Clinical Haemotology Flashcards
Anaemia
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
low circulating RBC’s
Types
1)Microcytic:
- Insufficient haemoglobin production
- MCV <80
Defective haem synthesis: iron def, anaemia of chronic disease
Defective globin synthesis: thalassaemia
2)Normocytic
- Decreased blood volume or decreased erythropoiesis
- MCV 80-100
Hameolytic anaemia: Sickle cell (haemoglobinopathy), G6PD deficiency (enzyme deficiency), Hereditary spherocytosis (membrane defect), autoimmune haemolytic anaemia (extrinsic)
- Warm hameolytic anaemia : refers to autoantibodies that are only active at certain temperatures,, associated with IgG antibodies, SLE and chronic lymphocytic anaemia
- Cold haemolytic anaemia: hameolysis from another autoantibody that tags the RBC for destruction too but only works at 3 degrees. Associated with IgM antibodies, Mycoplasma pneumonia, mononucleosis, lymphoma
Non haemolytic: blood loss, aplastic anaemia (parvovirus B19 infection), chronic diseases like RA
3) Macrocytic
- Defective DNA synthesis or repair
- MCV >100
Megaloblastic: B12 and folate deficiency
Non-megaloblastic: liver disease, alcohol (ig have GGT raise), Methotrexate, Myelodysplasia (pancytopenia and bone marrow issue), Hypothyroidism
CLINICAL FEATURES
- Pallor
- Dyspnoea on exertion
- Fatigue
- Tachycardia
- Glossitis
- Angular stomatitisRed patches in corner of mouth where lips meet seein in Iron deficiency anaemia
- Koilonychia: Spoon shaped nails seen in Iron deficiency anaemia
- Pica- eating disorder (eating non food)
INVESTIGATIONS
Reticulocytes
High in : haemolytic crisesor haemorrhage
Low in: Parvovirus B19 infection, aplastic crises in sickle cell crisis and blood transfusion
1) MICROCYTIC ANAEMIA
iron studies, Peripheral Blood Smear, Hb electrophoresis, HbA2
- Iron deficient : low ferritin, high transferrin, high total iron binding capacity (TIBC). must screen for coeliac
Normal peripheral blood smear
Electrophoresis Lowered HbA2
- Anaemia of chronic disease: high ferritin!!!, low transferrin, reduced TIBC, increased hepcidin, history of a chronic disease
Normal peripheral blood smear - Siderobloastic anaemia (body makes enough iron but cant put it into Hb) high iron, high ferritin, high transferrin. History of lead exposure or alcohol use.
Peripheral blood smear: basophilic stippling and sideroblasts.
If see sideroblasts must do bone marrow biopsy
-Thalassaemia:
Only one with normal RBC count, very low MCV under 70 usually, normal iron studies
Peripheral blood smear: basophilic stippling
On electrophoresis: reduced or absent HbA, elevated levels of HbA2, and increased HbF. HbA2 raised in beta thalassemia trait, not good for babies growth so important for women who plan to get pregnant
- Sickle Cell
Signs of lysis: high LDH, unconj bilirubin, low haptoglobin
Hb HbSDG
Blood Film:
- pencil poikilocytes
- hypochromic and microcytic red cells
- target cells
- anisopoikilocytosis (RBC’s of different shapes and sizes)
MACROCYTIC ANAEMIA:
Vitamin B12 and folate levels
Blood film: if B12, folate or alcohpl Megaloblastic anaemia (hypersegemented neutrphils)
Homocysteine (high if vitamin B-12 or folate) and methylmalonic acid levels (B12 def)
TFT (hypothyroidism)
LFT (cirrhosis can see acanthocytes (spikey RBCs)
Look at medications: methotrexate, hydroxy urea, HIV meds, trimethoprim, epilepsy valporates and alcohol can cause
NORMOCYTIC ANAEMIA:
Iron studies
- In normocytic anaemia ferritin is normal
DAT test/Coombs test: check for autoimmune
Check for lysis: In haemolytic anaemia (high unconjugated bilirubin, LDH and reticulocytes) (low haptoglobin)
Blood Film/Peripheral Smear
- in hameolytic anaemia shows spherocytes
TFT (hypothyroidism)
LFT (cirrhosis can see acanthocytes (spikey RBCs)
If pancytopenia: low RBC, low WBC, low platelets do Bone Marrow biopsy (aplastic anaemia, myelodysplastic anaemia, pure red cell anaemia)
MANAGEMENT
if severe: Blood transfusion with RBCs
Iron deficieny: Ferrous sulfate, if cant tolerate oral IV iron
Hameolytic anaemia: Steroids (prednisolone) +/- rituximab
What is the presentation of G6PD deficiency
Which drugs can cause G6PD deficiency
What do you see on blood film
WHat investigations are needed
- Neonatal jaundice
- Infection/drugs precipitate haemolysis
- Gallstones
- Afro american
The Sulfs + quinolones (e.g. ciprofloxacin)
- Sulfonamides e.g. sulfasalazine
- Sulfonylureas (e.g. gliclazide)
- Heinz bodies
- Bite cells
- Blister cells
Investigations:
Measure G6PD enzyme activity : but can only do when not actively haemolysing
What is the presentation of Hereditary Spherocytosis
What do you see on blood film
WHat investigations are needed
Presentation
- Neonatal jaundice
- Chronic symptoms but haemolytic crises may be precipitated by infection
- Gallstones
- Splenomegaly
Blood film
Spherocytes
Investigation?
EMA binding test
sideroblastic anaemia
- blood film finding
- causes
- management
Blood Film : Basophilic stippling of RBC’s (red cells look granular)
Causes:
Myelodysplasia
Alochol
Lead
Anti-TB meds
Management:
Supportive
Underlying cause treatment
Pyridoxine may help
Sickle Cell Disease
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Sickle cell anaemia: autosomal recessive gene defect in Hb beta chain resultin in production of sickle cell Hb.
8% black people carry sickle cell trait
positive selection for sickle cell trait in regions endemic for malaria
Sickle cell trait:
- Occurs if HbS is inherited from one parent and the normal HbA from the other
- Sickle cell disease is when the child inherits sickle gene from each parent
HbAA = normal
HbAS = carrier (sickle cell trait)
HbSS = sickle cell disease
In HbS:
- Glutamic acid (polar) is replaced by valine (non-polar) at the sixth amino acid of the beta globin chain
- Therefore RBCs become rigid and distorted into a crescent shape
Sickle cell disease presents at 6months when HbF production decreases and HbS increases: Hand-foot syndrome → swelling, pain (crying baby), erythema in hands and feet
CLINICAL PRESENTATION
Before:
- Hypoxia
- Acidosis
- Dehydration
- Infection
SCD features:
- Anaemia: tiredness, SOB, pallor
- Dactylitis (Swollen dorsa of the hands and feet)
- High temperature
- Bone pain
- Lethargy
Crises:
- Persistent pain in skeleton, chest or abdomen= vaso-occlusive crises: sickle cells haemolyse making blocks in small blood vessels causing infarction
- Splenic sequestration/splenomegaly: sickle cells build up in spleen and undergo phagocytosis leading to functional hyposplenism, reducing the immune function
- Acute chest syndrome: most dangerous, get pain, fever and respiratory symptoms (dyspnoea, wheeze, cough), caused by pulmoanry infiltrates seen on Chest X ray.
- Gallstones, chronic cholecystitis: cholecystectomy needed
INVESTIGATIONS
Clinically- Acute painful vaso-occlusive crisis
Gold standard- Hameoglobin electrophoresis
- Shows HbS
- No HbA
- Raised HbF
Blood Film
- Sickle-shaped cells
- Howell-jolly bodies and target cells due to hyposplenism
FBC
- Haemolytic anaemia
- Elevated reticulocyte count if sequestration crises (+splenomegaly)
Iron study:
For distinguishing haemolytic anaemia from iron-deficiency anaemia
MANAGEMENT
Vaso-occlusive crisis:
- Fluids
- Analgesia (strong)
- Oxygen
- Antibiotics → if suspect inefection
- Blood transfusion → if Hb low
If doesnt resolve or they present with stroke :Exchange therapy → reduces sickle cells and increases normal cells
Acute chest Syndrome: Management AO(A)T: attack on a titan- analgesia, oxygen (spirometry), ABx, tranfusion
Chronic Disease:
- Hydroxurea/hydroxycarbomide: Increases HbF level which reduces frequency and duration of crises
-Crizanlizumab is approved to reduce the frequency of vaso-occlusive crises in patients aged ≥16 years.
- Repeated blood transfusions
- Regular vaccinatons: specifically encapsulated bacteria such as pneumococcus due to hyposplenism
Repeated splenic sequestration crises: Splenectomy
COMPLICATION
Aplastic crises due to infection with parvovirus B19 which can lead to temporary cessation of erythropoiesis
- Can cause sudden drop in haemoglobin
- Reduced reticulocytes
median survival: 58 years
Polycythaemia
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
An increase in RBC and therefore haemoglobin concentration.
Increases the risk of thrombosis as causes hyperviscosity, which slows blood flow and therefore inc chance of thrombosis
Usually middle and older ages
1) RELATIVE= Normal red blood cell mass but low plasma volume
-dehydration
-stress
2) TRUE= Increased red cell mass
3) polycythaemia VERA: chronic myeloproliferative neoplasm : erythropoietin-independent, irreversible increase in RBC erythrocyte, WBC granulocyte and platelet counts aka making too much RBCs and is cancerous. Can lead to acute myeloid leukaemia and myelofibrosis. Budd Chiari syndrome is a RF.
4) Secondary polycythaemia : excess EPO driven
EPO naturally increases due to chronic hypoxia like chronic lung issues aka COPD and living at higher altitudes.
EPO is inappropriately increased in hepatocellular carcinoma, renal carcinoma and EPO abuse by athletes
CLINICAL FEATURES:
- weight loss, fatigue, sweating
- Facial redness/purple/blue (plethora)
- Erythromelalgia : Tenderness or painful burning and redness of fingers, palms, heels or toes
- Pruritus- worsens when skin comes in contact with warm water
- Splenomegaly
- Headache
- Tinnitus
- Thrombosis- stroke, DVT, haemorrhage features
OTHER:
- Gangrene
- Choreiform movements: jerking, writhing
- Hyperviscosity Syndrome: mucosal bleeding, neurological symptoms (dizziness, headaches), visual changes
INVESTIGATIONS
Bloods: high haematocrit, high haemoglobin, high platelets, may have iron def
EPO: low in polycythaemia vera, high in secondary polycythaemia
JAK2 gene mutation screen- polycythaemia vera
Bone marrow biopsy: needed for diagnosis unless low EPO with JAK mutation and high RBC
MANAGEMENT
Phlebotomy, venesection: mechanically reduce RBC numbers
Antiplatelets: Aspirin to prevent thrombotic events
Manage CVD risk: hypertension, diabetes, lipids and lifestyle : smoking, weight
Higher risk of thrombosis or platelets over 1000:
Cytoreductive therapy (hydroxyurea/hydroxycarbamide): reduces RBC number
If all fails salvage therapy : JAK2 inhibitors (Ruxolitinib)
COMPLICATIONS
- Thrombosis
- May progress to AML or myelofibrosis
thrombotic events post highest risk of mortality and morbidity
Pancytopenia
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Decrease in the number of RBCs, WBCs and platelets in the peripheral blood flow
Causes:
- Aplastic Anaemia: due to bone marrow failure: see normochromic, normocytic
- Myelofibrosis
- Multiple myeloma
- Chemotherapy and radiotherapy
- Methotrexate: Can lead to bone marrow suppression causing pancytopenia
- B12 or folate deficiency
- Acute & chronic leukaemia
- Lymphoma
CLINICAL FEATURES
Symptoms of anaemia, leukopenia, thrombocytopenia which are:
- SOB
- Pale skin
- Fatigue
- Weakness
- Fever
- Recurrent infection
- Easy bruising
- Petechiae
- Purpura
- Bleeding gums and nosebleeds
INVESTIGATIONS
- FBC
- Blood smear
Coagulations profile, Viral serology (HIV, EBV), autoimmune, B12, folate, LFTs
- Bone marrow aspiration and biopsy : look for bone marrow cause
MANAGEMENT
- RBC and platelet transfusion
- Bone marrow and stem cell transplant
How does an aplastic crisis appear on bloods and what is a common cause
Parvovirus B19
- Low reticulocytes
- Sudden anaemia (drop in Hb)
Disseminated Intravascular Coagulation
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factor.
Makes thrombi and clots for no reason
Causes: conditions that cause coagulation
- Sepsis (ACUTE DIC)
- Trauma e.g. surgery (ACUTE DIC)
- Malignancy (more chornic)
- Obstetric disorder
- Pancreatitis
- Transfusion (ACUTE DIC)
CLINCIAL FEATURES
- oliguria (small amounts of pee)
- hypo and tachy
- delerium and coma
Acute DIC:
Bleeding issues
- Petechiae- <4mm bruises
- Purpura- 4-10mm bruises
- Ecchymoses- >10mm bruises
- Epistaxis
Chronic DIC:
Clotting issues
- Signs of DVT
- Arterial thrombosis
INVESTIGATIONS
- FBC: low platelets, low Hb
- Clotting Screen: low fibrinogen, high d dimer (fibrinogen degradation product), prolonged PT and APTT
- Blood FIlm : Schistocytes (fragmented)
MANAGEMENT
- treat underlying disease
- Fresh frozen plasma- contains clotting factors
- Cryoprecipitate - replaces fibrinogen
- Heparin to anticoagulate
COMPLICATIONS
- Acute renal failure
- Life-threatening haemorrhage
- Haemothorax
- Gangrene
high mortality but can resolve if remove primary cause
Hameochromatosis
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Too much iron: Autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation
Commonly in males over 40
Primary: hereditary, most common, autosomal recessive, mutations of HFE gene: C282Y
Secondary: iron overload due to transfusion
CLINICAL FEATURES
- Fatigue
- Arthralgia (often of the hands)
- ED (loss of libido due to hypogonadism)
Other:
- Diabetic signs: polyuria, polydipsia, brown skin pigmentation
- Liver issues: cirrhosis, hepatomegaly
INVESTIGATIONS
Iron Studies: high serum iron and ferritin, over 45% serum transferrin saturation but low transferrin, Low TIBC (blood has no more capacity to bind to iron)
(transferrin is an iron carrier protein, is high when deficient in iron and low when too much iron.
transferrin saturation is how much transferrin is bound to iron, if its low theres no iron, if too high then iron overload)
Genetic testing: if first degree relative with haemochromatosis then HFE mutation likely
MANAGEMENT
diet low in iron
Stage 0 C282Y homozygous but no blood symptoms = 3 year follow up
Stage 1 homozygous but only raised tranferrin sats over 45%= yearly follow up
Stage 2,3,4 tranferrin saturations and ferritin high
1- Therapeutic phlebotomy (regular) : monitor ferritin and tranferrin saturation
2- If cant do venesection then deferoxamine (induced iron chelation to lower iron levels)
COMPLICATION
Hepatocellular carcinoma- may need ultrasound screening
What is Wilsons Disease (NOT LISTED)
what diseases point towards this condition
WHat are the findings
What is the treatment
Autosomal recessive disorder, which leads to excess copper deposition in tissues, hence low copper in serum
If have liver and neurological disease :
- Hepatitis
- Cirrhosis
- Basal ganglia degeneration
- Asterixis (inability to maintain stable posture cuz you have brief shock-like movements)
- Chorea
- Dementia
Findings:
Kayser-Fleischer rings → green-brown rings in the periphery of the iris
Bloods:
- Low copper
- Low caeruloplasmin
Treatment
Penicillamine
Haemoglobinopathies
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Group of recessively inherited conditions affecting the haemoglobin component of blood
Hb types:
HbF= 2 alpha, 2 gamma
HbA= 2 alpha 2 beta
HbA2= 2 alpha, 2 delta
Types of globinopathies
1) Structure change: Haemoglobin variants such as HbS (sickle cell)
2) Quantity change : Alpha or beta thalassaemia (reduced globin synthesis)
Thalassemia types
1) alpha (missing one alpha chain): common in asian and african descent
-Silent carrier (one defective allele)
-Alpha thalassaemia trait (two defective alleles)
-Haemoglobin H disease (three)
-Haemoglobin bart (four)
2) beta (missing a beta chain, miron if only one allele affected, major if two): common in those of medeterrainian decent
CLINICAL FEATURES
1) Beta Thalassaemia
- minor: mild microcytic hypochromic anaemia
- major: haemolytic anaema, hepatosplenomegaly, skeletal deformities
2) Alpha Thalassaemia
- silent carrier: nothing
- alpha thalassaemia trait: microcytic hypochromic red cells, no anaemia
- Haemoglobin H: microcytic hypochromic anaemia, splenomegaly
- Haemoglobin Bart: intrauterine death
INVESTIGATIONS
Bloods:
- Microcytic hypochromic anaemia
- Raised reticulocytes
1) Beta Thalassaemia
Electrophoresis:
- HbA2 levels raised in beta thalassaemia trait and major
- Absent HbA
- Raised HbF : because HbA (2 alpha and 2 beta chains) can not be produced
2) Alpha Thalassaemia
Electophoresis : HbH band
- Hb slightly low in trait
- raised iron and ferritin
MANAGEMENT
Beta Thalassaemia:
trait: avoid iron supplementation uless deficient + genetic councelling
major: regular tranfusion, monitor iron (chelation if required), genetic councelling
- risk of iron overload so Iron chelation therapy (desferrioxamine)
Alpha Thalassaemia:
silent carrier + trait: avoid iron supplementation
HbH disease: folic acid supplement
Offer relatives:
- Genetic counselling
- Screening tests
Haemophilia
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
A bleeding disorder, usually inherited with an x-linked recessive inheritance pattern, which results in the deficiency of a coagulation factor leading to impaired secondary haemostasis.
X linked so women may be carriers and show symptoms but only affects men
- Haemophilia A: deficiency in factor VIII
- Hameophilia B: deficiency in factor IX
CLINICAL FEATURES
- Recurrent or severe bleeding
- Bleeding into muscles
- Haemarthrosis without trauma- bleeding into joints (knee swells up not bruised)
- Excessive bruising/haematoma
- Epistaxis
- Neonates: prolonged bleeding following heel prick or circumcision
INVESTIGATIONS
APPT: 8, 9, 11, 12
PT: 3, 7
Common :1, 2, 5, 10, 13
APTT prolonged, PT normal, prolonged bleeding time
If APTT prolonged
- Test for plasma factor VIII and IX assay
- Mixing study: correction of APTT suggests its coagulation factor deficiency
MANAGEMENT
- Substitution of clotting factors- factor concentrates
- Desmopressin: mild Haemophilia A: Triggers release of VWF from endothelial cells, leading to increase in factor VIII plasma concentration
- Antifibrinolytic therapy : Aminocaproic acid or tranexamic acid- Inhibits break down of clots to reduce risk of bleeding
- Hameophilia A: Emicizumab prophylaxis
COMPLICATIONS
- Compartment syndrome
- Joint or muscular damage
- Bleeding or life-threatening haemorrhage
PROGNOSIS
near-normal lifestyle and lifespan for most patients with haemophilia A and B
Hyposplenism/Splenectomy
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Spleen Function:
- Producing protective humoral antibodies
- Production and maturation of B and T cell and plasma cells
- Removal of unwanted particulate matter (e.g. bacteria)
- Reservoir for blood cells- white cells and platelets in particular
Causes of hyposplenism:
- Operative splenectomy
- Sickle cell anaemia
- Coeliac disease
- Chronic lymphoid leukaemia
- Inflammatory bowel disease
Indications for splenectomy:
- Trauma
- Spontaneous rupture in infectious mononucleosis due to minor trauma
- Hypersplenism
- Neoplasia- Lymphoma or leukaemic infiltration
Those with no spleen or dysfunctional spleen at risk of encapsulated bacterial infections such as:
NHS
- Neisseria meningitidis
- Haemophilus influenzae type b (Hib)
- Streptococcus pneumoniae (pneumococcus)
CLINICAL FEATURES
after splenectomy may see sepsis: pyrexia, hypotension, tachycardia
INVESTIGATIONS
Blood FIlm:
- Howell-jolly bodies
- Target cells
- Pappenheimer bodies (siderocytes) (RBC containing extra iron
Imaging- US, CT or MRI
MANAGEMENT
Splenectomy - Immunisations against N. meningitidis, H. influenzae type b, S. pneumoniae and influenza virus
- pneumococcal vaccine: 2 weeks before elective splenectomy or every 5 years
- influenza vaccine: yearly
After splenectomy : Prophylactic aspirin due to thrombocytosis
Patients at risk of pneumococcal infection: penicillin or amoxicillin (still at risk of Haemophilus influenzae since it makes beta lactamase)
Leukaemia
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Uncontrolled proliferation of immature WBCs that then accumulate in the blood or bone marrow
4 types:
1) Acute Lymphoblastic Leukaemia : 2-5 years old, common in down syndrome
2) Acute Myeloid Leukaemia : 65 years old ususally have pre-existing haematopoietic disorders (aplastic anaemia and myeloproliferative disorders like polycythaemia vera). 1/3 of myelodysplasias progress to acute myeloid leukaemia. See Auer rods (pink/red needle structures), associated with downs syndrome
3) Chronic Lymphocytic Leukaemia : Low-grade B-cell lymphoma caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells, usually 70-72 years old (most common in adults smudge cells
4) Chronic Myeloid Leukaemia: Overexpression of cells of myeloid lineage, especially granulocytes, 50-60 years old, See Philadelphia chromosome (translocation between crmsm 9 and 22, causes BCR-ABL gene which codes for a protein that has too much tyrosine kinase activity
CLINICAL FEATURES
1) Acute Lymphoid Leukaemia:
bone pain, splenomegaly, hepatomegaly, testicular, swelling LYMPHADENOPATHY AND FEVER
2)Acute Myeloid Leukaemia:
anaemia (fatigue, pallor, weakness), neutropenia but high WCC, frequent infections, thrombocytopenia (epistaxis, bleeding gums, petechiae, purapura, easy bruising), splenomegaly/early satiety, bone pain
3) Chronic Lymphoid Leukaemia: SOB, painless lymphadenopathy, splenomegaly anaemia (on bloods warm autoimmune haemolytic anaemia, IgG), thombocytopenia, recurrent infections as lack IgG, late diagnosis as remain asymptomatic for ages
4) Chronic Myeloid Leukaemia: weight loss, fever, night sweats, massive splenomegaly, anaemia, hyperviscosity symptoms)
INVESTIGATIONS
ACUTE:
- FBC: neutropenia, thrombocytopenia, anaemia
- Peripheral blood smear: Blast cells : ALL= lymphoblasts, MLL=myeloblast and auer rods (meyloblast hs a ring og cytoplasm, lymphoblasts have very thin cytoplasm)
- Bone marrow aspiration and biopsy: confirms biopsy,, in ALL see hypercellular marrow with most being lymphoblast cells
CHRONIC LYMPHOID LEUKAEMIA:
FBC:
- Persistent lymphocytosis
- With high percentage of small sized, mature lymphocytes
Peripheral Blood Smear:
- Smudge cells
CHRONIC MYELOID LEUKAEMIA:
FBC:
- Leukocytosis
- Thrombocytosis
- Basophilia
- Eosinophilia
- High band cells
Blood Film: left shift (imature granulocytes)- granulocytosis and myeloblasts
Leukocyte alkaline phosphatase (LAP)- decreased
Cytogenic testing: For confirmation of Philadelphia chromosome
IMMEDIATE SPECIALIST REFERRAL FOR URGENT FBC: if under 24 years old with unexplained petechiae or hepatosplenomegly
rule:
1. Low Lymphocytes → the answer should be AML or CML
2. WBC > 100 → Chronic causes so Consider CML (rule out AML)
3. Presence of bands cell → confirm CML
- blast → Acute
- bands → Chronic
MANAGEMENT
- Chemotherapy +/- radiotherapy
- Stem cell transplantation
AML: cytarabine for 7 days followed by an anthracycline (e.g., daunorubicin or idarubicin) for 3 days (7+3 regimen)
ALL: corticosteroid (prednisolone or dexamethasone), cyclophosphamide, vincristine, and an anthracycline (doxorubicin, daunorubicin, or idarubicin)
CLL: tyrosine kinase (BTK) inhibitor (e.g., acalabrutinib, zanubrutinib, ibrutinib)
CML: Tyrosine kinase inhibitors (imantinib)
COMPLICATIONS
Tumour lysis syndrome:
- Hyperphosphataemia
- Hyperuricaemia
- Hyperkalaemia
- Hypocalcaemia
(PUKE calcium: phosphorus, uric acid, potassium elevation, calcium reduced)
To diagnose need these results and:
- Increased serum creatinine or
- Cardiac arrhythmia or
- Seizure
Give Allopurinol to prevent risk of
What is a complication of Chronic Lymphocytic Leukaemia
richter transformation (CLL to aggressive large cell non-hodgkins lymphoma)
peresents as:
- Lymph node swelling
- Fever
- Weight loss
- Night sweats
Lymphoma
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Malignant proliferation of lymphocytes (B and T cells) which accumulate in lymph nodes or other organs
Hodgkins Lymphoma: malignant B cell origin, characterised by Reed-sternberg cells (2+ cells merged). Most affect males 25-30 years or 50-70 years. Associated with EBV, immunodeficiency and autoimmune like RA and sarcoidosis. Types:
- Nodular sclerosing- associated with lacunar cells- most common
- Mixed cellularity
- Lymphocyte predominant- best prognosis
- Lymphocyte depleted- worst prognosis
Non-hodgkins lymphoma: every other types (aka no reed sternburg cells). Incidence increases with age, 2 subtypes: (1) diffuse large B cell lymphoma (2) Burkitt’s lymphoma : burkitts has starrys sky appearace on microscopy common in HIV, youn patients and immunoosuppressed (has risk of tumour lysis syndrome).
Causes of NHL:
- Chromosomal translocations
- Infections
- EBV
- HIV
- H.pylori
- Autoimmune diseases
- Immunodeficiency
CLINICAL FEATURES:
Hodgkins:
- Painless lymphadenopathy- mostly cervical or supraclavicular nodes
- Involvement of single group of lymph nodes
- Alcohol induced pain
- Pruritus
- B symptoms (FLAWS)
Non-hodgkins:
- Rubbery painless lymphadenopathy associated with fatigue
- Affects multiple nodes
- Splenomegaly
- Extranodal disease
- Affects GI: - Dyspepsia, Dysphagia, Abdo pain
- Bone marrow: Bone pain
- Neurological: Headache
- B symtpoms maybe - much later than Hodgkins
INVESTIGATIONS
-bloods: lymphocytosis, low Hb, low platelets
- Raised LDH= poor prognosis
- HIV screening
Hodgkins
- Lymph node Histology and biopsy: - Reed- sturnberg cells (binucleate lymphocytes) can also be called mirror image nucleoli or large multinucleate cells with eosinophilic nucleoli
Non Hodgkins
- Lymph node biopsy: psotivie
- Immunohistochemistry: determines cell type and markers
Both for mets:
- PET CP CAP: Ann Arbor staging
1- 1 node
2- more than one node but both above diaphragm
3- nodes on both sides of diaphragm
4- extra nodal involvement: spleen, bone marrow, CNS
-Chest X ray : widened mediasteinum and bihilar lymphadenopathy
MANAGEMENT
1) Hodgkins:
If asymptomatic and a lymph node less than 10cm cna just watch or do radio.
After this stage all:
Chemotherapy +/- radiotherapy
2 cycles: ABVD (chemo drugs)
- adriamycin/doxorubicin
- bleomycin
- vinblastine
- dacarbazine
Then interim PET/CT scan to assess metabolic response then radio
Non-hodgkins:
Chemotherapy +/- radiotherapy
R-CHOP-21 (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisolone given on day 1 of a 21-day cycle)
PROGNOSIS
hodgkins has a better prognosis than non
Multiple Myeloma
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Haematological malignancy characterised by plasma cell proliferation (results in excessive monoclonal immunoglobulin production) & infiltration of the bone marrow by plasma cells. Type is based on immunoglobulins produced usually IgG or IgA
70 years old and male
CLINICAL FEATURES
CRABBI
- Hyper calcaemia : abdo pain, constipation, nausea, anorexia, consuision, polyuria, polydipsia
- Renal Impairment: light chain depositin in renal tubules (acute tubular necrosis), will have dehydration, thirsty, proteinurea, NSAIDs like naproxen can trigger this in MM patients
- Anaemia: fatigue and SOB
- Bone pain or practure (due to osteoporosis): back pain
- B symptoms
- Infection risk
INVESTIGATIONS
1st: blood or urine electrophoresis
- serum: high conc of monoclonal IgA/IgG proteins (one in excess) over 30g/L
- urine: urine monoclonal protein over 500mg/day, Bence jones proteins
Bone marrow aspirate and bipsy to confirm: will see increased plasma cells (over 10%)
Bloods: low Hb, thrombocytopenia, raised urea and creatinine if renal impairment, high calcium (low PTH secondary to this), normal ALP, normal phosphate, raised ESR
Peripheral blood smear: Rouleaux formation- stacking of red blood cells
WHole body low dose CT: look for lesions in bone: may see Rain-drop skull (multiple osteolytic lesions)
if negative do MRI
MANAGEMENT
Stem cell transplant elligible:
- Induction therapy (Thalidomide and dexamethasone)(-mide, -mib + dexamethosone
- Conditioning regimen: high dose melphalan
- Followed by autologous stem cell transplantation
Stem cell transplant ineligible:
Induction therapy (-mide + -mab/mib + dexamethosone/prednisolone
chemotherapy
If either have bonde disease: bisphosphonates (zoledronic acid, pamidronate) or denosumab
Avoid NSAIDs as renal failure risk
COMPLICATIONS
-pancytopenia
-VTE
PROGNOSIS
incurable, will relapse after 2-5 years
Myeloproliferative Disorders
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
Some examples:
- Chronic myeloid leukaemia
- Polycythaemia vera (too much RBC)
- Essential thrombocytosis: dysregulated megakaryocyte proliferation in bone marrow increasing platelets usually 50-70 with JAK2 mutation
- Primary myelofibrosis: scarring of bone marrow causing severe anaemia, massive splenomegaly, pancytopenia, dry tap when try to aspirate bone marrow, tear drop poikilocytes on blood film (flat elongated RBC): only treat if symptomatic do haemopoeitic stem cell transplant and Ruxolitinib (JAK 2 inhibitor) can be used to manage splenomegaly and B symptoms
Massive splenomegaly= CML or myelofibrosis
CLINICAL PRESENTATIOn
- Erythromelalgia (burning pain in extremities, pain worse with heat and better with cold
- Splenomegaly
- Arterial and venous thrombosis
- Bleeding
INVESTIGATIONS
FBC: Platelet count ≥450 x 10^9/L
JAK2 mutation testing
Bone marrow biopsy- needle aspirate: dry tap
Myelofibrosis:
- Anaemia
- Thrombocytosis
- Raised LDH
- Raised uric acid
MANAGEMENT
Hydroxycarbamide: reduce platelets
if emergency, Do plateletpheresis
Aspirin: antiplatelet to reduce thrombotic risk
Myelofibrosis: if not symptomatic observe, symptomatic = JAK2 ruxolitinib
COMPLICATIONS
- Thrombosis
- Bleeding
- Abortion
- Intrauterine death of foetus
PROGNOSIS
normal life expectancy
Patient on anti-coagulant therapy
- what types of anticoagulants
- examples
- calculate bleeding risk
- management
Used for treating and preventing embolic events
Most common oral:
- Vitamin K antagonists e.g. Warfarin
- DOACs e.g. Apixaban
Most common paraenteral:
- Heparin
1) Warfarin: Vitamin K produces factors 2,7,9,10. Warfarin blocks vitamin K which prolongs PT not APTT. ADV: This means Vitamin K replacement can revere warfarin. DISADV:
- Long half-life
- Regular monitoring of PT and INR
- Lots of drug-drug interactions
- Not used in PE and DVT
Target INR is 2.5, if after VTE or for AF or metallic aortic valve then 2.0-3.0, if have mitral valve replacement 2.5-3.5, recurrent PE’s 3.5
High INR indicated high bleeding risk so warfarin should be withheld and vitamin K given with FFP
Warfarin must be stopped 5 days before surgery and surgeru can only start if INR is less than 1.5. If over 1.5 then give vitamin K a day before surgery
If emergency surgery:
6-8 hours before surgery give IV 5mg vitamin K
If surgery cant wait give 25-50 units/kg four-factor prothrombin complex
Avoid warfarin in pregnancy
Warfarin activity:
REDUCED by : P450 inducers (induce= reduce INR) SCARS
- Smoking
- Ciroc (alcohol)
- Anti-epileptics e.g. Carbamazepine or Phenytoin
- Rifampicin
- St Johns wart
INCREASED by: P450 inhibitors (increase INR) ASS ZOLES
- Antibiotics : ciprofloxacin, isoniazid, clarithromycin, erythromycin
- SSRIs e.g. fluoxetine, sertraline
- Sodium valproate
- zoles: ketoconozole, fluconazole, omeprazole
TOO MUCH WARFARIN GIVEN:
1) major bleeding: stop warfarin, iv vitamin k 5mg, prothrombin complex concentrate
2) INR over 8 and minor bleeding: stop warfarin, iv vitamin k 1-3mg , repeat vit k if still too high after 24 hours, restart warfarin when INR is less than 5
3) INR over 8 and no bleeding: top warfarin, vit k 1-5mg by mouth, repeat dose of vitamin K if INR still too high after 24 hours, restart when INR less than 5
4) INR 5-8 with minor bleeding: stop warfarin, iv vitamin k 1-3mg , restart warfarin when INR is less than 5
5) INR 5-8 no bleeding: withold 1 or 2 doses of warfarin, reduce dose after this
6)If INR is less than 2: increase warfarin and start LMWH
2) DOAC:
Apixaban and Rivaroxaban: Factor 10a inhibitors to reverse must give Andexanet alfa
Dabigatran: Direct thrombin inhibitor. To reverse must give Idarucizumab
preferred to warfarin as less monitoring
3) Heparin
Unfractionated heparin is short acting: given by IV, measure with APTT
LMWH is long acting (e.g. Enoxaparin or dalteparin), given subcut, measure via anti-factor 10a
LMWH preferred as lower risk of thrombocytopenia. Heparin activates antithrombin III which forms a complex that inhibits factor 10a
Protamine sulfate reverses heparin
Heparin may be stopped on day of surgery due to half life
BLEEDING RISK
Orbit score
Patient on antiplatelet therapy
- Anti platelet drugs and examples
Decrease platelet aggregation and inhibit thrombus formation in the arterial circulation, because in faster-flowing vessels, thrombi are composed mainly of platelets with little fibrin
1) Aspirin: Inhibits COX 1 and 2, hence blocking thromboxane A2 synthesis and reducing platelet aggregation
Used for prevention in pts with CVD
- Following coronary bypass surgery
- Intermittent claudication
- Stable angina
- Acute coronary syndromes
- Following placement of coronary stents
- Stroke
Aspirin monotherapy is indicated after transcatheter aortic valve impnatation, switch to clopidogrel if cant tolerate
2) Clopidogrel (P2Y12 receptor antagonist): inhibits activation of platelets. Used to prevent atherothrombotic events if have a history of ischaemic events.
Used in combination with low-dose aspirin for prevention of atherothrombotic and thromboembolic events in patients with atrial fibrillation.
Monotherapy only if aspirin is contraindicated
3) Dipyridamole: Secondary prevention of ischaemic stroke and transient ischaemic attacks
4) Prasugreal: prevent atherothrombotic events in people with ACS undergoing percutaneous surgery: given up to 12 motnhs
5) Ticagrelor (P2Y12 receptor antagonist): Prevention of atherothrombotic events in patients with acute coronary syndrome; the combination is usually given for up to 12 months
6) Cangrelor: expert supervision only
MANAGEMENT
patients selected for PCI with the placement of a coronary stent require:
Dual antiplatelet therapy with aspirin and either cangrelor, clopidogrel, prasugrel or ticagrelor- aspirin therapy should continue indefinitely
Following PCl for stable angina with a drug eluting stent: give clopidogrel and aspiran for 6 months (if metallic stent no drug then at least 1 motnhs). If discontinue early then risk of stent thrombosis
GLYCOPROTEIN 2b/3a inhibitors
Prevent platelet aggregation by blocking the binding of fibrinogen to receptors on platelets
TEA
Tirofiban- for the reduction of major cardiovascular events in patients with ST-segment elevation myocardial infarction intended for primary percutaneous coronary intervention
T for STEMI of PCl
Eptifibatide- (and tirofiban) prevent early myocardial infarction in patients with unstable angina or non-ST-segment-elevation myocardial infarction
E for NSTEMI
Abciximab- prevention of ischaemic complications in pt undergoing percutaneous transluminal coronary intervention
A for preventing complications in PCl so AFTER
Transfusion Reactions
- aetiology: define, types, risk factors, stages
- clinical features
- investigations
- management
- prognosis + complication
safe because
- Due to extensive screening
- Pretransfusion testing
Threshold for tranfusions:
Non urgently these are transfused over 90-120 mins
- Without ACS → 70 g/L
- With ACS → 80 g/L
Adverse events in blood transfusions: Interaction of recipient antibodies to foreign antigens contained in blood product
1) Acute Reaction : within 24 hours of transfusion
- Acute haemolytic: Result of ABO red-cell incompatibility → leads to RBC destruction by IgM antibodies. fever, rigor, tachycardio, hypotension, abdo or chest pain, dark urine
- Allergic/Anaphylaxis: Hypersensitivity reactions to allergens in the transfused component , common in patients who have IgA deficiency and thus anti-IgA antibodies. Hypotension, dyspnoea, wheezing, angioedema, urticaria
- Febrile non-haemolytic transfusion: Immune-mediated → Often the result of sensitisation by previous pregnancies or transfusions. Fevers and chills but systemically well
- Transfusion-related acute lung injury: Result of granulocyte activation in the pulmonary vasculature resulting in increased vascular permeability. Fever, hypotension, dyspnoea, cough, hypoxia. On CXR see pulmonary oedema and white out. Tx: stop transfusion, oxygen and supportive care
2) Delayed Reaction: Occurs within days to weeks after transfusion
- Delayed haemolytic tranfusion reactions: Non-preventable, result of amnestic antibody response to non-ABO red cell antigens
- Transfusion associated graft versus host disease: in immunodeficient pts, tranfused white cells react with recipients antigen. Jaundice, watery or bloody diarrhoea, N+V, culture-negative fever, painful maculopapular rash (neck,palms, soles may progress to erythroderma or toxic epidermal necrolysis-like syndrom). Prevent by usine irradiated blood products
- Post transfusion pura pura: prior sensitisation to foreign platelet antigen, usually during pregnancy
3) Transfusion associated circulatory overload: too much transfusion in someone with pre-existing heart failure. Raised JVP, pulmonary oedema, S3, hypertention (hypertention distignuishes this from transfusion related acute lung injury). Tx : stop transfusion, IV furosemide and oxygen
INVESTIGATIONS
Direct Coombs Test: Positive result from a direct antiglobulin test means haemolytic reaction has occured
Repeat ABO testing
MANAGEMENT
Acute haemolytic reactions: stop transfusion, fluid rescuscitation
Allergic reactions: stop transfusion, IM adrenaline
Minor allergic reactions (urticaria without anaphylaxis): temp stop transfusion, antihistamine (chlorphenamine)
Febrile non-hameolytic reactions: paracetomol and slow transfusion
COMPLICATIONS
- Acute renal failure
- Acute respiratory failure
- Death
