Week 03 Haematology

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mewinstanley@googlemail.com
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Week 03 Haematology
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2012-02-01 12:33:59
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Haematology glasgow uni third year medicine
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Haematology week
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  1. What are the requirements for RBC synthesis [4] and define anaemia.
    • Requirements
    • Drive for erythropoeisis
    • Correct genes
    • Ingredients [Folate, B12, iron etc]
    • Functioning Bone Marrow

    Balance between too much [polycythaemia] & too little [anaemia]

    • Anaemia
    • can be ^^ destruction
    • underproduction
  2. Outline the Iron Cycle
    • Req ~1-2mg/day
    • Absorbed in gut [HFe, duodenum & upper jejunum]
    • Trasnport via Transferrin [hepatic glycoprotein, 2Fe, norm = 30% sat]
    • Transport to all TfR tissues [BM, RBC, myoglobin enzymes]
    • RBC [Menstrual losses for Females]
    • Degraded in RES [t-port via serum ferritin, ^^^Fe sites]
    • No regulated excretion [Enterocyte shedding]

    **should be able to draw picture**
  3. Explain the pathophysiology of Macrocytic Anaemia?
    Caused by B12 & folate [B9] deficiency

    • B12 [Cobalamin]
    • convert homocysteine → methionine [all prot AA precursor]
    • Absorbed w intrinsic factor [parietal] in ileum

    • Folate [B9]
    • Absorbed in majority of small bowel
    • Thymine formation

    • Both are involved in DNA synthesis so deficiency → cell abnormalities
    • ineffective erythropoeisis → lysis, ^bilirubin & LDH

    • Causes of deficiency
    • Malabsorption → UC, Crohns, Pernicuous Anaemia
    • Dietary → vegan
  4. For Microcytic anaemia give;
    -Causes
    -CF
    -Pathophysiology
    • Iron deficient anaemia [IDA] <15% Tf saturation
    • Less Hb → microcytic & hypochromic

    • Causes → TAILS
    • Thalassaemia
    • Any Chronic Disease
    • IDA
    • Lead Poisoning
    • Sideroblastic Anaemia → BM prod ringed sideroblasts [abn nucleated erythrocytes]

    Ix Low SF Pt = IDA

    CF → spooned nails, angular stomatitis, atrophic glossitis [pale & painless] Oesophageal web [Plummer Vinson]
  5. Outline Tx of IDA
    • Replace iron, but not BTx
    • Ferrous sulphate/ IV iron
    • Discover cause → males/ post menopausals, GI unless proven otherwise, young women, menstrual
  6. Describe Anaemia of Chronic Disease [include lab results & Pathophysiology]
    • Pathophysiology
    • failure of Fe utilisation, trapped in RES
    • reduced response to EPO → depressed marrow activity
    • Common

    • Laboratory Results
    • Normochromic, normocytic
    • ^ESR
    • normal/ high SF
    • TIBC [Total iron binding capacity (Tf)] → low
    • Histology → RBC rouleaux [stack of coins]
  7. Outline Thalasaemia [2]
    • inherited condition
    • relative lack of globin gene [missing alpha/beta]
    • No genes -> Thalasaemia Major
  8. Describe Alpha Thalasaemia [and Hb H disease]
    • 4 genes involved
    • Missing 1 → mild microcytosis
    • Missing 2 → Microcytosis, ^RBC, mild anaemia
    • Missing 3 → Significant anaemia [Hb-H disease]
    • Missing 4 → death

    • Hb-H disease [3 genes missing]
    • lack of alpha genes, excess beta
    • beta join → Hb-H
    • Hb ~75g/l
    • Req BTx during times of stress
  9. Describe Beta Thalasaemia [Major & Minor]
    2 genes involved [B = 2]

    • Beta-Thalasaemia Major
    • AR inheritence
    • unable to make adult Hb
    • Significant Dyserythropoeisis
    • Bone marrow expands → hair on end in skull [@ CXR]
    • Anaemia & Splenomegaly
    • BTx dependant → Fe overload [chelation Therapy]

    • Beta-Thalasaemia Minor
    • Only 1 Mt → microcytic
  10. Describe Sickle Cell Disease
    • Abnormal Beta Hb [Glu for Val]
    • HbS formed
    • continuous polymerisation/depolymerisation
    • cells do not flow well

    • CF
    • Multisystem disease
    • Brain → CVA/ Moya Moya [Abn cerebral vasculature]
    • Lungs → Acute chest syndrome [cells sickle in lungs, deoxygenation → ^^sickle]
    • Bones → swollen hands & fingers
    • Spleen → hypospleenic due to infarcts
  11. Outline Mx of SCD
    • Prevent Crisis
    • Hydration, analgesia & early intervention
    • Education
    • Prophylactic vaccinations & AntiB
    • Folic Acid

    • Acute Mx
    • O2, fluids, analgesia, specialist care [OFAC....Oh Fuck]
    • BTx [Exchange BTx]
  12. Define Haemolytic anaemia including intravascular & extravascular [2]
    • Haemolysis → ^ RBC destruction
    • BM can ^^ RBC output so lifespan <15-20d before anaemia

    • Intravascular → destruction in circulation
    • Extravascular → occurs in RES [Spleen, Liver & BM]
  13. Describe Congenital Haemolytic Anaemia [3 types]
    [Memb-Hb-Enzy]
    • Abnormalities of RBC Membrane
    • Hereditary Spherocytosis
    • AD inheritance
    • CF → RBC spherical & Polychromatic, Jaundice [adulat & Neonatal], Splenomegaly
    • Tx → Splenectomy & Hyposplenic prophylaxis [encapsulated orgs → minigococcus, haemphilus & pneumococcus]

    • Haemoglobinopathies
    • SCD
    • Thalasaemias

    • Abnormal RBC Enzymes
    • Pyruvate kinase deficient → AR inheritance, ATP depletion, extravascular [Chronic]
    • G6P dehydrogenase deficient → XL-R inherit, acute IV haemolysis from oxidative stress [favabeans, drugs]
  14. Describe Acquired Haemolytic Anaemia [3]
    [Auto/Iso/Non-immune]
    • Autoimmune
    • Warm Type [IgG]
    • idiopathic/ autoimmune assoc, lymphoproliferative disease [NHL, CLL] Drugs [cephalosporins]
    • RBC → spherocytic & polychromatic
    • Tx → stop culprit drug, steroids, splenectomy

    • Cold Type [IgM]
    • haemolysis in peripherys/ cold conditions
    • mostly idiopathic [some PMH mycoplasma infection]
    • Blood film → cold agglutinins, +ve direct Coombs
    • Tx → Keep Warm

    • Isoimmune
    • Haemolytic disease of Newborn
    • +ve direct coombs

    • Non-immune
    • Fragmentation Haemolysis → Mechanical Heart Valves
  15. Describe the Direct & Indirect Coombs test & their indications
    • Direct Coombs
    • To detect if Ab/Complement have bound to RBC
    • [Monoclonal Ab to FcR]
    • Agglutination = +ve [Immune mediated haemolytic disease]

    • Indirect Coombs Test
    • invitro antibody-antigen reactions prior to BTx [Crossmatching]
    • Compatability test, RBC phenotyping etc.
  16. Breifly outline Haemopoiesis [look at more detailed notes from 2nd year]
    • Lymphoid/Myeloid
    • occurs in bone marrow

    HSc→ selfrenewal/ daughter cells [differentiate]
  17. Define Myeloproliferative Disorder and explain the relevance of JAK2 Mt in these Pts
    • Myeloproliferative Disorders
    • Clonal Disorder of blood, ≥ 1 Myeloid Progeny
    • Spectrum of disease
    • e.g. Polycythaemia rubra vera [^RBC], essential thrombocytosis, myelofibrosis [BM replaced by scar]
    • ~ transform to AML

    • JAK2 Mt
    • Results in continuous activation of JAK2 [Regardless of ligand e.g. EPO]
    • inhibited by Ruxolitinib → reduces splenomegaly, no reduction in alleilic burden, causes thrombocytopenia
  18. Outline the CF & Tx of Essential Thrombocytosis [ET]
    • ET
    • Plts >600 [megakaryocyte proliferation]

    • CF
    • Thrombotic complications [microvascular occlusion]
    • Some present w haemorrhage
    • Splenomegaly
    • Can transform to PRV/ Myelofibrosis
    • ~3% transform to leukaemia
    • High risk features → PLTs >1500, previous thrombosis, thrombotic RF [diabetes/ HBP]

    • Tx
    • Low risk → [<40yo, no ^ risk features] Antiplatelet e.g. aspirin/clopidogrel
    • Intermediate → [40-60yo, no ^ risk features] Aspirin +/- hydroxycarbamide
    • High risk → [>60yo, >1 risk feature] Aspirin + hydroxycarbamide/ Anagrelide [2nd line, inhibit MK differentiation]
  19. Describe Fanconis Anaemia
    • Aplastic Anaemia, underproduction [bone marow failure]
    • AR inheritance → 7 subtypes [FANC A-G]

    • CF
    • Appearance → short stature, cafe au lait, GU & GI malformed, LDs, hearing loss, micropthalmos, may look normal
    • CNS → Hydrocephalus
    • Haemo → petechiae, bruising, pallor, fatigue, infections

    • Tx
    • Allogenic SC TPx
    • Supportive care [blood & PLTs]
    • Corticosteroids
    • Surveillance for 2ndry tumours
  20. Outline Myelodysplastic Syndromes
    • Myelodysplastic Syndromes
    • Dysplasia & ineffective haemopoeisis in >1 myeloid
    • ~prev Ct/Rt
    • Various subtypes [morphology & % blasts]
    • Acquired cytogenetic abn → monosomy 5 & 7
    • Progressive BM failure
    • May progress to AML

    • CF
    • elderly
    • incidental
    • recurrent infections
    • fatigue [anaemia]

    • Tx
    • supportive care [Blood PLTs]
    • Growth factors [G-CSF & EPO]
    • ?Immunosuppression [Low Grade]
    • Low dose Ct → demthylating agents
  21. Define Lymphoma & describe a simple classification.
    • Lymphoma
    • Ca of lymphoid Cells
    • develop in lymph nodes [also extra nodal]


    • Classification
    • Hodgkin's
    • Non-Hodgkins → B-cell, T-cell, NK cell
  22. Outline the Ix of Lymphoma
    • Excision Biopsy → ideal [invasive, slow turn over]
    • Core Biopsy → [no scar, easier]
    • Pre-Tx evaluation → FBC [anaemia → BM infiltration], LDH, ESR, U&E
    • Staging investigations → CT [ neck, chest, abdo-pelvis], PET/CT [radiolabelled Glucose] ~ BM aspirate & trephine
  23. How would you stage Lymphoma
    • Ann Arbor Staging
    • I → single LN region
    • II → 2 LN same side of diaphragm
    • III → both sides of diaphragm, incl 1 organ/ area near LN/Spleen
    • IV → diffuse involvement of >1 extralymphatic organs [liver, BM, Lungs]

    • Modifiers → B symptoms
    • Fever [>38]
    • Night sweats
    • weight loss [10% in 6m]
  24. Describe the CF & pathology of Hodgkin Lymphoma
    • CF
    • Bimodal age [young adults & older peeps]
    • Painless Lymphadenopathy [above diaphragm usually]
    • May have B Symptoms [fever, night sweats, weight loss]
    • Also → generalised itch, ~alcohol induced lymph node pain

    • Pathology
    • Majority = classical HL
    • Malignant cell = Reed Sternberg cell, bi-nucleate [owl head]
    • Majority of cellularity in node = reactive to RS
    • Initial spread from one node to next
    • Later haematogenous spread [liver, lungs & BM]
  25. Describe the CF & Pathology of Non-Hodgkins Lymphoma
    • CF
    • wide variety of Pc
    • extra-nodal may mimin carcinoma
    • Low Grade → indolent clinical course, incurable, painless peripheral adenopathy e.g. follicular lymphoma
    • High Grade → more localised, rapid growth, ^^extranodal sites e.g. Diffuse Large B cell lymphoma

    • Pathophysiology
    • progressive clonal expansion of B/T/ NK cells
    • 90% = B cell
    • Malignant lymphocytes can look normal → immunocytochemistry
  26. Describe 2 high grade Lymphomas [Diffuse Large B cell & T cell]
    • Diffuse Large B Cell Lymphoma
    • Commonest high grade
    • Aggressive, but curable
    • CF → painless lymphadenopathy, hepatosplenomegaly, systemic upset
    • Ix → Bloods [LDH], CT [neack, abdo & pelvis], BM aspirate [infiltration common]
    • Tx → R-CHOP [Rituximab + Ct] [Rituximab target CD20 → expressed on B cells]

    • T cell Lymphoma
    • Uncommon
    • Multiple subtypes
    • Poor Prognosis
    • No CD20 [cant use rituximab]
  27. Describe a low grade Lymphoma [Follicuar lymphoma]
    • Follicular Lymphoma
    • ~ responsive to Tx, but recurrent relapsing
    • can convert to High grade
    • CFpainless lymphadenopathy, widespread LNs, hepatosplenomegaly, B symptoms
    • Ix → Bloods [LDH/Anaemia] CT [chest, neck, abdo & pelvis] BM aspirate [infiltration paratrabecullar]
    • Tx → ?early [localised Rt] ?Late [watch & wait, symptomatic Rituximab + Ct R-CHOP]
  28. Define Multiple myeloma & state the Patho, CF, Ix & Tx
    • Multiple Myeloma
    • Neoplasm of plasma cells in BM

    • Patho
    • >10% of BM
    • Mature B cells
    • Skeletal Destruction

    • CF
    • Lytic Lesions in bones
    • anaemia
    • renal failure
    • Hypercalcaemia [confusion, constipation, Abdo pain]
    • Infections [Pneumonia]

    • Ix
    • FBC, Biochem [^^Ca]
    • Ig Electrophoreisis [Monoclonal band → 1 abn prot]
    • BM aspirate [ ^^plasma cells]
    • Skeletal Survey [multiple lytic lesion, pepperpot skull]

    • Tx
    • Incurable, median 3-4yr
    • Thalidomide based Tx
  29. Outline the classification of leukamias
    • Based on cell lineage
    • 4 types:
    • ALL → acute lymphoblastic → ALL children get leukamia
    • AML → acute myeloblastic
    • CLL → chronic lymphoblastic
    • CML → chronic myeloblastic → Philedelphia chromosome
    • CML
  30. What is the clinical presentation of acute leukamia [Hx, bloods, BM]
    • Hx
    • rapid onset
    • lethargy
    • infections
    • bruising & bleeding
    • bone pain
    • gum swelling
    • Lymphadenopathy

    • Peripheral Bloods
    • Anaemia
    • Neutropenia
    • Thrombocytopenia
    • Blasts [immature cells]

    • Bone Marrow
    • Hypercellular
    • Dysplasia
    • Blasts 20-100%
  31. Outline the Mx of Acute Leukamia
    • Supportive
    • BTx → if symptomatic [^QoL], FFP [for DIC]
    • Prophylactic Antibiotics → [AML no granulocytes], common infections → HSV, VZV, CMV, Discitis, cellulitis

    • Chemotherapy
    • Most Pt into trials [ALL]
    • Aim to iradicate abn clone
    • ^morbidity [bleeding, infections, hair loss, sterility, mucousitis]
    • AML → Anthracycline & cytarabine, ^^myelotoxic, ~allogenic TPx
    • ALL → Complex, CNS Tx = vital, polypharma incl steroids
  32. Describe Chronic Leukamia and outline its Pc [CF, Bloods, BM]
    • Chronic Leukamia
    • more mature cells
    • CML → neutrophils, eosinophils & basophils [rare]
    • CLL → B lymphocytes, Commonest, ~67yo

    • CF
    • ~none [incidental FBC → lymphocytosis]
    • lethargy, night sweats, weight loss
    • lymphadenopathy
    • recurrent infections

    • Bloods
    • Mature Lymphocytosis [Clonal expansion, CD5,19, 20]
    • condensed chromatin
    • ^n:c ratio
    • no blasts

    • BM
    • Diffuse nodular infiltration
  33. CLL [Cytogenetics, transformation, beware]
    • Cytogenetics
    • 11q22 deletions → ~20%, ^^aggressive, younger. Refractory to Tx
    • 17p deletions → 5-10%, ^^ aggressive, loss of p53, trasnform to CLL/PLL [really bad CLL]

    • Transformation [Richter Transform]
    • CLL → high grade B cell lymphoma [esp if loss p53]
    • <5%
    • ^^Aggressive + B symptoms

    • Beware
    • CLL → AIHA & Immune thrombocytopenia, limits treatment [precipitated by Ct/Rt]
    • ^^infections → hypo Ig, low T cells, neutropenia, poor compliment = serious morbidity & mortality, Tx can worsen
  34. What is the philadelphia chromosome & why is it important?
    • Philadelphia Chromosome
    • 9:22 translocation
    • switches on receptor tyrosine kinase [Brc-ABL]
    • results in cell proliferation & failure of apoptosis
    • Diagnostic of CML, but assoc w ALL
    • Tx → Imatinib [Block ABL]
  35. Draw the Clotting Cascade
  36. Text For Clotting Cascade
    • Intrinsic → 12, 11, 9, 8
    • Extrinsic → 7 & TF
    • Common → 10, 5, 2, fibrinogen → fibrin

    Vit K dependant → 2, 7, 9, 10
  37. Pt has ^APTT, ^PT, low fibrinogen & low PLTs wat de got boi?
    • DIC [Disseminated Intravascular coagulation]
    • massive activation of clotting cascade [uses everything up]
    • give anticoagulants
    • Causes → brain inj, meningococcal septisaemia, trauma, malignancy]

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