Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

Haemostasis and Thrombosis
Major Components of Coagulation:

Vessel Wall
The Endothelial Lining prevents clot formation, is a barrier between platelets
and thrombogenic subendothelium, and produces Nitrogen Oxide (Muscle
Relaxant) and Prostacyclin (Vessel Dilation)
...
They are
fragments of megakaryocytes from bone marrow
...





Functions of Platelets:
• Shape change from disc to sphere with pseudopodia
• Release: ADP (dense granules), PF4 and β-thromboglobulin (α granules),
TXA2, vWF, P-selectin, thrombin
• Aggregation and adhesion
• Reversible: GP1b-1X platelet receptor binds to connective tissue
with vWF, and GPIIb-IIIa platelet receptor binds to connective
tissue and other platelets with fibrinogen
• Irreversible - ADP, thrombin and TXA2 stimulate further activation
and aggregation
• Consolidation and control: fibrinogen -> fibrin to stabilise platelet
aggregate, prostacyclin and nitric oxide, antithrombin III in plasma
inactivates thrombin, and ADPase degrades ADP
...
Presents as bleeding from
nose, mucous membranes, GI tract, skin, puncture sites, and Petechial rashes
...
g
...
g
...
g
...

The latter is commonly seen as idiopathic thrombocytopenic purpura (ITP) in
adults, newborn alloimmunisation, viral infections, vaccination, drug ingestion,
AIDS, malignancy
...
g
...
g
...
This is Autosomal and results in
mucocutaneous bleeding and joint bleeds if severe
...


Coagulation

This is a cascade of coagulation factors in plasma (I - XIII)
...
Coagulation is divided into three parts -
intrinsic, extrinsic, final common pathway
...



Intrinsic

There is no extrinsic factor added, only contact with nonendothelial surface
...


Partial Thromboplastin Time (25-35s)
Blood is taken from patient
...
A patient suffering from vWF
(no Factor VIII) will have a longer PTT time
...
Approximately 1/5000 male birth have Haemophilia A
(sex-linked), and is a spontaneous mutation in 1/3 cases

Haemophilia B
This is a deficiency in Factor IX where deletions, point mutations, frame shift of
IX gene on long arm of X chromosome occur
...


Haemophilia results in frequent, spontaneous bleeds into joints, muscles and
vital organs, and a risk of major haemorrhage with surgery and trauma
...
The activated AT III
inhibits thrombin and factor Xa
...
It has a short half-life (one hour) so given
continuously or regularly
...


Prothrombin Time
Brain Thromboplastin, Citrated Plasma, and Ca Ions activate Factor VII
...


Warfarin

Prothrombin, F VII, F IX and F X produced in liver require vitamin K to be active
...

International Normalised Ratio
This is the ratio of patient prothrombin time - standard plasma prothrombin
time
...
0 – 1
...
0 – 3
...


Vitamin K Deficiency
This results in increased INR e
...
in liver disease, poor diet, poor absorption,
antibiotics
...




CS – Contact Surface, HMWK – High Molecular Weight Kallinogen, TF – Tissue
Factor
...
g
...
Clotting factors and platelets are depleted through
intravascular process, resulting in uncontrolled bleeding
...


Thromboembolism
This accounts for almost 50% of adult deaths in UK
...
Venous thrombosis (fibrin rich) is associated with venous
stasis or hypercoagulability and leads to thrombus in deep leg veins
...
This is usually Prophylactic
...
Plasmin is a serine protease that breaks down fibrinogen and
fibrin (fibrinolysis)
...
Warfarin interferes with vitamin K metabolism and is
a long-term oral anticoagulant, monitored with PT
...
One example is Factor V Leiden
(20% people with venous thrombosis)
...
Leiden is a mutation that activated
protein C cannot work on
...
There is also an Antithrombin deficiency
...
Protein C is
activated by thrombin and works with Protein S to destroy factors V and VIII

---