Haematology COPY

Question 1

list 4 risk factors of DVT

Answer 1

increasing age, pregnancy, synthetic oestrogens (pill, HRT), trauma, surgery, past DVT, cancer, obesity, immobility, thrombophilia

Question 2

what other disease may a DVT present as?

Answer 2

pulmonary embolism

Question 3

describe the clinical features of a DVT

Answer 3

warm, tender calf, with erythema. fever. pitting oedema.

Question 4

what investigations would you do on a patient with a suspected DVT?

Answer 4

D-dimer - -ve result excludes DVT, +ve doesn’t mean it is DVT.
doppler US.

Question 5

give 4 features included in the Wells score

Answer 5

active cancer, immobility, major surgery in last 4 weeks, local tenderness, swollen leg, pitting oedema, collateral superficial veins

Question 6

how would you manage a patient with a DVT?

Answer 6

LMWH or fondaparinux - short term anticoagulation.
warfarin or NOAC - long term anticoagulation.
compression stockings.
mobilise, stop the pill.

Question 7

what steps can be taken to prevent DVT?

Answer 7

stop the pill.
early mobilisation.
compression stockings/leg elevation.
LMWH/fondaparinux.

Question 8

how does fondaparinux work as an anticoagulant?

Answer 8

factor Xa inhibitor - prevents the final coagulation pathway from continuing, preventing formation of fibrin clot.

Question 9

how do heparins work as anticoagulants?

Answer 9

activate antithrombin, which inactivates thrombin and factor Xa.
LMWHs also act to inhibit factor Xa directly.

Question 10

how would you stop bleeding in an over-anticoagulated patient?

Answer 10

IV vitamin K - warfarin ‘antidote’

protamine = heparin antidote

Question 11

what must you assess before giving anticoagulation therapy? how would you assess this?

Answer 11

bleeding risk.
HAS-BLED.
Hypertension.
Abnormal liver/renal function.
Stroke.
Bleeding.
Labile INR.
Elderly.
Drugs/alcohol.

Question 12

give a main advantage and disadvantage of NOACs

Answer 12

adv - no need for regular INR monitoring - easier for patient.
dis - don’t have an antidote, so patient at risk of massive haemorrhage if injured etc.

Question 13

what is haemosiderosis?

Answer 13

iron deposition at liver, kidney and heart.

this is why you use iron chelation for repeated transfusions etc.

Question 14

what’s the normal structure of haemaglobin for adults/babies?

Answer 14

babies have HbF = 2xalpha + 2xgamma.
adults HbA = 2xalpha + 2xbeta.
HbA2 = 2xalpha + 2xdelta - found normally, but is increased in beta thalassaemia.

Question 15

what is haemolysis and where can it happen?

Answer 15

premature destruction of RBC. can happen in two places:

1) intravascular - trauma (e.g. mechanical heart valve), complement mediated lysis
2) reticuloendothelial system/extravascular - macrophages of liver, spleen, or accelerated due to immune targeting by antibodies.

Question 16

what does Coombs’ negative/positive mean?

Answer 16

direct antiglobulin test.
used in haemolytic anaemia.
positive = immune mediated
negative = non-immune mediated.

Question 17

what does the bone marrow do? where are biopsies taken?

Answer 17

haemopoiesis - at axial skeleton and long bones (vertebrae, sternum, ribs, skull, limbs)

biopsy is at iliac crest

Question 18

what are megaloblasts?

Answer 18

• large structurally abnormal RBCs
  due to defective DNA synth - leads to leukopaenia + thrombocytopaenia.

causes - B12/folate deficiency, drugs (hydroxyurea).
often asymptomatic as such slow onset means body adjusts.

Question 19

what are the two main types of haematological malignancies?

Answer 19

1) bone marrow origin - myeloid disorders

2) lymphatic origin - lymphoid disorder - B or T cell

Question 20

list the main haematological malignancies and define them

Answer 20

• leukaemias: excess of abnormal white cells in peripheral blood (myeloid or lymphoid)
• lymphomas: tumour presentation w/ local/scattered lumps in lymphatic system
• myeloproliferative disorders: involve BM, liver + spleen w/ peripheral blood features

Question 21

which haematological malignancies tend to follow an acute course with rapid progression?

Answer 21

myeloid = AML
lymphoid = ALL (T or B cell), high grade lymphoma

Question 22

which haematological malignancies tend to follow a slowly progressive course with years between presentation + clinically relevant condition?

Answer 22

myeloid = CML, myeloproliferative neoplasm (e.g. MDS, PRV)
lymphoid = CLL, low grade lymphoma, myeloma

Question 23

what is tumour lysis syndrome

Answer 23

Electrolyte and metabolic disturbance due to breakdown of large number of e.g. leukaemic cells

you get: hyperuricaemia, hyperphosphataemia, hyperkalaemia, hypocalcaemia,renal impairment

Question 24

what is myelodysplastic syndrome (MDS)?

Answer 24

group of malignant haematopoietic disorders characterised by:

1) dysplastic changes in one or more cell lineages
2) ineffective haematopoiesis
3) predilection to develop AML

90% is primary, secondary is due to radio/chemo therapy and has worse prognosis.
usually >70yrs, M, smoker

Question 25

how does myelodysplastic syndrome (MDS) present?

Answer 25

1) anaemia - unexplained macrocytic anaemia. usual anaemia symps, worsening angina, CCF. 2) neutropenia - can get granulocyte depletion --> recurrent infections/sepsis 3) thrombocytopenia - *bleeding*, petechia, bruising, nosebleeds/gums etc

Question 26

how do you diagnose MDS?

Answer 26

diagnosis of exclusion: - FBC - anaemia (normo/macrocytic), neutropenia, thrombocytopenia, neutrophilia, thrombocytosis. - blood film: dimorphic red cells, Pappenheimer bodies, anisocytosis, poikilocytosis. - Ferritin + B12 normal - BM biopsy - hypercellular with blast cells.

Question 27

how do you manage MDS?

Answer 27

supportive blood/plt transfusions + monitoring of iron status - for anaemia/thrombocytopenia. neutropenia - broad spec abx if sepsis, G-CSF if recurrent infections. high-intensity chemo!

Question 28

possible complications of MDS?

Answer 28

- Anaemia, thrombocytopenia, low WCC - Transfusion related iron overload -> desferrioxamine - Transformation to AML - Bone marrow failure (leading cause of death) *Median survival - 2 years*

Question 29

what is Fanconi anaemia?

Answer 29

a mostly autosomal recessive bone marrow failure syndrome. | cells are sensitive to DNA cross-linking.

Question 30

how does Fanconi anaemia present?

Answer 30

1) congenital dysmorphic features - triangle face, café au lait + hyperpigmented skin, cardiac and renal malformations, abnormal thumbs 2) pancytopenic BM failure 3) susceptibility to cancer - AML, solid tumours (H&N SCCs, gynae) presents at <7yrs in similar way to aplastic anaemias, AML, MDS

Question 31

explain how liver disease + vitamin K stuff relates to bleeding problems

Answer 31

- liver is site of coagulation factor and fibrinogen synthesis - disease = bleeding + prolonged PT - vit K needed to synthesis of 2, 7, 9, 10 - fat soluble vitamin so deficient in malabsorption esp. obstructive jaundice - treat vit K deficiency/liver related bleeding with IV vit K

Question 32

learn coag cascade/platelet physiology if you cba

Answer 32

??

Question 33

what drugs influence bleeding?

Answer 33

aspirin and clopidogrel = antiplatelets heparin (factor Xa) and warfarin (factor 2, 7, 9, 10) = affect coag cascade steroids thin the skin and cause bleeding/bruising

Question 34

what is the mechanism of aspirin?

Answer 34

irreversible inhibits COX1 | prevents production of thromboxane A2 - TXA2 induces platelet aggregating and vasoconstriction.

Question 35

what is the mechanism of clopidogrel?

Answer 35

irreversible P2Y12 antagonist. P2Y12 is activated by ADP - amplifies platelet activation by activating glycoprotein Gp2b3a. so clopidogrel inhibits ADP induced platelet aggregation.

Question 36

how does warfarin work?

Answer 36

vitamin K antagonist, long half life, orally available but super complicated dosing. prolongs PT. prevents synthesis of factors 2, 7, 9 and 10. monitor with INR (derived from PT): aim 2-3 some may have higher range 3-4.5

Question 37

give examples of NOACs and mechanisms (might need to check if this is up to date)

Answer 37

factor Xa inhibitors = apixaban, rivaroxaban thrombin (factor IIa) inhibitor = dabigatran. indicated for DVT/PE and AF. equivalent to warfarin INR 2-3 but no monitoring. not easily reversible.

Question 38

list some thrombotic disorders you might screen for if someone presents with DVT. what causes DVTs generally?

Answer 38

- protein C or S deficiency (test = assay) - factor V Leiden - AD condition, test with PCR - antithrombin deficiency - prothrombin gene mutation BUT 95% are due to hypercoagulable state instead - antiphospholipid synd, cancer, obesity, pregnancy, immobility, nephrotic synd, slow blood flow e.g. sickle cell, PRV etc etc

Question 39

try and learn the ABO system for who can give/receive what blood

Answer 39

``` O = universal donor AB = universal receiver ```

Question 40

what are the group and save/screen and cross match blood tests?

Answer 40

group and screen - order if any chance pt needs blood. checks group and Rh status. screens for abs to other antigens. cross match done for most surgery pts. order if 1 in 10 chance of needing blood - checks the specific blood to be given against pt blood by mixing donor RBCs w/pts serum.

Question 41

list some causes of splenomegaly

Answer 41

CHINA - MMM - Congestion: portal HTN, portal vein thrombosis, Budd-Chiari, HF - Haem: haemolytic anaemia, red cell defects, thalassaemia, sickle cell, leukaemias, PRV - Infection: malaria, EBV, CMV, HIV, TB - Neoplasm: CML, lymphoma, splenic mets/cysts - Autoimmune: RA, sarcoidosis, amyloidosis, SLE, Feltys - chronic Myeloid leukaemia - Myelofibrosis - Malaria

Question 42

list some indications for splenectomy

Answer 42

1) Spontaneous rupture at massive splenomegaly (infectious mononucleosis) precipitated by trauma 2) Hypersplenism: ITP, hereditary spherocytosis 3) Neoplasia: lymphoma or leukaemic infiltration 4) Splenic cyst or abscess

Question 43

list some possible complications of splenectomy

Answer 43

1) thrombocytosis - platelet count peaks at 7-10/7 2) overhwleming infection - esp. encapsulated bacteria prophylactic abx + vaccine = oral phenoxymethylpenicillin or macrolides; pneumococcal + flu vaccine. carry health alert card.

Question 44

give some indications for BM transplant

Answer 44

malignant - ALL, AML, CML, HL, MM | non-malignant - thalassaemia, sickle cell anaemia, aplastic anaemia, Fanconi anaemia

Question 45

outline the procedure for a haematopoietic stem cell transplant

Answer 45

- chemo/radiotherapy given before transplant - harvest: BM removed from pelvis under GA or peripheral blood stem cells removed from blood via apheresis. - given GM IV as inpatient - engraftment

Question 46

what's the difference between autologous and allogenic BM transplants?

Answer 46

autologous - stem cells harvested from own BM. pt undergoes ablative/reduced treatment. good as rapid immunity, less infection risk, less risk rejection. BUT not suitable for AML due to high relapse. allogenic - healthy donor and patient. HLA matching to pt HLA at 3 loci. usually sibling/relative match.

Question 47

list possible complications of a BM transplants

Answer 47

- infection - veno-occlusive disease - mucositis - graft vs host disease (immune response launched by graft against host tissue): occurs at <3/12 - maculopapular rash, N&V, cholestatic jaundice. - graft v tumour effect can be beneficial - donor T cells react to diseased lymphocytes of recipient - reduces likelihood of relapse.