Haematology1.txt

• 1. vasoconstriction
• 2. platelet aggregartion to form PRIMARY HAEMOSTATIC PLUG
• 3. activation of clotting cascade to form a fibrin plug (SECONDARY HAEMOSTATIC PLUG)

• megakaryocytes in bone marrow
• platelets: anucleate, but cytoplasm has electron dense granules, lysosomes, mitochondria

8-12 days

liver

thrombin

plasmin

due to increased circulating plasma volume

iron supplements

no vary rare. due to excess alcohol

atrophy of gastric mucosa so failure of IF and gastric acid production (achlorhydria) and so B12 malab

• iron deficiency anaemia
• megaloblastic anaemia: folate, B12 deficiency

hypersegmented neutrophils

• pancytopenia in the absence of reticulocytes
• bone marrow failure: hypocellular

• megaloblastic anaemia: due to the toxic effect of alcohol on erythropoiesis or dietary folate deficiency
• macrocytic anaemia

RBC in which nuclear maturation is delayed compared with the cytoplasm so you get hypersegmented neutrophils (immature)

• B12 (cobalamin) deficiency
• folate deficiency
• cytotoxics

• alcohol excess
• hypothyroidism
• haemolytic anaemia: get reticulocytosis
• pregnancy: increased demand from foetus

defective DNA synthesis so get hypersegmented neutrophils, leucopenia, thrombocytopenia, MCV > 110

• glossitis: beefy red sore tongue
• lemon tinge to skin - pallor (anaemia), jaundice (haemolysis)
• angular stomatitis
• paraesthesia, peripheral neuropathy
• depressed, irritable, psychosis
• subacute combined degeneration of the spinal cord (not seen in folate deficiency): peripheral neuropathy, optic atrophy (vision changes), dementia, both symmetrical DC loss (LMN signs) and symmetrical corticospinal tract loss (UMN signs) so get classic triad of extensor plantar reflex (UMN) (positive babinski), absent knee jerk (LMN), absent ankle jerk (LMN)

subacute combined degeneration of the spinal cord - get ataxia due to JOINT POSITION and vibration sense affected and optic atrophy (reduced vision)

spinothalamic tracts are not affected

normocytic normochromic anaemia

• take NSAID - gastritis and chronic blood loss - microcytic hypochromic anaemia (IDA)
• normocytic normochromic anaemia (ACD)

Direct antiglobulin test (Coombs' test): detects autoAb on surface of red cells

• normocytic normochromic anaemia
• spherocytes

unconjugated hyperbilirubinaemia

• temperature at which Ab attaches better to the RBC
• warm:
• cold: lower than 37

• IgG
• bind at body temp 37 degrees
• autoimmune diseases: eg SLE
• lymphoproliferative disease: e.g. CLL, lymphoma

• IgM mediated
• bind at lower temp <4degrees, activating cell surface complement
• following infection e.g. mycoplasma pneumonia, EBV

steroids or immunosuppressants (think autoimm disease and lymphoprolif)

• keep warm
• chlorambucil may help

• RBC enzyme defect: glucose-6phosphate dehydrogenase deficiency. asymp but susceptible to oxidative crisis due to reduced glutathione prod precip by drugs, fauvism; pyruvate kinase deficiency
• membrane defect: hereditary spherocytosis - less deformable spherical RBC so trapped in spleen - extravasc haemolysis
• Hb defect: sickle cell, thalassaemia

• aplastic anaemia due to BM stops working
• rheumatoid arthritis
• adults: gets better on own.
• children: slapped cheek syndrome - bright red rash over cheeks

• oxidative crises - so oxidised denatured Hb - form Heinz bodies
• bite cell and blister cell: after removal of Heinz body by spleen.

Reed-Sternberg cells: have mirror image nuclei (2nuclei)

• young adults
• elderly

enlarged PAINLESS non tender rubbery LN - cervical or axillary or inguinal (the superficial ones)

alcohol

• mass effect: bronchial or SVC obstruction
• direct extension: causing pleural effusion

malignant proliferation of lymphocytes which accumulate in LN

• blood: FBC, film (RSC), LDH (raised as inc cell turnover), Ca, urate, LFT, high ESR, low Hb worse pro
• tissue diagnosis: LN excision biopsy

• chemo, radio or both (SE both: AML, NHL, infertility)
• chemo: ABVD
• stem cell transplantation
• radio SE: solid tumours (lung, breast, thyroid) near radiation field, IHD, hypothyroid, lung fibrosis
• chemo SE: alopecia, BM suppression, nausea, infection

• infection
• SVC obstruction: inc JVP, fullness in head, dyspnoea, blackouts, facial oedema

nodular sclerosing

mixed cellularity - admixture of lymph, histio, eosino, plasma

lymphocyte deplete. bad prognosis

• infection: CMV, EBV, HIV, TB
• infiltration: RA, SLE, sarcoid
• Drugs
• Lymphoma

• all lymphomas WITHOUT Reed-Sternberg cells
• most derived B-lymphocute

• congenital immunodeficiency
• acquired immunodeficiency: HIV, EBV, drugs, H.pylori (in MALT), toxins in environ, HTLV-1

• low: (indolent, incurable, widely disseminated at presentation) eg follicular lymphoma, CLL, mantle cell lymphoma inc MALT assoc. with chronic H.pylori infection, if eradicate H.pylori lymphoma remission
• high: more aggressive but long term cure possible e.g. diffuse large B cell lymphoma
• v.high: Burkitts lymphoma, lymphoblastic lymphoma

Sezary syndrome

repeat biopsy in case histological transformation to DLBCL

• stage I: involved field radio, may cure
• R-CHOP or R-CVP chemo for others

• t(14:18) gene Bcl-2/IgH
• Bcl is anti apoptotic gene

• DLBCL, high grade, aggressive, can be cured
• Rx: RCHOP

• v high grade, major risk of dissemination to CNS
• one type is endemic in Africa, assoc. with EBV (jaw lymphadenopathy)
• immunodeficiency assoc HIV or post transplant

• if rapidly and aggressively treated then good prognosis as cells are very active and proliferating therefore susceptible to chemotherapy so in young and fit cure rates are high
• Rx: short course v.intenseive therapy and CNS prophylaxis - intra thecal chemo and ones cross BBB

• Ann Arbor staging system
• 1: single node region
• 2: 2 or more node regions, SAME side of diaphragm
• 3: nodes BOTH sides of diaphragm
• 4: EXTRALYMPHATIC involvement eg liver and BM
• suffix A: absence of B symptoms
• suffix B: B symptoms (fever, night sweats, weight loss)

malignant clonal proliferation of B-lymphocyte derived plasma cells

IgG, IgA

myeloma due to deposits in vertebrae, ribs, skull

IgG

presence of Ig made by a single clone of plasma cells in the blood

monoclonal band (M band) on serum electrophoresis

• multiple myeloma
• waldenstroms macroglubulinaemia
• primary amyloidosis (AL amyloid)
• MGUS: monoclonal gammopathy of uncertain significance: can develop myeloma or lymphoma in future

• lymphoplasmacytoid lymphoma making monoclonal IgM.
• get hyperviscosity with CNS and ocular symptoms.

• lymphadenopathy, splenomegaly
• inc ESR
• IgM paraprotein on serum electrophoresis

Bence-Jones proteins which are excreted by the kidney into the urine - light chains (either kappa or lambda type) from the paraprotein

• over 70s=peak age
• afrocaribbean:caucasian 2:1

• osteolytic bone lesions: backache, fractures, vertebral collapse due to increased osteoclast activation from signalling by myeloma cells
• symptoms of hypercalcaemia: due to osteoclast activity
• pancytopenia symptoms: due to BM infiltration of proliferating plasma cells causing anaemia, bleeding, infection
• recurrent bacterial infection: immunoparesis, low neutrophils
• impaired renal function: light chain deposition
• systemic AL amyloidosis in 15% only

• FBC: normocytic, normochromic anaemia
• persistently high ESR, PV
• increased urea and creatinine (as renal impairment)
• increased calcium
• alk phase normal (unless healing fracture)

serum and urine electophoresis

B2 microglobulin

• punched out lesions e.g. pepper pot skull
• vertebral collapse
• fractures
• osteoporosis

rouleuax formation

• serum or urine electrophoresis: monoclonal protein band
• BM biopsy: increased plasma cells
• end organ damage from myeloma: hypercalcaemia, renal impairment, anaemia, bone lesions

• bone pain: analgesics (avoid NSAID..as risk kidney impairment)
• to reduce fracture rate: bisphosphonates eg zolendromate, pamindronate
• to help focal disease: local radiotherapy
• vertebral collapse: vertobroplasty, kyphoplasty
• anaemia: blood transfusions and EPO
• renal failure: rehydrate at least 3l/day avoid light chain nephropathy, dialysis if ARF
• infections: treat rapidly with broad spec antibiotics until culture, may need regular ivIg infusion if recurrent infection

• chemotherapy
• old ppl: melphalan/cyclophosphamide with prednisolone
• young/fit ppl: VAD (vincristine, adriamycin, dexamethasone); SCT, allogeneic transplantation can be curative but high mortality (30%)
• Thalidomide in relapsed disease

B2 microglobulin

• renal failure
• infection

• hypercalcaemia: rehydrate with iv saline, iv bisphosphonates
• spinal cord compression: urgent MRI, dexamethasone, local radiotherapy
• hyperviscosity: causes reduced cognition, vision probs, bleeding. plasmapheresis to remove light chains
• ARF: rehydrate, urgent dialysis

• extracellular deposits of protein
• in abnormal fibrillar form
• resistant to degradation

• kidney: glomerular lesions: proteinuria and nephrotic syndrome
• heart: restrictive cardiomyopathy, arrhythmia, angina
• Nerves: peripheral and autonomic neuropathy, carpal tunnel syndrome
• Gut: macroglossia, malab, perf, haemorrhage, obstruct, hepatomeg
• Vascular: purpura, esp periorbital

periorbital purpura

• chronic myeloid leukaemia
• reciprocal translocation between chr 9 and 22
• fusion of Bcr gene and abl proto-oncogene
• tyrosine kinase activity

• uncontrolled clonal proliferation of myeloid cells
• myeloproliferative disorder

age: 40-60yrs, rare in childhood. male more

• chronic and insiduous
• B: wt loss, tired, fever, sweats
• gout: purine breakdown
• bleeding: plt dysfunction
• abdo discomfort: splenomegaly

• hepatosplenomeg
• anaemia
• bruising

high WBC: whole spectrum of myeloid cells - neutro, myelocytes, baso, eosin, may see lots of granulocytic cells at different stages of differentiation, low/N Hb

hypercellular

• chemo: imatinib (Glivec) tyrosine kinase inhibitor but may cause myelosupp
• hydroxycarbamide if imatinib ineffective
• stem cell transplantation: allogeneic HLA matched - only cure

monoclonal proliferation of non-functional MATURE Blymphocytes

m:f 2:1; elderly 65yo

none, infection, anaemia, B symp

• enlarged, rubbery, non-tender nodes
• splenomegaly
• hepatomegaly

• increased lymphocytes
• marrow infiltration so low Hb, low neutro, low platelets

smear cell: fragile cell so damaged in preparation

• autoimmune haemolysis
• infection as hypogammaglobulinaemia (low IgG) - bacterial, viral esp herpes zoster
• marrow failure: pancytopenia

CLL

• asymp: monitor
• chemo: chlorambucil reduce lymphos, improve BM, reduce node size
• steroids: Autoimmune haemolysis
• radio: relief of lymphadenopathy, splenomeg
• supportive: transfusions, ivIg if recurrent infections

• autoimmune haemolytic anaemia in CLL too
• warm IgG

• RBC: polycythaemia rubra vera - hyperviscosity so get headache, tinnitus, dizziness.
• WBC: CML
• platelet: essential thrombocythaemia. abnormal plt so may cause bleeding, thrombosis, chest pain, light headed
• fibroblasts: myelofibrosis - B symptoms, hepatosplenomeg, blood film: leucoerythroblastic cells (nucleated RBC), teardrop RBC

• polycythaemia rubra vera: venesection, hydroxycarbamide if high risk e.g. over 60/previous thrombosis, aspirin 75mg PO
• essential thrombocythaemia: low dose aspirin 75mg PO, hydroxycarbamide if over 60/previous thrombosis
• myelofibrosis: marrow support, allogeneic SCT curative but high mortality

ALL (rare in adults)

• uncontrolled proliferation of immature T or B lymph blast cells with BM failure, tissue infiltration
• CNS involvement common

• marrow failure: low Hb, infection, bleeding
• infiltration: hepato, spleno megaly, lymphadenopathy, orchidomegaly
• CNS involvement: CN palsy, meningism

blasts, need to know blast count on FBC

• blood film & BM: blasts
• CXR, CT: mediastinal and abdo lymphadenopathy
• LP: CNS involvement

• supportive: blood transfusions, platelet transfusions, iv fluids, allopurinol (prevent tumour lysis), Hickman line
• infection: immediate iv Abx. neutropenic regimen, prophylactic drugs
• chemo: for remission induction, CNS prophylaxis (intrathecal methotrexate)
• marrow transplant

• neoplastic proliferation of blast cells from marrow MYELOID elements
• very rapidly progressive, death in 2 months if untreated!

• age: old.
• long term complication of chemo e.g. for lymphoma!
• assoc. with myelodysplasia

• marrow failure: anaemia, infection, bleeding
• infiltration: hepato, spleno megaly, GUM HYPERTROPHY, skin, NB CNS involvement rare

• FBC: WCC high but can be low/normal!
• BM biopsy: blast cells
• microscopy: Auer rods
• immunophenotyping

• put in a side room as LOW neutrophils so risk of infection
• blood and platelet transfusion
• iv fluids
• allopurinol: prevent tumour lysis
• blood culture and iv antibiotics

• APML
• use all trans retinoic acid with chemo

CML