Haematology Flashcards
RFs for Hodgkins lymphoma
EBV, FH, young adults, 16-65, peak in 30s, M>F, HIV
What is Hodgkins lymphoma
B cell tumours, no apoptosis, divides uncontrollably, don’t produce Ig, usually surrounded by t cells
Contiguously spread rarely extranodal.
Classical
95%, Reed-Sternberg cells (2 cells fused, owl eyes). CD15/30
Nodular sclerosis: 70%, young adults, neoplastic inflam cells surrounded by collagen from fibroblasts, forming nodules, lacunar cells (RS cells with shrunken cytoplasm, nucleus appears as if in middle of lake).
Mixed: 20%, HIV, mixed inflam, background, eosinophils, neutrophils, plasma cells, histiocytes surrounding RS cells, good prognosis.
Lymphocyte rich: 5% RS cells surrounded by lymphocytes, best prognosis.
Lymphocyte poor: rarest, 30-37, no reactive lymphocytes, abundance of RS cells, HIV, worst prognosis.
Nodular lymphocyte predominant
M>F, 5%
CD20/45. No RS cells
Large groups of lymphocytes form nodules around lobulate-nucleated popcorn cells
Slow growing, highly curable.
Features of Hodgkins lymphoma
Painless cervical/ supraclavic/ mediastinal (cough, SVCS, abdo pain, dyspnoea) lymphadenopathy, rubbery, painful with alcohol.
Cytokine release: fever, drenching night sweats, weight loss. NS 50%, mixed cellularity/ lymphocyte depleted common
Pruritis
Hepatosplenomegaly
Tonsillar enlargement
Pel Ebstein fever: cyclical fever, periods of high + normal temp.
Complications of Hodgkins lymphoma
Nodular lymphocyte predominant: transformation to aggressive NHL.
Poor prognosis: >45, stage 4, Hb <10.5, lymphocyte coung <600/8%, male, albumin <40, WBC >150,000
Diagnosis of Hodgkins lymphoma
Ann Arbor 1 LN/group of adjacent LN >2 LN regions, both on same side of diaphragm LN on both sides of diaphragm Liver/ spleen/ lungs/ bone marrow. A: no Sx other than pruritis B: B Sx E: organs/ tissues beyond lymph system
CT/PET scan Gallium scan: involved sites appear bright LN biopsy ↑LDH Normocytic anaemia, eosinophilia FBC: ↓Hb, plts, WBC ↑↓ ESR: ↑ CXR: mediastinal mass, large mediastinal lymphadenopathy
Tx of Hodgkins lymphoma
Rituximab: NLP > binds CD20 induces apoptosis.
Classical: ABVD /BEACOPP + radio
NLP: early > radio, advanced, R-CHOP
R-CHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, pred
BEACOPP: bleomycin etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, pred
ABVD: doxorubicin, bleomycin, vinblastine, radiotherapy.
RFs for NHL?
ataxia telangiectasia, >50, M>F. Wiskott-Aldrich, Chediak Higashi, Klinefelter, HTCL virus, H pylori, IS, HIV, AI disease, aromatic hydrocarbons eg benzene, radiation, pesticides,
What is Non-Hodgkins lymphoma?
80% B cell, 20% t cell
Usually LN can be extra-nodal
Small bowel lymphoma: small intestine, MALT, coeliac, intra epithelial T cell.
B cell
Most common, aggressive
CD20
Diffuse large B cell: most common. Aggressive. t(3,4) BCL6. Germinal/ activated b cell.
Follicular: slow growing, 2nd most common. Middle > later life, rare in childhood. T(14, 18) > BCL2 gene.
Burkitt: highly aggressive, commonest childhood malig, M>F. endemic (EBV, Africa, rapidly growing maxilla/ mandible tumour), sporadic (30% EBV, most marrow involvement, or abdo mass > ileo-ceacal), AIDs. T(8, 14) > MyC.
Mantle cell: aggressive, t(11, 14) > BCL1 > cyclin D1
Marginal zone: indolent, MALT (chronic inflam eg H pylori), LN/ spleen.
Lymphoplasmacytic: ↑age indolent, uncommon, bone marrow, LN spleen. Waldenstrom macroglobulinulinemia > neoplastic cells produce IgM, ↑blood viscoscity t(9,14)
Cutaneous: extranodal marginal/ follicle centre
Hairy cell leukaemia: BRAF mutations
T cell
Less freq
Angioimmunoblastic, extranodal natural killer/ T cell lymphoma nasal type enteropathy associated T cell lymphoma, anaplastic, periph T cell lymphoma.
Middle aged > elderly.
Adult t cell lymphoma: leukaemia, human t lymphotropic virus
Mycosis fungoides: t cell lymphoma of skin, resembles fungal infection, confined to skin. Long Hx, preceded by scaly pre-mycotic phase.
Features of NHL?
DLBC: intra-abdo disease, bowel Sx due to compression/ infiltration of GIT. 30% present at extranodal site as opposed to nodal disease with extranodal spread.
Burkitt: abdo mass, bone marrow involvement, CNS, kidney, testis.
Lymphoplasmacytic: anaemia Sx, hyper viscosity (headaches visual disturbances), Raynauds.
Cutaneous: single or clustered lesions
Angioblastic: fevers, rashes, electrolyte abnormalities
Mycosis fungoides: multiple erythematous lesions, plaques + tumours, when spreads to blood/ bone becomes Sezary syndrome.
Generalised erythroderma.
Painless lymphadenopathy, non-tender, rubbery, asymmetrical
B Sx: fever, drenching night sweats, weight loss, malaise
Waldeyer’s ring: oropharynx Dx, sore throat, obstructed breathing.
Splenomegaly: marginal zone
Hepatomegaly, jaundice
SOB: pleural involvement
Cough: mediastinal mass/ lymphadenopathy, pneumonia
Anaplastic: t(2,5)
MALT: T(11,18)
B Sx appear later in NHL than HL.
Testicular mass
Complications of NHL?
Bone marrow involvement: fatigue, weakness, anaemia, bleeding, infections.
Extra-nodal: bowel obstruction.
SCC, motor/sensory deficits.
Meningeal involvement: headache, mental status
Bone pain
Follicular, transform into more aggressive NHL.
Diagnosis of NHL?
Follicular: large plasmablasts/ immunoblasts. Diagnostic biopsy may not be represenetative esp if abdo mass but periph LN biopsied. Percut needle biopsy of abdo may reveal DLBCL transformation.
Burkitt: starry sky, stars (tangible bodies, macrophages with phagocytosed dead neoplastic cells), sky (dark neoplastic lymphocytes)
Mycosis fungoides: CD4 helper t cells, cerebriform nucleus (looks like brain).
CT/PET
LN biopsy, skin biopsy
Adverse prognostic factors: >60y/o, stage 3/ 4, ↑LDH, performance status, >1 extranodal site involved
FBC: thrombocytopenia, pancytopenia, lymphocytosis, pancytopenia
Blood smear: nucleated RBCs, left shift
Immunohistochemistry/ flow cytometry: determines tumour surface markers
Lymphoplasmacytic: large amounts of basophilic cytoplasm, nucleus contains spoke wheel like chromatin.
Mantle: cells have notched nuclei.
Hairy cell: dry tap on bone marrow aspiration due to fibrosis, CD11c marker, leucopenia.
Ann Arbor system
Management of NHL?
DLCB: Tx immediately, R-CHOP, radiotherapy
Follicular: R-CHOP
Burkitt: rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate.
Mantle: rituximab, R-CHOP
Marginal: H pylori eradication, prognosis good, 6 monthly endoscopy, if spread chemo.
Lymphoplasmacytic: in emergency lower paraprotein by plasmapheresis. Chemo + rituximab.
Cutaneous B cell: excision, radiation. Good prognosis. If multiple sites rituximab.
Angioblastic: responsive to CS or low dose alkylating agents.
Allopurinol for TLS.
T cell: CHOP > no rituximab as no CD20
High grade lymphoma has a worse prognosis but higher cure rate.
Summary of tumour lysis syndrome?
Rapid destruction of tumour cells, massive release of intracellular components, damage kidneys > renal failure
Features - V/N/D, Lethargy, Haematuria, Muscle cramps, Paraesthesia
Complications - Ca phosphate crystals obstruct renal tubules > AKI, urate nephropathy, Cardiac arrhythmias, Tetany
Diagnosis - ↑K, P, ↓Ca due to phosphate binding
Management - Prophylaxis: hydration, avoid NSAIDs, allopurinol.
Tx electrolyte abnormalities
Haemodialysis
Rasburicase
Fluids, ± loop diuretics to aid renal excretion of uric acid crystals.
What is acute lymphoblastic leukaemia?
Most common malignancy affecting children and accounts for 80% of childhood leukaemias.
Lymphoblasts accumulate in BM, suppression, prevent maturation.
peak incidence is at around 2-5 years of age
B>G
common ALL (75%), CD10 present, pre-B phenotype
T-cell ALL (20%)
B-cell ALL (5%)
RFS for ALL?
most common leukaemia in children. B > 3, T > 15-20. 2 peak incidences, 2-5 + >50. Down syndrome (>5), Klinefelter’s, radiation exposure, genetic, Hx of malig, Tx with chemo, smoking
Features of ALL?
Abrupt onset
Pleural effusion
Hyperuricaemia, TLS
anaemia: lethargy and pallor
neutropaenia: frequent or severe infections
thrombocytopenia: easy bruising, petechiae
bone pain (secondary to bone marrow infiltration)
splenomegaly
hepatomegaly
fever is present in up to 50% of new cases (representing infection or constitutional symptom)
testicular swelling
Thymus: palpable mass, airway compression
Lymphadenopathy
Orchidomegaly: unilat
Abdo pain: splenomegaly
Skin infiltration by blast cells
Renal enlargement: infiltration of renal cortex by blast cells
Poor prognostic factors for ALL?
age < 2 years or > 10 years WBC > 20 * 109/l at diagnosis T or B cell surface markers non-Caucasian male sex
Complications for ALL?
Meningeal infiltration: headache, vomiting, nerve palsies, nuchal rigidity, papilloedema
Bone pain, limp in young child
Focal neurological signs: CN 3/4/6/7 CNS leukaemia
DIC
Diagnosis of ALL?
Blood count: ↑lymphocytes, WBCs
BM smear: hypercellular bone marrow, lymphoblast domination >20%. T-ALL starry sky of phagocytosing macrophages.
Condensed chromatin, scant cytoplasm, small nucleoli
↓WCC until spill out causing ↑
↑LDH
CT: mediastinal mass, LN involvement/ CNS infiltration.
B-ALL: CD10/19/20
T-ALL: CD1/2/5/7/H
Terminal deoxynucleotidyl transferase: pos, distinguish from AML
Management of ALL?
Aggressive chemo: prophylactic injections into scrotum, CSF as chemo can’t cross BBB or testicular. Methotrexate
95% remission, 75% cute rate.
Tyrosine-kinase inhib: imatinib
Blood/plt transfusion
Poor prognostic factors: <2 or >10, WBC >20, T/B cell surface markers, non-Caucasian, M
Induction: pred/ dexamethasone + cyclophosphamide + vincristine + doxorubicin
Consolidation Tx
Rituximab if CD20
What is acute myeloid leukaemia?
Acute myeloid leukaemia is the more common form of acute leukaemia in adults. It may occur as a primary disease or following a secondary transformation of a myeloproliferative disorder.
Myeloblasts accumulate in BM, suppression > prevents maturation, normal haematopoiesis ↓
Acute promyelocytic: t(15,17) > disruption of retinoic acid receptor > promyelocytes accumulate (cells with heavy granulation in cytoplasm). Good prog Fusion of PML + RARα genes
T(8:21), (q22:q22), inv(16 (p12:q22), t(16, 16)(p13q22) t(15:17), (q22:q12).
RFs for AML?
adult (60), M>F, radiation, benzene, dark coloured hair dyes, smoking, alcohol, agricultural workers, pesticides, fertilisers, chemo (alkylating agents eg cyclophosphamide, melphalan, nitrogen mustard, latency 4-8yrs, topoisomerase inhibs (etoposide, teniposide) latency 1-3yrs), myeloprolif/ haematological disorders eg myelodysplastic synd, anaplastic anaemia, paroxysmal nocturnal haemoglobinuria, polycythaemia vera, essential thrombocytopenia, downs, Klinefelter’s, Patau’s. p53.
Features of AML?
Abrupt onset
Bone marrow failure = Anaemia, thrombocytopenia, neutropenia, splenomegaly, bone pain
Skin or testicular mass
Abdo pain
Sx less common in AML than ALL: bone pain, thymus mass/ airway compression, hepatosplenomegaly, lymphadenopathy, meningeal infiltration.
Sx more common in AML than ALL: skin (leukaemia cutis, nodular skin lesion, purple or gravy-blue colour), Sweet’s syndrome (fever, leukocytosis, tender erythematous well demarcated papules + plaques which show dense neutrophilic infiltrates), pyoderma gangrenosum. Gum swelling, granulocytic sarcomas.
Poor prognostic features of AML?
> 60 years
> 20% blasts after first course of chemo
cytogenetics: deletions of chromosome 5 or 7
Complications of AML?
DIC Death in 2 mnth if untreated High relapse rate Mediastinal or thymic infiltration: SVCS, airway compromise Febrile neutropenia Leukostasis: ↑blood viscosity
Diagnosis of AML?
Blood smear: granulated + Auer rod content of blasts
Bone marrow smear: ↑myeloblasts >20%, auer rods. Large nucleus, prominent nucleoli, more cytoplasm visible than in ALL. Bone marrow hypercellularity.
↑WCC
Acute promyelocytic: abnormal WBCC, bi lobed nuclei, hyper granulated blasts, bundles of auer rods. DIC + thrombocytopenia at presentation.
FBC: anaemia, macrocytosis, leukocytosis, neutropenia, thrombocytopenia, ↓reticulocytes.
Classification - French-American-British (FAB) MO - undifferentiated M1 - without maturation M2 - with granulocytic maturation M3 - acute promyelocytic M4 - granulocytic and monocytic maturation M5 - monocytic M6 - erythroleukaemia M7 - megakaryoblastic
Management of AML?
Cytarabine, daunorubicin, idarubicin
Stem cell transplant
APML: tretinoin, arsenic > causes blasts to differentiate,
What is chronic lymphocytic leukaemia?
Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%).
It is the most common form of leukaemia seen in adults.
Mature, functionally abnormal B lymphocytes in BM/ blood. Escape PCD + undergone cell cycle arrest in GO/G1. Suppression.
99% B cells, full maturation + apoptosis prevented, defective, non functional lymphocytes.
Premalig: monoclonal B cell lymphocytosis, where less than requires no of B cells for CLL diagnosis.
CD19/20 + CD5 B cells
Features of CLL?
late onset
B Sx - fever, chills, night sweats, fatigue, WL, anorexia
anaemia, thrombocytopenia, neutropenia
bone pain, hepatosplenomegaly, lymphadenopathy
meningeal infiltration
thymus mass - airway compression
often none: may be picked up by an incidental finding of lymphocytosis
constitutional: anorexia, weight loss
bleeding, infections
lymphadenopathy more marked than chronic myeloid leukaemia
Diagnosis of CLL?
full blood count:
lymphocytosis
anaemia
blood film: smudge cells (also known as smear cells)
immunophenotyping is the key investigation
LN biopsy - prolif centres, lymphocyte infiltration
Coombs test - positive if haemolytic present
Rai and Binet staging system
RFs for CLL?
most common leukaemia in adults, M>F, >60, white, FH, agent orange exposure
Complications of CLL?
Abnormal Ig secretion: hypogamma globulinemia, AI haemolytic anaemia
Richter syndrome: progresses to aggressive lymphoma eg DLBC, LN swelling, fever w/o infection, WL, night sweats, nausea, abdo pain
Management of CLL?
Median survival 10 yrs
Chemo
Immunotherapy
Radiation
Bone marrow transplant
Tx if: symptomatic, immunoglobulin genes unmutated, 17p deletion, marrow failure, recurrent infection, splenomeg/ lymphadenopathy, progressive Dx (doubling of lymphocyte count in 6mnths), systemic Sx, haemolysis or AI cytopenias.
What is chronic myeloid leukaemia?
Prolif of mature granulocytes/ precursors, accumulate in BM
Philadelphia Chr: t(9:22) BCR-ABL1 fusion. Strong tyrosine kinase activity
RFs for CML?
adult, >40, M, radiation, benzene
Features of CML?
60-70 years
Gout, purine breakdown, TLS
anaemia, WL, sweating, splenomegaly
Chronic phase: 85% at time of diagnosis. Leucocytosis (pred neutrophils), fatigue, WL, loss of energy, fever, sweats, pallor, abdo discomfort, malaise, headache, priapism.
Blast count <10%
Accelerated: >20% basophils in blood/BM, 10-19% myeloblasts in blood/BM, anaemia, SOB, bleeding, petechiae, ecchymosis, retinal haem, epistaxis, hepatosplenomeg, lymphadenopathy, arthralgia, sternal tenderness (BM expansion of sternum).
Blast crisis: terminal phase, rapid progression, >20% myeloblast in blood/BM. Sig splenomegaly. ↑anaemia, thrombocytopenia, basophilia.
Bone pain, fever.
Complications of CML?
may undergo blast transformation (AML in 80%, ALL in 20%)
Diagnosis of CML?
↑granulocytes > basophils, eosinophils, neurophils, WBCC WBCs bigger, more mature + blast like. ↑urate, B12, K, LDH ↓Plt Normochromic normocytic anaemia BM biopsy: hypercellularity, granulocytic hyperplasia Karyotypic analysis: BCR-ABL1, t(9,22). Pseudo Gaucher cells in marrow ↓leukocyte alkaline phosphatase
Management of CML?
Tyrosine kinase inhib: imatinib Hydroxycarbamide Hydroxyurea IFNα Bone marrow transplant
Summary of hairy cell leukaemia?
a chronic and rare form of adult leukemia
Prolif of abnormal B or very rarely T cells which accumulate in BM + spleen
Features - gradual onset, Anaemia Fever Weight loss, weakness Splenomegaly, lymphadenopathy neutropenia, thrombocytopenia, low monocyte counts
Diagnosis - Blood/BM film: irregular outline due to presence of filament like cytoplasmic projections (hairy rim), immunophenotyping, bone marrow biopsy
Management - Purine analogues 2 chloradenosine acetate Pentostatin Cladribine Rituximab IFN alpha
What is multiple myeloma?
a haematological malignancy characterised by plasma cell proliferation
It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells.
MM is the second most common haematological malignancy
Presentation of MM?
median age of onset - 70 yrs
CRABBI
Calcium
- Hypercalcaemia occurs as a result of increased osteoclast activity within the bones
This leads to constipation, nausea, anorexia and confusion
Renal
- Monoclonal production of immunoglobulins results in light chain deposition within the renal tubules
- This causes renal damage which presents as dehydration and increasing thirst
- Other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis
Anaemia
- Bone marrow crowding suppresses erythropoiesis leading to anaemia
- This causes fatigue and pallor
Bleeding
- bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising
Bones
- Bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions
- This may present as pain (especially in the back) and increases the risk of fragility fractures
- SCC pain
Infection
- a reduction in the production of normal immunoglobulins results in increased susceptibility to infection
Investigations for MM?
Bloods - anaemia, thrombocytopenia, raised urea and creatinine, raised calcium
peripheral blood film - rouleaux formation
serum or urine protein electrophoresis - raised concentrations of monoclonal IgA/IgG proteins will be present in the serum. In urine known as Bence Jones proteins
bone marrow aspiration and trephine biopsy - confirms diagnosis if number of plasma cells is significantly raised
whole-body MRI - surgery skeleton for bone lesions
Xray - rain drop skull - due to bone lysis
Symptomatic multiple myeloma is defined at diagnosis by the presence of the following three factors:
- Monoclonal plasma cells in the bone marrow >10%
- Monoclonal protein within the serum or the urine (as determined by electrophoresis)
- Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures
Management of MM?
It is important to accurately diagnose multiple myeloma, as unlike its pre-malignant counterparts (Monoclonal gammopathy of undetermined significance and Smoldering myeloma), treatment must begin immediately due to the risk of complications occurring as a result on end-organ damage.
Myeloma is a chronic relapsing and remitting malignancy which is currently deemed incurable. Management aims to control symptoms, reduce complications and prolong survival.
treatment begins with induction therapy:
For patients who are suitable for autologous stem cell transplantation* induction therapy consists of Bortezomib + Dexamethasone
For patients who are unsuitable for autologous stem cell transplantation*, induction therapy consists of Thalidomide + an Alkylating agent + Dexamethasone
After completion of treatment, patients are monitored every 3 months with blood tests and electrophoresis.
Many patients do relapse after initial therapy. If this occurs the 1st line recommended treatment is Bortezomib monotherapy
Autologous transplant: remove own SC prior to chemo + replaced after chemo
Complications of MM?
Pain: treat with analgesia (using the WHO analgesic ladder)
Pathological fracture: Zoledronic acid is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly.
Infection: patients receive annual influenza vaccinations. They may also receive Immunoglobulin replacement therapy.
VTE prophylaxis
Fatigue: treat all possible underlying causes. If symptoms persist consider an erythropoietin analogue.
RFs for MM?
alcohol consumption, obesity, radiation exposure, petroleum exposure, FHx, monoclonal gammopathy can progress to MM (initial conc of serum monoclonal protein sig predictor of progression, other prognostic factors< IgA or IgM monoclonal protein, BM plasmacytosis, bence jones proteinuria, ↓in polyclonal serum immunoglobulin, ↑ESR.
Causes of microcytic anaemia?
Find those small cells last: Fe def Thalassaemia minor Sideroblastic Chronic disease Lead poisoning
What is iron deficiency anaemia?
Microcytic, hypochromic
↓Fe for Hb synthesis, impaired erythropoiesis
Most absorption in proximal SI, duodenum + jejunum.
Causes of iron deficiency anaemia?
Low intake: EDs (e.g. pica, anorexia, bulimia), diet restrictions (e.g. vegan), food insecurity
Low absorption: celiac, surgical resection of GIT, bariatric surgery, XS dietary Ca, tannates, oxalates, gastrectomy/ achlorhydria, H pylori
↑need: pregnancy, lactation
↑growth: infants, children, adolescents
Overt loss: haematemesis, trauma, heavy menses, haematuria, multiple blood donations, haemodialysis
Occult: GI bleed (e.g. peptic ulcer, tumour), vascular lesions (e.g. haemorrhoids), hookworm/other helminthic infections
Features of iron deficiency anaemia?
Pallor
Fatigue, activity intolerance, exertional dyspnoea, angina
Palpitations, ↑HR, ↑CO, ↑RR
Selective shunting of blood to vital organs eg skin to kidneys
Glossitis: red, beefy tongue
Angular stomatitis: sores in corner of mouth
Cheilosis: scaling, fissuring: dryness, lip scaling
Koilonychia: spoon-shaped, concave nails.
Brittle hair + nails. Hair loss
Oesophageal stricture + dysphagia
Gastric atrophy, gastritis, absent/↓ acid secretion in stomach
Blue sclerae
Obsessive consumption of ice.
Pica = abnormal craving, for non food substances eg dirt, ice, paint or clay
RLS
Post cricoid webs
Complications of iron deficiency anaemia?
High ouput HF
Angina
Cardioresp failure
Impaired growth/ development
Infections.
Diagnosis of iron deficiency anaemia?
↓ RBCC, low/normal reticulocytes, ↓ Hb, haematocrit. 🡩RDW (>14.6%)
Hypochromic-microcytic erythrocytes
↓MCV, MCH, MCHC
Blood smear: central pallor, target cells. Poikilocytosis (abnormally shaped), pencil cells.
↓iron, ferritin, transferrin saturation ↑total iron binding capacity + transferring receptors.
Older pt: malig til proven otherwise
Endoscopy to rule out malig in males + post menopausal females
Management of iron deficiency anaemia?
Ferrous sulfate, furmarate or gluconate. SE = constipation, black stools. Nausea, diarrhoea, faecal impaction. Continue for 3mnth after def corrected to replenish stores.
Ascorbic acid: aid dietary absorption
Parenteral iron: dextrate/sucrose, severe persistent anaemia, intolerance of PO iron, malabsorption
↑ dietary iron: heam > meat absorbed better than non haem eg eggs, legumes, nuts. Dark leafy vegetables.
Blood transfusion
Levothyroxine, Ca/ bisphosphonates, Quinolones, tetracyclines.
Summary of lead poisoning anaemia?
Lead exposure, toxicity, interferes with enzymatic steps in haem pathway, ↓Hb synthesis, impairs Na/K ATPase in erythrocytes > haemolysis.
RF: water contaminated with industrial waste/ from lead pipes. Leaded paint. Older homes. Breathing industrial emissions (smelters, refineries, battery manufacturing, recycling), food/beverages from lead glazed ceramics.
Small hypochromic RBCs
Dyspnoea
Activity intolerance
Lead toxicity: abdo pain, headache, difficulty concentrating, muscle/joint, confusion, ataxia. Peripheral neuropathy (mainly motor), constipation, blue lines on gum margin.
Ix - ↑ serum blood lead level Basophilic stippling Clover leaf morphology ↓/normal MCV ↓ mean MCH Haemolysis: ↑ indirect bilirubin, LDH, ↓ haptoglobin ↑urinary coproporphyrin
Tx - Eliminate exposure Chelation therapy: dimercaptosuccinic acid (DMSA, aka succimer), CaNa2EDTA D-penicillamine EDTA Dimercaprol
What is thalassaemia?
People with thalassaemia produce either no or too little haemoglobin
AR, microcytic hypochromic, rigid less deformable membranes > extravascular haemolysis, phagocytosis by reticuloendothelial macrophages.
Deficient α/β chains > imbalanced, aggregate + precipitate > unstable Hb tetramer.
What is alpha thalassaemia?
deficiency of alpha chains in haemoglobin
2 separate alpha-globulin genes on each Chr 16
If 1 or 2 alpha globulin alleles are affected then the blood picture would be hypochromic and microcytic, but the Hb level would be typically normal
If are 3 alpha globulin alleles are affected results in a hypochromic microcytic anaemia with splenomegaly. This is known as Hb H disease
If all 4 alpha globulin alleles are affected (i.e. homozygote) then death in utero (hydrops fetalis, Bart’s hydrops)
Minima: carrier, no Sx 1 gene missing
Minor: trait, mild anaemia, 2 genes missing.
HbH disease: 3 genes missing, mild anaemia.
Major: 4 genes missing, hydrops fetalis, Hb Barts (γ tetramer), incompatible with extrauterine life.
What is beta thalassaemia?
Absence of beta globulin chains
Point mutation in Chr11
Minor: 1 gene, trait. Asymptomatic carrier /mild hypo chromic, microcytic anaemia, ↑HbA2 (2 α + 2 delta). No haemolysis
Intermedia: 2 genes. Moderate anaemia Sx, may be transfusion dependent in later life. Haemolysis: splenomeg + gall stones.
Major: no β globin trains produced, transfusion dependent, Cooley’s anaemia. Presents once fully switched from fetal Hb few mnths of life, FTT + hepatosplenomegaly. Microcytic anaemia, HbA2 and HbF raised, HbA absent
Management of thalassaemia
Beta- thalassaemia major - repeated transfusion - leads to iron overload (organ failure) so iron chelation therapy (desferritoxamine) is important
Folic acid
Splenectomy
Blood transfusions >9g.dL
Allogenic haematopoietic cell transplantation
Features of thalassaemia?
Pallor, fatigue, activity intolerance
Tachycardia, ↓BP, arrhythmias
Chronic haemolysis: jaundice, dark urine, hepatosplenomeg
Failure to gain weight
Large head, frontal + parietal bossing, chipmunk facies, misaligned teeth.
Diagnosis of thalassaemia?
β thalassaemia major: microcytic anaemia, ↑reticulocytes. ↑HbA2 + HbF. Absent HbA. Extramedullary haematopoiesis: hepatomeg, bone expansion, XR > hair on end of bones as marrow expands into cortical bone.
↑reticulocytes
↑WBC > generalised haematopoietic hyperactivity, all ↓ as spleen enlarges.
MCHC ↑ related to erythrocyte dehydration
↓MCV ↑RCDW
Blood smear: poikilocytosis (teardrop shaped cells), anisocytosis, erythroblasts (nucleated RBCs), target cells. Inclusions (precipitated globin chains), basophilic stippling
Haemolysis: ↑LDH, UBR, ↓haptoglobin
↑iron, transferrin saturation, ferritin.
β thalassaemia minor: microcytosis often disproportionate to anaemia
α thalassaemia: Heinz bodies. Target cells
What is sideroblastic anaemia?
condition where iron available but red cells fail to completely form haem, whose biosynthesis takes place partly in the mitochondrion.
This leads to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast. It may be congenital or acquired.
Congenital cause: delta-aminolevulinate synthase-2 deficiency
Acquired causes myelodysplasia alcohol lead anti-TB medications
Features of sideroblastic anaemia?
Syndromic: exocrine pancreatic insuff, hepatic/ renal failure, sensorineural deafness, myopathy
Fatigue, dyspnoea, palpitations, pallor
Mild jaundice if haemolysis significant
Investigations for sideroblastic anaemia?
full blood count
- hypochromic microcytic anaemia (more so in congenital)
- low reticulocyte count
iron studies (haemochromatosis)
- high ferritin
- high iron
- high transferrin saturation
blood film
- basophilic stippling of red blood cells, anisocytosis, poikilocytosis, hypochromic, iron containing inclusions (Pappenheimer bodies),
bone marrow
- Prussian blue staining will show ringed sideroblasts
Management of sideroblastic anaemia?
supportive
treat any underlying cause
Via B6 pyridoxine may help
Chelation - deforxamine
Complications of sideroblastic anaemia?
Iron overload > haemochromatosis
Anaemia induced acceleration of erythropoiesis > erythroid hyperplasia of BM
↑risk of infection
Acute leukaemia
Causes of normocytic anaemia
Insuff production of erythrocytes:
Anaemia of chronic disease
CKD
Anaplastic anaemia
Haemolytic anaemia
Causes of anaemia of chronic disease?
Infection, RA, malig, CKD, IBD, TB, endocarditis, hypopit/thyroid/adrenal
↓iron release from BM to developing erythroblasts, inadequate EPO response to anaemia, ↓RBC survival
Inhibition of erythropoiesis, ↓erythrocyte lifespan
Features of anaemia of chronic disease?
Hypoxia, pallor, fatigue, dyspnoea, activity intolerance
Sx of underlying condition
Investigations of anaemia of chronic disease?
↓Hb, iron, (TIBC), transferring sat, reticulocyte count.
↑/normal ferritin as acute phase protein.
↑ESR/CRP/IL6
↓EPO
Normochromic normocytic or hypochromic microcytic
BM: ↑iron in macrophages, erythroid precursors.
Management of anaemia of chronic disease?
Treat cause
Renal failure: recombinant EPO
Supplemental iron: IV iron due to systemic inflam
Transfusion
What is aplastic anaemia?
Characterised by pancytopenia (low RBC, WBC and plts) and a hypoplastic bone marrow
due to BM hypoplasia/aplasia
↓reduction in no of pluripotent SC, inefficiency with remaining ones.
Peak incidence of acquired = 30 years old
Features of aplastic anaemia?
normochromic, normocytic anaemia
leukopenia, with lymphocytes relatively spared
thrombocytopenia
may be the presenting feature acute lymphoblastic or myeloid leukaemia
a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia
Fanconi - ↑risk of AML, neurological Sx, short stature, Café Au Lait spots. Hearing loss
Dyskeratosis congenita: osteoporosis, premature hair loss/ premature greying, hyperhidrosis, dysphagia due to oesophageal stricture, extensive dental carries or tooth loss.
Schwachman-Diamond: steatorrhea, skeletal dysplasia
GATA2: monocytopenia, non TB mycobacterial infection, pulmonary alveolar proteinosis, congen lymphoedema, Emberger syndrome. Hearing loss, persistent warts.
Causes of aplastic anaemia?
idiopathic
congenital: Fanconi anaemia, dyskeratosis congenita
drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold
toxins: benzene
infections: parvovirus, hepatitis
radiation
Investigations for aplastic anaemia?
Prolonged bleeding time
↓Hb, haematocrit, neutrophils, plts reticulocytes.
Normal erythrocyte morphology
BM: hypocellular, ↑fat spaces, some lymphocytes, plasma cells, stromal elements eg blastoid cells, no ↑ in blasts/ dysplasia.
Leukopenia with lymphocytes relatively spared.
Management of aplastic anaemia?
Antimicrobials for infections
Stem cell transplant
Transfusions: plts, RBCs. ↑risk of alloimmunisation, graft rejection after BM transplant.
GFs: granulocyte colony stimulating factor for freq/ severe infections, thrombopoietin receptor agonists with immunosuppressive therapy.
IS therapy: lymphocyte immunoglobulin, anti-thymocyte globulin, methylprednisolone, ciclosporin.
