Chapter 23: Haematology and Transfusion Medicine Flashcards

1
Q

Define haematopoiesis and where does it occur

A
  • formation of blood cells
  • during development occurs in yolk sac, liver, spleen and lastly red bone marrow in all bones
  • in childhood, red marrow is replaced by fat yellow marrow
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2
Q

What does increased number of circulating reticulocytes (reticulocytosis) reflect?

A

erythropoeises

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3
Q

Describe how red cells are developed from precursors

A
  1. Red blood cell precursor = erythroblast or normoblast
  2. These divide and acquire Hb
  3. Late normoblast, nucleus condenses and is extruded from cell
  4. FIRST NON-NUCLEATED CELL = RETICULOCYTE (but they contain ribosomal material)
  5. Reticulocytes lose ribosomal material and mature over 3 days and released into circulation
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4
Q

What stimulates proliferation and differentiation of red blood cells

A

Erythropoietin

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5
Q

Describe the composition of haemaglobin

A

4 globin chains surrounding iron containing haem

2 alpha and 2 non-alpha (beta) chains

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6
Q

What does decreased oxygen affinity mean?

A

Oxygen is released more readily

Important for when you have hypoxic tissues

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7
Q

What causes a right shift on the oxygen dissociation curve?

A
Increase in:
2,3 BPG
H+ 
CO2 
Temp

Decrease in pH

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8
Q

What causes a left shift on the oxygen dissociation curve?

A
Decrease in:
2,3 BPG
H+ 
CO2 
Temp 

Increase in CO
Increase in pH

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9
Q

How long do RBC last and how are they cleared?

A

RBCs last 120 days
Phagocytosed by the reticulo-endothelial system

Amino acids from globin chains are recycled and iron is removed from haem for reuse in haemoglobin synthesis

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10
Q

Describe the degradation of the haem structure in RBC

A
  1. Degraded to unconjucated bilirubin
  2. conjugated with glucuronic acid in the liver before excreted in bile
  3. Conjugated Bilirubin is converted to stercobilin in the small bowel
  4. Most of this stercobilin is excreted, some is reabsorbed by kidney as urobilinogen
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11
Q

What happens in increased red cell destruction

A
  • Jaundice
  • Increased urinary urobilinogen
  • decreased haptoglobins (they bind to free RBC)
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12
Q

Which is the most common white blood cell in the body

A

Neutrophils

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13
Q

Where do majority of mature neutrophils exist?

A

bone marrow

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14
Q

how many hours do neutrophils spend in the circulation before removal

A

6-10hrs

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15
Q

What 2 system/organ/processess remove neutrophils

A
  1. spleen

2. consumed in inflammatory process/undergo apoptosis

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16
Q

Second most common WBC

A

Eosinophil

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17
Q

Which WBC contains granultes and proteins which can intracellularly kill protozoa and hemlinths

A

Eosinophil

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18
Q

Which is the largest WBC

A

Monocytes

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19
Q

Monocytes can migrate and become what cells: (3)

A

macrophages, Kupffer cells or antigen presenting dendritic cells

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20
Q

80% of lymphocytes are ___ cells

A

T cells

21
Q

Describe the 3 stages of normal haemostasis

A

Stage 1: Vascular endothelium produces substances (NO, prostacyclin, heparans) to prevent adhesion of platelets and WBC to wall

Stage 2: Endothelium is injured, subendothelial collagen exposed and Tissue Factor (TF) released. Platelets adhere to collagen binding to recepeotr GP1a, causing shape change in platelet shape and adhering to GP1b and GpIIb/IIa to von Willebrand factor and fibrinogen. COAGULATION is activated by Tissue factor extrinsic pathway generating thrombin

Stage 3: Fibrin cot formation: platelets become activated and aggregate, Fibrin formation is supported by platelet membrane. and you get stable fibrin.
Adherent platelets are further activated by many other pathways:
- binding of ADP
- binding of collagen, thrombin, adrenaline
- Cyclo-oxygenase pathway, converts arachidonic acid from platelet membrane into thromboxane A2, which also causes aggregation of platelets

22
Q

Megakaryocytes form what type of cells and where

A

Platelets, in the bone marrow

23
Q

Platelets circulate for how many days before destruction

A

8-10 days

24
Q

which lasts longer platelets or neutrophils

A

PLATELETS

25
Q

Drugs that inhibit platelet formation include:
cyco-oxygenase inhibitor
ADP mediated inhibitors
GPIIb/IIIa inhibitors

NAME 1 example of each

A
  1. Aspirin
  2. clopidogrel, prasugrel, ticagrelor
  3. abciximab, tirofiban
26
Q

What are the two pathways by which coagulation occurs

A

Extrinsic (tissue factor) pathway

Intrinsic pathway

27
Q

All clotting factors are produced by the ______ except Factor __ which is produced by____

A

liver

Factor V, produced by platelets and endothelial cells

28
Q

Which factors need post-translational carboxylation and the enzyme which does is, is dependent on which vitamin __

A

Factor II, VII, IX, X
(tv channels)

Vitamin k

29
Q

Vitamin K is converted to an epoxide in the post translational carboxylation of the VitK dependent clotting factors. However it must be reduced to its active form by a reductase enzyme. Warfarin inhibits which part of this process?

A

The reductase is inhibited by warfarin

30
Q

In which disorders do you see microcytosis ?

A

Iron deficiency anaemia
Thalassaemia
Sideroblastic anaemia

31
Q

If a person is Vitamin B12 or folate def, or has liver disease (alcoholic), or has hypothyrodism or on certain drugs e.g. trimethoprin, methotrexate, what do we expect the red cell appearance to be

A

macrocytosis (increased average cell size)

32
Q

Prothrombin Time (PT) assess which pathway

A

Tissue Factor (extrinsic) pathway

33
Q

Intrinsic pathway is assessed by which coagulation screening test

A

Activated partial thromboplastin time (APPT)

34
Q

If both PT and APTT are prolonged what does this indicate

A

deficiency or inhibition of the final common pathway (Factor X, V, prothrombin and fibronogen)

35
Q

Why do we use the international normalised ratio (INR)

A

To assess the theraputic effect of coumarin anticoagulants (e.g. warfarin)

36
Q

Measurement of plasma levels of Fibrin degraded d-dimers are useful in what situation

A

in excluding the diagnosis of active venous thrombosis

37
Q

Thrombophillia is defined as

A

Abnormal propensity to develop clots

38
Q

What investigations would you order for a person who presents with Venous thrombosis <45 years, has recurrent VTEs, family history of unprovoked or recurrent thrombosis, combined arterial and venous thrombosis OR a venous thrombosis at an unsual site e.g. cerebral, hepatic vein, portal vein

A

this person has suspected thrombophillia

Order:
1. Full Blood count + antithrombin levels, protein C, protein S, antiphospholipid antibodies

  1. Genetic testing
    Factor V Leiden, Prothrombin G20210A, JAK2 VG17F mutation, CALR mutation
  2. Flow cytometry to screen for GPI-linked surface proteins
39
Q

Anaemia is defined as:

A

The state in which level of haemoglobin in the blood is below the reference range appropriate for age and sex

40
Q

Two broad reasons for anaemia

A
  1. Decreased or ineffective marrow production (lack of iron, vit B12, folate, invasion of malignant cells, renal failure)
  2. Normal marrow production but increased removal of cells
    (blood loss, haemolysis, hypersplenism)
41
Q

When should someone with a high haematocrit be investigated

A

for more than 2 months

> 0.6 males
0.56 females

42
Q

Explain what true vs relative/low polycythemia means

A

True = excess red cells
(called polycythemia rubra vera)

Relative/low = due to decreased plasma volume (therefore gives the appearance that there is more RBC)

43
Q

4 causes of polycythemia

A

increase in bone marrow activity (myeloproliferation)

increased EPO in chronic hypoxaemia

inappropriate secretion of EPO (renal disease or tumours)

Athletes injecting EPO

44
Q

High altitude, and cardiorespiratory disease can cause tissue hypoxia causing high production of ______ and resulting in _____

A

erythropoietin and resulting in polycythemia

45
Q

Polycythemia rubra vera is also considered what type of disorder

A

Myeloproliferative disorder

46
Q

Patient presents with erythrocytosis with raised Haematocrit, normal red cell mass, reduced plasma volume and also has HTN, Smokes, drinks alcohol and uses diuretics

A

Secondary polycythemia called:

“Gaisböck’s syndrome”

47
Q

Over 90% of cases with polycythaemia rubra vera (PRV) have which mutation

A

JAK - 2 V617F

48
Q

Reduction in total number of WBC is called

**can be all types of WBC or an individual cell in isolation

A

Leucopenia

49
Q

Neutropenia is defined as

A

reduction in neutrophil count <1.5 x 10^9