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Lectures > Haematology > Flashcards

Haematology Flashcards

1
Q

What is myeloma?

A

Myeloma: neoplastic proliferation of bone marrow plasma cells
Characterised by:
Monoclonal protein in serum or urine
Lytic bone lesions/CRAB end organ damage (increased calcium level, renal dysfunction, anemia, and destructive bone lesions)
Excess plasma cells in bone marrow
40 cases per million

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2
Q

What is MGUS?

A

MGUS (monoclonal gammopathy of unknown significance) is a non-cancerous condition where the body makes an abnormal protein, called a paraprotein. MGUS is not a cancer, but people with it have a slightly higher risk of developing myeloma.

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3
Q

What are the common presenting features of myeloma?

A 
Tiredness and malaise
Bone/back pain and potentially fractures
Infections
Non specific
Lab: anaemia/abnormal FBC, renal failure, hypercalcaemia, raised globulins, raised ESR, serum/urine paraprotein
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4
Q

What chromosomal abnormalities may be associated with myeloma?

A

t(11;14) most common

13-q associated with treatment resistance and poorer prognosis

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5
Q

What myeloma investigations would you perform?

A

X-rays of chest, skull, spine and pelvis to look for holes in the bones
MRI is used in investigation in patients with back pain with elevated paraprotein
PET scans in patients you are trialing novel experimental treatments

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6
Q

How do you treat myeloma?

A

Supportive and Cytotoxic
Cytotoxic
Radiotherapy - radiation in high intensity targeted to specific areas or whole body
Chemotherapy - conventional cytotoxic, novel biological thalidomide/proteasome inhibitors

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7
Q

Are myeloma patients prone to relapse?

A

If the patient relapses after a year following the high dose therapy, they have a poor prognosis.
Many respond to treatment, but all will eventually relapse
Strategies to prolong survival by keeping the disease in plateau phase rather than try and cure.
Both the disease and treatment have morbidity - sickness and mortality.

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8
Q

What are the common presenting symptoms with acute leukemia?

A

Symptomatic anaemia - tiredness, fatigue, lightheadedness, palpitations, SOB on exertion
Symptomatic thrombocytopenia - bruising/bleeding, can be severe/atypical including intracranial bleeds
Symptomatic low white cell counts - infections (recurrent, persistent, severe, atypical_
Symptomatic high white cell counts due to leukostasis or tumour lysis

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9
Q

What are the uncommon presenting symptoms with acute leukemia?

A

Extramedullary disease - disease infiltration most common in skin, gums and/or other soft tissue. ‘Sanctuary sites’ e.g. testicules
Coagulopathy - disseminated intravascular congestion

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10
Q

What are the differential diagnoses for acute leukaemia?

A

Acute leukaemia/haematological disorder - AML/LL, CML in blast crisis, Myelofibrosis with circulating blasts
Severe sepsis
Post-op reactive changes

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11
Q

How would you investigate potential acute leukaemia?

A

Do an FBC
Do a blood film
Check haematinics +/- haemolysis screen, biochemistry profile
Rapid change in FBC needs urgent follow up
Ask a haematologist for advice

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12
Q

What is a Bone marrow aspirate and trephine biopsy?

A

Used in patients with acute leukaemia
Bone marrow aspirate and trephine biopsy - needle goes through the pelvic bone (painful)
Increase in blasts >20%
Background abnormalities to suggest pre-existing bone marrow abnormalities
Cytogenetics for prognosis
Molecular genetics for prognosis
Immunophenotyping (confirmatory/prognosis)

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13
Q

How would you identify leukemic blast cells?

A

CD34 is present on leukemic blast cells.
Antibodies that are fluorophores against the CD34 markers are introduced.
Can find out the type of cells that are present.
Forward scatter - how big the cells are
Side scatter - whether granulations are present
Fluorescence - what is their profile of antibodies

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14
Q

What is the treatment for acute myeloid leukeamia?

A

Chemotherapy and supportive measures
Take into account age, fitness, comorbidities, AML features, potential benefit vs. toxicity/tolerability of treatment
Chemo causes damage preferentially to rapidly dividing cells
Combinations of drugs are commonly used
Dosing has to be carefully managed to optimise balance between damage to healthy and unhealthy cells

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15
Q

What should you consider before giving a AML patient chemotherapy?

A

Supportive measures - fertility cryopreservation
Clinical trial availability
Bystander damage to other organs - need to obtain baseline cardiac function, liver and renal function to ensure that they are ‘fit’ enough to proceed

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16
Q

What are the side effects of chemotherapy?

A 
Nausea/vomiting
Altered bowel habit
Reduced fertility
Loss of appetite
Fatigue
Cytopenias - anaemia, neutropenia, low platelet and risk of bleeding, bruising
Bystander organ damage
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17
Q

What is CAR-T therapy?

A

Taking blood from a patient, filtering out T cells, introducing a virus to modify T cells to recognise cancer cells. Modified T cells are then injected back into the body.

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18
Q

What are the symptoms of lymphoma?

A

Lymph node enlargement, loss of appetite, loss of weight, night sweats (difficult to distinguish from menopausal sweats)

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19
Q

What are the investigations for lymphoma?

A

Biopsy, blood tests, scans, bone marrow biopsy

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20
Q

What are the differential diagnoses for lymphoma?

A

Reactive lymph node to bacterial or viral infection or TB (tend to be transient, tender)
Malignant (tend to be progressively larger and non-tender, 6 weeks or more) - lymphoma, metastatic, primary head and neck cancer
Thyroid gland enlargement
Embryologic remnant

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21
Q

What’s the prognosis of lymphoma?

A

Follicular lymphoma - tends to wax and wane, slow growing.

Prognosis can vary massively, can be controlled for many years.

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22
Q

What is Anaemia?

A

Reduced red cell mass +/- reduced haemoglobin concentration

Plasma volume - the red cell number have changed, there just looks like there’s less because of the increased fluid

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23
Q

What is the normal range for haemoglobin?

A

Male Hb 131-166 g/L

Female Hb 110-147 g/L

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24
Q

What are the consequences of anaemia?

A

Reduced O2 transport
Tissue hypoxia - not enough oxygen to meet demand
Physiological compensatory changes - body will try to counteract the anaemia first of all. Increase tissue perfusion (tachycardia), O2 transfer to tissues, red cell production

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25
Q

What are the pathological consequences of anaemia?

A 
Myocardial fatty change
Aggravate angina/claudication
Fatty change in liver
Skin and nail atrophic changes
CNS cell death (cortex and basal ganglia)
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26
Q

What happens in the life of a red blood cell?

A

Red cell life span is approx 120 days.
Production in the bone marrow.
Removal in the spleen, liver, bone marrow and through blood loss.

Reticulocytes are immature red blood cells (RBCs). In the process of erythropoiesis (red blood cell formation), reticulocytes develop and mature in the bone marrow and then circulate for about a day in the bloodstream before developing into mature red blood cells.

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27
Q

What are the different types of anaemia?

A

Microcytic
Normocytic
Macrocytic

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28
Q

What causes microcytic anaemia?

A 
Iron deficiency
Chronic disease
Thalassaemia - haemoglobinopathy
Rarely
Congenital sideroblastic anaemia
Lead poisoning
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29
Q

What causes normocytic anaemia?

A

Acute blood loss
Anaemia of chronic disease
Combined haematinic deficiency - two factors (iron deficiency and B12 deficiency)

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30
Q

What causes macrocytic anaemia?

A 
B12/folate deficiency
Alcohol excess/liver disease
Hypothyroid disease
HAEMATOLOGICAL
–Antimetabolite therapy
–Haemolysis
–Bone marrow failure
–Bone marrow infiltration
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31
Q

How would you investigate iron deficiency?

A 
Tests of deficiency
Ferritin
Iron studies
Tests of causes
Treatment
32
Q

How would you investigate B12 deficiency?

A

IF antibodies
Schilling test
Coeliac antibodies

B12 replacement

33
Q

What investigations would you do in suspected anaemia?

A 
Thorough history and examination
FBC and blood film
Reticulocyte count - to check whether there is abnormal production or destruction
U&Es, LFTs, TSH
B12, folate, ferritin
Discuss with haematologist
34
Q

What are Haemoglobinopathies?

A

Disorders of quality (abnormal molecule or variant haemoglobins) e.g. Sickle cell disease
Disorders of quantity (reduced production)
e.g. a or b thalassaemia

35
Q

How can sickle cell disease offer protection?

A

Carriers of HbS are symptom free
Carriage offers protection against falciparum malaria
Sickle cell diseases arise in the homozygous state (SS) or in combined heterozygotes (SC or Sb thalassaemia)

36
Q

What are the complications of sickle cell disease?

A

Acute complications
Painful crisis
Sickle chest syndrome
Stroke

Chronic complications
Renal impairment
Pulmonary hypertension
Joint damage

37
Q

How is sickle cell disease treated?

A 
Transfusion
Hydroxycarbamide – improves a lot of the complications
Stem cell transplant 
Gene therapy
Gene editing
38
Q

What is thalassaemia?

A

Globin chain disorders resulting in diminished synthesis of one or more globin chains with consequent reduction in the haemoglobin
Heterogeneous disorders of world wide distribution
A variety of genetic lesions including deletions (mainly a thal) & mutations (b thal)

39
Q

How is thalassaemia classified?

A

Thalassaemia Major
Transfusion dependent

Thalassaemia Intermedia
Less severe anaemia and can survive without regular blood transfusions

Thalassaemia Carrier/heterozygote
Asymptomatic

40
Q

What is B Thalassaemia Major?

A

Age at presentation: 6-12 months
Clinical presentation with severe symptoms: failure to feed, listless, crying, pale
Blood results:
HB 40-70 g/l, mean corpuscular volume & mean corpuscular hemoglobin very low
Blood film: large and small (irregular) very pale red cells, nucleated RBCs
Hb F > 90% (neonatal sample)
Ferritin normal

41
Q

How is B Thalassaemia Major treated?

A 
Regular transfusion
Iron chelation
Endocrine supplementation
(fertility)
Bone health
Psychological support

Monitoring: Ferritin, Cardiac and Liver MRI, Endocrine testing, Gonadal function, Diabetes screening, Growth & puberty, Vit D, Calcium, PTH, Thyroid, Dexa scanning

42
Q

How can transfusional iron overload be deadly in thalassaemia major patients?

A

Increase in body iron load. As there is no natural means for the body to eliminate the excessive iron, these patients inexorably develop a clinically worsening hemosiderosis. The excessive iron is deposited mainly in the liver and spleen, leading to liver fibrosis and cirrhosis. The excessive iron is also deposited in the endocrine glands and the heart, resulting in diabetes, heart failure and premature death. Death ultimately occurs, mainly due to cardiac hemosiderosis.

43
Q

What is a thalassaemia?

A

Carriage very common
Because of distribution of a thalassaemia significant a thal disease (HbH or Barts Hydrops) confined to Eastern Med and Far East

44
Q

What are Membranopathies?

A

Autosomal dominant conditions
Spherocytosis & elliptocytosis most common
Deficiency of red cell membrane proteins caused by a variety of genetic lesions
Neonatal jaundice
Mild to moderate haemolytic anaemia with occasional exacerbations during infection
Predisposed to gallstones
Folic acid and splenectomy in selected cases (mostly benign diseases)

45
Q

How can Parvovirus cause anaemia?

A

Common upper respiratory tract infection in children
Occurs in epidemics
“slapped cheek syndrome”
Leads to decreased RBC production
Dramatic Hb drop in patients who already have reduced red cell lifespan.

46
Q

What are Enzymopathies?

A

Provides the fuel for the red cell
Generates redox capacity to protect red cell
Inherited enzyme deficiencies lead to shortened red cell lifespan from oxidative damage.
G6PD deficiency and pyruvate kinase deficiency most common

47
Q

What is Glucose 6 phosphate dehydrogenase deficiency?

A

Caused by a wide variety of mutations within G6PD gene
Most asymptomatic
X linked but women may also be affected
Diagnosed by screening test for NADPH
Crises characterised by haemolysis, jaundice, anaemia.
Precipitated by broad beans, infection, drugs
Usually self limiting
Symptomatic patients rare.

48
Q

What does Polycythaemia mean?

A

A high concentration of red blood cells in your blood.

49
Q

What might be cause of Polycythaemia?

A 
Reactive/Secondary
Smoking
Lung disease
Cyanotic heart disease
Altitude
Epo/Androgen excess

Primary/Proliferative
Polycythaemia Rubra Vera

50
Q

What does Neutrophilia mean?

A

An increase in circulating neutrophils above that expected in a healthy individual

51
Q

What might be the cause of Neutrophilia?

A

Reactive
Infection
Inflammation
Malignancy

Primary
CML

52
Q

What does Lymphocytosis mean?

A

A higher-than-normal amount of lymphocytes, a subtype of white blood cells, in the body

53
Q

What might be cause of Lymphocytosis?

A

Reactive
Infection
Inflammation
Malignancy

Primary
CLL

54
Q

What does Thrombocytopaenia mean?

A

Not enough platelets - reduced production

55
Q

What might be the cause of Thrombocytopaenia?

A

Reactive
Infection
Inflammation
Malignancy

Primary
Essential Trombocythaemia

56
Q

What does Neutropaenia mean?

A 
Not enough neutrophils
Normal 		1.7 – 6.5 
Mild			1.0 – 1.7
Moderate		0.5 – 1.0
Severe		<0.5

Severe neutropaenia –major infection risk

57
Q

What might be the cause of Neutropaenia?

A

Underproduction
Marrow failure
Marrow infiltration
Marrow toxicity e.g. drugs

Increased removal
Autoimmune
Felty’s syndrome
Cyclical

58
Q

What is the basic physiology of platelets?

A

Produced in bone marrow – arising from megakaryocytes (multinucleate, plentiful cytoplasm)
Megakaryocyte fragments – break off, enter the blood stream
Approx 4000 per megakaryocyte
Regulated by thrombopoietin (made in the liver)
Anucleate cell
Lifespan 7-10 days
Shorter when bleeding because they are consumed.
Adhesion and aggregation to form platelet plug
Main part of Primary haemostasis
Removed by spleen

59
Q

What are the surface proteins of platelets?

A

ABO
HPA
HLA Class I (not class II)
Glycoproteins e.g. GP1a

60
Q

What happens when platelets are activated?

A

Activated by
Adhesion to collagen via GPIa,
Adhesion to vWF via GPIb and IIb/IIIa

Activation leads to

  • Release of α granules containing PDGF, Fibrinogen, vWF, PF4
  • Dense granules
  • Membrane phospholipids activate clotting factors II (Prothrombin), V and X
61
Q

What is platelets’ role in primary haemostasis?

A

) Platelets adhere to vascular endothelium via collagen & vWF (von Willebrand factor)

2) Binding of platelets to collagen stimulates cytoskeleton shape change within the platelets, and they ‘spread’ out
3) This increases their surface area and results in their activation, leading to the release of platelet granule contents including ADP, fibrinogen, thrombin and calcium. These components facilitate the clotting cascade ending with the production of fibrin.
4) Aggregation of platelets then occurs, which involves the cross-linking of activated platelets by fibrin
5) Activated platelets also provide a negatively charged phospholipid surface, which allows coagulation factors to bind and enhance the clotting cascade.

62
Q

How can platelets be tested?

A

Number: FBC

Appearance: blood film, drop of blood on the glass slide, dried, and stained.

Function:
PFA (platelet function  i.e. response to aggregating agents e.g. ADP, collagen
Bleeding time (unreliable results)

Surface proteins:
Flow cytometry – antibodies with fluorophores looking for platelet-specific surface proteins

63
Q

What problems cause bleeding?

A 
Injury
Vascular disorders
Low platelets
Abnormal platelet function
Defective coagulation
64
Q

What are the clinical features of platelet dysfunction?

A 
Mucosal bleeding
Epistaxis, gum bleeding, menorrhagia
Easy bruising
Petechiae, purpura
Traumatic haematomas (inc subdural)
65
Q

What causes low platelets?

A 
Production failure
Congenital
Acquired
Drugs
Marrow suppression
Marrow failure
Marrow replacement

Increased removal
Immune
Consumption
Splenomegaly – aggregation of platelets

Artefactual
EDTA induced clumping

66
Q

What are the causes of impaired platelet function?

A 
Congenital
Platelet disorders
Storage pool disorders
Glanzmann 
Reduction/deficiency of GP IIb/IIIa
Bernard Soulier 
Reduction/deficiency of GP1b=VW receptor
von Willebrand disease

Acquired
Uraemia
Drugs – Aspirin and NSAIDs

67
Q

What are the different types of Thrombocytopenia?

A

Congenital thrombocytopenia
Absent / reduced / malfunctioning megakaryocytes in BM

Infiltration of bone marrow
Leukaemia, metastatic malignancy, lymphoma, myeloma, myelofibrosis

68
Q

How can Thrombocytopenia occur?

A

Decreased production of platelets by the bone marrow due to low B12/folate, reduced TPO (e.g. liver disease), Methotrexate, chemotherapy, Toxins: e.g. Alcohol, Infections: e.g. viral (e.g. HIV) TB or Aplastic anaemia (auto immune).
OR
Dysfunctional production of platelets in bone marrow
OR
Increased destruction of platelets due to autoimmune, hypersplenism, drug-related immune destruction or consumption of platelets

69
Q

What is immune thrombocytopenia?

A

IgG antibodies form to platelet and megakaryocyte surface glycoproteins
Opsonized platelets are removed by reticuloendothelial system

Primary:
May follow viral infection / immunisation esp in children
Secondary:
Occurs in association with some malignancies, such as Chronic Lymphocytic Leukaemia (CLL)
Infections e.g. HIV / Hep C

70
Q

How would you investigate and treat thrombocytopenia?

A

Investigations:
No specific test
Is there any underlying cause?
Diagnosis of exclusion

Treatment:
Immunosuppression e.g. steroids / IVIG
Treat underlying cause
If bleeding – give platelets - but will disappear quickly
Tranexamic acid inhibits breakdown of fibrin - Good for mucosal bleeding but NOT if urinary tract bleeding (clot retention)

71
Q

What is Disseminated Intravascular Coagulopathy?

A

An acquired syndrome characterised by activation of coagulation pathways, resulting in formation of intravascular thrombi and depletion of platelets and coagulation factors.

72
Q

What is the pathophysiology of Disseminated Intravascular Coagulopathy?

A

Cytokine release in response to SIRS
(Sepsis, trauma, pancreatitis, obstetric emergency, malignancy)
Leads to Systemic activation of clotting cascade
- May lead to micro-vascular thrombosis and organ failure
- May lead to comsumption of platelets and clotting factors and bleeding

73
Q

What would you investigate in Disseminated Intravascular Coagulopathy?

A 
Underlying cause (usually sepsis or malignancy or obstetric causes)
Thrombocytopenia, prolonged PT + APTT, low fibrinogen, high d-dimers 
\+/- evidence of organ failure
74
Q

How would you treat Disseminated Intravascular Coagulopathy?

A 
Treat underlying cause
Supportive provision of:
- Platelets
- FFP: contains clotting factors 
- Cryoprecipitate: contains fibrinogen and some clotting factors
75
Q

What is Thrombotic Thrombocytopenic Purpura?

A

Spontaneous platelet aggregation in microvasculature in brain, kidney, heart.
Reduction in a protease enzyme – ADAMTS13
Acquired – due to antibodies against ADAMTS13
Failure to break down high molecular weight vWF multimers

76
Q

What are the clinical signs of Thrombotic Thrombocytopenic Purpura?

A

Consumption of platelets
Microangiopathic haemolytic anaemia - Rbc fragments (schistocytes)
Renal / CNS / cardiac impairment
Fever

77
Q

What’s the treatment for Thrombotic Thrombocytopenic Purpura?

A

Urgent plasma exchange (replaces ADAMTS 13 and removes antibody)
Immunosuppression (reduce antibody level)
Do NOT give platelets –increases thrombosis

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