primary (ataxia-telangectasia) or secondary (HIV, transplant)
Infection (EBV)
Autoimmune (SLE)
117
Hodgkin Lymphoma pathophys
Impaired immunosurveillance of B-cells (EBV infected esp). B cells escape regulation and proliferate
118
Hodgkin Lymphoma Presentation
Painless lymphadenopathy (supraclavic/cervical)
B-symp (25%) - night sweats, fever, weight loss
Pruritus
Alcohol induced pain
mediastinal lymphadenopathy (dry cough, SVC obstruct, chest pain)
119
Diagnosis Hodgkin Lymphoma
ESR - Raised = poor prognosis
CXR - mediastinal mass
Lymph node biopsy - Reed sterberg
120
Hodgkin Lymphoma Tx
Chemo BDDV + Radiotherapy
Bleomycin
Doxorubicin
Dacarbazine
Vincristine
121
Multiple myeloma 3 main features
1) Osteolytic bone disease (inhibitor of osteoprogenitor cells and thus osteoblasts in BM) + hypercalcemia
2) Anaemia - accumulation of plasma cells in BM
3) Renal disease - Bence-Jones proteins (immunoglobulin light chain found in urine of MM)
122
Multiple Myeloma
- Description
- Common symptoms
Clonal proliferation of plasma cells in BM assoc with monoclonal banding of Ig in serum/urine (bence-jones)
Bone pain, Anaemia, Fatigue, Hypercalcaemia
123
MM diagnosis
Serum and urine protein electrophoresis shows monoclonal bands of Immunoglobuilin (M-proteins)
M-Protein over 30g/L OR BM clonal cells over 30%
124
Tissue/Organ involvement in MM
CRAB
Calcium elevation
Renal insufficiency (Creatinine over 173mmol/L)
Anaemia
Bone disease (lytic or osteopathic)
125
MM Osteolysis, BM infiltrate and renal pathophys
Osteolytic due to Osteoclastic stimulation and low osteoblastic progenitors (BM) - Backache, pathological fracture, vertebral collapse
Pancytopenia: BM infiltration. neutropenia = infection
Renal impairment due to light chain depsition and precipitation with Tamm-horsfall protein in ascending loop of Henle
126
MM investigations
Serum and urine is gold standard:
- spike of IgG / IgM
- light chain urinary excretion (Bence-Jones
Skeletal survey (Bone scan)
Osteopenia
Osteolytic lesions (Raindrop skull)
Pathological fracture
BM aspirate: Plasma cell infiltrate over 30% = major
FBC = Anaemia
Serum Ca raised
Urine = Cr raised
127
MM Tx
Thalidomide + Dexamethasone + autologous stem cell transplant
Bone disease - bisphosphonates
Anaemia - EPO, transfuse
Infection - Abx, pneumococcal/flu vaccine
AKI - rehydration
128
What is Polycythemia
Inc proportion of Hb in blood
Relative = dec plasma vol
Absolute = Inc RBC number
129
Polycythemia cause
Overactive BM (predominantly RBC but also others)
130
Polycythemia complications
Hyperviscosity: thrombosis (Stroke, MI, DVT), haemorrhage
Myelofibrosis, AML
131
Polycythemia mutation
95% JAK2
132
Polycythemia presentation
Plethoric (RED and full) appearance
Pruritus, redness and pain in fingers/toes after hot bath
133
Investigations for Polycythemia vera
Raised Hb
Raised haemocrit
Raised Pt and WCC
BM: hypercellularity
134
Polycythemia Tx
Venesection, low dose aspirin,
135
Myelodysplastic syndrome
- Description
1) dysplastic changes in one or more cell lineages
2) Pancytopenia (anaemia, infection, bleeding)
3) predilection to develop AML
136
Myelodysplastic syndrome Causes
90% are primary
Radio/chemo causes 10% of Cases
137
What is Fanconi anaemia
Autosomal recessive BM failure syndrome
138
Cells which produce platelets
Megakaryocytes
139
Bleeding causes
Reduced platelet number
Reduced platelet function
140
Causes of dec platelet production
- BM infiltrate (leukaemia, myeloma, myelofibrosis)
- Liver disease (Thrombopoietin dec)
- Dec BM prod. (aplastic anaemia, B12/folate)
Dysfunctional Pt: Myelodysplasia
141
Causes of inc Pt destruction
Autoimmune - ITP
Hypersplenism
Drug - Heparin
Inc Consumption - DIC, TTP, HUS, Haemorrhage
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What is ITP
Pres
Tx
Idiopathic thrombocytic purpura
Autoimmune antibodies to platelets
Petechiae, mucosal bleeding, menorrhagia
Immunosuppression
-> IVIG+Corticosteroid+Pt trasfuse
(chronic cases get Rituximab)
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What is TTP
Why important
Absent VW breakdown enzyme (autoimmune) = spontaneous Pt aggregate in micro vasc (brain, kidney, heart)
Uses up Pt
95% fatal
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TTP Pentad Pres
Due to microvasc Thrombophilia
1. Fever
2. Renal failure 3. Haemolytic anaemia
4. Thrombocytopenia 5. Neurological change (coma, focal, seizure)
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TTP Tx
Urgent Plasma exchange + Prednisolone + Antiplatelet (aspirin)
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DIC pathophys
Coagulation pathways activated (e.g. due to endotoxin)
Diffuse fibrin deposition in microvasculature
Consumption of coal factors & Its (Bleeding)
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DIC Pres
Systemic collapse: Oliguria, Hypotension, Tachycardia
Bleeding: bruis, purpura (fulminant = necrotic), haemorrhage, petechiae, haematuria
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What is increased in DIC
PT (prothrombin time - extrinsic pathway)
aPTT (activated partial thromboplastin time - intrinsic pathway)
D-dimer
Fibrin degradation products
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What is decreased in DIC
Platelet count (thrombocytopenia)
Fibrinogen
Factor V, Factor 8
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DIC Tx
Treat underlying cause (usually sepsis)
To ITU
Supportive care:
- Pt transfusion
- FFP: replace coagulation factors
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Haemophilia
- Genetics
- Pres
X-linked recessive (Only in boys)
Bleeding pattern to muscles and joints
Presents in Toddlers
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VWD
- Genetics
- Pres
Autosomal dominant
Bleeding into mucus membranes/skin
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What is Haemophilia A and B
A = no Factor VIII
B = no Factor IX
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Haemophilia Tx & what to avoid
Recombinant F8 (A) and F9 (B)
Desmopressin (DDAVP - trade name) for mild type A
Avoid IM injections, Aspirin and NSAIDs
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vWD
- Pathophys
- Pres
- Tx
Defective vWF = defective platelet plug and factor 8 deficiency (vWF is protective usually)
Bruis, prolonged bleeding, mucosal bleed, epistaxis, menorrhagia
DDVAP (Demopressin)
Recombinant F8 if severe
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Clotting products synthesised by liver?
Coal factors
| Fibrinogen
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Vit K required for which factors
1972
Factors: II, VII, IX, X
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Cause of Vit K deficiency + Tx
Malabsorption (fat soluble vit so esp in obstructive jaundice - bile for fat)
Tx = Vit K
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Intrinsic pathway initiating factor
Factor XII --> XIIa
160
Extrinsic pathway initiating factor
Tissue factor
| Factor VII-->VIIa
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Coagulation cascade common pathway
X-->Xa
Xa =
Prothrombin --> Thrombin
Thrombin =
Fibrinogen --> fibrin
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What is the coat pathway
Proteolytic enzyme cascade circulating in inactive state
Activation generates Thrombin that cleaves fibrinogen to fibrin = stable fibrin clot
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Platelets:
- activated by
- adhere via
- bound together by
Endothelial damage (TF, vWF)
Collagen, vWF and GP1b
Cross linking of Pt with fibrin
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What occurs on Pt activation
Shape change to active form
Degranulation
- alph: PDGF, TGF-beta
- delta: ADP, ATP, Ca2+
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Aspirin&Clopidogrel
Vs
Heparin&Warfarin
Affect Pt function
Affect coagulation cascade
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Aspirin mech
Irreversibly inhibits COX1
| Prevent Thromboxane A2 thus prevent Pt aggregation and vasoconstriction
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Clopidogrel mech
Irreversible P2y12 antagonist (usually activated by ADP)
Inhibits ADP induced PT aggregation
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Heparin Vs Warfarin
Factors affected and testing effect
Heparin = Intrinsic/common pathway: Xa and thrombin (aPTT)
(LMWH: Dalteparin only does Xa - less risk bleed)
Warfarin = extrinsic pathway: 1972 (Vit K anatag)
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Risk of Heparin
Heparin induced thrombocytopenia: Bleeding
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What is INR?
This is way of monitoring Warfarin derived from PT
```
Aim = 2-3
higher range (e.g. mechanical valve) 3-4.5
```
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NOACs
- examples
- effect
- indications
- benefit
- problem
Apixiabn, rivaroxiban, dabigatran
Direct Xa or Thrombin inhibitors
DVT/PE and AF
Require no monitoring
NOT easily reversible
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Difference between arterial and venous thrombosis
Arterial - Platelet rich.
Seen with atherosclerosis + RF
Venous - fibrin rich (DVT/PE)
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Tx of DVt/PE
LMWH s/c then oral Warfarin 3 months if provoked, 6 if unprovoked)
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Wirkows triad
Contributors to Thrombosis (arterial and venous)
Venous stasis
Hypercoagulable state
Endothelial injury
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Acquired hyper coagulable state
```
95%
Antiphospholipid syndrome
Cancer
Slow flow - sickle cell, PRV (viscous)
Nephrotic syndrome
Obesity
Pregnancy
```
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Inherited hyper coagulable state (5%) - Screen these for DVT
Protein C deficiency (break clot)
Protein S deficiency (break clot)
Factor V Leiden (AD)
Factor 5 is a cofactor for factor Xa to activate prothrombin to thrombin
In Leiden factor 5 is resistant to degradation
Antithrombin deficiency (break clot)
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Blood type A (can sub for B)
- antigen
- antibody in plasma
- Can receive from
- Can donate to
A
Anti-B
A & O
A and AB
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Blood type AB
- antigen
- antibody in plasma
- Can receive from
- Can donate to
A and B
Neither
O, A, B & AB
AB only
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Blood type O
- antigen
- antibody in plasma
- Can receive from
- Can donate to
None
Anti-A and Anti-B
O only
All
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What needs to be checked in women before giving blood
Rhesus status
Rhesus positive = fine
Rhesus -ve cant get +ve blood
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Group and Screen:
- what it looks at
- when might be needed
Group - ABO and Rh (C,D,E) status
Screen - Screen’s for antibodies to other antigens
Any chance might need blood: trauma, haemorrhage, surgery
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When is whole blood given
Correcting hypovolaemia rapidly
| e.g. following blood loss
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When are packed red cells given
How much does 1 unit raise Hb
Acute haemorrhage and chronic anaemia
Not given unless Hb less than 70g/L
1 unit raises by 10g/L
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when are Pts given
Thrombocytopenia + Bleeding
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When is FFP given
Factor V and VII in plasma
| Given in DIC, Liver disease
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What can be given to cancer/chemo patient unresponsive to Abx
Granulocytes
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Blood transfusion complications (3 categories)
Infection
Acute (non-infectious)
Delayed (non-infectious)
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Blood transfusion related infection
HBV, HCV, HIV
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Acute transfusion reactions
Haemolytic: ABO incompatible
Febrile non-haemolytic: antibodies to leukocytes
Anaphylaxis
Transfusion related lung injury
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Delayed reactions
Iron overload
| Delayed haemolytic reaction
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Acute haemolytic reaction Pres and Tx
Fever, Chest pain, infusion site pain
discontinue blood + give Fluids
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Allergic transfusion reaction (anaphylaxis)
Flushing, dyspnoea, pruritus, hypotension
discontinue blood + adrenaline + secure airway (intubate) + salbutamol ± antihistamine
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Febrils transfusion reaction
Fever
Stop blood, Antipyretic
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Definition of Hypersplenism
pancytopenia in patients with an enlarged spleen.
| Causes CHINA - MMM
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CHINA MMM causes for hypersplenism
```
Congestion (Portal HTN, Budd-Chiari)
Haematological (haemolysis, Sickle, PRV)
Infection (Malaria, EBV, HIV)
Neoplasm (CML, Lymphoma)
Autoimmune/connective tissue (RA, SLE, Sarcoid)
```
chronic Myeloid leukaemia
Myelofibrosis
Malaria
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Hyposplenism:
- what is it
- causes
- complications
Hyposplenism (physiological loss of function)
e.g. sickle cell (splenic infarct) Coeliac
Splenectomy
This leads to an increased risk of infection from encapsulated bacteria (strep)
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Hyposplenism Management
Oral phenoxymethylpenicillin + or macrolides (azithromycin/clarithromycin)
Pneumococcal vaccine and influenza vaccine
Carry health alert card
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Types of BM transplant
Autologous (own BM harvested
- reduced chance reject
- lower risk infection
Allogenic (healthy donor)
- must match HLA to patient (at 3 loci)
- normally sibling/relative
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BM transplant procedure
1) BM Harvest under GA (Self or Donor) / Stem cells collected form blood
2) ablative chemo/radiotherapy
3) BM/stem cells given IV as inpatient
200
BM transplant complications
infection - post procedure immunosuppression
Mucositis (chemo damages mouth/throat
Graft Vs Host if non-self (donated marrow recognises body as non-self and immune response ensues)
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Use of hydroxycarbamide
Sickle cell
| decreased production so upreg fatal Hb
