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Arjun's Copy- Owen's Path > Haematology > Flashcards

Haematology Flashcards

1
Q

What is leukoerythoblastic anaemia

A

Presence of nucleated red blood cells and myeloid precursors in the blood

Leukoerythroblastic anemia is a hematologic disorder characterized by the presence of immature white blood cells (leuko-) and nucleated red blood cells (erythroblasts) in the peripheral blood. This condition indicates bone marrow dysfunction or pathology that disrupts the normal process of blood cell production.

Leukoerythroblastic anemia is caused by space-occupying lesions in the bone marrow that prevent normal production of blood cells.

Leukoerythroblastic blood findings are typically seen in disorders associated with bone marrow fibrosis including myelofibrosis and other myeloproliferative disorders, and cancers with metastatic disease to the bone marrow

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2
Q

What see on blood film of leukoerythoblastic

A

Tear drop cells
Nucleated RBC (ie immature-erythroblasts, reticulocytes have NO nucleus but still have some RNA hence bluish)
Myelocyte (myeloid precursors)

Leukoerythroblastic anemia describes the presence in the peripheral blood of nucleated erythrocytes and immature white cells of the neutrophilic myeloid series.

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3
Q

What could cause leukoerythoblastic

A

Malignant
- non haemaoptoetic
- leukaemia, myeloma, lymphoma

Myelofibrosis

Severe infection
- miliary TB
- severe fungal infection

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4
Q

How are haemolytic anaemias classified

A

Acquired
Inherited

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5
Q

Blood finding of haemolytic anaemia

A

Anaemia- raised MCV (as reticulocytes)
Reticulocytosis
Bilirubinaemia
LDH up
Haptoglobin decreases (as bound to Hb?)

In intravascular hemolysis, free hemoglobin will be released into circulation and hence haptoglobin will bind the hemoglobin. This causes a decline in haptoglobin levels.

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6
Q

How to tell if haemolytic anaemia is immune

A

Spherocytes (remember spherocytosis is key feature of immune HA)
DAT+ve
(DAT -ve spherocytosis = hereditary spherocytosis, DAT +ve = haemolytic anaemia)

direct is for HA, indirect for ABO incompatibility?

Spherocytes are found in all hemolytic anemias to some degree. Hereditary spherocytosis and autoimmune hemolytic anemia are characterized by having only spherocytes.

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7
Q

Causes of immune haemolytic anaemia

A

SLE
Cancer- CLL, lymphoma
Mycoplasma (cold agglutinins)
Adenocarcinoma

infection (mycoplasma), inflammation (SLE), malignancy (CLL/Lymphoma)

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8
Q

Causes of non-immune haemolytic anaemia

A

Malaria
MAHA

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9
Q

What is often underlying condition in MAHA

A

Adenocarcinoma
HUS
DIC
TTP
Pre-eclampsia (HELLP)

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10
Q

Blood film of MAHA

A

RBC fragments- schistocytes
Thrombocytopenia

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11
Q

What happens in MAHA

A

Mechanical RBC destruction for example through fibrin/plt mesh or metallic heart valve

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12
Q

Differing between reactive and malignant neutrophilia

A

Reactive (ie to infection etc.)- toxic granulation and no immature cells
Malignant- basophilia and myelocytes in CML

remember neutrophilia in infection usually pyogenic bacterial infection

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13
Q

When do you get reactive eosinophilia

A

Parasitic infection
Allergic disease
Neoplasms which release eosiniphilic growth factor
Drug reactions in particular erythema multiforme

the price we pay for parasite defence is allergy

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14
Q

What causes raised lymphocyte count

A

EBV,CMV, toxolplasma, rubella, herpes
Hepatitis
Autoimmune
Sarcoid

viruses as intracellular- so CD8+ kill

Infection (viral), inflammation (AI, sarcoid), malignancy (lymphoma/lymphoid leukaemia)

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15
Q

How to determine whether reactive or malignant in B cells

A

Look at light chains- ratio of kappa and lambda
If reactive will be equal (60:40)
If malignant will be 1 predominating (99:1)- as monoclonal expansion?

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16
Q

Blood findings of iron deficiency anaemia

A

Microcytic hypochromic anaemia
Low ferritin, transferrin saturation
Increased TIBC

Remember transferrin saturation = serum iron/TIBC. If <20% then indicates IDA.

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17
Q

What are spherocytes

A

RBC without central pallor
Are spherical and smaller

Seen in any haemolysis (need to differentiate if immune haemolysis or HS)

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18
Q

Neutropenia and myeloblasts

A

AML

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19
Q

What causes chronic eosinophilic leukaemia

A

FIP1L1-PDGFRa fusion gene

Chronic eosinophilic leukemia (CEL) is a chronic myeloproliferative disease of unknown etiology in which clonal proliferation of eosinophilic precursors results in a persistently elevated number of eosinophils in blood, bone marrow or peripheral tissues resulting in organ injury, and mortality.

form of CML (as eosinophils are myeloid lineage)

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20
Q

What causes a monocytosis

A

TB, brucella, typhoid
Viral- CMV, varicella
Sarcoidosis
Chronic myelomonocytic leukaemia

(granulomas + viral infection + CMML)

Chronic myelomonocytic leukemia (CMML)
Is an uncommon blood cancer that has features of two other types of blood cancers. For this reason, the World Health Organization (WHO) classifies CMML as myelodysplastic/myeloproliferative neoplasms.

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21
Q

Lymphopenia causes

A

HIV
Auto-immune disorders
Inherited immune deficiencies
Chemo

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22
Q

What is thrombophlebitic syndrome and when does it occur

A

Is a complication of thromboembolism
- recurrent pain
- swelling
- ulcers

same as post-thrombotic syndrome?

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23
Q

Inherited causes of VTE

A

Antithrombin deficiency
Protein S deficiency
Protein C deficiency
Factor V leiden

All of these are thrombophilias (factor V Leiden is most common)

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24
Q

How does injury to vessel wall make it prothrombotic

A

Anticoagulant molecules like thrombomodulin down regulated
Prostacyclin production reduced (prostacyclin is anti-thrombotic as reduces plt function)
Vwb factor release

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25
Q

What can causes vessel wall prothrombotic

A

COVID19
Malignancy
Vasculitis
Trauma

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26
Q

How does stasis promote thrombosis

A

Accumulation of activated factors
Promotes platelet adhesion
Hypoxia produces inflammatory effects on endothelium
- adhesion and release of VWF

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27
Q

What are the anticoagulant drugs and how are classified

A

Immediate
- heparins
- direct anti Xa and anti IIa
Delayed
- vit K antagonists (initially pro-thrombotic as prot C and S (co-factor to C) also down but this occurs first, before 2,7,9,10 are down)- given with LMWH to prevent this

remember vit K- 1972 (10,9,7,2)

Immediate-
Heparins and DOACs
Delayed-
Warfarin

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28
Q

What are 3 options of heparins, their method of administration and if need monitoring

A

Unfractionated heparin IV and needs monitoring- APTT
LMWH subcut no monitoring
Pentasaccharide subcut no monitoring ( ie. Fondaparinux is a synthetic anticoagulant (blood thinner) that is administered subcutaneously (under the skin). It belongs to a class of drugs known as factor Xa inhibitors)

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29
Q

Long term disadvantages of heparins

A

Osteoporosis and injections

long term use of UFH = osteoporosis (mechanism is blurry)

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30
Q

MOA of heparins

A

Potentiate antithrombin III which inactivates thrombin and factors 9,10,11

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31
Q

What are the DOACS

A

Anti-Xa
- rivaroxaban, apixaban, edoxaban
Anti- IIa
- dabigatran

X in it then Xa inhibitor

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32
Q

Monitoring needed for DOACS

A

None

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33
Q

Difference in peaks of anticoagulants

A

DOAC and heparin 4 hours
Vitamin K a delayed

ie immediate vs delated anti-coagulants

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34
Q

MOA of warfarin

A

Indirectly prevents the recyclin of Vit K which reduces levels of 2,7,9 and 10

Hence takes bit more time as prevents recycling not immediate inhibition

vit k epoxide reductase enzyme inhibition

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35
Q

How is warfarin given

A

Oral

remember monitor with INR (>3 is abnormal- 3 letters in INR)

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36
Q

Antidote for heparin

A

Protamine sulphate

Protamine sulfate works by binding to heparin molecules, neutralizing their anticoagulant effects.
For warfarin it’s vitamin K

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37
Q

Antidote for DOACs

A

In dabigatran is an antibody none for Xa

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38
Q

How is unfractionated heparin monitored

A

APTT
(anti-Xa or heparin levels in some trusts - when have to monitor LMWH (e.g. renal failure)/UFH)

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39
Q

What is given as thromboprophylaxis

A

Tinzaparin 4500u
Enoxaparin 40mg

both LMWHs
why is LMWH preferred over UFH usually- LMWHs have more predictable pharmacokinetics compared to UFH. This allows for fixed dosing without the need for frequent monitoring of activated partial thromboplastin time (aPTT), which is required with UFH.

LMWHs are administered by subcutaneous injection, making them more convenient than UFH, which is typically given intravenously. This allows for outpatient administration and self-administration in certain situations.

lower osteoporosis risk
lower risk of HIT (heparin induced thrombocytopaenia)- HIT is an immune-mediated reaction that can cause a significant drop in platelet count and an increased risk of thrombosis.

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40
Q

What is given as thromboprophylaxis if upcoming surgery or heparin CI

A

TED stockings

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41
Q

What is given sometimes to post op ortho patients

A

DOAC and aspirin

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42
Q

Differnece in length of DOAC given after VTE

A

Surgical precipitant
- no need for long term
Idiopathic with no identified risk
- long term
Minor precipitant like trauma or flights
- 3 months

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43
Q

Risk factors for myeloma

A

Age
Obesity
Black

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44
Q

What is MGUS and how diagnosed

A

Precursor to myeloma where are free light chains in blood or urine
- serum m protein less than 30g/L
- bone marrow clonal plasma cells less than 10%
- no evidence of organ damage/lesions- no CRABBI

Mayo criteria used to Dx?

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45
Q

Risks of MGUS

A

Increased risk of osteoporosis, thrombosis, bacterial infection
Myeloma transformation if IgG or IgA (not IgM as waldenstom’s i think?)
Waldenstroms lymphoma if IgM (waldenstroms macroglobulinaemia ie an ‘indolent lymhoma’ and a plasma cell dyscrasia (like other MM precursors)

At one end of this spectrum of hematological disorders, detection of one of these myeloma proteins in an individual’s blood or urine is due to a common and clinically silent disorder termed MGUS, i.e. monoclonal gammopathy of undetermined significance. At the other end of this spectrum, detection of the myeloid protein is due to a hematological malignancy, i.e. multiple myeloma, Waldenström macroglobulinemia, or other B cell-associated neoplasm, that has developed, often in a stepwise manner, from their MGUS precursors.

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46
Q

How is MGUS risk stratified

A

MAYO

Mayo MGUS risk stratification.
*Low risk: 5% risk of progression in 20 years; intermediate risk: 20% risk of progression in 20 years; high risk: 60% risk of progression in 20 years.

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47
Q

Difference between smouldering myeloma and MGUS

A

Smouldering myeloma
- M spike over 30g/L or urinary monoclonal protein over 500 mg or bone marrow clonal plasma cells over 10%
- BUT no CRAB criteria or amyloidosis

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48
Q

Typical primary genetic events leading to myeloma

A

Hyperdiploidy

Hyperdiploidy refers to a condition in which a cell or organism has a chromosome number that is higher than the typical diploid number for its species. For example, in multiple myeloma, hyperdiploidy may manifest as the presence of more than 46 chromosomes in the cancerous plasma cells. The detection of hyperdiploidy and other chromosomal abnormalities is often performed through cytogenetic testing or fluorescence in situ hybridization (FISH).

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49
Q

Presentation of myeloma

A

CRAB
Calcium- hypercalcaemia sx
Renal failure- amyloidosis (AL amyloidosis in MM as L for light chain) and nephrotic syndrome
Anaemia- pancytopenia
Bones- pain (esp back as crush fractures of vetebrae), osteoporosis, lytic lesions, fractures

CRABBI HA
(B for bleeding as BM crowding, I for infection, H for hyperviscosity, A for AL amyloidosis)

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50
Q

Diagnostic criteria for myeloma

A

Over 10% plasma cells in bone marrow or plasmacytoma plus atleast 1 CRAB or MDE
CRAB
- calcaemia over 2.75
- creatine over 177 or eGFR under 40
- Hb under 100 or drop by 20
- one or more bone lytic lesion
MDE (myeloma defining events)
- bone marrow plasma cells over 60%
- FLC ration over 100
- over 1 focal lesion (evidence of ROD- myeloma Related Organ Dysfunction?)

A plasmacytoma is a localized, solitary mass or tumor consisting of plasma cells.

“myeloma-defining events” to include biomarkers that, when present along with clonal bone marrow plasma cells of 60% or more, can also indicate a diagnosis of multiple myeloma.

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51
Q

Imaging for myeloma bone disease

A

Never use X rays
Whole body CT scan (v good at finding lytic lesions)
PET
MRI

While X-rays can detect bone lesions, they are not as sensitive as more advanced imaging modalities for detecting early or subtle bone involvement in multiple myeloma. X-rays may not show abnormalities until a significant amount of bone destruction has occurred. In the case of multiple myeloma, the disease often involves the bone marrow, and X-rays primarily visualize changes in the bone structure, not the marrow itself.

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52
Q

Main surgical emergencys in myeloma

A

Cord compression and hypercalcaemia

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53
Q

How to manage cord compression

A

MRI scan
- dexamethasone
- radiotherapy
- rarely require neurosurgery

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54
Q

How can myeloma cause renal damage

A

High serum free light chains
Dehydration
Treatment drugs are nephrotoxic

(Also AL amyloidosis deposits- nephrotic syndrome?)

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55
Q

Diagnostic work up for myeloma

A

Serum protein electrophoresis (M protein spike)
Serum free light chains
24 hour urine collection for bence jones protein (aka urine free light chains)
Bone marrow aspirate and biopsy
- stain for CD138

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56
Q

What is stained for in myeloma

A

CD138

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57
Q

How is myeloma staged

A

Internaltional staging system/salmon durie

ie ISS/R-ISS

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58
Q

Most common presentation of myeloma amyloid

A

Nephrotic syndrome

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59
Q

What is monoclonal gammopathy of renal significance (MGRS)

A

At least 1 renal lesion causesd by free light chains
Does not meet haematological criteria for myeloma diagnosis

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60
Q

How is MGRS treated

A

In same way as myeloma

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61
Q

Problem of bortezomib

A

Neuropathy

Myeloma is a chronic relapsing and remitting malignancy which is currently deemed incurable. Management aims to control symptoms, reduce complications and prolong survival.

A combination of drugs is used to treat myeloma - ‘induction therapy’ :
targeted drugs (such as thalidomide, lenalidomide, bortezomib, daratumumab)
chemotherapy (such as cyclophosphamide or melphalan)
steroids (such as prednisolone or dexamethasone)

The particular combination depends on whether a patient may be suitable for autologous hematopoietic cell transplantation or not.

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62
Q

Problems of carfilzomab

A

Thrombocytopenia and IV infusion

Carfilzomib belongs to a class of drugs known as proteasome inhibitors. The proteasome is a cellular structure responsible for breaking down and removing proteins. By inhibiting the proteasome, carfilzomib disrupts the normal protein degradation process, leading to the accumulation of proteins within myeloma cells and ultimately causing their death.

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63
Q

Polycythaemia in neonate/fetus causes

A

Twin to twin transfusion
Intrauterine hypoxia
Placental insufficiency

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64
Q

Anaemia causes in fetus/neonates

A

Twin to twin transfusion
Fetal-maternal-transfusion
Parvovirus B19
Haemorrhage
Dammage from irradiation, anticoagulant drugs, antibodies

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65
Q

When can some of the first mutations leading to leukaemia often occur

A

In utero
If twins can even pass from one twin to another

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66
Q

What is significant risk factor for congenital leukaemia (transient abnormal myelopoiesis)

A

Down syndrome

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67
Q

Features of congenital leukaemia

A

Myeloid with huge involvement of megakaryocyte lineage

Congenital leukemia refers to leukemia that is present at birth or diagnosed shortly after birth

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68
Q

Difference between thalassaemia and haemoglobinopathy

A

Thalassaemia- reduced synthesis of globin chains
Haemoglobinopathies- synthesis of abnormal globin chains

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69
Q

What are 3 types of haemoglobin and what globin chains make up them

A

A- alpha and beta
A2- alpha and delta
F- alpha and gamma

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70
Q

Haemoglobin proportions through life

A

When foetus principally F and a bit of A
As grow is A with a bit of A2

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71
Q

Triggers for sickling episodes

A

Hypoxia
Dehydration
Acidosis

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72
Q

Where does vascular obstruction occur in sickle cell disease

A

After elongation to pass from capillary bed to venule

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73
Q

Mutation in SCD

A

Point mutation of glutamate replaced by valine codon 6 of beta chain coding for beta globin chain on Chr 11
1 in sickle cell trait
2 in sickle cell anaemia

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74
Q

What are 4 types of sickle cell disease

A

Remember sickle cell disease is an umbrella term
- sickle cell anaemia HbSS
- sickle cell trait HbAS
- sickle-haemoglobin C disease HbSC
- sickle beta thalassaemia HbS/beta

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75
Q

What happens in sickle-haemoglobin C disease

A

Inherit one HbS and one HbC which is a defective beta chain of a different source to sickle cell disease

Hemoglobin C (abbreviated as HbC) is an abnormal hemoglobin in which glutamic acid residue at the 6th position of the β-globin chain is replaced with a lysine residue due to a point mutation in the HBB gene.[1] People with one copy of the gene for hemoglobin C do not experience symptoms, but can pass the abnormal gene on to their children.

HbSC is milder than SCA

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76
Q

Presentation of sicke cell beta thalassaemia present

A

Very severely- is similar to HbSS

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77
Q

How are haemoglobinopathies and thalassaemias normally discovered

A

Guthrie blood spot

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78
Q

How does SCD problems differ between the ages

A

In younger people- hand foot syndrome very common
Splenic sequestration occurs in young as still have functioning spleen
Then in older people when spleen is fibrosed get hyposplenism which leads to increased infection risk
Infants immune system has not developed immunity to parvovirus or pneumococcus which can be deadly as susceptible to red cell aplasia
Children are growing which has immense demand for folic acid
- growth spurts require folic acid
- red cell lifespan a lot less
- hyperplastic erythopoiesis requires folic acid

strokes v common in SCD children

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79
Q

What is splenic sequestration and how can present

A

When blood pools in the spleen
Severe anaemia, shock and possible death

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80
Q

Complications of iron overload

A

HF
Gonadal failure

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81
Q

Problems of anaemias from haemoglobinopathies and thalassaemias in children

A

Lead to growth retardation
HF

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82
Q

Treatment for iron overload

A

Chelation therapy
- desferrioxamine
- deferipone

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83
Q

Classifications of haemolytic anaemias in children

A

Red cell membrane
- hereditary spherocytosis
- hereditary elliptocytosis
Haemoglobin defects
- sickle cell anaemia
Glycolytic pathway
- PK deficine
Pentose shunt defects
- G6PD

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84
Q

What is most common acute leukaemia in children under 1

A

AML

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85
Q

How does VWD present

A

Mucosal bleeding
Bruises
Post traumatic bleeding

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86
Q

What is transient abnormal melopoiesis

A

resembles AML, it presents in neonates at birth or just later
Very megakaryoblastic

common in Down Syndrome

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87
Q

Differences between congenital leukaemia and tranisent abnormal myelopoeisis

A

Congenital- symptoms at birth, cell markers, high blasts
TAM- everything normal

Not necessarily true? True for silent TAM

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88
Q

What is translocation in acute promyelocytic leukaemia

A

t(15;17)
PML-RARA or FLT3-ITD

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89
Q

How does acute promyelocytic leukaemia often present

A

Bleeding and DIC

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90
Q

Which chromosome duplications can lead to AML

A

8
21

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91
Q

Common translocations associated with AML

A

15;17
5;8
8;21
16;16

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92
Q

Chromosomal loss or deletion associated with AML

A

Deletions loss of 5/5q and 7/7q

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93
Q

What are the principles of leukaemogenesis in aml

A

At least 2 interacting molecular defects
Type 1- promote proliferation and survival of cells
Type 2- block differentiation

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94
Q

What chromosome inversion can lead to AML

A

16

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95
Q

Cytology of AML versus ALL

A

Both have elevated WCC blasts
AML- auer rods and granules
ALL- the blasts have blebs of cytoplasm

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96
Q

What is main accepted aetiology for AML

A

Unknown

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97
Q

How to tell difference between AML and ALL

A

Immunophenotyoping

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98
Q

What method is used for immunophenotyping in acute leukaemia

A

Flow cytometry

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99
Q

ALL versus AML flow cytometry

A

Common to all- CD34 as on precursor cells
ALL
- T lymphocytes CD3, CD4, CD8
- B-lymphocytes CD19, CD23
AML
- CD13, CD33 and MPO

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100
Q

What is AML which presents with hypokalaemia, gum and skin infiltration

A

Monocytic

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101
Q

Which AML often presents with CNS disease

A

Acute monocytic leukaemia

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102
Q

If suspect acute leukaemia what investigations do in order

A

Blood film to look for auer rods/granules
Immunophenotyping to look for specific markers
If no leukaemic cells in blood do a bone marrow aspirate

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103
Q

Main clue differentiating acute leukaemia in history

A

Lymphadenopathy very common in ALL but not AML

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104
Q

Supportive care for AML

A

Red cells
Platelets
FFP if DIC
Abx

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105
Q

What is used to treat DIC

A

FFP/cryoprecipitate

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106
Q

Chemo regime for AML
- induction of remission and maintenance

A

Induction of remission
- danorubicin
- cytarabine
Consolidation
- cytarabine

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107
Q

Management of AML and ALL if poor prognosis/high risk of relapse

A

Allo-SCT

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108
Q

Management of APML

A

All-trans-retinoic-acid (ATRA) and A2O3

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109
Q

What can be given for CD33 AML

A

Gemtuzumab- CD33 immunotherapy

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110
Q

What is given in Ph postive leukaemias

A

Imatinib

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111
Q

What are the differences on examination of T-ALL vs B-ALL

A

Thymic enlargement in ALL

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112
Q

Which genetic abnormalities are associated with good and bad prognosis in ALL

A

Good- hyperdiploidy
Bad- Ph chromosome (BCR-ABL)

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113
Q

What are the 2 specialised treatments for ALL

A

Ph-chr- imatinib
CD20- rituximab

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114
Q

Why are allopurinol and electrolytes given in acute leukaemia

A

Prevent TLS

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115
Q

What is TdT

A

Marker of immature lymphocytes

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116
Q

When are spherocytes seen

A

HS
Haemolytic anaemia

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117
Q

What is MCV in B12

A

Extremely high

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118
Q

Why do you get pancytopenia in B12 deficiency

A

Needed for DNA synthesis
-RBC the most rapid turnover so thats why anaemia most marked symptom
Plt and neut maturation still need B12 just not as quickly

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119
Q

What is most common cause of renal failure in myeloma

A

Cast nephropathy

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120
Q

What are myelodysplastic syndromes

A

Group of heterogenous haematopoeitic stem cell disorders which results in aberrant cells produced from myeloid lineage
Seen in elderly

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121
Q

What are ringed sideroblasts seen in

A

Myelodysplastic syndromes

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122
Q

What are micromegakaryocytes and platelts with hypolobated nuclei seen in

A

Myelodysplastic syndromes

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123
Q

What is pegler huet anomaly seen in

A

Myelodysplastic syndromes

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124
Q

Morophological anormalities associated with myelodysplastic syndromes

A

RBC- ringed sideroblasts where get nucleated blast surrounded by iron granule ring
Neutrophil- pelger huet anomaly where bilobed neutrophil
Platelet- micromegakaryotype and hypolobated nuclei

These 3 features are examples of abnormal differentiation which characterises the pathogenesis of MDS

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125
Q

Difference between acute myeloid leukaemia and myelodysplastic syndromes

A

AML over 20% blasts

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126
Q

Prognosis of myelodysplastic syndromes

A

1/3 die from infection
1/3 die from bleeding
1/3 die from acute leukaemia

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127
Q

Treatment of myelodysplastic syndromes

A

Supportive – transfusions, EPO, G-CSF, ABx
• Biological modifiers – immunosuppressive drugs, lenalidomide, azacytidine
• Chemotherapy – similar to AML
• Allogeneic SCT

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128
Q

What is aplastic anaemia

A

Where bone marrow fails to produce the required number of red cells but can be pancytopenic

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129
Q

What is bone marrow described as in aplastic anaemia

A

Hypocellular

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130
Q

Difference between myelodysplastic syndromes and aplastic anaemia

A

Both have pancytopenia
In MDS there is disorder of differentiation so BM is full of blasts- hypercellular
In AA failure to produce so BM is hypocellular

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131
Q

Causes of aplastic anaemia

A

Primary
- inherited
- idiopathic

Secondary
- radiation
- infections- hepatitis, P19
- SLE
- drug (mainly chemo)

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132
Q

Treatment of idiopathic aplastic anaemia

A

Supportive- abx, transfusions and chelation if needed
If young then aim for stem cell transplant with sibling if not explore other treatment non-family
If old or donor not found then use immunosuppression
Immunosuppressive agents- ciclosporin, anti-lympocyte globulin, eltrobopag

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133
Q

What immunosuppressive agents are used for idiopathic aplastic anaemia

A

Anti-lymphocyte globulin
Ciclopsorin
Second line- eltrombopag

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134
Q

What are 2 inherited causes of aplastic anaemia need to know

A

Fanconi anaemia- most common
Dyskeratosis congeinta

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135
Q

Genetic basis of fanconi anaemia versus dyskeratosis congenita

A

FA- multiple genes involved
DC- abnormal and short telomeres
Inheritance- FA is AR, DC is x linked

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136
Q

When does fanconi anaemia present

A

5-10 years old

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137
Q

Complications of fanconi anaemia

A

Risk of congenital and somatic abnormalities
- short stature
- cafe au lait spots
- microcephaly
- developmental delay
- abnormality of thumbs
- hypogonadism
Cancer risk
- AML and MDS

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138
Q

Childhood aplastic anaemia with strange thumbs, short, delayed and pigmented spots

A

Fanconi anaemia

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139
Q

Triad for dyskeratosis congenita

A

Skin pigmentation
Nail dystrophy
Leukoplakia which are white areas in the mouth

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140
Q

Pancytopenia, skin pigmentation, nail issues and white patches in mouth

A

Dyskeratosis congenita
(nail dystrophy and leukoplakia)

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141
Q

What happens to platelets in malaria

A

Can drop acutely

like in dengue too!

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142
Q

What are hypersegmented neutrophils seen in

A

Megaloblastic anaemia- where BM produces large cells due to B12 deficiency

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143
Q

What is paroxysmal cold haemoglobinuria

A

Get AIH anaemia from RBC lost in urine during an infection- measles, syphyllis, VZV

Donath-Landsteiner antibodies

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144
Q

Haematuria versus haemoglobinuria how to tell

A

Centrifuge and if haematuria, RBC will sit at bottom

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145
Q

How is APML diagnosis confirmed

A

Cytogenetic analysis

t(15;17) - PML-RARA

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146
Q

Blood findings of MDS

A

Typically- macrocytic anaemia
Can get pancytopenia

pelger-huet, ringed sideroblasts

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147
Q

What are metamyelocytes seen in

A

Megaloblastic anaemia

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148
Q

What is difference between megaloblastic macrocytic anaemia and non-megaloblastic

A

Megaloblastic is impaired DNA synthesis from folate or B12 deficiency
Non-megaloblastic is from liver disease and hypothyroidism where just slow at producing cells

macrocytic to do with DNA formation, microcytic to do with Hb problems

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149
Q

What is rouleaux formation and what seen in

A

RBC stacked on one another
Myeloma
Chronic inflammation (as acute phase proteins etc.)

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150
Q

What does facial plethora suggest

A

Is red swelling and puffiness
Polycythaemia vera

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151
Q

Which tumour produces IgM antibodies

A

Waldenstroms lymphoplacytic lymphoma

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152
Q

What are parts to antibody and how relate to myeloma

A

Common portion (Fc) (base) made up of heavy chains
Variable portion (Fab) made of kappa or lamda light chains
Myeloma get production of IgA or IgG

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153
Q

Most important drug in myeloma kidney disease treatment

A

Bortezomib

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154
Q

Management of myeloma

A

Depends if transplant eligible (under 65 or not)

Eligible
- anti-CD38 (daratumumab)
- proteasome inhibitors ( bortezomib)
- immunomodulatory drugs (lenalidomide)
Then ASCT

Non-eligible
- daratumumab
- lenalidomide
- dexamethasone

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155
Q

What is a lymphoma

A

A malignant tumour of lymphoid cells found in either the LN, BM, spleen or tissue specific lymphoid tissue

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156
Q

What factors involved in our immune system make it a common site for malignancy

A

Constant cutting and recombining TCR and Ig leads to potential for errors and point mutations
Rapid cell proliferation in response to infection increases chance of mutation
Process dependant upon apoptosis which provides opportunity for apoptosis mutations

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157
Q

What are the risk factor categories for non-hodgkins lymphoma

A
  1. constant antigenic stimulation from bacterial infection or chronic AI conditions
  2. viral infection
  3. EBV infection when loss of t cell function
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158
Q

What lymphoma is associated with sjogrens

A

Marginal zone lymphoma of parotid gland

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159
Q

What lymphoma is associated with hashimotos

A

Marginal zone lymphoma of the thyroid

160
Q

What lymphoma is asscoaited with coeliac disease

A

Enteropathy associated T-cell NHL

161
Q

Example of virus causing lymphoma from direct viral integration

A

HTLV-1 infects T cells from vertical transmission causing adult t cell leukaemia lymphoma
Common in japanese and carribean

162
Q

What are the 3 parts of the lymphoreticular system

A

Generative: generate and maturation of lymphoid cells
- thymus
- BM

Reactive: develop the immune reaction
- LN
- Spleen

Acquired: develop the local immune reaction
- extranodal lymohoid tissue in the skin, stomach etc

163
Q

What is route of a b cell in a LN

A

Enters B cell area and in mantle zone is a naive B cell
Enters the germinal centre and those wich bind antigen epitopes are activated and selected
Will then enter post germinal centre
This process is why B cell lymphomas much more common

164
Q

In lymphoma which CD suggest B cell versus T cell

A

T- CD3, CD5
B- CD20

165
Q

What are the B cell NHL

A

Low grade
- follicular lymphoma
- small lymphocytic
- marginal zone

High grade
- diffuse large B cell
- Burkitts lymphoma

Aggressive
- mantle cell lymphoma

166
Q

Clinical features of follicular lymphoma

A

Lymphadenopathy - waxing and waning
Elderly/middle age
Very indolent - virtually incurable

167
Q

Molecular features of follicular lymphoma

A

14,18 transformation involving production of bcl-2 gene

168
Q

Histology of follicular lymphoma

A

Follicular pattern or nodular appearance of germinal cell origin CD10
Stain for bcl-2/6

169
Q

What causes marginal zone lymphomas

A

Chronic antigen stimulation
ie sjogrens- parotid marginal zone lymphoma
Can be treated just by removing the trigger

170
Q

What lymphoma does chronic Hpylori infection cause

A

Gastric MALT lymphoma

171
Q

Histology of large B cell lymphoma

A

Sheets of large lymphoid tissue (B cells)

172
Q

What are 3 types of burkitts lymphoma

A

Endemic- found in africa, EBV, jaw movement and abdo mass
Sporadic- EBV, jaw less involved
Immunodeficiency- non EBV associated. HIV/post transplant

173
Q

What presents with jaw or abdo mass in young adults

A

Burkitts lymphoma

174
Q

Histology of burkitts lymphoma

A

Germinal centre
Starry sky appearance- macrophages containing phagocytosed lymphocytes

175
Q

Molecular findings of burkitts lymphoma

A

8;14 translocation
C-myc production

176
Q

Histology of mantle cell lymphoma

A

Pregerminal centre cells in mantle zone
Angular, clefted nulei
Cyclin D1 overexpression

177
Q

Molecular findings of mantle cell lymphoma

A

11;14 translocation
Cyclin D1 overexpression

178
Q

What are the NH T-cell lymphomas

A

Peripheral T cell lymphoma
Enteropathy associated T cell lymphoma
Cutaneous T cell lymphoma
Anaplastic large cell lymphoma
Adult T cell leukaemia/lymphoma

PLACE-order of aggressiveness as well!

179
Q

What is associated with cutaenous t cell lymphoma

A

Mycosis fungoides

180
Q

Histology of peripheral t cell lymphomas

A

Large t lymphocytes in old people

181
Q

Histology of anaplastic large cell lymphoma

A

Large epithelioid lymphocytes

182
Q

Clinical features of anaplastic large cell lymphoma

A

Occurs in children young adults
Lymphadenopathy

183
Q

Molecular findings of anaplastic large cell lymphoma

A

2;5 translocation
Alk-1 protein expression

184
Q

Pain in lymph nodes after drinking and cyclical fever

A

Hodgkins lymphoma
Has bimodal presentation- 20-29 and over 60

185
Q

Difference between NHL versus HL in presentation

A

NHL- involves multiple sites and spreds randomly anywhere
HL- single node involved and spreads to adjacent one

186
Q

How is hodgkin lymphoma staged

A

Ann arbor
1- 1 node site affected (includes spleen)
2- 2 or more regions on same side of diaphragm
3- 2 or more regions on other sides of diaphragm
4- extra nodal site like like liver or BM affected (cant be spleen)

Can be A or B
B = constitutional symptoms and A they do not

187
Q

Histology of classical Hodgkins lymphoma

A

Sclerosis
Reed steenberg cells and hodgkin cells
Germinal or post germinal B cell origin
EBV associated
CD15,20,30+ve

188
Q

What are subtypes of hodgkins lymphoma

A

Classical
- Nodular sclerosing
- Mixed cellularity
- Lymphocyte rich and lymphocyte depleted

Nodular lymphocyte predominant

189
Q

Histology of nodular lymphocyte predominant Hodgkins lymphoma

A

Germinal centre B cell
B cell rich nodules
CD20+ve only

popcorn cells, lack of R-S cells

190
Q

How can lymphomas present

A

Lymphadenopathy
Extrinsinc pressure from LN
Constitutional symptoms
Recurrent infections

191
Q

What is most common hodgkins lymphoma

A

Nodular sclerosing

has best prognosis as well

192
Q

How is hodgkin lymphoma investigated

A

Lymph node biopsy and relevant immunohistochemistry and molecular studies
PET scan to stage

193
Q

Treatment of classical hodgkins lymphoma

A

ABVD
Adriamycin
Bleomycin
Vinblastine
DTIC
Long term SE- pulmonary fibrosis, cardiomyopathy

194
Q

How is follicular NHL treated

A

Depends if treatment indicated by
- nodal extrinsic compression
- massive painful nodes
- recurrent infections
IF NOT WATCH AND WAIT
If any of above then R-CAVP
R- rituximab
C- cyclophosphamide
A- adriamycin
V- vincristine
P- prednisolone

195
Q

Blood count and film findings of CLL

A

Massive lymphocytosis
Cytopenia
Smear cells on film

196
Q

Flow cytometry of CLL

A

Normal B-cell would be CD5-ve and CD19+ve but CLL is both positive

197
Q

In CLL prognosis which mutation is important to assess

A

TP53 (chr 17deletion)
Ruins prognosis

198
Q

What is the danger of CLL

A

Typically very indolent however can undergo Richter transformation to diffuse large B cell lymphoma if acquires another mutation

199
Q

Treatment of CLL

A

Often watchul waiting unless need
If is need
BCR inhibitor- ibrutinib (BTK inhibitor)
BCL2 inhibitors- venetoclax
Chimeric antigen receptor T cells

200
Q

What is main risk of venetoclax

A

TLS when intiate treatment

201
Q

What is sickle cell disease

A

Encompassing term for diseases associated with pathological effects of sickling

202
Q

What happens in sickle cell beta thalassaemia

A

Inherit 1 beta thalassaemia globin chain
Inherit 1 sickle cell beta globin

203
Q

What are signs of an increased erythopoietic drive

A

Bone expansion
Hepatomegaly
Splenomegaly

204
Q

What are the 2 types of beta thalassaemia

A

Beta thalassaemia trait
Beta thalassaemia homozygosity

205
Q

How is beta thalassaemia major treated

A

Transfusions

206
Q

What can trigger G6PD

A

Infections
Drugs
Fava beans

207
Q

Treatment of von willebrand disease

A

Lower factor purity factor VIII concentrates

208
Q

What are signs of hyposplenism on blood film

A

Howell jewell bodies
Target cells (codocytes- ‘codo’ means hat)

209
Q

Differentials for raised Hb

A

Is it due to reduced plasma? (relative-i.e. pseudo PC as RBC mass is normal)
True
- secondary (raised EPO)
- primary (myeloproliferative neoplasm) (low EPO)

210
Q

How are primary causes of polycythaemia split

A

Ph chr negative
- essential thrombocythaemia
- polycythaemia vera
- primary myelofibrosis

Ph chr positive
- CML

211
Q

What can cause relative/pseudo polycythaemia

A

Alcohol
Obesity (gaisbock?)
Diuretics

212
Q

How is secondary polycythaemia split

A

Depends if EPO being raised is appropriate
Appropriate
- high altitude
- hypoxic lung disease
- cyanotic heart disease

Inappropriate
- renal disease causing increased EPO
- uterine myoma (suggested they produce EPO)
- ectopic EPO from other tumours

213
Q

Presentation of polycythaemia vera

A

Visual issues
Fatigue/dyspnoea
TIA
Headaches
Aquagenic pruritus (histamine release)
Peptic ulceration (histamine release)

214
Q

Tests for polycythaemia vera

A

FBC- raised Hb, can also raise plts and WCC
Low EPO
JAK2 mutation testing

215
Q

Management of polycythaemia vera

A

Venesection with hydroxcarbamide
Need to control VTE risk too with aspirin

216
Q

Essential thrombocythaemia presentation

A

Arterial or venous thrombosis; DVT, PE, CVA, gangrene
GI bleeding
Bleeding from mucous membranes
Headaches and dizziness

217
Q

Management of essential thrombocythaemia

A

Aspirin
Hydroxycarbamide (stops plt production)
Anagrelide to inhibit plt formation

218
Q

What can essential thrombocythaemia progress

A

Leukaemic transformation
Myelofibrosis

219
Q

Presentation of primary myelofibrosis

A

Cytopenias
Thrombocytosis
Splenomegaly causing budd chiari
Hypermetabolic syndrome
- wt loss
- fatigue
- night sweats

220
Q

Blood film of primary myelofibrosis

A

Tear drop dacrocytes
Giant platelets
Circulating megakaryocytes

221
Q

What mutations may be seen in primary myelofibrosis

A

JAK2
Calreticulin (CAL-R)

222
Q

Bone marrow trephine findings of primary myelofibrosis

A

Dry tap
Reticulin or collagen fibrosis
Megakaryocyte hyperplasia
New bone formation

223
Q

Treatment for myelofibrosis

A

RBC and platelets transfusions
Hydroxycarbamide for thrombocytosis
Ruxolotininb
Allogenic SCT in high risk cases

224
Q

Why do transfusions tend not to work in primary myelofibrosis

A

Splenomegaly

225
Q

What is ruxolotinib and what used in

A

JAK2i
Used in primary myelofibrosis

226
Q

What does hydroxycarbamide do

A

Reduce number of platelets

227
Q

Presentation of CML

A

Constitutional sx
Bruising
Infections

228
Q

Examination finding of CML

A

Massive splenomegaly
May have hepatomegaly

229
Q

FBC and blood film findings of CML

A

Hb and plt preserved or raised
Massive leukocytosis
On film lots of neutrophils and basophils
Myelocytes (not blasts)

rare to get high basophils but CML doesn’t discriminate

230
Q

Mutation causing CML

A

Philadelphia chr
9:22
BCR-ABL

231
Q

What are the phases to CML

A

Chronic
Accelerated/acute ( blasts 10-19%)
Blast (over 20% blasts)

232
Q

Management of CML

A

Chronic phase- imatinib (TK inhibitor)
Blast phase- treat like acute leukaemia

233
Q

How can heparin affect platelet count

A

Thrombocytopenia

234
Q

What are encoded by HLA (MHC) class I

A

HLA-A, B, C
Recognised by CD8 cells

235
Q

On what chromosome are HLA genes found

A

6

236
Q

What are encoded by HLA (MHC) class II

A

HLA- DP, DQ, DR
Present to CD4 cells

237
Q

What are the odds of a sibling being HLA identical

A

35%

238
Q

How can you work out the odds of a match with a sibling

A

1- (3/4)^n
n=number of siblings

239
Q

How does an autologous stem cell transplant work

A
  1. given growth factor to promote production of stem cells
  2. collect the stem cells and freeze them3
  3. high dose chemo to kill any cancerous cells without issue of doing so at expense of BM as..
  4. reinfuse stem cells
240
Q

What organs does acute graft versus host affect

A

Skin
Liver
GI tract

241
Q

When do you tend to use autologous stem cell transplants more often

A

Myeloma
Lymphoma
Normally in case of relapse

not so much in leukaemia
i.e. used in diseases where BM isnt source of the problem

242
Q

How is graft versus host disease prevented

A

Methotrexate
Cyclosporin

243
Q

How is acute graft versus host disease treated

A

Corticosteroids
Can also use calcineurin inhibitors- cyclosporin A

244
Q

Which organs does chronic graft versus host disease affect

A

Skin
Mucosal membranes
Lungs
Liver
Eyes
Joints

245
Q

What is main risk factor for chronic graft versus host disease

A

Prior acute Graft versus host disease

246
Q

Post stem cell transplant which organisms are most likely to cause mortality

A

Gram neg- pseudomonas, e coli

247
Q

Consequences of haemolytic anaemia

A

Folic acid demand increased
Erythroid hyperplasia with circulating reticulocytes
Propensity to gallstones (worsened by gilberts)
Very susceptible to effects of Parvovirus B19

248
Q

Co-inheritance of what condition increases risk of gallstones in haemolytic anaemia

A

Gilberts

249
Q

Blood findings of haemolytic anameia

A

High bilirubin
High LDH
Low haptoglobin

250
Q

Inheritance of HS

A

Autosomal dominant
25% of cases no family history

251
Q

How to diagnose HS

A

Osmotic fragility test- increased sensitivty to hypertonic saline
Reduced binding of dye eosin-5-maleimide on flow cytometry (modern method used)

252
Q

Difference between heterozygous and homozygous hereditary elliptocytosis clinically

A

Hetero- no anaemia
Homo- anaemia at birth requiring exchange transfusion

253
Q

Difference between heterozygous and homozygous hereditary elliptocytosis on blood film

A

Hetero- elliptocytes and oval shaped RBCs
Homo- elliptocytes, fragments of RBC and reticulocytosis

254
Q

What is G6PD epidemiology linked to

A

Malaria heavy areas as is protective

255
Q

What are bite cells seen in

A

G6PD

256
Q

What are heinz bodies seen in

A

G6PD (blue deposits of oxidised Hb)

257
Q

What are RBC with short projections seen in

A

PK deficiency

echinocytes i.e. burr cells (look like urchins)

258
Q

Pathophysiology of paroxysmal nocturnal haemoglobinuria

A

Acquired loss of surface GPI markers on RBC leading to chronic intravascular haemolysis at night mediated by complement

PIGA gene mutation

259
Q

Presentation of paroxysmal nocturnal haemoglobinuria

A

Morning haemoglobinuria
Increased risk of thrombosis in particular budd chiari

260
Q

Differentiating between Fe deficiency and anaemia of chronic disease

A

Low ferritin would show Fe deficinency however raised in ACD
Therefore look a transferrin which high in IDA as well as TIBC which is raised in IDA

I think TIBC is low in ACD

ACD usually normochromic normocytic

Remember in IDA due to eg IBD- ferritin won’t be low as acute phase protein

261
Q

What causes anaemia of chronic disease

A

In inflammatory states hepcidin increases which sequesters GI absorption of iron and prevents release of iron from macrophages

Hepcidin regulates iron metabolism by binding to ferroportin, a protein responsible for exporting iron from cells into circulation. When hepcidin binds to ferroportin, it triggers its degradation, leading to decreased iron absorption from the intestines and reduced release of iron from macrophages

262
Q

Causes of pancytopenia

A

Non malignant
- B12/folate deficiency
- aplastic anaemia from drugs etc or idiopathic

Malignant- ONLY TIME SEE LEUKOERYTHROBLASTIC PICTURE
- bony metastases
- myeloma/lymphoma/ acute leukaemia infiltration
- myelodysplasia

263
Q

How is CLL diagnosed

A

Immunophenotyping showing B cells CD5+

Even though CD5 is a T cell marker!

264
Q

What do myeloma plasma cells produce

A

IgA or IgG
Can get myelomas which only produce light chains (hence % plasma cells isnt needed for dx)

265
Q

What is prognostic marker of myelomas in the blood

A

Beta-2-microglobulin

266
Q

What are the phases to coagulation

A

Initiation- formation of complex of FXa and FVa
Amplification- the amplificatory effects of thrombin
Propagation- thrombin burst creates stable fibrin clot

267
Q

What happens in the intrinsic pathway

A

Starts with 12
11
9
8
10a and here joins with factor 5m

Remember in common pathway, after fibrin there’s factors 13- Cross-link fibrin clot

268
Q

What happens in the extrinsic pathway

A

Tissue factor exposed from endothelial injury leads to activation of factor 7
The complex between TF and FVIIa activates FIX and FX

269
Q

What happens in the initiation phase

A

Tissue factor exposed from endothelial injury leads to activation of factor 7
The complex between TF and FVIIa activates FIX and FX

270
Q

What to APTT, PT and TT all represent

A

APTT- intrinsic pathway
PT- extrinsic pathway
TT- common pathway

Thrombin time (TT) measures fibrin formation caused by the action of thrombin—the last step in the coagulation cascade.

271
Q

What happens in amplification phase of coagulation

A

The FXa /FVa complex converts small amounts of prothrombin to thrombin
This then activates FVIII, FV, FXI and platelets which themselves bind these factors

272
Q

What happens in propagation phase of coagulation

A

FVIIIa/FIXa complex activates FX on surface of activated platelets which converts large amounts of prothrombin to thrombin
This creates a stable fibrin clot

273
Q

What is difference between coagulation and platelet bleeding

A

Platelet- skin, mucosal petechiae and purpura
Coagulation- haematoma and joint bleeding

Post surgery/wound the bleeding is immediate in platelet
Post surgery/wound the bleeding is delayed but severe if coagulation problem

274
Q

MOA of clopidogrel

A

Inhibitor of ADP receptor which prevents platelet aggregation

275
Q

MOA of aspirin

A

Inhibits cyclo-oxygenase enzyme which reduces thromoxane A2 production from arachidonic acid

promotes aggregation

276
Q

How are disorders of platelets classified

A

Decreased number
- decreased production (BM failure)
- decreased survival (ITP, MAHA)
- increased use (DIC)

Reduced function
- acquired (aspirin, uraemia)
- inherited (thrombasthenia)

277
Q

What are ecchymoses typical of

A

Coagulation factor disorders

278
Q

How are coagulation factor disorders classified

A

Inhertied
- haemophilia
- vWB disease

Acquired
- DIC
- liver disease
- Vit k deficiency or OD

279
Q

Inheritance of vWB

A

Type 1 and 2- Autosomal dominant
Type 3- autosomal recessive

280
Q

Causes of Vit k deficiency

A

Malnutrition and malabsorption (green vedgetables)
Biliary obstruction
Abx

281
Q

Treatment of vit k deficiency

A

Vitamin K
FFP

282
Q

What is vit K needed for

A

Factors II, VII, IX and X
And protein S and C which is why warfarin is procoagulant initially

283
Q

Blood findings of liver disease association coagulation disorders

A

High levels of VIII and VWF
Low II, V, VII, IX, X and XI

VIII is only CF NOT made in liver! made in endothelial cells etc.

284
Q

What can cause DIC

A

Malignancy
Sepsis
Trauma
Obstetric complications
Toxins

285
Q

Blood findings of DIC

A

Low platelets
Low fibrinogen
Long PT, APTT, TT and INR
High D dimer
See schistocytes on blood film

286
Q

Treatment of DIC

A

Platelet transfusion
FFP
Cryoprecipitate

287
Q

Pathogenesis of DIC

A

Systemic activation of coagulation leads to depletion of plts and coagulation factors causing bleeding
Intravascular deposition of fibrin causing thrombosis leading to organ failure

288
Q

Differentiating VwB disease from haemophilia A

A

Both have low factor 8 (as VwB bound )
Both have a high APTT but VwB can be normal
VwB will have however a low ristocetin cofactor activity and ristocetin activity

289
Q

What happens in factor V leiden

A

Is mutation in FV which means protein C can’t degrade it leading to increased VTE risk
Resistance to factor V

290
Q

tHow is factor V leiden diagnosed

A

Protein C functionality

291
Q

What is thromboangiitis obliterans

A

Vasculitis of small/medium vessels in the limbs which leads to arterial and venous thrombosis

292
Q

Investigation for thromboangiitis obliterans

A

Angiogram showing corkscrew appearance

293
Q

What happens in protein S deficiency

A

Reduced breakdown of activated factor 5 and 8 as this is its role

294
Q

BM finding of essential thrombocythaemia

A

Megakaryocyte hyperplasia with giant platelets

295
Q

What happens to RBC in pregnancy

A

Get bigger
Mild anaemia from dilution

296
Q

What happens to platelets and neutrophils in pregnancy

A

Neutrophilia
Gestational thrombocytopenia but they increase in size

297
Q

If get low MCV anaemia in pregnancy what do if known haemoglobinopathy

A

Check serum ferritin
If less than 30 treat with oral iron

298
Q

Differentials for thrombocytopenia in pregnancy

A

Gestational
Pre-eclampsia
ITP
MAHA (HELLP, TTP etc)

299
Q

What changes induce hypercoagulable state in pregnancy

A

Increase in factor VIII & VII, VwB
Reduction in protein S

rememebr reduced factor XI too but this is hypocoagulable

300
Q

Biggest risk factor for VTE mortality in pregnacy

A

BMI over 25

301
Q

What does warfarin in pregnancy cause

A

Chondrodysplasia punctata in first trimester

302
Q

Causes of DIC in pregnancy

A

Sepsis
Placental abruption
Amniotic fluid embolism
Pre-eclampsia
Retained dead fetus

303
Q

How to differentiate IDA from thalassaemia trait on FBC

A

RBC increased in thalassaemia trait

just Hb that’s down as not being made

304
Q

Difference in antibody between anti AB and RhD

A

Anti- A or B is IgM
Anti-RhD- IgG

305
Q

What antibodies cause delayed transfusion reaction

A

Anti-D IgG

306
Q

Which cells should you give to RhD positive patients

A

RhD positive as using negative is a waste

307
Q

Can you give RhD positive blood to a rhesus D negative person

A

Yes if in short supply but avoid in woman of child bearing age

308
Q

What reaction happens against non-RhD, A and B antigens

A

Delayed transfusion reaction as IgG

309
Q

How long are transfusion records kept for

A

30 years

310
Q

What red cells give in emergency

A

O-

311
Q

Management of a red cell transfusion

A

Stored at 4^C for 35 days
Must be transfused within 4 hours
Transfuse 1 unit over 2-3 hours

312
Q

Management of platelet transfusions

A

Stored at 20^C for 7 days
Transfuse over 30 mins

313
Q

What antigen must be compatible with platelet transfusion

A

D

314
Q

What is maximum surgical blood ordering schedule

A

Planned agreement between surgeons and haem lab

315
Q

When are plt transfusions contraindicated

A

Heparin induced thrombocytopenia thrombosis
HITTP

316
Q

Indications for cryoprecipitate

A

When bleeding due to hypofibrinogenaemia
- liver disease
- DIC

317
Q

What is intra-operative cell salvage

A

Collect lost blood
- centrifuge
- filter and wash
Reinfuse
Used in majority of surgeries including obstetric

318
Q

When is cell salvage contraindicated

A

Cancer
Bowel surgery

319
Q

When is only time have CMV negative blood

A

Intra-uterine or neonatal transfusions
Pregnant women

320
Q

When give washed blood cells

A

Severe allergic reactions to blood

321
Q

When is post operative cell salvage used

A

Knee surgery

322
Q

Most common blood group

A

O

323
Q

Which transfusion is infection most likely associated with

A

Platelet
If get fever during or soon after
take blood cultures and give broad spectrum abx

324
Q

Acute reactions to transfusions

A

ABO haemolytic
Allergic
Infection
Febrile non-haemolytic
Resp
- TACO- transfusion associated cardiovascular overload
- TRALI- transfusion related acute lung injury

325
Q

How are transfusions monitored

A

Baseline temp before
Repeat 15 mins later
After an hour
End of transfusion

326
Q

How do febrile non-haemolytic transfusion reaction

A

Temp rise
Chills Rigor

327
Q

How manage febrile non-haemolytic transfusion reaction

A

Paracetamol
Slow down maybe

328
Q

What causes febrile non-haemolytic transfusion reaction

A

Donor WCC cytokine release

329
Q

Presentation of allergic transfusion reactions

A

Mild urticarial reaction with a wheeze

330
Q

Management of allergic transfusion reaction

A

IV antihistamines and slowing/stop tranfusion

331
Q

Prsentation of ABO incompatibility post transfusion

A

Shocked fever
Chest, loin pain, collapse, flushing, haemoglobinuria

332
Q

Management of ABO incompatibility

A

Stop transfusion
Take FBC, coagulation
Repeat x-match and DAT
Discuss with haem

333
Q

Presentation of bacterial contamination

A

Restless
Fever
Shock
Collapse

334
Q

What causes bacterial contamination

A

Bacterial growth may mean release of endotoxin
From donor
- GI, dental, skin infection
During processing (skin)

335
Q

Presentation of anaphylaxis in response to transfusion

A

Facial, laryngeal oedema
Wheeze
Shocked

336
Q

Presentation of TACO

A

SOB
Reduced sats
HR and BP up
Raised JVP
CXR- fluid overload

337
Q

Who does TACO occur in

A

Cardiac failure
Renal impairment
Hypo-albuminaemia
On fluid replacement

338
Q

What is risk factor for anaphylaxis in response to transfusion

A

IgA deficiency

339
Q

How does TRALI present

A

SOB
Low sats
HR and BP up
Dry cough
Fever

340
Q

MOA of TRALI

A

Aggregates of WBC in pulmonary capillaries

341
Q

What is alloimunisation in transfusions

A

Develop an immune antibody to a RBC antigen they lack

342
Q

Problem of alloimunisation in transfusions

A

In future transfusions with thay antigen will get extravascular haemolysis from IgG

343
Q

Tests for delayed haemolytic transfusion reaction

A

Raised LDH, reticulocytes, Hb, DAT, haemoglobinuria
U&Es as get renal failure

344
Q

What is transfusion assocaited graft versus host disease

A

Where lymphocytes from donor aren’t destroyed by immune system in extremely immunosuppressed patients

345
Q

How is transfusion assocaited graft versus host disease prevented

A

Irradiate the blood if immunosuppressed

346
Q

Presentation of transfusion assocaited graft versus host disease

A

Diarrhoea
Liver failure
Skin desquamation
BM failure

347
Q

Presentation of post transfusion purpura

A

Purpura a week after tranfusion which will resolve however can get life threatening bleeding

348
Q

Management of post transfusion purpura

A

IVIG

349
Q

Where is labelling of tube made

A

At the bedside

350
Q

What do if woman at screening found to have alloantibodies for RBC antigens

A

Check ffDNA for antigen status of baby
Monitor mothers antibodies level
Screen for anaemia with MCA doppler
Deliver early as it gets a lot worse later in pregnancy

351
Q

How can baby be treated for HDN

A

As a feotus with known anti-D antibodes in mother can give intrauterine transfusions
At birth phototherapy or exchange transfusion

352
Q

What dose of anti-D is given at certain parts of pregnancy

A

After sensitising event
Before 20 weeks- 250
After 20 weeks- at least 500 but do kleihauer test to confirm

353
Q

What other antibodies can cause HDN

A

ABO
Anti-D
Anti-Kell
Anti-c

354
Q

Feature anti-kell HDN

A

Reticulocytosis

355
Q

How does Group assessment in G&S work

A

Column agglutination technology
Get forward group whereby anti-A, anti-B and anti-D reagents mixed with patients RBCs
Get reverse group where known A and B RBCs added to patients plasma containing IgM antibodies
If is positive then get agglutination

356
Q

How are antibodes to non-ABO antigens formed

A

Do not naturally occur
Will develop after exposure like in previous transfusion or pregnancy

357
Q

What is G&S

A

Group and screen
Blood group identified
Screen- screen for non-ABO antibodies like Kell

358
Q

How does screen part of G&S work

A

Indirect antiglobulin technique
Patients plasma mixed with 2 or 3 reagent cells which between them contain all of non AB antigens on them
If agglutination shows presence of antibodies

359
Q

How does crossmatch work

A

Mix patients and donor RBCs together at 37^C for 30 mins and will pick up antibody-antigen reaction resulting in potential future extravascular haemolysis

i.e. mix bloods, you dont acc see anything but reaction is detected

360
Q

What are 2 options for cross matching

A

Indirect antiglobulin technique
- this does full crossmatch including non ABO screen and ABO screen
Immediate spin
- antiglobulin reagent added to crosslink IgG antibodies

Immediate spin
- done at room temperatute for 5 mins
- only detects ABO incompatibility

361
Q

When would you do an immediate spin for serological crossmatch

A

Emergency

362
Q

What is added in indirect antiglobulin technique

A

Antiglobulin reagent to crosslink IgG that would not normally mix

363
Q

What is FFP

A

Plasma is separated from cells and thawed

364
Q

What is indication for FFP

A

Bleeding due to coagulopathy like DIC, TTP and replacement of a single clotting factor

365
Q

What is cryoprecipitate

A

Concentrated FFP which gives a lot of fibrinogen

366
Q

Red blood cell transfusion indication

A

Less than 70
Less than 80 if symptomatic (SOB, IHD, ECG changes)

367
Q

What level of platelets aim for to prevent bleeding in surgery

A

Over 50
Over 100 if critical location like eye or CNS

transfusion threshold for plts after trauma = 75 (i.e. half of lower limit of normal)

368
Q

What compatibility is important in FFP and cryo

A

ABO

369
Q

Inheritance of hereditary elliptoctosis and spherocytosis

A

Autosomal dominant

370
Q

What must do before giving folate supplements

A

Check B12 as can exacerbate neuropathy

371
Q

Pathophysiology of sideroblastic anaemia

A

Body has produced too much iron it cant put into RBC so iron deposited around mitochondria

372
Q

Causes of sideroblastic anaemia

A

MDS
Alcohol
Chemo and irradiation

373
Q

MOA of venetoclax and ibrutinib

A

Ibrutinib- tyrosine kinase inhibitor
Venetoclax-BCL inhibitor which promotes apoptosis

374
Q

How to remember the translocations and respective associated proteins in B cell lymphomas

A

In terms of aggressiveness the first number decreases and the proteins are in alphabetical order
Follicular- 14:18 + BCL-2
Mantle- 11:14 + Cyclin d
Burkitts- 8:14 + C-myc

375
Q

Bleeding time in VWB versus haemophilia A

A

VWB prolonged but not in haemophilial

376
Q

How do neutrophils appear on blood film

A

3x larger than RBC, multisegmented with speckly stained nucleus

377
Q

How do monocytes appear on blood film

A

3x size of RBC
Kidney shaped nucleus

378
Q

How do basophils appear on blood film

A

3x larger than RBC
Deep blue granules- bilobed nucleus

379
Q

How do eosinophils appear on blood film

A

3x size of RBC
Reddish purple granules- bilobed nucleus

380
Q

How do lymphocytes appear on blood film

A

About same size as RBC
Giant nucleus takes up most of cell with no granules

381
Q

What is scoring system for myelodysplasia

A

International prognosis scoring system (IPSS)

382
Q

What is benefit of modern ABVD treatment for hodgkin lymphoma

A

Infertility prevented

383
Q

Which congenital coagulopathy has highest thrombosis risk

A

Antithrombin deficiency

commonest is factor v leiden

384
Q

What cells stain in sudan black

A

Myeloblasts

385
Q

Differnece in mutations between alpha and beta thalassaemia

A

Alpha- deletions on chromosome 16
Beta- point mutations on chromosome 11

386
Q

When do bite cells vs heinz bodes appear in G6PD

A

Heinz are early
Bite are later

387
Q

What is indication for platelet transfusion

A

Platelets under 30 and with active bleeding

388
Q

What medications can be given for TLS

A

Allopurinol
Rasburicase

389
Q

What are types of VWB

A

Type 1- slight reduction- AD
Type 2- defective- AD
Type 3- complete absence- x linked? AR

390
Q

How are febrile non haemolytic reactions prevented

A

Leukodepletion- done in long term transfusion patients

391
Q

What is MCV in sideroblastic anaemia

A

Low

392
Q

What is difference in staining between classical HL and lymphocyte predominant

A

Classical- CD15 and 30 positive
Lymphocyte predominant- CD20

393
Q

Histology of small lymphocytic

A

Small B cells
CD5 and CD23

like how in CLL there are t and b cell markers on the B cells

394
Q

HL has worst and best prognosis

A

Best- nodular sclerosing
Worst- lymphocyte depleted

395
Q

What is bad prognostic marker for CLL

A

TP53

396
Q

What can small cell lymphoma progress to

A

DLBC- just like CLL

397
Q

Management of diffuse large cell

A

R CAVP
Rituximab
Cyclophosphamide
Adriamycin
Vincristine
Prednisolone

Arjun's Copy- Owen's Path (8 decks)

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