Haematology Flashcards
1
Q
Define microcytic anaemia
A
Low haemoglobin concentration and low MCV on blood test
2
Q
List causes of microcytic anaemia
A
- Iron deficiency anaemia (blood loss, pregnancy, decreased absorption due to coeliac disease and h.pylori, nutritional deficiency)
- Thalassemia
- Sideroblastic anaemias (very rare - alcoholism)
- Anaemia of chronic disease
- Lead poisoning
3
Q
List signs on examination of microcytic anaemia
A
Iron deficiency
- Koilonychia
- Angular cheilosis
- Pallor
- Atrophic glossitis
- Tachycardia, murmurs, cardiac enlargement
- Dry skin/hair
- Alopecia
Thalassemia
- Hepatosplenomegaly
- Bony deformities
- Jaundice
- Pallor
- Cardiac flow murmur
4
Q
List symptoms of microcytic anaemia
A
- Dyspnoea
- Fatigue
- Cognitive dysfunction
- Restless leg syndrome
- Vertigo
- Dysphagia
- Syncope
- Dizziness
- Irritability
- Weakness
5
Q
Describe epidemiology of iron deficiency anaemia
A
- Iron deficiency anaemia is the most common cause of anaemia, affecting 500 million people worldwide
- Especially prevalent in low income populations
- 2-5% adult men and post-menopausal women
- Higher incidence in childbearing years (38% pregnant, 29% non-pregnant women worldwide. 23% pregnant and 14% non pregnant UK)
6
Q
Describe epidemiology of thalassemia
A
- 1.5% population are carriers of B thallasemia. Especially prevalent in mediterranean, middle east, southern china, central, south and southeast asia
- 5% carriers of a-thallaemia. Most prevalent in southease asia, africa, india
- Typically presents from 3rd - 6th month of life in B, in a present from birth
7
Q
Describe epidemiology of sideroblastic anaemia
A
- More common in males
- Onset usually before 30
- Rare
8
Q
List investigations to diagnose microcytic anaemia
A
- FBC
- Ferritin
- Transferrin, transferrin saturation, iron, ferritin, transferrin binding capacity
- B12 and folate
- Coeliac screen
- Top and tail
- Iron deficiency: Low MCV, low iron, low hb, high transferrin, low transferrin saturation, low ferritin, high transferrin binding capacity. Pencil cells on smear
- Thalassemia increased ferritin and saturation, electrophoresis for diagnosis, no normal blood test history. HbA2 raised
- Sideroblastic anaemia sideroblasts seen in mcicroscopy
- Anaemia of chronic disease – low iron, low iron binding capacity, high or normal ferritin
9
Q
Describe management of microcytic anaemia
A
- Treat underlying cause
- If iron deficiency oral ferrous sulphate
- If sideroblastic, transfusion may be needed, withdraw causative agents
- Screen for coeliac
- If thalassemia blood transfusion, with chelating agents. Bone marrow transplants are curative
10
Q
List complications of microcytic anaemia
A
- Heart failure
- Adverse immune status
- Cognitive and behavioural impairment in children
- Impaired muscular performance
- In pregnancy, iron deficiency associated with increased morbidity, preterm delivery, depressive symptoms, infant iron deficiency
- Thalasemia major carries 80% mortality in the first 5 years of life. Stem cell transplant associated with 85-90% survival
11
Q
What is red cell distribution width? What makes it abnormal?
A
- Red cell distribution width (RDW) – a measure of the variation in RBC size.
- If high this suggests a large variation in sizes, seen in iron deficiency, myelodysplastic syndrome and haemoglobinopathies.
12
Q
List causes of macrocytic anaemia
A
- Megaloblastic B12 and folate deficiency (methotrexate, trimethoprin, dietry deficiency, excessive requirements eg.in pregnancy, excessive urinary excretion, genetic disorders)
- Non-megaloblastic (liver disease, alcohol, hypothyroidism, myelodysplasic syndrome, acute leukaemia)
Alcoholics (alcohol raised GGT)
Myelodysplasia (pancytopaenia and bone marrow)
Have (hypothyroidism)
Liver (liver disease)
Failure (folate/B12 deficiency)
13
Q
Define macrocytic anaemia
A
- Abnormally large red blood cells
- High MCV, low Hb
14
Q
Describe epidemiology of macrocytic anaemia
A
- In the UK (and the US) the prevalence of vitamin B12 deficiency is around 6% in people aged less than 60 years.
- For people aged over 60 years, this rises to around 20%.
- For people with vegan diets, around 11% are deficient in vitamin B12.
- Adult pernicious anaemia (the most common cause of B12 deficiency and megaloblastic anaemia) occurs most commonly in people aged 40–70 years, with a mean age of onset of 60 years among white people.
- In black people the mean age is 50 years, with a biomodal distribution due to an increased occurence in young black females.
- The prevalence of folate deficiency (serum folate below the World Health Organization [WHO] clinical threshold for folate deficiency [7 nanomol/L]) amongst adults and children is no more than 5%.
- Medication 40%
- Alcoholism 25%
- Vit B12 and folate deficiency 6%
- Liver disease 6%
15
Q
List symptoms of macrocytic anaemia
A
- Fatigue
- SOB
- Angina
- Headache
- Palpitations
- Reduced sensation, parasthesia, ataxia, reduced proprioception
16
Q
List signs of macrocytic anaemia
A
- Pallor (nail beds, tongue, conjunctiva)
- Lemon tinge skin colour in pernicious anaemia
- Bounding pulse
- Systemic flow murmur
17
Q
List investigations for macrocytic anaemia
A
- Blood test and film (absent reticulocytes suggests non-megaloblastic, target cells indicates non-megaloblastic)
- Vit B12, anti-intrinsic factor antibody (pernicious anaemia)
- Folate
- Thyroid function tests
- Liver funciton tests (for liver disease - B12 and folate deficiency may have raised bilirubin)
- Coeliac serology if indicated
18
Q
Describe management of macrocytic anaemia
A
- Pernicious or B12 deficiency (B12 injections every 3 months)
- Folate deficiency (folic acid 5mg faily for 4 months. Must treat B12 first if both are low)
- Refer if neurologicalsymptoms, pregnancy, suspected haematological malignangy, no cause identified
- Gasto referal if malabsorption
19
Q
List complications of macrocytic anaemia
A
- Heart failure
- B12 - neruological symptoms, optic atrophy and severe psychiatric symptoms
- Folate - Prematurity, cardiovascular disease and some cancers
- Neural tube defects
- Ineffective production of any blood cells from the bone marrow
- Sterility
20
Q
Describe prognosis of macrocytic anaemia
A
- Generally good once cause is identified
- Vitamin deficiencies can be replaced
- Can cause permanent damage to the nervous system
21
Q
Define normocytic anaemia
A
- Low Hb
- Normal MCV
22
Q
Compare neutrophilia to lymphocytosis
A
- Neutrophilia acute inflammation
- Lymphocytosis chronic inflammation
23
Q
Describe causes of microangiopathic haemolytic anaemia
A
- DIC (decreased platelets and fibrinogen, increased PT and APTT, increased D dimer and fibrin degradation products)
- Haemolytic uraemic syndrome (increased Hb decreased bilirubin, uraemia, decreased platelets)
- Thrombocytic thrombocytopenic purpura (HUS, fever and neurological manifestations)
24
Q
List causes of haemolytic anaemia
A
Hereditary
- Red cell membrane (hereditary spherocytosis, elliptocytosis)
- Enzyme deficiency (G6PD deficiency)
- Haemoglobinopathy (Sickle cell disease, Thalassaemias)
Acquired
- Autoimmune
- Drugs
- Infection
- MAHA
25
Describe hereditary haemorrhagic telangiectasia
- Autosomal dominant
| - Abnormal blood vessels in (skin, mucous membranes, lungs, liver, brain)
26
List presentations of polycythaemia
- Headache
- Pruritis after hot bath
- Blurred vision (hyperviscosity)
- Tinnitus
- Thrombosis (stroke, DVT)
- Gangrene
- Choreiform movement
27
Define polycythaemia
High red blood cell count
28
Define sickle cell anaemia
- An autosomal-recessive single gene defect in the beta chain of haemoglobin, which results in production of sickle cell haemoglobin (HbS).
- Other forms of sickle cell disease may occur if HbS is inherited from one parent and another abnormal haemoglobin, or beta thalassaemia, is inherited from the other parent (e.g., HbSC or HbSB thalassaemia).
- Sickle cell disease is associated with varying degrees of anaemia, red cell haemolysis, and obstruction of small blood capillaries.
- Sickle cell trait occurs if HbS is inherited from one parent and the normal HbA from the other.
29
Describe epidemiology of sickle cell disease
- In England, sickle cell disease affects more than 1 in 2000 live births
- Sickle cell trait or disease offers a protective effect against malaria in endemic regions and this has led to positive selection for the gene mutation.
- Its prevalence is 10% to 30% in sub-Saharan Africa.
- Between 25% and 30% of newborns in western Africa are carriers of the sickle cell trait. Prevalence is also high along the southern coast of the Arabian peninsula, in central and coastal areas of the Indian subcontinent, Southeast Asia, and people of Mediterranean origin
30
Describe aetiology of sickle cell disease
- In sickle cell anaemia, valine replaces glutamic acid at the sixth amino acid of the beta globin chain, as a result of a recessive single gene mutation.
- Valine can fit into the hydrophobic pocket of another haemoglobin molecule, causing the haemoglobin to polymerise within the red cell, thus forming long stiff fibres of haemoglobin tetramers.
- Forms crescent shaped red blood cells
31
List risk factors of sickle cell disease
- Parents with sickle cell disease
- Inherited in an autosomal recessive pattern. When both parents carry the recessive sickle cell gene, there is a 1 in 4 chance that their offspring will inherit two recessive alleles, causing sickle cell anaemia.
32
List symptoms of sickle cell disease
- Persistant pain due to vascular occluson
- Dactylitis (swollen dorsal surface of the hand)
- Pneumonia-like symptoms (chest pain, fever, dyspnoea, tachypnoea, and hypoxaemia)
- Bone pain
- Visual floaters
- Failure to thrive
- Lethargy
33
List signs of sickle cell disease
- Tachycardia
- Tahcypnoea
- Pallor
- Jaundice
- Maxillary hypertrophy with overbite
- Protuberant abdomen with umbilical hernia
- Cardiac systolic murmur
- Shock
34
List investigations for sickle cell disease
- DNA assays for HbS
- Hb IEF
- Cellulose acetate electrophoresis
- High performance lipid chromatography
- Haemoglobin solubility testing
- Blood smear (sickled cells, howell jolly bodies in poor splenic function). Sodium etabisulfide causes sickling
- FBC and reticulocyte count
- Iron studies
35
Describe management of sickle cell disease
Vasoocclusive crisis
- Analgesia
- Supportive care (oxygen, keep warm)
- Antihistamine
- Hydration
- Antibiotics
- Blood transfusion
- In sequestration crisis, splenectomy.
- In chronic cholecystitis, cholecystectomy
Acute chest syndrome
- Oxygen and incentive spirometry
- Analgesia
- Broad spectrum antibiotics
- Antihistamine
- Blood transfusion
- Hydration
Chronic disease
- Supportive care (immunisations, antibiotics prophylactically, nutritional counselling, education)
- Hydroxycarbamide
- Blood transfusion
- Bone marrow transplant
36
List complications of sickle cell disease
- Anaemia
- Parvovirus B19 causing aplastic crisis (anaemia and reticulocytopaenia)
- Opioid addiction
- Iron overload
- Liver complications and cholithiasis (gallstones commonly pigmented as bilirubin levels are HIGH)
- Avascular necrosis
- Leg ulcers
- Cardiovascular manifestations
- Priapism
- Splenic sequestration
- Pulmonary hypertension
- Renal abnormalities
- Growth delay
- Stroke
- Retinopathy
37
Describe prognosis of sickle cell anaemia
- Without bone marrow transplantation (the only potentially curative treatment), median age at death is 42 years for men and 48 years for women in patients with sickle cell anaemia (SS), and 60 years for men and 68 years for women with haemoglobin SC disease.
- In parts of Africa, 50% of children with sickle cell disease die before their first birthday.
- Morbidity and mortality are declining because of improvements in the management of infections and other complications in childhood, new interventions, active health maintenance for adults, and patient counselling.
- More than 90% of patients of all phenotypes will survive past 20 years of age, and significant numbers are older than 50 years of age.
38
List causes of anaemia with increased reticulocyte count
- Haemolytic crises
39
List causes of anaemia with low reticulocyte count
- Parvovirus B19
- Aplastic crisis in sickle cell
- Blood transfusion
40
Describe aetiology of normocytic anaemia
- Anaemia of chronic disorders (inflammation, neoplasia)
- Renal failure
- Endocrine failure (hypothyroidism, hypopuitarism)
- Marrow failure (pure red-cell aplasia, aplastic anaemia, infiltration)
- Acute blood loss
- Polymyalgia rheumatica
41
How are crohns and celiac disease linked with megaloblastic anaemia?
- Coeliac disease causes reduced absorption of folate in the proximal jejunum
- Chrons causes reduced absorption of B12 in the terminal ileum
42
List neurological associations with B12 deficiency
- Dementia
- Subacute combined degeneration of the spinal cord
- Peripheral neuropathy
43
List lab evidence of haemolysis
- LDH rasied
- Unconjugated hyperbilirubinaemia
- Reduced haptoglobins
- Reticulocytosis
44
List factors suggesting G6PD defiency
- Oxidising agent exposure precipitating jaundice and anaemia
- Heinz bodies on smear
45
List advice given to patients with G6PD deficiency
- Avoid oxidant drugs
- Dont eat fava beans (broad)
- Avoid napthaline
- Be aware anaemia may follow infection
46
Which tests is done in presence of haemolytic anaemia?
- Coombs test
| - Direct antiglobulin test (if positive, autoimmune haemolytic anaemia)
47
How do autoimmune diseases affect most likely anaemia diagnosis?
- Organ specific autoimmune disease and B12 deficiency pernicious anaemia
- Global autoimmune disease (eg. SLE) anaemia most likely due to haemolytic anaemia
48
List symptoms and signs of bone marrow infiltration
- Failure for reticulocyte count to respond
- Normocytic
- Low Hb
- Low neutrophils and WBC
- Back pain, loss of appetite and weight
49
Define polycythaemia vera
- A chronic myeloproliferative neoplasm that is characterized by an erythropoietin-independent, irreversible increase in erythrocyte, granulocyte and platelet counts.
- The elevated blood cell mass results in hyperviscosity, which is associated with slow blood flow and an increased risk of thrombosis.
- The disorder typically initially has a long asymptomatic period, then assumes a chronic, insidious course.
50
Describe aeitiology of polycythaemia vera
- The JAK2 V617F mutation is implicated in about 95% of cases of polycythaemia vera
- This increases tyrosine kinase activity leading to erythropoietin-independent proliferation of the myeloid cell lines, increased blood cell mass (erythrocytosis, thrombocytosis, and granulocytosis), hyperviscosity + slow blood flow
- As a result increases risk of thrombosis and poor oxygenation.
51
List risk factors of polycythaemia vera
- Age >40 years
- Budd-Chiari syndrome
- Affected family members.
52
Describe epidemiology of polycythaemia vera
- Rare in children
- Gender distribution is 1:1
- Complications are more common in women
53
List symptoms and signs of polycythaemia vera
- Thrombosis features (hyper-viscosity)
- Haemorrhage features
- Frequently asymptomatic
- Generalised weakness and fatigue
- Pruritis
- Erythromelalgia
- Redness of fingers, toes, palms heels
- Splenomegaly
- Facial redness
54
List investigations for polycythaemia vera
- Haemoglobin (high)
- Haematocrit (high)
- White blood cell (WBC) count (high)
- Platelet count (high)
- Mean corpuscular volume (MCV) (low)
- Liver function tests (LFTs) (normal)
- JAK2 gene mutation screen
- Oxygen sats
- P50
- Bone marrow biopsy (hypercellilarity with trilinear growth)
55
List symptoms of normocytic anaemia
- Asymptomatic
- Pallor
- Exertional dyspnea; and fatigue
- Pica (craving for ice or dirt)
- Jaundice (in hemolytic anemia)
- Muscle cramps
- Worsening of angina pectoris
- Features of hyperdynamic state
- Bounding pulses
- Tachycardia/palpitations
- Flow murmur
- Pulsatile sound in the ear
- Paravertebral mass
- Widening of diploic spaces of the skull
56
List investigations for normocytic anaemia
- FBC
- Reticulocyte count
- > 2%: reassess history for blood loss, consider FOBT (see GI bleeding)
- Obtain LDH, haptoglobin, and unconjugated bilirubin to evaluate for hemolytic anemia
- Reticulocyte count < 2%: obtain iron studies, serum vitamin B12 and folate levels; if normal, obtain a metabolic panel
57
Describe epidemiology of normocytic anaemia
- Prevalence increases with age, reaching 44 percent in men older than 85 years.
- Normocytic anemia is the most frequently encountered type of anemia.
- Anemia of chronic disease, the most common normocytic anemia, is found in 6 percent of adult patients hospitalized by family physicians
- Bone marrow aspirate/bipsy
58
Describe management of normocytic anaemia
- Identify and treat the underlying cause
- Blood transfusion with RBCs for severe anemia: Hb ≤ 7 g/dL, Hb ≤ 8 g/dL if the patient either has a preexisting cardiovascular disease or is undergoing cardiac or orthopedic surgery
- Consider hospital admission or observation in: Acutely symptomatic anemia, actively bleeding patient, as clinically indicated, patients requiring blood transfusion
- Bone marrow transplantation may be indicated in certain cases (e.g., aplastic anemia).
- EPO and iron suppliments
59
Describe prognosis of normocytic anaemia
- A mild normocytic anaemia in older people, in the absence of an obvious cause, is not associated with significant differences in outcomes but is associated with poorer independence and a trend to lower survival.
- Depends on cause
60
List risk factors for normocytic anaemia
- Old age
- Kidney disease
- Cancer
- Rheumatoid arthritis and thyroiditis
- Long standing chronic illness
61
Define immune thombocytopenic purpura
- a haematological disorder characterised by isolated thrombocytopenia (platelet count <100 × 10⁹/L [<100 × 10³/microlitre]) in the absence of an identifiable cause.
- The thrombocytopenia is secondary to an autoimmune phenomenon and involves antibody destruction of peripheral platelets
62
Describe epidemiology of immune thrombocytopenic purpura
- 1.6 to 5.9 cases in 100000 in europe per year
- Increasing incidence with older age
- 3:1 female to male ratio in younger patients
- 3.9 cases per 100000 person years UK
- Childhood equal distribution between the sexes, results in spontaneous remission
63
Describe aetiology of immune thrombocytopenic purpura
- Unknown
- Genetic influences and immune dysregulation, mainly through autoreactive T cell abnormalities and environmental triggers, may contribute to progression of the disease
64
List risk factors for immune thrombocytopenic purpura
- Women of childbearing age
| - Age under 10 or over 65
65
List signs and symptoms of immune thrombocytopenic purpura
- Bleeding (eg. bruising, petechiae, haemorrhagic bullae, bleeding gum)
- Absence of systemic symptoms
- Absence of medicines that cause thrombocytopenia
- Absent splenomegaly or hepatomegaly
- Absent lymphadenopathy
66
List investigations of immune thrombocytopenia
- FBC and peripheral blood smear
- Platelet count below 100v10^9/L
Consider HIV, H pylori, hep C, thyroid function, quantitative immunoglobulins, bone marrow biopsy, pregnancy test
67
Define haemophilia and list the types
- Haemophilia is a bleeding disorder, usually inherited with an X-linked recessive inheritance pattern, which results from the deficiency of a coagulation factor.
- Haemophilia A results from the deficiency of clotting factor VIII.
- Haemophilia B results from the deficiency of clotting factor IX.
- Acquired haemophilia is a separate non-inherited condition. It is much rarer than congenital haemophilia and has an autoimmune-related aetiology with no genetic inheritance pattern
68
Describe epidemiology of haemophilia
- Haemophilia A 1 in 5000 boys/men
- Haem B 1 in 30000 boys/men
- Affects all ethnic groups, X linked inheritence, boys exclusively affected
- Acquired affects 1-3 people per million of the population
69
List risk factors for haemophilia
- Family history
- Male sex
- Age over 60 (acquired)
- Autoimmune disorders, IBD, hepatitis, pregnancy, postnatal, malignancy (acquired)
70
List symptoms and signs of haemophilia
- History of recurrent or severe bleeding
- Bleeding into muscles causing pain, swelling, decreased range of motion, erythema, increased warmth
- Prolonged bleeding after heel prick or circumcision
- Mucocutaneous bleeding (epistaxus, gums)
- Intracranial bleeding (hypoactivity, decreased oral intake, irritability, bulging or tense fontanelle, seizures, pallor)
- Haemarthrosis
- Excessive bruising.haematoma
- Fatigue
- Menorrhagia in female characters
- Extensive cutaneous purpura (acquired)
- GI bleeding, haematuria
- Distended and painful abdomen
- Pallor, tachycardia, tachypnoea, hypotension
71
List investigations for haemophilia
- aPTT (prolonged)
- VIII and IV assay (decreased/absent)
- Mixing study (aPTT corrected)
- FBC (normal)
- PT
- Von willebrand factor asssay
- V and VII assay, XI and XII assay
- Bleeding time/ platelet aggregation studies normal
- AST and ALT
- X rays of bony sites (acute joint bleeding or bone changes more consistent with chronic arthropathy)
- CVS/amniocentesis
72
Define disseminated intravascular coagulation
An acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors.
- Acute overt is life threatening, chronic non-overt is slower with less bleeding
73
Define epidemiology of DIC
- 59% mortality in DIC patients, compared to 13.8% in non-DIC patients
- Many conditions cause it so difficult to determine incidence. Age and sex poor predictors.
74
Describe aetiology of DIC
- Sepsis/severe infection, major trauma or burns
- Some malignancies (acute myelocytic leukemia or metastatic mucin-secreting adenocarcinoma)
- Obstetric disorders (amniotic fluid embolism, eclampsia, abruptio placentae, retained dead fetus syndrome)
- Severe organ destruction or failure (severe pancreatitis, acute hepatic failure)
- Vascular disorders (Kasabach-Merritt syndrome or giant haemangiomas, large aortic aneurysms)
- Severe toxic or immunological reactions (blood transfusion reaction or haemolytic reactions, organ transplant rejection, snake bite).
- Can follow HUS
Acute rapid onset underlying conditions, chronic malignancies and other less acute disorders
75
List signs and symptoms of DIC
- Oliguria, hypotension or tachycardia
- Symptoms specific to underlying disorder
- Purpura fulminans, gangrene, acral cyanosis (associated with DIC)
- Delirium or coma
- Petichiae, ecchymosis, oozing or haematuria (generalised bleeding at at least 3 unrelated sites characteristic)
- Chronic DIC presents with clotting features eg. DVT
76
List risk factors for DIC
- Major trauma/burn/organ destruction or sepsis/severe infection
- Severe obstetric disorders or complications
- Solid tumours and haematological malignancies
- Severe toxic or immunological reactions
- Major vascular disorders (large aortic aneurysms or giant haemangiomas)
77
List investigations for DIC
- Platelet count (decreased)
- PT (prolonged)
- Fibrinogen (decreased)
- D dimer/fibrin degradation products (elevated)
- aPTT (prolongued)
- Imaging studies or other tests
- Schistocytes on smear
- Thrombin time (prolonged)
- Protamine test (fibrin monomers - positive)
- Factor V, VIII, X, XIII (decreased)
78
Define thrombotic thrombocytopenic purpura
A clinical syndrome characterised by microangiopathic haemolytic anaemia and thrombocytopenic purpura (blood clot formation)
79
Describe epidemiology of thrombotic thrombocytopenic purpura
- Rare
- TPP+ haemolytic uraemic syndrome 2.2 per million per year in the UK
- Increasing incidence
- Higher in women and black people
- If due to von willebrand factor cleaving enzyme between 20-59 most common
80
Describe aetiology of thrombotic thrombocytopenic purpura
- Unusually large von willebrand factor multimers. ADAMTS-13 is dysfunctional, deficiency of protease
- Lack of von willebrand factor cleaving enzyme
- Acquired, lack of cleaving enzyme due to autoimmune process
81
List risk factors for thrombotic thrombocytopenic purpura
- Black ethnicity
- Female gender
- Obesity
- Pregnancy (near term or post-partum period)
- Cancer therapies
- HIV infection
- Bone marrow transplantation
- Antiplatelet agents
- Quinine
82
List signs and symptoms of thrombotic thrombocytopenic purpura
- Prodrome (non-specific)
- Severe neurological symptoms (coma, focal abnormalities and seizures - swinging CNS)
- Headache, confusion
- Fever
- Digestive symptoms (bowel microthrombi- nausea, vomiting, diarrhoea, abdo pain)
- Weakness
- Bleeding symptoms (purpura, ecchymosis, menorrhagia)
- AKI and MAHA
83
List investigations of thrombotic thrombocytopenic purpura
- Platelet count (low)
- Haemoglobin (low)
- Haptoglobin (low - decreased by haemolysis)
- Peripheral smear (microangiopathic with schistocytes)
- Reticulocyte count (raised)
- Urinalysis (proteinuria)
- Urea and creatinine (raised)
- Direct coombs test (negative)
84
Define haemolytic uraemic syndrome
Characterised by microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury.
85
Describe epidemiology of haemolytic uraemic syndrome
- Shiga toxin E coli HUS more common in young children (under 5)
- Seen at any age, decreasing frequency with increasing age
- 532 E coli O157 infections in 2017 england
- 3% developed HUS
86
Describe aetiology of haemolytic uraemic syndrome
- Damage to endothemium of glomerular capillary bed
- Caused by shiga toxin producing E coli O157:H7
- If familial, defect in proteins which regulate the complement system
87
List risk factors for haemolytic uraemic syndrome
- Ingestion of contaminated food or water
- Known community outbreak of toxicogenic E coli
- Exposure to infected individuals in institutional settings
- Genetic predisposition (atypical HUS)
- Bone marrow transplant
- Exposure to ciclosporin, some chemotherapy agents, targeted cancer agents, and quinine
- Pregnancy- or postpartum-related
88
List signs and symptoms of haemolytic uraemic syndrome
- Diarrhoea, especially bloody diarrhoea
- Thrombocytopenia (petechiae, purpura, mucosal bleeding, prolonged bleeding after minor cuts)
- Microangiopathic hemolytic anemia (fatigue, dyspnea, and pallor, Jaundice)
- Impaired renal function (hematuria, proteinuria, oliguria, anuria)
89
Describe investigations of haemolytic uraemic syndrome
- FBC (anaemia, thrombocytopenia)
- Peripheral blood smear (schistocytes)
- Renal function/creatinine (raised)
- Serum electrolytes (sodium, potassium, chloride and bicarbonate, calcium and phosphorus- hyperkalaemia, hyponatraemia, hypernatraemia, acidosis)
- PT, PTT (normal)
- LDH (normal)
- Haptoglobin (low)
- Stool culture on sorbitol-MacConkey agar to detect Shiga toxin-producing Escherichia coli (appears white)
- Polymerase chain reaction (PCR) to detect Shiga toxin 1/Shiga toxin 2 (positive)
- Proteins involved in complement regulation
- Urinalysis (haematura, proteinuria, elevated creatinine)
- ADAMTS13 level (normal)
- LFTs
- Serum amylase, lipase, glucose
90
Define multiple myeloma
A plasma cell dyscrasia characterised by terminally differentiated plasma cells, infiltration of the bone marrow by plasma cells, and the presence of a monoclonal immunoglobulin (or immunoglobulin fragment) in the serum and/or urine.
91
Describe epidemiology of multiple myeloma
- 4.5-6 per 100000 per year incidence in europe
- 4.1 per 100000 per year mortality in europe
- Median age at diagnosis 72
- Less common in white people, and most uncommon in Asian people
- More common in men than women
92
Describe aetiology of multiple myeloma
- No clear agent
- Evidence of inheritance
- Possible association with exposure to ionising radiation and petroleum products, but no evidence of causality
- Obesity, increasing age, more common in black population
93
List risk factors for multiple myeloma
- Monoclonal gammopathy of undetermined significance (MGUS)
- Abnormal free light-chain ratio (kappa/lambda)
- Radiation exposure
- Petroleum products exposure
- Agricultural work, HIV, HHV8
94
List signs and symptoms of multiple myeloma
CRAB
- High calcium (polyuria, polydipsia, constipation)
- Renal impairment
- Anaemia (breathlessness, lethargy)
- Bone (osteoporosis, pain esp back)
May also cause cachexia or paralysis
95
List investigations for multiple myeloma
- Serum/urine electrophoresis (paraprotein spike, light chain urinary excretion - bence jones protein)
- Normal ALP, raised urea, creatinine, calcium
- Skeletal survey (osteopenia, osteolytic lesions, pathological fractures)
- Whole body, low-dose computed tomography (osteolytic lesions, pathological fractures)
- Serum free light chain assay (increased free light chain)
- Bone marrow aspirate and trephenine is diagnostic (monoclonal plasma cell infiltration)
- Serum calcium (high)
- FBC (normocytic, normochromic anaemia)
- Creatinine, urea (renal impairment)
- Serum B2 microglobulin (<3.5mg/L or >5.5mg/dL)
- Serum albumin (>35g/L)
- Whole body MRI (>1 focal lesion, bone marrow infiltration)
- FDG-PET (bone disease and bone marrow infiltration)
- CRP (high or increasing amount)
- LDH (higher level= more extensive disease)
- Cytogenetics and fluorescence in situ hybridisation analysis
96
Define acute lymphoblastic leukaemia
- A malignant clonal disease that develops when a lymphoid progenitor cell becomes genetically altered through somatic changes and undergoes uncontrolled proliferation.
- This progressive clonal expansion eventually leads to ALL, characterised by early lymphoid precursors replacing the normal haematopoietic cells of the bone marrow and further infiltrating various body organs.
97
Describe epidemiology of ALL
- Worldwide incidence 3 in 100000, with 75% of cases in children under 6
- First peak under age 5 (5.3 per 100000)
- Second peak age 35 (2 per 100000)
- Third peak age 80-04 (2.3 per 100000)
- Incidence rate two times higher in white people
- Male to female ratio 1.2 to 1.0
98
Describe aetiology of ALL
- Unknown.
- Genetic (associated with trisomy 21, klinefelters and other conditions)
- Environmental (radiation exposure and smoking)
- Viral infections
- Folate metabolism polymorphisms
99
List risk factors for ALL
- Children less than 6 years of age
- Age in mid to late 30s
- Age in mid 80s
- Genetic factors
- Family history of acute lymphocytic leukaemia (ALL)
- Viruses
- Environmental factors
- History of malignancy
- Treatment with chemotherapy
- Male sex
- White population
- Downs syndrome and exposure to radiation in the womb
100
List symptoms of ALL
- Fatigue, dizziness, palpitations and dyspnoea
- Epistaxis, menorrhagia
- Painless unilateral testicular enlargement
- Bony pain
- Abdo pain
101
List signs of ALL
- Lymphadenopathy
- Hepatosplenomegaly
- Pallor, echmosis, petechiae
- Fever
- Papilloedema, nuchal rigidity, meningismus
- Focal neurological signs (eg. cranial nerves)
- Renal enlargement
- Mediastial or abdo mass
- PE
- Skin infiltrations
102
List investigations for ALL
- FBC (anaemia, leukocytosis, neutropenia and/or thrombocytopenia)
- Peripheral blood smear (leukaemic lymphoblasts). Sudan black B positive
- Serum electrolytes
- Renal function
- Liver function
- Lactic dehydrogenase (may be elevated)
- Coagulation profile
- Bone marrow aspiration and trephine biopsy (hypercellularity and infiltration with lymphoblasts)
- Immunophenotyping (on bone marrow, or peripheral blood if cell count is raised - exibit markers of one type, rarely simultaneous lymphoid and myeloid markers)
- Thiopurine methyltransferase (TPMT) phenotype
- Cytogenetics
- Molecular studies (for philadelphia chromosome)
- HLA-typing
- Chest x-ray (mediastinal mass, pleural effusion, lower RTI)
- Lumbar puncture (LP)
- Pleural tap
- CT/MRI brain
- CT
- Minimal residual disease molecular samples
- Bone marrow biopsy more than 20 lymphoblasts
103
Define acute myeloid leukaemia
- Clonal expansion of myeloid blasts in the bone marrow, peripheral blood or extramedullary tissues.
- Acute promyelocytic leukaemia is a form of APL with normal WBC, bi-lobed nuclei, hypergranulated blasts and auer rods (faggot cells). t(15:17)
104
Describe epidemiology of AML
- In 2014 3072 cases in UK
- More common in older adults - in UK 55% of cases in age 70 and over)
- Higher for males over age 55
105
Describe aetiology of AML
- Exposure to radiation, benzene, chemotherapy drugs
- Abnormalities of chromosome 5 and 7 increased by these
- Prior treatment of topoisomerase II inhibitors
- 11q23 abnormalities
- Translocations
- May occur in pre-existing haematological malignancies
106
List risk factors for AML
- Age over 65 years
- Previous treatment with chemotherapy
- Previous haematological dyspoiesis
- Genetic factors
- Constitutional karyotype abnormalities
- Radiation exposure
- Benzene exposure
- Environmental exposures
- Male sex
107
List symptoms of AML
- Fatigue
- Dizziness
- Aplpitations
- Dyspnoea
- Infections/fever
- Mucosal bleeding
- Skin or testicular mass
- Bone pain
- Abdo pain
- Swollen gums
108
List signs of AML
- Pallor
- Ecchymoses or petechiae
- Lymphadenopathy
- Hepatosplenomegaly
- Skin infiltration
- Gingival enlargement
109
List investigations for AML
- FBC with differential (anaemia, macrocytosis, leukocytosis, neutropenia, thrombocytopenia)
- Peripheral blood smear (blasts and auer rods - biopsy needed for diagnosis)
- Coagulation panel
- Serum electrolytes
- Renal function
- LFTs
- Serum lactic dehydrogenase (may be elevated)
- Bone marrow biopsy or aspiration (bone marrow hypercellularity and infiltration by blasts, blasts over 20%, auer rods)
- Immunophenotyping and molecular studies (surface antigens eg. CD34/33 in ALL positive for terminal deoxynucleotidyl transferase and lack staining for myeloperoxidase)
- Lumbar puncture
- HLA antigen typing
- Chest x-ray
- Echocardiogram
- Multi-gated acquisition scan
110
Define CML
A malignant clonal disorder of the haematopoietic stem cell that results in marked myeloid hyperplasia of the bone marrow
111
Describe epidemiology of CML
- Incidence peaks between age 65-74
- Male predominance
- Median age at diagnosis 65
- 14% of leukaemia in US CML
112
List risk factors for CML
- Age 65-74
- Ionising radiation exposure
- Male sex
- Associated with philadelphia chromosome 80% patients
113
List symptoms of CML
- 50% asymptomatic
- SOB
- LUQ discomfort or fullness
- Epistaxis
- Arthralgia
- Weight loss
- Excessive sweating
- Headaches (hyperviscosity)
114
List signs of CML
- Splenomegaly (90%)
- Retinal haemorrhages
- Bruising
- Fever
- Sternal tenderness
- Pallor
115
List investigations of CML
- FBC (high WBC, anaemia, normal platelet, thrombocytosis or thrombocytopenia)
- Complete metabolic profile (elevated potassium, LDH or uric acid)
- Peripheral blood smear (mature or maturing myeloid cells, elevated basophils and eosinophils)
- Bone marrow biopsy (granulocytic hyperplasia)
- Cytogenetics (philadelphia chromosome positive t(9,22)
- Quantitative reverse transcription PCR (qRT-PCR) including breakpoint analysis (BCR-ABL fusion, philadelphia chromosome)
- Fluorescent in situ hybridisation (FISH - t(9,22) positive)
- Low leukocyte alkaline phosphatase
116
Define chronic lymphocytic leukaemia
- An indolent lymphoproliferative disorder in which monoclonal B lymphocytes (>5 x 10⁹/L [>5 x 10³/microlitre]) are predominantly found in peripheral blood.
- If these cancer cells are found predominantly in lymph nodes, the disorder is called small lymphocytic lymphoma.
117
Describe epidemiology of CLL
- Most common leukaemia in the western world
- 3515 new cases in UK in 2014
- More common middle age to older - median age 70 years at diagnosis
- Male to female ratio 2:1
- White to black 1.48, white to hispanic 2.31
118
Describe aetiology of CLL
- Exact cause unclear
- Thought to be an accumulation of multiple genetic events affecting oncogenes and tumour suppressor genes
- Increased cell survival and resistance to apoptosis
119
What is philadelphia chromosome?
t(9,22) - CML
120
List risk factors for CLL
- Age over 60
- Male
- White
- Family history
121
List symptoms of CLL
- 50% asymptomatic
- SOB
- Fatigue
- B symptoms (fever, chills, night sweats, weight loss, fatigue 10% cases)
- Recurrent infections
122
List signs of CLL
- Lymphadenopathy (enlarged, rubbery, non-tender)
- Splenomegaly
- Hepatomegaly
123
List investigations of CLL
- WBC count with differential (absolute lymphocytosis (over 5x10^9/L)
- Blood film (smudge/smear cells, spherocytes and polychromasia)
- Haemoglobin (Hb low)
- Platelet count (less than 100x10^9/L)
- Flow cytometry (positive for specific markers dim surface immunoglobulin, CD5,19,20,23)
- Fluorescent in situ hybridisation (FISH - cytogenic abnormalities)
- Molecular genetic analysis
- Direct antiglobulin test (DAT - positive in autoimmune haemolytic anaemia)
- Immunoglobulin levels (hypogammaglobulinaemia)
- Bone marrow aspirate and trephine biopsy (marrow infiltration, reduction in haematopoetic precursor compartment)
- CT scan (Variable - hepatosplenomegaly, retroperitoneal or mediastinal adenopathy)
124
List causes of sickle cell crisis
- Hypoxia
- Dehydration
- Acidosis
- Infection
125
Define haemolytic anaemia
A number of conditions that result in the premature destruction of RBCs. Common causes include autoantibodies, medications, and underlying malignancy, but the condition can also result from a number of hereditary conditions, such as haemoglobinopathies.
126
Describe epidemiology of haemolytic anaemia
- G6P deficiency is the most common cause. 400 million people worldwide. 50% in Kurdish Jews. Common in sub-saharan africa.
- 11% prevalence in black males
- Warm antibody haemolytic anaemia is the most common autoimmune form, affecting more women than men
127
Describe the aetiology of haemolytic anaemia
Hereditary causes fall into 3 broad categories:
- Inherited RBC defects (membrane defects) - hereditary spherocytosis, elliptocytosis, pyropoikilocytosis
- Enzyme deficiencies - glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency
- Abnormal Hb production - sickle cell anaemia, thalassaemia.
Acquired haemolytic anaemia can be subdivided into immune and non-immune aetiologies:
- Autoantibodies are the cause of immune-mediated haemolytic anaemias, most often as part of other autoimmune conditions (e.g., SLE, rheumatoid arthritis, scleroderma) or related to a lymphoproliferative disorder (non-Hodgkin's lymphoma, chronic lymphocytic leukaemia).
- Immune haemolytic anaemias can be divided into warm- or cold-reacting antibodies, depending on the temperature at which the antibody binds most avidly to the RBCs.
- Alloimmune haemolytic anaemias include haemolytic disease of the newborn or transfusion reaction.
- Drugs
- Infection, trauma in various forms (microangiopathic haemolysis such as DIC, thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome), hypersplenism, and liver disease.
128
List risk factors for haemolytic anaemia
- Autoimmune disorders
- Lymphoproliferative disorders
- Prosthetic heart valve
- Family origin in Mediterranean, Middle East, Africa, or Southeast Asia
- Family history of haemoglobinopathy or RBC membrane defects
- Paroxysmal nocturnal haemoglobinuria
- Recent exposure to cephalosporins, penicillins, quinine derivatives, or NSAIDs
- Recent exposure to naphthalene or fava beans
- Thermal injury
- Exceptional exertion
- Recent exposure to nitrites, dapsone, ribavirin, or phenazopyridine
- Recent paraquat ingestion
- Malaria
- Babesiosis
- Bartonellosis
- Leishmaniasis
- Clostridium perfringens infection
- Haemophilus influenzae type B infection
- Liver disease
129
List signs and symptoms of haemolytic anaemia
- Pallor
- Jaundice
- Fatigue
- SOB
- Dizziness
- Splenomegaly
- Dark urine
- Active infections
130
List investigations for haemolytic anaemia
- FBC
- MCHC
- Reticulocyte count
- Peripheral blood smear (schistocytes, heinz bodies mean active haemolysis while bite cells mean previous haemolysis in G6PD deficiency, spherocytes in hereditary spherocytosis)
- Unconjugated bilirubin
- LDH
- Haptoglobin
- Urinalysis
- Direct antiglobulin or coombs test (positive means immune aetiology)
131
List causes of DAT/ coombs +ve
Warm IgG antibodies
- Idiopathic
- SLE
- CLL
Cold IgM antibodies
- Idiopathic
- Mycoplasma
- Mononucleosis
132
Define myelofibrosis
A reactive and reversible process common to many malignant and benign bone marrow disorders. It is characterised by abnormal production of red blood cells, white blood cells, and platelets, in association with marrow fibrosis (scarring) and extramedullary haematopoiesis.
133
Describe epidemiology of myelofibrosis
- 0.4-1.4 per 100000 people in the US
- In europe, incidence 0.1-1 per 100000 people
- More common in white people
- Male adults and female children more likely to be affected
- Median age at diagnosis 65, 20% less than 65
134
Describe aetiology of myelofibrosis
- Radiation
- JAK2 gene
- Cloncal disorder, multipotent haematopoietic progenitor cell
- Fibroblasts in the bone marrow become overactive and proliferate
135
List risks for myelofibrosis
- Over 65
| - Radiation
136
List symptoms and signs of myelofibrosis
- Weight loss, night sweats, fever, cachexia, fatigue, pruritis
- SPlenomegaly and hepatomegaly
- Infections
- Bleeding
- Joint and bone pain
137
List investigations for myelofibrosis
- FBC
- Peripheral blood smear (teardrop shaped RBCs (dacrocytes), metamyelocytes, nucleated RBCs)
- Bone marrow aspiration (dry tap fibrosis)
- Bone marrow biopsy (fibrosis)
138
Define aplastic anaemia
Defined by pancytopenia with hypocellular marrow and no abnormal cells.
- At least 2 of the following peripheral cytopenias must be present: haemoglobin <100 g/L (<10 g/dL), platelets <50 × 10⁹/L, absolute neutrophil count <1.5 × 10⁹/L
139
Describe epidemiology of aplastic anaemia
- 5 cases per million per year
- Any age, peaks from 10-25 and over 60 years
- Higher in east asia
- Fanconi anaemia most common congenital cause
140
Describe aetiology/risks of aplastic anaemia
- Drug exposure (chloramphenicol, NSAIDs)
- Hepatitis
- Autoimmune disease
- Pregnancy, eosinophilic fasciitis, coeliac, SLE
- Paroxysmal nocturnal haemoglobinuria
- Congenital fanconi, dyskeratosis congenita, GATA2 and shwachman-diamond syndrome
141
List symptoms and signs of aplastic anaemia
- Bleeding or easy bruising
- Dyspnea
- Fatigue
- Infection, sepsis
142
List conditions which cause secondary polycythaemia
- High altitude
- Hypoxic lung disease
- Heart disease
143
List investigations for aplastic anaemia
- Bone marrow aspirate is hypocellular, no abnormal cell population or fibrosis
- FBC (low everything)
- Reticulocyte count (low)
144
Define anti-phospholipid syndrome
- Autoimmune mediated thrombosis
| - Often manifests in pregnancy
145
Describe epidemiology of anti-phospholipid syndrome
- 1-5.6% in normal health populations, increases with age
- Associated with SLE and ra
- 14% of patients with thrombosis, and 20% of patients with pregnancy loss
- More common in white females
- Age 15-50
146
Describe aetiology/risks of antiphospholipid syndrome
- Persistently elevated antiphospholipid antobodies results in thrombus formation and pregnancy associated morbidity
- SLE
- Autoimmune conditions
147
List signs and symptoms of antiphospholipid syndrome
- Recurrent miscarriages
- VTE
- Stroke/MI/ HTN
- Livedo reticularis
148
List investiagions for antiphospholipid syndrome
- Anti-cardolipin positive
- Lupus anti-coagulant test positive
- Anti-beta2 glucoprotein 1 antibodies
- ANA, dsDNA
- FBC (may show thrombocytopenia)
- Creatinine and urea
149
List causes of polycythaemia
Risk factors for secondary erythrocytosis include:
- Generalized hypoxia — may be due to smoking, lung or cardiac disease, sleep apnoea, residing at high altitude, or carbon monoxide poisoning.
- Localized renal hypoxia — may be due to renal artery stenosis, end stage renal disease, hydronephrosis, polycystic kidney disease, or post-renal transplant erythrocytosis.
- Pathological erythropoietin production — may be due to cerebellar haemangioblastoma, meningioma, parathyroid carcinoma or adenoma, hepatocellular carcinoma, renal cell carcinoma, pheochromocytoma, or uterine leiomyoma.
- Exposure to certain drugs — such as diuretics, testosterone or anabolic steroids, or erythropoietin.
- Genetic mutations which lead to upregulation of erythropoietin (rare) — mutant forms of haemoglobin with an increased affinity for oxygen, and mutations which affect oxygen sensing lead to increased erythropoietin production.
150
Define myelodysplasa
- A group of clonal stem cell disorders, characterised by ineffective and dysplastic haematopoiesis resulting in 1 or more cytopenias, and a varying predilection to develop acute myeloid leukaemia (AML - 30%).
- MDS is diagnosed when bone marrow demonstrates significant dysplasia, clonal cytogenetic abnormality, quantitative changes in at least one of the blood cell lines, and blasts <20%.
- Patients with blasts ≥20% are considered to have AML.
- MDS can arise primarily without any inciting event or may be related to previous treatment with either chemotherapy or radiation.
151
Describe epidemiology of myelodysplasia
- Primary age 65-70
- Secondary in younger people
- More common in males
- 20 in 100000 incidence in over 70s
- Incidence among all ages 4 in 100000
152
Describe aetiology of myelodysplasia
- Chromosomal abnormalities in 40-70% patients, and 90% of those with secondary
- Most commonly deletions
- 80% primary disease
- Secondary to chemo or radiotherapy. Greatest risk is long term DNA alkylating agents (eg. chlorambucil and cyclophosphamide)
- Environmental risk: tobacco and benzene
- Congenital neutropenia, downs syndrome, fanconi anaemia, blooms syndrome, aplastic anaemia or paroxysmal nocturnal haemoglobinuria
153
List signs and symptoms of myelodysplasia
- Often asymptomatic
- Fatigue, exercise intolerance (80% anaemia)
- Pallor
- Petechiae/ purpura (25% thrombocytopenia)
- Bacterial infections (40% neutropenia)
- Splenomegaly, hepatomegaly, lymphadenopathy (Chronic myelomonocytic leukaemia)
154
Describe investigations for myelodysplastic syndrome
- FBC (one or more cytopenias - anaemia, neutropenia, thrombocytopenia)
- Reticulocyte count (innapropriately normal or low)
- RBC folate (normal)
- B12 (normal)
- Iron studies (noraml)
- HIV testing (-ve)
- Bone marrow aspiration with iron stain (single or myltilineage dysplasia, bone marrow blasts over 20%)
- Bone marrow core biopsy (hypercellular marrow, ring sideroblasts)
- Bone marrow cytogenic analyss (chromosomal abnormalities)
- Serum erythropoietin (raised)
- HLA typing
- Flow cytometry (clonal population)
155
Define lymphoma
- Cancer of the lymphatic system, malignant proliferation of lymphocytes
- Hodgkin (Reed-Steinberg or mirror image nuclei cells) or non-hodgkin. Burkett is a form of non-hodgkin starting in B cells
156
Describe risk factors/ aetiology of lymphoma
Hodgkin
- Infected sibling
- EBV
- Post transplantation.
- SLE
Non Hodgkin
- HIV
- Drugs
- Immunosufficiency, Sjogrens
- HTLV1
- H pylori
- Toxins
- Congenital
157
Describe epidemiology of lymphoma
Hodgkin
- 1 in 360 for men
- 1 in 505 for women
- Most commonest malignancy age 15-24, also peaks in the elderly
Non-Hodgkin
- 6th most common cancer in UK
- 45% non-Hodgkin are female, 55% male
- 4% of all new cancer cases
158
List symptoms of Hodgkin Lymphoma
- The most common symptom of lymphoma is lymphadenopathy (rubbery, mobile, non-tender), sometimes accompanied by other symptoms such as fever, pruritus, weight loss, or night sweats
- Difficulty breathing or coughing.
159
List signs of hodgkin lymphoma
- Enlarged lymph nodes (supraclavicular and neck)
- Enlarged spleen/liver
- Cachexia, anaemia
- Excoriations
160
List symptoms and signs of non-hodgkin lymphoma
- Superficial lymphadenopathy
- Systemic features (night sweats, fever, weight loss, less common than in Hodgkin)
- Pancytopenia and bone marrow involvement (anaemia, infection, bleeding)
Extranodal disease (gut commonest)
- Gastric MALT can cause gastric cancer symptoms
- Non-malt gastric lymphomas diffuse large cell B lymphomas
- Small bowel lymphomas (IPSID or EATCL presents with diarrhoea, vomiting, abdo pain, weight loss)
- Skin (2nd commonest)
- Oropharynx (waldeyers ring lymphoma causes sore throat/obstructed breathing)
- Bone, CNS, lung
161
List investigations for lymphoma
- Blood count – can be normal, or there can be normocytic, normochromic anaemia.
- There may also be lymphocytopaenia (abnormally low lymphocytes) or eosinophilia (abnormally high eosinophils)
- Neutrophilia in Hodjkin and neutropenia in non-hodgkin
- ESR – may be raised
- Liver biochemistry
- Serum lactate dehydrogenase (LDH)– a raised level is a bad prognostic indicator, due to increased cell turnover
- Uric acid – may be normal or raised
- CXR
- CT scan
- Bone marrow aspirate and trephinine – very rarely done, but will show involvement in advanced disease
- Lymph node biopsy – required for definitive diagnosis – looking at the histology for Reed sternberg cells indicating hodgkin lymphoma (lacunar histiocytes, giant malignant cells with multiple nuclei, owls eye appearance)
162
Define von willebrand disease
- The most common inherited bleeding disorder, due to either a quantitative or qualitative abnormality of von Willebrand factor (VWF).
- VWF provides the critical link between platelets and exposed vascular subendothelium, and also binds and stabilises coagulation factor VIII.
163
Describe epidemiology of von willebrand disease
- The most common inherited bleeding disorder, affecting 66 to 100 people per million of the general population
- Prevalence up to 1% but may be asymptomatic
- Women more commonly diagnosed due to blood loss via menorrhagia
- Type 1 75% cases, Severe (type 3) 1-3 per mill of the general population
- Type 2 20% of cases
164
Describe aetiology/risks of VWD
- Usually due to a mutation in VWF gene, but linkage not seen in 30% type 1 cases
- Age, blood type, hypothyroidism, inflammation, stress and hormone levels affect VWF levels
- Type 1 mutations affecting gene expression or clearance (reduced level, mildest disease)
- Type 2 encoded by exon 28 (does not work properly)
- Type 3 nonsense or frameshifts due to small insertions or deletions (most severe and rarest, virtually complete definity)
- Acquired rarely occurs, associated with lymphoproliferative disorders (eg. monoclonal gammaopathy, multiple myeloma) and aortic stenosis
165
List signs and symptoms of VWD
- Bleeding from minor wounds
- Post-operative bleeding
- Easy and excessive bruising
- Menorrhagia
- GI bleeding (type 2 or 3)
- Epistaxis
- Haemarthrosis (rare)
- Central nervous system bleeding
- Haematuria
Type 1 and 2 superficial bleeding, type 3 reduced factor 8 so deep bleeding
166
List investigations for VWD
- PT (extrinsic pathway - normal)
- aPTT (prolonged)
- FBC (normal, but in 2B platelet count reduced)
- VWF antigen (diagnostic- if under 0.30 - normal in type 2)
- VWF function assay (diagnostic if uner 0.3 IU, ratio of function to antigen <0.6 type 2 VWD)
- Factor VIII activity (decreased)
- Multimer analysis (type 1 all multimers present but decreased, 2A loss of medium and high weight, type 2B loss of high weight, 2M normal)
- Platelet aggreggometry for type 2B
167
Define thalassemia
- Thalassemias are a group of hereditary hemoglobin disorders characterized by mutations on the α- or β-globin chains (resulting in alpha or beta thalassemia).
- Thalassemias can be further classified according to the specific genotype: the α-chain is coded by four alleles, resulting in four possible variants depending on the number of alleles affected, while the β-chain is coded by two alleles, resulting in two possible variants.
168
Describe epidemiology of thalassemia
- Beta thalassemia most commonly seen in people with Mediterranean descent
- Alpha thalassemia most commonly seen in people of Asian and African descent
- Partial resistance against malaria
169
Describe aetiology and types of thalassemia
- Beta thalassemia due to point mutations in promotor sequences or splicing sites - short arm of chromosome 11. Minor 1 defective allele, major 2 defective alleles. Sickle is one B globin defective and one HbS
- Alpha thalassemia due to a deletion of at least one of four existing alleles, located on chromosome 16. May be a silent carrier (one defective allele), haemoglobin H disease three defective alleles, haemoglobin bart disease all four alleles are defective.
- Autosomal recessive inheritance pattern
170
List signs and symptoms of beta thalassemia
Minor - unremarkale symptoms (sometimes splenomegaly)
Major
- Severe haemolytic anaemia, secondary haemochromatosis due to transfusions
- Hepatosplenomegaly
- Growth retardation
- Skeletal deformities (high forehead, prominent zygomatic bones, maxilla - chipmunk facies)
- Transient aplastic crisis
Sickle cell beta thalassemia
- Features of sickle cell disease
- Severity depends on the amount of B-globin synthesis
171
List symptoms and signs of alpha thalassemia
Silent carrier - asymptomatic
Trait
- Mild anaemia (normal RBC and RCDW)
Haemoglobin H disease
- Jaundice and anaemia at birth
- Chronic haemolytic anaemia that may require trnasufions, iron overload
- Hepatosplenomegaly
- Skeletal deformities (less common)
- Less severe in adults
Hb-Barts
- Intrauterine ascites and hydrops fetalis (severe hepatosplenomegaly, cardiac and skeletal anomalies)
- Incompatable with life
172
List investigations for thalassemia
- FBC (microcytic hypochromic anaemia, normal RDW, higher RBC than iron deficiency)
- Coombs test negative
- Raised LDH and reticulocytes, reduced haptoglobin
- Hyperbilirubinaemia
- Iron studies normal
- Blood smear - HBH inclusion bodies, target cells, teardrop cells, anisopoikilocytosis, erythroblasts
- Hb electrophoresis, HPLC (in B thalassemia major, no HbA, raised HbF and HbA2, in alpha thalassemia normal/low HbA2 and HbF, with HbH present sometimes)
- Genetic studies
- May do bone marrow aspiration to rule out other conditions
- Imaging for bone abnormalities/ extramedullary haematopoiesis
173
List pentad of thrombotic thrombocytopenic purpura
- Haemolytic anaemia
- Trombocytopenia
- Fever
- Neurologic symptoms
- Uraemia
174
Describe burkett lymphoma
- Sybtype of Non-Hodgkin's lymphoma
- Risks: EBV, chronic malaria, HIV
- Presents with rapidly enlarging lymph node in the jaw
- Starry sky appearance under microscopy
175
What is the Ann Arbor staging system used for?
Lymphoma
176
Describe monoclonal gammopathy of unknown significance
- Pre-malignant condition where there is accumulation of monoclonal plasma cells
- 1% acquire additional mutations and becomes multiple myeloma
- CRAB symptoms are absent
177
List the types of myelodysplasmia
- Refractory anaemia
- Refractory anaemia with ringed sideroblasts
- Refractory anaemia with excess blasts
- Refractory anaemia with excess blasts in transformation
- Chronic myelomonocytic leukaemia
178
List the types of VWD and their inheritence
Type 1
- Reduced amount of normal VWF
- Autosomal dominant
Type 2
- Normal amount of abnormal VWF
- Autosomal dominant
Type 3
- Absent VWF
- Reduced factor 8
- Autosomal recessive
179
Describe management of a warfarin induced bleed
- 5mg vitamin K
| - Prothrombin complex concentrate (octaplex)
180
Descrbe reversal of heparin anticoagulation
- Protamine sulfate (used to reduce effects after delivery/cardiac surgery)
181
Describe follicular lymphoma
- A type of non-hodgkin lymphoma
| - Painless peripheral lymphadenopathy with nodular growth pattern
182
Describe waldenstroms macroglobulinaemia
- A type of non-hodgkin lymphoma
| - Production of monoclonal IgM
