Haematology Flashcards
When are eosinophils elevated
Parasitic infections
What is elevated in myelodysplastic syndrome
Monocytes
Define thrombocytosis
Too many platelets
> 400 x 10^9 / L
Define thrombocytopenia
Platelet deficiency
<150 x 10^9 / L
Define lymphocytosis
Too many lymphocytes
> 3.5 x 10^4
Define lymphocytopenia
Less lymphocytes
<1.3 x 10^4 / L
Define neutrophilia
Increased neutrophils
> 7.5 x 10^9 / L
Define neutropenia
Low neutrophil count
<2 x 10^9 / L
What might give you neutrophilia
Acute bacterial infection
What might give you neutropenia
Myeloma
Lymphoma
What might cause lymphocytosis
Chronic infection
What is clotting screening
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
What is prothrombin time
PT / INR shows…
Coagulation speed through the EXTRINSIC PATHWAY
PT:10-13.5s
Normal INR: 0.8-1.2 ; if on warfarin: 2-3!!!
Define INR
International normalised ratio
Ratio of…
Tested PT / Normal PT
I.e.
Patient PT / Reference PT
What factors are included in the extrinsic coagulation cascade
3 … 7 … 10
What clotting factors are included in intrinsic coagulation cascade
12 … 11 … 9 … 8 … 10
What increases INR
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)
What is APTT
Activated Partial Thromboplastin Time
Coagulation speed through intrinsic pathway
35-45s ; if on heparin: 60-80s
Which diseases is APTT affected by
Haemophilia A (factor 8)
Haemophilia B (factor 9)
VWF disease
All these condition cause PT normal & prolonged APTT!!
Define thrombin time
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
What is the common pathway of coagulation cascade
10 .… 2 … 1
|
5
What is mean corpuscular volume
Size and volume of RBC
What are the ranges for MCV and what do they indicate
Microcytic [< 80]
Normocytic [80-95]
Macrocytic [> 95]
Types of microcytic anaemia
Thalassaemia Alpha / Beta (actually haemolytic too)
Anaemia of chronic disease
Iron deficiency anaemia
Lead poisoning
Sideroblastic anaemia
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
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]
Normal lifespan of RBC
120 days
I.e. 3 months
Lifespan of RBC in haemolytic anaemia
5-10 days!!!
What’s haemoglobin range for anaemia
Men < 130 g/L
Women < 120 g/L
For anaemia when should transfusions be considered
When…
Hb < 70
Or
Hb < 80 + cardiac comorbidity
Types of Macrocytic anaemia
Megaloblastic:
B12 deficiency
Folate deficiency
Non-Megaloblastic:
Alcohol
Hypothyroidism
Non-alcoholic liver disease [NALD]
General symptoms of anaemia
Pallor
Fatigue
Exertional SoB
Chest pain + Tachycardia + hypotension + palpitations
What is most common anemia worldwide
Iron deficiency
Epidaemiology of iron deficiency anaemia
Most common anaemia
F>M
Over 500 million cases
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
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
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
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
Iron deficiency anaemia for investigation for > 60y/o
Endoscopy - high risk of colon cancer
What’s are target cells
Non-specific bulls eye pattern RBC
What are howell jolly bodies
Non-specific uncleared RBCs
Where remanent of DNA is not removed via spleen
Treatment for iron deficiency anaemia
Treat underlying cause + oral iron…
ferrous sulphate
Side effects of ferrous sulphate
Given in iron deficiency
black stool
Diarrhoea / constipation
GI upset
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
Condition which is autosomal recessive haemoglobinopathy
Thalassaemia
Can also be Sickle Cell Anaemia
Epidaemiology for Thalassaemia
Autosomal recessive
Mediterranean ancestry
Prevalent where malaria is (carrier of Thalassaemia - protective against malaria)
Types of haemoglobin
HbF
X2 Alpha
X2 Gamma chains
HbA
X2 Alpha
X2 Beta chains
HbA2
X2 Alpha
X2 delta chains
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
Signs and symptoms of alpha Thalassaemia
General anaemia Sx
Pallor, Exertional dyspnoea, fatigue, tachycardia+hypotensive, chest pain
+
Skeletal deformities
Hepatosplenomegaly
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
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
Give an iron chelating drug + its side effect
Desfemoxamine
Side effect : deafness, cataracts
Chromosome affected in alpha Thalassaemia
Chromosome 16
4 genes ; Mutations leading to gene deletion
Chromosome affected in beta Thalassaemia
Chromosome 11
2 genes ; mutations lead to defective genes
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
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
Complication of beta thalassaemia
Arrythmias, Pericarditis, Cirrhosis, hypothyroidism and D.M
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
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.
In which condition is chipmunk facies seen in
Beta thalassaemia major
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)
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
Enzyme deficiency in Sideroblastic anaemia
ALA synthetase deficiency
Inheritance pattern for siderblastic anaemia
X linked
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
What type of anaemia is sickle cell anaemia
Normocytic
Inheritance pattern for sickle cell anaemia
Autosomal recessive
Haemoglobinopathy
Which chains are affected in SS anaemia
Beta globin chains
Epidaemiology for SS anaemia
Commonest in Africa - antimalarials properties as carrier against falciparum malaria
Affected genotype for SS anaemia
HbS HbS - sickle cell disease (autosomal recessive)
HbS - the abnormal variant for sickle cell haemoglobin
Chromosome affected leading to HbS in sickle cell anaemia
Chromosome 11 - beta globin chain defect
same in beta thalassaemia
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)
Signs and symptoms of SS anaemia
General Sx of anaemia (pallor, dyspnoea, fatigue)
+ jaundice (haemolytic anaemia = pre-hepatic)
+ splenomegaly
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
What is SS anaemia precipitated by
infection
cold
hypoxia
acidosis
Dehydration
Which anaemia is osteomyelitis
Common in sickle cell
Osteomyelitis is usually due to S. Aureus, but in those with SS = salmonella
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)
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
Inheritance pattern for G6PDH deficiency
X linked recessive
Enzymopathy
Role of G6PDH
G6PDH is protective against oxidative damage
It’s involved in glutathione synthesis
Which protects against reactive oxidative species like H2O 2
Epidaemiology of G6PDH deficiency
Causes half lifespan and degradation of RBC
Africa & Asia
Signs & symptoms of G6PDH deficiency
Asymptomatic unless precipitated
Could cause an attack
rapid anaemia
Jaundice
Type of haemolysis in G6PDH deficiency
Intravascular haemolysis
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.
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
Treatment for G6PDH deficiency
Avoid precipitants
Blood transfusion when attacks ensure
Inherited pattern for hereditary spherocytosis
Autosomal dominant
Membranopathy
Epidaemiology of hereditary spherocytosis
N. Europe + America
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)
Signs & symptoms of hereditary spherocytosis
General anaemia symptoms (pallor, dyspnoea, fatigue)
+
Neonatal jaundice
Splenomegaly
Gallstones (50%)
Investigation / diagnosis for hereditary spherocytosis
FBC + blood film
Normacytic normochromic + increased reticulocytes
Spherocytes
Direct Coombs -ve ;
+ve in AHA (autoimmune haemolytic anaemia!!!)
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
Type of haemolysis in hereditary spherocytosis
Extravascular haemolysis
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
What other conditions is Cold type AHA secondary too
Lymphoma, leukaemia, systemic lupus erythematosus and infections (EBV, CMV, HIV)
Type of haemolysis in AHA
Extravascular + intravascular haemolysis
Investigation / diagnosis for AHA
Direct Coombs +ve
(as there’s agglutination of RBCs with Coombs reagent)
Remember Coombs -ve in hereditary spherocytosis
Types of non-haemolytic anaemia
All normocytic
CKD
Aplastic Anaemia
Myelophthisic anaemia
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…
Define aplastic anaemia
Pancytopenia - where bone marrow fails so no production of heamopoetic stem cells
Aetiology / cause of aplastic anaemia
Idiopathic (mostly)
Might be triggered by infection (parvovirus, EBV)
Investigation / diagnosis of aplastic anaemia
FBC - normocytic anaemia with reduced reticulocytes
Bone marrow biopsy - hypocellularity
Treatment for aplastic anaemia
Increased risk of infection (neutropenia) - give broad spec Antibiotic
+
Bone marrow transplant
Define Myelophthisic anaemia
Normocytic non haemolytic anaemia
When bone marrow is replaced with something else like malignancy
What type of anaemia is pernicious anaemia
Macrocytic Megaloblastic anaemia
Give types of Macrocytic anaemia
Megloblastic :
Pernicious / B12 deficiency
Folate deficiency
Non-megaloblastic / Normoblastic Macrocytic :
Alcohol
Liver disease
NALD - non-alcoholic liver disease
Hypothyroidism
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
How does alcohol cause anaemia
Toxic to RBC
Also depletes folate (+ B1 -Thiamine)
How does hypothyroidism lead to anaemia
Interference with EPO ; multi factorial
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
Define pernicious anaemia
AKA B12 deficiency
Epidaemiology of B12 deficiency
Older patients - takes years to develop
Increased in long-term vegans
Causes of B12 deficiency
Malnutrition
Malabsorption - Crohns
Pernicious anaemia (antibodies against parietal cells + Intrinsic Factor)
Which cells are produced to help with b12 absorption
Parietal cells in stomach
Produce intrinsic factor
Where is b12 absorbed
Ileum
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.
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.
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…
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.
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
Treatment for pernicious anaemia
Dietary advice (salmon, eggs)
+
B12 supplements (PO, hydroxycobalamin)
Name for vitamin b12
Cobalamin
Time of development for folate deficiency
Months
B12 deficiency takes years
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)
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
Investigation / diagnosis of folate deficiency anaemia
FBC + blood film:
Macrocytic anaemia
Megaloblasts
Serum folate (low)
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
Complication for folate deficient anaemia
Ischaemic heart disease
Ischaemic Stroke
What is the most inherited bleeding disorder
Von willebrands disease
Give types of bleeding disorders
Von willebrands
Haemophilia a
Haemophilia b
DIC (disseminated intravascular coagulopathy)
Inheritance pattern for VWF disease
Autosomal dominant mutation on VWF gene
Chromosome 12
Define VWF disease
Responsible for basis of platelet plug so decrease in VWF means more spontaneous bleeds + bruising
Investigation or diagnosis of VWF disease
Normal PT
Increased APTT
Normal factor 8/9 assay
Decreased VWF
Treatment for VWF disease
Not curable but managed
Desmopressin
Helps increased VWF from endothelial Weibel palade bodies!!
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
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
Causes / triggers DIC
Trauma
Sepsis (e.g. meningococcal meningitis — non-Blanching Petechiae rash)
Malignancy
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
Treatment of DIC
FFP (fresh frozen plasma) - to replace clotting factors
Cryoprecipitate (replace fibrinogen)
Platelet transfusion + RBC transfusion (if needed)
Inheritance pattern for haemophilia A and B
X linked recessive
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.
Define both haemophilia
Haemophilia A is caused by a deficiency in factor VIII.
Haemophilia B is caused by a deficiency in factor IX.
Signs and symptoms of haemophilia
Spontaneous bleeding — joints (haemoathrosis) and muscles
Epistaxis
Very easy bruising
episodic
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
Treatment for haemophilia
Haemophilia A : IV factor 8 + desmopressin (releases factor 8 stores from vessel wall)
Haemophilia B : IV factor 9
Give 3 conditions in which desmopressin can be used as treatment
Diabetes insipidus
VWF disease
Haemophilia A
Define polycythaemia
Erythrocytosis (increased RBC production) of any cause
Aetiology of polycythaemia
Primary - polycythaemia vera
JAK2 V617 mutation (accounts for 95% cases)
Secondary
Hypoxia
Ectopic EPO (renal cell carcinoma)
Dehydration
Alcohol
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
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
Treatment for polycythaemia Vera
Non - curative but managed
1st line = VENESECTION + aspirin
Consider chemotherapy - hydroxycarbamide (aka hydroxyurea) : in high risk patients
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
Complication of polycythaemia Vera
Thromboemboli
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
Risk factors for multiple myeloma
Older age (70y/o)
Male
Black African ethnicity
Family history
Obesity
Signs and symptoms of multiple myeloma
Remember as OLD CRAB
Old - 70+ y/o
Calcium raised —— remember the Sx of Hypercalcaemia
Bones, stones, Abdo groans, Psych moans
Renal failure
Anaemia
Bone pain / lesions
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
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
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
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
What is differential diagnosis for m . Myeloma
MGUS - Monoclonal Gammopathy of Undermined Significance
Give 3 features of MGUS
< 10% plasma cells in bone marrow
Little / no paraprotein spike
Asymptomatic
What is MGUS
MGUS - Monoclonal Gammopathy of Undermined Significance
A precursor of myeloma
Treatment of m. Myeloma
Chemotherapy
Bisphosphonates (for bone protection) - alendronate
Dialysis
Consider bone marrow stem cell transplant
Define lymphoma
Lymphomas are a group of malignancies that affect the lymphocytes inside the lymphatic system
Types of lymphomas
2 types :
———— Reed sternberg cells = Hodgkin’s
———— Non reed sternberg = Non-Hodgkin’s
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
Epidaemiology of Hodgkin’s
Bimodal ; ** Teens and Elderly** (to peaks of increased incidence)
Associated with EBV (aka glandular fever)
What are B symptoms for lymphomas
Fever
Night sweats
Unintentional weight loss
+
Lymphadenopathy
Signs and symptoms of Hodgkin’s lymphoma
B symptoms (fever, night sweats, unintentional weight loss)
+
painless rubbery lymphadenopathy - painful after drinking alcohol
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
What staging is used for lymphomas
Ann arbour staging (1-4)
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
Treatment for hodgkins lymphoma
ABVD chemotherapy
Side effects for ABVD chemotherapy
Alopecia
Nausea + vomiting
Infection
Myelosupression / bone marrow failure
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)
What can burkitts lymphoma cause
Jaw lymphadenopathy in children
Linked to EBV
Signs / symptoms of non-hodgkins lymphoma
B symptoms
+
Painless rubbery lymphadenopathy - not affected by alcohol
Symptoms vary on subtypes
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
Treatment for non-hodgkins lymphoma
R-CHOP chemotherapy
Risk factors for lymphomas
FHx
EBV
HIV
+
Hodgkin’s :
autoimmune condition
Non- hodgkins :
Hep b/c
H. Pylori
Give examples of anti coagulation meds
Aspirin (COX inhibitor)
Heparin / LMWH (binds to antithrombin 3 & inhibits factor X)
Clopidogrel (P12Y12 inhibitor) - antiplatelet
Thrombolytics (Alteplase)
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
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
Types of leukaemia
Acute lymphoblastic leukaemia (ALL)
Chronic lymphocytic leukaemia (CLL)
Chronic myeloid leukaemia (CML)
Acute myeloid leukaemia (AML)
Age acute lymphoblastic leukaemia presents
Remember ALL CeLLmates have CoMmon AMbitions
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)
Age acute myeloid leukaemia presents
Remember ALL CeLLmates have CoMmon AMbitions
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)
Age chronic lymphocytic leukaemia presents
Remember ALL CeLLmates have CoMmon AMbitions
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)
Age chronic myeloid leukaemia presents
Remember ALL CeLLmates have CoMmon AMbitions
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)
Define A. L. Leukaemia
Neoplastic lymphoblasts (immature) proliferation
Mostly B cells
Has good prognosis
Most common childhood malignancy
Acute lymphoblastic leukaemia
75% cases
> / = 6y/o
Translocation for ALL
T(12:21)
Condition associated with ALL
Down syndrome; x30 risk
+
Radiation
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
Signs and symptoms of ALL
General leukaemia Sx:
6y/o with Down syndrome
Hepatosplenomegaly
Investigation and diagnosis of ALL
FBC:
Pancytopenia
Blood film:
Increased lymphoblasts
Bone marrow biopsy (diagnostic) :
> / = 20% lymphoblasts
Treatment for ALL
Chemotherapy (+/- allopurinol)
Define chronic lymphocyte leukaemia
Chronic neoplastic proliferation of lymphocytes - mainly b cells
Most common type of leukaemia
Chronic lymphocyte leukaemia
CLL prognosis
75% with 5 year survival
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
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
Treatment for CLL
It’s progressive so give
Chemo + palliative care (if old)
Also, if hypogammaglobinaemia give IV Ig
Complication for CLL
Richter transformation
B cells massively accumulate in lymph nodes —> leading to lymphadenopathy
+ transformation from CLL —> aggressive lymphoma
Define acute myeloid leukaemia
Neoplastic myeloblasts (immature)proliferation
Translocation mutation of AML
T(15;17)
Prognosis for AML
Has rapid progression
If not treated ASAP; 3 year survival = only 20%
Therefore v. Severe
Risk factors for AML
Pre-existing myeloproliferative disorders - polycythaemia Vera
Congenital disorders - Down’s syndrome
Prior chemo / radiation
Signs and symptoms of AML
General leukaemia Sx +
Hepatosplenomegaly
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
Give a subtype of AML
Acute promyelocytic leukaemia
It is : AML + DIC
Treatment for AML
Chemotherapy + allopurinol
+ ATRA
Consider prophylaxis for neutropenia / transfusion for anaemia
Last resort = bone marrow transplant
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
Define CML
Neoplastic proliferation of myelocytes - baso / eosino / neutrophils
Genetic translocation mutation for CML
T(9;22)
Philadelphia chromosome
BCR-ABL gene fusion causes tyrosine kinase irreversibly switched on
Role of tyrosine kinase
Increased cell proliferation
Sign and symptoms of CML
General Sx of leukaemia - weight loss, fatigue, fever, infections, bruising, excessive bleeding
+ huge Hepatosplenomegaly
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
Treatment of CML
Chemo +
IMANTINIB - Tyrosine kinase inhibitor
Also, consider allopurinol
if not treated, risk of progression onto AML
Define RBC inclusions
When RBCs are Beta globin chain deficient, free alpha chains build up in them causing inclusions
Side effect to thrombolysis
Major bleed - if given in PE might leads to intracranial bleed
When in if piperacillin and tazobactam given
Give if px has fever 7-14 days after chemotherapy… neutropenia sepsis
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
What do you haem arthritis in and epistaxis
Haemophilia a and b
Give an example antifibrynolytic agent and where is it given
Tranexamic acid
Haemophilia A/B and VWF disease
Give the drugs name that opposite action to alteplase
Tranexamic acid
Give 3 sign of essential thrombocytosis
Splenomegaly
Erthromelagia (discolouration and burning peripheries)
Livedo reticularis (purple rash)
