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.     

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.     

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.     

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.     

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.     

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.     

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).     

Psychosocial complications and management of sickle cell disease

Five adolescent girls with Turner syndrome (mean age 13.9 years, mean bone age 12.0 years) were treated with both recombinant human growth hormone (rhGH) and oxandrolone for 2 years with an average increment in height of 13.4 cm. The mean bone age advanced by only 1.2 years, providing an increase in the mean estimated mature height of 9.2 cm. We conclude that rhGH and oxandrolone benefit older teenagers with Turner syndrome because of an increased growth rate with slow progression of skeletal maturation.     

Management of the patient with sickle cell disease

A discrete neural circuit mediates the production of learned vocalizations in oscine songbirds. Although this circuit includes some bilateral pathways at midbrain and medullary levels, the forebrain components of the song control network are not directly connected across the midline. There have been no previous reports of bilateral projections from medullary and midbrain vocal control nuclei back to the forebrain song system, but the existence of such bilateral corollary discharge pathways was strongly suggested by the recent observation that unilateral stimulation of a forebrain song nucleus during singing leads to a rapid readjustment of premotor activity in the contralateral forebrain. In the present study, we used neuroanatomical tracers to demonstrate bilateral projections from (a) the rostral ventrolateral medulla (RVL), which may control respiratory aspects of vocalization, to nucleus uvaeformis (Uva), and (b) the dorsomedial intercollicular nucleus (DM), a midbrain vocal control region, to Uva. Both RVL and DM receive descending projections from the forebrain song nucleus robustus archistriatalis, and Uva projects directly to the forebrain song nuclei interfacialis and high vocal center. We suggest that the bilateral feedback projections from DM and RVL to Uva function to coordinate the two hemispheres during singing in adult songbirds and to convey internal feedback of premotor signals to the forebrain in young birds that are learning to sing.     

Acute normovolemic red cell exchange for cardiopulmonary bypass in sickle cell disease

A patient with sickle cell disease (hematocrit, 28.5%; hemoglobin S fraction, 79%), required mitral valve repair. Partial red cell removal and blood component sequestration with an autotransfusion device before cardiopulmonary bypass initially decreased the sickle red cell mass. This was followed by an acute one-volume whole blood exchange transfusion performed upon the initiation of cardiopulmonary bypass, resulting in a further reduction. Both techniques yielded fresh autologous plasma for use; sequestration yielded a platelet-pheresis product. Adequate postbypass hemostasis was demonstrated.     

Erythrocyte dehydration in pathophysiology and treatment of sickle cell disease

A prominent feature of sickle cell disease is the presence of cells with markedly increased sickle cell hemoglobin concentration, as a consequence of the loss of potassium, chloride, and water from the erythrocyte. Because of the extreme dependency of the kinetic of polymerization on sickle cell hemoglobin concentration, these dehydrated erythrocytes have an increased tendency to polymerize and sickle. Thus blockade of the loss of potassium from the erythrocyte should prevent the increase in sickle cell hemoglobin concentration and reduce sickling. The availability of this potential therapeutic option is based on a detailed knowledge of the mechanisms leading to cell dehydration. Two ion transport pathways, the K-Cl cotransport and the Ca(2+)-activated K+ channel, play a prominent role in the dehydration of sickle erythrocytes. Possible therapeutic strategies include inhibition of K-Cl cotransport by increasing erythrocyte Mg2+ content and inhibition of the Ca(2+)-activated K channel by oral administration of clotrimazole.     

Multisystem damage associated with tricorporal priapism in sickle cell disease

It is demonstrated that fowlpox virus (FPV) protein FP26 located in the HindIII D fragment of the genome is related to the human deoxycytidine kinase (dCK) and probably possesses the same enzymatic activity. A homologous protein is not encoded by vaccinia virus. A multiple alignment of the amino acid sequences of the human and FPV dCKs, the thymidine kinases (TK) of herpesviruses, and cellular and vaccinia virus thymidylate kinases (ThyK) was generated and the conserved motifs, at least two of which are implicated in ATP binding, were characterized. An apparent duplication of ATP-binding motif B in the dCKs was revealed, leading to the reassignment of one of the catalytic residues. Phylogenetic analysis based on the multiple alignment suggested that the putative dCK of FPV probably has diverged from the common ancestor with the human dCK at a later stage of evolution than the herpesvirus TKs, with the ThyKs being peripheral members of the family. These results are compatible with hypothesis that genes for enzymes of nucleotide metabolism could be acquired independently by different DNA viruses (Koonin, E.V. and Senkevich, T.G., Virus Genes 6:187-196, 1992).