What is the role of cyclooxygenase (COX) deficiency in platelet dysfunction?

Updated: Feb 19, 2019
  • Author: George T Griffing, MD; Chief Editor: George T Griffing, MD  more...
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Answer

Answer

Platelets have 3 distinct roles in coagulation: (1) initial adhesion, (2) phospholipid externalization, and (3) platelet aggregation.

Research suggests that TXA2, the final product of platelet arachidonic acid metabolism, is necessary for normal platelet function. Aggregation occurs as TXA2 diffuses from the platelet and binds to glycoprotein IIb-IIIa (GPIIb-IIIa) platelet membrane receptors to enhance alpha-granule and dense-granule secretion. The alpha granules store platelet activation markers, whereas the dense granules store calcium, serotonin, and ATP. Thus, inhibition of COX diminishes platelet secretion and inevitably disrupts normal platelet function.

Platelets are unique in that they do not regenerate COX. This becomes apparent in the face of irreversible inhibitors, including, notoriously, aspirin. [18] COX inhibition by aspirin results in diminished TXA2 production and, inevitably, in the loss of platelet aggregatory properties for the life of the platelet (ie, 7-10 days). [19, 20]

However, studies have demonstrated that high concentrations of strong promoters (eg, thrombin, collagen) are not dependent on TXA2. In fact, it has been reported that total inhibition of platelet COX does not alter a complete platelet response, suggesting that multiple pathways of platelet activation exist. [21] Perhaps this observation accounts for the normal hemostasis observed in persons who are taking aspirin.

Inherited disorders of platelet function are diverse and probably underreported. One of these disorders is the aspirinlike defect (ALD), which produces a mild impairment in hemostasis. ALD is a rare, inherited autosomal dominant dysfunction of the intraplatelet arachidonic acid pathway, leading to impaired TXA2 signalling. ALD should be suspected when platelet-type bleeding symptoms are present. Platelet aggregation studies can be performed to identify ALD; if ALD is present, family studies are important for identifying individuals who may be at risk of increased hemorrhage during surgical procedures. [22]


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