Haematology Flashcards
Define microcytic anaemia
Low haemoglobin concentration and low MCV on blood test
List causes of microcytic anaemia
- 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
List signs on examination of microcytic anaemia
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
List symptoms of microcytic anaemia
- Dyspnoea
- Fatigue
- Cognitive dysfunction
- Restless leg syndrome
- Vertigo
- Dysphagia
- Syncope
- Dizziness
- Irritability
- Weakness
Describe epidemiology of iron deficiency anaemia
- 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)
Describe epidemiology of thalassemia
- 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
Describe epidemiology of sideroblastic anaemia
- More common in males
- Onset usually before 30
- Rare
List investigations to diagnose microcytic anaemia
- 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
Describe management of microcytic anaemia
- 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
List complications of microcytic anaemia
- 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
What is red cell distribution width? What makes it abnormal?
- 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.
List causes of macrocytic anaemia
- 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)
Define macrocytic anaemia
- Abnormally large red blood cells
- High MCV, low Hb
Describe epidemiology of macrocytic anaemia
- 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%
List symptoms of macrocytic anaemia
- Fatigue
- SOB
- Angina
- Headache
- Palpitations
- Reduced sensation, parasthesia, ataxia, reduced proprioception
List signs of macrocytic anaemia
- Pallor (nail beds, tongue, conjunctiva)
- Lemon tinge skin colour in pernicious anaemia
- Bounding pulse
- Systemic flow murmur
List investigations for macrocytic anaemia
- 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
Describe management of macrocytic anaemia
- 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
List complications of macrocytic anaemia
- 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
Describe prognosis of macrocytic anaemia
- Generally good once cause is identified
- Vitamin deficiencies can be replaced
- Can cause permanent damage to the nervous system
Define normocytic anaemia
- Low Hb
- Normal MCV
Compare neutrophilia to lymphocytosis
- Neutrophilia acute inflammation
- Lymphocytosis chronic inflammation
Describe causes of microangiopathic haemolytic anaemia
- 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)
List causes of haemolytic anaemia
Hereditary
- Red cell membrane (hereditary spherocytosis, elliptocytosis)
- Enzyme deficiency (G6PD deficiency)
- Haemoglobinopathy (Sickle cell disease, Thalassaemias)
Acquired
- Autoimmune
- Drugs
- Infection
- MAHA
Describe hereditary haemorrhagic telangiectasia
- Autosomal dominant
- Abnormal blood vessels in (skin, mucous membranes, lungs, liver, brain)
List presentations of polycythaemia
- Headache
- Pruritis after hot bath
- Blurred vision (hyperviscosity)
- Tinnitus
- Thrombosis (stroke, DVT)
- Gangrene
- Choreiform movement
Define polycythaemia
High red blood cell count
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.
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
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
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.
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
List signs of sickle cell disease
- Tachycardia
- Tahcypnoea
- Pallor
- Jaundice
- Maxillary hypertrophy with overbite
- Protuberant abdomen with umbilical hernia
- Cardiac systolic murmur
- Shock
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
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
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
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.
List causes of anaemia with increased reticulocyte count
- Haemolytic crises
List causes of anaemia with low reticulocyte count
- Parvovirus B19
- Aplastic crisis in sickle cell
- Blood transfusion
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
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
List neurological associations with B12 deficiency
- Dementia
- Subacute combined degeneration of the spinal cord
- Peripheral neuropathy
List lab evidence of haemolysis
- LDH rasied
- Unconjugated hyperbilirubinaemia
- Reduced haptoglobins
- Reticulocytosis
List factors suggesting G6PD defiency
- Oxidising agent exposure precipitating jaundice and anaemia
- Heinz bodies on smear
List advice given to patients with G6PD deficiency
- Avoid oxidant drugs
- Dont eat fava beans (broad)
- Avoid napthaline
- Be aware anaemia may follow infection
Which tests is done in presence of haemolytic anaemia?
- Coombs test
- Direct antiglobulin test (if positive, autoimmune haemolytic anaemia)
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
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
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.
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.
List risk factors of polycythaemia vera
- Age >40 years
- Budd-Chiari syndrome
- Affected family members.
Describe epidemiology of polycythaemia vera
- Rare in children
- Gender distribution is 1:1
- Complications are more common in women
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
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)
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
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
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
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
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
List risk factors for normocytic anaemia
- Old age
- Kidney disease
- Cancer
- Rheumatoid arthritis and thyroiditis
- Long standing chronic illness
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
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
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
List risk factors for immune thrombocytopenic purpura
- Women of childbearing age
- Age under 10 or over 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
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
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
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
List risk factors for haemophilia
- Family history
- Male sex
- Age over 60 (acquired)
- Autoimmune disorders, IBD, hepatitis, pregnancy, postnatal, malignancy (acquired)
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
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
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