Phase 2 - Haem Flashcards
3 catagories of anaemia
Microcytic (MCV <80)Normocytic (MCV 80-95)Macrocytic (MCV >95)
Causes of microcytic anaemia
TAILS- Thalassaemias- Anaemia of chronic disease- IRON DEFICIENCY(lead poisoning)- Sideroblastic - unable to put iron into haemoglobin - linked to alcohol excess, heavy metal poisoning, VIt B deficiency (Als deficiency - iron trapped in mitochondria - autosomal recessive)
Causes of normocytic anaemia
- BLOOD LOSS (acute - too rapid to adjust)
- HAEMOLYTIC (high cell turnover)
- SICKLE CELL
(- Malaria) - Hereditary spherocytosis
- spherocytes are more fragile (a membranopathy) - G6PDH (glucose 6 phosphate dehydrogensase) deficiency
- haemolysis occurs when exposed to certain triggers
- Autoimmune Haemolytic anaemia
- SICKLE CELL
- Non-haemolytic (low reticulocytes)
- aplastic anaemia
- CKD
- normal cells, just fewer present)
- Myelophthisic
- bone marrow failure due tp malignant invasion
- HAEM MALIGNANCY
Causes of macrocytic anaemia
- Megaloblastic causes (related to impaired DNA synthesis) - B12 DEFICIENCY - Folate deficiency* Non-megaloblastic (nothing wrong with DNA synthesis) - HYPOTHYROID - ALCOHOL - LIVER disease (increase membrane cholesterol of RBCs - increased surface area) - esp NAFLD - CKD - Bone marrow failure (esp MDS - increased immature RBCs) - drugs (Methotrexate, hydroxyurea)(Haemolytic anaemia - more rbcs destroyed so more young, large reticulocytes present)
Iron metabolism process
~15-20mg average daily intake but only ~1mg (or 10%) absorbed in DUODENUM- actively transported into DUODENAL EPITHELIAL CELLS by intestinal HAEM TRANSPORTER (HCP1) - highly expressed in duodenumSome stored intracellularly bound to FERRITIN (usually - more easy to mobilise) in:- reticuloendothelial cells (e.g. monocyte derived - esp in liver)- hepatocytes- skeletal muscleor in HAEMOSIDERIN:- in macrophages (esp liver, spleen, bone marrow)Circulating iron bound to TRANSFERRIN - transports to bone marrow to make erythrocytes
Iron deficiency anaemia - causes
most common cause of anaemiaBlood loss:- menorrhaegia- Hookworm (leading cause of deficiency worldwide)- GI bleedingPoor diet: - esp in children (uncommon in adults) - esp in poverty- PROLONGED BREAST FEEDING in infants (poor Fe source)Malabsorption - Coeliac disease, IBDIncreased demands (growth, pregnancy)RARE in ELDERLY - RED FLAG SIGN for COLON CANCER BLEEDING (recomen urgent endoscopy for any >60y/o w/ Fe def)
Risk factors for iron deficiency
- Less developed countries/poverty- High veg diet (iron best absorbed from animal products) - VEGAN- premature infants- Delayed introduction of mixed feeding (breastmilk contains less iron)
Signs and symptoms of anaemia
Symptoms (non-specific):- FATIGUE, headaches and faintness* Dyspnoea * Intermittent claudication (ischaemic pain in peripheries)* COLD* PALPITATIONS* Angina (if there is pre-existing coronary disease)* AnorexiaSigns (may be absent even in severe anaemia):* Pallor (esp conjunctival)* Brittle hair* Leukonychia (white patches on nails)* Tachycardia* Systolic flow murmur* Cardiac failure
presentation of iron deficiency
- anaemic symptoms- Brittle nails/hair- spoon nails (koilonychia - dip in nails)- tongue papillae atrophy (atrophic glossitis)- ulceration of corners of mouth (angular cheilitis/stomatitis)
Diagnosis of iron deficiency anaemia
- Blood film * low blood count * MICROCYTIC and HYPOCHROMATIC * pokilocytosis (variation in shape); anisocytosis (variation in size) - TARGET CELLS (bulls eye pattern - non specific) - HOWELL JOLLY BODIES (nucleated RBCs - non-specific)- LOW FERRITIN (diagnostic) * tho it is an acute phase protein so will be normal/high in inflammation even if anaemic- IRON STUDY: * low serum iron (not very useful) * LOW TRANSFERRIN SATURATION <19% (more transferrin made to bind as much iron as possible so higher quantity of transferrin which is not saturated) * HIGH TOTAL IRON BINDING CAPACITY (lots of transferrin so highly bound)(high serum soluble transferrin receptors)- LOW RETICULOCYTE countFurther examinations if blood loss (e.g. GI tract exam)
Management of iron deficiency
Treat underlying causeORAL IRON - FERROUS SULPHATE- Side effects: * nausea, abdo discomfort, diarrhoea/constipation, black stools (from increased free iron)- Vit C improves absorption- Alt: FERROUS GLUCONATEIf severe:- IV/IM iron * rare anaphylaxis; potential sub epidermal stainingHb should increase by 20 every month - continue for 3 months after Hb/MCV normal to replenish stores
Define thalassaemia
reduced production of a specific Hb chain type - IMBALANCE OF Hb SYNTHESIS- causes INEFFECTIVE ERYTHROPOIESIS (death of precursors in bone marrow from precipitation of globin chain imbalance)- precipitation in mature RBCs -> HAEMOLYSISBeta Thalassaemia - reduced B chainAlpha thalassaemia - reduced A chain
Beta thalassaemia - pathophysiology
low B chain synthesis = EXCESS A CHAINS- combine with delta + gamma chains- increased HbA2/HbFUsually caused by point mutations (>200 varieties)-> defects in transcription, RNA splicing/modification, translation -> UNSTABLE B-GLOBIN - can’t be utilisedIf heterozygous - ASYMPTOMATIC microcytosis; maybe MILD anaemia
3 variations in b-thalassaemia presentation
B-THALASSAEMIA MINOR (aka carrier/trait)B-THALASSAEMIA INTERMEDIA (symptomatic but not requiring regular transfusions)B-THALASSAEMIA MAJOR (severe homozygous - requires lifelong transfusions)
How do you differentiate between B-thalassaemia minor and iron deficiency
Both have hypochromic, microcytic RBCsBUT serum ferritin/iron stores normalHb electrophoresis -> raised HbA2 and often raised HbF
Presentation of B-thalassemia intermedia
- SPLENOMEGALY (from haemolysis)- Bone deformaties- Recurrent leg ulcers- Gallstones- Infection
Presentation of B-thalassaemia major
Presents in children in 1ST YEAR OF LIFE- failure to thrive - recurrent bacterial INFECTION- severe ANAEMIA from 3-6 months (when switch to HbA)- EXTRAMEDULLARY HAEMATOPOIESIS - ineffective RBC OUTSIDE MARROW -> HEPATOSPLENOMEGALY (from haemolysis) - bone marrow expansion (distictive appearance)Clinically:- hair on end skull x-ray- bone abnormalities- Low MCV - MICROCYTIC- Blood film: large and small irregular hypochromic RBCs- NORMAL SERUM FERRITIN
Diagnosis of homozygous b-thalassaemia
BLOOD COUNT and FILM- HYPOCHROMIC, MICROCYTIC anaemia- RAISED RETICULOCYTES- NUCLEATED RBC in PERIPHERALSHaemoglobin electrophoresis - increased HbF; absent/less HbA
Treatment of beta-thalassaemia
In more severe:- regular (2-4 weeks) LIFE-LONG transfusions to keep Hb above 90g/L AND SUPPRESS ineffective EXTRAMEDULLARY HAEMATOPOIESIS -> to allow normal growth- Splenectomy if hypersplenism persists -> INCREASING TRANSFUSION DEMANDS - do after childhood -> reduce infection risk- Bone marrow transplant- Long term FOLIC ACID
Complications of blood transfusion
INCREASED IRON LOADING -> overload- Mainly deposit in liver/spleen -> liver fibrosis/cirrhosis- also in endocrine glands + HEART -> * Diabetes * Hypothyroidism * Hypocalcaemia * Premature death
Treatments for the complications of blood transfusions
IRON-CHELATING agents - STOP iron OVERLOAD- oral DEFERIPRONE - sub-cutan DESFERRIOXAMINE - side effects: cataracts, deafnessASCORBIC ACID (large dose) -> increases urinary exc of iron
Pathophysiology of Aplha-thalassaemia
- 2 copies of gene for a-goblin on both chromosomes 16 normally - in a-thalassaemia: 1 (most common) or both of the genes are deleted on one or both chromosomes
Clinical presentation of 4 alpha-globin gene deletion
INCOMPATIBLE WITH LIFE - stillborn/die shortly after birth- HYDROPS FETALIS * Pale * Oedematous * hepatosplenomegaly(Only Hb Barts present - 4 gamma chains - can’t carry O2)
Presentation of 3 gene alpha-globin deletion
HbH disease (common in parts of asia) - severe alpha reductionHbH = 4 beta chainsModerate ANAEMIA and SPLENOMEGALYUsually not transfusion dependant
Presentation of 2 gene a-globin deletion
trait/ CARRIERMICROCYTOSIS - potential MILD ANAEMIA
Presentation of 1 gene a-globin deletion
Usually normal blood picture
Treatments for a-thalassaemia
DAILY FOLIC ACIDBlood transfusions as needed (-> chelation therapy)May need splenectomy or venesectomy
Pathophysiology of sickle cell anaemia
SINGLE BASE MUTATION: ADENINE -> THYMINE- VALINE substituted for GLUTAMIC ACID (6th CODON) in BETA-GLOBIN chain-> HbS -> INSOLUBLE + POLYMERISES when DEOXYGENATED -> sickling (RIGID)Initially reversible but repeated sickling -> lose membrane flexibility -> IRREVERSIBLY SICKLED- DEHYDRATED + DENSE- shortened RBC survival -> HAEMOLYSIS- impaired passage through microcirculation -> OBSTRUCTION, INFARCTION, PAINAlso get cytopenias of other cell types (esp NEUTROPENIAS) as bone marrow focusses on producing more ineffective RBCs
What precipitates sickling
- Infection- Dehydration- Cold- Acidosis- Hypoxia
Why do sickle cell patients often feel well despite being anaemic (when not in crises)
HbS release oxygen more readily (lower oxygen binding affinity)
Clinical presentation of sickle cell trait
Symptom free but can sickle under increased hypoxia/stress e.g. anaesthesia, upressurised aircarft- vaso-occlusion may occurPROTECTIVE against FALCIPARUM MALARIASlight increased risk of renal disease/cancer
Conditions caused by homozygous sickle cell anaemia
Vaso-occlusive crisesACUTE CHEST SYNDROMEPulmonary hypertensionAnaemia- can complicate to BONE MARROW APLASIA (usually after PARVOVIRUS B19 infection)
S&S of vaso-occlusive crisis + complications
- ACUTE PAIN - HANDS and FEET (dactylitis) in KIDS - LONG BONES such as the femur, spine, ribs and pelvis - ADULTS * vaso-occlusion of small vessels and AVASCULAR NECROSIS of BONE MARROW- Possible CNS infarction in children -> stroke, seizures and cognitive defects- Attacks vary in frequency - can occur as much as every day to once a year depending on patient
What occurs in Acute chest syndrome + S&S + causes
PULMONARY VASO-OCCLUSIVE CRISIS(occurs in 30%)Caused by INFECTION (CHLMYDIA, MYCOPLASMA, STREP PNEUMONIAE)-> FAT EMBOLISM from NECROTIC BONE MARROWOR-> PULMON INFARCT - SEQUESTRATION of sickle cellsSOB, CHEST PAIN, HYPOXIA (vicious cycle)
Define pulmonary hypertension
Mean pulmonary artery pressure greater than 25mmHg (checked by right heart CATHETERISATION - inserted into right heart)
Pulmonary hypertension in sickle cell
Occurs in 10% of patients- Most probably caused by damage from repeated chest crises and repeated thromboembolism and intravascular haemolysis- Increases the risk of hypoxaemia and worsening sickle cell crisesCommon cause of death in adults with SCD
Anaemia in SCD
Stable low haemoglobin in CHRONIC HAEMOLYSISACUTE FALL:- SPLENIC SEQUESTRATION -> splenomegaly + acute fall in Hb -> Fibrotic, non-functioning spleen (potentially) - BONE MARROW APLASIA - PARVOVIRUS B19 (slapped cheek appearance) INVADES PROLIFERATING ERYTHROID PROGENITORS -> NO RETICULOCYTES IN PERIPHERAL - FAILURE OF ERYTHROPOESIS in marrow * Aplastic crisis
Long term complications of SCD
Growth + development delayedAvascular necrosis of hips, shoulder; compression of vertebrae; shortening of peripheral small bones- Osteomylelitis from S. aureus, S. pneumoniae, SalmonellaCardiomegaly, arrhythmias (+ iron overload cardiomyopathy)- MI25% -> TIA, fits, cerebral infarcts, comaChronic hepatomegaly + dysfunctionChronic tubulointersitial nephritisRetinopathy/detachment, vitreous haemorrhageImpaired placental flow in pregnancy -> spontaneous abortion
Diagnosis of SCD
Blood count:- Hb 60-80 g/L- RAISED RETICULOCYTESBlood film - SICKLED ERYTHROCYTESSICKLE SOLUBILITY TEST - positiveHb ELECTROPHORESIS [- DIAGNOSTIC]- 80-95% HbS (NO HbA)Best to diagnose with CORD BLOOD at BIRTH -> PROMPT PNEUMOCOCCAL PROPHYLAXIS
General reatment of SCD
Avoid/rapidly treat precipitating factors e.g. prophylaxis vaccineFOLIC ACID for all HAEMOLYTIC ppl
Treatment for acute painful attacks in SCD
IV fluidsANALGESIA (morphine, codeine, paracetamol, NSAIDs)O2 + antibiotics if needed
Treatment for SCD anaemia
BLOOD TRANSFUSION (iron overload risk)- Acute chest syndrome- Acute anaemia due to acute splenic sequestration- Aplastic crisis- Stroke- Heart failureORAL HYDROXYCARBAMIDE/HYDROXYUREA- Increases HbF concStem cell transplant
How long can body store folate
Low stores for ~ 4 months
Where is folate absorbed
Duodenum/proximal jejunum
Folate deficiency pathophys
Folate - essential for DNA synthesisIn deficiency:-> impaired DNA synthesis-> DELAYED NUCLEAR MATURATION-> large RBCs + decreased RBC productionAffects all cells in body but BONE MARROW most affected due to HIGH ACTIVITYAlso needed for fetal development so -> neural tube defects
Causes of folate deficiency
POOR INTAKE (main cause)Increased demand (pregnancy, increased cell turnover - haemolysis, malignancy, inflam disease, renal dialysis)MALABSORPTION (coeliac/crohn’s)ANTIFOLATE DRUGS (METJOTREXATE, TRIMETHOPRIM)
Risk factors for folate deficiency
- Elderly- Poverty- Alcoholic- Pregnant- Crohn’s/coeliac
Presentation of Folate deficiency
May be asympSymptoms of anaemiaGLOSSITIS can occur (sore tongue)NO NEUROPATHY (unlike B12)
Diagnosis of folate deficiency
Blood count/film:- MEGALOBLASTIC- MACROCYTIC RBCs- OVAL MACROCYTES and HYPERSEGMENTED NEUTROPHILS (>=6 lobes) in peripheral filmSERUM + RBC folate - LOWGI investigation to excludeSerum bilirubin may be high - from ineffective erythropoiesis -> increased haemolysis
Treatment of folate deficiency
FOLIC ACID TABLETS daily for 4 months - BUT ONLY WITH NORMAL B12/B12 SUPPLEMENTS! (may worsen B12 def -> spinal cord degeneration)Treat underlying cause
What food is folate found in
Green veg (spinach, broccoli)NutsYeastLiver
What food is B12 found in
MeatFishDairy(NOT PLANTS)
How long do B12 body stores last
4 years
How is B12 absorbed
Binds to INTRINSIC FACTOR from PARIETAL CELLS (in stomach)Absorbed in TERMINAL ILEUM
Pathophys of B12 deficiency
ESSENTIAL for THYMIDINE -> DNA synthesisIMPAIRED DNA synth -> DELAYED NUCLEAR MATURATION-> Megaloblasts + reduced RBC productionBone marrow most affected (high activity)
Causes of B12 deficiency
Dietary (vegans)Malabsorption (lacking intrinsic factor, ileal resection)PERNICIOUS ANAEMIA (most common)
Risk factors for Pernicious anaemia
Elderly (>60)FEMALEFair-haired, blue-eyedBlood group AOTHER AUTOIMMUNE (Thyroid, Addison’s)
Pathophys of pernicious anaemia
- Parietal cell antibodies (present in 90% - but NON-SPECIFIC)- INTRINSIC FACTOR ANTIBODIES (only present in 50%)-> Autoimmune gastritis of FUNDUS - plasma cell/lymphoid INFILTRATIONParietal/CHIEF cells REPLACED BY MUCIN-SECRETING cells-> ACHLORHYDRIA (reduced HCl)-> ABSENT INTRINSIC FACTOR secretion
Presentation of B12/Pernicious anaemia
INSIDIOUS ONSET - increasing symp of anaemiaPotential LEMON-YELLOW skin - pallor + mild jaundice (from haemolysis)GLOSSITIS + ANGULAR CHEILOSIS/STOMATITIS (potentially)NEURO FEATURES if V. LOW B12:- Symmetrical parasthesia - fingers + toes- LOSS OF VIBRATION + PROPROCEPTION (1ST thing lost)- Progressive weakness/ataxia -> potential PARAPLEGIADementia, psychiatric problems, hallucinations, delusions and optic atrophy may occur (from vitamin B12 deficiency)
Diff diagnosis for pernicious anaemia (megaloblastic + B12 def)
Folate def (also megaloblastic) - no neuropathyOther causes of B12 deficiency- Terminal ileum disease/bacterial overgrowthGastrectomy
Diagnosis of pernicious anaemia
Blood count/film:- MEGALOBLASTIC- MACROCYTIC- Peripheral: OVAL MACROCYTES + HYPERSEGMENTED NEUTROPHILSPotential raised biliirubinLOW SERUM B12 LOW Hb + RETICULOCYTE COUNTINTRINSIC FACTOR ANTIBODIES (DIAGNOSTIC) (- low sensitivity, not present in all patients)
Treatment of B12 deficiency
If malabsorption - INJECTIONS -> IM HYDROXOCOBALAMINOral B12 if dietaryTreat other underlying causes
Prophylactic folate in pregnancy (dose)
400mg for first 12 weeks
Types of leukaemias
Acute Lymphoblastic leukaemia (lymphoblast)Acute Myeloid lukaemia (myeloblast)Chronic myeloid leukaemia (myeloid progenitor???)Chronic Lymphocytic leukaemia (B lymphocyte)
Markers of high cell turnover in haemolytic anaemia
INCREASED LDH (lactate dehydrogenase - enzyme of cell turnover), and UNCONJ BILIRUBIN (from haemolysis)LOW HAPTOGLOBIN (protein that binds to free haem - lots of free haem in haemolysis so haptoglobin being used up)
How do you differentiate between Normocytic anaemias
Non haemolytic (CKD, malig, Endocrine, mixed) have low reticulocytesCan differentiate between Blood loss/haemolysis by presence of cell turnover markers in haemolysis
How to differentiate between microcytic anaemias
IRON PANEL:- Ferritin low, TIBC high (iron def)- Feritin normal, TIBC low, low serum iron (chronic disease)- HIGH serum iron + low TIBC (Thal/Sideroblastic)
Risk factors for AML
- AGE > 65- Down’s, Patau’s (trisomy 13) and Klinefelter’s (XXY) syndrome- Chemo (METHOTREXATE) - previous treatment- Previous heamatological disorders e.g. MDS- Irradiation- Benzene exposure- inherited genetic conditions (e.g. Fanconi’s anaemia, ataxia telangiectasia, germilne TP53 mutation (tumour suppressor gene))
Pathophys of AML
Rapid proliferation of immature myeloid blasts in bone marrow, peripheral blood or extramedullary tissues (Granulocytes are not being made)Rapid progression if not treated quickly (3y survival)Defined by >= 20% blast cells in BM OR PERIPHERAL bloodAcute promyelocytic leukaemia subtype is particularly characterised by hypergranular promyelocytes + Auer rods and is linked to t(15:17)
Presentation of AML
BONE MARROW FAILURE:- functional pancytopaenia * Anaemia = pallor, fatigue, dizzy, palpitations * Neutropenia = infections * Thrombocytopaenia = bruising (ecchymosis or petechiae), bleeding (esp muscosal)- bone painTISSUE INFILTRATION:- swollen gums- skin/testicular mass- Hepatoplenomegaly- lymphadenopathy
What is Plummer-Vinson syndrome
Web-like growth of membrane in throat from iron deficiencyDysphagia, Upper oesophageal webs, IRON DEFICIENCY ANAEMIA
Diagnosis of AML
FBC/Blood film:- AUER RODS (dark rods in cytoplasm of neutrophils)- neutropenia (can have normal/high WCC)- Anaemia- Thrombocytopenia - coag panel typically normal tho - abnormal suggests DIC- serum LDH may be raised+ U+E, LFTs, RFTs, etcBone marrow BIOPSY (aspirate or trephine) or Peripheral BLOOD SMEAR >= 20% MYELOBLASTS (definitive, gold standard)- typicaly paler nuclei + lack of cell varietyHistory of pre-esisting malignancy (esp MYELODYSPLASTIC SYNDROME or Myeloproliferative neoplasm e.g. polycythaemia vera)Acute promyelocytic leukaemia = t(15:17)Immunophenotyping = -ve for TdT (terminal deoxynucleotidyl transferase) + +ve for myeloperoxidase
Differential diagnosis of AML
- Haematinic deficiency (B12/folate/iron)- Infection (e.g. retroviral, herpervirus)- Meds- Autoimmune- Liver disease
Management of AML in fit individual
CHEMO - ~4-6 weeks (~4 cycles)(ATRA for acute promyelocytic leukemia - subtype)- HICKMAN/PICC LINE or portacathSupportive measures:- transfusions- treat infections(- fertility cryopreservation)Check basline cardiac, liver + renal function (blood tests, ECHO etc.) - damage can occur from chemo
Side effects of chemo
- Nausea/vomiting (antiemetics routinely given)- Altered bowel habit (diarrhoea/ constipation)- Loss of appetite- Reduced fertility- Fatigue- Allergic reactions to chemo +/- other supportive medicationsCYTOPENIAS (need transfusions + prophylactic antimicrobials)Bystander organ damageHair loss
Less intensive (non curative) treatments for AML
Outpatient - for older/less fit- Azacytidine +/- venetoclaxLow dose subcutaneous cytarabineTrial drugs e.g. targeted therapy FLT3i, IDH2i (specifc genes)Supportive measures
Pathophysiology of CML + Risk Factors
presence of BCR-ABL gene fusion in PHILADELPHIA CHROMOSOME (t(9:22))-> IRREVERSIBLY ACITIVATES TYROSINE KINASETYROSINE KINASE INCREASES CELL PROLIFERATION - inhibits apoptotic pathway - JAK-STAT -> increased haematopoesis-> myeloid hyperplasia of bone marrow>=20% blasts on BM biopsy = Blast crisis -> AMLRFx:- AGE 65-74- Ionising radiation- Male
Symptoms of CML
General leukaemia symptoms (BONE MARROW FAILURE + BONE PAIN)- hyperviscosity (headaches, thrombosis)MASSIVE HEPATOSPLENOMEGALY (if alongside malaria esp) -> abdo discomfortB symptoms potentially (hypermetabolic) - weight loss, malaise, night sweats (from tissue infiltration) + fever
Diagnosis of CML
Genetic/Cytogenic tests for BCR-ABL/Philadelphia chromosome - use either qRT-PCR or fluorescent in situ hybridisation (FISH)- FBC - pancytopenia (but granulocytosis/leukocytosis) + raised WCC- Metabolic panel (potential raised K+, LDH, uric acid)- Peripheral blood smear: mature/maturing myeloid cells - Basophil >= 20% = accelerated phaseBlast cell % shows severity - phases(>10 chronic - best; accelerated phase - >=15, <30; >=20 BLAST CRISIS - can accelerate into AML)BM biopsy - INCREASED GRANULOCYTES (diagnostic)
Treatment for CML
IMATINIB (400mg daily) - TK inhibChemo- monitor FBC for haem normalisation- reassess/monitor every 3 months May need allogenic transplantVery treatable - 40% chance of no recurrence after deep remission
Differentials for high WCC
Common - infection (c. difficle, tb, shigella)Steroids or g-csf (granulocyte colony stimulating factor - growth factor)Ethylene glycol (in polyester + antifreeze - poisoning I suppose)MIMesenteric ischaemiaGangreneParaneoplastic (non-haem malignancies - abnormal bone marrow response to neoplasm)(haem malignancies uncommon)
Pathophys of acute lymphoblastic leukaemia
Genetic mutation + rapid uncontrolled proliferation of lymphoblasts/lymphoid progenitor cell -> replacing normal haematopoetic cells in BM + infiltrating organs- B cell lineage more commonly affected - linked to t(12:21)Good prognosis
Risk factors for ALL
Particularly affects children <5 y/oGenetic:- DOWN’S- Neurofibromatosis (tumors that affect nervous system)- FHxFolate metabolism polymorphisms- Hx of malignancy- Radiation- Chemo
Presentation of ALL
BONE MARROW FAILURE + BONE PAIN- Anaemia (pallor, fatigue)- Thrombocyotpenia (bruising, bleeding etc)- Neutropenia -> infections + feverTissue infiltration:- Hepatosplenomegaly- Swollen testes, kidneys, lymph nodes, skin- B symptoms - weight loss, malaise, night sweats (MORE COMMON than in AML/CML)Can get CNS involvement -> neuro signs, raised ICP, meningism etc
Diagnosis of ALL
FBC - pancytopeniaBloodfilm - INCREASED LYMPHOBLASTSBlood film - 1x10^9 lymphoblasts per LBM BIOPSY - >=20% LYMPHOBLASTS (DIAGNOSTIC)+ hypercellular + lymphoblastic infiltrationImmunofluroscence/phenotyping - TdT +ve lymphoblasts, but myeloperoxides -ve (opposite of AML)(TdT = terminal deoxynucleotidyl transferase - oligoclonal market characterising undifferentiated/poorly differentiated lymphoid blasts)
Treatment for ALL
Chemo:- prednisolone/dexamethasone- cyclophosphamide- vincristine- doxorubicin/daunorubicin+ Methotrexate for CNS prophylaxisconsider allo transplantTyrosine kinase inhib if philadelphia chromosome +ve
Pathophys of Chronic lymphocytic leukaemia
INSIDIOUS/Indolent accumulation of incompetent mature lymphocytes, esp B cells (become continuously activated -> monoclonal b-cell lymphocytosis -> CLL) that occurs with increasing age- failure of cell apoptosis- lymphocytosis is sustained for at least 3 months- >5 x 10^9/Laccumulation in BM (can crowd out functional cells?) -> BM failure
Presentation of CLL
Oft asympLymphadenopathy (NON TENDER)- BM FAILURE - pancytopenia- HepatosplenomegalyPotentially B symps
Risk factors for CLL
Age > 60MaleGenetics - FHx; White ethnicity
Diagnosis of CLL + Tx
FBC - WCC = lymphocytosis; cytopenia for rbcs, plts, other wcBlood film - SMUDGE CELLS (old, broken)May do BM biopsy (infiltration/overcrowding); CT scan (hepatosplenomegaly)Tx:- If asymp: observation- Symp: immunochemotherapy e.g. - High dose methylprednisolone + anti-CD20 (e.g. Rituximab)
Complication of CLL
Richter transformation- massive B cell acumulation in lymph nodes-> massive lymphadenopathy-> transforms to aggressive lymphoma
Most common leukaemia in kids
ALL
Most common leukaemia in general/adults
CLL
Reactive vs cancer lymph nodes
Reactive - TENDER (+ has hilum?)Cancer - rounded, rubbery, growing, NON-TENDER
Define lymphoma
Accumulation of cancerous lymphocytes forming tumour in lymph nodes
Risk factors for Lymphoma
EBV - glandular fever (in developing)HIV (in developed)SLESjogrens (reduced fluid production e.g. tear/spit)AGE (Hodgekin’s esp in TEENS + ELDERLY)
Presentation of Hodgekin’s lymphoma
- RFx- B SYMPTOMS PAINLESS, RUBBERY LYMPHADENOPATHY- PAINFUL AFTER DRINKING ALCOHOL
Diagnosis of Hogekin’s
LYMPH NODE BIOPSY (incisional or needle core biopsy, NOT fine needle biopsy)- REED STERNBERG cell +ve (big, paler, looks multinucleated)- subtype (nodular lymphocyte predominant Hodgekin’s) -> POPCORN CELLS (popcorns are nodular)Bloods:- HIGH LDH (turnover - from metabolic panel)- LOW Hb (anaemia of chronic disease)- HIGH ESR (inflam)CT/MRI for staging
Staging of lymphomas
ANN ARBOUR STAGING1 - single lymph node2 - 2 or more on one side of diaphragm3 - 2 or more on both sides of diaphragm4 - extra-nodal metastasisA - no B symptomsB - B symptoms present
Treatment for Hodgkin
ABVD chemo - 2 cycles:Doxorubicin (Adriamycin)BleomycinVinblastineDacarbazine+ interim PET/CT
Severe complication of chemo
FEBRILE NEUTROPENIA- esp on high doseFever, tachycardia, sweats, rigors, tachypnoeaTREAT WITH BROAD SPECTRUM ANTIBIOTIC (amoxicillin, fluroquinolone)
Types of non-Hodgkin lymphomas
Low grade/indolent - slow growing, don’t always require treatment, generally incurrableHigh grade/aggressive - rapid but can be cured with timely treatment
Which cells can lymphomas affect
B, T (rare, poor prognosis) or natural killer cellsB lymphocytes most common (due to somatic hypermutation when trying to get right antibodies)
Types of indolent lymphomas
Marginal Zone lymphomaFollicular LymphomaMantle cell lymphoma
Types of high grade lymphomas
Diffuse Large B cell lymphomaBurkitt Lymphoma
Complication of Low grade lymphoma
Richter’s transformation -> aggressive, diffuse B cell lymphomaCompression syndrome (could also get in high grade - fast growing)
Which drug is a risk factor for indolent lymphomas
Methotrexate (chemo + arthritis)
Symptoms of non-hodgkin lymphomas
PAINLESS RUBBERY LYMPADENOPATHY- NOT AFFECTED BY ALCOHOLB SYMPTOMSindolent oft ASYMP or a LUMP - usually advanced at presentation
Diagnosis of Non-hodgkin lymphoma
FBCLDHESRCORE NEEDLE/EXCISION LYMPH NODE biopsy:- NO RS/POPCORN- BURKITT’S - CHARACTERISTIC STARRY SKYCan also do BM biopsyCT/PET/MRI - for stagingfor differentials:Organ functionsViral screenG6PDUric acidB2 microglobulin
Why are fine needle biopsies unhelpful for lympadenopathy
They only extract fluid not tissue
Treatment of Low grade lymphoma
Asymp:- watch + wait- REGULAR follow-up (3-6 months)Symp:- Radiotherapy (could potentially cure)Biologics:BCL2 INHIBITOR - prevents anti-apoptosisIMiDs (immunomodulatory imide drugs)BiTE and CAR-T (risk of cytokine release syndrome)
Treatment of high grade lymphoma
Immunochemotherapy, with autograftRadiotherapyCheck Point inhib (release host immune -> increased activity/ability)Mononuclear antibodiesBITE/CAR-TAllogenic transplant (uncommon)
Complication of allogenic transplant
Graft vs Host disease (tho a stronger immune reaction tends to fight off cancer better in long-run if graft is tolerated)
What is the standard Chemo used for non-Hodgkin lymphoma
R-CHOP:Rituxumab (CD20 Ab), Cyclophosphamide, Hydroxydaunorubicin, Vincristine, Prednisolone (steroid)
Define multiple myeloma
Malignant monoclonal proliferation of plasma cells - typically 1 specific Ab - esp IgG (55%) and IgA (20%)(“monoclonal paraprotein”)>10% PLASMA CELLS IN BONE MARROW
Risk factors for multiple myeloma
AGE (>70)AfrocarribeanHIV
Symptoms of MM
Old CRAB or CRABBIOld (>70)hyperCALCAEMIA RENAL Failure - hypercalcaemia -> calcium oxalate stones - Ig light-chain deposition (nephrotoxic) - BENCE JONES PROTEINANAEMIA (BM failure)BONE LYTIC LESIONSBleedingInfections
Pathophys of MM
Lack of apoptosis of differentiated b-lymphocytes. These plasma cells return to the bone marrow and overcrowd it reducing the production of other haem cells. This leads to bone marrow failure -> anaemia (tired all the time), thrombocytopaenia (bruising/bleeding), neutropenia (infections) except increased plasma cells.Also causes bone lytic lesions -> hypercalcaemia as calcium from bone is releases. Some osteoporosis so pathological fractures can occur. Overall some profound bone deformity.Hypercalcaemia increases risk of calcium oxalate renal stones. The increased deposition of the light kappa chains of immunoglobulins (ie Bence jones protein) in the kidneys is also NEPHROTOXIC -> kidney failure and Bence Jones protein in urine.
Diagnosis of MM
Bloods - pancytopenia (NORMOCYTIC NORMOCHROMIC anaemia); - HYPERCALCAEMIA- Raised ESRBlood film:- Peripheral Rouleaux formation (RBCs stacking like coins in a line) - PATHOGNOMONICU+E - renal failure- XR to check for stonesUrine dipstick - BENCE JONES proteinBONE profile - HYPOcalcaemia + RAISED ALPBM ASPRIATE - >10% PLASMA CELLSSERUM ELECTROPHORESIS- BAND for specific Ig paraprotein (hypergammaglobulinaemia - normally spread out)XR SKULL - PEPPER POT SKULL- osteolytic lesions
Differential diagnosis of MM
MGUS (mammyloid gammopathy undefined significance)- precursor to myeloma (found in 10% at 80 y/o)ASYMP<10% BM plasma cellsno/little paraprotein spikeAmyloidosis (green on histology)oft get end-stage renal failure
Treatment of MM
ONLY TREAT IF SYMPTOMATICCHEMO MONOCLONAL ANTIBODIES - DARATUMUMABBisphosphates (alendoronate)Kyphoplasty - inject cement to support vertebrae- blood transfusionConsider BM stem cell transplant
Complication of MM
Richter transformation
Primary causes of Polycythaemia
POLYCYTHAEMIA VER (JAK2 V617 mutation)EPO receptor mutation(High O2 affinity Hb? seems more secondary)
Secondary causes of polycythaemia
HYPOXIAHIGH EPO secretioncan also get RELATIVE POLYCYTHAEMIA from:- ACUTE DEHYDRATION - CHRONIC = apparent polycythaemia e.g in: - EXCESS ALCOHOL, - OBESITY, - HTN
Pathophys of polycythaemia vera
Malignant proliferation of a pluripotent stem cell clone (clonal disordaer) caused by JAK2 mutation (a tyrosine kinase) which transduces signals (esp from things like erythropoietin)The clones DON’T NEED EPO to AVOID APOPTOSISExcess proliferation of all haematopoietic cell lines = polycythaemia = raised haematocrit = HYPERVISCOSITY + THROMBOSIS
Presentation of polycythaemia vera
May be ASYMP - more common >60 y/oVague symp (common normally in old ppl anyways) from hyperviscosity:- Headaches- Tired- Dizziness- Visual disturbance- TinnitusSEVERE ITCHING AFTER HOT BATH/when WARMErythromelalgia - burning sensation in fingers/toes- HTN- Angina- Intermittent claudication- Plethoric complexion - congested with blood in facial skinHEPATOSPLENOMEGALY - distinguishes it as a malignancy- may also get gout from high turnover
DIagnosis of PV
FBC:- EVERYTHING raised (distinguishes from RBC only)- RAISED Hb/HAEMATOCRITGenetic screen - JAK2 MUTATIONBM biopsy (prominent erythroid, granulocytic andmegakaryocytic proliferation)LOW serum EPO
Treatment of PV
VENESECTION - LOWER HAEMATOCRIT + PLTS- remove 400-500ml WEEKLY(ft sole treatment)Chemo:- Hydroxycarbamide + Bulsulfan (esp if poorly controlled e.g. thrombocytocsis)- Low dose ASPIRINRadioactive Phosphorus seeds (ONLY >70 y/o - increased risk of leukaemia)
Medication for gout
ALLOPURINOL - block uric acid production
In which diseases may Howell Jolly bodies be seen on microscopy
- MEGALOBLASTIC ANAEMIAS- Sickle cell disease– Iron deficient anaemia
Presentation of essential thrombocytosis
- SPLENOMEGALY- ARYTHOMELALGIA (red/blue discoloration + burning in peripheries)- LIVEDO RETICULARIS (purply rash)
Types of Haemophilia
- Haemophilia A – Factor 8 deficiency - Treatment – IV Factor 8- Haemophilia B – Factor 9 deficiency
Epidemiology of Haemophilia
- X-linked recessive disorders – mainly affects men- Haemophilia A is more common
Pathophysiology of Haemophilia A
X linked gene mutation causes FVIII deficiency. Leads to insufficient formation of tenase complex (IXa, VIIIa - ie the things that activate X), reduced thrombin generation, impaired fibrin deposition and poor clot formation.The extrinsic pathway is also unable to compensate for the intrinsic deficit as it is down-regulated by TFPI (tissue factor pathway inhibitor) and the fibrinolytic pathway is up-regulated due to the low thrombin.(2nd paragraph is extra info)
Symptoms/signs of Haemophilia
Depends on plasma levels of F8/9- Levels <1 IU/dL (SEVERE) - associated with frequent spontaneous bleeding into muscles and joints -> crippling arthropathy- 1-5 IU/dL - severe bleeding following injury + occasional apparently spontaneous episodes- >5 IU/dL - mild disease: bleeding only with trauma/surgeryGeneral s&s:- Cerebral haemorrhage more common (than in general pop)- Easy bruising- Haematomas- Prolonged bleeding after cut- GI bleeding- Haematuria- Severe epistaxis- Haemarthrosis
Investigations for Haemophilia
Bloods + PT + APTTFactor 8/9 not extrinsic so:- PT = normal- VWF = normalPROLONGED ACTIVATED PARTIAL THROMBOPLASTIN TIME (intrinsic)Reduced plasma levels of factor 8/9
PT vs APTT
PT = Prothrombin time = part of the EXTRINSIC pathway (Warferin + vit K affects)APTT = activated partial thromboplastin time = INTRINSIC pathway (Heparin affects)
Management of Haemophilia
- IV recombinant factor 8/9 concentrate – given as prophylaxis (before and after surgery) or to treat an acute bleeding episode- Synthetic vasopressin – IV, s/c or intranasal administration, raises level of factor 8/9 - Hep A/B vaccinations- Encouragement to join exercise regimes and avoid contact sport and aspirin
Complications of Haemophilia
Joint deformities and arthritis from recurrent bleeding into joints
VWF disease - pathophys
Autosomal DOMINANT mutation of VWF gene on chromasome 12Reduced VWF (responsible for basis of platelet plugs) = more spontaneous bleeds/bruisingMOST COMMON inherited bleeding disorder
Diagnosis of VWF def
Affecting the intrinsic pathway so NORMAL PT but RAISED APTTBloods: normal Factors 8/9 (use an assay)- reduced plasma VWF
Treatment of VWF def
No cureDESMOPRESSIN - causes increased release of VWF from endothelial WEIBEL-PALADE BODIES (eleongated secretory organelles specifically in endothelial cells - contain VWF + other proteins for inflam, angiogenesis + tissue repair)
Pathophysiology of Disseminated Intravascular Coagulation
- Widespread generation of fibrin at points throughout the vascular system caused by the initiation of the coagulation pathway - typically the extrinsic pathway, starts with tissue factor- Consumption of platelets/coag factors - Secondary activation of fibrinolysis -> production of Fibrin + Fibrinogen Degredation Products (broken up fibrin) which inhibit fibrin poylmerisation and contribute to bleeding- Activation of Tissue Plasminogen activator -> increased fibrinolysis/worse clottingThere is initial widespread thrombus formation throughout blood vessels (causing ischaemia) -> depletion of clotting factors -> increased tendency to bleed
Causes of DIC
Imbalance between formation of new clots and breaking down old clots- Anything that causes mass activation of clotting cascade (ie severe inflam states)- Malignancy – leukaemia t(15:17) translocation (acute promyelocytic leukaemia)- Septicaemia- Trauma - Infections - meningitis- Obstetrics causes – amniotic fluid embolism - abruptio placentae (detaches from inner wall before delivery)- Haemolytic transfusion reactions- Liver disease
Presentation of DIC
Range of presentation from no bleeding to complete haemostatic failure- Bleeding - typically from venepuncture/IV sites + nose/mouth- Bruising- SOB (bleeding into lungs/ischaemia/necrosis)- HaemoptysisCan get ischaemia/necrosis -> organ damage
Investigations of DIC
Diagnosis suggested by history (severe sepsis, trauma, malignancy), clinical presentation and presence of severe thrombocytopenia- Prolonged PTT, APTT and Thrombin Time (TT)- Decreased fibrinogen and increased FDPs- Blood film – shows schistocytes (fragmented red cells - cut up by excess fibrin strands)
Treatment of DIC
- Treat underlying cause – maintain blood volume and tissue perforation- May need transfusions – platelets, RBCs and Fresh Frozen Plasma (FFP)- Activated C protein (inhibts V and VII -> less clotting)
General causes (not specific) of thrombocytopenia
- Reduced platelet production in BM- Excess peripheral destruction of platelets- Problems of enlarged spleen
Types of Thrombocytopenias
- Immune thrombocytopenic purpura (ITP) - MORE COMMON- Thrombotic thrombocytopenic purpura (TTP)
Epidemiology of ITP + types of ITP
- Type 1: in children 2-6 y/o (acute/primary) - often follows viral infection, - rapid onset or purpura which is usually self-limiting- Type 2: in adults, esp young women (chronic/secondary) - usually less acute than in children - esp women with malig, HIV, other autoimmune
Pathopys of ITP
Autoimmune destruction of platelets (IgG antibodies to platelets and megakaryocytes)- Often triggered by viral infection or malignancy- The IgG antibodies coat the platelets which are then removed by binding to Fc receptors on macrophages
Presentation of ITP
- Easy bruising- Purpura – red or purple spots on skin caused by bleeding underneath- Epistaxis – nose bleed- Menorrhagia- Gum bleedingOtherwise systemically well
Investigations for ITP
- FBC: Thrombocytopenia – low levels of platelets- Increased megakaryocytes on BM examination- May have detection of platelet autoantibodies
Treatment of ITP
- 1st LINE: Corticosteroids - PREDNISOLONE- IV Immunoglobulin (e.g. IV IgG) - Decreases splenic platelet destruction- 2nd line: Splenectomy
Pathophysiology of TTP
- deficiency in ADAMTS 13 - protease which is normally responsible for VWF degradation- Causes extensive microvascular clots to form in small vessels -> low platelet count (due to platelet consumption) + organ damage
Epidemiology of TTP
- Adult FEMALES esp with: - Malig - HIV - other Autoimmune
Presentation of TTP
- Easy bruising- Purpura/PURPURIC RASH- menorrhagia- AKI- (Microangiopathic) haemolytic anaemia (physical damage due to occlusion by fibrin deposition/platelet aggregation)- neurological Sx- Fever (SYSTEMICALLY UNWELL)
Diagnosis of TTP
- FBC: - thrombocytopenia - normal/increased megakaryocytes - Reduced ADAMTS 13- Coagulation screen: normal but LDH raised due to haemolysis- Blood film: SCHISTOCYTES (fragmented parts of RBCs)
Treatment of TTP
- PLASMAPHERESIS/plasma exchange (remove blood through needle/catheter; circulate through machine; plasma is filtered out + altered/discarded -> removes ADAMTS 13 Ab)- IV METHYLPREDNISOLONE- IV RITUXIMAB
Define PT and INR. Normal PT and INR ranges
- PT = coag speed of EXTRINSIC PATHWAY (related to time taken for prothrombin -> thrombin) - Normal ~ 10-13.5s- INR (international normalised ratio) = patient PT/referance PT - ~0.8-1.2
When may PT/INR be raised
- If on anticoag- Liver disease- Vit K deficiency- DIC
INR if on Warferin
2-3
Define APTT + give normal range
- APTT (activated partial thromboplastin time) = coagulation speed of INTRINSIC PATHWAYS - Normal ~ 35-45s
What is APTT raised in
- Haemophilia A + B- VWF(PT normal in both of above)- can be prolonged if on Heparin (it inhibits intrinsic pathway at various points e.g. prothrombin)
APTT while on Heparin
~60-80s
Define G6PDH def
X-linked recessive enzymopathy -> halving of RBC life time + degradation
Epidemiology of G6PDH def
- X linked so more common in males- typically in Mediterranean, African + Middle/Far Eastern ppl- Protective against malaria falciparum
Pathophys of G6PDH def
- G6PDH catalyses first step in pentosephosphate pathway (makes NADPH). - This pathway maintains GLUTATHIONE in reduced state.- Glutathione protects RBCs from OXIDATIVE STRESS (i.e ROS like H2O2 which -> haemolysis)-in deficiency -> increased haemolysis -> NORMOCYTIC Anaemia
Presentation of G6PDH def
- Asymp until exposed to triggering factors that cause oxidative stress -> Haemolytic anaemia - Presents with JAUNDICE Diff types:- Neonatal presentation (jaundice)- CHRONIC HAEMOLYTIC ANAEMIA- Acute haemolysis - RAPID ANAEMIA (fatigue, pallor etc) - JAUNDICEAlso:- BACK PAIN - DARK URINE (haemoglobinuria)
Triggers of G6PDH def attack
- FAVA BEANS (common in kids) - contain GLUCOSIDES which are metabolised to ROS- Drugs: - quinine, quinalones (antimalarials), - sulphonamides (sulphametoxazole, sulphasalazine), - NITROFURANTOIN - Aspirin- Infections
Investigations for G6PDH def
- FBC – anaemia and raised reticulocytes (normal if inbetween attacks)- Blood film – BITE CELLS (look like bite taken out) and blister cells, Heinz bodies (precipitated denatured haemoglobin in RBCs) (normal inbetween attacks)- Enzyme assay (low G6PDH)
Management of G6PDH def
- Avoid precipitants (e.g. fava beans, henna)- Blood transfusion if/when severe
Pathophys of Hereditary Spherocytosis
AUTO DOMINANT membranopathy- Mutation causes deficiency in STRUCTURAL MEMBRANE PROTEIN - SPECTRIN - increases permeability to sodium -> requires increased rate of active transport out of cells - makes RBCs more SPHERICAL + RIGID (reduced SA:V ratio) - Increased splenic recycling (extravascular haemolysis) -> splenomegaly due to rigid cells getting stuck in splenic microcirculation + destroyed -> risk of autosplenomegaly (spontaneous infarction -> hyposplenism)-> NORMOCYTIC ANAEMIASpecifically, RBCs lose part of their cell membrane as they PASS THROUGH THE SPLEEN - as lipid bilayer not adequatly structurally supported
Epidemiology of hereditary spherocytosis
Most common inherited haemolytic anaemia in N Europe + America
Presentation of hereditary spherocytosis
- Anaemia symps- NEONATAL JAUNDICE- SPLENOMEGALY - exacerbated during infection- GALL STONES (50% - due to excess bilirubin)- can get leg ulcers
DIagnosis of spherocytosis
FBC + blood film:- NORMOCYTIC NORMOCHROMIC anaemia- Increased RETICULOCYTES- SPHEROCYTES (-Osmotic fragility test will show fragility in hypotonic solutions)DIRECT COOMBS TEST = -VE (to rule out AHA)
Treatments for her spherocytosis
- SPLENECTOMY(as the main damage + destruction to RBCs occurs as they are going through the spleen) - wait till at least 6y/o due to sepsis risk (spleen fights off encapsulated bacteria) - Requires lifelong penicillin prophylaxis post-op- folate supps- transfusionsFor neonatal jaundice:- PHOTOTHERAPY (conjugates bilirubin)- risk of KERNICTERUS if untreated (bilirubin accumulation in basal ganglia)
Pathophys of Autoimmune haemolytic anaemias
Can either be warm or cold subtype depending on what it is precipitated by.Auto Ab bind RBCs -> intra/extravasc haemolysis
Presentation of AHA
- anaemia- potential jaundice- splenomegaly
Diagnosis of AHA
FBC + Blood film:- NORMOCYTIC NORMOCHROMIC anamia- increased reticulocytes- oft see SPHEROCYTESDIRECT COOMBES +VE (agglutination of RBCs w/ Coomb reagent) - diff from spherocytosis which is coombs -ve
Tumour lysis syndrome
Oncologic emergency caused by massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids into the systemic circulationCan cause renal AKI/failure as uric acid, calcium phosphate or hypoxanthine can precipitate in tubules -> Acute tubular necrosis-> electrolyte disturbances -> arrhythmias, siezures etc
Define sideroblastic anaemia
Oft X LINKED inherited ALA synthetase deficiency -> FUNCTIONAL Fe DEFICIENCY due to DEFECTIVE Hb synthesis in the MITOCHONDRIACan also be due to B6 deficiency- Fe is raised but is not used in Hb synth so becomes trapped in mitochondria
Diagnosis of Sideroblastic anaemia + treatment
FBC + Blood film:- MICROCYTIC- RINGED SIDEROBLASTS- BASOPHILIC STIPPLING (increased granules)Fe studies:- raised serum iron- raised serum ferritin- raised transferrin saturation- Decrease Total Iron Binding CapacityTx:- Pyridoxine (vit B6), thiamine/folate supps- Blood transfusion- Desferroxamine chelation for overload
RFx of Hodgkin’s lymphoma
- Age 20-34 years AND >55 years - esp young adults from higher socio-economic class- EBV INFECTION- FHx- certain HLA types (tho no HLA class 2 expression has been associated with adverse prognosis)- Jewish ancestry
Felty syndrome
Rare, potentially seriousDefine by presence of triad:- RA- splenomegaly- neutropenia -> repeated infections
