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MSRA > Haematology > Flashcards

Haematology Flashcards

1
Q

What does a high reticulocyte count mean?

A

This is the concentration of immature RBCs.

High - increased brood loss and haemolytic anaemia as bone marrow is working harder to replace lost cells

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2
Q

What causes a microcytic anaemia?

A

Iron deficiency
Thalassemia
Sideroblastic anaemia (production of ringed abnormal RBCs)

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3
Q

What causes a normocytic anaemia?

A

Acute blood loss
Anaemia of chronic disease
Haemolytic anaemia
Multiple myeloma

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4
Q

What causes a macrocytic anaemia ?

A

B12/folate deficiency
Alcohol
Reticulocytosis
Liver disease
Pregnancy

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5
Q

What are the signs of iron deficiency ?

A

Koilonychia
Angular stomatitis
Glossitis

Blood tests show elliptocytes and abnormal nuclei

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6
Q

What is thalassaemia?

A

Beta thalassemia trait (minor):
- Mild hypochromic, microcytic anaemia (microcytosis dispropriate to anaemia)
- Raised hbA2
- Usually asymptomatic

Beta thalassemia major:
- Severe symptoms
- Usually require regular blood trasnsfusions with chelation therapy alongisde to remove excess iron (DFO, DFP, DFX)

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7
Q

What causes B12 anaemia?

A

Perniocuious anaemia
Malabsorption
Dietary (veggie/vegan)

B12 is absorbed in the terminal ileum via intrinsic factor

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8
Q

What causes folate anaemia?

A

Dietary (not enough green veg)
Malabsorption
Drugs (trimethoprim, phenytoin, methotrexate)

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9
Q

What causes haemolytic anaemia?

A

Any anaemia due to premature destruction of RBC (this can be intravascular or extravascular)

EXTRAVASCULAR:
Heritable:
- Haemoglobinopathies: sickle cell, thalassemia
- Membrane defects: hereditary spherocytosis/elliptocytosis
- Enzyme defects: G6PD deficiency, pyruvate kinase deficiency
Acquired:
- Autoimmune (DAT+) - drug induced
- Hypersplenism
- Infection (malaria)

INTRVASCULAR:
(brown urine!!):
Mechanical valves
Infusion of hypotonic solution
Acute transfusion reaction

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10
Q

What is Coombs test?

A

DAT direct antiglobulin test which looks for autoimmune haemolytic anaemia

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11
Q

What causes erythropoiesis?

A

The kidney produces erythropoietin due to:
- RBC haemolysis
- Lack of oxygen
- Androgens
- Thyroid hormone

This then leads to reticulocyte formation and after 3 days these will leave the bone marrow and become RBC

For this reason, chronic hypoxia or increased ego will cause secondary polycythemia

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12
Q

What blood test results do you get in haemolytic anaemia and why?

A

High reticulocyte count
High LDH
High globin (due to haemoglobin being broken down )
High haem > more iron and more unconjugated bilirubin
Howell-Jollybodies

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13
Q

What is G6P deficiency?

A

G6P is an enzyme which contributes to reducing free radical formation during energy production, this keeps the cell healthy

Deficiency causes build up of free radicals causing damage to the RBCs - this means they will be cleared by the reticuloendothelial system

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14
Q

What causes a high/low neutrophil count?

A

High:
Bacterial infection
Steroids
Inflammation
Malignancy

Low:
Chemotherapy
Agranulocytosis by the 4Cs - carbamazepine, clozapine, colchicine, carbimazole

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15
Q

What causes a high/low lymphocyte count?

A

High:
Viral infection
CLL
Chronic infection

Low:
Viral infection
HIV
Chemotherapy
Bone marrow failure

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16
Q

What causes a high/low monocyte count?

A

High:
Bacterial infection
Autoimmune disease
Leukemia

Low:
Acute infection
Steroids
Leukemia

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17
Q

What causes a high/low eosinophil count?

A

High:
Allergy
Parasites
Drug reactions

Low:
Nil

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18
Q

What causes a high/low basophil count?

A

High:
Leukemia
Hypersensitivity
Myeloproliferative disorder

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19
Q

What causes thrombocytopenia?

A

Decreased production of platelets - bone marrow failure, megaloblastic anaemia

Increased destruction - DIC, TTP, ITP, SLE, CLL, viruses, drugs

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20
Q

What causes thrombocythemia ?

A

Primary - myeloproliferative disorders

Secondary - bleeding, inflammation, infection, malignancy

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21
Q

What is a myeloproliferative disorder?

A

A group of neoplastic disorders involving the bone marrow cells that produce RBCs, platelets or fibroblasts (everything except WBCs)

  1. Polycythaemia vera
  2. Essential thrombocythaemia
  3. Chronic myeloid leukemia
  4. Primary myelofibrosis
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22
Q

What do myeloid cells and lymphoid cells produce?

A

Myeloid - All blood cells except for lymphocytes

Lymphoid - lymphocytes

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23
Q

What are granulocytes and how is production stimulated?

A

Granulocytes encompasses neutrophils, basophils and eosinophils

Production stimulate by GM-CSF

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24
Q

What are the features of a myeloproliferative disorder ?

A
  • Diseases of the elderly
  • All cell lines affected but one cell line affected more than most
  • Hypercellular bone marrow
  • Splenomegaly (if bone marrow not able to produce sufficiently)
  • Rapid cell turnover causing HIGH URIC ACID and GOUT
  • Can transform into acute myeloid leukaemia
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25
Q

Which genetic mutations tend to cause myeloproliferative disorders?

A

CML - BCR-ABL translocation (9;22) on philadelphia chromosome

Polycythaemia vera, primary myelofibrosis, essential thrombocythemia - V617F mutation causing activation of JAK2

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26
Q

What does JAK2 kinase do?

A

Stimulates erythropoietin and thrombopoeitin RECEPTORS but not the GM-CSF

(epo and tepo will actually decrease in these conditions due to negative feedback mechanism)

This causes huge increase in RBC and platelets but not WBCs

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27
Q

How does PV usually present?

A

Raised Hb
Plethoric appearance
Pruritis (itchy!!) after a hot shower
Splenomegaly
Hypertension
Hyperviscosity in the form of thrombus
Low ESR

Blood is THICK! Think what this would cause

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28
Q

How is PV investigated?

A

FBC/film - all cell lines high
JAK2 (present in 95%)
Serum ferritin
Renal, LFTs

If JAK negative:
- Red cell mass
- Arterial oxygen sats
- Abdo USS
- Serum EPO (low)
- Bone marrow aspirate and trephine
- Cytogenetic analysis
- BFU-E culture

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29
Q

What are the criteria for JAK2 postive PV?

A

Must have:
1. High hct or raised red cell mass
2. Mutation in JAK2

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30
Q

What are the criteria for JAK2 negative PV?

A

Must have:
1. High hct or raised red cell mass
2. Absence of JAK2 mutation
3. No cause of secondary erythrocytosis

Plus either one of:
- Palpable spleen
- Presence of acquired genetic abnormality

Or 2 of:
- High platelts
- High neutrophils
- Radiological evidence of splenomegaly
- Low serum epo

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31
Q

How is polycythemia vera treated?

A

Frequent blood withdrawals
Daily low dose aspirin
Hydroxycarbamide (slight increased risk of secondary leukaemia)
Cytoreductive surgery

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32
Q

How does essential thrombocythemia usually present?

A

Can be asymptomatic
Headache
Dizziness
Bruising
Thrombosis

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33
Q

How is ET investigated?

A

FBC/film - high platelets
JAK2/CALR/MPL mutation

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34
Q

How is ET treated?

A
  1. Aspirin to reduce clot risk
  2. Cytoreductive surgery
  3. Hydroxycarbamide
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35
Q

How does CML usually present?

A

Neoplastic disease of mature myeloid cells (basophils, eosinophils, neutrophils)

Incidental finding
Fever and night sweats
Splenomegaly
Weight loss
Bleeding and petechia
Gout (uric acid production from cell breakdown)
Hyperviscosity syndrome

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36
Q

What are the 3 clinical phases of CML?

A
  1. Chronic
  2. Accelerated
  3. Blast crisis (symptoms of AML)
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37
Q

How is CML investigated?

A

FBC/film - increased myeloid cells
Cytogenetics - translocation (9:22) involving the ABL:BCR genes on the philadelphia chromosome

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38
Q

How is CML treated?

A
  • Tyrosine kinase inhibitors (imatinib); taken as a tablet daily
  • PCR monitoring of BCR:ABL
  • Hydroxyurea and interferon alpha 2nd line
  • Stem cell transplant
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39
Q

What are the side effects of imatinib?

A

Pleural effusion, rash, cramps, vomiting, oedema

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40
Q

What is primary myelofibrosis and how does it present?

A

Build up of scar tissue in the bone marrow impairing its ability to make normal cells. As a result, cell production moves to the SPLEEN
It can arise as a progression of PV/ET

Fatigue, weakness
Fullness in left upper abdomen (splenomegaly)

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41
Q

How is MF investigated?

A

FBC/film - pancytopenia or pancythemia, tear drop pokilocytes/dacrocytes and nucleated RBCs

Bone marrow biopsy - collagen fibrosis, JAK2/MLP/CALR mutations

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42
Q

How is myelofibrosis managed?

A

Generally incurable except for allogenic stem cell transplant

Symptomatic treatment includes transfusion, allopurinol, splenectomy, folic acid, JAK2 inhibitors (-nibs)

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43
Q

A blood test shows normal Hb with microcytosis - what causes this?

A

Polycythaemia vera
(May cause iron deficiency secondary to bleeding)

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44
Q

What are the lymphoproliferative disorders?

A

B lymphocytes overproduction > plasma cell dyscrasia > multiple myeloma/waldenstroms

T lymphocytes overproduction > ALL/CLL/hairy cell

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45
Q

What is multiple myeloma and how does it present?

A

Neoplastic disease of PLASMA cells

CRAB presentation:
Calcium increased
Renal impairment
Anaemia
Bony lesions

BACK PAIN!!!! due to paraprotein clogging
African ethincity common

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46
Q

What is the pathophysiology of multiple myeloma?

A

Plasma cells proliferate and produce paraprotein which is a faulty monoclonal antibody

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47
Q

How is MM diagnosed?

A

Serum paraprotein (immunoglobulin electrophoresis)
Serum free light chain blood test
Blood film rouleax - increased plasma viscosity due to immunoglobulin overproduction

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48
Q

How is MM treated?

A
  • Chemotherapy
  • Bisphosphonates
  • Stem cell transplant
  • Stop nephrotoxic drugs
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49
Q

What is Waldenstroms macroglobulinaemia?

A

A rare type of blood cancer which affects B-lymphocytes (which produce IgM).

B-lymphocytes abnormally divide and accumulate, causing damage to blood vessels

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50
Q

What are the symptoms of Waldenstrom’s macroglobulinaemia ?

A

Epistaxis and other bleeding
Impaired/blurred vision (These are due to the effect of blood flow changes on small blood vessels)

Anaemia
Parasthesia
Enlarged LN, spleen and liver (due to abnormal cell accumulation)

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51
Q

How is Waldenstrom’s macroglobulinaemia investigated?

A

FBC/film - anaemia, low platelets
Electrophoresis - M-spike due to IgM levels
Cytogenetics - MYD88 and CXCR4 gene mutation

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52
Q

How is Waldenstroms treated?

A

If asymptomatic - watchful waiting
If symptomatic - plasmapheresis, RBC/platelet transfusion, chemotherapy (eg. rituximab)

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53
Q

What is acute leukemias?

A

Neoplastic disorder of immature myeloblasts or lymphoblasts (early haematopeitic stem cells) in the bone marrow

  • Immature cells proliferate and replace most of the bone marrow cells, crowding out normal haematopoeisis
  • Increased blasts in the peripheral blood then cause leukostasis
  • These blasts metastasize throughout the body
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54
Q

What investigations should be done in a patient with suspected acute leukemia and what would they show?

A

Bloods - anaemia (normocytic or microcytic), pancytopenia, high number of blasts *can also get WBC >100,000
Tissue biopsy - huge nuclei
Bone marrow biopsy - blast cells (>20%)
Cytochemical analysis - PAS, peroxidase, esterase, sudan black
Cytogenetics -

Remember - early cells (blasts) are larger and immature, they lose their ability to differentiate but are able to replicate = CANCER !

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55
Q

What are the risk factors for the acute leukemias?

A
  • Genetic predisposition eg. Downs syndorme
  • Haematological disease (hodgkin’s lymphoma and MM)
  • Ionizing radiation (UV, x-ray, gamma ray)
  • Chemotherapy
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56
Q

What are the symptoms of acute leukemias and why?

A

CLINICAL FEATURES ARE ABRUPT

Bone pain - blast accumulation in bone marrow
Fatigue - pancytopenia
Infections - pancytopenia
Bleeding - pancytopenia
Painless lymphadenopathy
Testicular enlargement - blast cells travel to testes
Hepatosplenomegaly - as bone marrow not producing normal cells

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57
Q

How are the acute leukemias treated (2 phases)?

A
  1. Remission induction phase:
    - High dose chemotherapy to suppress all cell lines (its prone to infection)
    - Give myeloid growth factors (decrease morbidity but not mortality)
    - Give RBC and platelets
  2. Consolidation phase:
    - Purpose is to prolong remission and increase survival
    - Start once WCC normalised
    - Chemo, radiation or bone marrow transplant
    - Use gene expression profiling to guide therapy

If chemotherapy not suitable, can give cytarabine and azacitidine

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58
Q

What are the specific features of ALL?

A
  • More common in children (newborn - 14)
  • Parotid and testicular involvement
  • Extramedullary involvement (outside bone marrow)

Do lumbar puncture to assess for CNS involvement

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59
Q

What are the specific features of AML?

A
  • More common in adults (40-60)
  • Assoc with Downs syndrome, NF1, males
  • Risk of DIC
  • Previous MDS/CML
  • Auer rode and peroxidase +ve
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60
Q

What is CLL and what are the features?

A

A lymphoproliferative disorder causing accumulation of mature, functionally incompetent lymphocytes

  • Often asymptomatic and diagnosed incidentally
  • Typically elderly, caucasian males
  • Hepatomegaly and lymphadenopathy
  • Prognosis via ‘The Rai System’ (I-VI)
  • Often no treatment required
  • Can progress to DLBCL
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61
Q

What do investigations show in CLL?

A

FBC - anaemia and thrombocytopenia (if severe)
Blood film - many small, mature lymphocytes with SMUDGE cells

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62
Q

10% of patients with CLL will progress to diffuse large B cell lymphoma. What are the features of this?

A

Fever, increased lymphadenopathy and high LDH = think DLBCL

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63
Q

What is the prognosis of the chronic leukemias?

A

CML - chronic, accelerated and blast phase (in which it can transform to AML)
CLL - often never progress, better prognosis

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64
Q

What is a lymphoma?

A

A neoplastic disorder of mature lymphocytes in lymphoid tissue, in which abnormal lymphocytes collect in lymph nodes, particularly in the armpits, groing and neck.

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65
Q

What is the difference between leukemias and lymphomas?

A

Both originate in lymphocytes. However leukaemia typically originates in bone marrow and spreads through the bloodstream, whereas lymphoma usually orignitias in lymph nodes or spleen and spreads through the lymphatic system

66
Q

What are the symptoms of lymphoma?

A
  • Painless rubbery LN’s
  • B symptoms; weight loss, night sweats, pruritus, fever
67
Q

When should you refer enlarged LNs?

A

6 week history of a node >1.5cm
OR
6 week history of generalised lymphadenopathy

68
Q

What blood tests should be done in lymphoma and what would they show?

A

Bloods - FBC, U&E, LFT, ESR (usually normal!!, low Hb and high ESR indicate worse prognosis)
Monospot - EBV is a reactive cause of lymphadenopathy
Viral screen - HIV is associated with lymphoma
Blood film
LDH

69
Q

What is the diagnostic test for lymphoma?

A

Excision node/core biopsy

Can also do FISH genetic sequencing and PET scan -shows increased glycolytic tissue

70
Q

What is the difference between low grade and high grade lymphoma?

A

Low grade - slow growing but incurable, treat if symptomatic
High grade - fast growing but cured with chemotherapy

71
Q

How is lymphoma sub-categorised?

A
  1. Hodgkins lymphoma
    - Classical
    - Nodular lymphocyte predominant
  2. Non- Hodgkins lymphoma
    - DLBCL
    - Burkitt
    - Follicular
72
Q

What are Hodgkins lymphomas?

A

Classical
- Characterised by the presence of Reed Sternburg cells (‘owl eyes’)
- Two age spikes (15-34, >60)

NLPHL:
- Characterised by a variant of Reed Sternberg cells which are lymphocyte-predominant (‘popcorn cells’)
- Best prognosis

These are curable with months-years survival if left untreated
Poorer prognosis if B symptoms (night sweats, fever >38, weight loss>10% in 6 months)

73
Q

What are Non-Hodgkins Lymphomas?

A

Over 60 types but split into:
Indolent - incurable, survival years (eg. follicular)
Aggressive - chemo, survival months (eg. DLBCL)
Very aggressive - chemo, survival weeks (eg. Burkitts)

74
Q

How is follicular lymphoma managed?

A

Usually stage IV at presentation, treat if symptomatic with:
- Chlorambucil and steroids
- Rituximab
- Bone marrow transplant

75
Q

How is DLBCL managed?

A

R-CHOP:

Rituximab
Cyclophosphomide
Hydroxydaunorubicin
Vincristine (oncovin)
Prednisolone

76
Q

How is Burkitts managed?

A

Most aggressive !
R-CHOP + chemotherapy

77
Q

How is lymphoma staged?

A

Ann Arbour system
1 - 1 lymph node
2 - >2 lymph nodes on same side of diaphragm
3 - >2 lymph nodes on different sides
4 - Disseminatd

A - no B symptoms
B - weight loss, fever, night sweats

78
Q

What are the 3 main complications of lymphoma and how are they managed?

A
  1. Tumour lysis syndrome
    - Hx of person with lymphoma being started on chemotherapy with high K, high phos and low ca
    - Suspect in anyone with AKI + high phos + high rate
    - Give allopurinol/rasburicase (even as prophylaxis in high risk patients) and hydrate
  2. Spinal cord compression
    - MRI, steroids, surgery
  3. Hypercalcemia
    - Give IV bisphosphonates
79
Q
A
80
Q

What are the categories of causes of bone marrow failure?

A

Peripheral blood cytopenias due to decreased production in the bone marrow

  1. Aplastic anaemia
  2. Megaloblastic anaemia
  3. Infiltration of the bone marrow with malignancy
  4. Myelodysplasia
81
Q

What is asplastic anaemia?

A

A rare stem cell disorder involving pancytopenia and hypo plastic bone marrow

Causes include:
1. Drugs - benzene, chemo, gold, suphonamide, chloramphenicol
2. Congenital
3. Idiopathic

82
Q

How is aplastic anaemia managed?

A
  1. Treat underlying cause
  2. Supportive care - infusions, infection check
  3. Stem cell transplant from HLA matched sibling
83
Q

What is megaloblastic anaemia?

A

Production of large, abnormal immature RBCs by the bone marrow, usually due to B12 or folate deficiency

84
Q

How is megaloblastic anaemia treated? What should you not do?

A

Treat with B12/folate replacement

DON’t given Hb transfusion and the patient will have adapted to the anaemia overtime and overload will lead to heart failure

85
Q

What are myelodysplastic syndromes?

A

A category of cancer in which the bone marrow doesn’t make enough normal blood cells. As the condition develops, the bone marrow becomes full and these abnormal cells spill out into the blood stream > start causing symptoms

86
Q

How are myelodysplastic syndromes investigated?

A

FBC
FIlm
Cytogenetics - 5q deletion, SF3B1 mutation, TP53 mutation
Bone marrow biopsy - blasts <20%

87
Q

How are myelodysplastic syndromes managed?

A

Treatment dependent on risk group and whether they have a 5q deletion

Supportive - blood transfusions, epo agents
Chemotherapy
Allogeneic stem cell transplant

May progress to AML however most deaths occur prior to this

88
Q

What is primary haemochromatosis?

A
  1. Mutation in HFE gene which means that hepcidin isn’t produced
  2. As a result too much iron is absorbed from the blood
  3. It is stored in the liver and heart causing cirrhosis and cardiomyopathy
89
Q

What is secondary haemochromatosis?

A

Iron overload secondary to chronic haemolysis, multiple transfusions, excess dietary iron

90
Q

How is haemorchromatosis managed? What investigation should be done to look for complications?

A
  1. Phlebotomy
  2. DFO/DFP (bind iron)

MRI for liver and heart

91
Q

What is hereditary spherocytosis ?

A

A disorder causing abnormally shaped but functioning erythrocytes. The spleen attacks these, causing anaemia with high reticulocytes and splenomegaly.
Also causes chronic haemolysis and gallstone formation > biliary colic

THINK - splenomegaly, jaundice, fatigue, cholecystitis

92
Q

Clotting cascade - which factors are involved in the extrinsic pathway and how is this measured?

A

7 - PTT

Warfarin affects this - causes prolonged PT

93
Q

Clotting cascade - which factors are involved in the intrinsic pathway and how is this measured?

A

8, 9, 11, 12 - APTT

Heparin affects these - causes prolonged APTT

94
Q

Clotting cascade - which factors are Vit K dependent?

A

2, 7, 9, 10

95
Q

Describe the process of clot formation

A
  1. Vasconstriction of the blood vessel
  2. Platelet activation and plug formation - granules release ADP, TXA2
  3. Endothelial trauma causes VWF release from WP bodies, this creates a bridge between the platelet plug and collagen in the vessel wall, allowing it to attach
  4. This activates the clotting cascade
  5. Production of a fibrin mesh which stabilises the clot
96
Q

What is a correction study?

A

A blood test performed if you have a long APTT/PTT. Add normal plasma to the blood sample
- If APTT/pTT corrects - it is a clotting factor deficiency, do an assay
- If it does not correct - the blood has an abnormal factor inhibitor

97
Q

What is the most common clotting factor inhibitor found in the blood?

A

Lupus anticoagulant

98
Q

What is haemophilia?

A

A disorder causing excessive bleeding and arthralgia. Subdivided into:
- Haemophilia A
- Haemophilia B

99
Q

What is the pathophysiology of Haemophilia A?

A

X linked recessive deficiency in factor 8, causing high APTT

30% are de novo mutations so don’t always expect a family history

100
Q

What is the pathophysiology of Haemophilia B?

A

X linked recessive deficiency in factor 9, causing high APTT

101
Q

How is Haemophilia treated?

A
  • Recombinant factor 8/9
  • Desmopressin
  • Analgesia and joint immobilisation
  • Physiotherapy
  • Avoid aspirin/NSAIDs/heparin
102
Q

How does desmopressin work in management of haemophilia and VWF deficiency?

A

It causes the release of Von Willebrands antigen, which is the protein that carries factor 8

103
Q

What is the pathophysiology of Von Willebrand Disorder? What are the subtypes?

A

Autosomal dominant deficiency in VWF which usually binds platelets and factor 8 to damaged endothelium. MOST COMMON CLOTTING DISORDER!

Type 1 - asymptomatic (normal VWF but not enough)
Type 2 - mild symptoms such as epistaxis and menorrhagia (abnormal VWF)
Type 3 - severe symptoms (no VWF - autosomal recessive)

104
Q

How is VW disorder diagnosed?

A
  • VWF levels and functionality with a Gp1b assay
  • Reduced ristocetin cofactor activity
  • Reduced factor 8, increased APTT
105
Q

What is acquired haemophilia?

A

An autoimmune process in which the body starts making antibodies to factor 8 or 9.
Often this is due to occult malignancy.

Blood tests show grossly elevated APTT which does NOT correct

105
Q

How is VW disorder managed?

A

Tranexamic acid for mild bleeding
Desmopressin
Pooled plasma containing VWF/factor 8

Often treatment only needed before surgery or dental procedures

106
Q

Why do you get excessive bleeding in
A) renal disease?
B) liver disease?

A

a) Uraemia > platelet aggregation > bleeding

b) Impaired production of clotting factors

107
Q

What is haemorrhage disease of the newborn?

A

All babies are born vitamin K deficient so there is impaired production of 2,7,9,10 and protein C/S

Babies are at risk if:
- Don’t receive preventative Vitamins K at birth
- Exclusively breastfed
- Mums with seizures/anticonvulsant meds

108
Q

What is DIC?

A

Widespread activation of coagulation from release of procoagulants. TF is released in response to exposure to cytokines and this binds to coagulation factors that then trigger the extrinsic pathway (via factor 7) which then triggers the intrinsic pathway (12 to 11 to 9). Eventaully these factors get used up leading to bleeding.

Blood tests show:
Low platelets
Low fibrinogen
High PT/APTT
High fibrinogen degradation products
High D dimer
Schistocytes (due to microangiopathic haemolytic anaemia)

Caused by sepsis, malignancy, obstetric catastrophe, major haemorrhage

109
Q

How is DIC managed?

A

Treat underlying cause
Resuscitate with RBC, plasma, platelets, cryoprecipitate (rich in factor 8), blood warmers

110
Q

How is the clotting cascade initiated?

A

Factor 7 and tissue factor form a complex which activates factor 10

111
Q

What is the reversal agent for DOACs?

A

Dabigatran - darucizumab
Rivaroxaban/apixaban - Andezenetalfa
Edoxaban - none

112
Q

What is the reversal agent for warfarin?

A

Vitamin K (if high INR)
Prothrombin complex (major bleed)

Sometimes FFP is used if prothrombin complex not available

113
Q

What is the reversal agent for heparin?

A

Protamine

114
Q

What does it mean if a blood film has large numbers of immature granulocytes but no blast cells?

A

Chronic leukemia

Blast cells = acute

115
Q

How does wells score influence DVT investigation?

A

DVT likely (2 points or more):
- USS within 4h
- If negative, D dimer test
- If unable to get scan, do D Dimer and started DOAC
- If scan negative but high D dimer, don’t treat and rescan in 6-8 days

DVT unlikely (1 point)
- D dimer within 4h
- If positive, do USS within 4h
- If unable to do above, give DOAC in meantime (perform within 24h)

116
Q

Which anticoagulant should be offered first- line following diagnosis of DVT OR if suspected?

A

DOAC - including if pt has active cancer

(this guidance is new, used to be LMWH if suspected)

117
Q

How long should those with DVT receive anticoagulation?

A

No active cancer:
Provoked - 3 months
Unprovoked - 6 months

Active cancer:
Provoked - 3-6 months
Unprovoked - 6 months

Use ORBIT score to assess risk of bleeding.

118
Q

Name 7 conditions that causes thrombosis

A

Factor V Leiden
DVT/PE
Antiphospholipid syndrome
Central sinus thrombosis
Arterial embolus
Metallic heart valves
Ventricular pacemaker

119
Q

What is Factor V Leiden?

A

A point mutation in factor V gene, leading to slow inactivation of Va and hence a tendency to form clots

120
Q

How is Factor V Leiden managed?

A

Most people do not form abnormal clots therefore require no treatment

If a patient develops a clot, they will be started on a DOAC

121
Q

What are protein C/S deficiencies?

A

Deficiency of vitamin K dependent natural anticoagulants - this gives a 5 fold increase in VTE risk

122
Q

What is antiphospholipid syndrome?

A

The association of persistent antiphospholipid antibodies (lupus anticoagulant, anticariolipini antibody, anti-beta1-glycoprotein 1) with a variety of clinical features characterised by thromboses and pregnancy-related morbidity (3 miscarriages before 10 week or 1 or more unexplained deaths after 10 weeks)

123
Q

What are the risk factors for antiphospholipid syndrome?

A

History of SLE or other rheumatological autoimmune disorders

124
Q

What are the 1st line investigations for antiphospholipid syndrome?

A

Lupus anticoagulant, anticardiolipin antibodies, anti-bet1-dlycoprotein 1 antibodies, ANA, dsDNA

125
Q

How is antiphospholipid syndrome managed?

A

Thrombotic APS:
Warfarin (INR 2-3)

Obstetric APS:
Aspirin + heparin during pregnancy
If pre-eclampsia/FGR, just give aspirin

Catastrophic APS:
Anticoagulant with heparin/warfarin
Immunomodulatory therapies including plasampheresis, IV IGG, rituximab, steroids

126
Q

What is central sinus thrombosis?

A

A rare form of stroke -formation of a blood clot in the brains venous sinuses, preventing blood from draining. This can lead to haemorrhage.

Symptoms include headache, blurred vision, fainting, weakness, seizures, coma

127
Q

What is an arterial embolus?

A

A clot forming in the artery which can travel to the legs, heart or brain

Risk factors include AF, clotting disorders, damaged artery wall (atherosclerosis), infective endocarditis and mitral stenosis

128
Q

What is the difference between arterial and venous thrombosis?

A

Arterial:
- Occur on atherosclerotic lesions with active inflammation
- Higher platelets ‘white clot’
- Much slower formation (decades)
- Treatment focuses on risk factor modification (statins, smoking cessation) + antiplatlet

Venous:
- Higher fibrin and red cells ‘red clot’
- Occur rapidly
- Treatment involves blood thinners

129
Q

How does iron deficiency cause thrombosis?

A

Induces thrombocytosis which can lead to a hypercoagulable state

130
Q

What may a blood film of someone with IDA show?

A

Elliptocytes and hyperhsegmented neutrophils

131
Q

What is sickle cell disease?

A

Sickle cell disease is a group of inherited health conditions, caused by abnormal Hb S, causing sickling of RBCs

Types include:
- Sickle cell anaemia (SS genotype)
- Sickle beta thalassemia
- Sickle HbC disease

132
Q

What is a thrombotic/vaso-occlusive crisis?

A
  • Precipitated by infection, dehydration, deoxygenation
  • Diagnosed clinically due to +++++ pain
  • Can cause infarcts in bones (AVN), hand-foot syndrome, lungs, spleen, brain

Management:
Aggressive analgesia, rehydration, antibiotics

133
Q

What are the symptoms of sickle cell disease?

A
134
Q

What is a chest crisis?

A
  • Vaso-occlusion within the pulmonary microvasculature causing infarction
  • Presents as dyspnoea, chest pain, infiltrates on CXR, hypoxia

Management:
Analgesia, oxygen, abx, transfusion/plasmapheresis

135
Q

What is an aplastic crisis?

A
  • Crisis precipitated by infection with parvovirus
  • Associated with sudden drop in Hb >20 and reduced reticulocyte count

Management:
Oxygen, hydration, RBC transfusion

136
Q

What is a splenic sequestration crisis?

A
  • Sickling within organs such as spleen or lungs, causing pooling of blood with worsening of anaemia
  • Sudden spleen enlargement associated with increased reticulocyte count and sudden Hb drop >20
  • Typically occurs in infants
  • Recurrent sequestration and infarction can lead to auto-splenectomy

Management:
Oxygen, hydration, RBC transfusion

137
Q

What causes massive splenomegaly?

A

Myelofibrosis
CML
Visceral leishmaniasis
Malaria
Gauchers syndrome

138
Q

What causes paraproteinemia?

A

Benign:
- Monoglobal gammopathy of undetermined significance
- Transient paraproteinaemia

Malignant:
- Multiple myeloma
- Waldenstroms
- Primary amyloidosis
- B cell lymphoproliferative disorders

139
Q

What is ITP?

A

Immune/idiopathic thrombocytopenic purpura is an immune mediated reduction in the platelet count

Antibodies form against glycoprotein IIB/IIIa or Ib-V-IX complex

Children tend to have an acute thrombocytopenia following infection or vaccination, whereas adults will have a more chronic course

140
Q

How is ITP investigated?

A

Bloods - isolated thrombocytopenia
Blood film

141
Q

How is ITP treated?

A

1st line - oral prednisolone (steroids work by decreasing production of antibodies against platelets, can take 2-4 weeks)
2nd line - IVIG (can also be used in emergency as raises platelet count quicker than steroids)

142
Q

What is post-thrombotic syndrome? How is it managed?

A

Chronic venous hypertension post DVT causes venous outflow obstruction and venous insufficiency

Symptoms include painful calves, pruritus, swelling, varicose veins, venous ulceration

Treat with compression stockings and leg elevation

143
Q

How soon before surgery should the COCP be stopped to reduce risk of VTE?

A

4 weeks

144
Q

What are the different types of blood product transfusion complications?

A
  1. Immunological
    - acute haemolytic
    - non-haemolytic
    - allergic/anaphylactic
  2. Infective
  3. Transfusion related acute lung injury (TRALI)
  4. Transfusion associated circulatory overload (TACO)
  5. Other
    - hyperkalemia
    - iron overload
    -clotting
145
Q

What are the features of a non-haemolytic febrile reaction? How is it managed?

A

Thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage

Symptoms:
Causes fever and chills

Management:
- Slow or stop the transfusion
- Paracetamol
- Monitor

146
Q

What are the features of a minor allergic reaction during blood transfusion?

A

Thought to be caused by foreign plasma proteins

Symptoms:
Pruritus and urticaria

Management:
- Temporarily stop the transfusion
- Antihistamines
- Monitor

147
Q

What are the features of an anaphylactic blood transfusion reaction? How is it managed?

A

Can be caused by patients with IgA deficiency who have anti-IgA antibodies

Symptoms:
Hypotension, dyspnoea, wheezing, angioedema

Management:
- Stop the transfusion
- IM adrenaline
- ABC support

148
Q

What are the features of an acute haemolytic blood transfusion reaction?

A

ABO incompatible blood eg. secondary to human error

Symptoms:
Fever, abdo pain, hypotension

Management:
- Stop transfusion
- Confirm diagnosis
- Send blood for Coombs test
- Supportive care incl fluids

149
Q

What is TACO? How is it managed?

A

Excessive rate of transfusion in pre-existing heart failure

Symptoms:
Pulmonary oedema, hypertension

Management:
- Stop or slow transfusion
- Consider IV loop diuretics and oxygen

150
Q

What is TRALI? How is it managed?

A

Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by sustances in donated blood

Symptoms:
Hypoxia, pulmonary infiltrates on CXR, fever, hypotension

Management:
- Stop the transfusion
- Oxygen and supportive care
- Potentially fatal

151
Q

What is the definition of neutropenic sepsis?

A

Neutrophil count <0.5 in a patient who is having anticancer treatment and has one of the following:
- A temperature > 38C
- Other signs or symptoms consistent with clinical sepsis

152
Q

What is the most common bacteria causing neutropenic sepsis? What abx should be started?

A

a) Gram positive bacteria including staphylococcus epidermidis (due to indwelling lines)
b) Tazocin

Give meropenem if previous or suspected ESBL, acute leukemia or history of allogeneic stem cell transplants
Give teicoplanin if penicillin allergy

153
Q

How is neutropenic sepsis managed?

A
  • Start tazocin immediately, do not wait for WBC
  • If still febrile/unwell after 48h, escalate to meropenem +/- vancomycin
  • If not responding in 4-6 days, order investigations for fungal therapy
  • There may be a role for G-CSF in selected patients
154
Q

What should be given to patients as prophylaxis for neutropenic sepsis ?

A

Floroquinolone

155
Q

What blood prodcut poses the highest risk of bacterial contamination? What is its shelf life?

A

Platelets - this is because refrigeration causes irreversible glycoprotein clustering on the platelet surface, which causes the platelts to be recgonised by liver macrophages and rapidly cleared by phagocytosis

They have a shelf life of 5 DAYS

156
Q

What is the transfusion threshold for platelets?

A

<30

Transfusion thresholds are higher (max <100) for patients with severe bleeding or bleeding at critical sites

157
Q

How long can you keep packed red cells in the refrigerator from donation?

A

Up to 42 days

158
Q

What will iron studies show in IDA?

A

Low ferritin
High TIBC
High transferrin
Low transferrin satuation
Poikilocytes, aniscocytosis and target cells (because bone marrow pumps out incomplete RBCs)

159
Q

How is IDA managed?

A
  • Treat underlying cause
  • Exclude malignancy
  • Oral ferrous sulphate (take for 2 months after IDA corrected)
  • Iron rich diet
160
Q

What is G6PD deficiency?

A
  • X-linked disorder leading to haemolytic crises within hours of exposure to oxidant stress
  • Stressors include viral/bacterial infecton/ drugs (sulfa and quinines), fava beans
  • Presents with SOB palpitations and headache
  • Hb becomes denatured and leads to formation of Heinz bodies
  • Treat supportively to maintain urine output and prevent future episodes

MSRA (24 decks)

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