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
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
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
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
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
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)
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