Haematology Flashcards
Anaemia definition
Defined as blood with an insufficient concentration of haemoglobin
Pregnant women over 15 years: Hb <11g/dL
Non-pregnant women over 15 years: Hb <12g/dL
Men over 15 years: Hb <13g/dL
Anaemia general presentation
Symptoms: fatigue. Lethargy, dyspnea, palpitations, headache
Signs: pale skin, pale mucous membranes, tachycardia (compensatory to meet demand)
Microcytic/normoytic/macocytic anaemia definition
Microcytic anaemia: several types of anaemia characterised by small RBCs (known as microcytes). It is defined as when the mean corpuscular volume (MCV) is less than 80fL. Mean corpuscular volume describes the average size of RBCs.
Normocytic Anaemia: Anaemia with a MCV 80-100fL (normal range). Can be further divided:
- hyperproliferative (reticulocyte count >2%): the proportion of circulating reticulates increases as a compensatory response to increased destruction or loss of RBCs. The cause is usually acute blood loss or haemolysis
- hypoproliferative (reticulocyte <2%): primarily disorders of decreased RBC production, and the proportion of circulating reticulocytes remains unchanged
Microcytic Anaemia: where RBCs are larger than their normal volume (MCV > 100fL). Can be further divided as:
- megaloblastic: deficiency of DNA production or maturation resulting in the appearance of large immature RBCs (megaloblasts) and hyperhsegmented neutrophils in the circulation
- non-megaloblastic: encompasses all other causes of microcytic anaemia in which DNA synthesis is normal. Megaloblasts and hyperhsegmented neutrophils are absent.
Microcytic/normoytic/macocytic anaemia aetiology
Micro:
- chronic disease (cancer, HF, CKD)
- thalassaemia
- Fe deficiency (blood loss, poor diet, malabsorption, hookworm)
Normo:
- acute blood loss
- anaemia of chronic disease
- pregnancy
- renal failure
- combined haematinic deficiency (Fe & B12/folate deficiency > needed for haematopeiesis > consider malabsorption as a cause
Macro:
- B12/folate deficiency
- excess alcohol/liver disease
- hypothyroidism
- bone marrow failure
Iron deficiency anaemia definition
Occurs when the body has insufficient Fe to support RBC production.
Most common cause of anaemia worldwide and in pregnancy.
Premenopausal women have a higher presence of IDA because of menstrual blood loss and pregnancy. Is considered a microcytic anaemia and is by far the most common cause of it.
Iron deficiency anaemia aetiology
Causes of iron deficiency may be classfied as those due to:
Excessive blood loss:
- blood loss from GI tract is the most common cause of IDA in adult men and postmenopausal women
- blood loss due to menorrhagia is the most common cause in pre-menopausal women
Dietary inadequacy:
- growing children and elderly people with iron-poor diets may become deficient
Failure of iron absorption:
- some drugs: tetracyclines and quinolones
- anatacids and PPIs may impair absorption
- Vitamin C deficiency
- malabsorption conditions such as coeliacs
- from gastrectomy
- H. pylori infection
- Hookworm
Excessive requirements for iron:
- times of rapid growth in children
- pregnancy, especially with twins
- exfoliative skin disease
Iron deficiency anaemia presentation
General signs and symptoms of anaemia
Specific:
- brittle hair and nails
- atrophic glossitis (tongue inflammation with smooth tongue)
- Koilonychia (spoon shaped nails)
- Angular Stomatitis (inflammation fo corners of mouth)
Iron deficiency anaemia diagnosis
Drug history - NSAIDs, SSRIs, clopidogrel, corticosteroids
FBC: shows hypochroic microcytic anaemia
- hypochromia means there is a low mean corpuscular haemoglobin (MCH)
Serum ferritin: measured to confirm iron deficiency (except during pregnancy)
- low
Reticulocyte count - reduces
Endoscopy - possible GI bleed related cause
Urinalysis - evaluate blood loss from renal tract
Iron deficiency anaemia management
Iron salts should be given by mouth:
- side effects include black stools, constipation, diarrhoea, nausea, GI upset, epigastric pain
Folate deficiency anaemia definition
Deficiency of Folate, a B vitamin (B9). CLassically presents as megaloblastic anaemia, without any neurological signs. Unlike B12, reserves of B9 are low and only sufficient for around 4 months.
Iron deficiency anaemia aetiology
Main cause is poor intake Dietary deficiency - malabsorption (coeliacs etc) - anorexia Excessive requirements - pregnancy, lactation, infancy - malignancy - blood disorders (haemolytic and sick anaemia) Antifolate drugs
Iron deficiency anaemia presentation
May be completely asymptomatic
Normal anaemia signs and symptoms:
Loss of appetite and weight loss is a symptom of megaloblastic anaemia and the hallmark of folate deficiency
Glossitis (inflammation of the tongue) may be present
Angular stomatitis (ulcers in corners of mouth)
Lemon-yellow skin
Neurological features: mild compared to B12 deficiency
Iron deficiency anaemia diagnosis
FBC:
- low haemoglobin with elevated MCV and MCH
Peripheral blood smear:
- macrocytic naemia and hypersegmented neutrophils seen with both folate and B12 deficiency
Erythrocyte folate level
Iron deficiency anaemia differential diagnosis
Vitamin B12 deficiency, alcoholic liver disease, hypothyroidism, myelodysplasia and aplastic anaemia
Iron deficiency anaemia management
Daily folic acid tablets (build up folate levels)
Dietary advice - good sources of folate include: broccoli, nuts
Iron deficiency anaemia complications
Infertility, cardiovascular disease, cancer, problems in childbirth, neural tube defects and folic acid
Haemolytic anaemia defintiion
Disorder in which RBCs are destroyed faster than they can be made
Haemolytic anaemia risk factors
Sickle cell disorders
Haemolytic anaemia aetiology
Genetic: sick cell, thalaseeaemia, G6PD deficiency, pyruvate kinase deficiency
Acquired: autoimmune, infections, secondary to systemic disease
Haemolytic anaemia presentations
Symptoms:
- gallstones (excess bilirubin)
Signs:
- jaundice (increase bilirubin from RBC destructions) - bilirubin stones may cause abdo pain (gallstone pain)
- leg ulcers
- splenomegaly
- signs of underlying disease (SLE malar rash)
Haemolytic anaemia diagnosis
FBC - low Hb
Reticulocyte count - increase
Blood film - presence of Schistocytes
Haemolytic anaemia management
Folate and iron supplementation
Immunosuppressives
Splenectomy
B12 deficiency anaemia definition
Deficiency of Cobalamin, a B vitamin (B12). Classically presents as megaloblastic anaemia, with neurological signs
B12 deficiency anaemia aetiology
Pernicious anaemia
- autoimmune destruction of instrinsic factor due to intrinsic factor targeting antibodies
- often associated with autoimmune destruction of parietal cells (which produce intrinsic factor)
Dietary insufficiency
- veganism
Gastric causes
- atrophic gastritis
- gastrectomy
- H. pylori infection
Intestinal causes
- Crohn’s disease
- malabsorption
Drugs
- PPIs
- neomycin
- metformin
B12 deficiency anaemia key presentations
Neurological changes (paraesthesia, numbness, cognitive changes)
B12 deficiency anaemia signs and symptoms
Normal anaemia presentation
B12 deficiency anaemia investigations
- blood film
- autoantibody screen - check for IF antibodies
- serum B12 (may be normal despite clinical B12 deficiency symptoms - ‘false normal B12 deficiency’)
B12 deficiency anaemia differential diagnosis
Folate deficiency
B12 deficiency anaemia management
- IM B12 supplementation (Hydroxocobalamin)
- care should be taken not to give folic acid (instead of B12) to any patient who is B12-deprived, as this may result in fulminant neurological deficit
B12 deficiency anaemia complications
- severe anaemia causes risk of cardiopulmonary complications
- predisposes to neural tube defects (such as spina bifida, anencephaly, and encephalocele) in the fetus
- sterility
Deep vein thrombosis definition
Development of a blood clot in a major deep vein in
- leg, thigh, pelvis, or abdomen
May result in impaired venous blood flow/consequent leg swelling and pain.
Deep vein thrombosis epidemiology
1-2 per 1000 population, but incidence of up to 37% in those who are critically ill
Deep vein thrombosis aetiology
Anything preventing blood flowing/clotting can cause a venous thrombosis. Main causes: damage to vein from surgery or trauma and inflammation from infection or injury
Deep vein thrombosis risk factors
Thromboembolic risk factors, such as cancer, trauma, major surgery, hospitalisation, immobilization, pregnancy, or oral contraceptive use.
Deep vein thrombosis pathophysiology
See Virchow’s triad (hyper coagulability, venous stasis, damage to vessel wall)
Commonest in lower limb below knee
Starts at low-flow site eg soleal sinus, behind venous valve pockets
Deep vein thrombosis key presentations
Calf swelling
Localised pain along deep venous system
Deep vein thrombosis signs and symptoms
Asymptomatic; Asymmetrical aedema Unilateral leg pain/dilation Distention of superficial veins Red/discoloured skin
Deep vein thrombosis 1st line investigations
- Wells’ score (point system) (2 or more means DVT is likely)
- quantitative D-dimer level (if <2 proceed to imaging)
- proximal duplex ultrasound
- whole-leg ultrasound (inability to fully compress lumen of vein using ultrasound transducer, reduced or absent spontaneous flow, lack of resp. variation, intraluminal echoes, colour flow patency abnormalities)
- FBC
Other:
- Doppler venous flow testing (low flow in veins)
- CT abdomen and pelvis with contrast (intraluminal filling defect)
- thrombophilia screen
Deep vein thrombosis gold standard investigations
Doppler Ultrasound Scan
Deep vein thrombosis deifferential diagnosis
- cellulitis
- peripheral oedema
- vasculitis
Deep vein thrombosis prevention
- stockings
- mobilisation
- leg elevation
Deep vein thrombosis management
Anticoagulants such as - warfarin - low molecular weight heparin - novel oral anticoagulants (NOACs) - typically apixaban IVC filter to prevent PE
Deep vein thrombosis monitoring
Oral antocoagulation continued for 3-6 months
In patients with significant thromboembolic risks, careful consideration should be given to maintaining oral anticoagulation indefinitely as long as bleeding risk = lower then risks of recurrent venous thrombosis
Deep vein thrombosis complications
Pulmonary embolism is heavily associated with DVT - the umbrella term venous thromboembolism (VTE) is often used to cover both conditions
Deep vein thrombosis prognosis
Recurrence is common after one incident of DVT
Without anticoagulation, the risk of recurrence of VTE (DVT or PE) is thought to be 50% within three months of a PE. Risk of recurrence within the first year of a VTE following three months of anticoagulation is thought to be 8%.
Pulmonary embolism definition
When a thrombus becomes loged in one of the pulmonary arteries. Usually travelled from another site eg DVT.
Multiple myeloma definition
Myloma is the cancer of plasma cells (chief plasma cell dyscrasia).
In myeloma the malignant plasma cell produces an excess of one type of immunoglobulin known as monoclonal paraprotein (mainly IgG 55%, can be IgA 20%, rarely IgM and IgD).
These plasma cell clones accumulate and crowd the bone marrow, preventing the production of normal levels of healthy blood cells -> anaemia, impaired immune function and low platelets.
Monoclonal oaraperotein can also deposit in other organs and cause dysfunction
Multiple myeloma epidemiology
Median age 70, more common in Afro-caribbeans and males
Multiple myeloma aetiology
Unknown
Multiple myeloma risk factors
Chromosomal abnormalities - t(11;14) (most comon) (t(11;14) means reciprocal translocation between chromosome 11 and 14) etc
Multiple myeloma pathophysiology
Affects plasma cells
- results in progressive bone marrow failure = excess IgG/IgA
Multiple myeloma key presentations
Mneumonic CRAB
C - hypercalcaemia (AKI, thirst, confusion, constipation)
R - renal impairment (nausea/vomiting, weight loss, uraemia)
A - anaemia/neutropenia/thrombocytopenia (dyspnoea, fatigue, pallor, bleeding, infection)
B - bone lesions (bone pain, spinal cord compression)
Multiple myeloma 1st line investigations
FBC:
- anaemia
- thrombocytopenia
- neutropaenia
- persistently high ESR (indicated inflammation)
U&E:
- hypecalcaemia
- high alkaline phosphatase
Blood film:
- rouleaux (aggregations of red blood cell stacks caused by increased serum proteins)
Serum and/or urine electrophoresis
Urine:
- bence jones protein (monoclonal globulin protein)
X-rays: lytic ‘punched-out’ lesions, ie
- pepper-pot skull
- vertebral collapse
- fractures
- osteoporosis
CT:
- bone lesions
- cord compression
Multiple myeloma differential diagnosis
Monoclonal gammopathy of undetermined significance (MGUS):
- MIg (monoclonal Ig) <30g/L (but still relatively higher than normal population)
- no significant increase in bone marrow plasma cells
- no related organ impairment
- 1% transform to myeloma per year so eg 20% in 20 years etc
- there is a paraprotein in the serum but no myeloma, with no bone lesions, no Bence Jones protein
Multiple myeloma management
1st line: induction chemotherapy
- thalidomide AND dexamethasone
PLUS:
DVT prophylaxis - aspirin
Stem cell transplant
Bisphosphates for bones - pamidronate disodium
Multiple myeloma monitoring
M protein levels in blood/urine determine extent of disease and monitor effectiveness of treatment
Multiple myeloma complications
- hypercalcaemia
- spinal cord compression
- hyperviscosity
- acute renal injury
- immune deficiency
Multiple myeloma prognosis
Although novel treatment strategies have resulted in improved outcomes (including response rates and survival), multiple myeloma (MM) remains an incurable disease. MM patients inevitably relapse 2 to 5 years after treatment.
Sickle cell anaemia definition
Disorder of quality; haemoglobinopathy
Autosomal recessive:
A point mutation in the beta globin chain results in haemoglobin S variant instead of HbBv. Polymerisation of the haemoglobin chains dmagaes RBCs, causing sickling. Sickled RBC get stuck easily
Offers protection against falciparum malaria
Heterosygotes may still, however, experience symptomatic sickling hypoxia, eg in unpressurised aircraft or anaethesia (so all those of African descent need a pre-op sickle-cell test)
Sickle cell anaemia epidemiology
It is most commonly seen in people of African origin
Sickle cell anaemia signs and symptoms
Acute - painful crises, sickle chest syndrome, stroke
Chronic - renal impairment, pulmonary hypertension, joint damage, infections
Sickle cell anaemia gold standard investigations
Hb electorphoresis: confirms the diagnosis and distinguishes ss, as states, and other Hb variants
Sickle cell anaemia management
Hydroxyurea (increases foetal haemoglobin levels)
Transfusion
Stem cell transplant
Sickle cell anaemia prognosis
Reduce life expectancy (around 50 y/o)
Acute myeloid leukaemia definition
Neoplastic proliferation of myeloblast cells (which normally gives rise to basophils, neutrophils, eosinophils). Progresses very rapidly, diagnosis is a medical emergency
Acute myeloid leukaemia epidemiology
Adults 40+
Most common type of acute leukaemia in adults
Associated with Down’s syndrome and radiation
Acute myeloid leukaemia aetiology
Can be a long-term complication of chemo eg for lymphoma
Myelodysplastic states
Radiation
Down’s syndrome (and other syndromes)
Acute myeloid leukaemia signs and symptoms
Anaemia, bleeding, infection (marrow failure)
Hepatosplenomegaly
Peripheral lymphadenopathy
GUM HYPERTROPHY
Acute myeloid leukaemia 1st line investigations
FBC: anaemia, thrombocytopenia, neutropenia
Blood film: leukamic blast cells
Bone marrow biopsy: increased cellularity and on biopsy, it is differentiated from all by Auer rods,
Immuni-phenotyping
Molecular methods
Cytogenic analysis (eg type of mutation) guides treatment recommendations and prognosis
Acute myeloid leukaemia differential diagnosis
Acute promyelocytic anaemia
Sub-type of Acute Myeloid Leukaemia (5-8% of AML in adults)
Abnormal accumulation of immature granulocytes called promyelocytes.
t(15;17) - PML/RARA gene - blocks differentiation of promyelocute to mature granulocyte
Targeted treatment ATRA (APL is unique among leukemias sue to its sensitivity to all-trans retinoic acid (ATRA; tretinoin, the acid form of vitamin A)
Acute myeloid leukaemia management
Blood and platelet transfusions
Allopurinol to prevent tumour lysis
Chemotherapy - Anthracycline, Cytarabine
Steroids
Sibling matched allogenic bone marrow transplant
Tretinoin (ATRA) if acute promyelocytic leukaemia suspected
Acute lymphoblastic leukaemia definition
Malignancy of immature lymphoid cells (which give rise to T cells and B cells).
Leads to arrest in the maturation of T and B cells, and promote incontrolled proliferation of lymphoblasts (a blast cell is a precursor cell which is a partially differentiated cell, it is unipotent)
Acute lymphoblastic leukaemia epidemiology
Commonest form of malignancy in children.
Associated with Down’s syndrome
Acute lymphoblastic leukaemia risk factors
Genetic predisposition, ionizing radiation (eg x rays) during pregnancy, and Down's syndrome are important associations, CNS involvement is common Previous chemo (certain meds eg etoposide)
Acute lymphoblastic leukaemia signs and symptoms
Anaemia, bleeding, infection (BM failure)
Hepatosplenomegaly
Peripheral lymphadenopathy
CNS involvement ( eg facial palsy)
Organ inflitration
SVC obstruction: red face, dilated superficial chest veins
Bone marrow failure and bone/joint pain
Acute lymphoblastic leukaemia 1st line investigations
FBC: anaemia,, thrombocytopaenia, neutropenia
Blood film: leukaemia blast cells
Bone marrow: increased cellularity
Lumbar puncture (should be performed to look for cns involvement)
CXR and CT scan to look for mediastinal and abdominal lymphadenopathy
Acute lymphoblastic leukaemia management
Chemo Steroids Intrathecal drugs eg methotrexate Blood transfusion IV fluids Infection control
Acute lymphoblastic leukaemia complications
Extremely vulnerable to infection
Prone to incontrolled and serious bleeding (lack of platelets)
Acute lymphoblastic leukaemia prognosis
The younger the patient is at diagnosis, the better the outlook
Chronic lymphocytic leukaemia (CLL) definition
Most common type of leukaemia
BM malignancy resulting in accumulation of mature B cells that fail to apoptose
Chronic lymphocytic leukaemia epidemiology
Most common leukaemia (>25%)
Adults 70+
Ppl with low immunity due to HIV/AIDS are three times more likely than the general population to develop leukaemia. Ppl on long term immunosuppression are at risk as well.
Chronic lymphocytic leukaemia key presentations
Often asymptomatic
Enlarged, subbery non-tender nodes
Chronic lymphocytic leukaemia signs and symptoms
Dependent on severity. may be:
- anaemic
- infection prone
- weight loss/sweats/anorexia
- hepatosplenomegaly
- enlarged render rubbery nodes
Chronic lymphocytic leukaemia 1st line investigations
FBC: high WCC with high lymphocytes
Blood film: small, mature lymphocytes
Chronic lymphocytic leukaemia management
- watch and wait
- blood transfusions
- stem cell transplant
- chemo
- monoclonal antibodies (eg anti-CD20 - rituximab)
- targeted therapy (eg bruton kinase inhibitors - ibrutinib)
Chronic lymphocytic leukaemia complications
Death is often due to infection or transformation to aggressive lymphoma (Richter’s syndrome)
- Autoimmune haemolysis, ITP
- Raised infection due to hypogammaglobulinaemia (= lower igg), bacterial, viral especially herpes zoster
- Marrow failure
- Progressive lymphadenopathy/hepatoplenomegaly
If someone comes in with repetitive similar infections (tonsilitis) do a blood count and blood film
Chronic myeloid leukaemia definition
BM malignancy that creates overproduction of mainly basophils, eosinophils, neutorphils
Chronic myeloid leukaemia epidemiology
Almost exclusively a disease of adults
Most often in people between 40-60 years old with a slight male predominance
CML is extremely rare (CLL is approx. 10x as common)
Chronic myeloid leukaemia aetiology
More than 80% patients have a translocation between chromosome 9 and chromosome 22 (‘Philidelphia chromosome’), which creates a ‘fusion gene’ from BCR and ABL kinase, which has tyrosine kinase activity that stimulates cell division
Chronic myeloid leukaemia signs and symptoms
Mostly chronic and insidious: wight loss, tiredness, fever, sweats
May be features of gout (due to purine breakdown)
Bleeding (platelet dysfunction)
Abdo discomfort - splenomegaly
Anaemia, infection (BM failure)
Signs: massive hepatosplenomegaly
Chronic myeloid leukaemia 1st line investigations
FBC: anaemia, raised myeloid cells
Bone marrow: increased cellularity
Reverse transcriptase PCR: Philidelphia chromosome t(9;22)
Chronic myeloid leukaemia management
Chemo
TKI (Tyrosine Kinase Inhibitor eg Imatinib)
Stem cell transplant
Chronic myeloid leukaemia complications
Can transform to ‘blast phase’ - acute leukaemia
Chronic myeloid leukaemia prognosis
Depends on treatment response, may be chronic controlled disease
Hodgkin lymphoma definition
Malignant tumour of the lymphatic system characterised by the presence of Reed-sternberg cells and associated abnormal and smaller mononuclear cells originating from B lymphocytes
Hodgkin lymphoma epidemiology
Young adults and elderly
Male predominance
Associated with Epstein-Barr virus and lupus
Hodgkin lymphoma presentation
Fever and sweating Chest discomfort with a cough or dyspnea Enlarged rubbery non-tender nodes Systemic 'B' symptoms eg fever Painful nodes on drinking alcohol
Hodgkin lymphoma diagnosis
FBC: anaemia, high ESR (erythrocyte sedimentation rate)
CXR: wide mediastinum: mediastinal masses
PET scan
Reed sternerg cells - giant cells usually derived from B cells
Ann Arbor staging system:
- Stage I: involvement of one lymph-nide region or lymphoid structure (eg spleen, thymus)
- Stage II: two or more lymph-node regions on the same side of the diaphragm
- Stage III: lymph nodes on both sides of the diaphragm
- Stage IV: involvement of extranodal dies
Hodgkin lymphoma management
Chemotherapy, ABVD: - Adriamycin - Bleomycin - Vinblastine - Dacarbazine Autologous marrow transplant
Non-Hodgkin lymphoma definition
Broad group of all lymphomas (malignancy originating from lymphocytes) except Hodgkins
Non-Hodgkin lymphoma epidemiology
Aduts 40+
Associated with EBV and Burkitt’s lymphoma
Family history increases risk
Over 5x more common than Hodgkins
Non-Hodgkin lymphoma presentation
Fever and sweating
Enlarged rubbery non-tender nodes
Systemic ‘B’ symptoms eg fever
GI and skin involvement
Non-Hodgkin lymphoma diagnosis
FBC: anaemia, high ESR Raised lactose dehydrogenase Lymph node biopsy Bone marrow biopsy for classification Can also use Ann Arbor staging
Non-Hodgkin lymphoma management
Steroids Monoclonal antibodies to CD20: Rituximad CHOP regimen: - cyclophosphatase - hydroxy-daunorubicin - Vincristine - Prednisolone
Malaria definition
Parasitic infection carried by mosquitoes - the protozoan parasite invades RBCs = causing an intermittent and remittent fever.
Malaria aetiology
Plasmodium parasites - 5 types cause malaria in humans Plasmodium falciparum - Africa - most common type of malaria parasite - causes most malaria deaths worldwide
Plasmodium vivax
- Asia/South America
- milder symptoms than PF
- can stay in liver for up to 3 years > relapses
Plasmodium ovale
- uncommon
- West Africa
- can remain in liver for several years without symptoms
Plasmodium malariae
- quite rare
- Africa
Plasmodium knowlesi
- very rare
- Southeast Asia
Malaria key presentations
Initial symptoms of malaria are flu-like and include:
- a high temp pf 38C or above
- feeling hot and shivery
- headaches
- vomiting
- muscle pains
- diarrhoea
- generally feeling unwell
Symptoms occur in 48-hour cycles
Malaria 1st line investigations
Travel history Thick and thin blood smears - negative film can be seen - if negative, 2 more films should be sent over the next 48 hours Rapid diagnostic tests Detect parasitic antigens PCR FBC, LFTs, U&Es, blood gases, blood culture CXR, lumbar puncture
Malaria differential diagnosis
Pharyngitis, bronchitis, pneumonia, bronchopneumonia, worsening of asthma, pleurisy
Malaria management
Prevention
- insect repellents
- antimalarials
For severe/complicated/P.Falciparum malaria:
- IV artesunate
- if IV artesunate not available: IV quinine and doxycycline
For uncomplicated/non-falciparum malaria:
- iral cholorquinine
- artemisinin combination therapy (ACT) for mixed infection
- Primaquine if P. ovale or P vivax (as these species can form hypnozoites in liver which lie dormant - primaquine eliminates these) - contraindicated in pregnancy, breastfeeding, or G6PD deficiency
Ensure that all cases of malaria have been notified to Public Health England
Malaria complications
Anaemia, cerebreal malaria, liver failure/jaundice, shock - drop n BP, pulmonary oedema, acute respiratory distress syndrome (ARDS), hypoglycaemia, kidney failure, swelling and rupturing of spleen, dehydration
Thalassaemia definition
Disorder of quantity; haemoglobinopathy
Reduced Hb production
Thalassaemia epidemiology
African Americans and in people of Mediterranean and Southeast Asian descent
Thalassaemia aetiology
Mutations in the Hb beta (HBB) gene
Thalassaemia risk factors
Family history
Thalassaemia pathophysiology
Globin chain disorders resulting in diminished synthesis of >1/= globin chains = reduced Hb
Hb will be destroyed by spleen for being abnormal
- Also RBCs can’t be made normally because of insufficient erythropoiesis from insufficient globin chains of both types
2 types of BT - alpha and beta
Beta-T occurs from mutational genetic abnormalities
Alpha-T occurs though delusional genetic abnormalities
What affects the phenotype of the disease?
ALPHA
Can be a carrier with just 1/2 abnormal genes.
Varying amounts of abnormal genes can change phenotype of disease:
- 1 abnormality - normal or minimal change to Hb, MCV and MCH (mean corpuscular haemoglobin)
- 2 abnormalities - more marked changes, MHC <25pg (can either be alpha 0 or alpha +
- 3 abnormalities - moderately severe Hb 30-100g/l, MCH 15-20pg (hbH disease)
- 4 abnormalities - hydrops fetalis (Hb Bart’s hydrops fetalis is the most severe form of alpha-thalassemia and is almost always lethal
BETA
Beta thalassemia can be
- thalassemia major (transfusion dependent)
- thalassemia intermedia (less severe anaemia/can survive without regular transfusions)
- thalassemia carrier/heterozygote (asymptomatic)
Gives partial malaria resistance
Thalassaemia key presentations
Beta Thalassemia Major - Age at presentation: 1st year of life (6-12 months as adult Hb starts to replace foetal).
Clinical presentation with severe symptoms: failure to feed, listless, crying, pale, hypertrophy of bone marrow causes bone deformities and facial structure changes
Hb 40-80g/l but normal ferritin
A-thalassaemia = anaemia symptoms
Thalassaemia 1st line investigations
Blood film shows large and small cells, pale cells and nucleated cells
- decreased Hb 30-70 g/l, MCV and MHC very low
- increased HbF >90%
ALPHA
- complete blood count (CBC). This test checks the size, number and maturity of different blood cells in a set volume of blood
- haemoglobin electrophoresis. A lab test that tells what type of haemoglobin is present
- ferritin. This test is done to ruleout iron-deficiency anaemia
- DNA testing. This test identifies which alpha globin genes are present, absent, or damaged
Thalassaemia gold standard investigations
PCR only diagnosis test (Hb electrophoresis which will show variant haemoglobins will not diagnose it)
Thalassaemia differential diagnosis
Other types of inherited / Fe deficiency anaemia
Thalassaemia management
Blood transfusions: most will need to have regular blood transfusions to treat anaemia
Chelation therapy: to remove excess iron (desferrioxamine)
Stem cell or bone marrow transplants: the only cute, but rarely done because of risks eg graft vs host
Splenectomy:
- many patients require splenectomy to decrease blood consumption and transfusion requirement with the ultimate goal of reducing iron overload
- it is only done in very severe cases
- vaccinations given as removal of spleen makes you much more at risk of developing severe infections
Thalassaemia complications
Iron overload due to transfusion therapy is a big problem. Iron deposits in the heart, liver, pituitary, pancreas etc. causing hypothyroidism, hypocalcaemia, and hypogonadism.
Can be mitigated by iron-chelators.
Splenectomy if hypersplenism persists with increasing transfusion requirements - this is best avoided until > 5yrs old due to risk of infections
Abnormal bone growth, osteoporosis etc
Extra medullary hematopoiesis
Polycythaemia vera definition
A type of philidelphia chromosome negative myeloproliferative neoplams. Characterised by erythrocytosis and often thrombocytosis, leukocytosis and splenomegaly
Polycythaemia vera epidemiology
PV is rare - approx. 2 cases/100,000 per year
Polycythaemia vera aetiology
Primary: Polycythaemia rubra vera - ‘overactive bone marrow’
- genetic mutation
Need more RBCs - body compensates by making too much, initiated by ‘secondary causes’
Secondary causes
- lung disease
- alcohol
- ‘apparent erythrocytosis’ - not enough liquid in blood (don’t actually have too many RBCs)
- EPO producing tumours
Polycythaemia vera pathophysiology
> 95% have an activating mutation in JAK2 ‘JAK2V617F’, that means EPO signally is constantly ‘switched on’
Polycythaemia vera key presentations
Elevated haematocrit and haemoglobin, may have splenomegaly. May present with thrombosis
Polycythaemia vera signs and symptoms
Plethoric appearance (red face)
Erythromelalgia - tenderness or painful burning and/or redness of fingers, palms, heels or toes
Pruritus - classically after contact with warm water
Splenomegaly
Polycythaemia vera 1st line investigations
Haemoglobin: high
Haematocrit: high (>52% in men, >48% in women)
WBC: usually high
Platelet count: usually high
MCV: usually low and coexisting with iron deficiency
JAK2 gene mutation screen
Polycythaemia vera differential diagnosis
‘Apparent erythrocytosis’ - not enough liquid in blood (don’t actually have too many RBCs)
Polycythaemia vera management
Venesection
Aspirin
Hydroxycarbamide - suppresses bone marrow
PLUS manage other CV risk factors
(ie blood pressure, cholesterol, diabetes)
Polycythaemia vera complications
Arterial thrombosis (stroke, myocardial infarction)
Venous thrombosis (deep vein thrombosis, portal vein thrombosis, splanchnic vein thrombosis)
Haemorrhage
‘Transform’ to acute leukaemia, myelofibrosis
Polycythaemia vera prognosis
Median 13 years
Bleeding - immune thrombocytopenic purpura (ITP) definition
Immune disorder in which the blood doesn’t clot normally
Bleeding - immune thrombocytopenic purpura epdemiology
ITP is more common among young women
Children
Bleeding - immune thrombocytopenic purpura aetiology
May be triggered by infection with HIV, hepatitis or H. pylori
Bleeding - immune thrombocytopenic purpura risk factors
Rheumatoid arthritis, lupus and antiphospholipid syndrome
Age <10 or >65
Bleeding - immune thrombocytopenic purpura pthophysiology
Mostly due to antibody production against platelets. Sometimes T-cells directly attack platelets.
Children may develop ITP after a viral infection and usually recover fully without treatment. In adults, the disorder is often long term.
Bleeding - immune thrombocytopenic purpura clinical manifestations
Easy or excessive bruising Superficial bleeding into the skin that appears as pinpoint-sized reddish-purples sports (petechiae) that look like a rash, usually on the lower legs Bleeding from the gums or nose Blood in urine or stools Unusually heavy menstrual flow
Bleeding - immune thrombocytopenic purpura investigations
FBC: low platelet count
- <100 x 10^9/L
Peripheral blood near
- distinguish true and pseudothrombocytopenia
- should be no evidence of myelodysplasia or other disorder
- RBC/WBC = normal
Additional investigations
- bone marrow biopsy = increased megakaryocytic
- HIV serology = negative
- helicobacter pylori breath test or stool antigen test = negative
- hepatitis C serology = negative
- thyroid function tests = maybe hyper/hypothyroid
Bleeding - immune thrombocytopenic purpura management
Regular monitoring and platelet checks If chronic will need treatment Combination therapy - corticosteroids - IV immunoglobulin - platelet transfusion
Medications
- steroids
- immune globulin
- drugs that boost platelet production (romiplostim - Nplate; eltrombopag - Promacta)
Splenectomy
Bleeding - immune thrombocytopenic purpura complications
Anaemia, tiredness, internal bleeding, infection
Bleeding - immune thrombocytopenic purpura prognosis
Good in children - 80% remission
Increased mortality with age
Von Willebrand disease definition
Congenital lifelong bleeding disorder in which your blood doesn’t clot well due to low levels of VWF
Von Willebrand disease aetiology
Autosomal dominant/recessive genetic mutation passed from parents
Autosomal recessive is more severe
Von Willebrand disease pathophysiology
There are 3 types Type 1: - mildest/most common type - reduced level of VWF in blood - bleeding is only a problem with surgery, injury
Type 2:
- VWF does not work properly
- bleeding = more frequent and heavier than in type 1
Type 3:
- most severe/rarest
- very low levels of VWF or none at all
- bleeding from mouth, nose and gut is common, and you can have joint and muscle bleeds after an injury
Von Willebrand disease clinical manifestations
Excessive bleeding from an injury or after surgery or dental work
Nosebless that don’t stop within 10 mins
Heavy or long menstrual bleeding
Blood in your urine or stool
Easy bruising or lumpy bruises
Von Willebrand disease investigations
FBC - see which proteins are present in blood
Pt test - test clotting time, factors 1,2,5,7,10
APTT - test clotting time, factors 8,9,11,12
Fibrinogen (CF1) test - ability to form clot
Von Willebrand disease diagnostic tests
Factor VIII clotting activity
- measure amount of factor VIII in the blood
Von Willebrand factor antigen
- measure the amount of VWF in blood
Ristocetin cofactor or other VWF activity
- to measure how well the VWF works
Von Willebrand factor multimers - to measure th makeup or structure of the VWF
Platelet aggregation tests - to measure how well the platelets are working
Von Willebrand disease differential diagnosis
Hemophilia A, Hemophilia B, Bernard-Soulier syndrome
Von Willebrand disease management
Can;t be cured instead managed
Medication to help stop bleeds
- desmopressin - available as a nasal spray or injection
- tranexamic acid - available as tablets, a mouthwash or an injection
- von willebrand factor concentrate - available as an injection
Treating heavy periods (oral contraceptive pill, IUS)
Von Willebrand disease complications
- anaemia
- swelling and pain
Thrombotic thrombocytopenic purpura definition
Blood disorder in which platelet clumps form in small blood vessels. This leads to a low platelet count (thrombocytopenia)
Thrombotic thrombocytopenic purpura epidemiology
TTP most often occurs after 40 years of age, but congenital forms can occur in children
Thrombotic thrombocytopenic purpura aetiology
30-50 yos
Black
Female
Thrombotic thrombocytopenic purpura risk factors
Obesity
Pregnancy
Thrombotic thrombocytopenic purpura clinical manifestations
- non-specific prodrome
- severe neurological symptoms (coma, focal abnormalities, seizures)
- mild neurological symptoms (headache, confusion)
- fever
- digestive symptoms (nausea, vomiting, diarrhoea, abdo pain)
- weakness
- bleeding symptoms (purport, ecchymosis, menorrhagia)
Thrombotic thrombocytopenic purpura investigations
- platelet count = decreased
- haemoglobin = <8 g/L
- haptoglobin = decreased
- peripheral smear = Schistocytes might be absent from the blood film
Thrombotic thrombocytopenic purpura management
ACUTE
Acquired (idiopathic) TTP: acute episode
ONGOING
Acquired (idiopathic) TTP: following resolution of acute episode
Haemophilia deinfiiton
Inherited bleeing disorder, characterised by deficiency of coagulation factor VIII or XI
Haemophilia definition
Inherited bleeding disorder, characterised by deficiency of coagulation factor VIII or XI
Haemophilia epidemiology
Almost exclusively in males due to an X-linked pattern of inheritance.
Family history
>60yrs
Haemophilia risk factors
Autoimmune disorders, inflammatory bowel disease, diabetes, hepatitis, pregnancy, postnatal, or malignancy (acquired haemophilia)
Haemophilia pathophysiology
Graded as mild, moderate, or severe, based on factor VIII or IX level
Haemophilia clinical manifestations
Musculoskeletal bleeding is the msot common type of haemorrhage - bleeding into muscles
- prolonged bleeding following heel prick or cricumcision
- excessive bruising/haematoma
- fatigue
- menorrhagia and bleeding following surgical procedures or childbirth (female carriers)
- extensive cutaneous purpura (acquired haemophilia)
Haemophilia investigations
Activated partial thromboplastin time (aPTT)
- usually prolonged
Plasma factor VIII and IX assay
- decreased or absent factor VIII or IX levels;
Mixing study
- aPTT corrected
FBC = usually normal PT = normal
Head or neck CT - may show acute bleeding
Head or neck MRI - may show acute bleeding
Abdo ultrasound or abdominopelvic CT scan
- may demonstrate acute intra-abdnominal bleeding
Oseophagogastroduodenoscopy or colonoscopy
- may demonstrate acute gastrointestinal bleeding
Haemophilia management
Preventitive
Haemophilia A
- regular injection of medicine octocog alfa (Advate) - engineered CF8 (causes rash)
Haemophilia B
- regular injections nonacog alfa (BeneFix) - engineered CF9. (causes headaches, nausea, altered taste)
On demand HA = injections of - Octocog alfa - Desmopressin - stimulates CF8 (causes headaches/nausea) HB = injections nonacog alfa
Haemophilia complications
COmplication of treatment is the development of inhibitory antibodies against infused factor VIII or IX
- joint problems
Haemophilia prognosis
People haemophilia lead a near normal life expectancy
Haemolytic Uraemic Syndrome (HUS) definition
Characterised by microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury. Around 90% occur in the paediatric population due to shiga toxin -producing E.coli
Haemolytic Uraemic Syndrome pathophysiology
Common feature is endothelial injury leading to microvascular thrombosis and resulting microangiopathic haemolytic anaemia, thrombocytopenia and AKI
Haemolytic Uraemic Syndrome key presentations
Diarrhoea, especially bloody diarrhoea in children under the age of 5
Haemolytic Uraemic Syndrome 1st line investigations
FBC: anaemia, thrombocytopenia
Blood smear: presence of schistocytes
Renal function: raised creatinine, electrolyte abnormalities
