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Haemeostasis Flashcards

1
Q

what is haemostasis?

A

tightly regulated process which maintains fluid state in normal vessels
allows for rapid formation of clot in vascular injury (thrombosis)

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2
Q

what are the 3 components of haemostasis?

A
  1. vascular wall
  2. platelets
  3. process of blood clotting
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3
Q

what is the process of haemostasis?

A
  1. contraction of vessel wall
  2. formation of a platelet plug at site
  3. formation of fibrin clot to stabalise platelet plug
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4
Q

what are the basic principles of platelets?

A
  • disc shaped an anucleate
  • made from cytoplasm of megakaryocytes
  • normal lifespan = 7-10 days
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5
Q

what is the role of platelets when vessels are damaged?

A

Platelet Adhesion: seconds
* damage to endothelium in vessel wall
* exposure of underlying tissue
* platelets adhere to collagen via vWF (von willebrand factor)

Platelet activation/secretion:
* platelets secrete granules - contain ADP, ATP, fibrin
* the release of ADP stimulates the recruitment of other platelets (activating the coagulation cascade)

Platelet aggregation:
* fibrinogen allows platelets to cross link forming platelet plug
* provides some stability but is still open to damage

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6
Q

what are some mediating factors involved in a platelet plug formation?

A
  • platelet receptors
  • vWF allow for platelet adherance
  • fibrinogen - links platelets together
  • collagen
  • thrombin - converts fibrinogen to fibrin
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7
Q

what happens in the coagulation/clotting cascade?

A
  1. multiple steps occur - at each step a zymogen is converted to an active enzyme
  2. there are 2 pathways, an intrinsic and extrinsic pathway - which meet at factor X to form a common pathway
  3. amplification system generates thrombin
  4. thrombin is super important because it converts soluble fibrinogen to insoluble fibrin
  5. converts platelet plug into a stable clot
    (tightly regulated process)
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8
Q

what coagulation factors are involved in the extrinsic pathway?

A

factor VII

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9
Q

what coagulation factors are involved in the intrinsic pathway?

A

factor VIII
factor IX
factor XI
factor XII

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10
Q

what drugs can be given to stop clotting and where in the coagulation process do they act?

A

antithrombin - stops clotting at factor X
TFPI (tissue factor plasminogen inactivator) - stops clotting at factor VII

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11
Q

what are some different coagulation factors and where are they made?

A

made in the liver:
* fibrinogen
* prothrombin
* factor 5
* factor 7
* tissue factor

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12
Q

what are some different natural anticoagulants and where are they made?

A

made in the liver:
* Protein C
* Protein S
* Antithrombin
* Tissue factor pathway inhibitor (TFPI)

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13
Q

what tests can be done to determine if a patient has clotting defects?

A
  1. activated partial thromboplastin time (APTT) - measures intrinsic pathway time
  2. prothrombin time (PT) - measures extrinsic pathway time
  3. thrombin time (TT) - measures time taken for conversion of fibrinogen to fibrin
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14
Q

what would a prolonged APTT + PT indicate?

A

indicates error in common pathway

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15
Q

how is clot broken down once vessel wall is repaired?

A
  • antithrombin III prevents conversion of fibrinogen to fibrin

Activated Protein C (APC):
* thrombin binds to endothelial cell receptor called thrombomodulin
* resulting complex activates protein C
* which inactivates factor VIIIa and Va

Tissue factor pathway inhibitor:
* acts in initiation phase of clotting
* binds to factor VIIa complex and inhibits factor Xa formation

Fibrinolysis:
* breaks down fibrin clot by activating plasminogen
* plasminogen is converted to plasmin which breaks down fibrin
* this forms D dimers

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16
Q

what may bleeding disorders be caused by?

A

abnormalities in vessel wall, platelets or coagulation factors

17
Q

what is thrombocytopenia?

A

deficiency in platelets causes:
* excessive bleeding
* brusing
* slow blood clotting

18
Q

what are common symptoms of thrombocytopenia?

A

patients present with:
* purpura
* petechiae
* mucosal bleeding
* epistaxis
* menorrhagia

18
Q

what are the different bleeding disorders which cause thrombocytopenia?

A

decreased platelet production:
* megloblastic anaemia
* sepsis

increased consumption of platelets: Immune
* immune thrombocytopenic purpura
* thrombotic thrombocytopenic purpura

increased consumption of platelets: non-immune
* haemolytic-uraemic syndrome
* hypersplenism

19
Q

what is immune thrombocytopenic syndrome?

A
  • isolated low platelet count with normal bone marrow
  • this diagnosis is given if the patient is normal for every other thing which could cause low thrombocytopenia
20
Q

what is thrombotic thrombocytopenic purpura?

A
  • blood disorder which causes too many clots to form in small blood vessels
  • this uses up all platelets present
21
Q

what is haemolytic-uraemic syndrome?

A
  • low RBC, acute kidney injury + low platelets
  • associated with infection by E.Coli
  • patients present with bloody diarrhoea, fever and vomitting
22
Q

what is hypersplenism?

A
  • spleen is functioning too much
  • removing too many blood cells including platelets
  • treated by splenctomy
23
Q

what are the different coagulation factor disorders which cause thrombocytopenia?

A

Congenital: Inherited disorders
* Haemophilia A or B
* Von Willebrands disease

Acquired disorders of coagulation:
* Liver disease

24
Q

what is haemophilia A?

A
  • X linked recessive
  • lack of factor VIII (intrinsic pathway affected so prolonged APTT + normal PT)
  • ranges from mild/moderate/severe
  • easily bruise
  • risk of haemorrhage
25
Q

what is haemophilia B?

A

X-linked recessive
reduction of factor IX (intrinsic pathway affected so prolonged APTT + normal PT)

26
Q

what is Von Willebrand disease?

A
  • lack of vWF so platelets cant adhere to collagen
  • prolonged bleeding time
  • results in excessive bleeding from wounds
  • spontaneous bleeding from mucous membranes
27
Q

what is Disseminated intravascular coagulpathy (DIC)?

A
  • type of microangiopathic haemolytic anaemia
  • triggers coagulation - lots of microthrombi form in circulation
  • results in consomption of clotting factors so cant stop bleeding if they are injured - results in haemorrhage
  • prolonged PT time + APTT time
  • low fibrinogen
  • raised D dimers
28
Q

what are thrombophilias?

A

congenital or acquired defects of haemostasis which increase patients risk of thrombosis
congenital causes:
* deficiency in natural anticoagulants
* abnormal factor V

acquired causes:
* antiphospholipid syndrome

29
Q

what are the different anticoagulant drugs?

A

warfarin - vitamin K inhibitor:
* affects vitamin K dependent factors (e.g. factor II, VII, IX + X)
direct oral anticoagulants
heparin
aspirin

30
Q

what are the complications of using anticoagulants?

A

bleeding

31
Q

how would you deal with complications associated with warfarin?

A
  1. stop giving warfarin
  2. give vitamin K
  3. if severe give prothrombin complex concentrate
32
Q

how would you deal with complications associated with heparin?

A
  1. stop giving heparin
  2. give protamine sulphate (if needed)

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