No abstract

Intravenous morphine is the treatment of choice for severe pain during vaso‐ occlusive crisis in sickle cell disease (SCD). However, side effects of morphine may hamper effective treatment, and high plasma levels of morphine are associated with severe complications such as acute chest syndrome. Furthermore, adequate dosing remains a problem since no objective measurement of pain severity exists and analgesia should be titrated upon the patient's reported pain. Patient‐controlled analgesia (PCA) may therefore be an interesting alternative since patients can titrate the level of analgesia themselves. In this randomized controlled study, the efficacy of intravenous morphine administration with PCA was compared with continuous infusion (CI) of morphine in patients with SCD during vaso‐occlusive crisis. Twenty five consecutive episodes of vaso‐occlusive crisis in 19 patients with SCD were included in the study. Patients in the PCA‐group had a markedly and significant lower mean and cumulative morphine consumption when compared with the patients in the CI‐group (0.5 mg/hr versus 2.4 mg/hr (P < 0.001) and 33 mg versus 260 mg (P = 0.018, respectively). The mean daily pain scores were comparable (4.9 versus 5.3). The lower mean and cumulative morphine consumption in the PCA‐group led to significant less nausea and constipation during treatment when compared with the CI‐group (area under the curve, respectively, 11 versus 18 (P = 0.045) and 30 versus 45 (P = 0.021). Furthermore, a nonsignificant reduction in the duration of hospital admission of 3 days was observed in the PCA‐group. PCA results in adequate pain relief at a much lower morphine consumption and should considered to be the first choice in morphine administration to sickle cell patients admitted with vaso‐occlusive crisis. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.

The role of von Willebrand Factor (VWF) in the pathophysiology of sickle cell disease is unclear. We assessed markers of VWF during admission for vaso‐occlusive crisis (VOC) and steady state. VWF reactivity was higher during VOC and was associated with inflammation and neutrophil activation. Hyper‐adhesive VWF may promote VOC in sickle cell disease. Summary BackgroundEndothelial activation plays a central role in the pathophysiology of vaso‐occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells. Upon activation, various adhesive molecules are expressed, including von Willebrand factor (VWF). Increased VWF levels have been observed in patients with SCD during steady state. However, the role of VWF in the pathogenesis of SCD vaso‐occlusion is unclear. ObjectivesTo longitudinally assess the quantity and reactivity of VWF and its regulating protease ADAMTS‐13 during vaso‐occlusive crisis (VOC). MethodsIn this observational study, we obtained sequential blood samples in adult SCD patients during VOC. ResultsVWF reactivity was significantly higher during VOC (active VWF, VWF glycoprotein Ib‐binding activity, and high molecular weight multimers), whereas platelet count and levels of ADAMTS‐13 antigen and ADAMTS‐13 activity were concomitantly lower than during steady state. Levels of VWF antigen, VWF propeptide (VWF:pp) and ADAMTS‐13 specific activity did not change during VOC. VWF reactivity correlated strongly with markers of inflammation and neutrophil activation, and was inversely correlated with the platelet count. In patients who developed acute chest syndrome, levels of VWF, VWF:pp and active, hyperadhesive VWF were significantly higher, whereas ADAMTS‐13 activity was lower, than in patients without this complication. ConclusionsWe provide the first evidence that VOC in SCD is associated with increased reactivity of VWF, without a pronounced ADAMTS‐13 deficiency. This hyper‐reactivity may be explained by resistance of VWF to proteolysis, secondary to processes such as inflammation and oxidative stress. Hyperadhesive VWF, scavenging blood cells in the microcirculation, may thereby amplify and sustain VOC in SCD.

In daily clinical practice, the frequency of painful crises (pain rate) is an important parameter of sickle cell disease severity. We assessed the prevalence of sickle cell disease-related organ damage and complications and their relation to pain rate. Organ damage and history of vaso-occlusive complications were obtained via systematic screening of consecutive patients and by chart review. In 104 adult sickle cell patients pain rate was related to a history of acute chest syndromes, avascular osteonecrosis, iron overload, priapism and cholelithiasis. However, major disease-related complications, such as microalbuminuria and pulmonary hypertension, were detected in 23% and 24% respectively of patients without painful crises in the study period underlining the importance of systematic screening for developing organ damage in sickle cell patients irrespective of pain rate.Key words: sickle cell disease, organ damage, pain rate, systematic screening. Citation: van Beers EJ, van Tuijn CFJ, Mac Gillavry MR, van der Giessen