An Overview of Platelets and Coagulants

Antiplatelet Therapy
As pharmacists, we provide prescription therapy directed at clot prevention.  Many of us older pharmacists remember a 60-Minute “hatchet job” done to our profession in the 1980’s when a staged patient was buying a bottle of aspirin, while the pharmacist dispensed his warfarin prescription. 
I remember an expert saying that this was a big “no-no”.  We all learned in pharmacy school that warfarin and aspirin should never be given together… those were the days!!  Today, it is rather commonplace to see triple therapy consisting of an anticoagulant, and two antiplatelets (aspirin/clopidogrel). It just depends on the source of the clot.
TRIPLE THERAPY for ANTI-COAGULATION   
Some older patients are at higher risk for conditions that require two antiplatelet drugs plus anticoagulation.
An example of such a patient:        

• coronary stent patient (needs Aspirin + clopidogrel (Plaxix®)
• plus has atrial fibrillation or mechanical valve or Venous thromboembolism (VTE)  (needs Warfarin)

In this case, TRIPLE therapy is warranted because there are 2 different kinds of clots:
White clot:

• mostly platelets
• usually forms in the arteries (high pressure)
• Use antiplatelet therapy such as Aspirin, Clopidogrel, prasugrel, or ticagrelor
• Protective against MI and stroke

 
Red clot:  

• rich in red blood cells and fibrin
• usually forms in the veins or atrium (low pressure)
• Use Anticoagulant therapy such as warfarin
• Protects against DVT (deep vein thrombosis) and PE (pulmonary emboli)

 
PLATELETS: stop the bleeding!
Platelets initiate hemostatic mechanisms that repair injured blood vessels. The platelet is a circulating disc-shaped cell that does not contain a nucleus.  Many references refer to them as “blood cell fragments.”
ROLE OF PLATELETS: Once a break in the lining of a blood vessel occurs, platelets go to work. Platelets interact with collagen fibrils, which provides a surface for platelet adhesion, as well as a strong stimulus for platelet activation.  Platelets change their shape, spread along the collagen fibrils and secrete Thromboxane A2 and ADP, which signals other platelets in the area to do the same.
Activated platelets do the following:

• Adhesion to the site of injury
• Activation and secretion
• Aggregation- form clumps to “plug the leaks”
• Interaction with coagulation factors especially with factor VIIa to promote local coagulation, and ultimately the generation of thrombin, the most potent of the platelet agonists.

 
Antiplatelet mechanisms of action… ways to block platelet activity

• Blocking the thrombin receptor (PAR-1): think vorapaxar (Zontivity®), which was removed from the US market
• Blocking ADP binding at the P2Y1 and P2Y12 receptors:  think clopidogrel (Plavix®), prasugrel (Effient®) and ticagrelor (Brilinta®)
• Blocking prostaglandin synthesis: think aspirin and other non-selective COX-1 inhibitors
• Blocking cyclic AMP: think dipyridamole

 
How many?
A normal platelet count ranges from 150,000 to 450,000 platelets per microliter of blood.

• Having more than 450,000 platelets is a condition called thrombocytosis or thrombocythemia
• Having fewer than 150,000 is known as thrombocytopenia.