Haematology And Oncology Flashcards
Causes of anaemia in infancy
Physiologic anaemia of infancy Anaemia of prematurity Blood loss Haemolysis Twin-twin transfusion Haemolytic disease of the newborn Hereditary spherocytosis G6PD deficiency
Physiologic anaemia of infancy
Normal dip in Hb at 6-9weeks
Due to high oxygen delivery, decreased production Hb
EPO production decreases in kidneys
Less bone marrow stimulation
Why are premature neonates more likely to become anaemic?
Less time in utero receiving iron from mother
RBC creation can’t keep up with rapid growth in first few weeks
Reduced EPO levels
Blood tests remove a significant portion of the circulating volume
Causes of anaemia in older children
Iron deficiency anaemia, diet Blood loss: menstruation in older girls Sickle cell anaemia Thalassaemia Leukaemia Hereditary spherocytosis Hereditary elliptocytosis Sideroblastic anaemia
Helminth infection:
Roundworm, hookworm, whipworms
Albendazole or mebendazole
Causes of microcytic anaemia
TAILS
Thalassaemia Anaemia of chronic disease Iron deficiency anaemia Lead poisoning Sideroblastic anaemia
Causes of normocytic anaemia
3As
2Hs
Acute blood loss Anaemia of chronic disease Aplastic anaemia Haemolytic anaemia Hypothyroidism
Causes of macrocytic anaemia
Megaloblastic
Megaloblastic anaemia: impaired DNA synthesis prevents cell from dividing normally
B12 deficiency
Folate deficency
Normoblastic macrocytic anaemia
Alcohol Reticulocytosis (haemolytic anaemia or blood loss) Hypothyroidism Liver disease Azathioprine
Symptoms of anaemia
Tiredness SoB Headaches Dizziness Palpitations Worsening of other conditions
Symptoms specific to iron deficiency anaemia
Pica: cravings for dirt, ice
Hair loss: iron deficiency anaemia
Genetic signs of anaemia
Pale skin
Conjunctival pallor
Tachycardia
Raised RR
Signs of iron deficiency anaemia
Koilonychia
Angular cheilitis
Atrophic glossitis
Brittle hair and nails
Sign of haemolytic anaemia
Jaundice
Sign of thalassaemia anaemia
Bone deformities
Complications of chemotherapy
Failure to treat leukaemia Stunted growth and development Immunodeficiency and infections Neurotoxicity Infertility Secondary malignancy Cardio toxicity
Investigations for anaemia
FBC Blood film Reticulocyte count Ferritin B12 and folate Bilirubin: raised in haemolysis Direct Coombs test: positive in autoimmune haemolytic anaemia Haemoglobin electrophoresis: thalassaemia, sickle cell anaemia
Iron deficiency anaemia causes
Dietary insufficiency
Loss of iron, heavy menstruation
Inadequate iron absorption, e.g. Crohn’s disease
PPI as iron needs acid in stomach to stay soluble 2+
Coeliac/ Crohn’s reduce absorption in duodenum and jejunum
How to calculate transferrin saturation
Transferrin saturation = serum iron/ total iron binding capacity
Should be around 30%
Increased value of results with:
Iron supplements
Acute live damage
Management of iron deficiency anaemia
Treat underlying cause
Dietician input
Ferrous sulphate or ferrous fumarate
SE: constipation and black stools
Leukaemia
Cancer of stem cells in bone marrow
Unregulated production of certain types of blood cells
Types of leukaemia
Acute lymphoblastic leukaemia: most common in children
Acute myeloid leukaemia
Chronic myeloid leukaemia: rare
Epidemiology leukaemia
All peaks at 2-5 years
Males > females
Pathophysiology leukaemia
Genetic mutations, infections
Disruption in regulation and proliferation of lymphoid precursor cells in bone marrow
Excessive production of immature blast cells
Drop in numbers of functional RBC, WBC, platelets
Leukaemia risk factors
Radiation exposure Down’s syndrome Kleinfelters syndrome Noonan syndrome Fanconis anaemia
History of leukaemia
Anaemia: lethargy, pale Thrombocytopenia: easy bruising, bleeding, petechiae Leukopenia: unexplained fevers, infections Bone pain: hyper plastic marrow Weight loss Malaise CNS involvement: headaches, seizures Night sweats Abdominal pain
Leukaemia examination
Pale
Unexplained bruising, bleeding
Lymphadenopathy
Hepatosplenomegaly
DD bruising
Leukaemia Immune thrombocytopenia Trauma Non-accidental injury Ehler-Danlos VitC deficiency
DD lymphadenopathy
Infective: Infectious mononucleosis HIV, seroconversion illness Eczema with secondary infection Rubella Toxoplasmosis CMV TB Roseola infantum
Neoplastic:
Leukaemia
Lymphoma
Others:
Autoimmune conditions: SLE, rheumatoid arthritis
Sarcoidosis
Drugs: phenytoin, allopurinol, isoniazid
Graft vs host disease
DD pallor
Pernicious anaemia Axillary/ brachial embolus Acute lymphoblastic leukaemia Neonatal hypoglycaemia Myeloma Neuroblastoma
Acute lymphoblastic leukaemia investigations
FBC: pancytopenia Blood film: blast cells CXR to exclude mediastinal mass Bone marrow aspirate/ trephine Lumbar puncture
Risk scoring acute lymphoblastic leukaemia
Cytogenetic testing
Age: 1-10 at presentation have a good prognosis
WCC>50 poorer prognosis
Females > male prognosis
CNS involvement: blasts within CSF, poorer prognosis
Leukaemia characteristics
Diagnosis of leukaemia
Urgent FBC within 48 hours
Management of acute lymphoblastic leukaemia
Immediate
Resuscitate and stabilise unwell child
If high WCC: hyperhydration to prevent hyper viscosity
If mediastinal mass: steroids to reduce airway compromises
Infection/ sepsis: broad spectrum antibodies
Definitive and long-term management of acute lymphoblastic leukaemia
UKALL 2011 protocol
IV chemotherapy, orally, intra-thecally (into CSF)
Supportive care with blood products (red cells, platelets)
Prophylactic anti-fungal therapy throughout treatment
No role for radiotherapy in management
Maintenance treatment is 2 years for girls and 3 years for boys
Prognosis and complications of acute lymphoblastic leukaemia
90% survival Infertility Avascular necrosis Peripheral neuropathy Anxiety
Regular follow-up and assessment for 5 years after completion of treatment
Acute myeloid leukaemia pathophysiology
Cancer of blood and bone marrow
Myeloid stem cell-> RBC, WCC, platelets
Self-renewal and developmental arrest of progenitor cells at a particular point in their differentiation
Creating immature cells (myeloblasts) that infiltrate bone marrow, RES
Less room in blood and bone marrow for health cells
Infection, anaemia or easy bleeding can occur
Leukaemia cells can spread to CNS, skin and gums. Occasionally leukaemia cells form a solid tumour called a chloroma or granulocytic sarcoma
FAB classification of AML
MO: AML with minimal evidence of myeloid differentiation M1: AML without maturation M2: AML with maturation M3: acute promyelocytic leukaemia M4: acute myelomonocytic leukaemia M5: acute monocytic/ monoblastic leukaemia M6: acute erythroleukaemia M7: acute megakaryoblastic leukaemia
Risk factors for acute myeloid leukaemia
Down’s syndrome Li-Fraumeni syndrome Aplastic anaemia Myelodysplasia Affected sibling
Clinical features of acute myeloid leukaemia
Classification signs of anaemia, thrombocytopenia, hepatosplenomegaly, or lymphadenopathy
Bone marrow failure in AML
Symptoms/ signs
Anaemia: pallor, lethargy, shortness of breath, dizziness, palpitations, reduced exercise tolerance
Neutropenia: fever, recurrent infections, unusual infections
Thrombocytopenia: brushing, petechia, epistaxis
Blast infiltration of other tissues in acute myeloid leukaemia
Symptoms/ signs
Bone marrow: limb pains
Reticuloendothelial: hepatosplenomegaly, lymphadenopathy, expiratory wheeze (secondary to a mediastinal mass due to lymphadenopathy or thymic infiltration/ expansion)
Testes: testicular enlargement
Systemic effects of cytokines released by leukaemic cells and of increased plasma viscosity (leucoastasis) due to extremely high WCC
Signs/symptoms
Acute myeloid leukaemia
Cytokine release: fever, malaise, fatigue, nausea
Leucostasis: headache, vomiting, cranial nerve palsies, seizures, stroke, shortness of breath, heart failure
DD of acute myeloid leukaemia
Acute lymphocytic leukaemia: pancytopenia
Iron deficiency anaemia: pallor, lethargy, SoB
Immune thrombocytopenic purpura
Immunodeficiency: recurrent infections
Acute myeloid leukaemia
Laboratory tests
FBC: pancytopenia
Blood film: blasts present, elevated overall WCC, atypical cells in blood film, presence of leukoerythroblastic features
Acute myeloid leukaemia
Imaging or invasive tests
CXR: information on whether any of the lymph glands in chest are enlarged
Bone marrow aspirate and trephine- bone marrow examination allows definitive diagnosis of acute leukaemia
Lumbar puncture: checks for leukaemia cells in CSF, may require intra-thecal chemotherapy as part of their treatment
Biopsy: AML diagnosed by biopsy of a chloroma
Bone marrow examination in acute myeloid leukaemia
Aspirate: morphological, immunological, genetic information. Information used alongside clinical factors and initial response to chemotherapy
Light microscopy: allows classification as acute lymphoblastic leukaemia or acute myeloid leukaemia
Immunophenotyping using flow cytometry, identifies patterns of cell surface antigens associated with particular subtypes of acute myeloid leukaemia
Management of acute myeloid leukaemia
Initial management
Indication; induces remission
Post-remission consolidation/ intensification; reduces risk of relapse
Management of acute myeloid leukaemia
Induction
Two cycles of chemotherapy given four weeks apart
Examining bone marrow after each cycle will allow monitoring of response to induction
Aim of induction: no evidence of leukaemia in bone marrow after induction is completed (remission)
Definitive and long term management of acute myeloid leukaemia
Post-remission therapy
Bone marrow transplant
Post-remission therapy AML
Further chemotherapy to destroy any remaining leukaemia cells and to prevent recurrence
Varying number of cycles of intensive chemotherapy and/or allogenic haematopoeitic stem cell transplantation
Bone marrow transplant AML
Reserved for children with an suboptimal response to standard chemotherapy Or if leukaemia relapses
20% of AML will require a transplant
Complications of treatment of acute leukaemia
Neutropenic sepsis: multi-organ failure Bone marrow suppression (myelosuppression), pancytopenia Nausea and vomiting Mucositis Hair loss
Specific side effects of chemotherapy agents
Doxorubicin- cardiotoxicity
Vincristine- peripheral neuropathy
Cyclophosphamide- reduced fertility
Cytarabine- hepatotoxicity
Lymphoma
Malignancy of the lymphatic system
Divided into Hodkin’s lymphoma and non-Hodgkins lymphoma
Epidemiology of lymphoma
Accounts for 10% of childhood cancers
More common in boys than girls
More common in older children
More than half of lymphoma cases are non-Hodgkin lymphoma
Pathophysiology of lymphoma
Multifactorial development; infection, genetic factors, environmental exposures
Lifestyle factors in adults: obesity, smoking, alcohol intake
History of lymphoma
EPV implicated in development of lymphoma. Immunosuppressed patients and those who have been treated for other cancers in the past are also at increased risk of lymphoma
B symptoms: weight loss, night sweats, fevers
Lethargy and anorexia
Visible or palpable mass
Examination of lymphoma
Non-tender lymphadenopathy
Non visible/ palpable if mediastinal or intra-abdominal lymph nodes are involved
Mediastinal lymphadenopathy: cough, wheeze or other difficulty in breathing, SVC obstruction or airway compromise can occur
DD of lymphoma
Reactive lymphadenopathy, History of recent infection. If lymph nodes themselves have become infected (lymphadenitis) they are likely to be tender and potentially fluctuant if an abscess has formed
Leukaemia: lymphadenopathy with signs/symptoms of anaemia and/or thrombocytopenia
Lymphadenopathy: can also be a sign of metastatic malignancy from another site
Lymphoma laboratory tests
Blood tests: FBC
U&E for tumour lysis syndrome can occur before treatment begins in lymphomas with rapid cell turnover
LDH: levels are usually elevated
Lymphoma imaging
USS of the area can help identify other nodes, and assists with biopsy
CXR: required if there are symptoms of mediastinal node involvement
Full body CT to determine extent of disease
Biopsy: lymph node biopsy for definitive diagnosis
Risk scoring lymphoma
Stage 1: single group of lymph nodes or a single organ
Stage 2: disease is present in 2 or more groups of lymph nodes or organs on the same side of the diaphragm
Stage 3: disease is present in lymph nodes or organs on both sides of the diaphragm
Stage 4: diffuse involvement of lymph nodes and organs such as the liver and bones
Lymphoma B symptoms
Associated with worse prognosis
Weight loss
Night sweats
Fevers
Immediate management of lymphoma
Presence of a mediastinal mass with potential airway compromise is an emergency
Treatment with high dose steroids and airway support if required
SVCO may require stenting of veins to keep them patent, usually resolve with treatment of the underlying malignancy
Suggestion of tumour lysis syndrome, then hyperhydration is important. Allopurinol or rasburicase are also used
Definitive and long-term management of lymphoma
Treatment is with chemotherapy ans possibly radiotherapy, depending on the stage of disease
Prognosis of lymphoma
Hodgkins > non-Hodgkins
Majority will recover coompletley
Complications of lymphoma
Tumour lysis syndrome: rapid lysis of tumour cells cases release of large amounts of phosphorous, potassium and calcium
Leading to potential kidney damage
Neutropenia, alopecia, sub-fertility
Life-long follow up for complications
Nephroblastoma
Wilm’s tumour
Most common renal tumour affecting children
Usually unilateral but can be bilateral
Nephroblastoma epidemiology
Affects 80 children per year in UK
Generally presents in the pre-school age group
3.5years being median age at diagnosis
Slight female predominance
Pathophysiology of nephroblastoma
Tumours arise from nephrogenic rests;embryonal remnants seen in around 1% of infants at birth
Risk factors for nephroblastoma
Children with certain genetic and overgrowth syndromes
WAGR (Wilms tumour, aniridia, genitourinary malformations, retardation)
Denys-drash and beckwith-wiedemann
Nephroblastoma history
Abdominal mass found incidentally
Noted by parents during bathing or dressing in an otherwise well child
Abdominal swelling, abdominal pain, fever, or haematuria
nephroblastoma examination
Abdominal distension
Unilateral or bilateral palpable masses
Hypertension may be noted
Rarely, in cases of advanced disease, signs of compression of other intra-abdominal structures
DD of nephroblastoma
Polycystic kidney disease and hydronephrosis
Most common malignant DD in a pre-school child is a neuroblastoma: presents with HTN, abdominal pain or fever
Neuroblastoma: periorbital ecchymosis, abdominal mass which crosses midline, signs of bone marrow infiltration
Nephroblastoma laboratory tests
FBC
U&E
Urine dip for haematuria
Evaluate child’s general heath at presentation
Nephroblastoma imaging or invasive tests
Initial characterisation of a renal/ abdominal mass: USS, CT/MRI for staging
Biopsy
Risk scoring nephroblastoma
1: tumour is only confined to the kidney and can be completely removed with surgery
2: tumour has begun to spread beyond the kidney, but can still be completely removed with surgery
3: tumour cannot be completely surgically resected because it has spread to neighbouring lymph nodes or ruptured before/during surgery
4: distant metastases, most commonly to lungs
5: bilateral tumours
Initial management nephroblastoma
Supportive care
Treat co-existing infection and ensure nutrition and hydration are optimised
Definitive and long-term management nephroblastoma
Stage 1 and 2 tumours may be treated solely with surgery
No additional benefit to giving chemotherapy which has additional risks later in life
Aim of surgery: preserve renal function while removing the malignant tissue
Chemotherapy: used to reduce the volume of malignant tissue before surgery, or to treat any areas of malignant disease not removed by surgery (nephrectomy)
Surgery consists of nephrectomy: in bilateral disease, attempt to preserve as much functioning renal tissue as possible
Complications and prognosis nephroblastoma
Steps must be taken to protect the remaining kidney
Maintain blood pressure
Avoidance of contact sports, which could lead to abdominal trauma
Monitor for cardiotoxicity and/or radiotherapy
Neuroblastoma
Paediatric cancer
Derived from neural crest cells, arising in adrenal glands or abdominal sympathetic chain
Most common cancer in children <1 year old, much less common in >5s
Epidemiology of neuroblastoma
Affects around 90 children per year in the UK
Most common solid tumour in children under one year of age
36% of neuroblastomas arise from the medulla of the adrenal glands, with another 18% arising from the sympathetic chain
10% are bilateral, 10% arise from an unknown source and are first diagnosed as secondary metastases
Pathophysiology of neuroblastoma
Neuroblastoma arises from poorly differentiating embryonic cells (blasts)
In this case from neural crest
Neural crest cells are derived from developing ectoderm, and normally migrate throughout the body to form SNS and adrenal medulla
When migration is stalled, neural crest cells have the potential to acquire mutations that eventually lead to neuroblastoma
Associated with genetic mutations, MYCN and ALK oncogenes, as well as loss-of-function of the tumour suppressor PHOX2B
Risk factors for neuroblastoma
No identified cause
Hirschsprung’s disease
Congenital central hypoventilation syndrome
History of neuroblastoma
Abdominal distension
Fatigue
Appetite loss
Weight loss
Increased catecholamine: sweating, agitation
Metastasis: bone pain that prevents sleep, recurrent infections
Compression of SNS can lead to urinary incontinence
Occasionally, neuroblastomas can arise from the thoracic portion of sympathetic chain, causes SOB and chest pain
Neuroblastoma examination
Dense abdominal swelling, across midline
Hypertensive and tachycardia due to excess catecholamine synthesis
Symptoms of metastasis: periorbital bruising for children with metastases to skull base
Neuroblastoma cells can metastasise to dermis: scattered purpura across skin to give blueberry muffin rash (non-specific)
Bone metastases: bone marrow infiltration, evidence of recurrent infections and thrombocytopenic purpura
Neuroblastoma differentials
Abdominal mass:
Cysts: hepatic, polycystic kidney disease
Hyperplasia: pyloric stenosis, hepatomegaly, splenomegaly
Neoplasia: Wilm’s tumour, lymphoma, rhabdomyosarcoma, hepatoblastoma
Blueberry muffin rash: TORCH infections or acute myeloid leukaemia
Lab tests neuroblastoma
Look for products of catecholamine breakdown: homovanilic acid, vanillylmandelic acid in urine
90% of patients will have raised HMA and VMA
Additionally: bone marrow and skin biopsies, evidence of metastasis to these sites
Neuroblastoma imaging
USS: paediatric abdominal lumps
MRI second line
For thoracic neuroblastomas: CXR
Definitive test for neuroblastoma: MIBG scan
Radioisotope of iodine is injected, and two scans are taken 24 hours apart
Iodine stays in tumour, becoming an intensely dark region on the scan
90-95% of children with neuroblastoma will have positive features on the MIBG-scan
Staging for neuroblastoma
Imaging
Neuroblastoma risk group
1: fully resectable at surgery
2A: tumour is unilateral but not fully resectable, no spread to local lymph nodes
2B: tumour is unilateral but is not resectable, with spread to ipsilateral lymph nodes
3: tumour has crossed midline, or spread to Contralateral lymph nodes
4: distant metastasis outside of local lymph nodes
4S: metastases confined to liver, skin or bone marrow in <18monyjhs
Staging for neuroblastoma
Surgical observations
L1: localised tumour that doesnt involve vital structures (surgically resectable)
L2: localised tumour that does involve vital structures (non-resectable)
M: distant metastases (excludes local lymph node metastases)
MS: metastases confined to liver, skin or bone marrow in patients <18months old
Management of neuroblastoma
<18months:
Will regress to a benign ganglioma
Monitoring
Older children, aggressive disease:
Surgery
L1- curative
L2;- need adjuvant chemotherapy or radiotherapy
Factors giving improved neuroblastoma prognosis
Younger age at diagnosis
Assigned female at birth
Lesser tumour stage at diagnosis
MYCN mutation absent
Complications of neuroblastoma
Relapse
Opsoclonus myoclonus ataxic syndrome: autoimmune disorder arising from antibody self-reactivity to proteins from dying neuroblast cells, which then lead to an immune reaction to CNS (cerebellum)
Opsoclonus: uncontrolled, irregular eye movements
Myoclonus: muscle spasm
Ataxia: lack of voluntary movement control
Confusion
Irritability
Astrocytoma
Low and high grade gliomas that develop from glial cells
Medulloblastoma
Usually develop in posterior fossa/ cerebellum
Ependymoma
Formed from CSF producing ependymal cells
Craniopharyngioma
Found at base of brain close to pituitary gland
Germ cell tumours
Arise from germ cells
Found close to pituitary gland and pineal gland
Choroid plexus tumours
Develop from network of ependymal cells
Risk factors primary brain tumours
Personal/family history of brain tumour, leukaemia, sarcoma and early onset breast cancer Prior therapeutic CNS irradiation Neurofibromatosis 1 and 2 Tuberous sclerosis 1 and 2 Von Hippel-Lindau
History of brain tumour
Headache: mass effect or hydrocephalus N/V Behavioural change: due to tumours found in frontal lobe Polyuria/poldipsia: diabetes insipidus Seizures Altered GCS
Primary brain tumour examination
General: behaviour, conscious level, alertness
Visual: diplopia, reduced visual acuity/fields, eye movement, fundoscopy
Motor signs: abnormal gait or coordination, swallowing difficulties, weakness
Delayed growth
Delayed, arrest or precocious puberty
Increased head circumference if under 2 years old (growth chart)
DD primary brain tumour
Migraine or tension headaches Meningitis/ encephalitis Intracranial haemorrhage/ stroke Otitis media: unsteady gait Neurofibromatosis
Brain tumour investigations
MRI
2nd: contrast enhanced CT
Management CNS malignancy
Analgesia, antiemetic, anticonvulsants, fluid/dietary support, treatment to lower ICP (steroids) Surgical resection CSF shunts for hydrocephalus Radiotherapy Chemotherapy: BBB? Proton therapy Stem cell transplantation
Complications of CNS malignancy
Epilepsy and seizures Sleep disturbance Effects on puberty/ fertility Hearing loss Impaired growth Cognitive impairment Secondary malignancy
Idiopathic thrombocytopenic purpura
Low platelet count Causing a purpuric rash TY2 hypersensitivity reaction Antibodies target platelets Non-blanching rash
Presentation of ITP
<10 years old Recent viral illness Symptoms onset 24-48hours Bleeding: gums, epistaxis, menorrhagia Bruising Petechiae or purpuric rash, caused by bleeding under the skin
ITP management
Urgent FBC for platelets
Exclude heparin induced thrombocytopenia and leukaemia
Resolve <3 months
Active bleeding or severe thrombocytopenia:
Prednisolone
IV immunoglobulins
Blood transfusions
Platelet transfusions: temporarily work until antibodies destroy them too
Advice for patients with thrombocytopenia
Avoid contact sports Avoid IM injections and lumbar puncture Avoid NSAIDS, aspirin, blood thinners Advice on managing nosebleeds Seek help after any injury that may cause internal bleeding
ITP complications
Chronic ITP
Anaemia
Intracranial and subarachnoid haemorrhage
GI bleeding
Sickle cell anaemia
Genetic condition that causes sickle shaped RBC
Makes them fragile and more easily destroyed, leading to haemolytic anaemia
Sickle cell anaemia pathophysiology
Haemoglobin is the protein in RBC that transports oxygen
HbF—>HbA at 6 weeks of age
HbS
Autosomal recessive
Abnormal gene for beta-haemoglobin on chromosome 11
Sickle cell and malaria
Sickle cell trait reduces risk of malaria
Selective advantage
Sickle cell diagnosis
Newborn screening heel prick test at 5 days of age
Sickle cell complications
Anaemia Increased risk of infection Stroke Avascular necrosis in large joints Pulmonary hypertension Painful and persistent penile erections Chronic kidney disease Sickle cell crises Acute chest styndrome
Sickle cell disease management
Avoid dehydration and triggers
Ensure vaccines are up to date
Antibiotic prophylaxis: Penicillin V (phenoxymethylpenicillin)
Hydroxycarbamide: stimulates production of HbF
Blood transfusion for severe anaemia
Bone marrow transplant can be curative
Sickle cell crisis
Low threshold for hospital admission Analgesia Rehydrate Oxygen Treat infection Keep warm Penile aspiration to treat priapism Blood transfusion
Vaso-occlusive crisis
Sickle cell disease
Sickle shaped blood cells clogging capillaries and causing distal ischaemia
Associated with dehydration and raised haematocrit
Symptoms: pain, fever, symptoms of triggering infection
Priapism in men: trapping blood in penis, urological emergency and treated with aspiration of blood from the penis
Splenic sequestration crisis
RBC blocking blood flow within spleen
Causes acutely enlarged and painful spleen
Pooling of blood in spleen: severe anaemia, circulatory collapse (hypovolaemic shock)
Emergency
Management is supportive, with blood transfusions and fluid resuscitation to treat anaemia and shock
Recurrent crisis: splenectomy is management, as recurrent crises can lead to splenic infarction and susceptibility to infections
Aplastic crisis
Temporary loss of creation of new blood cells
Most commonly triggered by infection with parvovirus B19
Leads to anaemia
Management is supportive: blood transfusions, usually resolves spontaneously within a week
Acute chest syndrome
Diagnosis:
Fever or respiratory symptoms
New infiltrates seen on a CXR
Acute chest syndrome can be due to infection (pneumonia or bronchiolitis) or non-infective causes (pulmonary vaso-occlusion or fat emboli)
Acute chest syndrome management
Antibiotics or antivirals for infections
Blood transfusions for anaemia
Incentive spirometry using a machine that encourages effective and deep breathing
Artificial ventilation with NIV or intubation may be required
Thalassaemia
Genetic defect in the protein chains that make up haemoglobin
Normal Hb: 2 alpha and 2 beta
Both conditions are autosomal recessive
Varying degrees of anaemia
RBC more fragile and break down more easily
Spleen removes dead RBC, splenomegaly
Bone marrow expands to produce extra red blood cells to compensate for the chronic anaemia
Susceptibility to fractures and prominent features, such as a pronounced forehead and malar eminences (cheek bones)
Thalassaemia potential signs and symptoms
Microcytic anaemia (low mean corpuscular volume) Fatigue Pallor Jaundice Gallstones Splenomegaly Poor growth and development Pronounced forehead and malar eminences
Diagnosis of thalassaemia
FBC: microcytic anaemia
Haemoglobin and electrophoresis: used to diagnose globin abnormalities
DNA testing: genetic abnormality
Pregnant women offered a screening test for thalassaemia at booking
Thalassaemia iron overload
Iron overload due to faulty creation of RBC, recurrent transfusions and increased absorption of iron in the gut in response to anaemia
Monitor serum ferritin levels in thalassaemia
Management of iron overload: limiting transfusions and performing iron chelation
Iron overload in thalassaemia
Effects
Fatigue Liver cirrhosis Infertility Impotence Heart failure Arthritis Diabetes Osteoporosis and joint pain
Management of alpha thalassaemia
Monitoring the FBC Monitoring for complications Blood transfusions Splenectomy may be performed Bone marrow transplant can be curative
Caused by defects in the alpha globin chains
Beta thalassaemia management
Caused by defects in beta globin chains
Gene defect can either consist of abnormal copies that retain some function or deletion genes where there is no function in beta globin protein at all
Thalassaemia minor
Thalassaemia intermedia
Thalassaemia major
Thalassaemia minor
Carries of abnormally functioning beta globin gene
One normal and one abnormal gene
Mild microcytic anaemia, usually patients only require monitoring and no active treatment
Thalassaemia intermediate
Two abnormal copies of the beta globin gene
Can either be two defective genes or one defective and one deletion gene
Causes a more significant microcytic anaemia
Patients require monitoring and occasional blood transfusions
Iron chelation to prevent iron overload, when they require more transfusions
Thalassaemia major
Homozygous for deletion genes
No functioning beta globin genes at all
Presents with severe anaemia and failure to thrive in eagerly childhood
Causes of thalassaemia major
Severe microcytic anaemia
Splenomegaly
Bone deformities
Management of thalassaemia major
Regular transfusions
Iron chelation and splenectomy
Bone marrow transplant can potentially be curative
Hereditary spherocytosis
Condition where RBC are sphere shaped, making them fragile and easily destroyed when passing through spleen
Most common haemolytic anaemia in Northern European
Autosomal dominant
Presentation of hereditary spherocytosis
Jaundice
Anaemia
Gallstones
Splenomegaly
Haemolytic crisis
Aplastic anaemia
Haemolytic crisis in hereditary spherocytosis
triggered by infections, where haemolysis, anaemia and jaundice is more significant
Hereditary spherocytosis aplastic crises
Increased anaemia, haemolysis, jaundice
Without normal response from bone marrow of creating new RBCs
No reticulocyte response
Often triggered by infection with parvovirus
Diagnosis of hereditary spherocytosis
FH, clinical features
Along with spherocytosis on blood film
Mean corpuscular Haemoglobin concentration is raised on FBC
Reticulocytes raised due to rapid turnover of RBCs
Management of hereditary spherocytosis
Treat with folate Supplementation
Splenectomy
Cholecystectomy if gallstones are the problem
Transfusions may be required during acute crises
Hereditary elliptocytosis
In hereditary spherocytosis
RBC ellipse shaped
Autosomal dominant
Presentation and management are very similar
G6PD deficiency
X-linked recessive, usually affects males
More common in Mediterranean, Middle Eastern, African patients
Crises that are triggered by infections, medications or fava beans (broad beans)
Pathophysiology of G6PD deficiency
Enzyme is responsible for helping protect cell from damage by reactive oxygen species
ROS are reactive molecules that contain oxygen, producing during normal cell metabolism and in higher quantities during stress on the cell
G6PD enzyme deficiency makes cells more vulnerable to ROS
Leading to haemolysis in RBC
Periods of increased stress, with higher production of ROS can lead to acute haemolytic anaemia
G6PD deficiency presentation
Neonatal jaundice Anaemia Intermittent jaundice Gallstones Splenomegaly
Heinz bodies may be seen on a blood film
Heinz bodies are blobs of denatured haemoglobin (inclusions) seen within RBCs
Diagnosis can be made by going a G6PD deficiency
Management of G6PD deficiency
Patients should avoid triggers of acute haemolysis where possible
Includes avoiding fava beans and certain medications
G6PD deficiency
Medications that trigger haemolysis and should be avoided
Primaquine Ciprofloxacin Nitrofurantoin Trimethoprim Sulphonylureas Sulfasalazine and other sulphonamide drugs
Henoch-schonlein purpura
IgA vasculitis
Presents with a purpuric rash affecting lower limbs and buttocks in children
IgA deposits in blood vessels
Inflammation occurs in the affected organs
Affects skin, kidneys, GI tract
Condition triggered by an upper airway infection or gastroenteritis
Most common <10 years
Four classic features of HSP
Purpura- lumps under skin containing blood
Joint pain
Abdominal pain
Renal involvement
HSP purpura
Purpura: Palpable under skin Start on legs and spread to buttocks Also affect trunks and arms Skin ulceration and necrosis can develop Red-purple in colour
Arthralgia or arthritis HSP
Arthralgia or arthritis:
Mostly affecting knees and ankles
Joints can becomes swollen and painful
Reduced range of movement
HSP abdominal pain
Abdominal pain: No GI involvement GI haemorrhage Intussusception Bowel infarction
HSP kidneys
Kidneys:
IgA nephritis
HSP nephritis
Microscopic or macroscopic haematuria and proteinuria
>2+ protein on urine dipstick, child has developed nephrotic syndrome and will have a degree of oedema
Diagnosis of HSP
Exclude meningococcal septicaemia, leukaemia, ITP, HUS
FBC and blood film: thrombocytopenia, sepsis, leukaemia Renal profile for kidney involvement Serum albumin: nephrotic syndrome CRP for sepsis Blood cultures Urine dipstick for proteinuria Urine protein: creatinine ratio Blood pressure for HTN
EULAR/PRINTO/PRES criteria for diagnosing HSP
Palpable purpura
+ one of
Diffuse abdominal pain
Arthritis or arthralgia
IgA deposits on histology (biopsy)
Proteinuria or haematuria
Management of HSP
Supportive, simple analgesia, rest, hydration
Urine dipstick for renal involvement
Blood pressure for HTN
Abdominal pain settles in a few days
Patients without kidney involvement recover in 4-6weeks
A third have a recurrence of disease within 6 months
ESRD in a small proportion
DIC
Tissue factor (transmembrane glycoprotein) Exposed to circulation after vascular damage: present on surface of endothelial cells, macrophages, and monocytes TF is released in response to exposure to cytokines (IL-1), TNF, and endo toxin Abundant in lungs, brain and placenta TF triggers extrinsic and intrinsic pathway
Causes of DIC
Sepsis
Trauma
Obstetric complications, e.g. amniotic fluid embolism or haemolysis, elevated LFT, low platelets (HELLP syndrome)
Malignancy
Diagnosis of DIC
Decreased platelets Decreased fibrinogen Increased PT & APTT Increased FDP Schiscocytes due to microangiopathic haemolytic anaemia
Diagnosis of hyposplenism
Radionucleotide labelled red cell scan
Causes of hyposplenism
Splenic artery embolizartion
Splenectomy for trauma
Management of hyposplenism
Pneumococcal, Haemophilus TYB, meningococcal TYC vaccines. 2 weeks prior to splenectomy or two weeks following splenectomy
Annual influenza vaccine
Post-splenectomy crisis, penicillin or macrolides prophylaxis for high risk individuals
Risk of malaria
Hyposplenism blood film
Target cells Howell-Jolly bodies Pappenheimer bodies Siderotic granules Acanthocytes
