Haematology_Medicine Flashcards
Anaemia - cause categorization? Ix? Deficiency-related anaemia - causes & relevant deficiencies?
Hb normal range: 130-175
MCV normal range: 82-98
Categorization:
- MICROcytic - IDA, thalassaemia, anaemia of chr disease (can be normocytic)
- NORMOcytic - acute bleed, aplastic anaemia, mixed anaemia (micro & macro)
- MACROcytic - B12/folate def, alcohol excess, haemolytic anaemia
Ix: FBC
- Microcytic - haematinics (Fe profile), Hb electrophoresis (thalassemia/SCD Dx)
- Macrocytic - B12, folate, DAT test (AI haemolytic anaemia Dx)
Deficiency-related anaemia:
- Poor dietary intake - Fe, B12, folate
- Malabsorption (IBD) - Fe, B12
- Pernicious anaemia (AI parietal cell destruction -> don’t prod intrinsic factor -> escorts B12 to terminal ileum for absorption) - B12
- Crohn’s disease (most common in terminal ileum where B12 is absorbed) - B12
- Bleeding (GI, menstrual) - Fe
Haem malignancies - Types?
Types:
- Leukemia
- Lymphoid
- Acute (ALL) - child, TdT+ve
- Can have BCR-ABL1, t(9;22)
- Chronic (CLL) - smear/smudge cells, IgH UNmutated = worse prognosis, 17p gene deletion
- Acute (ALL) - child, TdT+ve
- Myeloid
- Acute (AML) - Auer rods, MPO expression pattern
- Chronic (CML) - Basophils, Philadelphia chromosome (BCR-ABL1, t(9;22)), left shift
- Lymphoid
- Lymphoma
- Hodgkin
- Non-Hodgkin
- Other
- Myeloma
- Myelofibrosis
- Myelodysplasia
- Polycythaemia Vera
Leukaemia vs Lymphoma?
Blood cell dev? How does this relate to Leukemia?
Lymphoma types? Staging?
Leukemia vs Lymphoma:
- Same disease - characterised by abn prolif of lymphocytes
- Different location:
- Leukemia - blood & BM
- Lymphoma - LNs
Blood cell development & leukemia:
- Physiology:
- Differentiation (gene expression, morphology & cell function change –> mature cells right @end)
- Proliferation (number of cells increase)
- Acute - abn differentiation (not mature) + excessive proliferation –> acute onset, excessive blast cells, likely Sx (BM failure - anaemia, recurrent inf)
- Chronic - normal differentiation (mature) + excessive proliferation –> mature cells, can be asymptomatic
Lymphoma
- Hodgkin - B-cell only, single group of LNs, Reed-Sternberg cells (multinucleated lymphocytes)
- Non-Hodgkin - 90% lymphomas, B/T-cell, multiple groups of LNs
- Common features: painless lymphadenopathy, B-Sx, pruritis
- NOTE: type ultimately determined by LN biopsy
- Staging: Ann-Arbor staging
- I: 1 site, 1-side of diaphragm
- II: 2+ sites, 1-side of diaphragm
- III: Both sides of diaphragm
- IV: BM/splenic/solid organ involvement
- NOTE: stage classified as A/B – based on presence of B symptoms (fever>38, night sweats, unintentional >10% weight loss in 6 months – FLAWS)
Multiple myeloma - def? pathophysiology? Spectrum of disease? Ix? Dx? Mx?
Def: cancer of plasma cells –> excessive monoclonal Ig prod
- Plasma cell dyscrasia (humoral immune dysfunction) – clonal plasma cell population –> proliferate –> monoclonal Ig light chains (in blood = paraprotein, in urine = Bence Jones protein)
-
Pathophysiology:
- Normally e.g. 5 different types of plasma cells produce 5 different types of Ig
- In MM - one type of plasma cell outcompetes the others so lots of 1 type of Ig produced
Spectrum of disease:
-
Multiple Myeloma:
- >1 focal lesion on MRI
- BM plasma cells >60%
-
End organ damage (1+ of CRAB(S)):
-
Calcium (>2.75) - high: lytic bone lesions –> release Ca into circulation
- NOTE: stones, bones, abdo groans, thrones, psychiatric overtones
- Renal (from excess Ig) – creatinine clearance <40ml/min OR creatinine >177
- Anaemia (Hb <100g/l) - BM supression
- Bone lesions (lytic)
- Signs of amyloidosis – damage from misfolded protein prod
-
Calcium (>2.75) - high: lytic bone lesions –> release Ca into circulation
-
Smouldering/asymptomatic myeloma
- Serum monoclonal protein >3g/dL
- BM plasma cells 10-60% in marrow
- NO end-organ damage (CRABS) BUT most progress to MM untreated
-
Monoclonal gammopathy of unknown significance (MGUS)
- Serum monoclonal protein <3g/dL
- Plasma cells <10% in BM
- No end-organ damage (CRABS)
- NOTE: 1-2% progress to MM, very common in elderly (if low risk – yearly bloods)
Dx: plasma cells on BF + Rouleaux cells
Ix: ESR, Ca, U&E, serum & urine electrophoresis (to identify an excess of one type of Ig = 1 large band)
- Electrophoresis (spike in gamma region, isolated IgG Kappa):
- Normally polyclonal bands, in myeloma = monoclonal band
- CD138= diagnostic
Mx:
-
MM:
- Young –> chemo followed by autologous SCT
- Old –> chemo followed by maintenance therapy
- Smouldering myeloma – treat
- MGUS – annual blood test
Microcytic anaemia + GI features - Ix? Mx?
Ix:
- IDA + lower GI features –> 2WW for colonscopy
- IDA + dyspepsia –> 2WW OGD (oesopho-gastro-duodenoscopy)
Microcytic anaemia, disproportionately low MCV - Dx?
Thalassaemia
Normocytic anaemia, reduced renal function - Dx?
CKD-related renal function (EPO)
Macrocytic anaemia + mixed upper/lower motor signs - Dx?
B12 def –> subacute combined degeneration of spinal cord
CML Mx? CML chromosome? How to identify if in accelerated (blast) phase? Dx?
Tyrosine kinase inhibitor e.g. Imatinib
BCR-ABL1, t(9;22)
≥20% blasts, Basophils ≥20%, progressive splenomegaly
Dx: blood film/BM aspiration, definitive = cytogenetic analysis
Auer rods - Dx?
AML
DIC & t(15;17) - Dx?
Acute promyelocytic leukaemia
Haemophilia A Mx? Haemophilia A vs B? vWD difference?
A = factor 8
B = factor 9
vWD - bleeding time prolonged because platelet dysfunction
Haemophilia - bleeding time not prolonged because no platelet dysfunction
Menorrhagia + prolonged bleed time - Dx?
vWD
Low platelets + low fibrinogen?
DIC
Raised INR, low Pl, deranged LFTs - Dx?
Liver cirrhosis
Haem malignancy buzzwords
ALL - Testicular swelling, 3-5yrs
AML - Auer rods
CML - Philadelphia chr, t(9;22), BCR-ABL1, left shift
- Tx: Imatinib (BCR-ABL tyrosine kinase inhibitor)
CLL - Smear/smudge cells
Polycythaemia vera - JAK2 mut, high haematocrit, flushed appearance, strokes/budd chiari
Essential thrombocythemia - High platelets, strokes, ± JAK2 mut
Myelofibrosis - Dry tap, teardrop cells (poikilocytes), massive splenomegaly
Hodgkin’s lymphoma - Painful LNs w/ alcohol, Reed-Sternberg cells, EBV
Follicular lymphoma - t(14;18), centroblasts
Mantle cell lymphoma - t(11;14), mantle cells
Burkitt’s lymphoma - t(8;14), starry sky appearance, EBV, HIV
Myeloma - CRAB, bence jones protein, IgG/A >30
MGUS - NO CRAB, paraprotein <30
Causes of increased vs decreased reticulocyte counts?
Increased reticulocytes
Decreased reticulocytes
Haemolytic anaemia
Recent haemorrhage
Thalassemia
Pregnancy
Treatment response
Hypoxia
Leukaemia
Aplastic anaemia
Megaloblastic anaemia (B12, folate)
Anaemia of chronic disease
Cirrhosis
Radiation
Decreased ACTH/pituitary hormones
ALL - associated with what gene? Presentation? Ix? Mx?
ALL
- BCR-ABL1 t(9;22) assoc w/ 20-30% ALL in adults –> this genetic mutation also causes CML
-
Child Hx: 2-5yrs
- Hepatosplenomegaly
- Bone pain/limp
- Fevers, CNS Sx
- Testicular swelling (rare but specific)
- Adult Hx: like AML, lymphadenopathy
-
Investigations:
- Bloods - thrombocytopenia, anaemia, high WCC (blasts/lymphocytes)
- NOTE: circulating blasts = normal
- Blood film – high nucleus: cytoplasm ratio, can’t differentiate betw/ ALL/AML on BF
- Dx - BM + flow cytometry:
- TdT+
- CD19/22 = B cells (common)
- CD2/3/4/8 = T cells
- Bloods - thrombocytopenia, anaemia, high WCC (blasts/lymphocytes)
- Management (adults and children similar aim):
- Induction –> consolidation –> maintenance –> remission
- Covering all these stages = transplant ±novel targeted therapies (+ CAR T-cell therapy)
AML - Hx? Ix? Mx? AML vs CML difference on Ix?
-
Hx:
- Incidence increases w/ age
- Pre-existing myelodysplastic syndrome (MDS)
- Cytopenia Sx
- NOTE: AMML causes gingival hypertrophy (MM looks like gums)
-
Investigations:
- Bloods – anaemia (BM suppression), high WCC (neutropenia, excess circulating blasts), thrombocytopenia (BM suppression), only abnormal INR if DIC from acute promyelocytic leukaemia
- Blood film – single Auer rod = Dx, if none –> flow cytometry – MPO expression pattern
- Management:
- T(15;17) acute promyelocytic leukaemia – presents w/DIC, good prognosis, ALL-trans retinoic acid (ATRA) – causes cells to differentiate/stop prolif
- Others: manage like ALL, poor prognosis esp in elderly (can’t tolerate stem cell transplant
- AML VS CML- Basophils in CML
CML - gene associated? Hx? Ix? Disease phases? Mx?
- Most assoc w/ Philadelphia chromosome – BCR-ABL1 fusion gene from translocation of t(9;22) –> detected w/ FISH
- Hx/exam:
- Age 35-55yrs
- LUQ pain (from splenomegaly)
- Asymptomatic if Dx in chr phase ± lethargy, fever, night sweats
- Sx of acute leukaemia if in accelerate/blast phase (10%)
- Investigations:
- Bloods: raised basophils (specific), high WCC (neutrophilia), 50% thrombocytosis, low monocytes (high = CMML), unlikely sign anaemia (can be), precursor cells on blood differential (promyelocytes/myelocytes)
- High WCC causes:
- Acute bact inf (high neutrophil: lymphocyte ratio)
- Acute viral inf (low neutrophil: lymphocyte ratio BUT COVID-19 –> lymphopenia)
- Fungal/parasitic (high eosinophils)
- Monocytosis (in TB, endocarditis, inflame conditions)
- High WCC causes:
- Bloods: raised basophils (specific), high WCC (neutrophilia), 50% thrombocytosis, low monocytes (high = CMML), unlikely sign anaemia (can be), precursor cells on blood differential (promyelocytes/myelocytes)
- Features:
- Left shift – precursor cells present
- High WCC, eosinophilia, basophilia
- Hypo-lobated megakaryocytes – in BM
- Disease phases:
- Chr (90%)
- Accelerated (increased blasts in BM, poor Tx-response, additional chromosomal abn)
- Blast phase (>20% blasts in BM, behaves like acute leukaemia)
- Management:
- Chronic phase –> Tyrosine kinase inhibitors – 1st gen = Imatinib (2nd gen – Dasatinib/Nilotinib/Bosutinib, 3rd gen – Ponatinib)
- >90% 10yr survival –> small % need transplants
- Blast phase – Tx similar to AML (allogenic SCT for young)
CLL - presentation? Ix? Mx?
- Presentation:
- Asymptomatic – routine bloods
- >50yrs (incidence increases w/ age), X2 M>F
- Possible LNs/splenomegaly
- ITP (immune-mediated thrombocytopenic purpura)/haemolytic anaemia
- Investigations:
- Bloods: only anaemia if aggressive/haemolytic anaemia, high WCC (>100, mature lymphocytes)
- BF: smear cells/smudge cells, lymphocytosis
- Dx: flow cytometry – Kappa/Lambda light chains
- Mostly B cell CLL (but can be T cell)
- Same pathology as small lymphocytic lymphoma BUT different distribution (blood/BM Vs LNs)
- B-cells CD5 +ve (normal mature B-cells CD5 -ve), CD38 +ve = poor prognosis
- Immunoglobin gene mutations: IgH unmutated = worse prognosis
- FISH – 17p gene deletion (TP53 – contains p53 tumour suppressor gene) gene deletion –> worse prognosis
- Management:
- Staging:
- A – no cytopenia, <3 areas lymphoid involvement –> W&W
- B – no cytopenia, ≥3 areas lymphoid involvement –> consider Tx
- C – cytopenia –> TREAT
- BCL-2 inhibitors (Venetoclax) – allows the normal apoptosis of B-cells
- BCR-tyrosine kinase inhibitors (ibrutinib, idelalisib)
- CAR T-cell therapy (for B cell cancers e.g., B-cell lymphoma)
- NOTE: all very expensive
- Richters syndrome – transformation of CLL –> aggressive disease (ALL/high grade lymphoma)
- Staging:
Myeloproliferative disorders - characteristics? causes? Mx?
ALL = tyrosine kinase disorder (JAK2)
Essential thrombocythemia
- High Pls: >450 (other causes of raise: acute inf, chr infl, malig (5-10%), polycythaemia rubra vera)
- JAK2 mutation in 55%
- Mx: aspirin to reduce stroke risk, hydroxycarbamide to lower pl count
Polycythemia vera
- _High RBC_s:
- Haematocrit >0.52 (M) /0.48 (F)
- Often thrombocytosis – high risk of thrombotic event (MI, stroke, Budd-Chiari)
- JAK2 mutation in 90%
- Causes:
- Primary: polycythaemia rubra vera
- Secondary: altitude, chr hypoxia (severe COPD, cyanotic HD), erythropoietin-secreting renal cancers (RCC)
- NOTE: secondary polycythaemia = no JAK2 mutation
- Presentation: itchy (pruritus) after shower, peptic ulcers (increased histamine)
- If very high RBC count –> hyperviscosity Sx, splenomegaly, thrombosis, gout
- Mx:
- Aspirin to reduce stroke risk, hydroxycarbamide to lower pl count
- Venesection (removing blood –> lowers haematocrit)
Myelofibrosis
- decrease all myeloid cell lines: MASSIVE SPLENOMEGALY
- Clonal prolif of stem cells in BM –> cytokine release + fibrosis of BM –> pancytopenia
- Features:
- JAK2 mutation in 50%
- Pancytopenia
- Massive splenomegaly (extramedullary hematopoiesis)
- Dry tap – on BM aspiration
- Tear drop poikilocytes – on BF (leucoerythroblastic film)
- Mx: stem cell transplant = only cure, ruloxitinib (JAK inhibitor)
- NOTE: CML increases all myeloid cell lines (opposite)
Myelodysplastic syndromes
Dx? Characteristics? Ix findings? Prognosis?
Myelodysplastic syndromes (MDS)
- Pre-malignant BM failure/’early AML’ (<20% blasts; NOTE: >20% blasts = AML)
- All 3 myeloid cell lines can be affected (erythroid, megakaryocyte, granulocyte)
- Asymptomatic –risk progression–> AML
- Can be secondary to chemo
- Ix:
- Hyposegmented + hypogranular neutrophils
- Present w/ incidental pancytopenia, can have macrocytic anaemia (normal ferritin/B12/folate/erythropoietin –> suspicious of MDS)
- Prognosis: 30% progress to AML, risk assessed w/ IPSS score
Classical Hodgkin’s lymphoma - peaks when? presentation? histology? most common type? assoc inf? Mx?
- Peaks: young, older adults
- Presentation: localised LNs (freq mediastinal), B-symptoms (fever, WL, NS)
- NHL = multiple nodal sites
- Pain in LNs after alcohol
- Neck node “rubbery”
- Possibly assoc w/ EBV inf
- Histology: Reed-Sternberg cells (“Owl’s eye” inclusions) = Dx (only 1 needed)
- Other findings – eosinophils/macrophages, reactive fibrosis
- Dx markers: CD30/15
- Nodular sclerosing = most common type
- Mx: ABVD chemo + radiotherapy –> good prognosis –> sometimes SCT
MICROangiopathic haemolytic anaemia (MAHA)
- Haemolytic uraemic syndrome (HUS)
- Thrombotic thrombocytopenic purpura (TTP)
- Disseminated intravascular coagulation (DIC)
MICROangiopathic haemolytic anaemia (MAHA)
- Non-immune-mediated, small vessel disease, RBC breakdown
- Damage to endothelial BV lining –> fibrin deposition + platelet aggregation –> fragmentation of RBCs (Schistocytes)
- It is a mechanism NOT a disease
Haemolytic Uraemic Syndrome (HUS)
- Post-_diarrhoeal_ illness – do NOT give abx
- E.coli O157:H7 –> Shiga-like toxin can cause glomerular endothelial injury –> platelet plug forms (platelet consumption) –> shearing of blood vessels (MAHA) + reduced renal perfusion –> renal failure
- Can get type with complement factor H deficiency
- Diarrhoea in child –> triad:
- MAHA (features on peripheral blood smear e.g. schistocytes)
- Haemolysis signs - high LDH, low haptoglobins
- Thrombocytopenia
- acute renal failure (self-limiting in children)
- MAHA (features on peripheral blood smear e.g. schistocytes)
- Supportive Mx, anti-C5 Ab (ecluzimab)
TTP
- Pathophysiology:
-
vWF multimers are normally broken down by ADAMTS13 but in TTP Abs against this –> reduced ADAMTS13
- Causes: unknown, cancer, pregnancy
- Increased vWF multimers = very sticky –> attach to endothelium & platelet plug forms (platelet consumption) –> shearing of blood vessels (MAHA) + reduced end-organ perfusion (can happen anywhere) –> confusion (brain), renal failure (kidneys)
-
vWF multimers are normally broken down by ADAMTS13 but in TTP Abs against this –> reduced ADAMTS13
- Pentad: MAHA, thrombocytopenia, acute renal failure, NEURO Sx, fever
- Case: 40yrs, fever, headache, jaundice for 1wk, temp 39, confused
- Purpura, bleeding gums, haemoglobinuria
- Bilirubin & LDH high = MAHA
- Case: 40yrs, fever, headache, jaundice for 1wk, temp 39, confused
- Ab to metalloproteinase
- Supportive Mx - plasma exchange + FFP
DIC
- Trigger (sepsis, tumour, pancreatitis) –> increased exposure to Tissue factor –> factor 7 converted to 7a = coagulation cascade –> lots of miniclots formed throughout circulation - platelet & coagulation factor consumption
- Very bad bleeding, Low platelets, PT & aPTT low (all coagulation factors low), low fibrinogen
Case: 44yrs, admitted for Tx of staph cellulitis –> gangrene –> BP 86, bleeding from multiple sites
Ix: blood film shows schistocytes
Dx? Def? Findings on coag screen? Tx?
DIC - consumptive coagulopathy where you get massive activation of clotting cascade intravascularly (use up clotting factors and platelets) –> bleeding from multiple sites
- Mortality 70-80%
Coagulation screen: high APTT, high PT, low platelets, low fibrinogen
Tx: replace platelets, FFP & cryoprecipitate, activated protein C
Heparin vs Warfarin - how do they work? Warfarin reversal? INR target range?
Heparin: potentiates antithrombin III –> inactivates thrombin + factors 9, 10, 11 (effects the intrinsic (aPTT) and common pathways)
- LMWH: given SC OD, does not require monitoring (except late pregnancy/renal failure – anti-Xa lvls monitored)
- Unfractionated heparin (used if renal impairment): given IV, loading dose then infusion, monitor APTT (or anti-Xa/heparin lvls in some trusts)
- Antidote: protamine sulphate
- SEs: bleeding/heparin-induced thrombocytopenia (HIT), osteoporosis w/ LT use
- SEs more common with UFH
Warfarin: inhibits reductase enzyme that regenerates the active form of Vit K –> inhibits synthesis of factors 2, 7, 9, 10 + proteins C, S and Z (effects the intrinsic and extrinsic (PT/INR) pathways)
- Risk of teratogenicity
- How to start Warfarin:
- Check LFTs
- Concurrent LMWH until INR >1.8 (protein C reduced w/ warfarin = temp procoagulant state + thrombosis in venules –> skin necrosis)
- Warfarin reversal:
- Any bleeding: stop Warfarin AND IV vit K slowly (takes 6hrs)
- If major bleed = ADD dried PCC/FFP (takes 30 mins)
- INR @24hrs –> continue Tx if INR high, continue Warfarin when INR <5
- INR >8: stop Warfarin AND oral Vit K
- INR @24hrs –> continue Tx if INR high, continue Warfarin when INR <5
- INR 5-8: miss dose of Warfarin –> reduce maintenance dose
- Any bleeding: stop Warfarin AND IV vit K slowly (takes 6hrs)
- Therapeutic INR range:
- 2.5 (2-3) – 1st episode of DVT/PE/AF (+ cardiomyopathy, symptomatic inherited thrombophilia, mural thrombus, cardioversion
- 3.5 (2.5-3.5) – recurrent DVT/PE/mechanical prosthetic valve (+ coronary artery graft thrombosis, antiphospholipid syndrome)
Haematological malignancies - stem cell differentiation & associated malignancies?
Multipotent stem cell differentiation & associated malignancies:
- Common myeloid progenitor:
- Megakaryocytes (create platelets)
- Erythrocytes
- Myeloblasts –> Neutrophils, Basophils, Eosinophils, Monocytes
- NOTE: immature myeloid progenitor cells increase in AML
- NOTE: mature myeloid cells (N,B,E,M) increase in CML
- Common lymphoid progenitor:
- T-cells
- B-cells:
- Plasma cells
- NOTE: increased replication of abn plasma cell in MM –> produce huge amounts of one type of monoclonal Ig
- NOTE: immature lymphoid progenitor cells increase in ALL
- NOTE: mature lymphocytes increase in CLL
- NOTE: if you get abnormal replication of lymphocytes in lymphatic system = Lymphoma (most are B-cell lymphomas)
Leukaemia types - buzz words
- Acute myeloid leukaemia (AML)
- Acute, adults
- BM failure (anaemia, inf risk, bleeds)
- Extra: Acute myelomonocytic leukaemia (AMML) causes gingival hypertrophy (MM looks like gums)
- Auer rods
- Acute lymphoblastic leukaemia (ALL)
- Children
- BM failure (anaemia, inf risk, bleeds)
- Failure to thrive (don’t grow along the normal curve)
- Chronic myeloid leukaemia (CML)
- Adults, often detected incidentally (overproduction of mature cells so doesn’t always cause rampant bone marrow failure)
- t(9;22) = Philadelphia chromosome (BCR-ABL gene)
- Tx: Imatinib (BCR-ABL tyrosine kinase inhibitor)
- Chronic lymphocytic leukaemia (CLL)
- Older adults, often detected incidentally (overproduction of mature cells so doesn’t always cause rampant bone marrow failure)
- Smudge cells (fragile lymphocytes)
Myelodysplasia vs Myelofibrosis
In normal BM - stem cells –> differentiate & proliferate
Myelodysplasia - abn differentiation of myeloid progenitor cells
- Def: BM disorder resulting in pancytopenia AND production of functionally immature blood cells (essentially it is ‘early AML’, <20% blasts)
- Chemo is a RF
- Key facts:
- Pancytopenia (all 3 myeloid lines can be affected)
- 1/3 cases –> AML
Myelofibrosis
- Def: clonal BM disorder characterised by deposition of fibrous scar tissue (over time, less and less tissue in BM that can produce blood cells)
- Key facts:
- Pancytopenia
- Tear drop cells
- Dry tap (due to level of fibrosis)
- Massive splenomegaly (a site where body tries to compensate for low blood cell production in BM)
Hereditary haemorrhagic telangiectasia (HHT) - Def? Dx criteria?
Aka Osler-Weber-Rendu syndrome - AD condition characterised by multiple telangiectasias over skin & mucous membranes
- 20% cases spontaneous wo/ FHx
Dx criteria (2 = possible; 3 = definitive Dx):
- Epistaxis: spontaneous, recurrent nosebleeds
- Telangiectases: multiple @lips/oral cavity/fingers/nose
- Visceral lesions: GI telangiectasia, pulmonary (increased stroke risk)/hepatic/cerebral/spinal AV malformations (AVM)
- FHx: first-degree relative w/ HHT
SCD exposed to child with coryzal Sx & rash - what are we worried about?
Parvovirus B19 infection can cause pancytopenia (aplastic anaemia) in predisposing haem conditions
Haematinics - constituents? interpretation?
Iron studies - constituents? interpretation?
Haematinics - serum B12, folate, Intrinsic factor, ferritin
- Low IF –> consider pernicious anaemia (cause of B12 def)
Iron studies - MCV, Fe, ferritin, TIBC, transferrin, transferrin saturation
- Low MCV, low Fe, low ferritin & high TIBC/transferrin –> IDA (iron def anaemia)
- Normal MCV, low Fe, high ferritin & low TIBC/transferrin –> consider Anaemic of chronic disease/haemoglobinopathy (SCD)
Coagulation screen - constituents? interpretation?
PT, aPTT, Fibrinogen - light blue test tube
- PT /INR measures extrinsic pathway (factor 7) and common pathway - measures overall clotting factor consumption as factor 7 rarely def in isolation
- Raised in liver disease, DIC, vit K def, Warfarin
- aPTT measures intrinsic pathway (factor 8/9/11) & common pathways
- Raised by same as above + intrinsic pathway issues:
- Haemophilia A (factor 8 def - X-linked recessive)
- Haemophilia B (factor 9 def - X-linked recessive)
- von Willebrand disease (as vWF pairs with factor 8)
- NOTE: antiphospholipid syndrome can cause high aPTT despite causing clots as inactivates phospholipid used in intrinsic pathway
- Raised by same as above + intrinsic pathway issues:
- DIC - PT & aPTT raised, fibrinogen & platelets low
Types of blood products? Indications? Duration over which given?
Packed red blood cells (PRBCs)
- Indications: acute blood loss, Sx/chronic anaemia (Hb ≤70/80 with CVD)
- 1 unit blood increases Hb by 10g/L
- Given over 2-4hrs (must be completed within 4hrs of coming out of store)
Platelets
- Indications: haemorrhagic shock in a trauma patient, profound thrombocytopenia (<20), bleeding with thrombocytopenia, pre-op platelets <50
- 1 adult therapeutic dose (ATD) increases Pl by 20-40
- Given over 30mins
Fresh frozen plasma (FFP) = clotting factors
- Indications: DIC, haemorrhage secondary to liver disease, massive haemorrhage (after PRBCs)
- Given over 30mins
Cryoprecipitate = fibrinogen, vWF, factor 8, fibronectin
- Indications: DIC with low fibrinogen (<1g/L), vWD, massive haemorrhage
- Duration = STAT
Amyloidosis - def? types? Presentation? Ix? Mx?
Def: aggregates of proteins with fibrillar morphology & beta-pleated sheet structure depositing in body tissues
Types: occurs as a complication of other conditions
-
AA - serum amyloid A - chronic inflammation
- RFs:
- Inflammatory conditions (e.g. RA, psoriatic arthritis, ankylosing spondylitis, IBD esp. Crohn’s)
- Chr infections (bronchiectasis, TB, chr UTIs, osteomyelitis)
- RFs:
-
AL - Ig light chain - multiple myeloma
- RF: monoclonal gammopathy of undetermined significance (MGUS)
- ATTR - TransThyRetin - familial, wild-type (elderly)
Presentation:
- Purpura around the eyes, eyelid petechiae, enlarged tongue
- Carpal tunnel syndrome (bilateral)
- Peripheral neuropathy (not in AA) - symmetrical sensory loss of feet initially (temp, pain –> proprioceptive)
- Autonomic neuropathy (not in AA) - erectile dysfunction/orthostatic HTN, GI/urinary dysfunction
- Fatigue (amyloid cardiomyopathy/nephrotic syndrome), weight loss (cardiac/hepatic amyloidosis), dyspnoea on exertion (amyloid cardiomyopathy)
- Exam: proteinuria, high JVP + pitting oedema (from restrictive cardiomyopathy)
Ix:
- Serum & urine immunofixation (monoclonal protein in AL)
- Ig free light chain assay (abn kappa to lambda ratio in AL)
- FBC (anaemia), metabolic profile (hypoalbuminaemia, high ALP, low Ca)
- 24hr-urine collection (>3g/day = nephrotic syndrome)
Mx: treat underlying condition
Case:
- 45yrs, tingling in arms & legs, loss of balance
- Exam: loss of vibration sense in both feet
- Ix: macrocytic anaemia, gastric antrum biopsy - achlorhydria & atrophic gastritis
Dx? Presentation? Ix? Mx?
Dx: pernicious anaemia aka atrophic gastritis/AI gastritis
Presentation: >60yrs, female
- Subacute combined degeneration of spinal cord from B12 def:
- Weakness, lethargy
- Paraesthesia, difficulty ambulating
- Ataxia, shuffling gait, decreased proprioception, decreased vibration sense
- Memory loss, irritability, depression, dementia
- Exam: koilonychia, macroglossia
- Assoc w/ AI conditions e.g. Hashimoto’s thyroiditis
- Risk of gastric adenocarcinoma
Ix:
- Bloods:
- FBC, haematinics (megaloblastic anaemia from B12 def), increased serum gastrin (increases PUD)
- Abs: anti-IF (60% but more specific) & parietal cell abs (90% but can be normal variant)
- Imaging:
- Biopsy of corpus/fundus stomach (absence of parietal cell-containing oxyntic glands, achlorhydria, atrophic gastritis) + intra-gastric pH (ph>6 @rest rules out Dx)
Mx:
- If PUD with H. pylori –> triple therapy (PPI + 2abx)
- Replace deficiency (Fe, B12, Ca/Vit D)
What is Ham’s test for? What is there increased risk of? Tx? What can this condition transform into?
Paroxysmal nocturnal haemoglobinuria
- Acquired clonal abn of RBCs –> chr complement-mediated haemolysis + increased VTE risk (e.g. Budd-Chairi)
- RBCs lack PIG
- Tx: Eculizumab (anti-complement C5)
- Complication: transforms to aplastic anaemia/AML
What is osmotic fragility test for?
Spherocytosis
Case:
- Drowsy, visual disturbances, started on chemo & steroids by haem team
- Anxious, thirsty, palpitations
- ECG below
Dx? What happens? When is it high risk? Tx?
Tumour lysis syndrome - apoptosis of tumour cells (classical cause = steroids in leukaemia)
- Drowsy, visual disturbances –> SOL –> chemo/steroids bursts these cells
- Tumour cells contain - uric acid, PO4, K+ intracellularly
- Urate nephropathy –> AKI
- PO4 –> hypocalcemia; high K –> long QT; COMBO –> torsades de pointes
- High risk in leukostasis - massive WCC counts - drowsy, retinal haemorrhages, pul oedema
- Tx: hydrate + allopurinol before chemo
- Emergency - give Rasburicase (reduce uric acid)
Sickle cell crisis - Mx?
ACUTE (PAINFUL CRISES)
- Oxygen
- IV Fluids
- Strong analgesia (IV opiates)
- Antibiotics
- Cross match blood
- Give transfusion if Hb or reticulocytes fall sharply
