title: Low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.
abstract: BACKGROUND
  Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be broadly divided into two distinct clinical phenotypes characterized by either haemolysis or vaso-occlusion. Pain is the most prominent symptom of vaso-occlusion, and hypercoagulability is a well-established pathogenic phenomenon in people with sickle cell disease. Low-molecular-weight heparins might control this hypercoagulable state through their anticoagulant effect.
  
  
  OBJECTIVE
  To assess the effects of low-molecular-weight heparins for managing vaso-occlusive crises in people with sickle cell disease.
  
  
  METHODS
  We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches. We also searched abstract books of conference proceedings and several online trials registries for ongoing trials.Date of the last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 6 December 2012.
  
  
  METHODS
  Randomised controlled clinical trials and controlled clinical trials that assessed the effects of low-molecular-weight heparins in the management of vaso-occlusive crises in people with sickle cell disease.
  
  
  METHODS
  Study selection, data extraction, assessment of risk of bias and analyses were carried out independently by the two review authors.
  
  
  RESULTS
  One study (with an overall unclear to high risk of bias) comprising 253 participants was included. This study, with limited data, reported that pain severity at day two and day three was lower in the tinzaparin group than in the placebo group (P < 0.01, analysis of variance (ANOVA)) and additionally at day 4 (P < 0.05 (ANOVA)). Thus tinzaparin resulted in more rapid resolution of pain, as measured with a numerical pain scale. The mean difference in duration of painful crises was statistically significant at -1.78 days in favour of the tinzaparin group (95% confidence interval -1.94 to -1.62). Participants treated with tinzaparin had statistically significantly fewer hospitalisation days than participants in the group treated with placebo, with a mean difference of -4.98 days (95% confidence interval -5.48 to -4.48). Two minor bleeding events were reported as adverse events in the tinzaparin group, and none were reported in the placebo group.
  
  
  CONCLUSIONS
  Based on the results of one study, evidence is incomplete to support or refute the effectiveness of low-molecular-weight heparins in people with sickle cell disease. Vaso-occlusive crises are extremely debilitating for sufferers of sickle cell disease; therefore well-designed placebo-controlled studies with other types of low-molecular-weight heparins, and in participants with different genotypes of sickle cell disease, still need to be carried out to confirm or dismiss the results of this single study.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, Netherlands. E.J.van_Zuuren@lumc.nl.
authors.forename: Esther J
authors.initials: EJ
authors.lastname: van Zuuren
authors.forename: Zbys
authors.initials: Z
authors.lastname: Fedorowicz
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications*; D000925:Anticoagulants / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D016491:Peripheral Vascular Diseases / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D000078222:Tinzaparin
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin