Haematology Flashcards
LEUKAEMIA
What is Leukaemia?
Malignant neoplasms of hemopoietic stem cells, characterised by replacement of bone marrow with cells that often spills into the blood
LEUKAEMIA
What are the 4 different types of Leukaemia?
- Acute Lymphoblastic (ALL)
- Acute Myeloid (AML)
- Chronic Myeloid (CML)
- Chronic Lymphocytic (CLL)
LEUKAEMIA
What is the genetic abnormality in acute myeloid leukaemia?
t(15;17)
LEUKAEMIA
What is the genetic abnormality in chronic myeloid leukaemia?
t(9;22)
LEUKAEMIA
What may be the causes of Leukaemia?
1) Benzenes
2) Ionising Radiation
3) Alkylating Agents (chemo)
4) Pregnancy
LEUKAEMIA
What does Acute Myeloid Leukaemia involve and what age group is it found most commonly in?
- Proliferation of myeloblasts
- Middle aged- old ADULTS
LEUKAEMIA
What does Acute Lymphoblastic involve and what age group is it found most commonly in?
- Proliferation of lymphoblast’s
- usually CHILDREN
LEUKAEMIA
What are the Acute Symptoms and Signs?
- Bone Marrow failure
(Anaemia= low Hb. Infection= low WCC, bleeding= low platelets) - Infiltration (hepatosplenomegaly, lymphadenopathy, organomegaly)
- Weight Loss
LEUKAEMIA
What tests would you do for a patient with Leukaemia symtpoms?
1) FBC (Anaemia)
2) Peripheral blood film
3) Bone marrow aspirate ( characteristic blast cells seen)
4) Lumbar puncture
LEUKAEMIA
What would be found if someone had AML?
In AML, auer rods are the diagnostic finding
LEUKAEMIA
what is Phase 1 treatment?
- Induction (99% of leukemic cells killed)
LEUKAEMIA
What is Phase 2 Tretament?
Maintenance (remaining 1% of cells killed and maintaining remission)
LEUKAEMIA
Treatment
- Phase 1 and 2
- Chemotherapy and Bone marrow transplant
CHRONIC LEUKAEMIA
What age group is CML most commonly found and where is the genetic defect?
Middle aged adults
Philadelphia chromosome t(9;22)
CHRONIC LEUKAEMIA
What is Chronic Leukaemia?
proliferation of mature myeloid cells
CHRONIC LEUKAEMIA
What are the clinical features of CML?
1) Weight loss
2) Tired
3) Fever
4) Sweating
5) Hepatosplenomegaly
maybe anaemia and bleeding
SYMPTOMS PROGRESS SLOWLY BUT DEVELOP INTO AML AND RAPID DEATH
CHRONIC LEUKAEMIA
What would you test for in suspected CML?
- Bloods (anaemia and high WCC)
- Bone marrow aspirate (shows hypercellular marrow, increased in myeloid cells)
CHRONIC LEUKAEMIA
What is the treatment for CML?
Imatinib (Tyrosine kinase inhibitor- PREVENTS FORMATION OF PHILADELPHIA CHROMOSOME)
CHRONIC LEUKAEMIA
What is CLL?
Incurable disease of the elderly, with uncontrolled proliferation of mature B lymphocytes
CHRONIC LEUKAEMIA
What are the symptoms of CLL?
Usually indolent but may have marrow failure symtpoms (anaemia, infections, bleeding)
CHRONIC LEUKAEMIA
What tests would you do for CLL?
- Bloods (anaemia, high WCC, low platelets)thrombocytopenia= low platelets
lymphocytosis= high WCC
Bone marrow= heavy infiltration of lymphocytes
What is Anaemia?
Decreased level of Hb in blood, so fall in haematocrit, increased plasma volume
What is a Haematocrit?
volume percentage of red blood cells in blood. It is normally 47% ±5% for men and 42% ±5% for women.
Name some types of Microcytic Anaemia?
1) Iron- deficiency
2) Chronic disease
3) Thalassaemia
4) Sideroblastic
What does microcytic anaemia have in terms of MCV?
Microcytic anaemia has a low mean corpuscle volume
What does MCV mean?
mean corpuscle volume is the size of the RBC
Normocytic Anaemia has a normal MCV, name some types of Normocytic Anaemia
1) Acute blood loss
2) Chronic disease
3) Combined deficiency (malabsorption)
Name some types of macrocytic anaemia
1) B12/ folate deficiency
2) Alcohol
3) Hypothyroidism
What does macrocytic anaemia have in terms of MCV?
Macrocytic anaemia has a high mean corpuscle volume
ANAEMIA
General symptoms of anaemia?
- Fatigue
- Breathless
- Dyspnoea
- Faint
- Headache
- Anorexia
ANAEMIA
General signs?
Hyperdynamic circulation:
tachycardia
systolic flow murmur
pale skin
cardiomegaly
IRON- DEFICIENCY ANAEMIA
What is it?
Decrease in mean corpuscular Hb concentration
decrease in (MCHC, MCH, MCV)
IRON- DEFICIENCY ANAEMIA
Cause?
- Blood loss (menorrhagia/ GI bleed)
- Malabsorption ( poor diet, increased demand such as pregnancy)
- WORLDWIDE= hookworm (GI Blood loss)
IRON- DEFICIENCY ANAEMIA
What is Microcytosis?
Reduced Hb content in RBCs
IRON- DEFICIENCY ANAEMIA
What are specific features of IDA?
1) Angular Stomatitis (red/ sore corners of the mouth/lips)
2) Koilonychia (brittle, concave nails)
3) Atrophic glossitis (depapillation and sore tongue)
IRON- DEFICIENCY ANAEMIA
What do RBC’s look like on blood film if someone has IDA
- Hypochromic and microcytic RBC’s
- Anisocytosis (change in size)
- Poikilocytosis (change in shape)
IRON- DEFICIENCY ANAEMIA
Investigations?
- Colonoscopy (GI bleed)
- Coeliac serology
IRON- DEFICIENCY ANAEMIA
Treatment?
Oral iron (ferrous sulphate)
ANAEMIA OF CHRONIC DISEASE
Causes?
-RA, Crohns, SLE, TB, CKD
ANAEMIA OF CHRONIC DISEASE
Pathology?
Inflammatory cytokines reduce the sensitivity of bone marrow to EPO and results in failure of iron to be incorporated into RBC’s
ANAEMIA OF CHRONIC DISEASE
Stages of pathology
1) Poor use of iron in erythropoiesis
2) Cytokine induced shortening of RBC survival
3) Decreased production of/ response to EPO
ANAEMIA OF CHRONIC DISEASE
Tests?
blood film- normocytic/ normochromic anaemia
ANAEMIA OF CHRONIC DISEASE
Treatment?
give EPO
Why isn’t ferritin always accurate?
Ferritin is an acute phase protein like CRP so can increase in states of inflammation
what is ALPHA THALASSAEMIA?
disorder of haemoglobin chain- decreased alpha chains
BETA THALASSAEMIA
What is it?
Decreased number of beta haemoglobin chains
BETA THALASSAEMIA
how are more HbA2 and HbF chains formed?
- No beta chains = more alpha to compensate
- These alpha chains combine with any available alpha,beta or gamma chains available so produce more HbA2 and HbF.
BETA THALASSAEMIA
WHat is minor BT?
heterozygous
mild anaemia
RBC’s are hypochromic/ microcytic
BETA THALASSAEMIA
What is intermedia BT?
moderate anaemia but no trasnfusions needed
BETA THALASSAEMIA
What is major BT?
How does it present?
What does it require
- severe microcytic anaemia
Presentation
1st year= Hypertrophy of ineffective BM
- increased size of facial bones (skull bossing)
- Hepatosplenomegaly
Treatment = Transfusion
BETA THALASSAEMIA
tests
bloods= hypochromic, microcytic anaemia and increased reticulocytes
BETA THALASSAEMIA
management?
- blood transfusions (2-4 weeks)
- folate supplements
- iron chelation- prevent Fe overload (deferasirox)
- bone marrow transplant
- may die due to HF in 2nd decade
SIDEROBLASTIC
What is it?
microcytic hypochromic anaemia where bone marrow produces ringed sideroblasts instead of RBC’s
SIDEROBLASTIC
Cause?
enough iron but cant be incorporated into Hb
SIDEROBLASTIC
Diagnosis and treatment?
presence of sideroblasts on blood film
treat with pyridoxine and folic acid
MACROCYTIC ANAEMIA
Name the two types of Macro Anaemia
- megaloblastic (B12/folate)
- non megaloblastic (alcohol)- alcohol causes lipid deposition in RBC membranes
MACROCYTIC ANAEMIA
Causes of B12/folate deficiency?
- pernicious anaemia
- poor intake (diet, old age, alcohol)
- poor absorption (coeliac/ crohns)
- excess utilisation (pregnancy/ malignancy)
MACROCYTIC ANAEMIA
What is pernicious anaemia?
How is it tested/diagnosed?
when there is not enough intrinsic factor which is required for B12 absorption.
tested for by:
Intrinsic factor antibodies
anisocytosis/ poikilocytosis on blood film
Hb low/ MCV high
MACROCYTIC ANAEMIA
What can B12 deficiency cause?
- mild jaundice
- polyneuropathy
- dementia (subacute degeneration of spinal cord)
MACROCYTIC ANAEMIA
Tretament of B12/folate deficiency?
- B12 supplements (hydroxocobalamin)
- folate (green veg, kidney, nuts yeast, liver)
MACROCYTIC ANAEMIA`
Signs of folate deficiency
- anaemia and red cell folate/ serum folate is decreased
MACROCYTIC ANAEMIA
treatment of folate deficiency
oral folic acid 5mg daily
SICKLE CELL ANAEMIA
How is it caused?
Substitution of glutamine for valine in beta haemoglobin gene leads to production of HbS instead of HbA.
SICKLE CELL ANAEMIA
How does tissue infarction occur?
1) HbS POLYMERISES WHEN DEOXYGENATED= haemolytic anaemia
2) irreversibly sickled cells causes obstruction to microcirculation which results in TISSUE INFARCTION
SICKLE CELL ANAEMIA
Why does it take 6 months to manifest?
because foetal haemoglobin (HbF) works fine
SICKLE CELL ANAEMIA
Symptoms?
kids- occlusion in hands/feet= dactylitis= severe pain
adults- same but also affects long bones
- often asymptomatic as HbS offloads 02 better than normal Hb
- pulmonary HTN
SICKLE CELL ANAEMIA
What causes a decrease in Hb?
1) Splenic Sequestration= sickle cells trapped in spleen= enlargement
2) Bone marrow aplasia due to parvovirus B19= decreased Hb
SICKLE CELL ANAEMIA
Long term effects?
1) Growth problems due to avascular necrosis of bones = short bones
2) increased risk of infection due to splenic atrophy
3) Priapism due to sequestration of RBC in corpus callosum
4) Gallstones due to chronic haemolysis
5) leg ulcers
6) sickle chest syndrome
SICKLE CELL ANAEMIA
Investigations?
- Hb electrophoresis shows HbS
- increased reticulocytes
- sickle cells on blood film
SICKLE CELL ANAEMIA
Management?
- Hydroxycarbamide increases HbF
-vaccines to prevent infection
folic acid for haemolysis
GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY
what is the function of G6PD
Maintains glutathione in reduced state, this prevents RBC from oxidative injury
GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY
tests and treatment?
- direct enzyme measurement
- avoid precipitants (quinine/ fova beans)
- transfusions if severe
HAEMOLYTIC ANAEMIA
Types?
1) Thalassaemia
2) sickle cell
3) G6PD deficiency
these all increase reticulocytes
APLASTIC ANAEMIA
Causes?
Decrease in pluripotent stem cells and faults in those remaining
APLASTIC ANAEMIA
What is it?
Pancytopenia with hypocellularity of bone marrow
what is hypocellularity?
when bone marrow stops making cells
APLASTIC ANAEMIA
Symptoms?
- bleeding
- anaemia
- infections
APLASTIC ANAEMIA
Signs?
- epitaxis (nose bleeds)
- bleeding gums
- bruising
APLASTIC ANAEMIA
Investigations?
FBC and bone marrow aspirate
Pancytopenia/ absent reticulocytes
marrow is hypocellular
APLASTIC ANAEMIA
Treatment?
- withdraw offending agent
- BM transplant
- support blood count
MYELOMA
What is it?
- Malignant neoplasm of a plasma cell.
- clonal proliferation of BM cells, capable of producing monoclonal immunoglobulins, IgA or IgG
MYELOMA
What causes dysfunction to organs?
excessive quantities of one type of Ig
MYELOMA
What can be found in urine?
Excretion of bence-jones protein/ M protein
MYELOMA
Symptoms?
- Bone destruction due to increased osteoclast activity
1) back pain 2) spinal cord compression 3)hypercalcaemia - bone marrow infiltration
1) Anaemia 2) Infection 3) Bleeding - height and weight loss and fatigue
MYELOMA
What is an easy acronym to remember symtpoms of myeloma?
calcium
renal
anaemia
bone pain
CRAB
MYELOMA
Diagnosis and tests?
FBC- anaemia, thrombo/leukocytopenia, ESR increased
BIOCHEM- decreased renal function and hypercalcaemia
1) monoclonal protein in urine electrophoresis
2) X-rays- bone lesions
3) plasma cell increase on BM biopsy
4) evidence of end organ damage
(hypercalcaemia, renal insufficiency and anaemia)
MYELOMA
Treatment?
1) Analgesia for back pain
2) FLuids for kidney failure
3) EPO for anaemia
4) bisphosphonates- reduce the risk of fracture
specific= CHEMO
average survival = 5 years
LYMPHOMA
What is it?
- malignant neoplasm of lymphocytes. Accumulates in lymph nodes not the blood
(lymphadenopathy)
LYMPHOMA
What is the difference between Hodgkin’s and non- Hodgkin’s lymphoma?
Hodgkin’s lymphoma involves the presence of Reed-Sternberg cells. Non hodgkins lymphoma is B cells, which is more common and known as:
(diffuse large B cell lymphoma DLBCL)
LYMPHOMA
Features?
- Large, painless, non-tender lymph nodes (cervical)
- B symptoms (weight loss, night sweats, pyrexia-‘fever’)
LYMPHOMA
Signs?
- Lymphadenopathy
- cachexia
- anaemia
- hepatosplenomegaly
LYMPHOMA
Tests?
Biopsy (presence of reed-Sternberg cells)
bloods (increased ESR/LDH, decreased Hb)
blood films, BM aspirate
LYMPHOMA
Treat?
chemo and rituximab
low grade= mucosa-associated lymphoid tissue (MALT) lymphoma
high grade= diffuse large B cell lymphoma DLBC lymphoma
highest grade= Burkitt’s lymphoma
PLATELET PROBLEMS (thrombocytopenia)
What are the two basic types of platelet problems?`
- Reduced production (leukaemia, lymphoma, myeloma, aplastic anaemia)
- increased destruction (DIC, ITP, TTP)
PLATELET PROBLEMS (thrombocytopenia)
How do we know if it is either increased destruction, or reduced production
- increased megakaryocytes with increased destruction
- decreased megakaryocytes with decreased production
PLATELET PROBLEMS
Clinical Features?
- Epistaxis
- Menorrhagia
- Gum bleeding
- Easy bruising
- Purpura (red blotches on skin)
- Petachiae (red dots)
PLATELET PROBLEMS
What is ITP?
Immune Thrombocytopenic Purpura is immune mediated destruction of platelets
(IgG against platelets)
Cause of Immune Thrombocytopenic Purpura
Kids= virus
Adults= less acute- mainly young women, caused by autoimmune disorders
Diagnosis of Immune Thrombocytopenic Purpura
Thrombocytopenia with increased megakaryocytes
Treatment of Immune Thrombocytopenic Purpura
- steroids
- IV Ig
- platelet transfusion
What is TTP?
Thrombotic Thrombocytopenic Purpura
Cause of Thrombotic Thrombocytopenic Purpura
Deficiency of ADAMTS13
This normally degrades vWF
Pathology of Thrombotic Thrombocytopenic Purpura
1) Widespread aggregation of platelets
2) microvascular thromboses
3) thrombocytopenia
Treatment of Thrombotic Thrombocytopenic Purpura
- plasma exchange
- methylprednisolone
- Rituximab
DEEP VEIN THROMBOSIS
What is it
Thrombus in valves of veins
Accumulation of red cells and fibrin
DEEP VEIN THROMBOSIS
Risks?
- Surgery
- immobilisation
- pregnancy
- cancer
- oestrogen contraceptive
- > 60 years
- Obesity
DEEP VEIN THROMBOSIS
Symptoms?
- Swollen red leg
- tender and warm calf
- distended leg veins
- pitting oedema
DEEP VEIN THROMBOSIS
Prophylactic Measures?
- compression stockings
- early mobilisation
- leg elevation
DEEP VEIN THROMBOSIS
Investigations?
Low score D-diver: -ve= no DVT
high score: +be= do Doppler/ultrasound
Tests may be unreliable at a late stage for calf DVT so repeat if -ve
DEEP VEIN THROMBOSIS
Treatment?
AIM= prevent pulmonary embolism
- LMHW+ Warfarin (stop heparin at INR 2-3)
2nd: LMHW+ Heparin
Time scale-
If there’s a cause= 3 months
If no cause= 6 months + search for cancer
DEEP VEIN THROMBOSIS
How does treatment work?
It activates antithrombin III which inhibits factor Xa, so stops coagulation cascade
POLYCYTHAEMIA
What is it?
Increase in Hb/haematocrit/red cell count
POLYCYTHAEMIA
What is PCV?
Packed Cell Volume= haematocrit= % by volume of RBC in blood
(These measurements are all in concentrations therefore a decrease in plasma volume may increase RCC)
POLYCYTHAEMIA
What is absolute POLYCYTHAEMIA
Increase in red cell mass
POLYCYTHAEMIA
What is relative POLYCYTHAEMIA
Decrease in plasma volume
POLYCYTHAEMIA
How does primary polycythaemia occur?
1) polycythaemia vera
2) JAK-2 mutation
3) malignant haematopoietic stem progenitor cell
POLYCYTHAEMIA
Secondary causes of polycythaemia
- hypoxia (increased EPO)
- EPO secreting tumour
POLYCYTHAEMIA
Difference in symptoms of primary and secondary?
In secondary there is no hepatosplenomegaly and no increased WCC
POLYCYTHAEMIA
Symptoms and signs?
- Facial plethora
- Headache
- Dizziness
- Tinnitus
- Angina
- Intermittent claudication (pain in legs due to clocked arteries)
- Visual disturbances
- Pruritis
POLYCYTHAEMIA
Investigations and diagnosis?
- increase WCC, increased RCC, increase Hb/PCV
- Possible JAK-2 mutation
POLYCYTHAEMIA
Treatment?
- Low dose aspirin
- Venesection
Secondary Treatment:
Remove EPO secreting tumour
02 if hypoxic
DISSEMINATED INTRAVASCULAR COAGULATION
WHat is it?
Over activation of clotting cascade
Widespread: 1) generation of fibrin within vessels, this leads to 2) consumption of platelets/coagulation factors Leads to 3) widespread bleeding
DISSEMINATED INTRAVASCULAR COAGULATION
Causes?
- Burns
- major trauma
- sepsis
- surgery
- advanced cancer
- acute promyelocytic leukaemia- due to generation of procoagulant substances
DISSEMINATED INTRAVASCULAR COAGULATION
Signs?
Vary from none to complete haemostatic failure
DISSEMINATED INTRAVASCULAR COAGULATION
Diagnosis?
- Severe thrombocytopenia
- fragmented RBC in blood film
DISSEMINATED INTRAVASCULAR COAGULATION
Treatment?
Underlying cause treated
-give platelets, RBC’s and clotting factor
MALARIA
What is it?
It is a protozoan parasite widespread in tropics and subtropics
MALARIA
How is it transmitted?
Through the bite of infected female Anopheles mosquito
MALARIA
What is the most fulminating strain of malaria
P falciparum
MALARIA
Pathogenesis?
1) infective form of parasite passed through skin, into the blood to the liver
2) many enter hepatocytes and after a few days cause rupture. They are then released into the blood, enter erythrocytes and cause rupture of red cells.
3) rupture of red cells contributes to anaemia and cause fever
4) RBCs containing P falciparum adhere to endothelium of small vessels, cause occlusion and severe organ damage
5) some strains stay latent in liver and this is how relapse occurs
MALARIA
Clinical features?
- fever
- anaemia and hepatosplenomegaly
- cerebral malaria
- blackwater fever
- diarrhoea
MALARIA
Diagnostic tests?
Thick and thin blood smears
All types of blood test to see any complications
Rapid antigen tests
MALARIA
Treatment?
Uncomplicated falciparum=
Oral riamet/ oral quinine
Complicated falciparum=
IV artesunate/ quinine
Non falciparum malaria=
Oral chloroquine
What is prothrombin time?
Measures how long it takes to blood to clot. Expressed as INR (international normalised ratio)
What is activated partial thromboplastin time?
Tests for the intrinsic system of coagulation
What is thrombin time?
Thrombin is added to plasma to convert fibrinogen to fibrin-Time taken for blood to form a clot in plasma of a blood sample containing an anti-coagulant and an excess of thrombin
What is bleeding time?
Tests haemostasis. Done by making two small incisions into arm. Rarely done
What is the 3 roles of vWF in clotting?
1) to bring platelets intoccontact with exposed subendothelium
2) to make platelets bind to each other
3) to bind factor VIII, protecting it from destruction in the circulation
Deficiency leads to defective platelet function as well as factor VIII deficiency
What is Plasmin?
Enzyme that destroys blood clots by attacking fibrin. (Stops occlusion problems arising)
What foods are high in folate?
green veg, kidney, nuts yeast, liver
What is Vit B12 and folate required for?
DNA synthesis
