Sudden hearing loss in sickle cell disease: a case report

BACKGROUND: Endoscopic papillary balloon dilatation (EPBD) has been reported as a safe and effective alternative to endoscopic sphincterotomy in the management of common bile duct (CBD) stones; its effect on papillary function has yet to be elucidated. AIM: To investigate sphincter of Oddi (SO) motility before and after EPBD to determine its effect on SO function. PATIENTS AND METHODS: The papillary function of 10 patients with CBD stones was studied using endoscopic manometry before and one week after EPBD. The manometric studies were repeated one month after EPBD in seven patients. RESULTS: One week after EPBD, CBD pressure, SO peak pressure, SO basal pressure, and SO frequency decreased significantly. One month after EPBD, however, all parameters increased although the increases in SO basal pressure and CBD pressure were not significant. There was no significant difference in values of any parameter before and one month after EPBD. No serious complications occurred. CONCLUSION: These data suggest at least partial recovery of papillary function one month after the procedure. EPBD seems to preserve papillary function in treatment of CBD stones; a longer term follow up study with SO manometry should be performed to clarify the effect of EPBD on SO function.     

Splenic sepsis in sickle cell disease

We describe two patients with sickle cell disease (SCD) who developed infections situated in the spleen. One patient had a splenic abscess and there was strong clinical evidence for an infected splenic infarct in the second patient. SCD predisposes to splenic infection because of functional hyposplenism, defective phagocyte function and splenic infarction. Splenic infections can occur in patients who might be considered to have an absent spleen and the diagnosis of splenic abscess should be considered in individuals with SCD who present with fever and abdominal pain.     

Renal length in sickle cell disease: observations from a cohort study

Renal length has been measured by ultrasound in 237 subjects with homozygous sickle cell (SS) disease, 147 with sickle cell-hemoglobin C (SC) disease, and in 78 age-matched controls with a normal hemoglobin (AA) genotype. As expected, renal length increased with age in all genotypes but mean length was significantly greater in SS disease compared with SC disease (mean difference 4.3 mm after adjustment for height) and significantly greater in both genotypes than in AA controls (SS/AA difference 9.2 mm, SC/AA difference 5.0 mm after adjustment for height). Examination of relationships between renal length and some hematological indices (hemoglobin, fetal hemoglobin, reticulocyte counts, alpha thalassemia status) in SS or SC disease showed only a significant negative correlation with hemoglobin and positive correlation with reticulocyte count in SS disease. Further analysis suggested that the stronger relationship was between renal length and high reticulocyte count. The mechanism of renal enlargement is unknown although glomerular hypertrophy and increased renal blood volume are likely contributors.     

Homocysteine in sickle cell disease: relationship to stroke

This research project was conducted in the Ottawa-Carleton region of Ontario to provide information on reasons why students did not participate in a Grade 7 hepatitis B school immunization project, and to determine whether telephone contact increased attendance at the community catch-up clinics above that achieved by a notice sent home with the child from school. A matched comparison group design was used. The overall uptake of the first dose of the vaccine in the region was 94% of 8,560 eligible students; 90% were immunized at the school clinic and 4% at the community catch-up clinic. About 4% of the parents refused to have their child immunized at the school or catch-up clinics. Of parents in the intervention group 198 (95%) were contacted by phone. The major reasons for non-participation at the school clinics were: (1) the child was not at school on the clinic day, or the child was sick (51%), (2) there were problems with the consent form (21%), and (3) the parents did not know of the program (10%). More students from the intervention group (72%) came for vaccination than did those of the control group (50%) (p < 0.01).     

Plasma and red cell lipids in sickle cell disease

Lipids, in particular phospholipids, are essential components of membrane systems, and the measurement of phospholipids and cholesterol in plasma and tissues is helpful in diagnosis. Phospholipids represent about 60 to 70% of total red cell (RBC) lipids, while about 25% is free cholesterol. Lipids in RBC are present in a dynamic state of equilibrium, and the RBC have the capacity for rapid exchange of lipids with plasma in several ways. The present study examined the cholesterol and phospholipid levels of plasma and erythrocytes in male patients with sickle cell anemia and in healthy male individuals of comparable age. This was performed with a view to detecting possible differences that might be related to some of the RBC abnormalities which accompany the disease. The results show that plasma lipids are significantly reduced in patients with sickle cell anemia and that RBC cholesterol was higher in sickle cell patients than in normal subjects.     

Orbital compression syndrome in sickle cell disease

BACKGROUND: Orbital complications are an uncommonly reported finding in sickle cell disease. METHODS: The authors review the reported orbital manifestations of sickle cell disease and discuss a patient with hemoglobin sickle beta(0) thalassemia in whom rapidly progressive bilateral orbital compression developed. RESULTS: Computed tomography of the orbits in a patient with fever, headache, orbital swelling, and optic nerve dysfunction displayed bilateral superior subperiosteal cystic masses. Surgical exploration showed bilateral liquefied hematomas, which were evacuated. Recovery was complete 13 days after surgery. A mild recurrence 14 months later resolved with conservative treatment. The literature contains 11 reports of 16 young patients with sickle cell disease (15 sickle cell disease [Hb SS] and 1 hemoglobin sickle cell disease [Hb SC]) with rapidly developing findings ranging from frontal headache, fever, and eyelid edema to bilateral complete orbital compression syndrome. Including our patient, 60% had orbital hemorrhage on computed tomography. Ten of 12 patients tested were found to have orbital bone marrow infarctions. Sixteen of 17 patients had complete recovery; 13 were treated conservatively and 4 surgically. Only 2 of 17 had recurrence. CONCLUSIONS: Orbital complications in sickle cell disease are unusual manifestations in which a vaso-occlusive process in the marrow space around the orbit results in frontal headache, fever, eyelid edema, and often orbital compression syndrome. Subperiosteal hematomas are common and appear to result from bone marrow infarctions. Appropriate management requires a thorough evaluation to exclude other hemorrhagic, infectious or neoplastic processes, as well as vigilant ophthalmic monitoring. Supportive care is effective, unless optic nerve dysfunction or large hematomas are present, which would indicate that surgical evacuation is warranted to prevent loss of vision and to speed recovery.     

Psychosocial aspects of sickle cell disease

The study described in this article deals with sickle cell patients in Jamaica whose illness is accompanied by leg ulceration, a common complication of sickle cell disease. After exploring the disease's psychological, social, and economic effects, the authors suggest various ways for social workers to help sickle cell patients.     

Encephaloduroarterio-synangiosis in a child with sickle cell anemia and moyamoya disease

We report a black girl with sickle cell anemia. On prophylactic exchange transfusion protocol, she experienced cerebrovascular accidents at 3 and 3.5 years of age, both associated with transient right hemiparesis. At 7.5 years of age, she presented with a partial motor seizure and a left hemiparesis. A cerebral angiogram demonstrated stenosis at the origins of both middle and anterior cerebral arteries bilaterally with extensive basal collateralization. She underwent uncomplicated bilateral encephaloduroarteriosynangiosis (EDAS) procedures using both superficial temporal arteries. At age 9 years, the patient presented with a severe headache and tunnel vision secondary to a stenosis of both posterior cerebral arteries. She underwent bilateral EDAS procedures using both occipital arteries. No complication was encountered. Postoperative cerebral angiogram demonstrated impressive neovascularity at the sites of all four EDAS procedures. Different treatment options of moyamoya disease are discussed.     

Accuracy of pulse oximetry in sickle cell disease

Pulmonary complications and hypoxemia are common in sickle cell disease (SCD) and may exacerbate microvascular occlusive phenomena. Thus, detecting hypoxemia is of particular importance in SCD. To assess the accuracy of pulse oximetry in the diagnosis of hypoxemia in SCD, we compared 22 pulse oximetric measurements of arterial oxygen saturation (SpO2) in adult patients with SCD and acute vasoocclusive crisis with simultaneously drawn arterial saturation (SaO2 = oxyhemoglobin divided by oxyhemoglobin plus reduced hemoglobin) measured by co-oximetry. We accepted SpO2 readings only if they were stable and characterized by strong and regular photoplethysmographic waves on the oximeter screen. To assess the position of these patients' oxyhemoglobin dissociation curves, we plotted arterial and venous oxygen saturation (SaO2 and SvO2 ) against oxygen tension. We found right-shifted oxyhemoglobin dissociation curves, with pH-corrected p50s ranging from 28 to 38 mm Hg. Pulse oximetry slightly overestimated oxyhemoglobin percentage (by an average of 3.4 percentage points), but it almost always accurately estimated SaO2 (underestimating on average by 1.1 percentage points). The error in SpO2 was never enough to classify a hypoxemic patient erroneously as normoxemic or a normoxemic patient as hypoxemic. We conclude that, as long as strong and regular photoplethysmographic waves are present, pulse oximeters can be relied upon not to misdiagnose either hypoxemia or normoxemia in SCD.     

Platelet activation in patients with sickle cell disease

Vascular occlusion and vasculopathy underlie much of the morbidity in patients with sickle cell anaemia. Platelets may play a role in this vasculopathy. Samples from 43 patients with sickle cell disease (SCD) were examined for evidence of platelet activation using fluorescent-labelled monoclonal antibodies and flow cytometry. There was increased expression of activation-dependent antigens on the platelets from patients with SCD compared to those from both Caucasian and African-American controls. In addition, SCD patients had increased levels of platelet microparticles. Platelets are activated in patients with sickle cell disease. The contribution of platelet activation to sickle cell pathophysiology is under active investigation in our laboratories.     

Knockout-transgenic mouse model of sickle cell disease

When transgenic mice that expressed human sickle hemoglobin were mated with mice having knockout mutations of the mouse alpha- and beta-globin genes, animals were produced that synthesized only human hemoglobin in adult red blood cells. Similar to many human patients with sickle cell disease, the mice developed a severe hemolytic anemia and extensive organ pathology. Numerous sickled erythrocytes were observed in peripheral blood. Although chronically anemic, most animals survived for 2 to 9 months and were fertile. Drug and genetic therapies can now be tested in this mouse model of sickle cell disease.     

Hemoglobin sickle-lepore: an unusual case of sickle cell disease

We report the case of a newborn with a large left-sided congenital diaphragmatic hernia (CDH) who required extra corporeal membrane oxygenation (ECMO) for severe respiratory insufficiency. CDH repair had to be performed on bypass circulation. Intraoperatively, an atypical hemihepatectomy of the herniated lobe was conducted, because reposition of the liver led to a kinking of the vena cava and to a torsion of the right lobe, resulting in ischemia and compromised venous flow. The extraordinary anatomical indication and the potential danger of uncontrollable bleeding are discussed.     

Vascular cell adhesion molecule-1 is involved in mediating hypoxia-induced sickle red blood cell adherence to endothelium: potential role in sickle cell disease

We investigated the effects of hypoxia on red blood cell (RBC)-endothelial cell (EC) adherence and the potential mechanism(s) involved in mediating this effect. We report that hypoxia significantly increased sickle RBC adherence to aortic EC when compared with the normoxia controls. However, hypoxia had no effect on the adherence of normal RBCs. In additional studies, we found that the least dense sickle RBCs containing CD36+ and VLA-4+ reticulocytes were involved in hypoxia-induced adherence. We next evaluated the effects of hypoxia on the expression of EC surface receptors involved in RBC adherence to macrovascular ECs, including vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and the vitronectin receptor (VnR). Hypoxia upregulated the expression of both VCAM-1 and ICAM-1, whereas no effect on VnR was noted. Potential involvement of VCAM-1 and ICAM-1 in mediating hypoxia-induced sickle RBC-EC adhesion was next investigated using monoclonal antibodies against these receptors. Whereas anti-VCAM-1 had no effect on basal adherence, it inhibited hypoxia-induced sickle RBC adherence in a concentration-dependent manner, with 50% to 75% inhibition noted at 10 to 60 micrograms/mL antibody (n = 6, P < .05 to P < .01). Anti-ICAM-1 (10 to 60 micrograms/mL, n = 8) had no effect on either basal or hypoxia-induced adherence. As noted in the bovine aortic ECs, hypoxia stimulated the adherence of sickle RBCs to human retinal capillary ECs, and this response appeared to be mediated via mechanisms similar to those observed with macro-endothelium, ie, via the adhesive receptor combination VCAM-1-VLA-4. Our studies show that hypoxia enhances sickle RBC adhesion to both macrovascular and human microvascular ECs via the adhesive receptor VCAM-1. Our findings are of interest because hypoxia is an integral part of the pathophysiology of the vaso-occlusive phenomenon in sickle cell anemia.     

Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion

Vascular occlusion has a central role in the pathophysiology of sickle cell disease (SCD) and, although there is little evidence that thrombosis alone is responsible, patients with sickle cell disease are known to have an ill-defined but increased thrombotic risk. The most serious complication of this in childhood is stroke which occurs in 7-10% of children and a further 14% have asymptomatic cerebrovascular disease (CVD) on imaging. We have performed a comprehensive profile of coagulation inhibitors and markers of thrombin generation in 96 children (83 nontransfused [NTx] and 13 transfused [Tx]) with steady-state SCD and 18 healthy sibling controls. The levels of protein S (free and total) and heparin cofactor II were reduced in both the NTx and Tx groups compared to controls and protein C and APC resistance ratios were reduced in the NTx group only. Antithrombin levels were not different from controls. Thrombin-antithrombin complexes and prothrombin fragment F1+2 were increased in both patient groups. In the NTx subgroups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD. We conclude that children with SCD have a reduction in levels of the majority of the coagulation inhibitors and increased thrombin generation in the steady-state and these are only partially reversed by transfusion. However, these abnormalities do not appear to play a primary role in the development of cerebrovascular disease.