Vasoocclusion is a continuous process in
sickle cell disease (SCD) and accumulates to significant end organ damage, mostly irrespective of the occurrence of manifest acute vasoocclusive events. As there are indications that reversing the hypercoagulable state may be of clinical benefit in sickle cell patients, we performed a randomized, double blind, placebo-controlled, cross-over pilot study to assess the efficacy and safety of low-adjusted dose
acenocoumarol therapy (International Normalized Ratio: 1.6-2.0) in SCD. Treatment consisted of either
acenocoumarol or placebo for 14 weeks, after which treatment was discontinued for a period of five weeks. Then, patients initially on
acenocoumarol received placebo (and vice versa) for 14 weeks.
Therapy efficacy was assessed by comparing the frequency of vasoocclusive complications, the occurrence of
bleeding, and clotting activation between
acenocoumarol and placebo treatment of each individual patient. Twenty-two patients (14 homozygous [HbSS] and 8 double heterozygous sickle-C [HbSC]; aged 20-59 years) completed the entire study.
Acenocoumarol treatment did not result in a significant reduction of acute vasoocclusive events (three painful crises during
acenocoumarol, five painful crises during placebo). There was a marked reduction of the hypercoagulable state (depicted by a decrease in plasma levels of
prothrombin F1.2 fragments [P = 0.002],
thrombin-
antithrombin complexes [P = 0.003], and
D-dimer fragments [P = 0.001]) without the occurrence of major
bleeding. Even though no clinical benefit (pertaining to the frequency of painful crises) was detected in this pilot study, the value of low adjusted-dose
acenocoumarol for preventing specific events (such as
strokes) and as a long-term treatment of sickle cell patients should be subject of further study.