Low adjusted-dose acenocoumarol therapy in sickle cell disease: a pilot study.
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.
Schnog
J B
JB
Department of Internal Medicine, the Red Cross Bloodbank Curaçao, the Public Health Laboratory, St. Elisabeth Hospital, Curaçao, Netherlands Antilles.
Kater
A P
AP
Mac Gillavry
M R
MR
Duits
A J
AJ
Lard
L R
LR
van Der Dijs
F P
FP
Brandjes
D P
DP
ten Cate
H
H
van Eps
L W
LW
Rojer
R A
RA
D000074:Acenocoumarol / Q000008:administration & dosage* / Q000592:standards; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000925:Anticoagulants / Q000008:administration & dosage* / Q000592:standards; D000933:Antifibrinolytic Agents / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D019851:Thrombophilia / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome
D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D000074:Acenocoumarol