Haematology Flashcards
1
Q
Abnormal FBC for neutrophils?
A
High = neutrophilia, caused by acute bacterial infection
Low = neutropenia, caused by myeloma and lymphoma
2
Q
Abnormal FBC for lymphocytes
A
High = lymphocytosis, caused by chronic infection
Low = lymphocytopenia
3
Q
Abnormal FBC for platelets
A
High = thrombocytosis/thrombocythaemia
Low = thrombocytopenia
4
Q
FBC values for eosinophils and monocytes
A
- Eosinophils - elevated in parasitic infection
- Monocytes - elevated in myelodysplastic syndrome
5
Q
Splenectomy
What does spleen do so what are risks of splecetomy?
what age to wait after till?
A
-To remove spleen
- Wait till after 6 y/o
- Spleen plays defensive role vs encapsulated bacteria
- So wait due to risk of sepsis
6
Q
What are haematinimics?
A
- Nutrients needed for haematopoesis (B12, folate, Fe)
- Deficiencies cause angular stomatitis and glossitis
7
Q
What is angular stomatitis and glossitis?
A
-It affects one or both corners of your mouth and causes irritated, cracked sores. Although painful, angular cheilitis usually isn’t serious.
- Inflammation of the tongue
8
Q
Blast vs cyte
A
Blast - immature cell, eg: myeloblast
Cyte - mature cell, eg: myelocyte
9
Q
Thrombosis chart?
A
Thrombus = arterial or venous
Arterial (atherogenesis inside arteries) can lead to ischaemia in organs/ tissues
—–>cvd —>MI
—–>cerebrovascular—> I. stroke + TIA
—->Peripheral = pvd
Venous (Virchov’s triad) leading to occulded venous drainage
—–>DVT
—–> PE from DVT thrombus emboli
10
Q
Types of haemostasis
A
Primary: Initiation and formation of platelet plug - platelet activation
Secondary: Formation of the fibrin clot - coagulation cascade
11
Q
PT/INR
A
pt = prothrombin time
- Work out INR using equation: Patient PT/Reference PT
- Normal INR: 0.8 - 1.2
INR could be high due to:
- Anticoagulants (eg: warfarin usually INR of 2-3)
- Liver disease
- Vit K deficiency
- DIC (Disseminated intravascular coagulation)
12
Q
What is prothrombin time? (PT)
A
- Coagulation speed through extrinsic pathway
- Normally 10-13.5s
13
Q
What is activated partial thromboplastin time? (APTT)
A
- Coagulation speed through intrinsic pathway
- Usually 35-45s
- Patient on heparin may be 60-80
14
Q
Other values measured for coagulation
A
- Bleeding time
- Thrombin time
- Fibrinogen -> fibrin time (usually 12-14s)
15
Q
What are myelodysplastic syndromes?
A
- Bone marrow cells fail to make adequate numbers of healthy blood cells
- Abnormal cells crowd out healthy normal cells
16
Q
Diagnostic pathway for thrombocytosis?
A
if the platelet count is >450x10^9
order a blood film, iron status, acute phase reactants(CRP, ESR)
Iron deficincy = treat and then repeat blood count
acute phase response = reactive thrombocytosis
Normal = repeat blood count
if persistent unexplained thrombocytosis then investigate by bone marrow aspiration and biopsy, cytogenetics, molecular genetics( JAK2 etc)
Then diagnose
17
Q
Most common causes of splenomegaly
A
- Infection
- Liver disease
- Autoimmune conditions (eg: SLE, rheumatoid arthritis)
Once excluded these: myeloproliferative neoplasms and lymphomas
18
Q
What is budd chiari?
A
- Thrombus in hepatic artery
- Increasing pressure
- Leading to enlarged liver and spleen
19
Q
Reasons for decrease in RBCs
A
Decreased production
- Iron, folate or B12 deficiency
- Bone marrow failure
Increased loss
- Bleeding
- Haemolysis
20
Q
Symptoms of post thrombotic syndrome
A
- Skin hyperpigmentation
- Venous ulcers due to poor circulation in the leg
- Leg swelling
21
Q
What to do if someone is at high risk for DVT
A
Ultrasound scan and give anticoags while waiting for results
22
Q
HB structures
A
95% - HbA
- 2x alpha
- 2x beta
5% - HbA2
- 2x alpha
- 2x delta
Fetal - Fetal
- 2x alpha
- 2x gamma
Sickle cell
- 2x alpha
- 2x HbS
HbH ( alpha thalassemia in which moderately severe anemia develops due to reduced formation of alpha globin chains.)
- 4 x beta
23
Q
What to give in suspected neutropaenic sepsis and what is it?
A
(can happen when you have a low level of neutrophils and an infection at the same time.)
- One of the piperacillin (broad spec antibiotics) with tazobactam
- Do blood cultures
- IV fluids and oxygen
24
Q
Affects of warfarin and heparin on APTT and PT
A
- Heparin increases APTT
- Warfarin increases PT
25
What does ferritin increase in?
Infection - as it is an acute phase reactant
26
What is aplastic anaemia?
Pancytopaenia (deficiency of all three cellular components of the blood) with hypocellular bone marrow
27
signs of essential thrombrocytosis /thrombocythemia?
- Splenomegaly
- Erythromelalgia (red or blue discolouration in peripheries with burning sensation)
- Livedoreticularis - a skin condition caused by small blood clots that develop inside the blood vessels of the skin
28
Diagnosis of thrombocytosis/Essential thrombocythaemia
- Ferritin 221, Serum iron 15, % iron saturation 23% normal to exclude anaemia
- Blood film: Platelet anisocytosis (Platelets with size variation)
- BCR::ABL1 no rearrangement on FISH- means unlikely to be leukaemia
- JAK2V617F mutated- mutated in myleproliferative diseases
29
Causes of macrocytosis
(ddrrhab)
- Folate or B12 deficiency
- Reticulocytosis
- Raised Igs
- Hypothyroidism
- Alcohol
- Bone marrow failure, esp. myelodysplastic syndromes
- Drugs, eg: methotrexate (inhibits folate metabolism), hydroxyurea
30
What percentage of patients with DVT get post-thrombotic syndrome?
30%
31
MCV for different types of anaemia
<80 = microcytic
80-95 = normocytic
>95 = macrocytic
32
When would you consider transfusions for anaemia?
Hb <70g/L
or
Hb <80g/L + cardiac comorbidity
33
General symptoms of anaemia
- Fatigue
- Headache
- Dizziness
- Dyspnoea (especially on exertion)- difficult or laboured breathing.
- Chest pain
34
General signs of anaemia
- Tachycardia + hypotension
- Skin pallor
- Conjunctiva pallor (reds of eye pale)
- Intermittent claudication- muscle pain due to lack of oxygen that's triggered by activity and relieved by rest
35
What does full blood count check for
- RBCs
- Neutrophils
- Lymphocytes -
- Platelets
- Eosinophils
- Monocytes
35
What are megaloblasts?
- Hypersegmented nucleated neutrophils with 6+ lobes
- Less mature DNA = less compacted around histones
- So more lobes = more immature
35
Signs specific to B12 deficiency anaemia
- Angular stomatitis + glossitis
- Lemon-yellow skin
- Neurological symptoms
36
Ideal haemoglobin (g/L) and mean corpuscular volume values (femtolitres)
Haemoglobin:
- Women: 120-165g/L
- Men: 130-180g/L
anything less than the lower value is classed as anaemia
MCV:
- 80-100 femtolitres
36
How long do folate and B12 deficiency anaemia take to develop?
- Folate: months
- B12: years (more common in older patients)
37
Causes of B12 deficiency anaemia
- Pernicious anaemia (autoimmune, most common)
- Gastrectomy
- Malnutrition
- Intestinal problems such as Crohn's and celiac disease
- Chronic nitrous oxide use
- Oral contraceptives
- Vegan (cool people basically😎)
38
Normal metabolism of B12
- B12 binds to transcobalamin 1 in saliva (protects against stomach acid)
- Bind to intrinsic factor in duodenum
- Absorbed as B12-IF complex in terminal ileum
38
Pathophysiology of pernicious anaemia
- Anti parietal and intrinsic factor antibodies = low IF
- Low B12-IF complexes
- Less B12 absorption
39
Neurological symptoms of B12 deficiency
- Demyelination (DDx for folate deficiency)
- Symmetrical parathesia- abnormal sensation, typically tingling or pricking caused chiefly by pressure on or damage to peripheral nerves)
- Muscle weakness
- Altered mental state
39
Diagnosis of B12 deficiency
- FBC + blood film (Macrocytic and megaloblasts present)
- Low serum B12
- Anti parietal and anti IF antibodies (specific in pernicious anaemia)
39
Treatment for B12 deficiency
- Dietary advice
- B12 supplements (PO hydroxycobalamin)
39
Aetiology of folate deficiency anaemia
- Malnutrition
- Malabsorption
- Pregnancy
- Trimethoprim + methotrexate (dihydrofolate reductase inhibitors)
- Alcohol
- Bacterial overgrowth
39
Symptom of folate deficiency anaemia
Angular stomatitis
39
Diagnosis of folate deficiency anaemia
- FBC + blood film = macrocytic + megaloblasts
- Low serum folate
- Could have concomitant B12 deficiency
39
Treatment for folate deficiency
- Dietary advice (leafy greans, brown rice)
- Don’t replace folate without checking B12
- Folate supplements (if concomitant with B12 def., replace B12 first as giving folate first depleted B12)
39
Treatment for folate deficiency during pregnancy
- Prophylactic folate 400mg for first 12 weeks
- Ensure baby develops ok
39
Main complication of folate deficiency
Chronic Kidney Disease
CKD
39
How much folate is needed daily?
0.1-0.2mg/day is required as there are minimal body stores- only lasts a few months
39
Where is folate absorbed?
In the proximal jejunum
39
Causes of non-megaloblastic anaemia
- Alcohol - toxic to RBC and depletes folate and B1
- Hypothyroidism - inteference w/ EPO, multifactorial
- Liver disease - liver decompensated cirrhosis
- NAFLD (Non-alcoholic fatty liver disease)
- CKD
40
Types of microcytic anaemia
Thalassaemia
Anaemia of chronic disease
Iron deficiency
Lead poisoning
Sideroblastic
41
Signs specific to iron deficiency anaemia
- Koilonchia (spoon nails)
- Angular stomatitis
- Atrophic glossitis
- Brittle hair and nails
- Subconjunctival pallor
42
Iron deficiency anaemia
- Non-inherited Fe deficiency, impairing Hb synthesis
- Most common anaemia worldwide
- More common in females
43
Aetiology of iron deficiency anaemia
- Infants: malnutrition, prolonged breastfeeding
- Children: malnutrition, malabsorption
- Adults: malnutrition, malabsorption, menorrhagia, pregnancy, hookworm
- Elderly (60+): rare, red flag for colon cancer bleeding
44
NICE recommendation for iron deficiency anaemia age 60+
Urgent endoscopy in case of GI malignancy
45
What causes malabsorption of iron?
Conditions that result in inflammation of the duodenum and jejunum
- Coeliac
- IBD
- Crohn's disease
Medications that reduce stomach acid (eg: PPI)
- Because acid is needed to keep iron as the soluble Fe2+
46
Hookworm as a cause of iron deficiency anaemia
- Most common cause worldwide
- Results in GI blood loss
47
Normal iron function
- Absorbed
- Circulated bound to transferrin
- Stored as ferritin or incorporated into Hb
48
Diagnosis of iron deficiency anaemia
- FBC = microcytic
- Blood film - pencil cells (smol) platelet aggregates
- Iron studies
49
What would a blood film of iron deficiency anaemia show?
- Small, hypochromic (pale) RBCs
- Target cells - non-specific Bull's eye pattern
- Howell Jolly bodies - non-specific nucleated RBCs
50
Fe studies in iron deficiency anaemia
- Serum Fe: Low
- Ferritin: Low
- Transferrin saturation: Low
- Total iron binding capacity (and transferrin): High
51
Treatment for iron deficiency anaemia
- Blood transfusion - immediate correction but need to treat underlying cause
- Iron infusion
- Oral iron
52
Iron infusion
- eg: cosmofer
- Small risk of anaphylaxis
- CI during sepsis
53
Oral iron
- Ferrous sulphate 200mg 3x a day
- SE: constipation, black stools, GI upset
- If poorly tolerated, consider ferrous gluconate
- Unsuitable where malabsorption is the cause of the deficiency
54
What is sideroblastic aneamia?
- Defective Hb synthesis within mitochondria
- Often X inherited ALA synthetase deficiency
- High Fe but not used in Hb synthesis, trapped in mitochondria!
55
Diagnosis of sideroblastic anaemia
- FBC + blood film
- Fe studies
56
Fe studies for sideroblastic anaemia
- Serum Fe: High
- Ferritin: High
- Transferrin saturation: High
- Total iron binding capacity (and transferrin): Low
57
FBC and blood film for sideroblastic anaemia
- Microcytic
- Ringed sideroblasts (immature RBC)
- Basophilic stippling (increased basophilic granules)
58
Signs specific to thalassaemia
Bone deformities
59
What is thalassaemia?-what kinds of genetic haemoglobinopath?
- Autosomal recessive haemoglobinopathy
- A type of haemolytic anaemia
- Defective alpha-globin chain = alpha thalassaemia
- Defective beta-globin chain = beta thalassaemia
60
Pathophysiology of thalassaemia
- RBCs are more fragile and break down more easily
- Spleen collect all the destroyed RBCs, resulting in splenomegaly
- Bone marrow expands to produce extra RBCs -> susceptibility to fractures, pronounced forehead and molar eminence
61
Where is thalassaemia prevalent?
Where malaria is as it is protective from it (like sickle cell)
62
Alpha thalassaemia
- Less common
- 4 gene deletions on chromosome 16
- Associated with HbH
- Can cause death in utero if severe
63
Beta thalassaemia
- More common
- 2 gene mutations in chromosome 2
- Normal Hb isoforms, just depletion of beta chains
64
Presentation of thalassaemia
- Failure to thrive
- Hepatospenomegaly
- Gallstones
- Chipmunk face
65
Diagnosis of thalassaemia
- FBC + blood film
- Hb electrophoresis - diagnostic
- Xray - "hair on end" skull
66
FBC and blood film in thalassaemia
- Hypochromic (pale) RBCs
- Target cells
- Microcytic anaemia with high reticulocytes
67
Treatment for thalassaemia
- Regular transfusion
- Iron chelation to remove excess iron in body due to blood transfusions
- Splenectomy
- Ascorbic acid (vit C)
- Bone marrow transplant (curative)
68
Iron chelation
- Prevents Fe overload from transfusions
- Desfemoxamine
- SE: deafness, cataracts
69
Signs specific to haemolytic anaemia
- Prehepatic jaundice
- Dark urine
70
Types of haemolysis
- Intravascular - marked by haptoglobin (attaches itself to certain hb so if low then anaemia)
- Extravascular - @ spleen
- Can be both
71
What is autoimmune haemolytic anaemia precipiated by
Precipitated by temperature (warm most common but idiopathic)
72
Pathophysiology of autoimmune haemolytic anaemia
- IgM autoantibodies activate compliment system by binding to cell surface of RBCs
- Intra/extravascular haemolysis
73
Special test for autoimmune haemolytic anaemia
- Direct coombs +ve
- An abnormal (positive) direct Coombs test means you have antibodies that act against your red blood cells.
- Agglutination of RBCs with coombs reagent-the antibodies in the Coombs reagent bind to the antibodies attached to the erythrocytes, causing agglutination.
74
What conditions is autoimmune haemolytic anaemia secondary to?
- Leukaemia
- Lymphomas
- SLE -Systemic lupus erythematosus - an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs
- Any sort of infections (eg: EBV)
75
What is G6PDH deficiency
(glucose-6-phosphate dehydrogenase). This enzyme helps red blood cells work properly. A lack of this enzyme can cause hemolytic anemia.
- X linked recessive enzymopathy
- Causes 1/2 lifespan + RBC degeneration
76
What is G6PDH?
- Glucose-6-phosphate dehydrogenase
- Protects RBCs from vasoxidative damage
- Involved in glutathione synthesis (protects from ROS like H2O2)
77
Factors that can precipitate G6PDH deficiency
- Naphthelene (in moth balls (pesticide))
- Antimalarials, eg: quinine
- Aspirin
- Fava beans (contain glucosides that can be oxidised into ROS)
- Nitrofurantoin- Nitrofurantoin is an antibacterial medication of the nitrofuran class used to treat urinary tract infections
78
G6PDH attack
Rapid anaemia + jaundice (intravascular haemolysis)
79
Diagnosis of G6PDH deficiency
FBC + blood film
- Normal inbetween attacks
- Attack: normocytic, normochromic, increased reticulocytes, heinz bodies and bite cells
Low G6PDH levels
80
Treatment for G6PDH deficiency
- Avoid precipitants
- Blood transfusions when attacks ensue
81
Signs of G6PDH deficiency
- Neonatal or intermittent jaundice
- Anaemia
- Gallstones
- Splenomegaly
82
Risk factors for G6PDH deficiency
- X-linked recessive (men)
- West African, Mediterranean, Asian
83
Symptoms of G6PDH deficiency
- Fatigue
- Palpitations
- Dyspnoea
- Pallor
84
What is hereditary spherocytosis?
- Autosomal dominant membranopathy
- Instead of being shaped like a disk, the cells are round like a sphere. These red blood cells (called spherocytes) are more fragile than disk-shaped RBCs
- Common in Northern Europe and America
85
Pathophysiology of hereditary spherocytosis
- Deficiency in structural membrane protein spectrin
- Increased splenic recycling (extravascular haemolysis)
- Makes RBCs more spherical and rigid
86
Presentation of hereditary spherocytosis
- General anaemia
- Neonatal jaundice
- Splenomegaly
- Gall stones (50%)
87
Treatment for hereditory spherocytosis
Splenectomy
88
Treatment of neonatal jaundice in hereditory spherocytosis
- Treated with phototherapy
- Risk of kernicterus if untreated (bilirubin accumulates in basal ganglia, CNS dysfunction, death)
89
Diagnosis of hereditary spherocytosis
- FBC and blood film: Normocytic, normochromic, spherocytes, increased reticulocytes
- Direct coombs -ve
- Eosin-5-maleimide (EMA) test
- Cryohaemolysis
90
Types of malaria
- Plasmodium falciparum (most severe and dangerous, 75% in the UK)
- Plasmodium vivax
- Plasmodium ovale
- Plasmodium malariae
91
Pathophysiology of malaria
- Spread by female anopheles mosquitos
- When mosquito bites human, sporozoites are injected
- Travel to liver
- Mature into merozoites which enter blood and infect RBCs
- Merozoites replicate and RBCs rupture after 48 hours, cause a systemic infection
92
In what forms of malaria can sporozoites lie dormant in the liver for years?
- P.vivax and P.ovale
- Lie dormant as hypnozoites
93
Presentation of malaria
- Blackwater fever (malarial haemoglobinuria)-a severe form of malaria in which blood cells are rapidly destroyed, resulting in dark urine.
- Massive hepatosplenomegaly
- Pallor
- Jaundice
- Myalgia (muscle ache and pain)
- Headache
- Vomiting
94
Diagnosis of malaria
- Malaria blood film
- 3 samples over 3 consecutive days
95
Oral treatments for malaria
- Quinine sulphate
- Doxycycline
96
IV treatment for malaria
- Artesunate (most effective but not licensed)
- Quinine dihydrochloride
97
Complications of P.Falciparum
Cerebral malaria
Reduced GCS
AKI
Seizures
Haemolytic anaemia (severe)
DIC
Oedema
Multi-organ failure and death
98
Antimalarials
- 90% effective at preventing infections
Options:
- Proguanil and atovaquone (malarone)
- Mefloquine
- Doxycycline
99
Proguanil nad atovaquone (malarone) antimalarial
- Most expensive
- Best side effect profile
100
Mefloquinne antimalarial side effects
- Bad dreams
- Rarely psychotic disorders or seizures
101
Doxycycline antimalarial side effects
- Diarrhoea and thrush (as it's a broad spectrum antibiotic)
- Makes patients sensitive to the sun, causing a rash and sunburn
102
Malaria in children
- Convulsions (60-80%)
- High ICP, hypoglycaemia
- Rule out meningitis (examination and CSF analysis if no high ICP)
103
What is sickle cell anaemia?
- Autosomal recessive haemoglobinopathy affecting beta-globin chains
- Commonest in africa for antimalarial properties (vs plasmoduium falciparum)
- HbS variant
104
Pathophysiology of sickle cell anaemia
- Glutamic acid -> valine on 6th codon of beta-globin on chromosome 11
- Causes irreversible RBC sickling
- RBC more fragile so less efficient
- Bone marrow focuses more on reticulocytes, decreasing other cell lines (eg: causes neutropaenia)
- Intra+extravascular haemolysis
105
Presentation of sickle cell anaemia
General anaemia symptoms + prehepatic jaundice
106
What are sickle cell complications (crises) precipitated by?
- Cold
- Hypoxia
- Acidosis
- Dehydration
- Exertion
- Stress
107
Types of sickle cell crises
- Vaso-occlusive (aka painful crisis)
- Splenic sequestration
- Acute chest syndrome
- Aplastic crisis (from parvovirus)
- Osteomyelitis
108
Another common complication of sickle cell anaemia
- Osteomyelitis - an inflammation or swelling of bone tissue that is usually the result of an infection
- Usually due to s.aureus, but in those patients = salmonella
109
Diagnosis of sickle cell anaemia
- Sickle solubility test
- Newborn heel prick test
- Antenatal: Molecular genetics
- Hb electrophoresis - diagnostic when above 90% HbS (number 4 has sickle cell)
110
FBC and blood film in sickle cell anaemia
- Normocytic normochromic
- Increased reticulocytes
- Sickled RBC
- Howell Jolly bodies
111
Last resort treatment for sickle cell anaemia
Bone marrow transplant
112
Long term treatment for sickle cell anaemia
- Avoid precipitants
- Drugs - hydroxycarbamide (aka hydroxyurea) to increase HbF levels, folic acid supplements
- Transfusion + Fe chelation
113
Vaso-occlusive crisis
- Sickel shaped RBCs clog capillaries, causing distal ischaemia
- Dehydration and raised haematocrit
- Can cause priapism in men (treated with aspiration of blood from the penis)
114
Treatment for acute complicated attacks
- Low threshold for hospital admission
- Treat any infection
- Keep warm
- IV fluids
- Simple analgeisa
115
Splenic sequestration crisis
- RBCs block blood flow within the spleen - can cause autosplenectomy
- Splenomegaly
- Can lead to severe anaemia and circulatory collapse (hypovolaemic shock)
- Splenectomy used in cases of recurrent crisis
116
Aplastic crisis
- Temporary loss of the creation of new RBCs
- Most commonly triggered by infection with parvovirus B19
- Management is supportive with blood transfusions
- Usually resolves spontaneously within a week
117
Acute chest syndrome sickle cell crisis
- Caused by pulmonary vessel vaso-occlusion
- Fever or resp symptoms with new infiltrates seen on Xr
- Can be due to infection or non-infective causes
- Medical emergency with high mortality
118
Treatment for acute chest syndrome
Exchange blood transfusion - sickle cell blood replaced w healthy blood
119
Chronic complications of sickle cell anaemia
- Avasular necrosis of joints
- Silent CNS infarcts
- Nephropathy
- ED
120
What to give patients with sickle cell painful crisis?
- IV fluids
- Analagaesia - NSAIDs
- Oxygen if low
- Broad spectrum antibiotics due to neutropaenia
121
Haemolytic vs non-haemolytic anaemia
Failing bone marrow in non-haemolytic
122
Myelophthisic process in non-haemolytic anaemia
Bone marrow infiltrated with something else (eg: tumour cells)
123
Pathophysiology of aplastic anaemia
Pancytopenia where bone marrow fails and stops making haematopoetic stem cells
124
Cause of aplastic anaemia
- Idiopathic
- Could be infection (EBV, parovirus B19) or congenital
125
Diagnosis of aplastic anaemia
- FBC = normocytic anaemia with decreased reticulocytes
- Bone marrow biopsy = hypocellularity
126
Complication of aplastic anaemia
- Increased infection risk (neutropenia)
- Treat with broad spectrum antibiotic and bone marrow transplant
127
Signs specific to CKD
- Oedema
- Hypertension
- Excoriations on the skin (conscious repetitive picking of skin that leads to skin lesions and significant distress or functional impairment)
128
Pathophysiology of CKD anaemia
- Occurs in chronic diseases
- Decreased bone marrow stimulation for production of erythropoetin
129
Diagnosis of CKD anaemia
- Normocytic and normochromic
- Decreased reticulocytes due to low erythropoetin
130
What is antithrombin 3 deficiency
- Inherited (or aquired in nephrotic syndrome)
- Antithrombin 3 inhibits factor Xa by binding to its co-factor heparin
131
Pathophysiology of DIC- Disseminated intravascular coagulation
- Tissue damage causes release and activation of tissue factor
- Widespread activation of coagulation cascade and therefore platelet activation (crisis)
- Platelets unnecessarily consumed + microthrombose in small blood vessels
- Tissue plasminogen activator activated, leads to increased fibrinolysis - clotting removed
- Lack of systemic platelets -> increased bleed risk
132
Aetiology of DIC
- Trauma
- Sepsis (eg: meningococcal meningitis)
- Malignancy
133
Diagnosis of DIC
- Low platelets
- Low fibrinogen
- Increased D-dimer
- Long PT and APTT
134
Presentation of DIC
- Bleeding (epistaxis, bruising, rash, GI bleeding)
- Acute resp distress syndrome
135
Treatment for DIC
- Treat underlying cause
- Fresh frozen plasma to replace clotting factor
- Cryoprecipitate to replace fibrinogen
- Platelet transfusion
136
How does DIC cause infection
High clotting factors uses up platelets so systemic defences are down
137
Epidemiology of haemophilia?
X linked recessive clotting factor deficiency so way more common in males
138
Types of haemophilia
A - Factor 8 deficiency, most common
B - Factor 9 deficiency, also known as Christmas disease🎄
C - Factor 11 deficiency, very rare
139
Presentation of haemophilia
- Spontaneous bleeds
- Haemarthrosis (bleeding into joint)
- V. easy bruising
- Epistaxis🤧
140
When do most cases of haemophilia present?
- In neonates or early childhood
- Intercranial haemorrhage, haematomas, cord bleeding
141
Diagnosis of haemophilia
Diagnosis of haemophilia
- Normal PT, long APTT (as only intrinsic pathway is affected)
- Low CF assay (which factor depends on type)
142
Treatment for haemophilia A and B
A - high intensity IV factor 8 + desmopressin (releases F8 stored in vessel walls) every two days
B - IV factor 9
143
Risk factors for aquired haemophilia
- Age >60
- IBD
- Diabetes
- Pregnancy/ postnatal
- Malignancy
144
Pathophysiology of Von Willebrand disease
- Autosomal dominant mutation of VWF gene on chromosome 12
- Defect in quality or quantity of VWF
- VWF is responsible for the basis of the platelet plug -> more spontaneous bleeding and bruising
- Most common inherited bleeding disorder
145
Presentation of Von Willebrand disease
Mucocutaneous bleeding:
- Epistaxis
- GI bleeds
- Mennhoragia
- Bleeding gums with brushing 🪥
- Heavy bleeding during surgery
146
Diagnosis of Von Willebrand disease
- Normal PT, long APTT
- Normal factor 8/9 assay
- Low VWF
147
Treatment of Von Willebrand disease
- Desmopressin (releases VWF from endothelial Weibel palade bodies)
- IV factor 8 can also be infused for 2 weeks in severe cases
- Tranexemic acid (antifibrinolytic)
148
Treatment for glandular fever?
- Supportive therapy (fluids, analgesia)
- Avoid contact sports for 6 months eels to prevent splenic rupture
149
What's EBV associated with?
Epstein-Barr Virus
-mono
Many conditions inc:
- Hodgkin's lymphoma
- Burkitt's lymphoma
- Nasopharyngeal carcinoma
150
Incidence and spread of EBV
- 15-24 years old
- Spread via saliva or bodily fluids
151
Symptoms of EBV
and how long is treatment?
Varied mild symptoms:
- Fever
- Tonsilitis
- Hepatosplenomegaly
- Cough
Self limiting 2-4 weeks
152
Diagnosis of EBV
(Not with a green viral swab like most viruses)
- FBC = Atyptical lymphocytes on blood film
- Serology = EBV Igs with clotted sample
- ELISA TEST
153
Pathophysiology of haemolytics uraemic syndrome
- Paediatric condition
- Following infection with shiga-toxin producing bacteria like E.Coli/Shigella (typically 5 days after gastroenteritis)
- Microvascular clot formation, deposition of platelets and fibrin in small vessels
154
Presentation of haemolytic uraemic syndrome
- Mostly self limiting but presents as medical emergency
- AKI (oliguria, haematuria, hypertension) -> uraemia
- Hameolytic anaemia
- Thrombocytopaenia
155
Diagnosis of haemolytic uraemic syndrome
- FBC
- Blood smear
- Differentiate from TTP (Thrombotic Thrombocytopenia Purpura) with ADAMTS13 testing
156
FBC in haemolytic uraemic syndrome
- Thrombocytopaenia
- Anaemia
- High reticulocytes
- High LDH
- High bilirubin
157
Treatment of haemolytic uraemic syndrome
- Supportive fluids
- Antibiotics
158
Types of HIV
- HIV-1 - more common, most virulent
- HIV-2 - less common, less virulent
159
Transmission of HIV
- Retrovirus
- Sexual transmission
- Sharing needles
160
HIV RNA copies vs CD4 count
CD4 starts high, drops drastically after a stage, goes up again by stage 2 then dramatic drop baso 0 by group 3 then gone by stage 4
peaks at stage 1 then drops by stage 2, then increases, gets to AIDS by stage 4 then death
1 and 2 weeks then after years 3 and 4
1. CD4+ dip then 'set point'
2. Clinical latency (years)
3. Symptoms
4. AIDS (CD4+ <200/mm3)
161
Treatment for HIV
HAART - highly active antiretroviral therapy
- 3 drugs <, reverse transciptase inhibitors
- Aim is to maintain CD4 count and decrease HIV RNA copies
162
Risk factors of HIV
- Sharing needles, needle stick injury
- MSM - unprotected anal sex
163
Pathophysiology of HIV
- HIB gp120 binds to CD4 on TH
- Endocytoses RNA + enzymes
- Reverse transcriptase RNA -> DNA
- Integrase; viras DNA integrated into host's
- Protein synthesis
- Viral proteins + RNA exocytose and take part of CD4+ cell CSM
- Increased viral copies, decreased CD4+ (TH cells)
164
AIDS definining conditions
- CMV (eg: collitis -> owl eyes)
- Pneomocystis jirovecci pneumonia
- Kaposi sarcoma
- Cryptosporadium (fungal) infection
- TB
- Toxiplasmosis
- Lymphomas
165
Diagnosis of HIV
- History + Anti HIV Ig, p24 Ab (Elisa testing)
- Monitor progression - HIV RNA copies + CD4 count
166
Pathophysiology of leukaemia
- Neoplastic proliferation of WBC line (myeloblasts or lymphoblasts)
- Lose ability to differentiate but maintain ability to replicate
- Decreased production of other haematopoetic cells (functional pancytopaenia)
167
General signs of leukaemia
- Thrombocytopaenia - bleeding and bruising
- Leukopaenia - infections
- Anaemia symptoms
- Hepatosplenomegaly
- Fatigue
- Failure to thrive (children)
168
Testing for leukaemia
- FBC (shows pancytopaenia)
- Blood film
- Bone marrow biopsy - diagnostic
- Imaging (CT/CxR)
- Genetic testing
169
Blood films for leukaemia
- ALL - increased lymphoblasts
- AML - increased lymphoblasts with auer rods, myeloperoxidase positive
- CLL - smudge cells (Richter's transformation)
170
Leukaemia bone marrow biopsies
ALL - lymphoblasts ≥20%
AML - myeloblasts ≥20%
CLL - pancytopaenia (except lymphocytosis)
CML - increased granulocytes, blast cell percentage shows severity (diff card)
171
Chromosomal translocations in leukaemia
ALL - mostly t(12:21)
AML - t(15:17)
CLL - multifactorial
CML - t(9:22) (Philadelphia chromosome)
172
What do tyrosine kinases do
Increase cell proliferation
173
What is hypogammaglobulinaemia
- Low conc. of immunoglobulins present in CLL
- This is because B cells proliferate but don't differentiate to plasma cells (which are responsible for producing Igs)
174
What to give with chemo
✨allopurinol✨
- Chemo releases uric acid from cells which can accumulate in kidneys
- This would cause tumour lysis syndrome
- Allopurinol prevents it
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Acute lymphoblastic anaemia (ALL)
- Neoplastic proliferation of lymphoblasts, mostly B
- Terminal deoxynucleotidyl transferase expressed
- Patients typically under 6 (75%) and over 50
- Associated with Down's syndrome
176
Presentation of ALL
- General leukaemia symptoms
- Lymphadenopathy
- CNS infiltration -> headaches, CNS palsies
177
Philadelphia chromosome in ALL
- 30% in adults 3-5% in children
- Worse prognosis
178
Treatment of ALL
- Chemotherapy
- Typically good prognosis
179
Presentation of AML
- General leukaemia symptoms
- Gum hypertrophy
180
Acute myelogenous leukaemia (AML)
- Neoblastic proliferation of myeloblasts
- Present mostly in the elderly (over 65)
- Rapid progression if not treated asap
- 3 year survival 20%, 5 year survival 15%
181
AML + DIC
- Common subtype of AML
- Acute premyelocytic leukaemia (APML)
182
Treatment of AML
- Chemo + tretinoin (used for APML)
- Transfusion for anemia
- Abx (antibiotix) prophylaxis for neutropaenia
- Last resort: bone marrow transplant
183
Aetiology of AML
- Down's syndrome
- Radiation
184
Chronic lymphocytic leukaemia (CLL)
- Neoplastic proliferation of lymphocytes, mostly B
- Most common leukaemia in adults
- Over 70 year olds, men typically
- 5 year survival of 75%
185
Presentation of CLL
- General anaemia symptoms
- Often asymptomatic
- Rubbery non-tender lymphadenopathy
- Might have night sweats and weight loss
186
Treatment of CLL
- Watch and wait in early stages
- Monoclonal antibodies (rituximab)
- Bruton kinase inhibitors (ibrutinib)
- Palliative (if v old)
- IV Ig for hypogammaglobulinaemia
187
Complicaton of CLL
Richter transformations🥲
- B cells massively accumulate in lymph nodes
- Mahoosive lymphadenopathy and transformation from CLL to aggressive lymphoma
- #oops
188
Presentation of CML
- General leukaemia
- Massive hepatosplenomegaly when with malaria
189
Treatment for CML
Chemo + imantinib (tyrosine kinase inhibitor)
190
Severity of CML based on blast cell % in bone marrow biopsy
1. <10% - Chronic (best)
2. 10-19% - Accelerated
3. ≥20% - Blast crisis (worst, could progress to AML, poorer prognosis - often happens when CML is untreated or diagnosed late)
191
Chronic myelogenous leukaemia (CML)
- Neoplastic myelocyte proliferation - mainly neutrophils
- Adults around 60
- BCR - ABL gene fusion causing tyrosine kinase to be irreversibly switched on
192
What are B symptoms of lymphomas?
- Fever
- Night sweats
- Unintentional weight loss
193
Ages susceptible to lymphomas
Hodgkin: Bimodal distribution, with peaks in early 20s and in 70s
Non-Hodkin: Over the age of 40
194
Diagnosis of lymphoma
- Lymph node biopsy
- PET-CT/MRI chest/abdo/pelvis for staging
- Performance status score to establish treatment
195
How to distinguish between Hodgkin and non-Hodgkin lymphoma?
Lymph node biopsy (core needle/excision needle)
- Hodgkin's shows Reed-Sternberg cells🦉
- Abnormally large B cells with multiple nuclei and nucleoli
- These aren't present in Non-Hodgkin lymphoma, but you can still use the biopsy to determine NHL subtype, eg: Burkitt's shows starry sky🌌
196
Ann Arbor staging in both types of lymphoma
1. One region of lymph nodes
2. 2 or more lymph nodes on same side of the diaphragm
3. Lymph nodes on both sides of the diaphragm
4. Extranodal organ spread
also:
a - no B symptoms
b - B symptoms
197
Pathophysiology of Hodgkin lymphoma
Proliferation of lymphocytes in lymph nodes, typically in the cervical, axillary or inguinal lymph nodes
198
Risk factors of Hodgkin lymphoma
- HIV
- EBV (gladular fever)
- Autoimmune conditions
- Family history
199
Presentation of Hodgkin lymphoma?
- B symptoms (Hodgkin is a high grade B cell lymphoma)
- Non-tender rubbery lymphadenopathy which becomes painful after drinking alcohol
200
Other possible symptoms of Hodgkin lymphoma
- Fatigue
- Itching
- Cough
- Dyspnoea
- Abdo pain
- Recurrent infections
201
Popcorn cells🍿
- Seen in nodular lymphocyte predominant Hodgkin's
- (a subtype of Hodgkin lymphoma)
- They are a variant of Reed-Sternberg cells
202
Treatment of Hodgkin lymphoma
- ABVD immunochemotherapy (adriamycin, bleomycin, vinblastine, dacarbazine)
- +/- radiotherapy
- Marrow transplant
203
Side effects of chemo for Hodgkin lymphoma
- Alopecia
- N+V
- Myelosuppression
- BM failure
- Infection
- Infertility
- Leukaemia
204
Side effects of radiotherapy for Hodgkin lymphoma treatment
- Cancer
- Damage to tissues
- Hypothyroidism
205
Febrile neutropaenia
- Massive risk in patients with recent/high dose chemo (or on carbimazole)
- Fever, tachycardia, swears, rigors, tachypnoea
- Treated with immediate broad spectrum antibiotics
206
Diagnosis of Hodgkin lymphoma
- FBC: Anaemia, high ESR
- High LDH
- CXR - Wide mediastinum
- Blood film - Reed Sternberg cells
207
Types of Non-Hodgkin lymphoma
- Low grade - Follicular
- High grade - Diffuse large B cells
- Very high grade - Burkitt's
208
Cells affected in Non-Hodgkin lymphoma
- B cells (90%)
- T cells (10%)
- NK cells (<1%)
209
MALT lymphoma
- Affects mucosal-associated lymphoid tissue
- Associated with H.pylori infection or eye chlamydia infection
210
Other risk factors for Non-Hodgkin lymphoma
- Hep B or C infection
- Exposure to trichloroethyline (pesticide)
- Immunosuppression
211
Presentation of Non-Hodgkin lymphoma
- B symptoms
- Non-tender rubbery lymphadenopathy, not affected by alcohol
- Can get hepatosplenomegaly
212
Treatment of low-grade lymphoma
- Radiotherapy
- R-CHOP Chemotherapy
Rituximab (targets CD20 on B-cells)
Cyclophosphamide
Hydroxy-daunorubicin
Oncovin (brand name for vincristine)
Prednisolone
213
Indolent lymphoma
- Slow growing and advanced on presentation
- “Incurable”
- High on Ann Arbour scale
- Median survival 9-12 years variable across and within subtypes
214
Aetiology of indolent lymphoma
- Primary and secondary immunodeficiency
- Infection
- Autoimmune disease
215
Burkitt lymphoma
- Associated with EBV, malaria and HIV
- Often causes massive jaw lymphadenopathy in children
216
Two types of non-Hodgkin lymphomas
- Aggressive - quick onset but can be treated
- Indolent - worse prognosis
217
Pathophysiology of multiple myeloma
- Neoplastic monoclonal proliferation of a plasma cell
- Results in large quantities of a single type of antibody/monoclonal paraprotein being produced (55% IgG, 20% IgA)
218
Monoclonal gammopathy of undetermined significance (MGUS)
- Too much Ig released by abnormal plasma cells
- <10% BM plasma cells
- Asymptomatic
- 1% of cases develop into myeloma
219
Smouldering myeloma
- Progression of MGUS with higher levels of antibodies
- Premalignant, more likely to progress to myeloma than MGUS
- Waldenstrom's macroglobulinaemia is a type of smouldering myeloma with excessive IgM specifically
220
Epidemiology of myeloma
- Around 70 years old
- Afro-Carribeans
- Male
- Obesity
- 1% of cancers are myeloma
221
Presentation of multiple myeloma (🦀)
HyperCalcaemia
Renal failure
Anaemia
Bone lesions
222
What are anaemia and bone lesions caused by in multiple myeloma?
Bone marrow failure
223
What are hypercalcaemia and bone lesions caused by in multiple myeloma?
Increased osteoclast bone resorption due to cytokines released by plasma and stromal cells
224
What is renal failure caused by in multiple myeloma?
- Hypercalcaemia -> calcium oxalase renal stones
- Immunoglobulin light chain deposition - Bence Jones protein in pee
225
Testing for multiple myeloma
- FBC and blood film
- U+E = renal failure
- Bone profile = hypocalcaemia and increased ALP
- Serum electrophoresis
- Urine dipstick - Bence Jones protein
- Xr
226
FBC and blood film for multiple myeloma
- Normocytic normochromic anaemia
- Raised ESR
- Rouleaux formation in blood film (aggregation of RBCs)
227
Serum electrophorisis in multiple myeloma
- Ig paraprotein 'M spike'
- Hypergammaglobulaemia for that specific Ig
228
X-ray for multiple myeloma
- Pepper pot skull
- Osteolytic lesions -> "punched out holes"
229
Confirmatory diagnosis of multiple myeloma
- Bone marrow biopsy required - >10% plasma cells
- NICE recommends full body MRI (if not, then CT or Xray in that order of preference)
230
Treatment of multiple myeloma
- Bisphosphonates (eg: alendronate) to decrease octeoclastic activit and increase osteoblastic activity - protects bones
Older patients:
- Anti-myeloma chemotherapy
- Consider BM stem cell transplant
231
Plasma viscocity in multiple myeloma
- Increased due to large amounts of immunoglobulins in blood
Complications:
- Easy bruising and bleeding
- Reduced or loss of sight due to vascular disease in the eye
- Purple discolouration of extremities
- Heart failure
232
Supportive treatment for multiple myeloma
- Bisphosphonates
- Blood transfusion/EPO injection
- Antibiotics and pain-killers as needed
- GCSF to boost neutrophils
- Radiotherapy
- Kyphoplasty occasionslly indicated
- Psychological support
233
What is multiple myeloma characterised by?
- Monoclonal protein in serum or urine
- Lytic bone lesions/ CRAB end organ damage
- Excess plasma cells in bone marrow
234
Classic features of myeloma
- Osteoporosis
- Nephrotic syndrome
- Hypercalcaemia
- Thrombocytopaenia
235
What is the precursor condition to developing multiple myeloma?
Mammyloid gammopathy of undetermined significance
236
Pathophysiology of polycythaemia vera
- A high concentration of erythrocytes in the blood
- Due to JAK2V617 mutation
- The affected bone marrow can also produce excessive platelets and white blood cells
237
Relative vs absolute polycythaemia
Relative:
- Normal number of erythrocytes, reduction in plasma
- Causes include obesity, dehydration execessive alcohol and increased erythropoetin
Absolute:
- Increased number of erythrocytes
- Primary and secondary
238
Primary vs secondary polycythaemia
Primary: Polycythaemia vera - abnormality in the bone marrow
Secondary: Disease outside the bone marrow causing overstimulation of the bone marrow
239
General symptoms of polycythaemia
- Erythromalagia (fig 1)
- Reddish plethoric complexion
- Blurred vision
- Headache + dizziness
(features nonspeifically related to hyperviscosity)
240
Symptoms unique to polycythaemia vera
- Itchy after a bath (contact with warm water) 🛁
- Hepatosplenomegaly
241
Diagnosis of polycythaemia vera
- FBC = high WCC, high platelets, high RBCs
- High Hb
- Genetic tests JAK2V617 positive
242
Treatment of polycythaemia vera
Non-curative, main aim is to maintain a normal blood count
Low-risk:
- Venesection regularly (often used solely)
- Low dose aspirin
High risk:
- Consider chemotherapy (hydroxycarbamide) for patients at high risk of thrombus (60+, background of thrombosis)
243
What haematocrit is concerning in polycythaemia vera?
>45%
244
Differential diagnoses of abnormal or prolonged bleeding
- Thrombocytopaenia (low platelets)
- Haemophilia A and B
- Von Willebrand disease
- Disseminated intravascular coagulation (secondary to sepsis)
245
Ge symptoms of thrombocytopaenia (all of the symptoms of ITP)
- Purpuric rash
- Easy bleeds
- Mennhoragia
246
Heparin-induced thrombocytopenia
- Antibodies bind to heparin after administration -> prothrombotic state
- Onset of emboli
- Platelets <50%, D-dimer high
- Treatment: stop heparin, anticoagulate
247
Pathophysiology of ITP
- Autoimmune
- Antibodies (usually IgG) created against platelet, causing platelet destruction
- Specifically, Gpiib/iiia on platelets are destroyed
248
Types of ITP (immune thrombocytopenic purpura)
Type 1: Children 2-6, post viral infection, acute + severe
Type 2: Adult women w malignancy, HIV or other autoimmune condition. Chronic + mild
249
Diagnosis of ITP
- FBC - raised WCC, low Hb, low platelets
- Increased bone marrow megakaryocytes (due to negative feedback)
250
Treatment of ITP
First line: Prednisolone + IV IgG
this decreases splenic platelet destruction
Second line: Splenoctomy
251
Pathophysiology of TTP (Thrombotic Thrombocytopenia Purpura)
- ADAMTS13 (VWF cleaving protein) deficiency
- VWF remain as multimers and aggregate at endothelial injury sites
- Incidence same as Type 2 ITP
252
Symptoms unique to TTP
- AKI
- Fever
- Haemolytic anaemia
- Neurologicla symptoms
253
Diagnosis of TTP
- Same FBC as ITP
- Raised billirubin and creatinine
- Blood smear: schistocytes
- RBCs; microangiopathic haemolytic anaemia
- Genetic testing shows low ADAMTS13
254
Treatment of TTP
First line: Plasmapharesis
Second line: Prednisolone + rituximab
255
Pathophysiology of tumour lysis syndrome
- Collection of metabolic disturbances occuring with rapid destruction of neoplastic cells following chemotherapy
- More common in aggressive treatment of haem malignancies
256
Signs of tumour lysis syndrome
- Hyperuricaemia, hyperkalaemia, hyperphosphataemia
- Hypocalcaemia
- AKI
257
