Haemostasis - Bleeding: Disorders of Primary Haemostasis

Question 1

What is haemostasis?

Answer 1

the cellular and biochemical processes that enables both the specific and regulated cessation of bleeding in response to vascular injury

Question 2

What is haemostasis for?

Answer 2

Prevention of blood loss from intact vessels
Arrest bleeding from injured vessels
enable tissue repair

Question 3

Briefly outline the process of haemostasis.

Answer 3

vessel constriction > primary haemostasis > secondary haemostasis > fibrinolysis

Question 4

What is involved in primary haemostasis?

Answer 4

formation of an unstable platelet plug (platelet adhesion/aggregation)

Question 5

What is involved in secondary haemostasis?

Answer 5

stabilisation of the plug with fibrin (blood coagulation)

Question 6

What is involved in fibrinolysis?

Answer 6

vessel repair + dissolution of clot (cell migration/proliferation)

Question 7

Why do we need to understand haemostatic mechanisms?

Answer 7

diagnose/treat bleeding disorders, control bleeding, identify risk factors for thrombosis, treat thrombotic disorders, monitor drugs used for treatment

Question 8

Normal haemostasis is a balance between?

Answer 8

bleeding vs thrombosis

fibrinolytic factors, anticoagulant proteins vs platelets, coagulant factors

Question 9

What are two reasons why haemostatic balance is tipped towards bleeding?

Answer 9

lack of specific factor (production failure, increased clearance) or defective fx of specific factor (genetic or acquired)

Question 10

In what two ways does platelet adhesion occur?

Answer 10

indirectly via VWF + GIpIb or directly to collagen via GIpIa

Question 11

The release of what factors causes platelet aggregation?

Answer 11

release of ADP and thromboxane

Question 12

What factors are involved in platelet aggregation?

Answer 12

Ca2+

fibrinogen

Question 13

What is low numbers of platelets called?

Answer 13

thrombocytopenia

Question 14

Causes of low platelets?

Answer 14

bone marrow failure e.g. leukaemia, B12 deficiency

accelerated clearance e.g. ITP, disseminated intravascular coagulation

Question 15

What does ITP stand for?

Answer 15

immune thrombocytopenic purpura

Question 16

Categorise platelet disorders.

Answer 16

low numbers (thrombocytopenia) or impaired function

Question 17

How can platelet function be impaired?

Answer 17

hereditary absence of glycoproteins or storage granules, acquired from drugs (aspirin, NSAIDs, clopidogrel)

Question 18

How does aspirin act as an anti-platelet therapy?

Answer 18

irreversibly blocks COX

Question 19

How does clopidogrel act as an anti-platelet therapy?

Answer 19

irreversibly blocks the ADP receptor on platelets

Question 20

How do you get Von Willebrand Disease?

Answer 20

hereditary decrease of quantity/fx or acquired due to antibody

Question 21

What two functions does von willebrand factor have in haemostasis?

Answer 21

binding to collagen and capturing platelets

stabilising Factor VIII

Question 22

What inheritance pattern does von willebrand disease have?

Answer 22

autosomal

Question 23

What is type 1, 2, 3 von willebrand disease?

Answer 23

Type1/3 VWF deficiency

VWF with abnormal function

Question 24

List categories of primary haemostasis disorders.

Answer 24

platelets
VWF
vessel wall

Question 25

What are vessel wall causes of disorders of primary haemostasis?

Answer 25

inherited (Ehlers-Danlos, connective tissue disorders, hereditary haemorrhagic telangiectasia) acquired (steroids, ageing, vasculitis, scurvy)

Question 26

How does ITP (Idiopathic thrombocytopenic purpura) work?

Answer 26

antiplatelet autoantibodies bind to sensitised platelets > engulfed by macrophages

Question 27

Describe typical primary haemostasis bleeding.

Answer 27

immediate, prolonged bleeding from cuts, prolonged nose/gum bleeds, menorrhagia, bruising, prolonged bleeding after trauma or surgery

Question 28

Petechiae and purpura are caused by?

Answer 28

bleeding under the skin

Question 29

When purpura have pressure applied what happens?

Answer 29

do not blanch

Question 30

Clinical feature of thrombocytopenia?

Answer 30

petechiae

Question 31

Clinical feature of severe VWD?

Answer 31

haemophilia like bleeding

Question 32

Clinical features of disorders of primary haemostasis

Answer 32

ecchymosis petechiae purpura increased skin elasticity in connective tissue disorders

Question 33

What are tests for disorders of primary haemostasis?

Answer 33

platelet count/morphology, bleeding time, VWF assays, clinical observation

Question 34

What are the principles of treatment of abnormal haemostasis where production/function failure is the root cause?

Answer 34

``` replace missing factor/platelets (prophylactic/therapeutic) stop drugs (e.g. aspirin, NSAIDs) ```

Question 35

What are the principles of treatment of abnormal haemostasis where immune destruction is the root cause?

Answer 35

immunosuppression (e.g. prednisolone) | splenectomy for ITP

Question 36

What are the principles of treatment of abnormal haemostasis where increased consumption is the root cause?

Answer 36

treat cause | replace as necessary

Question 37

List some additional haemostatic treatments.

Answer 37

desmopressin tranexamic acid fibrin glue/spray other (oral contraceptive pill for menorrhagia)