Please enable JavaScript.
Coggle requires JavaScript to display documents.
Haematology (Myeloma (Myeloma = proliferation of plasma cells (B…
Haematology
Myeloma
Myeloma = proliferation of plasma cells (B lymphocytes) that produce antibodies - causes a single type of one autoantibody to be produced
Multiple myeloma - myeloma affects multiple areas of the body
MGUS (Monoclonal gammopathy of undetermined significance) - excess of a single type of antibody or antibody components without other features of myeloma or cancer
Pathophysiology: 1) Clonal proliferation of plasma cells cause increase in monoclonal Abs (usually IgG or IgA); 2) Clones also produce free light chains
paraproteins
- excreted by the kidneys (
Bence Jones
proteins), excretion damages the kidney; 3) Clones produce IL-6 which inhibits osteoblasts and activates osteoclasts --> increase in Ca (stones, thrones, groans, psychiatric moans)
Sx: Osteolytic bone lesions, anaemia, neutropenia/thrombocytopenia, recurrent bacterial infections, renal impairment
Cx: Hyperviscosity (stroke), hypercalcaemia, AL-Amyloid *light chains clump to form amyloid deposits in some organs)
Ix: Clonal BM Plasma cells >10%, serum and/or urinary monoclonal protein (M-protein)
Rx: Fit patients - induction chemo then allogenic BMT; Unfit patients - chemo only
NB: Waldenstroms Macroglobulinaemia: Is actually
Lymphoplasmacytoid Lymphoma
(Non-Hodgkins) characterised by the overproduction of
IgM paraprotein
Anticoagulation mechanisms
Heparins
LMWH
Dalteparin, Enoxaoarin, Tinzaparin
MOA: Potentiates Anti-Thrombin with preferential selectivity for F10a
Doesn't require monitoring but is irreversible and has a longer half life than heparin
Unfractionated Heparin
Activated antithrombin III that inhibits thrombin affecting factors 9-12
Required monitoring but has short half life; accumulates in renal failure, higher risk of SE's
SEs: Bleeding, osteoporosis, hyperkalaemia,
Heparin induced Thrombocytopenia
Warfarin
MOA: Anti-Vitamin K reductase (inhibits the gamma-carboylation of Vit K dependent factors
2, 7, 9, 10
)
CI: Bleeding diatheses, severe HTN, peptic ulcers,
pregnancy
Bleeding: Bleeding - stop warfarin, prothrombin complex/FFP +IV vit K; INR > 8 - stop warfarin+ IV vit K; INR 6-8 - Stop warfarin, restart when INR < 5; INR < 6- stop 1-2 doses restart when INR < 5
Fondaparinux
MOA: Pentasaccharide that potentiates anti-thrombin with 300x sensitivity for factor 10a - used instead of LMWH in certain circumstances
DOACs
Factor Xa inhibitors - Rivaroxaban, apixaban
Thrombin inhibitor - Dabigatran -->
has an antidote - Idarucizumab
Leukaemia
Acute Lymphocytic Leukaemia (<5 yrs >45yrs)
Children, Downs association
Tend to get majority B lymphoblasts and pancytopenia
Sx: Anaemia, thrombocytopenia, lymphadenopathy, bone pain, developmental arrest
Mx: Supportive e.g. transfusion; Bone marrow transplant - 85% survival rate
Acute Myeloid Leukaemia (>75 yrs)
Early myeloid precursors differentiate; can be caused by transformation from a myeloproliferative disorder e.g. polycythaemia ruby vera, myelofibrosis - most common auto adult cancer
Sx: Gum infiltration, auer rods
Rx: Supportive, chemo, bone marrow transplant
Chronic Lymphocytic Leukaemia (>55 yrs)
Commonest leukaemia in the western world; malignancy of intermediate B cells; Cells arrest in the diffrention pathway and are dysfunctional
Sx: Often incidental finding,
smear/smude cells
Cx: 10% Richter Transformation to
aggressive
Large B cell Lymphoma
; Evans syndrome - body destroys RBCs
Prognosis: 1/3rd never progress, 1/3rd progress with time, 1/3rd actively progressing
Rx: Steroids (Evans), Chemo (Rituximab anti CD20)
Chronic Myeloid Leukaemia (>65 yrs)
Increased proliferation of myeloid line, without loss in capacity to differentiate, associated with
Philadelphia Chromosome -
Bcr-Abl translocation t(9:22)
Phases: 1) Chronic phase (<10% blasts) - most commonly diagnosed; 2) Accelerated Phase (<20% blasts); 3) Acute phase (>20% blasts) i.e. transformation into an acute leukaemia can be refractive to treatment
Rx: Imatinib - Bcl-Abl TK small module inhibitor - 90% survival at 5 years
Sx: Non specific - fatigue, fever, pallor, failure to thrive, lymphadenopathy, hepatosplenomegaly, abnormal bleeding, petechiaei (due to thrombocytopenia)
Anaemia
Sx: Fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, pallor, tachycardia, flow murmur (EJS), cardiac enlargement, HF
Classification
Microcytic (MCV<80)
1) Fe deficiency
2) Thalassemia
Others - Anaemia of chronic disease (ACD), lead poisoning, Sideroblastic (very rare)
Normocytic (MCV 80-100)
Blood loss
Haemolytic anaemia
BM failure (aplastic anaemia)
Renal failure (no EPO)
Early ACD
Macrocytic (MCV >100)
Megaloblastic (less DNA synthesis)
Vit B12 or Folate deficiency
Anti-folate drugs e.g. Phenytoin/methotrexate
Non-megaloblastic
Reticulocytes
Alcohol/liver disease
Hypothyroidism
Myelodysplasia malignancy
Haemolytic anaemia
Can fit in to any of the other classifications
RBC Breakdown
: Unconjugated bilirubin, urinary urobilinogen, LDH, bile pigment stones
Intravascular
: Serum - haemoglobin + Haptoglobins + methaemalbuminaemia; Urine - Haemoglobinuria + Haemosiderin
Extravascular
: Splenomegaly
Acquired Causes
: Immune-Mediated DAT +ve - AIHA, drugs (penicillin, quinine, methyldopa), all-immune (acute transfusion reaction), PNH, mechanical (e.g. metallic Heart valve), infections (malaria), burns
Hereditary causes
: Enzyme (G6PD and pyruvate kinase deficiency), membrane (hereditary spherocytosis/elliptocytosis), haemoglobinopathy (sickle cell, thalassaemia)
Hereditary haemorrhage Telangiectasia: Autosomal dominant, abnormal vessel formation - prone to bleeding, telangiectasia, GI haemorrhage, haemoptysis, epistaxis, FE deficiency anaemia; Rx: Ferrous sulphate + cauterisation
Lymphoma
Hodgkins (15%)
Causes by proliferation of lymphocytes
Sx: B symptoms, "rubbery, enlarged, non-tender LN"
RF: EBV, HIV, FH, Autoimmune conditions e.g. RA
Ix: Biopsy showing
Reed Stern-berg cells
Rx: Chemo + Radio with curative intent - often risk of relapse
Non-Hodgkins lymphoma (85%)
Lots of different types;
Burkitts - EBV, HIV, Malaria -
high grade -->
Most Aggressive
; c-myc gene translocation on chromosome 8 t(8;14) - transposes c-myc (protocol-oncogene) onto immunoglobulin promoter
MALT Lymphoma - Mucosa Associated Lymphoid Tissue - usually in the stomach and associated with
H. pylori
infection
Diffuse Large B cell - often presents as a rapidly growing painless mass in its >65 yrs -
high grade
General RFs: HIV, EBV, H. pylori, Hep B/C, pesticide exposure especially
trichloroetylene
, FH
Sx: Similar to Hodgkins and diagnosis is based on lymph node biopsy
Rx: High Grade -
R-CHOP
= Rituximab, Cyclophosphamide, Hydrocydaunorubicin, Oncovin, Prednisolone; Bone marrow transplant if relapse
A group of cancers that affect the lymphocytes inside the lymphatic system - cancerous cells proliferate within the lymph nodes and causing lymphadenopathy
Ann Arbour Staging
Stage 1: Confined to one region of lymph nodes
Stage 2: In more than one region but on the same side of the diaphragm (either above or below)
Stage 3: Affects lymph nodes both above and below the diaphragm
Stage 4: Widespread involvement including non-lymphatic organs such as the lungs or liver
Neutropenic sepsis
Relatively
common complication of cancer therapy
Most commonly occurs 7-14 days
after chemotherapy
Defined as neutrophil count < 0.5 * 10^9 + a temperature >38 or any other signs of sepsis
Myeloproliferative disorder
Sickle Cell Anaemia
VTE
Thrombophylia
