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