scholarly journals Hereditary Spherocytosis

Blood ◽  
1951 ◽  
Vol 6 (11) ◽  
pp. 1073-1098 ◽  
Author(s):  
LAWRENCE E. YOUNG ◽  
MARY JANE IZZO ◽  
RICHARD F. PLATZER
Keyword(s):  
Body Temperature ◽  
Gene Mutation ◽  
Hereditary Spherocytosis ◽  
Osmotic Fragility ◽  
Red Cells ◽  
Laboratory Findings ◽  
Low Degree ◽  
Qualitative Test ◽  
Chronic Hemolytic Anemia

Abstract Clinical, hematologic and genetic data on 28 cases of hereditary spherocytosis are presented for the purpose of characterizing this disorder as completely as possible. On the basis of this experience it is recommended that the following typical laboratory findings be sought in establishing a diagnosis in suspected cases: (1) Presence of spherocytes or abnormally thick red cells in peripheral blood; (2) greater than normal osmotic fragility of the red cells; in cases in which the fragility of fresh cells is not significantly increased, determinations should be made after sterile incubation of the blood at body temperature for 24 hours; (3) greater than normal mechanical fragility of freshly drawn red cells; (4) negative antiglobulin (Coombs) test; (5) greater than normal lysis of the red cells during sterile incubation at body temperature for 48 hours; and (6) presence of similar abnormalities in relatives. Abnormality of the erythrocyte persisted in all of the 11 patients in this series followed one or more years after splenectomy. An unusual case of chronic hemolytic anemia is described but not included in the numbered series because (1) both parents were hematologically normal and (2) spherocytosis and abnormally great osmotic and mechanical fragility and autohemolysis could not be demonstrated after the fifth postoperative month. Classification of this case is deferred pending further experience. Demonstration in a parent, sibling or offspring of red cells showing the afore-mentioned abnormalities is necessary for an unequivocal diagnosis, but this requirement cannot always be met because relatives may not be available for examination. Moreover, when parents and/or several siblings are examined without positive findings, low gene expressivity, gene mutation and illegitimacy may be considered as explanations. Evidence is cited to suggest the possibility of a low degree of penetrance or expression in some cases and to illustrate the need for still more sensitive laboratory tests that might aid in diagnosis of the mildest forms of this disease. The lower incidence of spherocytosis in siblings of propositi than in offspring of propositi is cited as evidence bearing on the theory of gene mutation in some propositi. A simplified "qualitative" test of osmotic fragility of incubated red cells is described.

scholarly journals Atypical Familial Hemolytic Anemia

Blood ◽  
1956 ◽  
Vol 11 (4) ◽  
pp. 324-337 ◽  
Author(s):  
R. K. SMILEY ◽  
H. DEMPSEY ◽  
P. VILLENEUVE ◽  
J. S. CAMPBELL ◽  
BARBARA BEST
Keyword(s):  
Hemolytic Anemia ◽  
Hereditary Spherocytosis ◽  
Red Cells ◽  
Red Cell ◽  
French Canadian ◽  
Blood Group A ◽  
Group A ◽  
Red Cell Survival ◽  
Morphologic Abnormality ◽  
Chronic Hemolytic Anemia

Abstract 1. The genetic, clinical and hematologic features of an atypical chronic hemolytic anemia in two siblings of a French Canadian family have been described. 2. The anemia is normocytic, normochromic and not associated with any characteristic morphologic abnormality of the red cells. 3. Slight increases in osmotic and incubated mechanical fragility, as well as a more definite increase in aumtohemolysis were found which could not be demonstrated after splenectomy. 4. The survival time of normal red cells was shortened before splenectomy in one patient. Normal red cell survival was demonstrated in both patients after splenectomy. 5. The features which differentiate this hemolytic anemia from hereditary spherocytosis are discussed. 6. French or French Canadian ancestry has been noted in some of the reported patients most similar to our own. 7. The association of this type of hemolytic anemia with blood group A has been confirmed in our patients. 8. Splenectomy decreased the severity of the hemolytic process in both patients. This benefit may have resulted from removal of an extracorpuscuar hemolytic mechanism.

scholarly journals Physical Properties of Red Cells as Related to Effects in Vivo. III. Effect of Thermal Treatment on Survival of Red Cells in the Dog. Role of the Spleen

Blood ◽  
1968 ◽  
Vol 32 (6) ◽  
pp. 872-883 ◽  
Author(s):  
DENNIS J. CARLSON ◽  
THOMAS HALE HAM
Keyword(s):  
Sickle Cell Disease ◽  
Thermal Treatment ◽  
Peripheral Blood ◽  
Hereditary Spherocytosis ◽  
Osmotic Fragility ◽  
Red Cells ◽  
Cell Disease ◽  
Homozygous Sickle Cell Disease

Abstract Dog red cells heated at 49 C. for 15 minutes with no change in osmotic fragility, showed a decreased rate of survival in vivo, and increased sequestration by the spleen, and an increase in the osmotic fragility when recovered from the spleen. The peripheral blood showed normal osmotic fragility at all times. These changes were comparable to those seen in the spleen in homozygous sickle-cell disease and hereditary spherocytosis. There was no hemoglobinemia. Splenectomy decreased the rate of destruction of such heated red cells in vivo. In these studies the rigidity of the red cells with increased viscosity, but with normal osmotic fragility, may have resulted in the removal of the heated red cells by the spleen and subsequent conditioning of these cells in the spleen. In contrast to the 15 minutes heating, dog cells heated at 49 C. for 60 minutes had increased osmotic fragility and were rapidly removed from the circulation. There was sequestration by the spleen or by the liver with hemoglobinemia. The red cells with the greatest increase in osmotic fragility were not preferentially removed in vivo.

scholarly journals Hereditary Spherocytosis

Blood ◽  
1951 ◽  
Vol 6 (11) ◽  
pp. 1099-1113 ◽  
Author(s):  
LAWRENCE E. YOUNG ◽  
RICHARD F. PLATZER ◽  
DONALD M. ERVIN ◽  
MARY JANE IZZO
Keyword(s):  
Peripheral Blood ◽  
Fanconi Syndrome ◽  
Congenital Abnormalities ◽  
Hereditary Spherocytosis ◽  
Osmotic Fragility ◽  
Test Tube ◽  
Red Cells ◽  
Blood Samples ◽  
Selective Retention ◽  
Multiple Congenital Abnormalities

Abstract 1. Three patients with hereditary spherocytosis and 1 patient with the Fanconi syndrome (pancytopenia and multiple congenital abnormalities) were transfused prior to splenectomy with normal erythrocytes of types which could be differentiated serologically from those of the recipients. The proportions of donated and patient’s cells in peripheral blood and in blood washed from the minced spleens were determined by differential agglutination, and the osmotic and mechanical fragilities of the two types of cells in peripheral and splenic blood were measured by differential agglutination of the corpuscles remaining in each test tube after partial hemolysis had occurred. 2. In each case of hereditary spherocytosis the proportion of recipient’s cells was much higher in splenic than in peripheral blood, indicating selective retention of the thicker corpuscles within the spleen. Osmotic fragility of thie patient’s red cells was much greater in samples of splenic mince blood than in peripheral venous samples, while the fragility of the donated red corpuscles was normal or nearly normal in both splenic and peripheral blood. In the patient exhibiting the Fanconi syndrome, on the other hand, neither the patient’s red cells nor donated red cells were retained to any extent in the spleen and the fragility of neither type of cell was altered. 3. Spleens removed surgically from 3 patients with idiopathic thrombocytopenic purpura were perfused with mixtures of normal A or B cells and group O cells drawn from a splenectomized individual with hereditary spherocytosis. During perfusion the spheroidal cells were selectively removed from the mixtures and at the end of each experiment red cells of this type predominated in the blood samples washed from the minced spleens. A fourth excised spleen was perfused with a mixture of two types of normal cells, neither of which was retained to any extent by the spleen during perfusion. The perfusion experiments show that spleens from patients with nonhemolytic disease are also capable of selective trapping of spheroidal cells. 4. The experiments described indicate that the spleen acts as a filter and trap and as an "incubator" in accelerating destruction of red corpuscles in patients with hereditary spherocytosis.

scholarly journals Studies on Spontaneous In Vitro Autohemolysis in Hemolytic Disorders

Blood ◽  
1956 ◽  
Vol 11 (11) ◽  
pp. 977-997 ◽  
Author(s):  
LAWRENCE E. YOUNG ◽  
MARY JANE IZZO ◽  
KURT I. ALTMAN ◽  
SCOTT N. SWISHER
Keyword(s):  
Lactic Acid ◽  
Hereditary Spherocytosis ◽  
Substantial Reduction ◽  
Osmotic Fragility ◽  
Red Cells ◽  
Hemolytic Disease ◽  
Myeloid Metaplasia ◽  
Effect Of Glucose

Abstract Measurements of spontaneous lysis (autohemolysis) of red cells in sterile defibrinated blood after 48 or more hours of incubation at body temperature were found useful in the investigation of certain hemolytic states. Abnormally rapid autohemolysis was demonstrated most consistently in hereditary spherocytosis, but was also found in other types of spherocytosis and in several examples of non-spherocytic hemolytic anemia. Autohemolysis above the normal range can be regarded as strong presumptive evidence of a hemolytic disorder, but a normal rate of autohemolysis by no means excludes the possibility of a hemolytic process in any given case. Abnormalities of hereditary spherocytes causing increased autohemolysis were shown to be correlated with those responsible for spherocytosis as reflected in osmotic fragility tests. There appeared to be closer correlation with abnormalities causing increased osmotic fragility of the cells after 24 hours incubation. The autohemolysis test and the osmotic fragility test on incubated red cells were found to be equally sensitive in their capacity to detect spherocytosis of the hereditary type. Addition of adenosine, guanosine or inosine caused moderate to marked reduction in autohemolysis of nearly all types of red cells tested. Lysis of incubated spherocytes from active cases of autoimmune hemolytic disease was more markedly inhibited by a small amount of adenosine than was the lysis of hereditary spherocytes. Glucose regularly caused marked inhibition of autohemolysis of hereditary spherocytes and of red cells from patients with acute leukemia. The effect of glucose on HS red cells might have been due in part to a lowering of pH by formation of lactic acid since acidification of the blood with lactic, citric or hydrochloric acid also caused substantial reduction in autohemolysis. Glucose caused slight to marked increase in lysis of red cells in certain other cases of spherocytosis, notably in autoimmune hemolytic disease and in myeloid metaplasia. Addition of lactic acid to the blood from several of these patients had similar effect. In 2 atypical cases of chronic spherocytosis, with hematologically normal relatives, autohemolysis was accelerated by addition of glucose to the blood samples. Adenosine had little effect until after splenectomy when both glucose and adenosine inhibited hemolysis, much the same as in blood from typical cases of hereditary spherocytosis. It seems likely that when the abnormalities of carbohydrate metabolism of the red cells in certain hemolytic disorders are better understood, measurements of autohemolysis may be modified so as to enhance their usefulness in detecting and differentiating the various hemolytic states. It also seems likely that further studies on in vitro autohemolysis will help to elucidate some hemolytic mechanisms operating in vivo.

HEMOLYTIC DISEASE OF THE NEWBORN DUE TO ANTI-A AND ANTI-B

PEDIATRICS ◽  
1955 ◽  
Vol 15 (1) ◽  
pp. 54-62
Author(s):  
Clare N. Shumway ◽  
Gerald Miller ◽  
Lawrence E. Young
Keyword(s):  
B Cells ◽  
Red Blood Cells ◽  
Blood Group ◽  
Newborn Infant ◽  
Blood Cells ◽  
Osmotic Fragility ◽  
Red Cells ◽  
Hemolytic Disease ◽  
Abo Incompatibility

Ten infants with hemolytic disease of the newborn due to ABO incompatibility were studied. In every case the investigations were undertaken because of jaundice occurring in the first 24 hours of life. The clinical, hematologic and serologic observations in the infants and the serologic findings in the maternal sera are described. Evidence is presented to show that the diagnosis of the disorder rests largely upon the demonstration of spherocytosis, increased osmotic fragility of the red cells, reticulocytosis, and hyperbilirubinemia in a newborn infant whose red blood cells are incompatible with the maternal major blood group isoantibody and against whose cells no other maternal isoantibody is demonstrable. The anti-A or anti-B in each of the maternal sera tested in this series hemolyzed A or B cells in the presence of complement. Other serologic findings in the maternal sera were less consistently demonstrated.

scholarly journals Clinical and genetic diagnosis of thirteen Japanese patients with hereditary spherocytosis

2022 ◽  
Vol 9 (1) ◽  
Author(s):  
Keiko Shimojima Yamamoto ◽  
Taiju Utshigisawa ◽  
Hiromi Ogura ◽  
Takako Aoki ◽  
Takahiro Kawakami ◽  
...  
Keyword(s):  
Hemolytic Anemia ◽  
Hereditary Spherocytosis ◽  
Genetic Diagnosis ◽  
Genomic Analysis ◽  
Japanese Patients ◽  
Asian Countries ◽  
Target Capture ◽  
Detailed Family History ◽  
Target Capture Sequencing ◽  
Chronic Hemolytic Anemia

AbstractHereditary spherocytosis is the most frequent cause of hereditary hemolytic anemia and is classified into five subtypes (SPH1-5) according to OMIM. Because the clinical and laboratory features of patients with SPH1-5 are variable, it is difficult to classify these patients into the five subtypes based only on these features. We performed target capture sequencing in 51 patients with hemolytic anemia associated with/without morphological abnormalities in red blood cells. Thirteen variants were identified in five hereditary spherocytosis-related genes (six in ANK1 [SPH1]; four in SPTB [SPH2]; and one in each of SPTA1 [SPH3], SLC4A1 [SPH4], and EPB42 [SPH5]). Among these variants, seven were novel. The distribution pattern of the variants was different from that reported previously in Japan but similar to those reported in other Asian countries. Comprehensive genomic analysis would be useful and recommended, especially for patients without a detailed family history and those receiving frequent blood transfusions due to chronic hemolytic anemia.

scholarly journals Erythrocyte cellular and membrane deformability in hereditary spherocytosis

Blood ◽  
1979 ◽  
Vol 53 (3) ◽  
pp. 481-485 ◽  
Author(s):  
K Nakashima ◽  
E Beutler
Keyword(s):  
Cell Membrane ◽  
Hereditary Spherocytosis ◽  
Volume Ratio ◽  
Osmotic Fragility ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Relative Rigidity ◽  
Altered Surface ◽  
Red Cell Membranes ◽  
Expected Increase

In order to determine whether the relative rigidity of the hereditary spherocytosis (HS) red cell is due to membrane rididity or merely to an altered surface/volume ratio, we investigated the deformability of resealed red cell membranes from patients with HS. Whereas the osmotic fragility of intact red cells of HS patients showed the expected increase, the osmotic fragility of resealed HS membranes was normal, thus indicating that their surface/volume ratio was normal. Measurements with an ektacytometer showed that deformability of intact HS cells was markedly diminished, whereas deformability of resealed HS membranes was normal. These findings indicate that the HS red cell membrane is not intrinsically abnormally rigid, as has been suggested, but that the lack of deformability of the erythrocyte is primarily a function of the altered surface/volume ratio.

Sign in / Sign up

Export Citation Format

Share Document