HAEMATOLOGY Flashcards
Neoplasm of plasma cells - associated conditions
Multiple myeloma (most common); Localised Plasmacytoma (when a more discrete plasma cell tumor develops in or out of bone, eg in airways); Waldenstroms Macroglobulinaemia (monocolonal proliferation of IgM plus lymphocytes)
Pathology of myeloma
Malignant proliferation of plasma cells that leads to the production of one Ig or free light chains.
=immune paresis - infection risk
=hyper viscosity in blood - eye problems
=bone lesions - fractures, pain, neuro involvement if spine
=bone resorption - hypercalcemia
=Increased Ig’s and free light chains in blood - can be deposited in tissues = amyloidosis, renal failure.
Presentation of myeloma
Bone pain - back pain, neuro involvement
Tiredness/ fatigue - anaemia
Confused/ thirsty - older pt, hypercalcaemia
Investigations for myeloma
Bloods:
FBC - anemia, neutropenia, thrombocytopenia
Blood film - stacked RBCs
U&Es - elevated urea and creatinine in renal damage
Serology - raised Ig’s - probably IgG’s
Urine:
Ig’s and free light chains
X-ray:
Bone lesions - lytic
Skull - pepper pot
MRI:
If needed for spine
Signs of myeloma
Anaemia - pale mucus membrane of eyes
Amyloidosis - red/ purple patches around eyes; tongue
Treatment of myeloma
Analgesia
Bisphosphonates for bones & fracture prevention
Anaemia - transfusion, EPO
Renal - rehydrate
Infections - anti-viral prophylaxis, may need IgG transfusion
Chemo/ steroids/ radiotherapy
Causes of microcytic anaemia
- Iron deficiency
- Chronic conditions (through changes in hepcidin?)
- Thalassemia
Causes of normocytic anaemia
- Acute blood loss (GI, or menses)
- Chronic conditions (through changes in marrow/ production)
- Combined haemantic deficiency
Causes if macrocytic anaemia
- B12/ folate deficiency
- Liver disease/ alcohol excess
- Hypothyroid (rarer)
- Other haematological:
- Chemo
- Haemolysis
- Marrow failure - underlying blood disease/ aplastic cause
- Marrow infiltration - myeloma, leukemia etc
Anaemia investigations
FBC, Film, MCV
Reticulcyte count (tell you about marrow activity & haematopoiesis), LFT, U&E’s. B12, folate, Iron.
Serology - Intrinsic factor antibodies - pernicious anaemia; Coeliac disease
If can’t get diagnosis from this, may need marrow biopsy.
Anaemia symptoms
Tiredness/ fatigue SOB Faintness Palpitations Headache Tinnitus Anorexia Angina (if pre-existing coronary disease) If severe - tachy, flow murmurs (systolic), cardiac enlargement
Anaemia signs
Pallor - pale skin Pale mucous membrane - check eyes Brittle nails - may have spoon shape Brittle hair Ulcers at side of mouth
Anaemia managment
Treat the underlying cause, can use oral iron, b12, folate etc.
Some may need blood transfusion.
Examples of chronic diseases that cause anaemia
Chronic infection, vasculitis, rheumatoid, cancer, renal failure (EPO).
Inflammation causes hepcidin release, hepcidin inhibits ferroportin, t/f stored iron cant be used. Any chronic inflammatory disease may cause microcytic anaemia through this mechanism.
Causes of iron deficiency anaemia
Blood loss (GI bleed, menses)
Poor diet
Malabsoprtion
Hookworm (worldwide)
Causes of B12 deficient anaemia
Dietary - vegan
Malabsorption - think pernicious anaemia & problem with parietal cells (IF antibodies, autoimmune disease)
Congenital metabolic errors
Blood results for microcytic anaemia
Low Hb (<115 f; <130 m) + MCV <76
Blood results for normocytic anaemia
Low Hb (<115 f; <130 m) + MCV 76-96
Blood results macrocytic anaemia
Low Hb (<115 f; <130 m) + MCV >96
Physiological cause of macrocytic anaemia
Pregnancy
Groups of anaemias based on pathology
Hypoplastic anaemias (problem with marrow function - cancers etc)
Dyshaematopoietic (problem with how RBCs are made; low iron, B12, folate, chronic disease etc)
Haemolytic (RBCs killed - infection/ malaria, blood disease)
Post hemorrhage (GI - IBD, menses etc)
Pathological consequences of anaemia
Myocardial fatty change Fatty change in liver Aggravate angina/claudication Skin and nail atrophic changes CNS cell death (Cortex and basal ganglia)
What does TTP stand for, what is a distinguishing clinical feature of this disease that would differentiate it from HUS
Thrombotic thrombocytopenia purpura
Neurological involvement distinguishes this from HUS.
HUS - renal picture
TTP pathology - widespread microvascular thrombosis results in consumption of platelets leading to thrombocytopenia and secondary microvascular haemorrhage.
How would you identify HUS on a blood film
Schistocytes - fragmented RBCs. Fragments occur from RBCs passing through damaged microvasculature
What is a common autoimmune cause of TTP
Antibodies against ADAMTS13 protease.
It is a protease that breaks down von willebrand factor. Antibodies against it deplete it = deficiency = promote platelet rich thrombi.
Can also inherit as genetic mutation but rare.
What is the action of warfarin
It is a vitamin K inhibitor.
Vitamin K is required for synthesis of clotting factors X, IX, VII, II
Factor VII is specific to the extrinsic coagulation pathway
Warfarin tf prevents clotting by inhibiting the extrinsic coagulation pathway
What is the action of heparin
Heparin is an indirect inhibitor of Xa and IIa (thrombin)
Heparin binds to antithrombin - an enzyme that inhibits Xa and IIa
Bc heparin mainly acts on thrombin, it prevents clotting by inhibiting the indirect pathway
Why is low molecular weight heparin used over unfractioned heparin
Better (longer) plasma half life, so can give less doses per day - 1-2 injections
What is a DOAC and how does it work
Direct oral anticoagulant
Directly inhibits Xa and IIa
What is factor II and factor I
II = prothrombin I = fibrinogen
What is the function of the extrinsic and intrinsic coagulation pathways
Extrinsic gives a rapid burst of thrombin = useful for vessel rupture
Intrinsic gives a slow but longer lasting thrombin release = useful for inflammatory processes
What are platelet rich thombus formed in arteries and fibrin rich thrombi formed in veins
Think of Virkows tria - flow, coagulation, endothelium
In arteries, damage to the endothelium is the main cause for thombi to form - in this case platelet plugging is the immediate response and predominates
In veins, there is no vessel damage, the problem is with blood flow (i.e. stasis bc of valves and low pressure) - this means that platelets arent activates but clotting factors bump into each other more, so you get fibrin formation without platelets - fibrin rich
What is the fibrinolytic system
System that degrades firbin
Tissue plasminogen activation (from endothelium) - released on break to endothelium
Activates plasminogen -> plasmin
Plasmin degrades fibrin
What drug would you give to a patient that was heamodynamically unstable because of a PE
Thrombolytic drug
Alteplase
