. Author manuscript; available in PMC: 2019 Aug 1.

Published in final edited form as: Nat Rev Drug Discov. 2019 Feb;18(2):139–158. doi: 10.1038/s41573-018-0003-2

Table 3 |.

Anti-platelet agents and anticoagulants

Therapeutic agent	Properties	Comments
Anti-platelet therapies
Prasugrel	An oral P2Y₁₂ adenosine diphosphate (ADP) receptor antagonist that inhibits ADP-mediated platelet activation and aggregation	After early promising results, a large multicenter randomized placebo-controlled trial showed modest platelet inhibition but no significant difference in rate of VOC events or other clinical endpoints²²⁰
Ticlopidine	An oral P2Y₁₂ adenosine diphosphate (ADP) receptor antagonist that inhibits ADP-mediated platelet activation and aggregation; discontinued due to serious side effects and newer P2Y₁₂ inhibitors	Despite some mildly promising results of reduction in painful events^260,261, no further clinical trials have been pursued
Aspirin	NSAID; prostaglandin synthase inhibitor that irreversibly inhibits platelets by decreasing conversion of arachidonic acid to prostaglandin	Four trials of aspirin in SCD in the 1980s showed no consistent effect on frequency of VOC or RBC indices
Piroxicam	NSAID, inhibits prostaglandin synthesis to inhibit platelet aggregation	Peroxicam but not aspirin showed a reduction in mean pain scores and mean mobility scores, and was not associated with side effects²⁶²
Eptifibatide	Cyclic heptapeptide and reversible gp IIb/IIIa inhibitor	After small proof-of-principle study showed decreased platelet activation and reduction in CD40L shedding, a small randomized pilot study showed safety but no improvement in median times to discharge/crisis resolution or total opioid use²⁶³

Anti-thrombotic therapies
Warfarin, icumarol, acenocoumarol	Oral vitamin K antagonists that inhibit production of procoagulant factors II, VII, IX and X as well as anticoagulant factors (protein C and protein S)	Evidence limited to small studies; long-term use of dicumarol resulted in healing of leg ulcers but no benefit in VOC¹³²; warfarin showed modest reduction in VOC from 1.3 VOC/year to 0.9 VOC/year in one small study¹³¹; acenocoumarol reduced markers of coagulation activation but did not affect frequency VOC²⁶⁴
Heparin	Anti-thrombin	Mini-dose heparin for 2–6 years showed ~70% reduction in VOC hospitalizations/ED visits in one small study¹³³
Low-molecular weight Heparins	Anti-thrombin	One large phase 2 study showed reduction in VOC duration¹³⁴; a smaller randomized study of dalteparin (NCT01419977) showed reduction in D-dimer and thrombin generation, as well as pain scores²⁶⁵
Rivaroxiban, apixaban	Factor Xa inhibitors	Randomized placebo-controlled trials underway (NCT02072668, NCT02179177)