Platelets only attach to damaged cell membranes; not to normal endothelium
D. The Platelet Plug:
Aggregation of swollen and sticky platelets
Starts by platelets making contact with damaged cell (wall)
The platelets become swollen and sticky
Platelet secretion of ADP and thromboxane A2 activates other platelets (-> positive feed-back)
In the initial stage, the plug is weak and loose, quite delicate, easily rubbed off (and that then induces new bleeding)
E. Blood clot formation: coagulation
Development of fibrous threads into the platelet plug
Takes 15 sec – 2 minutes
Makes the plug strong and tight
Also shows retraction, by pulling at the fibrin
Uses fibrin stabilizing factor from the platelets
Promoting coagulation ->
procoagulants (such as blood factors)
Inhibiting coagulation ->
anticoagulants (such as heparine)
In the circulation, there is a delicate balance between pro- and anti-coagulations. To much pro-coagulation and you induce intravascular clotting, to little and you induce bleeding.
F. The Blood Coagulation System:
The Blood Coagulation System consists of three branches:
1. an intrinsiek pathway (inside the blood)
2. an extrinsiek pathway (outside the blood; i.e. in the tissue)
3. a common pathway.
The Clotting Factors and their Synonyms:
Factor III (tissue factor)
Proaccelerin; labile factor
SPCA; stable factor
antihemophilic factor A
antihemophilic factor B
plasma thromboplastin antecedent
After stopping the bleeding, the trauma must be repaired permanently. This is done mainly by plasmine that digests the fibrin threads.
Plasmine is already in the clot, in the form of plasminogen. Plasminogen needs to be activated by TPA (tissue plasminogen activator) that is already available in injured tissue and injured endothelium.
TPA and derivatives are now commercially available to treat clots (coronary clotting especially)
H. Excessive Bleeding: due to deficiency of clotting factors
Vit. K deficiency:
intestinal or liver diseases
a. shortage of factor VIII (85%)
b. shortage of factor IX (15%)
c. both are X-chromosome linked -> mother carrier; males affected
Thrombocytopenia (platelet deficiency; thrombocytopenia purpura) -> makes the daily wear and tear evident in all our tissues.
I. Thrombo-embolic conditions:
There is a big difference between a thrombus and an embolus.
Thrombus formation is caused by:
a) roughened endothelial surface (arteriosclerosis / infection / trauma)
b) very slow moving blood (femoral thrombosis when immobilized in bed) -> classic story: first attempt at standing up after weeks of immobilization -> acute death
Disseminated intravascular coagulation: in septic shock due to endotoxins.