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
What does the canalicular system do
Increases surface area to make pseudos
26
What do ADP and serotonin do
Activates platelets so they secrete more vWF/TXA2 so more platelets are activated
27
How to do a platelet count
By impedance or fluorescence/optical
28
Normal platelet count
150-400 x 10^9/L
29
What is IPF
Immature platelet fraction Uses fluorescence to detect young platelets
30
What does a raised IPF mean
More young platelets Increased destruction so body is trying to keep up
31
What does a low IPF mean
Less young platelets Bone marrow suppression or failure
32
Techniques for investigating platelets
Morphology Platelet function - PFA/bleeding times IPF Platelet count
33
Bleeding time test ref interval
2-8mins
34
Bleeding time test steps
1. Sphygmomanometer at 40mmHg to keep vessels open 2. Standardised incision 3. Blot blood every 30 secs on edges
35
Who is the bleeding time test not suitable for
Uncooperative patients like kids, thin skinned elderly , abnormal skin with scarring on forearms
36
What is a PFA
Platelet function assay Replaced bleeding test
37
Steps of platelet function assay (PFA)
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
Principle of PFA
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
Technical error with PFA
Shaking tube, age of specimen, temp, volume of blood, not using citrated blood
40
Bleeding time errors
Cuff pressure, skin thickness, superficial veins, plug dislodged by blotting, depth of cut
41
What can affect PFA and bleeding time
Drugs like aspirin Garlic, ginger, chocolate, alcohol
42
What is platelet aggregometry
Measuring how platelets aggregate in platelet rich plasma or whole blood by photometry or impedance
43
What induces aggregation in platelet aggregometry
Thrombin, ADP, adrenaline, college, arachidonic acid
44
What is measured in platelet aggregometry
The change in light transmission As platelets aggregate
45
Platelet count where a transfusion is needed
10 x 10^9/L Febrile then 20
46
How do you get selective depression of megakaryocytes (acquired thrombocytopenia)
Viral infections Drug induced hypoplasia
47
What causes global marrow failure (acquired thrombocytopenia)
Chemo Marrow infiltration Aplastic anaemia Megaloblastic anaemia
48
What is May-Hegin anomaly - presentation and treatment
Rare MYH9 inherited thrombocytopenia Dohle bodies No treatment maybe platelet transfusions
49
Thrombocytopenia from increased destruction causes
ITP - immune thrombocytopenia Drug induced thrombocytopenia
50
Drug induced thrombocytopenia methods
Antibiotics Marrow suppression Platelet autoantibodies Immune complexes Drug induced thrombotic microangiopathy
51
Thrombocytopenia from consumption causes
DIC MAHA- TTP/HUS Circulating immune complexes from viral infections/drug reactions/autoantibodies
52
ITP causes
Idiopathic - don’t know where antibodies are coming from Secondary to another infection/autoimmune disease/lympho proliferative disorder
53
What happens in ITP
Anti platelet antibodies react with platelet receptors Platelets are cleared by the macrophages as platelets are tagged with antibodies (IgG specific to spleen)
54
What happens to platelet production in ITP
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
ITP cause in children and prognosis
Post viral or vaccination Settles on its own over a couple weeks Less bleeding risk
56
ITP in pregnancy
Common in healthy women Caused by HELLP Wait and see approach
57
Drug induced ITP method
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
Platelet count in drug induced ITP
Severely low Less than 10
59
What drugs cause drug induced ITP
Anti malarial Quinine Quinidine Sulphonamides
60
What happens in heparin induced thrombocytopenia
Antibodies to platelet factor 4 and heparin complex Triggers activation and consumption
61
Lab findings for ITP
10-50 x10^9 platelets Raised IPF Less bleeding than patients with reduced patient function
62
IgG in ITP
Can cross the placenta Leads to fetus having thrombocytopenia at birth
63
Treatment of ITP
Watch and wait Treat underlying Stop drug used Corticosteroids high dose High dose IgG to compete Rituximab TPO receptor agonists Splenectomy
64
Do you give plasma concentrates in ITL
Only if life threatening bleeding
65
Odd thrombocytopenia causes
Splenomegaly DilutionL after a massive transfusion Pseud-thrombocytopenia
66
Pseudo thrombocytopenia
Clotted sample Large platelets counted as RBC EDTA- need citrate or dilute with gentamicin
67
Thrombocytopenia in pregnancy
Large playlets are common May be dilutional HELLP
68
HELLP stands for
Haemolysis, elevated liver enzymes, low platelets
69
Who does HELLP affect
Women with high BP/ pre eclampsia
70
HELLP solutions
Resolves after delivery Unknown mechanism
71
Acquired platelet function disorders from
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
NSAIDs affect on platelet function
NSAIDs block COX1 impairing platelet function Less thromboxane A2 made so less platelet aggregation will happen
73
How long does aspirin block COX1
Permanent
74
What is vWF
Having low of dysfunctional vWF Mild reduction in factor 8
75
Bleeding pattern in vWD
Bruising and oozing from cuts Mucosal bleeding, nose, heavy periods leading to IDA
76
3 types of vWD
1. Quantitative decrease but normal function 2. Qualitative defect - 4 subtypes 3. Complete or partial lack of vWF and so low factor 8
77
vWD treatment
Desmopressin Blood products with vWF (if moderate/severe or surgery) Avoid NASAIDs as platelet function worsens Fibrinolytic inhibitor
78
What does DDAVP do
Boosts endogenous release of vWF Good for mild cases
79
vWF activity assay reagents
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
What does the vWF activity assay measure
vWF binding to GP1b on platelets
81
Lab findings vWD type 1