Blood Coagulation Flashcards Preview

Physiology > Blood Coagulation > Flashcards

Flashcards in Blood Coagulation Deck (36)
Loading flashcards...
1

What are the main constituents of coagulation?

  • Vessel wall lined by endothelium.
  • Platelets - derived from megakaryocytes in marrow. 
  • Coagulation factors in un-activated state.
  • Inhibitors of coagulation.
  • Fibrinolytic system and inhibitors.

2

What are coagulation factors?

  • Coagulation factors = proteins which circulate in an inactive state and become activated in a cascade reaction and cause clotting.

3

Describe the role of endothelial cells. 

  • Line blood vessels and form a barrier.
  • Produce thrombomodulin and heparin sulphate to inhibit thrombin production. 
  • Enzymes to degrade platelet granule-derived molecules.
  • Prostacyclin and nitric oxide (NO) to reduce platelet adhesion. 

4

Describe platelets.

  • Fragments of megakaryocyte cytoplasm.
  • Budded off into lumen of marrow sinusoids. 
  • Production stimulated by thrombopoietin (TPO) - liver derived.
  • Cicrulate for 5-10 days with ~30% 'stored' in spleen. 
  • Form a plug when attracted by lowered prostacyclin and by collagen exposure. 
  • Thromboxane A2 and serotonin from platelets cause vasoconstriction. 

5

How do platelets adhere to the vessel wall?

Platelets adhere to the vessel wall via Von Willibrand's factor and Glycoprotein Ib.

6

How do platelets adhere to each other?

Platelets adhere to each other via glycoprotein IIb-IIIa and fibrinogen.

7

What are the functions of platelets?

  • Form a plug when attracted by lowered prostacyclin and by collagen exposure. 
  • Granule release.
  • Fibrin formation.

8

Describe what happens in the coagulation cascade.

  • Factors present in inactive state - activated by 'intrinsic or extrinsic' pathway. 
  • Fibrin is needed to form a clot. 
  • Diagram:
    • Black = accelerator 
    • Red = brakes (these try to prevent the coagulation cascade)

9

List the factors which inhibit coagulation.

  • Protein C activated by thrombomodulin-thrombin complex.
  • With co-factor - factor S - Va and VIIIa are degraded.
  • Antithrombin (previously antithrombin III) inhibit Xa and IIa. 
  • Heparin cofactor II inhibits IIa.
  • Heparin stimulated antithrombin and heparin cofactor II. 
  • Only a very small amount of coagulation factor is needed; its effects build faster and faster. Results in coagulation happening faster than it can be inhibited. 

10

Describe the fibrinolytic system.

  • Plasminogen activated to plasmin by tissue plasminogen activator (tPA) - from endothelial cells. 
  • Fibrin broken down into 'fibrin degradation products' including D dimers - a measurement of fibrinolysis (a measure of how well a clot has broken down).
  • Inhibitors of fibrinolytic system. 
  • Theraputic use with eg. streptokinase to tPA for 'clot busting' eg acute myocardial infarction or thrombotic stroke. 

11

What is fibrin?

Fibrin = meshwork of protein that can be brokwn down into its constituent parts.

12

What is the 'gold-standard' time frame for thrombolysis in stroke treatment?

Gold standard for stroke treatment - ideally in under 3 hours.

13

What is clot retrieval?

  • Clot retrieval - putting a cathater in to pull the clot out.
  • Arguably more effective than dissolving the clot.

14

How do you measure coagulation?

  • Full blood count - includes platelet count / size / granules, but is a poor assessment of platelet function - specialised tests of aggregation can be done.
  • Ref range 150-400 x109 /L

15

What is caused by an FBC <30-50 x109/L?

And <10 x109/L?

  • Easy bruising and purpura when FBC <30-50 x109 /L (thrombocytopaenia).
  • Risk of major bleeding if <10 x109/L.

16

Describe a bleeding time test.

  • In vivo test of overall clotting - mainly platelet function. 
  • Lots of poorly controlled variables, so not often done. 

17

Describe a prothrombin time (PT) test.

  • All coagulation tests are done on citrated plasma
    • Removes Ca2+
  • At 37℃, thromboplastin and Ca2+ are added. 
  • Measure time until clot forms - extrinsic and common pathway. 
  • Prolonged by low levels of II, X and VII.

18

Describe an activated partial thromboplastin test (APTT). 

  • Ca2+ kaolin and phospholipids added to citrated plasma. 
  • Measure of intrinsic and common pathway.
  • Prolonged in haemophilia and by heparin. 

19

What is fibrinogen?

How is it measured?

  • Fibrinogen is the final substrate for making fibrin. 
  • It can be measured by:
    • Clot density
    • Thrombin time - thrombin and Ca2+ added to citrated plasma

20

Describe the further tests which can be carried out on prolonged PT or APTT.

  • Correction tests and factor assays
  • A prolonged PT or APTT can be tested further:
    • 50:50 mix with normal plasma to see if the prolongation corrects.
    • Factor assays to look for specific deficiencies. 

21

Describe the genetic causes of haemophilia A and B?

  • Haemophilia A and B:
    • X-linked defect in VIII or IX gene. 
  • Commonly a new mutation so no family history. 
  • Female heterozygotes (carriers) are not affected. 

22

What is the prevalence of Haemophilia A&B?

~1:5000 males

23

Describe the variation in severity of haemophilia A&B.

  • Can be very mild - chance finding or issue for surgery.
  • Severe (<1% VIII level) - frequent bleeds into joints and soft tissues. 

24

Describe Von Willebrand disease.

  • Usually autosomal dominant.
  • Defect in platelet adhesion and binding of VIII. 
  • Up to 1% population.
  • Mild disease - easy bruisingm heavy periods. 
  • Severe disease - similar to haemophilia. 

25

Describe acquired coagulation disease of the liver. 

  • Liver disease - alcohol / autoimmune / hepatitis. 
    • All coagulation factors are produced in the liver. 
    • PT and fibrinogen abnormal, later APPT abnormal.
    • Bleeding due to abnormal clotting, low platelets. 
    • Portal hypertension causing oesophageal varices and upper GI bleeding. 

26

Describe acquired coagulation disease - disseminated intra-vascular coagulation (DIC).

How do you treat it?

  • Activation of clotting cascade due to:
    • Trauma
    • Malignancy eg. prostate cancer
    • Sepsis
    • Amniotic fluid embolism
  • Causes depletion of clotting factors and damage due to the clot. 
  • Treat the cause and replace the clotting factors.

27

What is thrombocytopaenia?

Low platelets

28

What could thrombocytopaenia be due to?

  • Could be due to:
    • Under-production
    • Increased use
    • Abnormal distribution

29

Describe thrombocytopaenia due to under production of platelets.

  • Abnormal marrow function - acute leukaemia, metastatic tumour, aplastic anaemia. 
  • Expected side effect of cytotoxic chemotherapy. 
  • Idiosyncratic and unexpected drug adverse effect eg. co-trimoxazole, anti-inflammatories. 

30

Describe thrombocytopaenia due to increased use.

  • Immune thrombocytopaenia (ITP)
    • Autoimmune disease of children or adults. 
    • May be triggered by infection or drug. 
    • Auto antibodies to platelets. 
    • Treated by:
      • Watch and wait
      • Steroids 
      • Immunoglobulins
      • Splenectomy
      • Drugs to mimic thrombopoetin