Abnormal Red Blood Cell Morphology Research Articles

Autosomal Recessively Inherited Glucose Transporter-1 Deficiency Syndrome with Acanthocytosis: A Case Report

AbstractGlucose transporter-1 deficiency syndrome (GLUT-1DS) is a rare, autosomal dominantly inherited disorder due to a heterozygous mutation in the gene solute channel 2A1 (SLC2A1).This gene encodes the glucose transporter protein-1. Autosomal recessive inheritance is extremely rare. Similarly, only very few reports are found in the literature of hematological manifestations in this syndrome. We report an autosomal recessively inherited GLUT-1DS, due to a de novo mutation, with the classical infantile presentation associated with concomitant acanthocytosis. In this case report, the second child born to consanguineous parents with initial refractory neonatal seizures and subsequent poorly controlled epilepsy and developmental regression is discussed. The most notable investigation findings supportive of his underlying diagnosis were very low cerebrospinal fluid (CSF) glucose and CSF lactate levels. His CSF:plasma glucose ratio was 1:7.6. He was anemic with a hemoglobin of 8.8 g/dL with his blood film showing marked acanthocytosis. His elder brother who also had refractory epilepsy and developmental regression had similar hypoglycorrhachia, low CSF:plasma glucose ratio, and mild anemia with acanthocytosis, and he died before establishment of a diagnosis. Our patient was diagnosed to have a novel mutation SLC2A1 c.184A > G p.(Thr62Ala), for which both parents were heterozygous, confirming autosomal recessive inheritance. Commencement of a ketogenic diet resulted in improvement of his seizures and slow gain in development. It also resulted in gradual disappearance of acanthocytes from his peripheral blood. This case describes a rare case of classical GLUT-1DS, autosomal recessively inherited, due to a novel mutation. The acanthocytosis in his blood smear is another rare association minimally reported in GLUT-1DS. The cause of his abnormal red blood cell morphology is unclear. It is possibly related to cation leakage reported in some rare mutations of the SLC2A1 gene needs reference.

ALECTINIB-RELATED ERYTHROCYTE MEMBRANE CHANGES, NON-IMMUNE HEMOLYSIS AND ERYPTOSIS

Alectinib is an anaplastic lymphoma kinase (ALK) inhibitor which standard initial treatment for patients with advanced ALK rearranged non-small-cell lung cancer (NSCLC). The current study was planned by the incidental observation of non-immun hemolysis signs in several alectinib-treated patients, and its aim was to comprehensively characterize eritrocyte changes under this drug. We analyzed retrospectively 13 patients treated with alectinib for ALK+ NSCLC at the Bakirkoy Sadi Konuk and Kartal Dr Lutfi Kırdar Hospital Medical Onkology Depertment.Almost all patients were consulted with the hematology clinic because of anemia and elevated lactate dehydrogenase during alectinib.Laboratory tests requested for characterization of anemia included reticulocyte count, indirect bilirubin,haptoglobin, direct antiglobulin test, and LDH.All patients were examined by peripheral smear The analyzed patients, hematological tests results are showed that: Anemia was present in approximately all of patients and was mostly mild, (lowest hgb 8.5gr/dl).Reticulocytes were increased and the direct antiglobulin (Coombs) test was negative in all patients. Peripheral blood smears showed signs of eryptosis, abnormal red blood cell morphology in all patients, with anisocytosis, a predominance of acanthocytes, as well as occasional echinocytes, spherocytes, dacrocytes and rare fragmentocytes We have reported 13 cases of significant alterations in erythrocyte morphology secondary to alectinib. Patients predominantly showed mild anemia, but one patient developed significant Coombs-negative hemolysis. In this case, hemolytic markers improved after alectinib was discontinued. This study highlights the need for both clinicians and haematologists to be observant for unrecognised off-target effects of novel agents.

Fast detection and quantification of Plasmodium species infected erythrocytes in a non-endemic region by using the Sysmex XN-31 analyzer

BackgroundDue to increased travel from endemic countries, malaria occurs more frequently in non-endemic regions. It is a challenge for diagnostic laboratories in non-endemic countries to provide reliable results, as experience of staff is often limited to only a few cases per year. This study evaluated the diagnostic accuracy of the fully automated Sysmex XN-31 malaria analyzer in a routine diagnostic setting in a non-endemic region was evaluated.MethodsSamples from 112 patients suspected for malaria were examined by the Sysmex XN-31 analyzer to determine the absolute count of malaria-infected red blood cells count (MI-RBC/µL). Microscopic examination of both Quantitative Buffy Coat capillary tubes and thick and thin blood films were used as reference methods. Limits of blank (LoB), detection (LoD) and quantification (LoQ) were investigated using an in vitro Plasmodium falciparum culture. Nine hundred twenty samples of patients with RBC abnormalities were included to determine which RBC abnormalities trigger indeterminate or false positive results.ResultsNo false positive nor false negative results were obtained for the examined patient samples suspected for malaria. For 3% of samples an indeterminate result by the XN-31 was obtained. The Passing-Bablok regression line for diagnostic accuracy of the parasitaemia was y = 39.75 + 0.7892 × showing a positive bias of about 21% when comparing the MI-RBC results to microscopy. The LoB, LoD and LoQ were calculated to be 4.7, 5.9, and 19.0 infected RBC/μL, respectively. From the 920 abnormal RBC samples collected, 4.6% resulted in a false positive MI-RBC result and almost half of the samples produced indeterminate results. These results were related to increases in nucleated red blood cells, reticulocytes and other abnormal RBC morphologies such as sickle cells.ConclusionsBased on the results, the XN-31 is a fast and reliable screening method in the detection and quantification of Plasmodium species in patients However, if an abnormal red blood cell morphology is present, the results of the XN-31 should be interpreted with caution as false positive results can be caused by interfering abnormal erythrocytes.

Severe neonatal haemolytic anaemia caused by compound heterozygous KLF1 mutations: report of four families and literature review

Mutations in the KLF1 gene, which encodes a transcription factor playing a role in erythropoiesis, have recently been demonstrated to be a rare cause of hereditary haemolytic anaemia. We described the genotypic and phenotypic spectra of four unrelated families with compound heterozygous class 2/class 3 KLF1 mutations. All patients had p.G176RfsX179 on one allele and either p.A298P, p.R301H or p.G335R on the other allele. All presented on the first day of life with severe haemolytic anaemia with abnormal red blood cell morphology, markedly increased nucleated red blood cells and hyperbilirubinaemia. Three patients later became transfusion-dependent. All parents with heterozygous KLF1 mutation without co-inherited thalassaemia had normal to borderline mean corpuscular volume (MCV) and normal to slightly elevated Hb F. Fifteen previously reported cases of biallelic KLF1 mutations were identified from a literature review. All except one presented with severe haemolytic anaemia in the neonatal period. Our finding substantiates that compound heterozygous KLF1 mutations are associated with severe neonatal haemolytic anaemia and expands the haematologic phenotypic spectrum. In carriers, the previously suggested findings of low MCV, high Hb A2 and high Hb F are inconsistent; thus this necessitates molecular studies for the identification of carriers.

Characterization of hereditary red blood cell membranopathies using combined targeted next-generation sequencing and osmotic gradient ektacytometry.

Hereditary red blood cell (RBC) membranopathies are characterized by mutations in genes encoding skeletal proteins that alter the membrane complex structure. Hereditary spherocytosis (HS) is the most common inherited RBC membranopathy leading to hereditary hemolytic anemia with a worldwide distribution and an estimated prevalence, in Europe, of about 1:2000 individuals. The recent availability of targeted next generation sequencing (t-NGS) and its combination with RBC deformability measured with a laser-assisted optical rotational ektacytometer (LoRRca) has demonstrated to be the most powerful contribution to lower the percentage of hereditary hemolytic anemia undiagnosed cases. In order to know the kind and frequency of RBC membrane mutations in our geographical area (Catalonia) and to better understand their pathophysiology, 42 unrelated, non-transfusion-dependent (NTD) patients with hereditary hemolytic anemia have been studied by combining t-NGS and LoRRca. The osmoscan module of LoRRca provides three rheological profiles that reflect the maximal deformability (EImax), osmotic fragility (Omin), and hydration state (Ohyper) of RBCs and contribute to a better understanding of the contribution RBC rheology to the severity of anemia. From the 42 patients studied, 37 were suspected to be a RBC membrane defect due to phenotypic characteristics and abnormal RBC morphology and, from these, in 31 patients (83.8% of cases) the mutation was identified by t-NGS. No definite diagnosis was achieved in 11 patients (26.2% of cases), including 6 out of 37 cases, with suspected membranopathy, and 5 with unclassifiable HHA. In all these undiagnosed patients, the existence of hemoglobinopathy and/or enzymopathy was ruled out by conventional methods.

Human radical scavenger α1-microglobulin protects against hemolysis in vitro and α1-microglobulin knockout mice exhibit a macrocytic anemia phenotype

During red blood cell (RBC) lysis hemoglobin and heme leak out of the cells and cause damage to the endothelium and nearby tissue. Protective mechanisms exist; however, these systems are not sufficient in diseases with increased extravascular hemolysis e.g. hemolytic anemia. α1-microglobulin (A1M) is a ubiquitous reductase and radical- and heme-binding protein with antioxidation properties. Although present in the circulation in micromolar concentrations, its function in blood is unclear. Here, we show that A1M provides RBC stability. A1M−/− mice display abnormal RBC morphology, reminiscent of macrocytic anemia conditions, i.e. fewer, larger and more heterogeneous cells. Recombinant human A1M (rA1M) reduced in vitro hemolysis of murine RBC against spontaneous, osmotic and heme-induced stress. Moreover, A1M is taken up by human RBCs both in vitro and in vivo. Similarly, rA1M also protected human RBCs against in vitro spontaneous, osmotic, heme- and radical-induced hemolysis as shown by significantly reduced leakage of hemoglobin and LDH. Addition of rA1M resulted in decreased hemolysis compared to addition of the heme-binding protein hemopexin and the radical-scavenging and reducing agents ascorbic acid and Trolox (vitamin E). Furthermore, rA1M significantly reduced spontaneous and heme-induced fetal RBC cell death. Addition of A1M to human whole blood resulted in a significant reduction of hemolysis, whereas removal of A1M from whole blood resulted in increased hemolysis. We conclude that A1M has a protective function in reducing hemolysis which is neither specific to the origin of hemolytic insult, nor species specific.

MYH9-related disease mutations cause abnormal red blood cell morphology through increased myosin-actin binding at the membrane.

MYH9-related disease (MYH9-RD) is a rare, autosomal dominant disorder caused by mutations in MYH9, the gene encoding the actin-activated motor protein non-muscle myosin IIA (NMIIA). MYH9-RD patients suffer from bleeding syndromes, progressive kidney disease, deafness, and/or cataracts, but the impact of MYH9 mutations on other NMIIA-expressing tissues remains unknown. In human red blood cells (RBCs), NMIIA assembles into bipolar filaments and binds to actin filaments (F-actin) in the spectrin-F-actin membrane skeleton to control RBC biconcave disk shape and deformability. Here, we tested the effects of MYH9 mutations in different NMIIA domains (motor, coiled-coil rod, or non-helical tail) on RBC NMIIA function. We found that MYH9-RD does not cause clinically significant anemia and that patient RBCs have normal osmotic deformability as well as normal membrane skeleton composition and micron-scale distribution. However, analysis of complete blood count data and peripheral blood smears revealed reduced hemoglobin content and elongated shapes, respectively, of MYH9-RD RBCs. Patients with mutations in the NMIIA motor domain had the highest numbers of elongated RBCs. Patients with mutations in the motor domain also had elevated association of NMIIA with F-actin at the RBC membrane. Our findings support a central role for motor domain activity in NMIIA regulation of RBC shape and define a new sub-clinical phenotype of MYH9-RD.

Preconceptional factors associated with haemoglobin concentration in early pregnancy: a community-based cohort study in rural northeastern Tanzania.

Maternal anaemia in early pregnancy is associated with poor pregnancy outcomes. Furthermore, preconceptional health can influence the health during pregnancy. The aim of this study was to investigate which preconceptional factors were associated with haemoglobin (Hb) concentration in early pregnancy. In Tanzania, 226 women were followed at preconception and during early pregnancy. Red blood cell (RBC) morphology, serum micronutrient concentration, demographic characteristics and health status were assessed in preconception and in early pregnancy. The association between preconceptional factors and Hb concentration in early pregnancy was investigated using simple and multiple linear regression analyses stratified by preconceptional anaemia status. Mean Hb was 123 and 119g/l before conception and during early pregnancy (median gestational age 53days) respectively. Preconceptional mid-upper arm circumference (MUAC) (adjusted coefficient (AC) 0.35 95% CI 0.9-0.61) and preconceptional Hb concentration (AC 0.45 95% CI 0.36-0.54) were positively associated with early pregnancy Hb concentration, whereas preconceptional microcytic hypochromic RBC morphology (AC -6.00 95% CI -9.56 to -2.44) was negatively associated with early pregnancy Hb concentration. In addition, treatment of preconceptional malaria was positively associated with early pregnancy Hb concentration (AC 6.45 95% CI 0.74-12.2) among women with preconceptional anaemia. In contrast, among preconceptional non-anaemic women, only preconceptional Hb concentration and medium socio-economic status was positively associated with early pregnancy Hb concentration. Mid-upper arm circumference (MUAC) and Hb measurements in preconception can help to detect women at increased risk of low Hb concentration in early pregnancy.

Effect of cyclodextrins on the structure and functions of blood components in vitro

Cyclodextrins have been extensively used in various biomedical and pharmaceutical applications. In these applications, cyclodextrins administered in vivo would inevitably enter blood stream. However, there is not enough information on the hemocompatibility of cyclodextrins until now. In this study, we investigated the influences of cyclodextrins (α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin) on human blood components and functions in vitro, that is, morphology and lysis of red blood cells, structure and conformation of fibrinogen, complement activation, and blood coagulation. It was found that 10 mg/mL of α- or β-cyclodextrins caused abnormal red blood cell morphology and serious hemolysis, while γ-cyclodextrin at 10 mg/mL did not impair red blood cell membrane morphology and integrity. The three cyclodextrins at up to 10 mg/mL affected the local microstructure but did not change the conformation of fibrinogen. The three cyclodextrins from 0.01 to 1 mg/mL all significantly activated the complement system in a concentration-dependent way. The three cyclodextrins at up to 5 mg/mL in blood plasma did not cause significantly different coagulation times compared with the negative control. In addition, the three cyclodextrins at up to 5 mg/mL in whole blood did not cause abnormal coagulation parameters. These results provide significant information on blood safety of the three cyclodextrins for their biomedical and pharmaceutical applications.

Reporting and grading of abnormal red blood cell morphology

In spite of the continual standardization of test result formats, the improvements of laboratory technologies, publications of reference guidelines, and the advancements in hematology analyzers, the methods of reporting or grading abnormal red blood cell morphology still vary among laboratories everywhere. This article describes the methods or systems of reporting abnormal red cell morphology and the conditions associated with the abnormalities.

English

BACKGROUND: This study was planned with an aim to identify the nature and distribution of cranial lesions on magnetic resonance imaging (MRI) and its correlation with clinical and laboratory data in eclampsia and severe preeclampsia. MATERIAL AND METHODS: 40 patients admitted for indication of severe preeclampsia or eclampsia with or without neurological signs were first stabilized and then underwent cranial MRI. Following MRI they were divided into two groups; Group MP (n=24) including patients with positive finding on the cranial MRI and Group MN (n=16) which included patients with normal Cranial MR imaging. Nature and distribution of the lesions were documented and statistical comparison was made on the basis of clinical findings, arterial blood pressure and laboratory data in both the groups. Patient with cerebral changes in the MRI were also called back for repeat MRI postnatal after two 2 months. RESULTS: Out of the 40 patients who underwent cranial MRI 24 patients had cerebral changes (Group MP) whereas 16 patients had normal scan (Group MN). In 21 out of 24 (87.5%) MRI finding positive patients the finding was consistent with diagnosis of posterior reversible encephalopathy syndrome (PRES). The most commonly involved areas in patients with PRES were parietal (85.7%,), frontal (71.42%) and occipital lobe (71.42), followed by temporal lobe (38.09) and basal ganglia (33.33) and cerebellum. All the patients who were diagnosed with PRES had a normal MR scan on the follow up at two months after the initial presentation. There was a significantly greater incidence of seizures and neurological disturbances in patients with positive MRI findings as compared to patients with no MRI findings (p<0.001). There was no statistical difference between the blood pressure measurements of the two groups. Markers of endothelial dysfunction like Serum LDH (p=0.002) Serum creatinine (p=0.006) and abnormal red blood cell morphology (0.002) was significantly higher in patients with positive MRI findings compared to MRI Finding Negative group. CONCLUSION: Our study suggests that PRES is the core component of the pathogenesis of cerebral findings of eclampsia and development of PRES is associated with endothelial dysfunction and not elevated blood pressure alone.

The effect of iron overload on red blood cell morphology

A 76-year-old man with an extremely high serum ferritin concentration (33 790 μg/L) was referred to the National Reference Laboratory for further laboratory testing to determine the cause. Genetic analysis showed that he was a carrier of a haemo chromatosis-associated allele (H63D/hetero zygous). Pathology con fi rmed renal insuffi ciency and liver damage, with an exceptionally high bilirubin concen tration of 730 μmol/L and an unconjugated bilirubin concentration of 272 μmol/L. This light micro scopy smear showed that most of the red blood cells have a changed morphology (fi gure). Scanning electron micro scopy, by which high magnifi cations of the red blood cells can be viewed, showed that the cells form pointed extensions with large membrane pores (fi gure). This abnormality is not seen in red blood cells from healthy individuals (fi gure). We suggest that the presence of the H63D haemochromatosisassociated allele is partly the cause of the exceptionally high serum ferritin concentrations, which brings about the abnormal red blood cell morphology.

A new paradigm in the diagnosis of hereditary hemolytic anemia

A new paradigm in the diagnosis of hereditary hemolytic anemia

Platelet and red blood cell indices in Harris platelet syndrome

Inherited thrombocytopenias, including inherited giant platelet disorders (IGPD) or macro thrombocytopenias are relatively rare, but their prevalence is likely underestimated from complexities of diagnosis and a spectrum of subclinical phenotypes. Harris platelet syndrome (HPS) is the most common IGPD reported from the Indian subcontinent. Of note there are an increased number of hemoglobinopathies reported from the geographic location. We analysed red blood cell and platelet indices of blood donors with HPS from the north eastern part of India and compared them with blood indices of blood donors of south India. We found a statistically significant lower platelet count in blood donors with HPS (median, range) 132 (71–267) vs. 252 (160–478) as compared to donors from south India (P < 0.001). Mean platelet volume (MPV) was higher in donors with HPS 13.1, (range 12–21.9 fl) as compared to donors from south India 7.35 (range 6–9.2 fl) (P < 0.001). This study showed that blood donors with HPS had a low median platelet bio-mass 0.17 (0.10–0.38%) vs. 0.19 (0.13–0.28%) in donors from south India. The platelet distribution width (PDW) was 17.4 (14.9–19.6) in donors with HPS vs. 16.38 (15.2–18.5) in south Indian blood donors (P < 0.001). Thirty-three donors with HPS had a normal platelet count with MPV more than 12 fL. Only donors with HPS had giant platelets and thrombocytopenia on peripheral blood smear examination. None of these donors had Dohle body inclusion in their leukocytes. Compared to donors from south India, donors with HPS had a significantly lower hemoglobin 13.8 (12–16.3 gm/dL) vs. 14.8 (12–18) respectively (P < 0.001) while red distribution width (RDW) was higher in HPS 13.6 (11.5–16.7) vs. 12.8 (11.4–15.1). However we did not find any statistically significant difference in MCV, MCH, MCHC between the two groups. Peripheral blood smear did not show any obvious abnormal red blood cell morphology. In the blood donors with HPS we found a statistically higher MPV, RDW and a lower platelet count and platelet biomass. A population-based study will be helpful in determining the existence of any hemoglobinopathies among subjects with HPS.

Deep brain pallidal stimulation for movement disorders in neuroacanthocytosis

Neuroacanthocytosis (NA) encompasses a heterogeneous set of neurodegenerative disorders associated with abnormal red blood cell morphology.1 The movement disorders of NA are often severe and incapacitating and may resist conventional drug therapy (i.e., neuroleptics and tetrabenazine). Encouraged by our previous experience in treating severe truncal spasms in a patient with chorea-acanthocytosis by chronic bilateral high-frequency stimulation of the posterior ventral oral nucleus of the thalamus2 and by the recent literature on the treatment of chorea by bilateral internal globus pallidus stimulation,3,4 we proposed this technique in two cases of NA with severe and intractable movement disorders. The first patient was a 32-year-old man with an 8-year history of choreatic-dystonic syndrome, dysarthria with recurrent distressing tasteless belching, and dramatic tongue biting. Walking was disturbed by intermittent moderate foot and back-arching dystonia. Cognitive impairment was obvious on clinical examination but impossible to test for linguistic reasons. The patient had 10% of acanthocytes among the circulating red blood cells, and an intronic mutation in the CHaC gene was consistent with the diagnosis of choreoacanthocytosis. Risperidone …

Abnormal Red Blood Cell Morphology in an Elderly Male

Questions: 1. What is (are) this patient’s most striking laboratory finding(s)? 2. How do you explain this patient’s most striking laboratory finding(s)? 3. What is this patient’s most likely diagnosis? 4. What are the incidence, geographical distribution, and inheritance pattern of this patient’s condition? 5. What are the principal clinical and hematological features of this patient’s condition? 6. What is (are) the defect(s) in the RBCs that cause this patient’s RBC abnormality? 7. What laboratory investigations can be carried out to diagnose this patient’s condition? 8. What other hematological conditions result from RBC membrane abnormalities?

Abnormal Red Blood Cell Morphology in an Elderly Male

Abnormal Red Blood Cell Morphology in an Elderly Male

Mutational spectrum of the CHAC gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is an autosomal recessive neurological disorder whose characteristic features include hyperkinetic movements and abnormal red blood cell morphology. Mutations in the CHAC gene on 9q21 were recently found to cause chorea-acanthocytosis. CHAC encodes a large, novel protein with a yeast homologue implicated in protein sorting. In this study, all 73 exons plus flanking intronic sequence in CHAC were screened for mutations by denaturing high-performance liquid chromatography in 43 probands with ChAc. We identified 57 different mutations, 54 of which have not previously been reported, in 39 probands. The novel mutations comprise 15 nonsense, 22 insertion/deletion, 15 splice-site and two missense mutations and are distributed throughout the CHAC gene. Three mutations were found in multiple families within this or our previous study. The preponderance of mutations that are predicted to cause absence of gene product is consistent with the recessive inheritance of this disease. The high proportion of splice-site mutations found is probably a reflection of the large number of exons that comprise the CHAC gene. The CHAC protein product, chorein, appears to have a certain tolerance to amino-acid substitutions since only two out of nine substitutions described here appear to be pathogenic.

A prospective, cross-sectional study of anaemia and peripheral iron status in antiretroviral naïve, HIV-1 infected children in Cape Town, South Africa

BackgroundAnaemia is a common manifestation of paediatric HIV infection. Although there are many causes, anaemia of chronic diseases is the most frequent type. In poor countries iron deficiency is widespread. It is probable that many HIV-infected children in these countries are also iron deficient. This study describes the relationship between paediatric HIV infection and anaemia, and documents the peripheral iron status of antiretroviral naive, HIV-infected children.MethodsSixty children were evaluated prospectively. Investigations included CD4+ count, haemoglobin concentration (Hb), red blood cell (RBC) morphology, and iron studies.ResultsAnaemia was present in 73% of children. Compared to mild HIV infection, median Hb was lower in children with moderate clinical infection (104 g/L v 112 g/L, p = 0.04) and severe clinical infection (96 g/L v 112 g/L, p = 0.006), and more children with severe infection were anaemic (92% v 58%, 0.04). There was a significant relationship between immunological status and Hb. 68% had abnormal RBC morphology. Significantly more children with moderate and severe disease, and severe immunosuppression had abnormal RBC morphology. 52% were iron-depleted, 20% had iron-deficient erythropoiesis and 18% iron deficiency anaemia (IDA). 16% (7/44) of anaemic children had microcytosis and hypochromia. Median soluble transferrin receptor concentration was significantly higher in those with microcytic hypochromic anaemia (42.0 nmol/L v 30.0 nmol/L, p = 0.008).ConclusionsBoth the proportion of anaemic children and the median Hb were associated with disease status. Iron depletion and IDA are major problems in HIV-infected children in South Africa.

Preeclampsia-eclampsia: clinical and neuroradiographic correlates and insights into the pathogenesis of hypertensive encephalopathy.

To investigate the clinical parameters that are associated with the development of brain edema of hypertensive encephalopathy in patients with preeclampsia-eclampsia. Twenty-eight patients with preeclampsia-eclampsia and neurologic symptoms underwent magnetic resonance (MR) imaging. Clinical parameters recorded at the time of MR imaging included serum electrolytes and various indices of hematologic, renal, and hepatic function. Several data were available 1 week prior to the development of neurologic symptoms in 11 patients. Univariate analysis and multivariate logistic regression analyses were performed to study possible associations between these parameters and brain edema at MR imaging. The 20 patients with brain edema at MR imaging had a significantly greater incidence of abnormal red blood cell morphology (14 [82%] of 17 patients vs two [25%] of eight, P: <.005) and higher levels of lactic dehydrogenase (LDH) (339 U/L +/- 65 [SD] vs 258 U/L +/- 65, P: =.007) than the eight with normal MR imaging findings; multivariate logistic regression analysis showed a strong association with red blood cell morphology only. Moreover, LDH levels were elevated before the development of neurologic abnormalities (P: <.05). Blood pressures were not significantly different between groups at any time. Brain edema at MR imaging in patients with preeclampsia-eclampsia was associated with abnormalities in endothelial damage markers and not with hypertension level.