Haemostasis Flashcards
1
Q
role of haemostasis
A
- Prevents bleeding
- Prevents unnecessary coagulation allowing blood to flow
2
Q
main principls of haemostasis
A
1) Make clot
2) Control clotting
3) Break it down
3
Q
what are essential for haemostasis?
A
- Movement of blood
- Heart
- Venous valves
- Calf pump
- Platelets
- Coagulation factors
- Anticoagulant factors
4
Q
Haemostasis pathway
A
-
Clot initiation
- Platelet aggregation at site of damage
- Activation of coagulation
-
Clot formation
- Activation of prothrombin to thrombin
- Thrombin converts fibrinogen to fibrin
- Fibrin polymers form
- Retraction
-
Fibrinolysis (during tissue repair)
- Fibrin fragments
5
Q
how are platelets produced
A
by megakaryocytes- bud from cytoplasm
6
Q
normal platelet count
A
150-400 x10^9/l
7
Q
lifespan of a platelet
A
- Lifespan 7-10 days
8
Q
what does a platelet look like
A
9
Q
what happens to the vessel wall after famage
A
vasoconstriction and production of von willebrand factor
10
Q
von willebrand factor
A
- Involved in platelet adhesion to the vessel wall,
- platelet aggregation
- and also carries and protects Factor VIII
11
Q
otulien the steps involvinf platelets
A
1) Platelet adhesion
2) Platelet activation
3) Platelet aggregation
12
Q
1) Platelet adhesion
- *
A
- Damage to vessel wall
- Exposure of underlying tissues
- Platelets adhere to collagen via vWF/receptors
13
Q
2) Platelet activation
A
- Secrete ADP, thromboxane and other substances to become activated and activate other platelets
- Involved in activation of clotting cascade
- Provide some coagulation factors by secretion from internal stores
14
Q
3) Platelet aggregation
A
Cross linking of platelets to form platelet plug
15
Q
mediating factors of platelets role in haemostasis
A
- Von Willebrand’s factors
- Fibrinogen
- Collagen
- ADP
- Thromboxane
- Thrombin
16
Q
the clotting cascade is an
A
amplficiation system
17
Q
the clotting cascade activates preucrosor molecules to generate
A
IIa (thrombin)
18
Q
Thrombin converts
A
- Fibrinogen to fibrin
- Enmeshes initial platelet plug to make a stable clot
19
Q
how is the clotting cascade controlled
A
- Natural anticoagulates that inhibits activation
- Also clot destroying proteins
20
Q
both the intrinsic and extrinsic pathwya lead to the activation of
A
Xa which actives prothrombin to thrombin (IIa)
21
Q
The intrinsic pathway is activated through
A
exposed endothelial collagen
22
Q
The extrinsic pathway is activated through
A
tissue factor released by endothelial cells after external damage.
23
Q
Coagulation factors and natural anticoagulants are made in the
A
liver
24
Q
coagulation factors
A
- Fibrinogen
- Prothrombin
- Factors5,7,8,9,10,11,12,13, tissue factor
25
natural anticoagulants
* Protein C
* Protein S
* Antithrombin
* Tissue factor pathway inhibitor
26
how do we measure coagulation
**Extrinsic/ PT (prothrombin time) test**
* VII
**Intrinsic/ APTT (activated partial thromboplastin time) test**
* VIII, IX,XI, XII
V,X, prothrombin and fibrinogen can be done for both x
27
**Fibrinolysis**
1. Plasminogen is activated by tissue plasminogen activator to form plasmin (e.g. T-PA, alteplase)
2. Plasmin breaks down the fibrin clot
3. Forms D-dimers- broken down by proteases in the blood
28
clinical relevance of haemostasis
* Bleeding disorders
* Arterial thrombotic disorders
* Venous thrombotic disorders
* Abnormal blood test results
* Drug therapy for pro-antithrombotic purposes
29
bleeding disorders can be due to
abnormalities in the vessel wall, platelts or coagulation factors
30
bleeding disorders can be
congenital or acquired
31
congenital bleeding disroders
* Haemophilia A (factor 8)
* Haemophilia B (Factor 9)
32
acquired bleeding disorders
* Liver disease
* Vit K deficiency
* Anticoagulants including warfarin (inhibit Vit K)
33
vessel wall abnormalities
* **Easy bruising**
* **Spontaneous bleeding from small vessels**
* **Skin mainly**
* **Can be mucous membranes**
34
congenital vessel wall abnormalities
* **Hereditary haemorrhagic telangiectasia (HHT)**
* **Connective tissue disorders- Ehlers Danlos**
35
Hereditary haemorrhagic telangiectasia (HHT)
* Autosomal dominant
* Dilated microvascular swellings increase with time
* GI haemorrhage can lead to iron deficiency anaemia
36
acquired vessel wall abnormalities
* Senile purpura
* Steroids
* Infection e.g. measles, meningococcal infections
* Scurvy-Vit C def causing defective collagen production (cant be hydroxylated)
37
**Coagulation factor disorders**
Clinical severity correlates with extent of deficiency
* Muscle haematomas
* Recurrent hemarthroses
* Joint pain and deformity
* Prolonged bleeding post dental extraction
* Life threatening post op and post traumatic bleeding
* Intracerebral haemorrhage
38
haemophilia A is an
x-linked recessive disease which causes lack factor VII (8)
39
severity of haemophilia A depends on
amount of VIII present
40
when is haemophilia A diagnoseed
pre-natally or soon after birth if family history or usually in infancy if new spontaneous mutation
41
where can bleeding occur with Haemophilia A
* Bleeding into muscle and joints, and post-operatively
42
treatment of haemophilia A
recombiannt factor VIII/ DDAVP
43
which test will show an abnormality with haemophilia A
intrinsic/ APTT test
44
haemophilia B has a
similar presentation to hameophilia A
45
what causes haemophilia B
congenital reduction in factor IX
46
**Von Willebrand’s disease**
* Relatively common
* Autosomal dominant, affects males and females
47
role of VWF
**carries factor VIII** and **mediates platelet adhesion to the endothelium**
48
von willebrand diseases causes abnormal
* Causes abnormal platelet adhesion to the vessel wall
* Reduced factor VIII amount/activity
* Factor 8 can be low in addition to low VWF levels
49
what causes VWD?
several genetic defects
50
symptoms of coagulation factor disorders
* Skin and mucous membrane bleeding
* Epistaxis
* Gum bleeding
* Bruising
* Prolonged bleeding after trauma
51
**Disseminated intravascular coagulopathy (DIC)**
* Type of microangiopathic haemolytic anaemia
* Pathological activation of coagulation
* Numerous microthrombi are formed in the circulation
* Leads to consumption of clotting factors and platelets and a haemolytic anaemia
* Clotting tests are affected- raised PT, raised APTT, low fibrinogen and raised D-dimers (fibrin degradation products)
52
disseminated intravascular coagulopathy (DIC)
* Type of microangiopathic haemolytic anaemia
* Pathological activation of coagulation
* Numerous microthrombi are formed in the circulation
* Leads to consumption of clotting factors and platelets and a haemolytic anaemia
*
53
test results for DIC
Clotting tests are affected- raised PT, raised APTT, low fibrinogen and raised D-dimers (fibrin degradation products)
54
triggers for DIC (always a trigger)
* Malignancy
* Massive tissue injury e.g. burns
* Infection
* Massive haemorrhage and transfusion
* ABO transfusion reaction
* Obstetric causes- placental abruption, pre-eclampsia, amniotic fluid embolism
55
**Thrombophilias**
* Acquired or congenital defects of haemostasis which cause **increased risk of thrombosis**
56
congenital causes of thrombophilia
* include **deficiency in natural anticoagulants** (protein C, protein S and antithrombin) and an abnormal factor V (factor V Leiden)
57
acquired thrombophilia
**Acquired** causes include **antiphosphopholipid syndrome**
58
thrombophilias are a relatively
rare conditions and many patients with them do not develop clots unless they have additional risk factors
