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Flashcards in Haematology Deck (72):
1

What are the elements of blood?

  • Plasma
  • Erythrocytes (RBCs)
  • Leukocytes (WBCs)
  • Thrombocytes (Platelets)

2

What is plasma composed of?

  • 92% water
  • 8% plasma proteins
    • albumin: osmotic pressure
    • globulin: antibodies and transport proteins
    • fibrinogens: blood clotting

3

What is the role of erythrocytes?

What do they lack?

What are their life span?

  • Transport oxygen from lungs to tissues
  • Transport CO2 from tissues to lungs
  • Lacks nucleus, ejected in development process
  • 120 day life span

4

What is the role of leukocytes?

  • Protect against pathogens
  • Remove toxins and waste
  • Remove abnormal/damaged cells

5

What is the role of thrombocytes?

  • Controls bleeding, normal blood clotting
  • No nucleus - can't produce proteins
  • 8-9 day life span

6

What is haematopoiesis and where does it occur?

  • Process by which blood cells are produced 
  • Begins and primarily occurs in bone marrow

7

What Growth Factors are involved in Haematopoiesis?

  • EPO - erythropoiesis - produced in kidneys
  • TPO - thrombopoiesis
  • GM-CSF - leukopoiesis - progenitor cells
  • G-CSF - leukopoiesis - production of granulocytes
  • M-CSF - leukopoiesis - production of monocytes

8

Describe the regulation of Erythropoiesis

  1. Hypoxia: lowered amount of O2 reaching tissues
    • reduces O2 levels in blood
  2. Kidney releases erythropoietin
    • EPO stimulates red bone marrow
  3. Enhanced erythropoiesis increases RBC count
    • increases O2 carrying ability of blood
  4. Homeostasis

9

What is an important component of haemoglobin?

  • Iron (Fe)
  • Critical to function of RBC

10

Where is iron absorbed?

  • Dietary iron absorbed in duodenum and upper jejunum
    • haeme iron (meat)
    • inorganic iron

11

What is Ferratin?

  • Storage form of iron
  • Iron stored in liver

12

What form of iron is greatest absorbed?

  • Haeme > Fe2+ > Fe3+
    • iron with Vitamin C supplement helps promote conversion of Fe3+ to Fe2+

13

Describe the process of haemoglobin recycling

  • 3 pathways
    1. death of RBCs and phagocytosis by macrophages. Iron from haeme recycled via liver to bone marrow for production of new RBCs
    2. death of RBCs and phagocytosis by macrophages. Globin broken down to amino acids which are reused for protein synthesis
    3. death of RBCs and phagocytosis by macrophages. Haeme breakdown product biliverdin converted to bilirubin, conjugated in liver and excreted in faeces and urine

14

What are the steps of Haemostasis?

  1. Vascular Phase/Vasoconstriction
  2. Platelet Phase/ Primary Haemostasis
    • Adhesion
    • Activation
    • Aggregation
  3. Coagulation Phase/Secondary Haemostasis
  4. Fibrinolytic Phase/Thrombosis Removal

15

Describe Haemostasis: Vascular Phase/Vasoconstriction

  • Short lived, localised to a specific area
  • Minimises blood loss, slows blood flow at site of injury

16

Describe Haemostasis: Platelet Phase/Primary Haemostasis - Adhesion

  • Platelets interact with von Willebrand factor to become 'stuck'
  • von Willebrand factor (vWF) secreted by injured endothelium

17

Describe Haemostasis: Platelet Phase/Primary Haemostasis - Activation

  • Platelet activation triggered by collagen and other factors
  • Platelets change shape to become spherical with long dendritic extensions
    • extensions facilitate adhesion to exposed collagen
  • Interaction with collagen activates phospholipase A2 to convert membrane phospholipids to arachidonic acid
    • cycloxygenase converts A.A into prostaglandin G2, which is then converted into thromboxane A2 by thromboxane synthetase
    • Granules are released (triggered by thromboxane A2)
      • ADP + TXA2 
        • increased surface expression of GPIIb-IIIa
        • more activation
      • vWF
        • more adhesion
      • Ca2+
        • required for coagulation

18

Describe Haemostasis: Platelet Phase/Primary Haemostasis - Aggregation

  • Platelet ADP and TXA2 increase surface expression of glycoprotein receptors

19

Describe Haemostasis: Coagulation Phase/Secondary Haemostasis

  • Platelet plug relatively unstable
    • reinforced with fibrin to allow healing
  • Cascade of enzymatic coagulation reactions that leads to conversion of soluble fibrinogen to insoluble fibrin to form a stable fibrin clot

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20

Describe Anticoagulation Factors

  • Tissue Factor Pathway Inhibitor
  • Protein C
  • Protein S
  • Antithrombin
  • Prostacyclin (PGE2) [antiplatelet]

  • Tissue Factor Pathway Inhibitor
    • Produced by endothelial cells, inhibits tissue factor pathway of coagulation (extrinsic pathway)
  • Protein C
    • Vitamin K dependent, activated by thrombin, inactivates factors Va & VIIa
  • Protein S
    • Vitamin K dependent, cofactor in activation of Protein C, inhibits factor Va-Xa complex
  • Antithrombin
    • Inactivates factors IIa (thrombin), IXa, Xa, XIa, XIIa, triggers prostacyclin production
  • Prostacyclin
    • Inhibits action of TXA2 to inhibit platelet aggregation

21

Describe Haemostasis: Fibrinolytic Phase: Thrombosis Removal

  1. Tissue plasminogen activator (tPA) released by endothelial cells, binds to plasminogen on fibrin surface
  2. Plasminogen in thrombus converted to proteolytic enzyme plasmin
  3. Fibrinolysis occurs and thrombus dissolves

22

What is Anaemia?

  • A condition in which the number of RBCs or their oxygen-carrying capacity is insufficient to meet physiologic needs
  • OVERALL: insufficient function of haemoglobin

23

What are the signs of anaemia?

  • Eyes: yellowing
  • Skin: Paleness, yellowing
  • Central: fainting

24

What are the symptoms of anaemia?

  • Skin: coldness, angula cheilosis, atrophic glossitis
  • Respiratory: shortness of breath
  • Muscular: weakness
  • GI: loss of appetite, pica
  • Central: fatigue, headache, dizziness
  • Heart: chest pain, rapid heart rate, heart failure
  • Spleen: enlargement

25

Describe the characteristics of acute blood loss and its treatment

  • Normocytic, normochromic
  • Reticulocyte count increased
    • more erythropoiesis occurs
  • Treatment: control the source of bleeding as soon as possible and replace fluid

26

Describe the Characteristics of Haemolysis - Thalassemia

  • Alpha or Beta chain is normal but under-expressed or not expressed at all
  • Microcytic, hypochromic
  • Excess of unaffected chain
    • precipitate, causing damage to the membrane and RBCs, making them more likely to undergo haemolysis
  • Treatment:
    • blood transfusions
    • stem cell transplant

27

Describe the Characteristics of Haemolysis - Sickle Cell Anaemia

  • Point mutation of Beta chain of haemoglobin
  • Normocytic, normochromic
  • Still produced in normal quantities, just not the structure
    • sickle shape causes blood flow to be blocked
  • Treatment
    • transfusions
    • stem cell transplant
    • hydroxycarbamide (hydroxyurea)
      • increases faetal Hb which produces more functional haemoglobin
        • highber binding affinity for oxygen than adult haemoglobin

28

Describe the characteristics of nutrient deficiency: iron deficiency anaemia

  • Microcytic, hypochromic
  • Low ferritin levels
  • Causes:
    • chronic blood loss
    • insufficient dietary iron intake
    • poor absorption of iron from diet
    • increased iron requirements

29

Describe how smaller erythrocytes are produced in iron deficiency anaemia

  • An iron deficiency leads to a reduced production of haemoglobin
    • Reduced production of erythrocytes 
  • Erythrocytes each contain less haemoglobin
  • Body produces smaller erythrocytes in attempt to maintain haemoglobin concentration

30

List Oral Iron Supplements

  • Ferrous sulphate
  • Ferrous fumarate
  • Iron polymaltose

31

What are adverse effects of Oral Iron?

  • Black stools
  • Constipation
  • Diarrhoea
  • Nausea
  • Vomiting
  • Tooth Staining

32

What drug interactions cause occur with Oral Iron?

  • Iron can cause drug interactions by forming iron-drug complexes
  • Ferrous or ferric ions bind to many functional groups in drug structures
  • Reduces extent of absorption of iron and the drug involved

33

Describe the characteristics of iron polymaltose?

  • Polynuclear ferric oxyhydroxide is complexed with polysaccharide groups
    • iron is released gradually and absorbed by active transport
    • fewer and milder side effects
    • water soluble and not affected by pH
    • does not chelate with drugs or food

34

Describe the characteristics of Iron Overload

What are the causes?

What is treatment?

  • Macrocytic
  • Causes:
    • excess dietary iron
    • repeated blood transfusions
    • primary haemochromatosis
      • hereditary condition - excessive iron absorption
    • African iron overload
  • Treatment
    • iron chelators
      • forming a complex with non-transferrin-bound iron
      • promote iron excretion predominantly biliary (faecal)
    • Deferasirox, deferiprone, desferrioxamine

35

What are the characteristics of Polycythaemia and what are the types?

  • Increase in hematocrit
  • Too many RBCs
  • Relative Polycythaemia
  • Absolute Polycythaemia
    • Primary Polycythaemia
    • Secondary Polycythaemia

36

Desccribe the Characteristics of Relative Polycythaemia and how it can be treated

  • Absolute amount of RBCs is normal, plasma component reduced
  • Decrease in plasma volume
  • Results from any  cause of dehydration
  • Usually temporary and resolves with fluid administration 

37

Describe the Characteristics of Absolute Polycythaemia - Primary Polycythaemia, what it can result from and what it may be associated with

What is its treatment?

  • Actual increase in RBCs
  • Can result from:
    • bone marrow abnormality (WBCs and platelets increased too)
  • May be associated with:
    • High blood pressure/clots
    • Aquagenic pruritis
  • Can progress to leukaemia
  • Treatment
    • Phlebotomy (removing blood)
    • Hydroxyurea which inhibits DNA synthesis
    • Ruxolitinib
      • Janus Kinase Inhibitor
      • JAK2 mutation very common in PV which drives hyperproliferation of stem cells
        • Patients with PV: JAK2 mutation causes signalling to be amplified
      • This drug binds to JAK2 which stops it from working

38

Describe the Characteristics of Absolute Polycythaemia - Secondary Polycythaemia

 

  • Hypoxia
  • Erythropoietin secreting tumours
  • Excess erythropoietin administration

39

Describe the Characteristics of Anaemia of Chronic Renal Disease

  • Normocytic, normochromic
  • RBC count reduced
  • In severe renal impairment or renal failure, kidney fails to produce sufficient erythropoietin
    • decreasing erythropoietin levels
      • leading to decreased erythropoiesis and therefore a decreased oxygen carrying capacity of the blood

40

What can be used to treat Anaemia of Chronic Renal Disease?

  • Erythropoietin agonists can be used to treat this
    • mimic actions of erythropoietin to stimulate erythropoiesis in bone marrow
      • bind to EPO receptors on progenitor cells
    • Recombinant Human Erythropoietin
      • rhEpo - Epoietin alpha and beta
      • half-life 6-9 hrs
    • Synthetic Erythropoietin Analogue
      • Darbepoetin alpha
      • Two additional CHO chains
      • Half-life 25hrs, less frequent dosing

41

Describe the Characteristics of Vitamin B12 and Folic Acid Deficiency Anaemia

  • Macrocytic, normochromic erythrocytes are produced
  • Folate and Vitamin B12 required for DNA synthesis
    • when deficient, erythrocytes cannot divide and mature
    • RNA and Protein Synthesis continues

42

What are the causes of Vitamin B12 deficiency?

Additional Symptoms?

Treatment?

  • Poor intake or absorption due to:
    • postsurgical malabsorption
    • dietary deficiency
    • pernicious anaemia
  • Additional Symptoms
    • numbness/tingling in hands or feet
    • difficulty walking
    • memory loss, disorientation
  • Supplementation
    • cyanocobalamin
      • synthetic
      • shorter half life
      • oral and IV
    • hydroxocobalamin
      • naturally occuring
      • longer half life
      • IV
    • ultimately they are both converted to methylcobalamin following absorption

43

What are the causes of Folic Acid Deficiency and how is it treated?

  • Poor dietary intake:
    • destroyed by cooking
    • malabsorption or increased loss or utilisation
  • Supplementation
    • treated with oral folic acid supplements
    • ensures sufficient folate in the form required for DNA synthesis

44

What is aplastic anemia?

  • Bone marrow is failing due to:
    • toxic chemicals, drugs, infections, autoimmune diseases

45

What is leukaemia?

  • A group of cancers of the blood forming cells 
    • Starts in bone marrow
    • Stops normal cells being produced

46

What is chemotherapy?

  • Toxic agent that kill rapidly dividing cells

47

What is leucocytosis?

  • Abnormally high WBC count
  • May be normal response to pathogens
  • Pathologic i.e. cancers

48

What is leucopenia?

  • Abnormally low WBC count
  • Many potential causes
  • Increased risk of infection

49

What is neutrophilia?

What is it caused by?

  • High number of neutrophils
  • Caused by:
    • bacterial infections
    • acute inflammation
    • leukamia

50

What is neutropenia?

What is it caused by?

What are the symptoms?

  • Low levels of neutrophils
  • Caused by:
    • Drugs i.e. chemotherapy 
    • Radiation exposure
    • Aplastic anaemia
    • Marrow replacement by tumour
  • Symptoms:
    • sore throat
    • mouth ulcers
    • fever
    • chills

51

What is agranulocytosis?

  • More severe subset of neutropenia
  • Refers to a virtual absence of neutrophils in peripheral blood

52

What are the consequences of chemotherapy-induced neutropenia?

  • May increase risk of life-threatening infection
  • May disrupt delivery of cancer treatment

53

How is chemotherapy induced neutropenia treated?

Lenograstim

Filgrastim

Pegylated Filgrastim

  • Recombinant G-CSFs
    • used for prevention and treatment of neutropenia
      • stimulate production and differentiation of neutrophils
      • administered at least 24hrs after chemotherapy
    • Lenograstim
      • produced in chinese hampster ovary cell
      • identical to G-CSF
      • 1 daily injection
    • Filgrastim
      • produced in E-coli
      • protein sequence has additional N terminal methionine and non-glycosylated
      • 1 daily injection
      • Pegylated Filgrastim
        • attachment of polyethylene glycol polymer chains typically to a protein or drug molecule, increasing its stability
        • prolongs circulation time

54

What is the pathophysiology of leukaemia?

  • Immature myeloblast or lymphoblast stop maturing correctly
  • Start to replicate uncontrollably in the bone marrow and crowd out other normal blood cells
  • Mutation in the DNA in the blast cell

55

What are the symptoms of leukaemia?

  • Decreased RBCs: Shortness of Breath, Fatigue
  • Decreased WBCs: Increased Infection
  • Decreased Platelets: Increased Bleeding/Bruising
  • Bone Damage: Bone Pain
  • Increased Energy Expenditure: Weight loss, Fatigue

56

What are the types of Leukaemia?

  • Acute: progress rapidly, worsen quickly 
    • Characterised by uncontrolled division of immature WBCs
    • Acute lymphotic leukaemia
    • Acute myeloid leukaemia
  • Chronic: progress slowly, worsen over time 
    • Characterised by uncontrolled division of more mature WBCs
    • Chronic lymphotic leukaemia
    • Chronic myeloid leukaemia

57

How is Leukaemia Treated?

  • Chemotherapy
    • cytotoxic drugs that preferentially destroy rapidly dividing cells
  • Radiotherapy
  • High dose chemotherapy and Stem Cell Transplantation
  • Targeted treatments
    • monoclonal antibody (MAb) therapy
      • antibody (alemtuzumab [CD52], blinatumomab [CD19], rituximab [CD20]) binds to antigen on the cancerous B cell leading to lysis of the cell via:
        • complement-dependent cytotoxicity
        • antibody-dependent cell-mediated cytoxicity
        • direct apoptosis
  • Tyrosine Kinase Inhibitor Therapy
    • BCR-ABL is an oncogene in a chronic myeloid leukaemia cell
      • signalling mediator that is essential for initiation, maintenance and progression of CML, can also occur in ALL

58

What are the Adverse Reactions of MAb targeting CD19 and CD20?

  • Lymphopenia
    • infection
    • progressive multifocal leukoenephalopathy (PML)
      • JC virus acquired in childhood
      • reactivated in immunosuppressed individual
  • Infusion Reaction
    • severe allergy-like reactions
      • symptoms:
        • fever, chills, itching, alterations in blood pressure, nausea

59

What can Infusion Reactions be divided into?

  • Anaphylactic - Allergic Reaction
    • IgE mediated - involves the release of histamine-like substances
  • Anaphylactoid - Non-allergenic
    • Mass release of cytokines in body

60

What does alemtuzumab target, where is it found and what are the adverse effects?

  • Specifically targets cells expressing CD52
  • Found on B and T lymphocytes, monocytes, macrophages and some granulocytes
  • Adverse Effects:
    • infections, PML
    • infusion reactions

61

What is Lymphoma? (incl. Hodgkin Lymphoma and Non-Hodgkin Lymphoma)

  • Cancers of lymphocytes which orignate in the lymphoid tissues
    • e.g. thymus, spleen, liver, lymphatic system
  • Hodgkin Lymphoma
    • Reed Sternberg cells present
      • lymphocyte that has become cancerous
    • Other cell types may also be present
  • Non-Hodgkin Lymphoma
    • More common
    • Expansion of B, T or NK cells

62

What are the symptoms of lymphoma?

  • Swelling of lymphnodes
  • Weight loss, fatigue
  • Fever
  • Itching
  • Shortness of Breath

63

What is the treatment of lymphoma?

  • Chemotherapy
  • Radiotherapy
  • Targeted Therapies
    • MAb
      • Brentuximab Vedotin
        • MAb with cytotoxic agent bound
        • CD30 - positive Hodgkin lymphoma
    • Tyrosine Kinase Inhibitors
      • Brutons TK
        • important for B cell signalling
        • Involved in pathogenesis of B cell lymphoma
      • BTK inhibitor
        • Ibrutinib

64

What is Thrombosis?

  • Pathological formation of a 'haemostatic' plug within the vasculature in the absence of bleeding

65

What is the difference between a blood clot and thrombus?

  • Blood Clot: Forms in vitro, amorphous clot, diffuse fibrin meshwork in which red and white blood cells are trapped indiscriminately
  • Thrombus: Forms in vivo, arterial and venous thrombi have distinct structures

66

What are the factors that contribute to Thrombosis?

  • Hypercoagulant State
    • malignancy
    • thrombophilia
    • IBD
    • oestrogen therapy
  • Vascular Wall Injury
    • trauma or surgery
    • chemical irritation
    • atherosclerosis
    • indwelling catheters
  • Circulatory Stasis
    • arterial fibrillation
    • left ventricular dysfunction
    • immobility or paralysis
    • venous insufficiency or varicose veins

67

What are the Types of Thrombi?

What are they triggered by and what are there common causes?

  • Arterial thrombi
    • Triggered by damage to the endotheliu,
    • 'White' thrombus, consist of platelets in fibrin meshwork
    • Common Causes:
      • Ruptured atherosclerotic plaques
      • High blood pressure
      • Turbulent blood flow
  • Venous thrombi
    • Triggered by stasis or changes in coagulability of blood
    • 'Red' thrombus, consists of small 'white' platelet head with large jelly-like red tail
    • Common Causes:
      • Immobility
      • Inherited disorders
      • Certain cancers
      • Pregnancy

68

What are the Consequences of Thrombosis?

  • Blocked coronary artery which reduces blood flow to heart
    • myocardial infarction
  • Deep Vein Thrombosis
  • Thrombus that has moved around the body 
    • Thrombus in right atrium can become dislodged in pulmonary artery
      • pulmonary embolism
  • Ischaemic stroke

69

What is the purpose of laboratory assessment of coagulation?

  • Monitor how the pathways are functioning
    • test clotting time
      • intrinsic pathway: aPTT
      • extrinsic pathway: PT
        • INR

70

Describe the physiology behind the fibrinolytic cascade and what are the effects?

  • Activated along side the coagulation cascade
    • plasminogen converted to plasmin by tissue plasminogen activator (tPA) and other activators
    • regulated by plasminogen activator inhibitors (PAI) and a2-antiplasmin
  • Effects: limit the breakdown of fibrin to the actual clot

71

What are the Adverse Effects of t-PA analogues?

  • Alter haemostasis more profoundly than any other anticoaguants
    • greatest risk for bleeding complications
  • Contraindications to fibrinolysis
  • Concurrent antiplatelet or anticoagulant drugs increase risk of bleeding but combinations can be required

72

Causes of Increased Bleeding?

  • Platelets disorders
    • Thrombocytopenia
      • decreased production
        • leukaemia
        • drug-induced bone marrow dysfunction
      • increased destruction
        • autoimmune
        • drug induced
  • Decreased coagulation
    • Vitamin K deficiency
      • haemorrhagic disease of the newborn
      • malabsorption - liver disease
    • liver disease
    • anticoagulants
    • haemophilia