Retinopathy in patient with AC hemoglobinopathy / Retinopatia em pacientes com hemoglobinopatia AC

Abstract Hemoglobin C is the second most frequent Hb variant in Brazil and the world. Hemoglobin C trait is described as a benign and asymptomatic condition. There is little information in the literature about the association of retinal vascular disease and the presence of hemoglobin AC, being this information restricted to a few case reports. This case report describes a 26-year-old female patient with hemoglobin C trait. She presents areas of non-perfusion and arteriovenous shunts in the retinal temporal periphery of the left eye, like changes in Goldberg's stage II of proliferative sickle retinopathy. After three years of follow-up, the patient exhibits the same the alteration in right eye as well.

Resumo A hemoglobina C é a segunda variante de hemoglobina mais comum no Brasil e no mundo. O traço C é descrito como uma condição benigna e assintomática. Há pouca informação na literatura sobre a associação de doença vascular retiniana e a presença de hemoglobina AC, sendo esta informação restrita a alguns poucos relatos de casos. Este relato de caso descreve uma paciente do gênero feminino de 26 anos de idade com traço C. Ela apresenta áreas de não perfusão e shunts artério-venosos na periferia temporal da retina do olho esquerdo, similar ao estágio II de Goldberg de retinopatia proliferativa falciforme. Após três anos de acompanhamento, a paciente apresentou a mesma alteração também em olho direito.

Hemoglobin C trait accentuates erythrocyte dehydration in hereditary xerocytosis.

A 17-year-old male presented with acute hemolysis with stomatocytosis, elevated mean corpuscular hemoglobin concentration (MCHC), and osmotic gradient ektacytometry consistent with marked erythrocyte dehydration. Erythrocytes from both parents also demonstrated evidence of dehydration with elevated MCHC and abnormal ektacytometry, but neither to the degree of the patient. Genetic studies revealed the patient had hereditary xerocytosis (HX) due to a novel PIEZO1 mutation inherited from his mother and hemoglobin C (HbC) trait inherited from his father. HbC trait accentuated the erythrocyte dehydration of HX. Coinheritance of interrelated disorders and/or modifier alleles should be considered whenever severe erythrocyte dehydration is observed.

Medullary Microvascular Thrombosis and Injury in Sickle Hemoglobin C Disease.

Sickle cell nephropathy is a common complication in patients with sickle cell hemoglobinopathies. In these disorders, polymerization of mutated hemoglobin S results in deformation of red blood cells, which can cause endothelial cell injury in the kidney that may lead to thrombus formation when severe or manifest by multilayering of the basement membranes (glomerular and/or peritubular capillaries) in milder forms of injury. As the injury progresses, the subsequent ischemia, tubular dysfunction, and glomerular scarring can result in CKD or ESRD. Sickle cell nephropathy can occur in patients with homozygous hemoglobin SS or heterozygous hemoglobin S (hemoglobin SC, hemoglobin S/ß(0)-thalassemia, and hemoglobin S/ß(+)-thalassemia). Clinical manifestations resulting from hemoglobin S polymerization are often milder in patients with heterozygous hemoglobin S. These patients may not present with clinically apparent acute sickle cell crises, but these milder forms can provide a unique view of the kidney injury in sickle cell disease. Here, we report a patient with hemoglobin SC disease who showed peritubular capillary and vasa recta thrombi and capillary basement membrane alterations primarily involving the renal medulla. This patient highlights the vascular occlusion and endothelial cell injury in the medulla that contribute to sickle cell nephropathy.

Severe proliferative retinopathy is associated with blood hyperviscosity in sickle cell hemoglobin-C disease but not in sickle cell anemia.

Little is known about the impact of blood rheology on the occurrence of retinopathy in sickle cell disease (SCD). Fifty-nine adult SCD patients in steady-state condition participated to the study: 32 with homozygous SCD (sickle cell anemia; SCA) and 27 with sickle cell hemoglobin-C disease (SCC). The patients underwent retinal examination and were categorized according to the classification of Goldberg: 1) no retinopathy (group 1), 2) non-proliferative or proliferative stage I-II retinopathy (group 2) and 3) proliferative stage III-IV-V retinopathy (group 3). Hematological and hemorheological (whole blood viscosity, RBC deformability and aggregation properties) measurements were performed for each patient. In the whole SCD group (SCA + SCC patients) and in SCC patients, the group 3 had higher platelets count than group 2 but the difference between group 3 and group 1 did not reach statistical significance. No difference was observed for the other parameters between the three groups. SCC patients from the group 3 exhibited higher whole blood viscosity than SCC patients from the group 1. No significant difference was observed between the three groups in SCA patients. This study revealed that severe sickle proliferative retinopathy is associated with blood hyperviscosity in SCC patients but not in SCA patients.

Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes.

The hemoglobins S and C protect carriers from severe Plasmodium falciparum malaria. Here, we found that these hemoglobinopathies affected the trafficking system that directs parasite-encoded proteins to the surface of infected erythrocytes. Cryoelectron tomography revealed that the parasite generated a host-derived actin cytoskeleton within the cytoplasm of wild-type red blood cells that connected the Maurer's clefts with the host cell membrane and to which transport vesicles were attached. The actin cytoskeleton and the Maurer's clefts were aberrant in erythrocytes containing hemoglobin S or C. Hemoglobin oxidation products, enriched in hemoglobin S and C erythrocytes, inhibited actin polymerization in vitro and may account for the protective role in malaria.

Rheumatoid arthritis in patient with homozygous haemoglobin C disease.

To date, few cases of hemoglobinopathies in patients with rheumatoid arthritis (RA) have been reported (Marino and Mcdonald in J Rheumatol 17:970-972, 1990; Gladman and Bombardier in Arthritis Rheum 30:1065-1068, 1987; Michel et al. in Semin Arthritis Rheum 38:228-240, 2008). These haemoglobin diseases are associated with characteristics abnormalities of the skeleton. Haemoglobin C disease is a benign hemoglobinopathy rarely associated with skeletal disorders [Piéron et al. in la semaine des hôpitaux 57(1-2):22-25, 1981]. We report a case of RA in a 60-year-old woman with homozygous haemoglobin C disease. This coexistence may be a pure coincidence, although we discuss the difficulties with RA treatment in this case due to the unknown effect of anti-rheumatic drugs on the progression of haemoglobin C disease.

Differing effects of HbS and HbC traits on uncomplicated falciparum malaria, anemia, and child growth.

The high prevalence of hemoglobin S (HbS) in Africa and hemoglobin C (HbC) in parts of West Africa is caused by the strong protection against severe falciparum malaria during childhood. Much less is known about the effect of HbS and especially HbC on Plasmodium falciparum infection, uncomplicated malaria, and anemia. A total of 1070 children from the Ashanti Region, Ghana, were enrolled at the age of 3 months and visited monthly until 2 years of age. The effects of the beta-globin genotype on the age-dependent incidence of malaria, levels of parasitemia, and hemoglobin as well as physical development were analyzed by population-averaged models. Infants with HbAS were protected from uncomplicated malaria (P < .005) and anemia (P < .001), had lower age-adjusted parasite densities (P < .001), and higher age-adjusted hemoglobin levels compared with children with the HbAA genotype (P = .004). In contrast, HbAC carriers had lower hemoglobin levels (P < .033) and were not protected against malaria or anemia. Notably, infants with HbAS were also significantly protected against stunting compared with carriers of HbAA or HbAC. This indicates differing mechanisms of protection against malaria of HbAS and HbAC and might help to understand why HbC is restricted to distinct areas of West Africa.

Perinatal and maternal outcomes in women with sickle or hemoglobin C trait.

OBJECTIVE: Recent studies have reported increased fetal loss and preeclampsia in women with sickle cell trait (hemoglobin [Hb] AS). There is a paucity of studies of outcomes in carriers of hemoglobin C. We examined the prevalence of hemoglobin C and S carrier status (Hb AC and Hb AS, respectively) and their effect on pregnancy outcomes. METHODS: This was a retrospective cohort study using data prospectively collected from 1991 to 2006. Perinatal and maternal outcomes for African-American women with Hb AS and Hb AC were compared with those with normal hemoglobin (Hb AA). Multivariable regression was performed by applying generalized estimating equations to account for correlation between births from the same woman. RESULTS: Among 22,096 eligible African-American women (36,897 pregnancies) with routine antenatal hemoglobin electrophoresis, 88.5% had a normal (Hb AA) pattern. Hemoglobin AS was identified in 8.2% and Hb AC in 2.4% of women. Hemoglobin SS and Hb SC each accounted for less than 0.2% and Hb CC for 0.01%. Prevalence and relative risks for adverse outcomes in 3,019 AS pregnancies (3,062 births) and 875 AC (886 births), compared with 32,724 AA pregnancies (33,213 births), were not increased. Adjusted relative risks (95% confidence intervals) for perinatal mortality and preeclampsia were 0.7 (0.5-1.0) and 1.0 (0.8-1.2), respectively, for AS and 0.7 (0.3-1.4) and 1.0 (0.6-1.3), respectively, for AC. Risks of stillbirths and pregnancy-associated hypertension were also not increased. CONCLUSION: Contrary to other recent reports, perinatal mortality and preeclampsia are not increased in carriers of sickle cell trait or hemoglobin C. LEVEL OF EVIDENCE: II.

Case report of HbC/beta(0)-thalassemia from India.

This 22-year-old women presented to the ante-natal clinic of this hospital for prenatal screening for beta-thalassemia. Cation exchange high performance liquid chromatography (HPLC) using 'Beta Thalassemia Short Program' on Bio-Rad 'Variant' system revealed HbC value of 81.6%. The CBC showed microcytic hypochromic anemia. The HPLC and CBC suggested the possibility of compound heterozygote state for HbC/beta-thalassemia. The alkali and acid electrophoresis findings were consistent with the above diagnosis. The DNA analysis confirmed compound heterozygote state for HbC/beta(0)-thalassemia (Fr 8/9 mutation). The studies on the parents showed that mother was a compound heterozygote for HbD(Punjab) and HbC while father had beta-thalassemia trait. To the best of our knowledge, this is the first confirmed report of HbC from India. The paper discusses the hematological findings in this subject and her mother (a compound heterozygote for HbD(Punjab) and HbC).

Association between haemoglobin variants S and C and Mycobacterium ulcerans disease (Buruli ulcer): a case-control study in Benin.

Risk factors for Buruli ulcer (BU) are poorly understood. We conducted a case-control study in southern Benin to investigate the association between haemoglobin variants S or C and BU, and particularly the association between haemoglobinopathies HbSS/SC and BU osteomyelitis. We compared the haemoglobin genotype of 179 patients with BU and 44 with BU osteomyelitis to that of 242 community controls. We found no evidence of an increased risk of BU according to the presence of haemoglobin variants S and/or C [odds ratio adjusted for sex, age, region of residence and ethnicity: 1.24 (95% CI: 0.80-1.93), P = 0.34]. Haemoglobin variants S and C are unlikely to play a role in the BU burden. However, haemoglobinopathies HbSS/SC were more frequent among BU osteomyelitis patients than among controls (6.8% vs. 1.0%, Fisher's exact P-value = 0.045), which may suggest that those disorders facilitate growth of Mycobacterium ulcerans in the bone matrix.

Managing leg ulceration in patients with sickle cell disorder.

Leg ulceration is a complication associated with sickle cell disorders. Caroline Dowsett outlines why this problem occurs and describes the management of a patient with sickle cell disorder who presented with an infected leg ulcer. She concludes that there is a need for more research into the management of these complex wounds.

Limited influence of haemoglobin variants on Plasmodium falciparum msp1 and msp2 alleles in symptomatic malaria.

Haemoglobin (Hb) S, HbC, and alpha(+)-thalassaemia confer protection from malaria. Accordingly, these traits may influence the multiplicity of infection (MOI) of Plasmodium falciparum and the presence of distinct parasite genotypes. In 840 febrile children in northern Ghana, we typed the P. falciparum merozoite surface protein genes (msp1, msp2) and examined effects of the Hb variants on MOI and parasite diversity. HbAC, HbAS, heterozygous, and homozygous alpha(+)-thalassaemia occurred in 21, 5, 29 and 4% of the children, respectively. Plasmodium falciparum was detected in 95%. The haemoglobinopathies did not influence MOI, nor did the Hb type bias the distribution of the msp allelic families. However, IC type parasites were most common among patients with homozygous alpha(+)-thalassaemia (93%), less frequent in heterozygotes (89%), and least frequent in alpha-globin normal children (84%, P(chi2 trend) = 0.03). The opposite was seen for Mad20 type parasites (34%, 47%, 53%, P(chi2 trend) = 0.02). Only a few of the 72 individual msp alleles were selected by the haemoglobinopathies. HbC and alpha(+)-thalassaemia are frequent in northern Ghana. In symptomatic children, the effect of Hb variants on parasite multiplicity and diversity appears to be limited. This may reflect an actual lack of influence or indicate abrogation in symptomatic malaria.

[Hemoglobinopathy C and splenomegaly in an Ivory Coast patient. Value of splenectomy]. / Hémoglobinopathie C et splénomégalie chez un patient ivoirien. Intérêt de la splénectomie.

We report the case of a young patient native of the Ivory Coast who suffered from homozygous hemoglobin C disease. He presented with the usual findings of this hemoglobinopathy: a moderate hemolytic anemia and a massive, painful and even disabling splenomegaly. Pain completely disappeared following splenectomy. However, postoperative course was complicated by portal venous thrombosis, which was medically treated. No deficiency of natural coagulation inhibitors could be demonstrated, so splenectomy was the only factor predisposing to thrombosis. We consider that in only very few cases of hemoglobin C disease, splenectomy (preceded by prophylactic antipneumococcic vaccine) may be indicated from pain and risk of spontaneous splenic rupture.

[Assessment of the use of transfusion therapy and complications in orthopedic surgery in patients with sickle-cell anemia: retrospective study]. / Analyse des pratiques transfusionnelles et complications chez le patient drépanocytaire en situation de chirurgie orthopédique: étude rétrospective.

Red blood cells (RBCs) transfusion is a common practice in the treatment or for the prevention of complications of patients with sickle-cell disease. In surgery, pre-operative transfusions are frequently given to prevent peri-operative complications. There is no consensus however on the best regimen of transfusion for this purpose. The transfusion techniques are muliple. In addition, pre-operative transfusion therapy is reported to be largely responsible for an increased morbidity and mortality in patients with sickle cell anemia undergoing surgery. During the period 1990-2000, 16 patients (4 men and 12 women) with a mean age of 37 years and various major sickle cell hemoglobinopathies underwent 32 total hip arthroplasty for femoral head necrosis. Nine patients with sickle-cell trait were included as control group. Twelve of them had haemoglobin SS (HbSS), 2/16 had HbSC, 2/16 had HbS/betathalassemia. Operative transfusion were given in only 12/32 procedures, 4 were performed pre-operatively and 8 intra-operatively. Simple transfusion (mean: 2.5 packed red cells) were administered in all the procedures. The main complications observed in our patients were anemia by hemolysis and haemorrhagic shock, vaso-occlusive crisis and chest syndrome. Anemia requiring transfusions was significatively related to the procedures with pre-operative transfusion. In the light of our result, we would like to propose transfusional protocol--if needed--only intra-operatively.

Pain, mood and opioid medication use in sickle cell disease.

Patients with sickle cell disease show wide variations in their experience of pain, and in the impact of pain on everyday functioning. This study examined relations between pain, mood, physical activity, and medication use in a longitudinal naturalistic self-monitoring study of 21 adult sickle cell patients over 12 months. Results suggest that opioid medication use is related to the impact of pain on daily life. Patients who use opioids more frequently for sickle cell pain show more disruption of their lives, with reduced activity levels and more pessimistic mood.