Home / Summaries / Class notes - MOD2 / platelet-aggregation-vwf

LT 42-43

46 important questions on LT 42-43

Balance when youg et bleedings?

Anticoagulant is more than procoagulant.

What are mucosal bleedings?

We often see in defects of platelets.

What is a muscle hematom?

bleeding is more deeper int he muscle and you see hematoma in the skin.

What is a subconjunctival bleeding?

Bleeding in the eye, patients that are using anticoagulant medication

What is the mechanism of hemostasis when we get vessel injury?

Vessel injury -> vasoconstriction -> reduced blood flow -> primary aehmostatic plug
Platelet adhesion -> platelet activation (shape, change, granule secretion and activation of GPIIb/IIa -> platelet aggregation -> primary haemostatic plug -> stable haemostatic plug

Tissue factor -> blood ocagulation cascade -> thrombin -> fibrin -> stable aemostatic plug (secondary hemostasis)

Which receptors bind immediately to the collagen, which indirectly?

GPVI and GPIa bind to the collagen via glycoprotein receptors on the platelet membrane.
GPIb binds to VWF.
VWF is often inactive, so it only becomes activated when it is bound to the collagen

What happens when the receptors become activated?

When receptors become activated, they activate the platelets. When the platelets become activated, they secrete all ind of substances, like ADP and thromboxane, that causes the paltelts in the surrounding to become activated as well.

GPIIb/IIa gets exposed on the cell surface (is only there when platelet is activated, and this binds to fibrinogen, fibronectin and Von Willebrand factor. Called aggregation.

To which receptor does thromboxane bind?

TXA2R

What is factor VIII?

Clotting factor in secondary hemostasis, that is carried by vWF.
It doesn't play a role int he platelet adhesion

In platelet aggregation you get a release reaction, what is released?

Alpha granules: VWF and fibrinogen
Dense granulse: serotonin -> increases vasoconstriction, ADP -> bind to othre ADP receptors and further activate the platelets
Thromboxane A2 (TxA2) : cyclo-oxygenase converts arachidnoic acid (AA) into TxA2

What is the function of ADP?

Binds to other ADP receptosr and causes fruther activation of the platelets.

relased by dense granules

What is the alfa-IIb-beta-3 integrin?

GPIIb/IIIa, becomes present on the cell surface when platelets are activated
Causes platelet aggregation and can bind fibrinogen, fibronectin and VWF

What is alfa2beta1 integrin?

GP1A, can bind collagen

What is the role of endothelial cells?

Endothelial is an important barrier to prevent the blood contacting with tissue.
Barrier between blood and tissue.
- no contact with collagen
- no contact with tissue factor.

Intact endothelium thus prevents
- adhesion and aggretation of platetlets
- initation of coagulation

What are anti-thrombotic properties?

Vasodilatation and inhibition of aggregation
- prostacyclin (PGI2)
- NO

Inhibition of coagulation
- thrombomodulin
- heparin-like glycosaminoglycans
- tissue factor pathway inhibitor (TFPI)

Activation of fibrinolysis
- tissue plasminogen activator (tPA)

What is the function of tPA?

fibrinolytic cascade

What happens when thrombin binds to thrombomodulin??

This activates protein C, which gives protelysis of factors Va and VIIIa

What are causes of a defective platelet function?

Thrombocytopathia
Causes:
- congenital platelet defects
- acquired platelet defects
- medication (platelet aggregation inhibitors), many medications are intended to reduce the platelet function, eg asprin

What is a congenital platelet functiond efect?

something wrong with the GPIb receptor, not able to make the connection with VWF.
This inhibits the affectiveness in adhesion. Inhibition of the adhesion is called Bernard-soulier syndrome or Glanzmann thrombasthenia.

Storage pool disease

receptor defect

What is Glanzmann thrombasthenia?

Glanzmann thrombasthenia, you can't have any aggregation. Only one receptor is involved. GPIIb/IIIa namelijk, en die is er niet meer

What is storage pool disease?

Reduction in number of content of granules
Dense and alpha granules
- alpha: VWF, fibrinogen
- dense: serotonin, ADP

What is receptor defect?

congenital paltelet dysfunction.
- ADP receptor -> if you lack ADP receptor you can still activate the platelet via other receptors
- thromboxane A2 receptor
- colalgen receptors (GPVI and GPIa)

What are required platelet function defects/

renal insufficiency: uremia
Liver cirrhosis: bad functioning of the platelets

What are platelet aggregation inhibitors/

Thromboxane is produced by the platelets out of arachidnoic acid via cyclo-oxygenase. It binds to the receptor and activates the platelets

aspirin: irreversible, not possible to make thromboxane, only a minimal amount, will not regain its enzyme function any more

NSAID: reversible, they inhibit the paltelet funtion

What does clopidogrel (PLAVIX?)

clopidogrel (plavix) blocks the ADP receptors.

What does prasugrel (efient)

Blocks the ADP receptors

What does abiciximab (reopro)?

blocks the GPIIb/IIa receptor, hierdoro kan VWF er niet meer aan binden. It completely inhibits the aggregation and induces a major risk of bleeding.
only used inside the hospital during procedures of the cardiologist

What is Von Willebrand Disease?

Bleeding disorder caused by inherited defects in the concentration, structure or function of von Willebrand Factor.

What is VWD type 2a?

Less affinity for the receptor, lack of high molecular multimers, less platelet binding

Inw hich classification of VWD do you ahve lack of high molecular HMW) multimers?

Type 1: everything is there, but in lower concentration
Type 2A: only the small bands, large bands are missing
Type 2B: spontaneous binding, due to this the large multimers also disappear from the circulation in the endothelial cells the multimers re in normal distribution
Typ 3, no HM

What is VWD type 2B?

No connection of VWF to the endothelium, but VWF is still able to bind GPIb.
The platelets are removed by the spleen and liver from the circulation
You get spontaneous platelet agglutination , consumption of VWF and platelets.

So increased affinity for GPIb, spontaneous binding

What is VWD type 2N?

Defects in VII and thereby looks like hemophilia
Reduced binding affinity for factor VIII
Normal platelet adhesion and aggregation, reduced FVIII levels, resembles hemophilia A

What diagnostic tests for primary hemostasis?

Screening:
platelet count
bleeding time
platelet function analyser

Specific test:
VWF concentration
VWF function
Platelet aggregation -> how are paltelets able to clot together, identify which receptors are msising

How do you measure the bleeding time?

Two incisions or three punctures in lower arm
Time until bleeding stops
Intertechnican variability

What is the paltelet function analyser?

PFA100 you measure the closure time
- vessel damage, platelets start to stick to the colalgen and some time it closes the gap. You measure when the gap is closed

In the machine, they draw blood from the patient, and that is sucked up through a capillary int he machine. Collagen coated membrane, with some substances that activate the paltelet. when the blood is flowing through a tiny hole, plateltes start tos tick to the collagen, VWF, and at some point it is cloed, recognize dby the machine as there is no flow any more

How do you test the paltelet aggregation?

Take the blood of the individual and centrifuge it.
Ultimately you will end up with plasma with only platelets.
If you put an agonist in it (ADP could activate paltelets by ADP recpetor), the plates are being activated and start to clot.

They make use of VWF in the plasma and all the receptors on the platelets.
You get a clump and when they clump the plasma becomes more clear.
Transmitted light through the tube, the more ligth through the tube, the better the plateelt aggregation

Explain why the platelet aggregation test is used to discriminate type 2B Vwd.

iF YOU ADD RISTOCETIN TO THE PLASMA, YOU ACTIVATE vwf, NORMALLY YOU HAVE TO ADD A LOT OF RISOCETIN,
BUT INT YPE 2B, vwf IS ALWAYS ACTIVATED, so the aggregation is increased as well.
even in the situation where you add low or very little ristocetin

What was the role of Trousseae, 1865?

If you ahve a thrombophlebitis is a presetingin sign of a malignancy that has not been recognized yet.
Superficial vessel that becomes thrombotic and inflamed may be a sign of thrombosis.

What did Jean-Baptiste Bouillaud say over cancer/

Peripheral edema may be a sign of cancer, due to obstruction of the vessels.

What is the pathway via selections of tumor cells?

Tumor cells express E-selectin and P-selectin
E-selectin endothelial cells -> actiation of eendothelials secreting evWF
P-selectin binds to platelets, this gives platelet aggregation and ultimately clotting -> meatasis or cancer coagulophathies

COX activates prostaglandins and thromboxanes, which alos leads to platelet aggregation

What is the risk of venous thrombosis in cancer patients?

Patients with cancer have an increased risk for developing venous thrombosis
OR: 7
Incidence: 24/1000/yr

Risk and time since diagnosis cancer
0-3 months: OR 54
3-12 months: OR 14
12-37 months: OR 4

What are determinants of risk for thrombosis in cancer paitents?

Type of malignancy
- hematological malignancy OR 28
- lung cancer OR 22
- gastro-intestinal malignancy OR 20
- breast cancer OR 5

Metastasis and chemotherapy

Prothrombic mutations with cancer
- Factor V Leiden: OR 12

What are the risks for cancer pateients for idiopathic venous thrombosis, provoked venous thrombosis and single episode of superficial thrombophleibits?

Idiopathic (unprovoked) venous thrmobosis: 10% will develop cancer in 3 years
Provoked venous thrombosis: 1,6% will develop cancer in 3 years
Single episoe of superficial thromboplebitis: no clear association with cancer

How great is the chance of dying in DVT/pulmonary embolism? Malignant disease? DVT/pE?

DVT/PE, 20%
Malignant disease: 40%
Patients with caner had a higher risk of dying when they also had thrombosis

How is venous thrombosis treated?

in cancer patients lower molecular weight heparin (LMWH) is more effective than vitamin K antagonists in prevention of recurent venous thrombosis.
During treatment for 6 months, recurrent thrombosis in:
- LMWH 27/336
- vit K antagonist 53/336

Hazard rate 0,48

However no difference in survival

So treatment for 6 months with LMWH in therapeutic dosage
If continuation after that time is necessary, switch to vitamin K antagonists

What is the relation between aspirin and cancer incidence?

Low dose asprin
- reduction of colorectal canceri ndicence by prophylactic use of aspirin
- reduction of metastasis by use of asprin

this is an indication that interfering witht he coagulation system may have influence on cancer prognosis

a PDF, study it super fast

No sign up, email or credit card needed!
AI makes unlimited flashcards
Get unlimited quizzes and tests
Ask AI anything

Create a notebook

No sign up, email or credit card needed!
Have and keep perfect overview
Make flashcards, notes and mind maps
Review, test and score!

The question on the page originate from the summary of the following study material:

MOD2

View summary

A unique study and practice tool
Never study anything twice again
Get the grades you hope for
100% sure, 100% understanding

Remember faster, study better. Scientifically proven.