Introduction to bleeding disorders.

Question 1

In haemostatic balance what 2 factors are balance

Answer 1

bleeding (anti-coagulant)

clotting (procoagulant)

Question 2

what is the first step which results in the activation of a haemostatic plug forming

Answer 2

disruption to the BV wall

Question 3

what molecule do platelets adhere to

Answer 3

vWF

Question 4

what molecule does vWF attach to

Answer 4

collagen

Question 5

what molecule does thrombin activate

Answer 5

fibrin

Question 6

where does thromboxane synthesis take place

Answer 6

inside the platelet

Question 7

what is the purpose of thromboxane

Answer 7

contacts blood vessels and activates platelets.

Question 8

2 important receptors found on the plasma membrane of a platelet.

Answer 8

IIaIIIA- receptor for fibrinogen= platelet aggregation.

IBIX- receptor for vWF=platelet adhesion

Question 9

aspirin inhibits cycloxygenase, what is the function of cycloxygenase

Answer 9

produce thromboxane.

Question 10

what molecule does clopidogrel inhibit

Answer 10

ADP

Question 11

what happens in the extrinsic pathway.

Answer 11

1. Tissue factor expressed on injurged cells= damage BV

2. Activates VII-VIIa, this activates X- Xa, this activated prothrombin to thrombin which converts fibrinogen to fibrin.

Question 12

what happens in the intrinsic pathway

Answer 12

1. XIIa-XIIa, which converts XI-XIa, which converts IX-IXa.

2. activates X- Xa, this activated prothrombin to thrombin which converts fibrinogen to fibrin.

Question 13

what are the procoagulant molecules.

Answer 13

platelets

clotting factors

Question 14

what are the anticoagulant molecules

Answer 14

Protein C
Protein S- co factor protein C.
Anti-thrombin III
Fibrinolytic system- breaks down the clot when it is no longer needed.

Question 15

what is the fibrinolytic pathway

Answer 15

Tissue plasminogen factor (TPA) breakdown plasminogen to plasmin.
Plasmin then converts fibrin into a fibrin degradation product.
This happens on the surface of a clot.
TPA use for clot busting in acute MI.

Question 16

What are the different types of bleeding disorders

Answer 16

congenital
acquired
platelet
vessel wall
coagulation defect

Question 17

What drug can cause abnormal platelet function (Blood thinner)

Answer 17

aspirin

Question 18

what condition is caused by abnormal interaction between the vessel wall and platelets

Answer 18

von willibrand factor.

Question 19

what are the major difference between platelet and coagulation defects

Answer 19

platelet defects- affect skin and mucosal membranes and form petichae and bruising on skin
coagulation defects- affect spreading haematoma and haemoarthrosis, affect retroperrtioneal bleeding which is often recurrent and prolonged.

Question 20

do petichae blache when pressure is applied

Answer 20

no.

Question 21

Von Willebrand disease is caused by a deficiency in which molecule

Answer 21

platelets

Question 22

what type of genetic disorder is von willebrand factor

Answer 22

autosomal dominant.

Question 23

what factor is reduced in von willebrand disease

Answer 23

factor 8 (FVIII)

Question 24

which blood group has lower levels of von willebrand factor

Answer 24

blood group O

Question 25

what are common consequences of von willebrand disease

Answer 25

* Mucocutaneous bleeding including menorrhagia | * Postoperative and post partum bleeding

Question 26

are there different types of von willebrand factor, in terms of disease.

Answer 26

yes there are mild and more severe forms.

Question 27

what is the treatment that is provided for von willebrand factor disease

Answer 27

Antifibrinolytics: tranexamic acid (important in mouth bleeds) DDAVP- releases VWF from stores in endothelial cells. factor concentrates of VWF vaccination against hepatitis COCP (combined oral contraceptive pill) for menorrhagia

Question 28

haemophilllia a is a deficnecy in which factor

Answer 28

factor VII

Question 29

haemophillia b is a deficnency in whihc factor

Answer 29

factor IX.

Question 30

what type of genetic inherited disorder are the haemophillias

Answer 30

x-linked.

Question 31

what is the function of the drug DDAVP

Answer 31

release vWF form endothelial cells.

Question 32

are there degrees of severity in haemophilia

Answer 32

yes | normal, mild, moderate and severe.

Question 33

what are the different types of bleeds occur in haemophilia

Answer 33

``` spontaneous/post traumatic joint bleeding- haemarthorosis. muscle- haemorrhage soft tissue- mouth bleed and intracranial bleed. life threatening bleed in the airways. ```

Question 34

what is acute and chronic haemophilic arthropathy- which is a complication of haemophilia

Answer 34

swollen bone deformity | muscle wasting

Question 35

treatment for haemophilia

Answer 35

``` Replacement of missing clotting protein DDAVP factor concentrates antifibrinolytic agents vaccine for hep A and hep B ```

Question 36

complications of treatment from haemophilia treatment

Answer 36

Infections- Hep A,B,C,G, HIV, paravirus, vCJD. Inhibitor development (more common in haemophilia A)- patients become resistant to replacement therapy.

Question 37

How is haemophilia managed

Answer 37

Haemophilia Centres and Comprehensive care Centres. Multidisciplinary Approach Home treatment Patient Education and Social Support Physiotherapy Orthopaedic Advice & Treatment Treatment & Diagnosis of Liver Disease Specialised Management for HIV Positive Patients Genetic Counselling & Parental Diagnosis

Question 38

appropriate investigations if you suspect a bleeding disorder.

Answer 38

``` Full blood count and blood film Coagulation screen Mixing studies if abnormal results Refer to a haematologist if history suspicious Von Willebrand profile platelet function tests ```

Question 39

what conditions does the bleeding /normal coagulation screen show.

Answer 39

```  Thrombocytopenia  Disorder of platelet function  vWD  Factor XIII deficiency  Mild coagulation factor deficiency  Vascular disorder  Disorder of fibrinolysis: rare ```