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MELS302 > Haemostasis > Flashcards

Haemostasis Flashcards

1
Q

What does glycocalyx do

A

Inhibits activation of platelets and coagulation

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2
Q

What does nitric oxide (NO) do

A

Promotes vasodilation
Inhibits platelet recruitment and activation

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3
Q

What does prostacyclin do (PGI2)

A

Primitives vasodilation
Inhibits platelet activation

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4
Q

What does normal endothelium secrets

A

Anti thrombosis things like NO, PGI2, glycocalyx and ADPase

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5
Q

What promotes thrombosis

A

Activated endothelium - when it is injuried it will release thromboxane A2, PAF, ET to aid this

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6
Q

What does endothelin do

A

Promotes vasoconstriction and helps platelets come together - crucial in larger vessels
Released by surrounding intact endothelial cells

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7
Q

What does thromboxane A2 do

A

Activates and recruits platelets

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8
Q

Inherited vascular disorders

A

Rare

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9
Q

Acquired vascular disorders

A

Old age - loss of collagen = purpura
Prolonged steroid purpura
Infection
Scurvy
Henoch

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10
Q

Platelet lifespan

A

7-10 days

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11
Q

Where are platelets made

A

From megKaryocytes in the bone marrow

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12
Q

Where are platelets found

A

In circulation
25% in spleen

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13
Q

What is endomitosis

A

The cytoplasm/cell doesn’t divide just the nucleus
This happens to the megakaryocytes and the platelets bud off it’s cytoplasm

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14
Q

What IL stimulates endomitosis

A

IL 6 and 11
TPO does the whole thing

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15
Q

GPIa does what

A

Helps platelets bind to collagen in BM/tissues

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16
Q

How do platelets bind to vWF

A

GPIIb/GPIIIa and GPIb/IX/V

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17
Q

What do cell adhesion ligand do

A

This links platelets to collagen in high shear force places and is made by endothelial cells and megakaryocytes

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18
Q

What does adhesion of platelets to endothelium lead too

A

Binding of GPIIb/GPIIIa
Leads to conformational changes
Now fibrinogen can bind and vWF and collagen

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19
Q

Where is vWF found

A

In platelet alpha granules
Endothelial cells weibel-palade bodies

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20
Q

Why does vWF bind to factor 8

A

To prevent proteolytic degradation

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21
Q

After platelet activation what happens to it physically

A

Shape changes from disk to sphere with pseudopodia
GPIIb/GPIIIa binds vWF/fibrinogen
Secretion of granules

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22
Q

Is platelet activation reversible

A

Depends on stimuli
If weak - partial degranulation is reversible
If strong - completely degranulatex then it is irreversible aggregation

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23
Q

What is inside platelet alpha granules

A

Fibrinogen, vWF, PDGF, PF4

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24
Q

What is inside dense platelet granules

A

ATP
ADP
Ca
Adrenaline
Serotonin

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25
Q

What does the canalicular system do

A

Increases surface area to make pseudos

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26
Q

What do ADP and serotonin do

A

Activates platelets so they secrete more vWF/TXA2 so more platelets are activated

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27
Q

How to do a platelet count

A

By impedance or fluorescence/optical

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28
Q

Normal platelet count

A

150-400 x 10^9/L

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29
Q

What is IPF

A

Immature platelet fraction
Uses fluorescence to detect young platelets

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30
Q

What does a raised IPF mean

A

More young platelets
Increased destruction so body is trying to keep up

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31
Q

What does a low IPF mean

A

Less young platelets
Bone marrow suppression or failure

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32
Q

Techniques for investigating platelets

A

Morphology
Platelet function - PFA/bleeding times
IPF
Platelet count

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33
Q

Bleeding time test ref interval

A

2-8mins

34
Q

Bleeding time test steps

A
  1. Sphygmomanometer at 40mmHg to keep vessels open
  2. Standardised incision
  3. Blot blood every 30 secs on edges
35
Q

Who is the bleeding time test not suitable for

A

Uncooperative patients like kids, thin skinned elderly , abnormal skin with scarring on forearms

36
Q

What is a PFA

A

Platelet function assay
Replaced bleeding test

37
Q

Steps of platelet function assay (PFA)

A

Fresh citrates blood onto analyser
Cartridge capillary is coated in collagen Adrenalin/ADP
So platelets are activated and adhere and release granules and get more platelets
Many aggregate to GPIIa/b receptors
Platelet plug made

38
Q

Principle of PFA

A

Blood is mixed with collagen-adrenaline or ADP to promote platelet activation and release
How long it takes for the platelet plug to be made is measured so we can see if platelets are working

39
Q

Technical error with PFA

A

Shaking tube, age of specimen, temp, volume of blood, not using citrated blood

40
Q

Bleeding time errors

A

Cuff pressure, skin thickness, superficial veins, plug dislodged by blotting, depth of cut

41
Q

What can affect PFA and bleeding time

A

Drugs like aspirin
Garlic, ginger, chocolate, alcohol

42
Q

What is platelet aggregometry

A

Measuring how platelets aggregate in platelet rich plasma or whole blood by photometry or impedance

43
Q

What induces aggregation in platelet aggregometry

A

Thrombin, ADP, adrenaline, college, arachidonic acid

44
Q

What is measured in platelet aggregometry

A

The change in light transmission
As platelets aggregate

45
Q

Platelet count where a transfusion is needed

A

10 x 10^9/L
Febrile then 20

46
Q

How do you get selective depression of megakaryocytes (acquired thrombocytopenia)

A

Viral infections
Drug induced hypoplasia

47
Q

What causes global marrow failure (acquired thrombocytopenia)

A

Chemo
Marrow infiltration
Aplastic anaemia
Megaloblastic anaemia

48
Q

What is May-Hegin anomaly - presentation and treatment

A

Rare
MYH9 inherited thrombocytopenia
Dohle bodies
No treatment maybe platelet transfusions

49
Q

Thrombocytopenia from increased destruction causes

A

ITP - immune thrombocytopenia
Drug induced thrombocytopenia

50
Q

Drug induced thrombocytopenia methods

A

Antibiotics
Marrow suppression
Platelet autoantibodies
Immune complexes
Drug induced thrombotic microangiopathy

51
Q

Thrombocytopenia from consumption causes

A

DIC
MAHA- TTP/HUS
Circulating immune complexes from viral infections/drug reactions/autoantibodies

52
Q

ITP causes

A

Idiopathic - don’t know where antibodies are coming from
Secondary to another infection/autoimmune disease/lympho proliferative disorder

53
Q

What happens in ITP

A

Anti platelet antibodies react with platelet receptors
Platelets are cleared by the macrophages as platelets are tagged with antibodies (IgG specific to spleen)

54
Q

What happens to platelet production in ITP

A

It increases to keep up with the demand but the platelets are just being mopped up by antibodies anyways
Can decrease if autoantibodies affect the megakaryocytes

55
Q

ITP cause in children and prognosis

A

Post viral or vaccination
Settles on its own over a couple weeks
Less bleeding risk

56
Q

ITP in pregnancy

A

Common in healthy women
Caused by HELLP
Wait and see approach

57
Q

Drug induced ITP method

A

Drug binds to plasma proteins
Acts as a hapten
Anti drug immune response
Next exposure makes immune complex with protein-drug-antibody-complement
This complex attaches to a platelet
Platelet activated or phagocytosed with immune complex

58
Q

Platelet count in drug induced ITP

A

Severely low
Less than 10

59
Q

What drugs cause drug induced ITP

A

Anti malarial
Quinine
Quinidine
Sulphonamides

60
Q

What happens in heparin induced thrombocytopenia

A

Antibodies to platelet factor 4 and heparin complex
Triggers activation and consumption

61
Q

Lab findings for ITP

A

10-50 x10^9 platelets
Raised IPF
Less bleeding than patients with reduced patient function

62
Q

IgG in ITP

A

Can cross the placenta
Leads to fetus having thrombocytopenia at birth

63
Q

Treatment of ITP

A

Watch and wait
Treat underlying
Stop drug used
Corticosteroids high dose
High dose IgG to compete
Rituximab
TPO receptor agonists
Splenectomy

64
Q

Do you give plasma concentrates in ITL

A

Only if life threatening bleeding

65
Q

Odd thrombocytopenia causes

A

Splenomegaly
DilutionL after a massive transfusion
Pseud-thrombocytopenia

66
Q

Pseudo thrombocytopenia

A

Clotted sample
Large platelets counted as RBC
EDTA- need citrate or dilute with gentamicin

67
Q

Thrombocytopenia in pregnancy

A

Large playlets are common
May be dilutional
HELLP

68
Q

HELLP stands for

A

Haemolysis, elevated liver enzymes, low platelets

69
Q

Who does HELLP affect

A

Women with high BP/ pre eclampsia

70
Q

HELLP solutions

A

Resolves after delivery
Unknown mechanism

71
Q

Acquired platelet function disorders from

A

Myeloproliferative disorders
Renal failure (toxic products in way of binding)
Hyperglobulinaemia (plasma cell myeloma)
Cardiac bypass surgery (platelet activation as it goes through pumps)
Drugs like aspirin inhibit platelets prostaglandin synthetic pathway

72
Q

NSAIDs affect on platelet function

A

NSAIDs block COX1 impairing platelet function
Less thromboxane A2 made so less platelet aggregation will happen

73
Q

How long does aspirin block COX1

A

Permanent

74
Q

What is vWF

A

Having low of dysfunctional vWF
Mild reduction in factor 8

75
Q

Bleeding pattern in vWD

A

Bruising and oozing from cuts
Mucosal bleeding, nose, heavy periods leading to IDA

76
Q

3 types of vWD

A
  1. Quantitative decrease but normal function
  2. Qualitative defect - 4 subtypes
  3. Complete or partial lack of vWF and so low factor 8
77
Q

vWD treatment

A

Desmopressin
Blood products with vWF (if moderate/severe or surgery)
Avoid NASAIDs as platelet function worsens
Fibrinolytic inhibitor

78
Q

What does DDAVP do

A

Boosts endogenous release of vWF
Good for mild cases

79
Q

vWF activity assay reagents

A

Polystyrene particles coated with anti GP1b antibodies
vWF in patient sample
Recombinant GP1b

All this aggregates and leads to increased absorbance measured by turbidity

80
Q

What does the vWF activity assay measure

A

vWF binding to GP1b on platelets

81
Q

Lab findings vWD type 1

A

MELS302 (6 decks)

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