HAEMATOLOGY

Question 1

Neoplasm of plasma cells - associated conditions

Answer 1

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)

Question 2

Pathology of myeloma

Answer 2

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.

Question 3

Presentation of myeloma

Answer 3

Bone pain - back pain, neuro involvement
Tiredness/ fatigue - anaemia
Confused/ thirsty - older pt, hypercalcaemia

Question 4

Investigations for myeloma

Answer 4

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

Question 5

Signs of myeloma

Answer 5

Anaemia - pale mucus membrane of eyes

Amyloidosis - red/ purple patches around eyes; tongue

Question 6

Treatment of myeloma

Answer 6

Analgesia
Bisphosphonates for bones & fracture prevention
Anaemia - transfusion, EPO
Renal - rehydrate
Infections - anti-viral prophylaxis, may need IgG transfusion

Chemo/ steroids/ radiotherapy

Question 7

Causes of microcytic anaemia

Answer 7

1. Iron deficiency
2. Chronic conditions (through changes in hepcidin?)
3. Thalassemia

Question 8

Causes of normocytic anaemia

Answer 8

1. Acute blood loss (GI, or menses)
2. Chronic conditions (through changes in marrow/ production)
3. Combined haemantic deficiency

Question 9

Causes if macrocytic anaemia

Answer 9

1. B12/ folate deficiency
2. Liver disease/ alcohol excess
3. Hypothyroid (rarer)
4. Other haematological:
   - Chemo
   - Haemolysis
   - Marrow failure - underlying blood disease/ aplastic cause
   - Marrow infiltration - myeloma, leukemia etc

Question 10

Anaemia investigations

Answer 10

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.

Question 11

Anaemia symptoms

Answer 11

Tiredness/ fatigue
SOB
Faintness 
Palpitations 
Headache
Tinnitus
Anorexia
Angina  (if pre-existing coronary disease)
If severe - tachy, flow murmurs (systolic), cardiac enlargement

Question 12

Anaemia signs

Answer 12

Pallor - pale skin 
Pale mucous membrane - check eyes
Brittle nails - may have spoon shape 
Brittle hair
Ulcers at side of mouth

Question 13

Anaemia managment

Answer 13

Treat the underlying cause, can use oral iron, b12, folate etc.
Some may need blood transfusion.

Question 14

Examples of chronic diseases that cause anaemia

Answer 14

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.

Question 15

Causes of iron deficiency anaemia

Answer 15

Blood loss (GI bleed, menses)
Poor diet
Malabsoprtion
Hookworm (worldwide)

Question 16

Causes of B12 deficient anaemia

Answer 16

Dietary - vegan
Malabsorption - think pernicious anaemia & problem with parietal cells (IF antibodies, autoimmune disease)
Congenital metabolic errors

Question 17

Blood results for microcytic anaemia

Answer 17

Low Hb (<115 f; <130 m) + MCV <76

Question 18

Blood results for normocytic anaemia

Answer 18

Low Hb (<115 f; <130 m) + MCV 76-96

Question 19

Blood results macrocytic anaemia

Answer 19

Low Hb (<115 f; <130 m) + MCV >96

Question 20

Physiological cause of macrocytic anaemia

Answer 20

Pregnancy

Question 21

Groups of anaemias based on pathology

Answer 21

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)

Question 22

Pathological consequences of anaemia

Answer 22

Myocardial fatty change
Fatty change in liver
Aggravate angina/claudication
Skin and nail atrophic changes
CNS cell death (Cortex and basal ganglia)

Question 23

What does TTP stand for, what is a distinguishing clinical feature of this disease that would differentiate it from HUS

Answer 23

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.

Question 24

How would you identify HUS on a blood film

Answer 24

Schistocytes - fragmented RBCs. Fragments occur from RBCs passing through damaged microvasculature

Question 25

What is a common autoimmune cause of TTP

Answer 25

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.

Question 26

What is the action of warfarin

Answer 26

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

Question 27

What is the action of heparin

Answer 27

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

Question 28

Why is low molecular weight heparin used over unfractioned heparin

Answer 28

Better (longer) plasma half life, so can give less doses per day - 1-2 injections

Question 29

What is a DOAC and how does it work

Answer 29

Direct oral anticoagulant | Directly inhibits Xa and IIa

Question 30

What is factor II and factor I

Answer 30

``` II = prothrombin I = fibrinogen ```

Question 31

What is the function of the extrinsic and intrinsic coagulation pathways

Answer 31

Extrinsic gives a rapid burst of thrombin = useful for vessel rupture Intrinsic gives a slow but longer lasting thrombin release = useful for inflammatory processes

Question 32

What are platelet rich thombus formed in arteries and fibrin rich thrombi formed in veins

Answer 32

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

Question 33

What is the fibrinolytic system

Answer 33

System that degrades firbin Tissue plasminogen activation (from endothelium) - released on break to endothelium Activates plasminogen -> plasmin Plasmin degrades fibrin

Question 34

What drug would you give to a patient that was heamodynamically unstable because of a PE

Answer 34

Thrombolytic drug | Alteplase