Haematology Flashcards
(227 cards)
1
Q
When are eosinophils elevated
A
Parasitic infections
2
Q
What is elevated in myelodysplastic syndrome
A
Monocytes
3
Q
Define thrombocytosis
A
Too many platelets
> 400 x 10^9 / L
4
Q
Define thrombocytopenia
A
Platelet deficiency
<150 x 10^9 / L
5
Q
Define lymphocytosis
A
Too many lymphocytes
> 3.5 x 10^4
6
Q
Define lymphocytopenia
A
Less lymphocytes
<1.3 x 10^4 / L
7
Q
Define neutrophilia
A
Increased neutrophils
> 7.5 x 10^9 / L
8
Q
Define neutropenia
A
Low neutrophil count
<2 x 10^9 / L
9
Q
What might give you neutrophilia
A
Acute bacterial infection
10
Q
What might give you neutropenia
A
Myeloma
Lymphoma
11
Q
What might cause lymphocytosis
A
Chronic infection
12
Q
What is clotting screening
A
AKA a coagulation screen…
a group of tests used for haemostatic assessment. The screen consists of the Prothrombin time, INR, APTT, APTT ratio and derived fibrinogen
13
Q
What is prothrombin time
A
PT / INR shows…
Coagulation speed through the EXTRINSIC PATHWAY
PT:10-13.5s
Normal INR: 0.8-1.2 ; if on warfarin: 2-3!!!
14
Q
Define INR
A
International normalised ratio
Ratio of…
Tested PT / Normal PT
I.e.
Patient PT / Reference PT
15
Q
What factors are included in the extrinsic coagulation cascade
A
3 … 7 … 10
16
Q
What clotting factors are included in intrinsic coagulation cascade
A
12 … 11 … 9 … 8 … 10
17
Q
What increases INR
A
Remember when using warfarin… INR is HIGHER (from 0.8-1.2 to 2-3)
So INR is higher the LESS coagulative the blood is…
Vit K deficiency
Anticoagulants
Liver disease
DIC (Disseminated intravascular coagulation)
18
Q
What is APTT
A
Activated Partial Thromboplastin Time
Coagulation speed through intrinsic pathway
35-45s ; if on heparin: 60-80s
19
Q
Which diseases is APTT affected by
A
Haemophilia A (factor 8)
Haemophilia B (factor 9)
VWF disease
All these condition cause PT normal & prolonged APTT!!
20
Q
Define thrombin time
A
AKA bleeding time
Measure of how long the blood’s plasma takes to form a clot.
This test shows how long it takes fibrinogen to turn into fibrin
12-14s
21
Q
What is the common pathway of coagulation cascade
A
10 .… 2 … 1
|
5
22
Q
What is mean corpuscular volume
A
Size and volume of RBC
23
Q
What are the ranges for MCV and what do they indicate
A
Microcytic [< 80]
Normocytic [80-95]
Macrocytic [> 95]
24
Q
Types of microcytic anaemia
A
Thalassaemia Alpha / Beta (actually haemolytic too)
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
25
Types of normocytic anaemia
Haemolytic:
Sickle cell anaemia
G6PD deficiency
AHA (autoimmune haemolytic anaemia)
Hereditary spherocytosis
Non-haemolytic:
Aplastic
Chronic disease [esp. CKD]
Pregnancy
Myelophthisic anaemia
26
What happens to Reticulocyte in Normocytic anaemia
In haemolytic anaemia get raised Reticulocytes
[lots of RBC death BUT as compensation, get good bone marrow response]
In non-haemolytic anaemia get reduced reticulocytes
[due to failing bone marrow]
27
Normal lifespan of RBC
120 days
I.e. 3 months
28
Lifespan of RBC in haemolytic anaemia
5-10 days!!!
29
What’s haemoglobin range for anaemia
Men < 130 g/L
Women < 120 g/L
30
For anaemia when should transfusions be considered
When…
Hb < 70
Or
Hb < 80 + cardiac comorbidity
31
Types of Macrocytic anaemia
Megaloblastic:
B12 deficiency
Folate deficiency
Non-Megaloblastic:
Alcohol
Hypothyroidism
Non-alcoholic liver disease [NALD]
32
General symptoms of anaemia
Pallor
Fatigue
Exertional SoB
Chest pain + Tachycardia + hypotension + palpitations
33
What is most common anemia worldwide
Iron deficiency
34
Epidaemiology of iron deficiency anaemia
Most common anaemia
F>M
Over 500 million cases
35
Causes of iron deficiency anaemia
**Malnutrition / less iron intake in diet**
[seen in vegetarians]
**Malabsorption**
[coeliac / IBD]
**Severe blood loss**
[trauma / menorraghia (F) / _hookworm_ (most common worldwide for GI blood loss) / colon cancer (RED FLAG for elderly > 60y/o with iron deficiency]
**increased requirement - pregnancy**
36
Pathophysiology of iron deficiency anaemia
Non-inherited iron deficiency leads to impaired synthesis of haemoglobin
Iron is an important component of heme which is used in the haemoglobin to help carry O2
**Absorption in duodenum / proximal jejunum - where its slightly acidic**
Iron either travels around the blood as ferric ions [Fe3+] bound to transferrin protein , stored as ferritin or incorporated into Hb!!
When your iron is deficient, there’s **less heme groups synthesis** and therefore smaller RBC - microcytic Anaemia
37
Signs and symptoms of iron deficiency anaemia
General anaemia +
**Koilonchya (spoon-shaped nails)
Angular stomatitis (mouth corner ulceration)
Atrophic glossitis (tongue enlargement)
Hair loss … Brittle hair + nails**
38
Diagnosis and investigation of iron deficiency anaemia
1st line:
FBC - microcytic anaemia
Blood film
*Hypochromic, target cells, Howell jolly bodies*
Fe studies
*low serum iron, ferritin, transferrin saturation*
*high TIBC*
Gold standard:
**Bone marrow biopsy** is for when all other cause for iron deficiency have been ruled out…
*idiopathic iron deficient anaemia*
39
Iron deficiency anaemia for investigation for > 60y/o
Endoscopy - high risk of colon cancer
40
What’s are target cells
Non-specific bulls eye pattern RBC
41
What are howell jolly bodies
Non-specific uncleared RBCs
Where remanent of DNA is not removed via spleen
42
Treatment for iron deficiency anaemia
Treat underlying cause + oral iron…
**ferrous sulphate**
43
Side effects of ferrous sulphate
Given in iron deficiency
**black stool**
Diarrhoea / constipation
GI upset
44
If ferrous sulphate is poorly tolerated, what is an alternative
**Ferrous gluconate**
Then…
**CosmoFer** (injection version if tablets can’t be taken)
*remember: risk of anaphylaxis & avoid during sepsis*
If all else fails…
Give blood transfusion
45
Condition which is autosomal recessive haemoglobinopathy
Thalassaemia
*Can also be Sickle Cell Anaemia*
46
Epidaemiology for Thalassaemia
Autosomal recessive
Mediterranean ancestry
Prevalent where malaria is *(carrier of Thalassaemia - protective against malaria)*
47
Types of haemoglobin
HbF
X2 Alpha
X2 Gamma chains
HbA
X2 Alpha
X2 Beta chains
HbA2
X2 Alpha
X2 delta chains
48
Pathophysiology alpha Thalassaemia
4 genes on chromosome 16
**deletion** of these genes causes defect in alpha globin chains
**Associated with HbH** - an abnormal Hb isoform where beta tetromers are formed
**1 gene deletion**
carrier
*asymptomatic*
**2 gene deletion**
alpha Thalassaemia minor
The deletion could be ‘Cis’ or ‘Trans’ :
Cis - deletion is on same chromosome - Prevalent in Asian populations
Trans - deletion is on each chromosome - Prevalent in African population
**3 gene deletion**
HbH disease - marked anaemia
HbH causes hypoxia in 2 ways :
**Haemolysis**
Intramedullary haemolysis - Breakdown of RBC in bone marrow
Extravascular haemolysis - Breakdown of RBC by macrophages in spleen
HbH has **high O2 affinity**
Oxygen isn’t released to tissues as readily
That means that because of the hypoxia the extramedullary tissues (liver & spleen) compensate by increasing RBC production
Overworking the bone marrow, liver and spleen as compensation causes them to **enlarge**
**4 gene deletion**
Hb BART’s hydrops fetalis
When all 4 alpha genes are deleted, as a foetus you end up with 4x gamma chain tetromer
This has extremely high O2 affinity (100x more) so, the tissue is supplied with little to no oxygen —> severe hypoxia
The hypoxia leads to heart failure, Hepatosplenomegaly, kidney failure
All of this causes full body oedema in foetus
**Incompatible with life in utero or soon after birth**
49
Signs and symptoms of alpha Thalassaemia
General anaemia Sx
*Pallor, Exertional dyspnoea, fatigue, tachycardia+hypotensive, chest pain*
+
Skeletal deformities
Hepatosplenomegaly
50
Investigations / diagnosis of alpha Thalassaemia
**FBC + blood film**
Hypochromic RBCs, target cells, microcytic anaemia with increased reticulocytes [haemolytic anaemia]
**Hb electrophoresis** (diagnostic)
Shows Hb type populations
**Genetic testing** - definitive diagnosis
Prenatally this can be done via fetal DNA :
- Using chorionic villus sampling
- Amniocentesis
51
Treatment for Alpha Thalassaemia
**Mild**
usually doesn’t need treating
**Severe Thalassaemia**
Blood transfusions
May need iron chelating to trap excess iron (prevent iron overload) - desfemoxamine
If Dx Hb BARTS hydops fetalis prenatally, can give Tx of intrauterine transfusion
Later on can give bone marrow transplant
Splenectomy - wait till after 6y/o (has defensive role using encapsulated bacteria
Definitive / curative = Bone marrow transplant (risky)
Haemolytic anaemia so give folate supplements
52
Give an iron chelating drug + its side effect
Desfemoxamine
Side effect : deafness, cataracts
53
Chromosome affected in alpha Thalassaemia
Chromosome 16
4 genes ; Mutations leading to gene deletion
54
Chromosome affected in beta Thalassaemia
Chromosome 11
2 genes ; mutations lead to defective genes
55
Pathophysiology for beta Thalassaemia
You have normal Hb isoform, just depleted beta chains
B- = reduced beta chain gene coding
B0 = absent beta chain gene coding
BB- / BB0 === carrier / asymptomatic (**thalassaemia minor**)
B-B0 / B- B- === marked anaemia (**Thalassaemia intermediate**)
B0B0 === severe anaemia (**thalassaemia major**)
When RBCs are Beta globin chain deficient, free alpha chains build up in them causing **inclusions**
56
What are RBC inclusions ad when are they seen
Seen When RBCs are Beta globin chain deficient, free alpha chains build up in them causing inclusions
Inclusions damage cell membrane of RBCs therefore the RBCs need to be broken down by either…
Haemolysis (in the bone marrow)
This results in the contents of the RBC to flow in the blood plasma.
Haem is recycled into unconjugated bilirubin and iron
Excess unconjugated bilirubin over time leads to jaundice
Iron deposits that can the lead to **haemochromatosis**
Haemochromatosis = An iron storage disorder that results in excessive total body iron and deposition of iron in tissues
57
Complication of beta thalassaemia
Arrythmias, Pericarditis, Cirrhosis, hypothyroidism and D.M
58
Investigation / diagnosis for beta thalassaemia
**FBC + blood film**
Hypochromic RBCs, target cells, microcytic anaemia with increased reticulocytes [haemolytic anaemia]
**Haemoglobin electrophoresis** (diagnostic)
- Low HbA
- High HbF and HbA2
Remember this is because excess Alpha chains end up binding to the gamma and delta chain
59
Treatment for beta thalassaemia
Beta-Thalassaemia doesn’t always need Treatment but for intermedia and major…
Regular blood transfusion
Prevent iron overload using iron chelating agents
Could do splenectomy when splenomegaly causes extra haemolysis.
60
In which condition is chipmunk facies seen in
Beta thalassaemia major
61
Signs and symptoms for beta thalassaemia
Mild, moderate may be asymptomatic
**General anaemia Sx** (pallor, dyspnoea and fatiguability)
+
**bone deformities**
_Chipmunk Facies_
- Enlarged forehead and enlarged cheekbones
- This is because for chronic anaemia the body compensated for the reduced RBC and undergo extramedullary haemopoesis + bone marrow expansion - as RBCs are produced from these sites.
+
Other signs and symptoms it causes:
**Hepatosplenomegaly
Jaundice
Gall stones** - Px might present with RUQ pain / swollen abdomen (haemolysis of RBC causes an increased breakdown of them releasing uric acid leading to gall stones and gout)
62
Define Sideroblastic anaemia
Microcytic
Defective Hb synthesis because of pathological accumulation of iron in RBC mitochondria with the inability for iron to be incorporated in the Hb as its **trapped in mitochondria**
Lack of incorporation due to ALA synthetase deficiency
I.e. *functional Fe3+ deficiency*
63
Enzyme deficiency in Sideroblastic anaemia
ALA synthetase deficiency
64
Inheritance pattern for siderblastic anaemia
X linked
65
Investigation / diagnosis for Sideroblastic anaemia
**FBC + blood film**
Microcytic with _ringed siderblasts_ + _basophilic stippling_ [increased basophilic granules]
**Iron studies**
High serum Iron
High ferritin
High transferrin
Low TIBC
66
What type of anaemia is sickle cell anaemia
Normocytic
67
Inheritance pattern for sickle cell anaemia
Autosomal recessive
Haemoglobinopathy
68
Which chains are affected in SS anaemia
Beta globin chains
69
Epidaemiology for SS anaemia
Commonest in Africa - antimalarials properties as carrier against falciparum malaria
70
Affected genotype for SS anaemia
HbS HbS - sickle cell disease (autosomal recessive)
HbS - the abnormal variant for sickle cell haemoglobin
71
Chromosome affected leading to HbS in sickle cell anaemia
Chromosome 11 - beta globin chain defect
*same in beta thalassaemia*
72
Pathophysiology for sickle cell anaemia
**GAG to GTG** (Glutamic acid - Valine) on 6th codon of beta globin gene
causes
Irreversible RBC sickling
More fragile RBC -> less efficient and more likely to get stuck in capillaries
Risk of sequestration
SS anaemia = haemolytic
Intravascular - inside vessels (marked by increased haptoglobin)
Extravascular - outside vessel (@ spleen)
73
Signs and symptoms of SS anaemia
General Sx of anaemia (pallor, dyspnoea, fatigue)
+ jaundice (haemolytic anaemia = pre-hepatic)
+ splenomegaly
74
Complication of SS anaemia
**Splenic sequestration** - can cause autosplenectomy
**Vaso-occlusive crisis** - clogging capillaries causing distal ischaemia + polymerise & trap in long bone blood vessel
**acute chest crisis** - pulmonary vessel Vaso-occlusion + cause of resp. Distress ; emergency
75
What is SS anaemia precipitated by
**infection**
**cold**
**hypoxia**
**acidosis**
Dehydration
76
Which anaemia is osteomyelitis
Common in sickle cell
Osteomyelitis is usually due to S. Aureus, but in those with SS = salmonella
77
Investigation / diagnosis for sickle cell anaemia
**Heel prick test** (tests for sickle cell, hypothyroidism, cystic fibrosis)
**FBC + Blood films** (normocytic normochromic with increased reticulocytes)
Sickled RBCs + Howell jolly bodies
**Hb electrophoresis** = **diagnostic** ; proportion of Hb (90% HbS)
78
Treatment of SS anaemia
For acute complicated attacks :
IV fluids + analgesia (NSAIDs) + O2 + (antibiotic for infection)
Avoid precipitants
**Hydroxycarbamide** (aka hydroxyurea) + Folic acid supplement
**transfusion + Fe chelation**
Last resort - bone marrow transplant
79
Inheritance pattern for G6PDH deficiency
X linked recessive
Enzymopathy
80
Role of G6PDH
G6PDH is protective against oxidative damage
It’s involved in **glutathione synthesis**
Which protects against reactive oxidative species like H2O 2
81
Epidaemiology of G6PDH deficiency
Causes half lifespan and degradation of RBC
Africa & Asia
82
Signs & symptoms of G6PDH deficiency
Asymptomatic unless precipitated
Could cause an attack
**rapid anaemia
Jaundice**
83
Type of haemolysis in G6PDH deficiency
Intravascular haemolysis
84
Precipitating factors for G6PDH deficiency
**FAVA / BROAD beans** - metabolised into R.O.S
**Anti-malarials** (e.g. quinine)
**Nephthelene** - in moth balls & pesticide (major cause)
**Nitrofurantoin** - Antibacterial for UTIs
Aspirin
The key piece of knowledge for **G6PD deficiency relates to triggers**. In your exam look out for a **patient that turns jaundice** and **becomes anaemic after eating broad beans**, developing an **infection** or being **treated with antimalarials**. The _underlying diagnosis might be G6PD deficiency._
85
Investigation / diagnosis for G6PDH deficiency
FBCS + blood films:
Normal in between attacks
During attacks : Normocytic Normochromic with increased reticulocytes
**Heinz bodies** + **bite** cells
*Remember : beans means Heinz!!! —— Bite beans to eat them*
**decreased G6PDH level**
86
Treatment for G6PDH deficiency
Avoid precipitants
Blood transfusion when attacks ensure
87
Inherited pattern for hereditary spherocytosis
Autosomal dominant
Membranopathy
88
Epidaemiology of hereditary spherocytosis
N. Europe + America
89
Define hereditary spherocytosis
Deficiency in structural membrane protein **spectrin**
Makes RBCs more spherical & rigid
… leads …
Increased splenic recycling causes splenomegaly as rigid cells get stuck in spleen (risk of autosplenctomy)
90
Signs & symptoms of hereditary spherocytosis
General anaemia symptoms (pallor, dyspnoea, fatigue)
+
**Neonatal jaundice**
**Splenomegaly**
**Gallstones** (50%)
91
Investigation / diagnosis for hereditary spherocytosis
FBC + blood film
Normacytic normochromic + increased reticulocytes
Spherocytes
**Direct Coombs -ve ;
+ve in AHA (autoimmune haemolytic anaemia!!!)**
92
Treatment for hereditary spherocytosis
Splenectomy
Wait till at least 6y/o due too sepsis risk - spleen fights off encapsulated bacteria
In neonatal jaundice - Tx = phototherapy
If untreated, risk of **kernicterus ** - bilirubin accumulates in CNS basal ganglia ; CNS dysfunction + death
93
Type of haemolysis in hereditary spherocytosis
Extravascular haemolysis
94
Subtypes of autoimmune haemolytic anaemia (AHA)
Warm (most common) - It is usually idiopathic
Cold - the antibodies against red blood cells attach themselves to the red blood cells and cause them to clump together (agglutination) - triggers immune system against RBC clumps and increased spleen degredation of RBC
95
What other conditions is Cold type AHA secondary too
Lymphoma, leukaemia, systemic lupus erythematosus and infections (EBV, CMV, HIV)
96
Type of haemolysis in AHA
Extravascular + intravascular haemolysis
97
Investigation / diagnosis for AHA
**Direct Coombs +ve**
(as there’s agglutination of RBCs with Coombs reagent)
*Remember Coombs -ve in hereditary spherocytosis*
98
Types of non-haemolytic anaemia
All normocytic
CKD
Aplastic Anaemia
Myelophthisic anaemia
99
What is bone marrow activity in CKD and why
Reduced bone marrow activity because CKD is a cause of non-haemolytic anaemia
Due to decreased erythropoietin secretion, reduced stimulation for erythropoiesis…
*In non-haemolytic there is no stimulation / turnover of RBC in Bone Marrow **but** in haemolytic anaemias, increased reticulocytes…*
100
Define aplastic anaemia
Pancytopenia - where bone marrow fails so no production of heamopoetic stem cells
101
Aetiology / cause of aplastic anaemia
Idiopathic (mostly)
Might be triggered by infection (parvovirus, EBV)
102
Investigation / diagnosis of aplastic anaemia
FBC - normocytic anaemia with reduced reticulocytes
Bone marrow biopsy - hypocellularity
103
Treatment for aplastic anaemia
Increased risk of infection (neutropenia) - give broad spec Antibiotic
+
Bone marrow transplant
104
Define Myelophthisic anaemia
Normocytic non haemolytic anaemia
When bone marrow is replaced with something else like malignancy
105
What type of anaemia is pernicious anaemia
Macrocytic Megaloblastic anaemia
106
Give types of Macrocytic anaemia
**Megloblastic** :
Pernicious / B12 deficiency
Folate deficiency
**Non-megaloblastic / Normoblastic Macrocytic** :
Alcohol
Liver disease
NALD - non-alcoholic liver disease
Hypothyroidism
107
What does it mean if RBCs are non Megaloblastic but are Normoblastic Macrocytic?
Megloblastic = impaired DNA synthesis causes cell to enlarge but not end up dividing
But Normoblastic Macrocytic is when the cell DNA synth is functional, RBCs just have high MCV
108
How does alcohol cause anaemia
Toxic to RBC
Also depletes folate (+ B1 -*Thiamine*)
109
How does hypothyroidism lead to anaemia
Interference with EPO ; multi factorial
110
How does liver disease lead to anaemia
Decompensated liver cirrhosis (HBV associated +/- HCC) - **strongly linked to Macrocytic anaemia**
Short-term predictor of mortality
*Several factors- increased LDL deposition on RBC surface;increasing MCV...OR... Related to b12 and folate deficiency*
111
Define pernicious anaemia
AKA B12 deficiency
112
Epidaemiology of B12 deficiency
Older patients - takes years to develop
Increased in long-term vegans
113
Causes of B12 deficiency
Malnutrition
Malabsorption - Crohns
Pernicious anaemia (antibodies against parietal cells + Intrinsic Factor)
114
Which cells are produced to help with b12 absorption
Parietal cells in stomach
Produce intrinsic factor
115
Where is b12 absorbed
Ileum
116
Pathophysiology of b12 deficient anaemia
Typically, b12 binds to transcolbamin-1 in saliva (protection against stomach acid)
Binds to intrinsic factor in duodenum
Absorbed as b12-IF complex in ileum
**but**
autoimmune condition where antibodies form against the parietal cells or intrinsic factor. A lack of intrinsic factor prevents the absorption of vitamin B12 and the patient becomes vitamin B12 deficient.
117
Signs and symptoms of b12 deficiency anaemia
General anaemia Sx (pallor, dyspnoae, fatigue) +
**Lemon yellow skin
Angular glossitis + stomatitis**
If severe :
**Neurological Sx** -
_Symmetrical paraesthesia_ (pins & needles),
Loss of proprioception / vibration
muscle weakness
* **For your exams remember testing for vitamin B12 deficiency and pernicious anaemia in patients presenting with peripheral neuropathy, particularly with pins and needles.**
118
Why does Px present with angular stomatitis / glossitis in pernicious anaemia
B12 helps **cell division by helping synthesis of DNA precursor**
Deficiency interrupts cell division… esp rapidly dividing ones
(Hence pancytopenia)
Tongue mucosa is rapidly dividing too so when damaged, cells aren’t replaced leading to inflammation etc…
119
Cause of neurological Sx in pernicious anaemia
Small amounts of methylmalonic acid is produced during metabolism (too much is harmful) - b12 is used to metabolise it
Deficiency means a build up of methylmalonic in myelin sheath of neuron - causing degeneration of myelin sheath
**Communication between neurons gets significantly slower, which leads to impairment of neurological and muscle function.**
120
Investigation / diagnosis for b12 deficiency anaemia
FBC + blood film:
Macrocytic anaemia
Megaloblasts - hypersegmented nucleated neutrophils (> 6 lobes)
*more lobes = more immature cell, as DNA mature becomes compact*
Serum b12 (low)
Auto Antibodies -
anti-intrinsic factor antibodies (_diagnostic_ - but not present in all Px)
Anti-parietal antibodies
121
Treatment for pernicious anaemia
Dietary advice (salmon, eggs)
+
B12 supplements (PO, hydroxycobalamin)
122
Name for vitamin b12
Cobalamin
123
Time of development for folate deficiency
Months
B12 deficiency takes years
124
Causes of folate deficiency anaemia
Malnutrition
**pregnancy**
Malabsorption
Drugs - **trimethoprim** + methotrexate + sulfasalazine
They are dihydrofolate reductase inhibitors … **so** …
mTHF ——x——> THF (THF is what folate is converted to in the lining to be used for DNA synthesis)
125
Signs and symptoms of folate deficiency anaemia
General Sx of anaemia (pallor, dyspnoea, fatigue)
+
Angular glossitis / stomatitis (like b12 deficiency anaemia)
(**Do not** see neurological Sx or lemon yellow skin - only seen in b12 deficiency)
In babies: if the embryo was folate deficient… baby may present with spina bifida / anencephaly because neural tube defect
126
Investigation / diagnosis of folate deficiency anaemia
FBC + blood film:
Macrocytic anaemia
Megaloblasts
Serum folate (low)
127
Treatment of folate deficient anaemia
Dietary advice (leafy greens, brown rice)
Folate supplements
**note: if accompanied with b12 deficiency… treat b12 FIRST - because giving folate first depletes b12 more** (complex DNA synthesis pathway)
For pregnant women: prophylactic folate 400mg for first 12 weeks
128
Complication for folate deficient anaemia
Ischaemic heart disease
Ischaemic Stroke
129
What is the most inherited bleeding disorder
Von willebrands disease
130
Give types of bleeding disorders
Von willebrands
Haemophilia a
Haemophilia b
DIC (disseminated intravascular coagulopathy)
131
Inheritance pattern for VWF disease
Autosomal dominant mutation on VWF gene
Chromosome 12
132
Define VWF disease
Responsible for basis of platelet plug so decrease in VWF means more spontaneous bleeds + bruising
133
Investigation or diagnosis of VWF disease
**Normal PT
Increased APTT**
Normal factor 8/9 assay
**Decreased VWF**
134
Treatment for VWF disease
Not curable but managed
**Desmopressin**
Helps increased VWF from endothelial Weibel palade bodies!!
135
Signs / symptoms for VWF disease
Patients present with a history of unusually easy, prolonged or heavy bleeding:
Bleeding gums with brushing
Nose bleeds **(epistaxis)**
Heavy menstrual bleeding **(menorrhagia)**
Heavy bleeding during surgical operations
136
Define disseminated intravascular coagulopathy
A crisis
Massive activation of coagulation cascade
* increased clotting in the blood cells leads to platelets being used up unnecessarily
* lack of systemic available platelets means increased bleeding risk
137
Causes / triggers DIC
Trauma
Sepsis (e.g. meningococcal meningitis — non-Blanching Petechiae rash)
Malignancy
138
Investigation / diagnosis of DIC
FBC / lab findings
Decreased platelets
Decreased fibrinogen
Increased D-DIMER (the more clots the more break-down byproducts of a clot) - also seen in DVT & PE
139
Treatment of DIC
FFP (fresh frozen plasma) - to replace clotting factors
Cryoprecipitate (replace fibrinogen)
Platelet transfusion + RBC transfusion (if needed)
140
Inheritance pattern for haemophilia A and B
X linked recessive
141
Epidaemiology for haemophilia
Haemophilia A is more common than B
Exclusively affects **males** for both - as its x linked recessive and men only have 1 X-chromosome
For a female to be affected they would require an affected father and a mother that is either a carrier or also affected.
142
Define both haemophilia
Haemophilia A is caused by a deficiency in factor VIII.
Haemophilia B is caused by a deficiency in factor IX.
143
Signs and symptoms of haemophilia
Spontaneous bleeding — joints (**haemoathrosis**) and muscles
Epistaxis
Very easy bruising
**episodic**
144
Investigation / diagnosis for haemophilia
Normal PT + increased APTT (factor 8/9 is a part of the intrinsic pathway which is why APTT is prolonged)
Low f8 / f9 assay
145
Treatment for haemophilia
Haemophilia A : IV factor 8 + desmopressin (releases factor 8 stores from vessel wall)
Haemophilia B : IV factor 9
146
Give 3 conditions in which desmopressin can be used as treatment
Diabetes insipidus
VWF disease
Haemophilia A
147
Define polycythaemia
Erythrocytosis (increased RBC production) of any cause
148
Aetiology of polycythaemia
Primary - polycythaemia vera
**JAK2 V617 mutation** (accounts for 95% cases)
Secondary
**Hypoxia
Ectopic EPO (renal cell carcinoma)
Dehydration
Alcohol**
149
Signs and symptoms of polycythaemia Vera
**Itchy after bath**
Erthyromelalgia - burning fingers and toes
Conjunctival plethora (excessive redness to the conjunctiva in the eyes) - blurred vision
A “ruddy” complexion - reddish / purply complexion
Splenomegaly
**Features of hyperviscosity - increased RBCs —> increased haematocrit —> more solid mass of blood**
150
Investigation / diagnosis of polycythaemia Vera
**FBC** :
Increased RBC, WBC, platelets
Increased Hb
**Bone marrow biopsy** - ‘dry’ bone marrow due to scar tissue development
**genetic testing**
+ve for JAK2 V617
151
Treatment for polycythaemia Vera
Non - curative but managed
1st line = **VENESECTION** + aspirin
*Consider chemotherapy - hydroxycarbamide (aka hydroxyurea) : in high risk patients*
152
Define a myeloma
**Malignancy of plasma cell** (a a type of B lymphocyte producing antibodies) leading to bone marrow failure
**Multiple myeloma** is where the myeloma **affects multiple areas** of body
As a definition learn it as…
**neoplastic monoclonal proliferation of a plasma cell**
153
Complication of polycythaemia Vera
**Thromboemboli**
154
Pathophysiology of myeloma
There is a genetic mutation in a specific type of plasma cell
Leads to production and proliferation of abnormal antibody (i.e. immunoglobulin — 50%: IgG ; 20% IgA) by all the **identical** cancerous plasma cells
Can be called a **monoclonal paraprotein** single type of abnormal protein
155
Risk factors for multiple myeloma
Older age **(70y/o)**
Male
**Black African ethnicity**
Family history
Obesity
156
Signs and symptoms of multiple myeloma
Remember as **OLD CRAB**
**Old** - 70+ y/o
**C**alcium raised —— remember the Sx of Hypercalcaemia
*Bones, stones, Abdo groans, Psych moans*
**R**enal failure
**A**naemia
**B**one pain / lesions
157
Why is Hypercalcaemia seen in myeloma
**Increased osteoclast activity leads to increased calcium reabsorption from bone resorption** - also leads to the bone pain and bone lesions *(because bone resorption is in patches)*
- the monoclonal proliferation of a single plasma cell leads to increased cytokine release from these plasma cells ; cytokines stimulate osteoclast activity
158
Why is renal failure seen in m. Myeloma
Hypercalcaemia from bone resorption can lead to calcium oxalate renal stones
Increased immunoglobulin light chains Kappa deposition in kidneys
- Nephrotoxic
- Sub-unit of these light chains = Bence-Jones protein - this is a marker found in urine
159
Why would m. Myeloma lead to anaemia
B cells produced in Bone marrow… malignancy of one type of plasma cell in bone marrow leads to bone marrow infiltration
Causing suppression of other cell lines
- anaemia
- neutropenia
- thrombocytopenia
160
Investigations / diagnosis of m. Myeloma
**FBC + blood film**
Normocytic + normochromic RBCs
- _ROULEAUX FORMATION_ - aggregation of RBC (pathognamonic)
Raised ESR
**Urine dipstick / electrophoresis**
_Bence-jones proteins_
**serum protein electrophoresis**
**Xray**
Osteolytic lesions —> punched out holes
Skull —> raindrop skull
**bone marrow biopsy** : > / = 10% plasma cells
Nice recommend - full body MRI to see systemic bone marrow filtration
161
What is differential diagnosis for m . Myeloma
MGUS - **Monoclonal Gammopathy of Undermined Significance**
162
Give 3 features of MGUS
< 10% plasma cells in bone marrow
Little / no paraprotein spike
Asymptomatic
163
What is MGUS
MGUS - **Monoclonal Gammopathy of Undermined Significance**
A precursor of myeloma
164
Treatment of m. Myeloma
Chemotherapy
Bisphosphonates (for bone protection) - alendronate
Dialysis
Consider **bone marrow stem cell transplant**
165
Define lymphoma
Lymphomas are a group of malignancies that affect the lymphocytes inside the lymphatic system
166
Types of lymphomas
2 types :
———— Reed sternberg cells = **Hodgkin’s**
———— Non reed sternberg = **Non-Hodgkin’s**
167
Give 3 examples/types of Non-Hodgkin’s lymphoma
Low grade = follicular
High grade = diffuse large B cell (most common- 80%)
Very high grade = burkitts
168
Epidaemiology of Hodgkin’s
Bimodal ; ** Teens and Elderly** (to peaks of increased incidence)
Associated with EBV (aka glandular fever)
169
What are B symptoms for lymphomas
**Fever
Night sweats
Unintentional weight loss**
+
Lymphadenopathy
170
Signs and symptoms of Hodgkin’s lymphoma
B symptoms (fever, night sweats, unintentional weight loss)
+
**painless rubbery lymphadenopathy** - painful after drinking alcohol
171
Investigation / diagnosis of Hodgkin’s lymphoma
**Lymph node biopsy :**
_reed sternberg +ve_ - diagnostic
*Note: a subtype of Hodgkin’s can also show popcorn cell (reed sternberg cell variant)*
**blood test**
_raised LDH_ (Lactate dehydrogenase)
Raised ESR
Low Hb
**CT / MRI / PET** - for staging lymphoma
172
What staging is used for lymphomas
**Ann arbour staging (1-4)**
173
Describe Ann arbour staging
**Ann arbour staging (1-4)**
1 : Single lymph node
2 : > / = 2 lymph nodes on **same** side of diaphragm
3 : Lymph nodes on **both** sides of diaphragm
4 : Spread to extra-nodal organs
+ either…
A : without “B” symptoms
Or
B : with “B” symptoms
174
Treatment for hodgkins lymphoma
ABVD chemotherapy
175
Side effects for ABVD chemotherapy
Alopecia
Nausea + vomiting
**Infection**
Myelosupression / bone marrow failure
176
Complication of chemo
Febrile neutropenia
Huge risk in patients who had recent / high dose chemo (/ on carbimazide)
Px : fever, tachycardia + pnoea, sweats, rigors
Tx : immediate broad spec antibiotics (amoxicillin + fluoroquinolone)
177
What can burkitts lymphoma cause
Jaw lymphadenopathy in children
Linked to EBV
178
Signs / symptoms of non-hodgkins lymphoma
B symptoms
+
**Painless rubbery lymphadenopathy** - not affected by alcohol
*Symptoms vary on subtypes*
179
Investigation / diagnosis of non-hodgkins lymphoma
**lymph node biopsy** - diagnostic
No reed sternberg cells
Helps confirm subtypes (e.g. burkitts = ‘stormy sky’ biopsy)
**CT / MRI / PET for staging** - Ann Arbour
180
Treatment for non-hodgkins lymphoma
R-CHOP chemotherapy
181
Risk factors for lymphomas
FHx
EBV
HIV
+
Hodgkin’s :
autoimmune condition
Non- hodgkins :
Hep b/c
H. Pylori
182
Give examples of anti coagulation meds
Aspirin (COX inhibitor)
Heparin / LMWH (binds to antithrombin 3 & inhibits factor X)
Clopidogrel (P12Y12 inhibitor) - antiplatelet
Thrombolytics (Alteplase)
183
Define leukaemia
A form of malignancy of WBC lines (myeloblasts ; lymphoblast) in bone marrow
A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell
184
Does leukaemia lead to anaemia and why
Yes
Leukaemia leads to anaemia but also pancytopenia (anaemia, neutropenia, thrombocytopenia) -
The excessive production of a single type of cell can lead to suppression of the other cell lines causing underproduction of other cell types
185
Types of leukaemia
Acute lymphoblastic leukaemia (ALL)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)
Acute myeloid leukaemia (AML)
186
Age acute lymphoblastic leukaemia presents
Remember **ALL C**e**LL**mates have **C**o**M**mon **AM**bitions
_Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)_
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)
187
Age acute myeloid leukaemia presents
Remember **ALL C**e**LL**mates have **C**o**M**mon **AM**bitions
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
_Over 75 – acute myeloid leukaemia (AMbitions)_
188
Age chronic lymphocytic leukaemia presents
Remember **ALL C**e**LL**mates have **C**o**M**mon **AM**bitions
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
_Over 55 – chronic lymphocytic leukaemia (CeLLmates)_
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)
189
Age chronic myeloid leukaemia presents
Remember **ALL C**e**LL**mates have **C**o**M**mon **AM**bitions
Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
_Over 65 – chronic myeloid leukaemia (CoMmon)_
Over 75 – acute myeloid leukaemia (AMbitions)
190
Define A. L. Leukaemia
Neoplastic lymphoblasts (immature) proliferation
Mostly B cells
Has good prognosis
191
Most common childhood malignancy
Acute lymphoblastic leukaemia
75% cases
> / = 6y/o
192
Translocation for ALL
T(12:21)
193
Condition associated with ALL
Down syndrome; x30 risk
+
Radiation
194
General signs & symptoms of leukaemia
Fatigue
Fever
Failure to thrive (children)
Pallor due to anaemia
Petechiae and abnormal bruising due to thrombocytopenia
Abnormal bleeding
Lymphadenopathy
195
Signs and symptoms of ALL
General leukaemia Sx:
6y/o with Down syndrome
Hepatosplenomegaly
196
Investigation and diagnosis of ALL
FBC:
Pancytopenia
Blood film:
Increased lymphoblasts
**Bone marrow biopsy (diagnostic)** :
> / = 20% lymphoblasts
197
Treatment for ALL
Chemotherapy (+/- allopurinol)
198
Define chronic lymphocyte leukaemia
Chronic neoplastic proliferation of lymphocytes - mainly b cells
199
Most common type of leukaemia
Chronic lymphocyte leukaemia
200
CLL prognosis
75% with 5 year survival
201
Signs and symptoms of CLL
men with general anemia Sx
**+ lymphadenopathy (non tender)**
+ Hepatosplenomegaly
Often it is asymptomatic but it can present with infections, anaemia, bleeding and weight loss. It can cause **warm autoimmune haemolytic anaemia**
202
Investigation and diagnosis of CLL
FBC:
Pancytopenia
Blood film:
**smudge/smear cells**
Immunoglobulin:
**Hypogammaglobulinaemia** - B cells proliferate but dont differentiate to plasma cells so no immunoglobulin production
203
Treatment for CLL
It’s progressive so give
Chemo + palliative care (if old)
Also, if hypogammaglobinaemia give IV Ig
204
Complication for CLL
**Richter transformation**
B cells massively accumulate in lymph nodes —> leading to lymphadenopathy
+ transformation from CLL —> aggressive lymphoma
205
Define acute myeloid leukaemia
Neoplastic myeloblasts (immature)proliferation
206
Translocation mutation of AML
T(15;17)
207
Prognosis for AML
Has rapid progression
If not treated ASAP; 3 year survival = only 20%
Therefore v. Severe
208
Risk factors for AML
Pre-existing myeloproliferative disorders - polycythaemia Vera
Congenital disorders - Down’s syndrome
Prior chemo / radiation
209
Signs and symptoms of AML
General leukaemia Sx +
Hepatosplenomegaly
210
Investigations / diagnosis for AML
FBC :
Pancytopenia
Blood smear :
**AUER RODS** and +ve myeloperoxidase
*Auer rods = myeloperoxidase cytoplasmic aggregates in neutrophils*
Bone marrow biopsy :
> / = 20% myeloid blasts
211
Give a subtype of AML
Acute promyelocytic leukaemia
It is : AML + DIC
212
Treatment for AML
Chemotherapy + allopurinol
+ ATRA
Consider prophylaxis for neutropenia / transfusion for anaemia
Last resort = bone marrow transplant
213
What is given with chemotherapy for leukaemia
Allopurinol
Prevent tumour lysis syndrome (chemo releases uric acid from cells, so can accumulate in kidney / cause gout) - allopurinol prevents uric acid build up
214
Define CML
Neoplastic proliferation of myelocytes - baso / eosino / neutrophils
215
Genetic translocation mutation for CML
T(9;22)
Philadelphia chromosome
BCR-ABL gene fusion causes **tyrosine kinase irreversibly switched on**
216
Role of tyrosine kinase
Increased cell proliferation
217
Sign and symptoms of CML
General Sx of leukaemia - weight loss, fatigue, fever, infections, bruising, excessive bleeding
+ **huge Hepatosplenomegaly**
218
Investigation / diagnosis of CML
**FBC**:
Pancytopenia
But granulocytosis (increased proliferation of eosinophils/baso/neutrophils)
Blood blast cell % =
> 10% (better prognosis) //// < 20% (blast crisis)
**Bone marrow biopsy** : increased granulocytes
**philadelphia chromosome genetic testing**
219
Treatment of CML
Chemo +
**IMANTINIB** - Tyrosine kinase inhibitor
Also, consider allopurinol
*if not treated, risk of progression onto AML*
220
Define RBC inclusions
When RBCs are Beta globin chain deficient, free alpha chains build up in them causing **inclusions**
221
Side effect to thrombolysis
Major bleed - if given in PE might leads to intracranial bleed
222
When in if piperacillin and tazobactam given
Give if px has fever 7-14 days after chemotherapy… neutropenia sepsis
223
In a px with iron deficiency when would ferritin be high
Ferritin would be falsely high when theres an infection
As its an acute phase reactant
224
What do you haem arthritis in and epistaxis
Haemophilia a and b
225
Give an example antifibrynolytic agent and where is it given
Tranexamic acid
Haemophilia A/B and VWF disease
226
Give the drugs name that opposite action to alteplase
Tranexamic acid
227
Give 3 sign of essential thrombocytosis
Splenomegaly
Erthromelagia (discolouration and burning peripheries)
Livedo reticularis (purple rash)
