Pathology - Haemostasis Flashcards Preview

CJ: UoL Medicine Semester Two (ESA2) > Pathology - Haemostasis > Flashcards

Flashcards in Pathology - Haemostasis Deck (40):

What is the definition of haemostasis?

The stoppage of bleeding or haemorrhage. May be via vasoconstriction, an obstruction, coagulation or surgical means.


What are the main functions of haemostasis?

- prevent bleeding
- prevent unnecessary coagulation, allow blood to flow
- make clot, control the clotting, break it down


Where are platelets produced?

In the bone marrow by megakaryocytes. They 'bud' from the cytoplasm


What is the normal life span of a platelet?

7-10 days


What is the normal platelet count?

150-400,000 per microlitre of blood


When does platelet adhesion occur?

When there is damage to the vessel wall and exposure of underlying tissues


What do platelets secrete?

ADP, thromboxane and other substances to become activated and activate other platelets. This helps initiate the clotting cascade.


Give some mediating factors of platelet clot formation

- Plt receptors - glycoproteins complexes
- Von willebrands factor
- fibrinogen
- collagen
- thromboxane/arachidonic acid
- thrombin


What is the clotting cascade?

Amplification system activation of precursor proteins to generate thrombin. Thrombin converts soluble fibrinogen into insoluble fibrin, which meshes the initial platelet plug to make a stable clot.


Where are clotting factors made?

In the liver


Give some examples of natural anticoagulants

Proteins C and S, antithrombin, tissue factor pathway inhibitor


Give some examples of coagulation factors made in the liver

Fibrinogen, prothrombin, factors 5, 7, 8, 9, 10, 11, 12, 13 and tissue factor


What is the intrinsic pathway activated by?

Factors VIII, IX, XI and XII


What is the extrinsic pathway activated by?

Factor VII


Describe the process of clot formation

Activation of coagulation leads to thrombin formation. Thrombin converts fibrinogen to fibrin, which forms fibrin polymers and blocks the wound. After 24-48 hours these are changed to fibrin fragments via fibrinolysis


How are the different routes of coagulation measured?

Intrinsic is measured by APTT and extrinsic is measured by PT


What is a 'thrombin burst'?

When lots of thrombin is produced by positive feedback of clotting factors. It converts fibrinogen to fibrin.


What is Von Willebrand factor?

It is involved with platelet adhesion to the vessel wall, platelet aggregation and also carries FVIII


What is the role of the vessel wall in haemostasis?

- first step is vasoconstriction
- production of Von Willebrands factor (essential for plt adhesion, carrier and 'protector' of factor 8)
- exposure of collagen and tissue factor which initiates activation of clotting factors


What do natural anticoagulants do?

These stop further coagulation, ensuring that the clot does not become too big


Give some examples of congenital coagulation factor disorders

- haemophilia A (factor 8)
- haemophilia B (factor 9)


Give some examples of acquired coagulation disorders

- liver disease
- vitamin K deficiency
- anticoagulants including warfarin (inhibits vitamin K)


Give some symptoms of coagulation factor disorders

- muscle haematomas
- recurrent haemarthroses
- joint pain and deformity
- prolonged bleeding post-dental extraction
- life threatening post-op and post-trauma bleeding
-intracerebral haemorrhage


What is haemophilia A and how is it inherited?

- congenital lack of factor VIII (varies in severity)
- X-linked recessive
- usually diagnosed in infancy (or soon after birth if family history)
- bleeding into muscles and joints


How is haemophilia treated?

Recombinant factor VIII or DDAVP


What is haemophilia B?

Congenital reduction in factor IX.


What is Von Willenbrand's disease?

Abnormal platelet adhesion to the vessel wall due to low amounts of VWF, which carries factor VIII.


How is Von Willenbrand's disease inherited?

Autosomal dominant, affects males and females.


What are the symptoms of Von Willenbrand's Disease?

- skin and mucous membrane bleeding
- epistaxis
- gum bleeding
- bruising
- prolonged bleeding after trauma, post-surgery and post dental extraction
- heavy periods


What are symptoms of vessel wall abnormalities?

- easy bruising
- spontaneous bleeding from small vessels
- mainly affects skin but can be mucus membranes


Give some examples of congenital problems with blood vessels

- Hereditary Haemorrhagic Telangiectasia
- connective tissue disorders eg. Ehlers-Danlos


Give some examples of acquired problems with vessels

- senile purpura
- steroids
- infection, eg. measles or meningococcal infection
- scurvy


What is immune thrombocytopenic purpura?

- Most common cause of immune destruction of platelets
- antibodies are formed against the body's own platelets
- can be secondary to autoimmune disorders
- treated with immunosuppression
- platelets transfusions do not work as the transfused platelets are destroyed too


Give some caused of reduced production of platelets

- B12/folate deficiency (failure of the building blocks)
- infiltration of bone marrow by cancer cells or fibrosis
- drugs eg. Chemotherapy, antibiotics
- viruses eg. HIV, infective hepatitis, EBV, CMV


What is thrombocytopenia?

Low platelet count


Give some consequences of severe thrombocytopenia

- easy bruising
- petechiae, purpura
- mucosal bleeding
- severe bleeding after trauma
- intracranial haemorrhage


Which is more common, hereditary or acquired disorders of platelet function?

Acquired is very common while hereditary is extremely rare


Give some causes of acquired disorders of platelet function

- aspirin/NSAIDs/clopidogrel
- uraemia
- hyper gammaglobulinaemia, eg. myeloma
- myeloproliferative disorders


What is disseminated intravascular coagulopathy?

- type of microangiopathic haemolytic anaemia
- pathological activation of coagulation leads to formation of numerous microthrombi in the circulation
- platelets and clotting factors are used up and haemolytic anaemia develops


What are the main triggers of disseminated intravascular coagulopathy?

- malignancy
- massive tissue injury eg burns
- infections (often gram neg sepsis)
- massive haemorrhage and transfusion
- ABO transfusion reaction
- obstetric causes

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