haematology intro Flashcards

1
Q

What is the difference between a primary and secondary blood disorder

A

Primary - inherited/acquired disease of the blood
Secondary - normal haem system reacting to non-haem condition

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2
Q

Eg of primary RBC conditions

A

Raised RBC - polycythaemia vera
Reduced - thalassaemia

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3
Q

Eg of secondary RBC conditions

A

Raised - high altitude
Low - auto-immune haemolytic anaemia

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4
Q

eg of Inherited primary haematological disorders

A

Inherited means germline mutation

FIX:
* deficiency > haemophilia B (bleeding tendency)
* Excess > FIX Padua (gene therapy use) thrombosis

Erythrocytes
* Deficiency> B globin gene mutation > Hb S
* Excess > High affinity Hb muation >Erythrocytosis

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5
Q

Acquired primary haematological disorders

A

Somatic gene mutation - bone marrow has a rapid turnover system

Erythrocytes:
* Excess> JAK2 > Polycythaemia vera
* Deficiency> PIG A > paroxysmal nocturnal haemoglobinuria (PNH)

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6
Q

Eg of secondary factor VIII disorder

A

Excess > inflammatory response/pregnancy

Deficiency> 2ndry to anti-FVIII auto antibodies (acquired haemophilia A)

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7
Q

Effect of chronic inflammation on blood

A

raised FVIII levels> increased Thrombosis risk.

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8
Q

Secondary causes of change in Hb

A

Raised
* {altitude/hypoxia or Epo secreting tumour}

Reduced
* BM infiltration or deficiency {Vit B12, or Fe} disease
* Shortened survival {Haemolytic anaemia}

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9
Q

Secondary causes of changes in plt

A

Raised
{Bleeding, Inflammation, splenectomy}

Reduced
BM infiltration or deficiency disease {Vit B12 }
Shortened survival {ITP, TTP}

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10
Q

Secondary causes of changes in leukocytes

A

raised
{Infection, Inflammation, corticosteroids}

Reduced
BM infiltration or deficiency disease {Vit B12 }

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11
Q

Lab findings for Fe deficiency and underlying malignancy

A

Microcytic hypochromic anaemia
Reduced ferritin, transferrin saturation
Raised TIBC

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12
Q

What is leuco-erythroblastic anaemia

A

Variable degree of anaemia with
specific morphological features in the blood film

Teardrop RBCs (+aniso and poikilocytosis)
Nucleated RBCs
Immature myeloid cells

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13
Q

What is suggested by a leucoerythroblastic picture

A

Either - malignant, severe infection, or myelofibrosis

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14
Q

malignant causes of bone marrow infiltration

A

haemopoietic:
* leukaemia
* lymphoma
* myeloma

non-haemopoietic:
* breast/bronchus/prostate

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15
Q

severe infection causing bone marrow invasion

A

miliary TB
severe fungal infection

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16
Q

briefly summarise myelofibrosis

A

massive splenomegaly
dry tap on BM aspirate
primary blood cancer - produce reactive fibrosis around malignant red cells - infiltrates marrow

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17
Q

What are the inherited haemolytic anaemias and the overall cause of each one

A

Membrane: eg Hereditary Spherocytosis
Cytoplasm/enzymes: eg G6PD deficiency
Haemoglobin: Sickle cell disease (structural Hbpathy) Thalassaemia (quantitative Hbpathy)

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18
Q

Lab results for haemolytic anaemia

A

Anaemia (though may be compensated)
Reticulocytosis (increased premature RBC) (may cause modest elevation of MCV – because reticulocytes are slightly larger than mature RBC)
Hyperbilirubinaemia (unconjugated/pre-hepatic cause)
LDH raised – intracellular enyme – released from inside the RBC when they are broken down
Haptoglobins reduced

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19
Q

Results for immune haemolytic anaemia - acquired haemolytic anaemiaResults for immune haemolytic anaemia - acquired haemolytic anaemia

A

Spherocytes - bits of membrane are broken off
DAT +ve (same as coombs test) - detect the Ab that are bound to the red cells.

Associated with systemic diseases:
Imunological disorders
Cancer of immune system: eg Lymphoma or Chronic lymphocytic leukaemia
Auto immune: SLE
Infection: eg mycoplasma
Idiopathic

20
Q

Types of acquired non-immune haemolytic anaemia

A

(DAT -ve)

Infection of erythrocytes Malaria

Micro-angiopathic Haemolytic anaemia (MAHA) - associated with systemic disease - RBC broken down in the small blood vessels
Underlying adenocarcinoma
Haemolytic uraemic syndrome
Metal aortic valve

21
Q

Summarise a microangiopathic film

A

RBC fragments
thrombocytopenia

22
Q

Pathophysiology of micro-angiopathy

A

In adenocarcinomas/low grade DIC

Plt activation
Fibrin deposition and degradation in microvascular
Red cell fragmentation
Bleeding - low plts and coag factor consumption

23
Q

White blood cells in the bone marrow

A

Blasts (myeloid & Lymphoid)
Promyelocytes
Myelocytes

If blasts are >5% of bone marrow cells - consider leukaemia or myelodysplasia

24
Q

What should you consider if bone marrow cells are in the blood

A

Leukaemia
Met cancer invading bone marrow

25
Q

WBC in peripheral blood

A
26
Q

Film for chronic lymphocytic anaemia

A

WBC increased mature cells

27
Q

Film for acute myeloid leukaemia

A

increased immature white cells

28
Q

Causes of reactive neutrophilia

A

Pyogenic infection
Steroids
Neoplasia
Tissue inflammation - colitis, pancreatitis, myocarditis, or MI

29
Q

Differentiate between reactive or malignant cause when high neutrophils/abnormal myeloid count in the peripheral blood

A

Reactive
* Neutrophilia
* Toxic granulation - more intense granules and vacuoles
* No immature cells

Malignant
* Abnormal cells in peripheral blood
* Neutrophilia + basophilia and myelocytes - suggestive of CML
* Neutropenia + myeloblasts - suggestive of AML

30
Q

Causes of reactive eosinophilia

A

Parasitic infestation
Allergic diseases e.g. asthma, rheumatoid, polyarteritis, pulmonary eosinophilia.
Neoplasms, esp. Hodgkin’s, T-cell NHL (reactive eosinophilia)
Drugs (reaction erythema multiforme)

31
Q

Summarise chronic eosinophilic leukaemia

A

Eosinophils part of the “clone”
FIP1L1-PDGFRa Fusion gene

32
Q

Causes of monocytosis

A

Rare
TB, brucella, typhoid
Viral; CMV, varicella zoster
sarcoidosis
chronic myelomonocytic leukaemia (MDS)

33
Q

Secondary causes of lymphocytosis

A

EBV, CMV, Toxoplasma (Infectious mononucleosis)
infectious hepatitis, rubella, herpes infections
autoimmune disorders
Sarcoidosis

34
Q

Secondary causes of lymphocytopenia

A

Infection HIV
Auto immune disorders
Inherited immune deficiency syndromes
Drugs (chemotherapy)

35
Q

Differentiate causes of lymphocytosis by looking at peripheral blood morphology

A

Mature lymphocytes
* reactive/atypical lymphocytes (infectious mononucleosis)
* small lymphocytes and smear cells (CLL/NHL)

Immature Lymphoid cells
* Lymphoblasts; Acute Lymphoblastic Leukaemia (ALL)

36
Q

How can you determine clonality in B cells

A

Look at the light chain type
If kappa or lambda only = clonal

37
Q

Summarise pathway of chronic and acute malignancy

A
38
Q

What cell does multiple myeloma originate from

A

plasma

39
Q

Acquired somatic mutations that cause cellular proliferation

A

In tyrosine kinase genes
= excess proliferation

BCR ABL -> CML
JAK2 -> MPD

40
Q

Acquired somatic mutations that cause cellular proliferation

A

In tyrosine kinase genes
= excess proliferation

BCR ABL -> CML
JAK2 -> MPD

41
Q

Acquired somatic mutations that impair/block cellular differentiation

A

In nuclear transcription factors
If also have proliferation mutation can -> acute leukaemia

PML RARA -> acute promyelocytic leukaemia

42
Q

Acquired somatic mutations that cause prolonged cell survival (anti-apoptosis)

A

In lymphomas

BCL2 - > follicular lymphoma

43
Q

Techniques for haemo-onch dx

A

Morphology
* Architecture of tumour
* Cytology
* Cytochemistry
Immunophenotype
* Flow cytometry
* Immunohistochemistry
Cytogenetics
* Karyotyping
* Flurescent in sity hypridisation
○ Interphase FISH
○ Metaphase FISH
Molecular genetics
* Mutation detection
○ Direct sequencing
○ Pyrosequencing
* PCR analysis
* Gene expression profiling
* Whole genome sequencing

44
Q

dx features of B cell acute lymphoblastic lymphoma

A
45
Q

dx features of multiple myeloma

A
46
Q
A