Haematology_Medicine Flashcards
1
Q
Anaemia - cause categorization? Ix? Deficiency-related anaemia - causes & relevant deficiencies?
A
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
2
Q
Haem malignancies - Types?
A
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
3
Q
Leukaemia vs Lymphoma?
Blood cell dev? How does this relate to Leukemia?
Lymphoma types? Staging?
A
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)
4
Q
Multiple myeloma - def? pathophysiology? Spectrum of disease? Ix? Dx? Mx?
A
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
5
Q
Microcytic anaemia + GI features - Ix? Mx?
A
Ix:
- IDA + lower GI features –> 2WW for colonscopy
- IDA + dyspepsia –> 2WW OGD (oesopho-gastro-duodenoscopy)
7
Q
Microcytic anaemia, disproportionately low MCV - Dx?
A
Thalassaemia
8
Q
Normocytic anaemia, reduced renal function - Dx?
A
CKD-related renal function (EPO)
9
Q
Macrocytic anaemia + mixed upper/lower motor signs - Dx?
A
B12 def –> subacute combined degeneration of spinal cord
10
Q
CML Mx? CML chromosome? How to identify if in accelerated (blast) phase? Dx?
A
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
11
Q
Auer rods - Dx?
A
AML
12
Q
DIC & t(15;17) - Dx?
A
Acute promyelocytic leukaemia
13
Q
Haemophilia A Mx? Haemophilia A vs B? vWD difference?
A
A = factor 8
B = factor 9
vWD - bleeding time prolonged because platelet dysfunction
Haemophilia - bleeding time not prolonged because no platelet dysfunction
14
Q
Menorrhagia + prolonged bleed time - Dx?
A
vWD
15
Q
Low platelets + low fibrinogen?
A
DIC
16
Q
Raised INR, low Pl, deranged LFTs - Dx?
A
Liver cirrhosis
17
Q
Haem malignancy buzzwords
A
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
18
Q
Causes of increased vs decreased reticulocyte counts?
A
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
19
Q
ALL - associated with what gene? Presentation? Ix? Mx?
A
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)
20
Q
AML - Hx? Ix? Mx? AML vs CML difference on Ix?
A
-
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
21
Q
CML - gene associated? Hx? Ix? Disease phases? Mx?
A
- 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)
22
Q
CLL - presentation? Ix? Mx?
A
- 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:
23
Q
Myeloproliferative disorders - characteristics? causes? Mx?
A
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)
24
Q
Myelodysplastic syndromes
Dx? Characteristics? Ix findings? Prognosis?
A
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
25
Q
Classical Hodgkin’s lymphoma - peaks when? presentation? histology? most common type? assoc inf? Mx?
A
- 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
26
**_MICRO_**angiopathic haemolytic anaemia (MAHA)
* Haemolytic uraemic syndrome (HUS)
* Thrombotic thrombocytopenic purpura (TTP)
* Disseminated intravascular coagulation (DIC)
**_MICRO_****angiopathic 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)
* 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)*
* 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
* 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**
27
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
28
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
* 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)
29
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)
30
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)
31
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)
32
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
33
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
34
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)
35
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
* DIC - PT & aPTT raised, fibrinogen & platelets low
36
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
37
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)
* **AL** - _Ig light chain_ - **multiple myeloma**
* RF: monoclonal gammopathy of undetermined significance (MGUS)
* **ATTR** - **_T_**rans**_T_**hy**_R_**etin - 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
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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)
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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
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What is osmotic fragility test for?
Spherocytosis
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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)
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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
