Platelets and Hemostasis
30 Aug

Platelets

  • Fragments of megakaryocytes Contains:
  • Contractile proteins: actin and myosin
  • Granules: adenosine diphosphate (ADP), calcium, serotonin, growth factors
  • Factor XIII, Fibrin stabilizing factor

Pathways

When non activated

  • Does not adhere to endothelial cells because of its "repulsive" glycoproteins

When activated, platelets secrete

  • Serotonin and thromboxane A2, to enhance spasms
  • ADP, to enhance platelet aggregation and secretion (positive feedback loop to first pt.)
  • Calcium, essential for clotting
  • Factor XIII, to convert convert fibrin
    polymer to stabilize fibrin

Formation of platelet plug

  • Platelets adhere to Von Willebrand factor, and are activated by exposed collagen
  • Platelets activate, and enhance aggregation
  • Eventual creation of platelet plug created

Intrinsic

Extrinsic

Fibrin

The all important cascading diagram

Thrombin

Converts Fibrinogen to Fibrin

Activates Factor XIII, to stabilise Fibrin

Releases PF 3, which aids in the intrinsic pathway

Releases TF, which aids in the extrinsic pathway

Enhances platelet activation

Plasminogen

Tissue plasminogen activator
Thrombin
Factor XII

Plasmin

Digests

Thromboembolism
Inappropriate clotting

Thrombocytopenia
Too little clotting

  • Platelet count too low

Hemophilia
Excessive bleeding

  • Hemophilia A: Deficiency of factor VIII, 83% of all Hemophilia cases, X-linked.
  • Hemophilia B: Deficiency of factor IX.
  • Hemophilia C: Deficiency of factor XI (mild type).

Prothrombin Time (PT)
Time for plasma sample to clot after adding Factor III (TF) and Factor IV (Calcium)

  • Extrinsic Pathway.
  • Average time is 11-13 seconds
  • International
    Normalized Ratio (INR) = Test/Normal

Activated Partial Thromboplastin Time (aPTT)
aPTT measures clotting time of plasma, by adding Factor XII activators, ie silica.

  • Reference range 25-40 seconds.

Anti coagulants

Heparin
Functions as co-factor to anti-thrombin III

Anti-thrombin III

Warfarin drugs

  • K antagonist

Removal of calcium ions

Vitamin K

Deficiency leads to excessive bleeding

Inhibits activation of X, XI, VII, II (1972)

Suppressed by:

Increased PT time and aPTT time

Regulates INR

Inhibitors

  • Prostacyclin
  • Nitric oxide