Phenotypic Evaluation of a Family Cohort with Hemolytic Anemia

Abstract Abstract 3214 Background: We have identified a kindred in Manitoba and Saskatchewan, Canada, affected by non-immune hemolytic anemia. Red cell morphology, an elevated MCHC and decreased osmotic fragility are consistent with hereditary xerocytosis, a rare hemolytic disorder, for which the causative genetic mutation is unknown. Objectives: To describe the clinical phenotype and inheritance of an uncharacterized chronic hemolytic disorder in a large kindred. Methods: With assistance from each consenting family member, a pedigree was constructed. A focused history was taken and the presence of splenomegaly was assessed by physical examination. Laboratory analysis included a CBC, reticulocyte count, osmotic fragility and peripheral blood film. Biochemical measurements of LDH, ALT, bilirubin, ferritin, haptoglobin, plasma hemoglobin and methemoglobin were performed. Glycolytic enzymes were evaluated in a subset of patients to rule out other rare causes of hemolysis. Results: The family pedigree captured the genetic relations of 342 individuals spanning 5 generations. Consent to participate in the detailed family study was obtained from 137 family members. The average age of the study population was 29 years (range 8 months to 76 years). Laboratory specimens were collected from 26 unrelated spouses and 111 related individuals. Males represented 48% of the studied population. The distribution of reticulocyte counts was distinctly bimodal with no overlap between the two populations, allowing classification of individuals as phenotypically affected or non-affected. The mean percent reticulocyte count of non-affected subjects (related family members and unrelated spouses) was 1.1% (± 0.4, range 0.5–2.3%). Affected subjects had a mean percent reticulocyte count of 9.7% (± 2.6, range 5.3–14.6%). Using this classification, the hemolytic process segregated in an autosomal dominant fashion with complete penetrance. A history of anemia (46 vs. 8%), jaundice (45 vs. 4%), red or brown urine (45 vs. 1%), and either gallstones or cholecystectomy (41 vs. 4%) was more prevalent in affected than unaffected individuals. Episodes of anemia tended to be associated with illness or stress. There was no association between the hemolytic phenotype and neuromuscular, cardiovascular, pulmonary, renal, hepatic, or endocrine disorders. Despite a mean percent reticulocyte count of 9.7% in affected individuals, the mean hemoglobin concentration was not statistically different between affected and unaffected individuals (13.5 ± 1.2 g/dL vs. 13.8 ± 1.4 g/dL, p=0.26). The MCV (96.7 ± 5.5 fL vs. 87.3 ± 5.2 fL, p<0.01) and MCHC (36.6 ± 0.6 g/dL vs. 33.8 ± 0.9 g/dL, p<0.01) were significantly elevated among affected individuals. Morphologically, target cells and stomatocytes were increased among affected individuals. Affected individuals had significantly elevated indirect bilirubin and decreased haptoglobin compared to unaffected or unrelated individuals. Serum ferritin was elevated in all age tertiles in affected individuals compared to non-affected or unrelated individuals, and 7/29 affected individuals had a serum ferritin >900 μg/L. Osmotic fragility performed on 4 affected individuals was decreased. Glycolytic enzymes, screens for unstable hemoglobins and hemoglobinopathies were normal in those tested. Conclusions: In this family study, elevated percent reticulocyte counts were used to characterize the presence of a well compensated, autosomal dominant hemolytic process associated with an elevated MCHC and decreased osmotic fragility. Clinically this condition is associated with gallstones and progressive iron loading. Features are consistent with hereditary xerocytosis. Molecular analysis is currently underway to locate the causative gene and identify the underlying mutation. Disclosures: No relevant conflicts of interest to declare.

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A-B Hemolytic Disease of the Newborn

Blood ◽

10.1182/blood.v10.1.17.17 ◽

1955 ◽

Vol 10 (1) ◽

pp. 17-28 ◽

Cited By ~ 69

Author(s):

RICHARD E. ROSENFIELD ◽

FLORENCE EISINGER

Keyword(s):

Reticulocyte Count ◽

Umbilical Vein ◽

Osmotic Fragility ◽

Blood Groups ◽

Direct Antiglobulin Test ◽

Hemolytic Disease ◽

Antiglobulin Test ◽

Plasma Bilirubin ◽

The Mean ◽

Positive Direct

Abstract A study was made of oxalated umbilical vein blood of nearly every infant born at The Mount Sinai Hospital in a nine month period. A specimen of maternal blood was available for intragroup antibody screening and six cases of Rh-Hr hemolytic disease were eliminated from the data. The umbilical vein blood was tested, where possible, for: (1) group and Rh, (2) direct antiglobulin test, (3) hemoglobin, (4) reticulocyte count and examination of red cell morphology, (5) plasma bilirubin, and (6) osmotic fragility in 0.52 per cent NaCl. From the mothers’ blood groups, the infants were classified into group compatible and group incompatible, and the arithmetic means of the hemoglobin, reticulocyte count, and plasma bilirubin obtained for each class. A third class of infants, those with positive direct antiglobulin test, were analysed separately for comparison. 1. A weakly positive direct antiglobulin test was obtained on the umbilical vein blood of over 11 per cent of group incompatible infants but in none of the group compatible infants. 2. It appears that the weakly positive direct antiglobulin test detects an abnormal class of group incompatible infants, since their mean hemoglobin is low, their mean reticulocyte count is high, and their mean bilirubin is high, when these means are compared with those of the other group incompatible infants. 3. Thirty-eight of thirty-nine mothers of incompatible infants with positive direct antiglobulin test were group O. In comparison with the distribution of the blood groups of the mothers of other incompatible infants, this disproportion is of significance. 4. The mean reticulocyte count of incompatible infants with negative direct antiglobulin test is slightly (but with statistical significance) higher than the mean reticulocyte count of compatible infants. This difference was found to be associated almost entirely with group O mothers. 5. Thirty-one out of thirty-eight infants with positive direct antiglobulin test had increased osmotic fragility in hypotonic NaCl. Two of the negative cases appeared to have slight spherocytosis on blood smear.

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COMPARISON BETWEEN FLOW CYTOMETERIC METHOD AND OTHER METHODS FORRETICULOCYTE COUNT IN DIAGNOSIS OF PHENYLHYDRAZINE-INDUCED HEMOLYTIC ANEMIA

International Journal of Advanced Research ◽

10.21474/ijar01/12537 ◽

2021 ◽

Vol 9 (02) ◽

pp. 938-952

Author(s):

Rania Mohammed Baker ◽

◽

Fatma Abdel-Monem Gad ◽

Khalid Mostafa Fararh ◽

◽

...

Keyword(s):

Hemolytic Anemia ◽

Blood Cells ◽

Reticulocyte Count ◽

Osmotic Fragility ◽

Flow Cytometer ◽

Control Group ◽

Albino Rats ◽

Flow Cytometric Method ◽

Flow Cytometric ◽

Manual Methods

Reticulocyte count is the salient evidence of the effectiveness of bone marrow to produce red blood cells. Currently, the reticulocyte counting is a challenge for clinical laboratoriesmainly for the ordinary ones, which still use the manual method.This study was designed to evaluate the performance of flow cytometer for reticulocytes counting comparing to traditional and optimized manual methods which helpful in diagnosis of phenylhydazine-induced anemia.For that 45 male white Albino rats were divided into 5 groups, control group,phenylhydrazine group (PHZ) which injected by phz(20 mg/kg b.w, I/P),quercetin+phz group (quercetin, 50 mg/kgb.w per os), silymarin+phz group (silymarin, 100 mg/kgb.w per os) and quercetin group. Whole blood samples of these groups were collected at day 3, 5 and 10 after 1st injection of phz which used for reticulocyte counts by flow cytometeric method and other manual methods in addition to measurement ofCBC and osmotic fragility. Analysis of the results showed that phenylhydrazine injection induced hemolytic anemia with significant reticulocytosis and using of flow cytometer in reticulocyte count more precise, easy and fast than traditional and optimized manual methods. Furthermore, degree of hemolysis was significantly increases in phz group comparing to other groups. Therefore, we concluded that flow cytometric method for reticulocyte counts was simple, fast and highly reliable comparable to traditional and optimized manual methods. Also optimized manual showed that more perfect than traditional manual method and nearly to accuracy of flow cytometeric method.

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The Flow Cytometric Osmotic Fragility Test Is an Effective Screening Method for Dehydrated Hereditary Stomatocytosis

Blood ◽

10.1182/blood.v130.suppl_1.929.929 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 929-929

Author(s):

Taiju Utsugisawa ◽

Takuya Iwasaki ◽

Takako Aoki ◽

Yoshio Okamoto ◽

Takahiro Kawakami ◽

...

Keyword(s):

Hemolytic Anemia ◽

Conflicts Of Interest ◽

Screening Method ◽

Osmotic Fragility ◽

Target Cells ◽

Next Generation ◽

Causative Gene ◽

Rbc Membrane ◽

Flow Cytometric ◽

Congenital Hemolytic Anemia

Abstract Introduction: Dehydrated hereditary stomatocytosis (DHSt) or hereditary xerocytosis (HX) is a form of congenital hemolytic anemia characterized by red blood cell (RBC) dehydration. Heterozygous mutations in PIEZO1, a mechanically-activated ion channel, cause DHSt. Recently, KCNN4, which encodes the Gardos channel, has been found to be the second pathogenic gene for DHSt. DHSt is characterized by an alteration in the RBC morphology in target cells, stomatocytes, and/or echinocytes, and RBC deformability assessments by ektacytometry as well as RBC ion flux measurements are currently the standard laboratory tests for DHSt, but their use in laboratories is limited. The flow cytometric osmotic fragility (FCM-OF) test is a useful diagnostic test for hereditary spherocytosis (HS) and also for hereditary elliptocytosis (HE). In this study, we showed that the FCM-OF test could also successfully diagnose DHSt. Subjects: A total of 46 cases of RBC membrane disorders were examined, and tentative diagnoses were made based on the RBC morphology, acid glycerol lysis time, and eosin 5'-maleimide binding tests, resulting in HS (n=31), HE (n=6), and DHSt (n=9). Methods: The number of RBCs in isotonic and hypotonic buffers were measured by flow cytometry. The degree of osmotic fragility was expressed as the "percentage residual RBCs (%RRC)". We confirmed the DHSt diagnosis by the massively paralleled sequencing using our custom panels targeting 68 hemolytic anemia-related genes with the next-generation sequencer. Results: Both HS and HE patients showed a decrease in %RRC; HS (18.0±8.9%, p<0.001) and HE (41.8±15.7%, p<0.001) compared to normal control (66.7±1.5%). DHSt patients showed a significant increase (112.6±34.5%, p<0.001) in FCM-OF. Additionally, next-generation sequencing revealed consistent causative gene mutations for DHSt; PIEZO1 (p.R2488Q and p.E2496ELE) or KCNN4 (p.P204R, p.A279T and p.R352H). Discussion: We examined 77 patients with congenital hemolytic anemia recently, and 59 cases were confirmed by diagnostic tests (76.6%). The results were as follows: 48 cases of RBC membrane abnormality (62.3%), 6 cases of RBC enzymopathy (7.8%), and 5 cases of hemoglobinopathy (6.5%). Of the cases of RBC membrane disorders, 31 cases of HS, 9 cases of DHSt, and 8 cases of HE were identified. These observations suggest that DHSt is the second-most common RBC membranopathy in Japan, and that the FCM-OF test and targeted sequencing efficiently discriminate DHSt from other RBC membrane disorders. Disclosures No relevant conflicts of interest to declare.

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An autosomal dominant locus, Nka, mapping to the Ly-49 region of a rat natural killer (NK) gene complex, controls NK cell lysis of allogeneic lymphocytes.

Journal of Experimental Medicine ◽

10.1084/jem.183.5.2197 ◽

1996 ◽

Vol 183 (5) ◽

pp. 2197-2207 ◽

Cited By ~ 81

Author(s):

E Dissen ◽

J C Ryan ◽

W E Seaman ◽

S Fossum

Keyword(s):

Nk Cells ◽

Natural Killer ◽

Autosomal Dominant ◽

Nk Cell ◽

Family Members ◽

High Expression ◽

Target Cells ◽

Gene Complex ◽

Class I Mhc ◽

Allogeneic Lymphocytes

Natural Killer (NK) cells can recognize and kill MHC-incompatible normal bone marrow-derived cells. Presently characterized MHC-binding receptors on NK cells, including the Ly-49 family in the mouse, transmit inhibitory signals upon binding to cognate class I MHC ligands. Here we study in vivo NK-mediated lysis of normal allogeneic lymphocytes in crosses between alloreactivity-competent PVG rats and alloreactivity-deficient DA rats. NK cells from both strains are able to lyse standard tumor targets. We identify an autosomal dominant locus, Nka, that controls NK-mediated alloreactivity. Individuals carrying the dominant PVG allele in single dose were fully competent in eliminating allogeneic target cells, suggesting that Nka encodes or regulates a gene product inducing or activating alloreactivity. By linkage analysis and pulsed field gel electrophoresis, a natural killer gene complex (NKC) on rat chromosome 4 is described that contains the rat NKR-P1 and Ly-49 multigene families plus a rat NKG2D homologue. Nka maps within the NKC, together with the most telomeric Ly-49 family members, but separate from NKG2D and the NKR-P1 family. The Nka-encoded response, moreover, correlates with the expression of transcripts for Ly-49 receptors in NK cell populations, as Northern blot analysis demonstrated low expression of Ly-49 genes in DA NK cells, in contrast to high expression in alloreactivity-competent PVG, (DA X PVG)F1, and PVG.1AVI NK cells. The low Ly-49 expression in DA is not induced by MHC haplotype, as demonstrated by high expression of Ly-49 in the DA MHC-congenic PVG.1AVI strain. Finally, we have cloned and characterized the first four members of the rat Ly-49 gene family. Their cytoplasmic domains demonstrate substantial heterogeneity, consistent with the hypothesis that different Ly-49 family members may subserve different signaling functions.

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Etiological study of microcytic hypochromic anemia

Journal of Pathology of Nepal ◽

10.3126/jpn.v6i12.16280 ◽

2016 ◽

Vol 6 (12) ◽

pp. 994-997

Author(s):

S Kafle ◽

M Lakhey

Keyword(s):

Bone Marrow ◽

Chronic Disease ◽

Hemolytic Anemia ◽

Serum Ferritin ◽

Reticulocyte Count ◽

Binding Capacity ◽

College Teaching ◽

Hypochromic Anemia ◽

Sideroblastic Anemia ◽

Distribution Width

Background: Microcytic hypochromic anemia is a distinct morphologic subtype of anemia with well- de ned etiology and treatment. The objective of this study was to determine the etiology and frequency of microcytic hypochromic anemia. Materials and Methods: This cross-sectional observational study was conducted at Kathmandu Medical College Teaching Hospital. One hundred cases of microcytic hypochromic anemia were included. Relevant clinical history, hemogram, reticulocyte count, iron pro les were documented in a proforma. Bone marrow aspiration and hemoglobin electrophoresis was conducted when required. Data was analysed by Microsoft SPSS 16 windows. Result: Iron de ciency was the commonest etiology (49%). Dysfunctional uterine bleeding (20.8%) was the commonest cause of iron de ciency, malignancy (24.3%) was the commonest cause of anemia of chronic disease. Mean value of Mean Corpuscular Volume was lowest in hemolytic anemia (71.0 ). Mean Red cell Distribution Width was normal (14.0%) in hemolytic anemia but was raised in other types. Mean serum iron was reduced in iron de ciency anemia (32.2μg/dl) and chronic disease (34.8μg/dl), normal in hemolytic anemia (83μg/dl) and raised in sideroblastic anemia (295μg/dl). Mean serum ferritin was reduced in iron de ciency anemia (7.6ng/ml), raised in chronic disease (158.6ng/ml) and normal in hemolytic anemia (99.2ng/ml). Serum ferritin was normal in sideroblastic anemia (93ng/ml). Mean Total Iron Binding Capacity was raised in iron de ciency anemia (458μg/dl) and normal in other microcytic hypochromic anemias. Conclusion: Diagnosis of microcytic hypochromic anemia requires a standardized approach which includes clinical details, hemogram, peripheral blood smear, reticulocyte count, iron pro le, hemoglobin electrophoresis and bone marrow examination.

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Recurrent Acute Splenic Sequestration in Two Children with Coinheritance of Sickle Cell Trait and Hereditary Spherocytosis.

Blood ◽

10.1182/blood.v120.21.2091.2091 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2091-2091

Author(s):

Min Hee Kim ◽

Vishwas S Sakhalkar ◽

Dana Tunnell ◽

Carlos S. Alvarado

Keyword(s):

Hemolytic Anemia ◽

Sickle Cell ◽

Hereditary Spherocytosis ◽

Reticulocyte Count ◽

Sickle Cell Trait ◽

Osmotic Fragility ◽

African American Female ◽

Red Cell ◽

Dramatic Rise ◽

Life Threatening

Abstract Abstract 2091 Background: Patients with sickle cell trait (AS) are generally asymptomatic, but they are known to be at risk of developing acute morbidity such as splenic infarction mainly occurring on exposure to high altitude. Much lesser known to most hematologists is that young children with AS who co-inherit hereditary spherocytosis (HS) seem to be at risk of developing acute splenic sequestration crisis (ASSC), which are undistinguishable from those observed in homozygous sickle cell anemia (SCA). Objective: The aim of this abstract is to report 2 patients with sickle cell trait and hereditary spherocytosis, presenting with recurrent episodes of severe hemolytic anemia with features characteristic of ASSC. Patients: Patient 1 is a 4-year-old African American female, whose birth history revealed hemoglobin (Hgb) AS phenotype on newborn screening and hyperbilirubinemia on the 4th day of life requiring phototherapy. At 3 years of age, she presented with severe hemolytic anemia (Hgb 4.6 g/dl, reticulocyte count 9.99%, indirect bilirubin 5 mg/dl, haptoglobin <15 mg/dl) and marked splenomegaly, associated with fever. Blood smear did not show microangiopathic changes or irreversible sickle cells. Hemoglobin electrophoresis confirmed diagnosis of sickle cell trait. Osmotic fragility test revealed increased red cell lysis; band 3 staining on flow cytometry was abnormal. G6PD and pyruvate kinase assays, as well as direct antiglobulin test, were all negative. Subsequently, 4 months apart, she had two similar episodes of severe anemia (Hgb 6.1 and 4.7 g/dl, respectively) and massive splenomegaly, associated with febrile respiratory illnesses. Each time, rapid resolution of splenomegaly and dramatic rise of Hgb following red cell transfusions were observed. On outpatient follow-ups, her baseline Hgb was determined to be 9–10 g/dl. Investigation on both parents disclosed AS phenotype on mother, and mild hemolytic anemia with microspherocytes on blood smear as well as normal Hgb phenotype on father. Due to the recurrent and life-threatening nature of her sequestration crisis, splenectomy was performed recently. Spleen was enlarged and weighed 92 grams; histologic examination showed a markedly congested red pulp and no evidence of recent or remote infarcts, findings felt to be consistent with the diagnosis of HS. Post-splenectomy, Hgb level was 11.8 g/dl. Patient 2 is a 5-year-old African American female with sickle cell trait confirmed by electrophoresis at age 2, when she first presented with fever, splenomegaly and severe hemolytic anemia (Hgb 5.7 g/dl, bilirubin 2.8 mg/dl). Diagnosis of HS was confirmed by abnormal osmotic fragility test. Direct antiglobulin test was negative. Thereafter, she was hospitalized 7 times in the span of 2 years for episodes of severe hemolytic anemia (Hgb ranging 2.6 to 6.3 g/dl and reticulocyte count 10.4 to 29.98%) with marked splenomegaly (as large as 12 cm below costal margin), associated with febrile illnesses. Her baseline Hgb concentration was 8–9 g/dl. She also experienced a dramatic rise in Hgb and rapid resolution of splenomegaly following red cell transfusions. Child underwent splenectomy recently. Her spleen weighed 307 grams; histologic findings were similar as for Patient 1. Conclusion: The above reported cases illustrate that children with combined heterozygosity of AS and HS clinically and hematologically manifest as classical HS (i.e. chronic hemolytic anemia, splenomegaly), but the sickle cell component adds recurrent ASSC to the picture. It has been suggested that the high MCHC characteristic of HS which results in elevated erythrocytic Hgb S concentration might be a predisposing factor for development of ASSC. In addition, we surmise that fever and dehydration during infections worsen the hypoxic and acidotic splenic milieu which predisposes to massive intrasplenic sickling. In a single previously reported experience on two other children with AS and HS whose clinical course was complicated by ASSC, splenectomy was performed. Based on our experience, we suggest that patients with sickle cell trait presenting with hemolytic anemia and splenomegaly should be thoroughly evaluated to exclude HS. Likewise, given the life-threatening nature of the splenic sequestrations observed in our patients, splenectomy (after due immunizations) appears to be the best treatment approach for these children. Disclosures: No relevant conflicts of interest to declare.

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Quality Assessment of Health Information about Scaphoid Fracture in Chinese Websites (Preprint)

10.2196/preprints.13412 ◽

2019 ◽

Author(s):

Yaobin Yin ◽

Jianguang Ji ◽

Peng Lu ◽

Wenyao Zhong ◽

Liying Sun ◽

...

Keyword(s):

Social Networks ◽

Health Information ◽

Search Engines ◽

Medical Information ◽

Scaphoid Fracture ◽

Family Members ◽

Online Information ◽

Specific Content ◽

The Mean

BACKGROUND With online health information becoming increasingly popular among patients and their family members, concerns have been raised about the accuracy from the websites. OBJECTIVE We aimed to evaluate the overall quality of the online information about scaphoid fracture obtained from Chinese websites using the local search engines. METHODS We conducted an online search using the keyword “scaphoid fracture” from the top 5 search engines in China, i.e. Baidu, Shenma, Haosou, Sougou and Bing, and gathered the top ranked websites, which included a total of 120 websites. Among them, 81 websites were kept for further analyses by removing duplicated and unrelated one as well as websites requiring payment. These websites were classified into four categories, including forum/social networks, commercials, academics and physician’s personals. Health information evaluation tool DISCERN and Scaphoid Fracture Specific Content Score (SFSCS) were used to assess the quality of the websites. RESULTS Among the 81 Chinese websites that we studied, commercial websites were the most common one accounting more than half of all websites. The mean DISCERN score of the 81 websites was 25.56 and no website had a score A (ranging from 64 to 80).The mean SFSCS score was 10.04 and no website had a score A (range between 24 and 30). In addition, DISCERN and SFSCS scores from academic and physician’s websites were significantly higher than those from the forum/social networks and commercials. CONCLUSIONS The overall quality of health information obtained from Chinese websites about scaphoid fracture was very low, suggesting that patients and their family members should be aware such deficiency and pay special attentions for the medical information obtained by using the current search engines in China.

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A Japanese hereditary spastic paraplegia family with a rare nonsynonymous variant in the SPAST gene

Human Genome Variation ◽

10.1038/s41439-021-00153-x ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Takuya Morikawa ◽

Shiroh Miura ◽

Takahisa Tateishi ◽

Kazuhito Noda ◽

Hiroki Shibata

Keyword(s):

Molecular Diagnosis ◽

Hereditary Spastic Paraplegia ◽

Autosomal Dominant ◽

Family Members ◽

Pathogenic Variant ◽

Lower Limbs ◽

Spastic Paraplegia ◽

Nonsynonymous Variant ◽

Japanese Family ◽

Functional Variants

AbstractSpastic paraplegia (SPG) type 4 is an autosomal dominant SPG caused by functional variants in the SPAST gene. We examined a Japanese family with three autosomal dominant SPG patients. These patients presented with typical symptoms of SPG, such as spasticity of the lower limbs. We identified a rare nonsynonymous variant, NM_014946.4:c.1252G>A [p.Glu418Lys], in all three family members. This variant has previously been reported in a Russian SPG family as a “likely pathogenic” variant.5 Ascertainment of additional patients carrying this variant in an unrelated Japanese SPG family further supports its pathogenicity. Molecular diagnosis of SPG4 in this family with hereditary spastic paraplegia is confirmed.

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THALASSEMIA-HEMOGLOBIN C DISEASE IN WHITE SIBLINGS

PEDIATRICS ◽

10.1542/peds.17.5.740 ◽

1956 ◽

Vol 17 (5) ◽

pp. 740-746

Author(s):

Marion Erlandson ◽

Carl H. Smith ◽

Irving Schulman

Keyword(s):

Blood Smear ◽

Family Members ◽

Microcytic Anemia ◽

Target Cells ◽

The Third ◽

Hemoglobin C ◽

Large Numbers

Two white sisters of Italian parentage in whom thalassemia-hemoglobin C disease was found, have been presented. This is the third report of such cases and the first in white individuals. This disease produces a microcytic anemia which is usually mild but which may be severe. Splenomegaly may or may not be present. The presence of large numbers of both microspherocytes and target cells in the blood smear should suggest the possibility of this diagnosis. Confirmatory evidence is found in studies of the blood of family members.

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Viral Dynamics of Acute HIV-1 Infection

Journal of Experimental Medicine ◽

10.1084/jem.190.6.841 ◽

1999 ◽

Vol 190 (6) ◽

pp. 841-850 ◽

Cited By ~ 186

Author(s):

Susan J. Little ◽

Angela R. McLean ◽

Celsa A. Spina ◽

Douglas D. Richman ◽

Diane V. Havlir

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Doubling Time ◽

Basic Reproductive Number ◽

Reproductive Number ◽

Target Cells ◽

Viral Dynamics ◽

Acute Hiv Infection ◽

Acute Hiv ◽

The Mean

Viral dynamics were intensively investigated in eight patients with acute HIV infection to define the earliest rates of change in plasma HIV RNA before and after the start of antiretroviral therapy. We report the first estimates of the basic reproductive number (R0), the number of cells infected by the progeny of an infected cell during its lifetime when target cells are not depleted. The mean initial viral doubling time was 10 h, and the peak of viremia occurred 21 d after reported HIV exposure. The spontaneous rate of decline (α) was highly variable among individuals. The phase 1 viral decay rate (δI = 0.3/day) in subjects initiating potent antiretroviral therapy during acute HIV infection was similar to estimates from treated subjects with chronic HIV infection. The doubling time in two subjects who discontinued antiretroviral therapy was almost five times slower than during acute infection. The mean basic reproductive number (R0) of 19.3 during the logarithmic growth phase of primary HIV infection suggested that a vaccine or postexposure prophylaxis of at least 95% efficacy would be needed to extinguish productive viral infection in the absence of drug resistance or viral latency. These measurements provide a basis for comparison of vaccine and other strategies and support the validity of the simian immunodeficiency virus macaque model of acute HIV infection.

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