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
WBC in peripheral blood
26
Film for chronic lymphocytic anaemia
WBC increased mature cells
27
Film for acute myeloid leukaemia
increased immature white cells
28
Causes of reactive neutrophilia
Pyogenic infection Steroids Neoplasia Tissue inflammation - colitis, pancreatitis, myocarditis, or MI
29
Differentiate between reactive or malignant cause when high neutrophils/abnormal myeloid count in the peripheral blood
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
Causes of reactive eosinophilia
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
Summarise chronic eosinophilic leukaemia
Eosinophils part of the “clone” FIP1L1-PDGFRa Fusion gene
32
Causes of monocytosis
Rare TB, brucella, typhoid Viral; CMV, varicella zoster sarcoidosis chronic myelomonocytic leukaemia (MDS)
33
Secondary causes of lymphocytosis
EBV, CMV, Toxoplasma (Infectious mononucleosis) infectious hepatitis, rubella, herpes infections autoimmune disorders Sarcoidosis
34
Secondary causes of lymphocytopenia
Infection HIV Auto immune disorders Inherited immune deficiency syndromes Drugs (chemotherapy)
35
Differentiate causes of lymphocytosis by looking at peripheral blood morphology
Mature lymphocytes * reactive/atypical lymphocytes (infectious mononucleosis) * small lymphocytes and smear cells (CLL/NHL) Immature Lymphoid cells * Lymphoblasts; Acute Lymphoblastic Leukaemia (ALL)
36
How can you determine clonality in B cells
Look at the light chain type If kappa or lambda only = clonal
37
Summarise pathway of chronic and acute malignancy
38
What cell does multiple myeloma originate from
plasma
39
Acquired somatic mutations that cause cellular proliferation
In tyrosine kinase genes = excess proliferation BCR ABL -> CML JAK2 -> MPD
40
Acquired somatic mutations that cause cellular proliferation
In tyrosine kinase genes = excess proliferation BCR ABL -> CML JAK2 -> MPD
41
Acquired somatic mutations that impair/block cellular differentiation
In nuclear transcription factors If also have proliferation mutation can -> acute leukaemia PML RARA -> acute promyelocytic leukaemia
42
Acquired somatic mutations that cause prolonged cell survival (anti-apoptosis)
In lymphomas BCL2 - > follicular lymphoma
43
Techniques for haemo-onch dx
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
dx features of B cell acute lymphoblastic lymphoma
45
dx features of multiple myeloma
46