Showing papers in "American Journal of Hematology in 1985"

Lupus anticoagulant: An analysis of the clinical and laboratory features of 219 cases

Abstract: To define clinical and laboratory characteristics of the lupus anticoagulant (LA), we reviewed our experience (219 subjects). Subjects were divided into group A, those with the LA and the diagnosis of lupus erythematosus, group B, those with the LA but nonlupus diagnoses, and group C, those with drug-related lupus syndromes. The typical laboratory findings consisted of a prolonged and inhibited plasma clot time (an average of 1.9 times control time) which was proportionately more prolonged than the partial thromboplastin time or activated partial thromboplastin time (APTT) (average 1.3 times control). Ninety-eight percent had a prolonged plasma clot time and 94% had a prolonged partial thromboplastin time. The prothrombin and thrombin times were prolonged in 33 and 25% of subjects, respectively. Washed platelets shortened the APTT in the 22 subjects so tested. Monoclonal protein peaks were seen in 7% of patients. Seventeen episodes of bleeding were observed, but in all but one instance there was another hemostatic defect present. In the 18 patients who underwent major operations, there were no hemorrhagic complications. Fifty-eight episodes of thrombosis were observed with the same incidence in group A (25%) as in group B (26%). Bleeding is rare with the LA but thrombosis is common even without SLE and lupuslike syndromes. The plasma clot time in platelet-rich plasma is more prolonged, and in our experience, is more sensitive in detecting the lupus anticoagulant than is the partial thromboplastin time.

The incidence of thrombotic and hemorrhagic disorders in association with extreme thrombocytosis: An analysis of 129 cases

Abstract: We have presented a retrospective study of 129 patients with platelet counts of 1,000 X 10(9)/L or more--72 with myeloproliferative disorders (MPD), and 57 with reactive thrombocytosis (RT)--in an effort to determine the incidence of thrombohemorrhagic complications. Thrombotic disorders occurred with approximately equal frequency in the two groups, being found in three patients (4%) with MPD and three (5%) with RT when the platelet count was over 1,000 X 10(9)/L and in 11% of the patients in each group when the platelet count was less than 1,000 X 10(9)/L. In contrast, bleeding manifestations were more common in MPD, where 36% of patients were affected on one or more occasions versus only 4% of those with RT. However, bleeding was generally not severe, with only six patients requiring transfusions, and three of these patients had been receiving aspirin or corticosteroids when they developed severe gastrointestinal bleeding.

Increased numbers of marrow basophils may be associated with a t(6;9) in ANLL.

Abstract: We have characterized another subset of acute nonlymphocytic leukemia (ANLL) based on the cytogenetic and morphologic findings in a group of nine patients. Five patients had chromosomal analyses performed at the University of Chicago, two patients were studied at the All-Union Cancer Research Center in Moscow, and one patient each was studied at the University of Maryland and at Fairfax Hospital in Fairfax, Virginia. All nine patients had a reciprocal translocation involving the short arm of chromosome 6 and the long arm of chromosome 9 [t(6;9)(p23;q34)]. The patients, four males and five females, ranged in age from 5 to 51 years; the median age of 38 years is lower than that typically seen in ANLL. Only two of eight treated patients entered a complete remission. Classification of bone marrow morphology according to FAB Cooperative Group criteria revealed AML-M1 in one patient, AML-M2 in four, and AMMoL-M4 in three. One patient had refractory anemia with excess blasts (RAEB) which evolved to AML-M2. All bone marrow specimens showed severe myelodysplasia, with Auer rods present in seven of the nine cases. Of note was the particular prominence of bone marrow basophils (greater than 1%) in eight of the nine (89%) patients. Among 160 evaluable patients with ANLL de novo seen at the University of Chicago whose cells lacked a t(6;9), only five (3%) had greater than 1% basophils in the marrow aspirates. It is of interest that the breakpoint in 9q involves the same chromosomal band as that in the t(9;22) observed in chronic myelogenous leukemia (CML), in which increased basophils are a prominent feature. Thus, the association of the t(6;9) with increased bone marrow basophils in ANLL may provide additional insight into the chromosomal location of genes regulating the production and/or maturation of basophils.

Therapy of chronic relapsing thrombotic thrombocytopenic purpura with prednisone and azathioprine

Abstract: As a 51-year-old woman recovered from an initial acute episode of thrombotic thrombocytopenic purpura (TTP), her plasma was found to contain unusually large von Willebrand factor (vWF) multimers. Clinical, hematological, and vWF studies of her siblings and children were normal. The unusually large vWF forms were presumably derived from endothelial cells, persisted in her plasma after recovery, and were associated with recurrent episodes of TTP during the subsequent 6 months. After the last episode of relapse they disappeared from her plasma following 3 1/2 weeks of therapy with prednisone and did not return during 17 months of treatment with prednisone and/or azathioprine. She is now receiving no drugs, has normal plasma vWF forms, and has not had any more episodes of TTP. We conclude that our patient had an acquired defect in the conversion of unusually large vWF multimers derived from endothelial cells to the somewhat smaller vWF forms usually present in circulation. The defect may have been immune-mediated, because it was eliminated during therapy with immunosuppressive drugs.

Beta2 microglobulin in multiple myeloma

Abstract: Serum beta 2 microglobulin levels (B2M) were evaluated before and during chemotherapy in 97 previously untreated patients with multiple myeloma. Pretreatment values were useful in confirming tumor mass grade, and marked reductions following chemotherapy correlated well with the onset of remission. No gain was evident from correcting the B2M for the level of serum creatinine. A pretreatment B2M value greater than 6 mg/L correlated with a low response rate and was the most important variable that predicted a short survival time.

Positive direct antiglobulin test associated with hyperglobulinemia in acquired immunodeficiency syndrome (AIDS)

Abstract: This study determined the prevalence and clinical significance of a positive direct antiglobulin test (DAT) observed in pretransfusion tests on red cells from patients with acquired immunodeficiency syndrome (AIDS). Transfusion service records showed that prevalence of a positive DAT on red cells was 18% (10/55) in AIDS patients compared to 0.6% in general hospital patients during a 2-year period (1981-1983). A similar rate of 18% (8/45) was observed in other hyperglobulinemic patients. Of the 10 AIDS patients whose red cells were DAT positive, four had IgG and complement, four had IgG, and two had complement alone on their red cells. The eluates were not reactive with normal red cells nor with penicillin or cephalothin-coated red cells. Clinically, no hemolysis was observed. In this series a positive DAT in AIDS patients appeared not to be associated with autoimmune hemolytic anemia. The positive DAT in AIDS patients may be due to the hyperglobulinemic state.

Liver involvement in multiple myeloma.

Abstract: One hundred twenty-eight records of patients with multiple myeloma were reviewed to assess the incidence and manifestations of liver involvement. Histologic study of the liver was available in 21 patients. Diffuse infiltration of the liver by plasma cells was observed in 10 patients, myeloid metaplasia in four, amyloidosis in two, toxic hepatitis in two, and extrahepatic cholestasis secondary to infiltration of the peripancreatic tissue by plasma cells in one. The clinical signs of plasma cell infiltration of the liver consisted of hepatomegaly in seven patients, mild elevation of liver enzymes in five, and portal hypertension in two. Jaundice was only observed in patients with hepatitis or extrahepatic cholestasis. Liver infiltration by plasma cells did not appear to have a major prognostic significance.

Immunofluorescent plasma cell labeling indices (LI) using a monoclonal antibody (BU-1).

Abstract: Tritiated thymidine labeling indices (LI), although useful in diagnosis and prognosis of multiple myeloma, have not found wide-spread application because autoradiographic analysis is diffucult and time consuming. Using a monoclonal antibody (BU-1) reactive with 5-bromo-2-deoxyuridine (BrdUrd), we have developed an immuno-fluorescent procedure that allows DNA S-phase measurements to be determined in 4 hr. Plasma cells are easily identified by reactivity with a fluorescein isothiocya-nate-conjugated antihuman immunoglobulin, and cells in DNA S phase are detected via BU-1 and a rhodamine-conjugated antimouse immunoglobulin. Results using this method on 12 patients with multiple myeloma compare favorably (correlation coefficient 0.84), with those obtained by tritiated thymidine. This immunofluorescent slide method will facilitate application of labeling indices as a clinical test to measure disease activity in patients with multiple myeloma and other hematologic neoplasms.

Hematopoiesis and aging III: Anemia and a blunted erythropoietic response to hemorrhage in aged mice.

Abstract: Whether the hematocrit normally declines in the aged or whether such a decline represents inapparent disease in addition to aging is a matter of dispute. Female B6D2f1 mice were studied at ages 3, 13, or 27-28 months, and there was no difference in hematocrit between the younger groups. The hematocrit of 45 aged mice was slightly lower than that of 66 younger mice; mean 43% vs 49% (p less than .001). However, rather unexpectedly, the total red cell mass was not decreased in the aged; rather, the plasma volume was expanded. Survival of mature red blood cells did not differ significantly between young and aged mice. Mice were bled 0.4 ml from the orbital sinus for 4 days, reducing the hematocrit of all groups to a nadir of 20-25%. Recovery of hematocrit began more slowly in aged than in young mice. That this reflected a difference in erythropoiesis rather than a difference in plasma volume equilibration was suggested by studies with 59Fe. 59Fe was given following the second bleed, and 1 day later RBC 59Fe was more than twice as high in young mice than in groups of aged mice. Aged mice that did not appear healthy had been excluded. Aged mice were divided into a group with significant amounts of gray hair and/or patches of hair loss and two groups with normal-appearing hair; the latter was subdivided into those weighing less (25-26 g) or more (30-34 g) than most aged mice. Neither hair condition nor weight influenced hematocrit or response to bleeding. These results suggest, but do not prove, that a mild "dilutional" anemia and a blunted erythropoietic response to hemorrhage may be an expected part of the murine aging process.

Characteristics of hexokinase, pyruvate kinase, and glucose-6-phosphate dehydrogenase during adult and neonatal reticulocyte maturation

Abstract: Erythrocytes from adults and newborn infants (at term and premature) were separated by Percoll density gradient centrifugation into four fractions of increasing density. Glycolytic enzymes, especially the age-dependent ones, hexokinase (EC 2.7.1.1, HK), pyruvate kinase (EC 2.7.1.40, PK), and glucose-6-phosphate dehydrogenase (EC 1.1.1.49, G6PD) were studied during reticulocyte maturation and further red cell senescence. Analysis of the fraction with lowest density showed an almost linear and steep decline of HK, PK, and G6PD activity with a decreasing number of reticulocytes. In the next three fractions of increasing density, the activity decline was far less. These data are therefore illustrative for a biphasic activity decay pattern of HK, PK, and G6PD during both adult and neonatal red cell aging. The strong decline in HK activity could not be ascribed to the disappearance of a particulate (mitochondrial) bound fraction of the enzyme during reticulocyte maturation. All hexokinase activity in human reticulocytes was found to be cytosolic in contrast with rabbit reticulocytes in which 70% of HK activity was particulate.

Defective complement activity in chronic lymphocytic leukemia

Abstract: Patients with chronic lymphocytic leukemia (CLL) are at an increased risk for infections with bacteria which require complement for osponization. We explored the possibility that patients with CLL have a defect in binding the potent opsonin C3b to bacteria. Bacteria selected for these experiments included Streptococcus pneumoniae type 3, which binds C3 by activating the classical complement pathway (CCP), type 25, which can bind normal amounts of C3b by the alternative complement pathway (ACP), type 14, which can activate both the CCP and ACP, and Staphylococcus aureus and Escherichia coli, both of which activate the CCP. Bacteria were treated with normal serum or serum from 15 patients with CLL, and the bound C3b was quantified spectrophotofluorometrically. Despite normal serum concentrations of C3, C4, Factor B, C-reactive protein, and total hemolytic complement activity, all 15 CLL sera bound reduced amounts of C3b to at least one bacterial species; 9 to S pneumoniae type 3, 8 to types 14 and 25, 11 to S aureus, and 13 to E coli. Mixing normal serum with CLL serum restored C3b binding to all bacteria, suggesting a deficiency rather than an inhibitor of activity. Serum from ten hypogammaglobulinemic CLL patients bound less C3b (62.7 +/- 5% of normal) (means +/- SEM) than those with normal immunoglobulin levels (81.9 +/- 5%) (p less than .005). Nevertheless, the addition of specific antibacterial antibodies to CLL serum did not enhance C3b binding to any of the bacteria. Serum from patients with a history of a bacterial infection bound less C3b (62.3 +/- 5%) than those without a history of infections (76.1 +/- 6%) (p less than .05). Thus, there is a defect in either the activation or activity of C3 in CLL serum which may contribute to the increased incidence of infections in these patients.

Human polymorphonuclear leukocytes of the bone marrow, circulation, and marginated pool: Function and granule protein content

Abstract: Polymorphonuclear leukocytes (PMN) demonstrate altered function during acute infections and after administration of corticosteroids. We questioned whether or not such changes are due to population shifts from functionally different compartments of the granulocyte pool. Volunteers were given epinephrine to induce demargination or hydrocortisone (HC) to promote egress of PMN from the bone marrow. PMN obtained before and after drug administration were compared for adherence, chemotaxis, luminol-enhanced chemiluminescence, and total content and release of lactoferrin (LF), myeloperoxidase (MPO), and beta-glucuronidase (beta-glu). Epinephrine induced a significant neutrophilia of mature PMN (segmented neutrophils), but there were no changes in function or granule protein content. HC induced a significant neutrophilia with segmented neutrophils and immature PMN (bands). Circulating PMN obtained 4 hr after HC administration demonstrated less adherence, increased chemiluminescence, increased MPO release, and decreased MPO content. Band neutrophils, however, were more adherent than segmented PMN and showed a similar decrease in adherence following HC in vivo. Thus alteration of PMN adherence following intravenous corticosteroids is not due to an influx of immature neutrophils. On the other hand, it is possible that MPO content and release and capacity for oxidative metabolism change as PMN mature.

Concomitant inheritance of alpha-thalassemia in beta 0- thalassemia/Hb E disease.

Abstract: Concomitant inheritance of alpha-thalassemia in patients with beta 0-thalassemia/hemoglobin (Hb) E disease was detected by restriction endonuclease DNA mapping. Among 42 patients with beta 0-thalassemia/Hb E disease, seven were found to have an alpha-thalassemia-2 haplotype. Of these, five belonged to the rightward or 3.7-kb type of alpha-thalassemia-2 and the remaining two the leftward or 4.2-kb type. All the seven patients with alpha-thalassemia-2 haplotype had hemoglobin levels of 7.4 g/dl or above; those without detectable alpha-thalassemia had hemoglobin levels both higher and lower than 7.4 g/dl. The latter attended the clinic regularly, the former did occasionally. These findings suggest that concomitant inheritance of alpha-thalassemia can alleviate the severity of beta 0-thalassemia/Hb E disease. Failure to find alpha-thalassemia-1 haplotype in these patients suggests that concomitant inheritance of alpha-thalassemia-1 with beta 0-thalassemia/Hb E might lead to so mild a condition that the individuals do not present clinically. The fact that many patients without a detectable alpha-thalassemia haplotype also had hemoglobin levels of 7.4 g/dl or higher suggests that there are additional factors responsible for the mildness of beta 0-thalassemia/Hb E disease.

Perfluorocarbon compounds: effects on the rheological properties of sickle erythrocytes in vitro.

Abstract: The effects of oxygenated perfluorotributylamine (Fluosol-43) on the rheological properties of sickle (HbSS) erythrocytes have been determined by means of microviscometry and positive pressure cell filtration. Incubation of deoxygenated sickled erythrocytes (pO2 congruent to 30 mmHg) with oxygenated Fluosol-43 reduced the percentage of sickled erythrocytes from about 63 to 33%. Deoxygenation of 40% suspension of sickle erythrocytes in autologous plasma increased the viscosity by about 160% at shear rate of 1.15 sec-1. Incubation of the deoxygenated sickled erythrocytes with oxygenated Fluosol-43 significantly reduced the viscosity at the low shear rates. Filtration of 0.2% suspension of deoxygenated sickle erythrocytes through capillary-sized Nuclepore filters showed high resistance at low flow rates. Oxygenated Fluosol-43 increased the deformability of HbSS erythrocytes and thereby reduced the resistance at flow rates less than 1 ml/min. These data suggest that perfluorocarbons may be useful in reducing the propensity of hemoglobin S polymerization and sickling and thereby prevent tissue infarction in vaso-occlusive crisis. Therefore, the concept of examining the potential application of perfluorochemicals for alleviating severe vaso-occlusive events may be useful.

Complications of heparin administration in normal individuals

Abstract: The incidence, severity, and pathogenic mechanism of heparin-associated thrombocytopenia with both bovine and porcine heparin administration were studied in forty normal males randomized to one of four treatment groups: beef lung heparin #1, beef lung heparin #2, porcine gut heparin, and saline control. All of the subjects receiving heparin developed a reversible increase in serum transaminases (SGOT, SGPT). However, other measurements of liver function were normal. Thirty-three percent of these heparinized normals had decreased platelet counts. The incidence of platelet count decrease was similar for both bovine and porcine heparins, but 4 of the 20 normals receiving bovine heparin had platelet counts less than 150,000/microliters. Immune pathogenesis was investigated by analyzing plasma from the volunteers for both platelet antibody and immune complexes. None of the men had increased platelet-associated IgG. Among the ten subjects with decreased platelet counts, IgG immune complexes were detected in three and C1q in seven. The heparin-associated thrombocytopenia appears not to be mediated by a platelet antibody. More probably it reflects a direct effect of the heparin on platelets.

Human T-cell leukemia virus (HTLV-I) p24 antibody in New York City blood product recipients.

Abstract: Human T-cell leukemia virus (HTLV-I) is known to be associated with certain hematologic malignancies, and a related virus, HTLV-III/LAV, might be the cause of AIDS. Some persons with AIDS have had evidence of HTLV-I infection. Unrelated to these findings, it has been suggested that HTLV-I is transmitted via blood products. We therefore evaluated the serologic status to the HTLV-I core antigen p24 of 48 persons with hemophilia (Hem A) receiving factor concentrate therapy (a group at risk for AIDS), 49 persons with beta-thalassemia major (Thal) receiving frozen packed red blood cells therapy (FPRC), 26 patients with sickle cell anemia (SCA) receiving FPRC, and 18 persons not receiving any blood products. All participants were clinically well; only one had a risk factor other than hemophilia for AIDS, and all were from New York City, an area with a high incidence of AIDS. No Hem A or nontransfused persons had serum antibody to HTLV core p24 antigen; three with Thal and one with SCA were antibody-positive. These results were confirmed by both radioimmunoprecipitation and Western blot techniques. Positive serology did not correlate with any immune findings or quantity of blood products used. These data support that HTLV-I is preferentially transmitted through cellular blood products and that it is an infection for which cellular blood product recipients in at least some areas of the United States are at risk. Concentrate products appear free of transmission risk relative to cellular blood products, but we cannot be certain that this safety is absolute. The public health implications of blood product transmission of HTLV-I merit active, long-term investigation.

Recurring thromboembolic disease and pulmonary hypertension associated with severe hypoplasminogenemia.

Abstract: In a patient with pulmonary hypertension and a history of recurrent venous thrombosis, plasma concentrations of all known coagulant and inhibitor proteins were normal except for severe deficiency of plasminogen. Repeated analyses showed the circulating plasma plasminogen level to be 30% of normal by either functional or immunologic methods. We sought evidence for either increased activation of plasminogen or for dysplasminogen. There was no evidence for the former. Purified plasminogen studies disclosed a normal number of active sites and normal activation. Generated plasmin had normal catalytic activity. Isoelectric focusing disclosed normal distribution of isoforms. Affinity chromatography with lysine-sepharose showed the presence of the two variant forms; however, an increased proportion of the protein eluted in the first peak. Danazol administration induced an increase in circulating plasminogen, but the differences in affinity chromatography elution profile remained. We conclude that this patient has a deficiency of normally functioning plasminogen, probably due to decreased synthesis.

Reproducibility of the French-American-British classification of acute leukemia: the southwest oncology group experience

Abstract: After initial French-American-British (FAB) diagnosis by a multiinstitutional Southwest Oncology Group panel, slides of acute leukemia cases were recirculated to panel members for second review. The reproducibility of the FAB classification is analyzed. The classification is reproducible in the 70% range in panel reviewer hands and allows remarkable reproducibility in the morphologic and cytochemical distinction of acute lymphoid leukemia (ALL) from acute myeloid leukemia (AML). The limitations of a morphologic and cytochemical classification of acute leukemia are discussed. A simplification of the FAB system, merging M1, M2, and M4 as M7, is proposed; this simplification improves the system's reproducibility.

Interferon-induced aplasia: evidence for T-cell-mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin.

Abstract: A severe and persistent pancytopenia occurred in a 42-year-old woman with a non-Hodgkin's lymphoma following a 10-day course of intramuscular human leukocyte alpha interferon (IFN, 9.0 IU/day). Within 2 weeks of IFN, marrow nucleated myeloid and erythroid precursor cells and megakaryocytes were nearly absent and marrow progenitor cells (CFU-E, BFU-E, CFU-GM) were undetectable. Analysis of marrow lymphocytes revealed that nearly 50% of the cells were E-rosette+, T gamma+, OKT8+ (suppressor/cytotoxic) T-and/or Leu 7+ natural killer (NK) lymphocytes and 50% were IgM Kappa, B1+, B-lymphocytes. In vitro erythroid culture studies were consistent with T-cell-mediated suppression of erythropoiesis. After 2 months without improvement on corticosteroid/androgen therapy, a 10-day course of intravenous antithymocyte globulin (ATG) was administered. This was followed by a prompt reticulocytosis and a rise in blood neutrophils. After ATG therapy, there was a sixfold reduction in marrow suppressor cells, loss of in vitro suppressor effects on erythroid progenitor cells, and complete reversal of blood and marrow OKT4/OKT8 (helper/suppressor) ratios. These studies suggest that interferon may suppress hematopoiesis in some patients by activating marrow suppressor T- and/or NK cells. Treatment aimed at reduction of marrow suppressor cells may aid in hematologic recovery without eliminating the infiltrating lymphoma.

Clinical manifestations and erythrocyte adhesion to endothelium in sickle cell syndrome

Abstract: Painful vasocclusive episodes are one of the most prominent pathological features of sickle cell disease. In addition to abnormal shape and poor deformability, increased adhesion of red cells to endothelium has been reported. On several occasions, we have studied the adhesion of erythrocytes from 30 patients with mixed sickle cell syndromes to evaluate the influence of clinical conditions. The percentage of erythrocytes adhering was significantly higher when erythrocytes from sickle patients were compared with controls (p less than 0.01). Furthermore, adhesion was significantly higher when the patients were in crises (p less than 0.01), and the highest values of all were observed in patients with inflammatory conditions. To investigate the possibility that a limited population of red cells could be responsible for the increase in red cell adhesion, we have measured the HbS concentration in the different washes and found that the HbS concentration was higher in the last washes compared to the first washes. Sickle red cells capable of protein synthesis (young red cells) were labelled with [3H] leucine. The adhesion to endothelial cells of [3H] leucine-labelled red cells was higher than that of the 51Cr-labelled red cells from the same patient. On the other hand, the most dense sickle red cells separated by density gradient adhered to a greater extent than the light red cells. This apparent discrepancy could be partly explained by the presence of [3H] leucine-labelled red cells in the dense fractions of sickle red cells separated by stractan gradient.

Multiple cerebral thrombosis in fletcher factor (prekallikrein) deficiency: A case report

Abstract: Despite markedly prolonged activated partial thromboplastin times (APTT) patients with Fletcher factor (prekallikrein) deficiency do not clinically bleed. However, there is one reported case of myocardial infarction associated with prekallikrein deficiency. These clinical observations suggest that the contact mechanism has a minor role in normal in vivo hemostatic function. We report a further two cases of prekallikrein deficiency in Caucasian siblings. The propositus presented with multiple cerebral thrombosis. Cautious anticoagulation resulted in massive cerebral hemorrhage and death of this patient. The sibling was investigated in an attempt to establish a possible defective fibrinolytic pathway in vivo. New sensitive tests for fibrinolysis were used. These included radioimmunoassay of fibrin degradation product "D," B beta 15-42, and in vitro 125I-labelled fibrin lysis assays. The plasma half-life of prekallikrein in this patient was calculated to be 58 hr. Family studies of heterozygotes were also performed. Prekallikrein deficiency is found not to be important in normal in vivo fibrinolysis, which possibly operates via tissue or vessel wall fibrinolytic activator release.

Red cell superoxide dismutase and sickle cell anemia symptom severity.

Abstract: Patients with sickle cell anemia vary in the severity of their symptoms but the basis of this variability is unknown. We have tested the hypothesis that this variability is related to differences in the activity of the antioxidant superoxide dismutase (SOD). The amount of superoxide dismutase I (SOD) enzyme activity in red cells of patients with different degrees of symptom severity and healthy black and white controls was measured and correlated with symptom severity in SCA patients. Blacks with normal (AA) hemoglobin had significantly (p less than .001) more SOD activity (1.82 U/mg Hb) than white controls (1.44 U/mg Hb). Patients with moderate or severe symptoms had less SOD activity (1.16 and 0.95 U/mg Hb, respectively) than control blacks or SCA patients with mild symptoms (1.62 U/mg Hb). The correlation of SOD activity and symptom severity was not a function of age or sex and was unrelated to reticulocyte count or fetal hemoglobin level.

T‐cell subpopulations in patients with monoclonal gammopathies: Essential monoclonal gammopathy, multiple myeloma, and Waldenstrom macroglobulinemia

Abstract: T-cell subsets defined by monoclonal antibodies (OKT3, OKT4, and OKT8) were analyzed in 117 patients with monoclonal gammopathies--69 multiple myeloma (MM) (30 untreated and 39 treated), 14 Waldenstrom's macroglobulinaemia (WM), and 34 essential monoclonal gammopathy (EMG) patients. The percentage and absolute numbers of total T-lymphocytes (E+, OKT3+ cells) were within the normal range in all groups except for the treated MM patients, in which a decrease in the absolute number could be observed. The percentages of OKT4+ cells were significantly lower in MM (35 +/- 1.7) than in EMG patients (43 +/- 2) and controls (50 +/- 2). In contrast, OKT8 cells correspondingly increased in MM (38 +/- 1.6) compared with EMG patients (29 +/- 1) and controls (27 +/- 1). The OKT4/OKT8 ratio was lower in MM than that in EMG patients and controls (p less than 0.01) and was shown to be one of the four most significant variables in a linear discriminant analysis used to distinguish between MM and EMG groups. The MM patients in clinical stage III as well as Bence-Jones myeloma patients showed a more pronounced OKT4/OKT8 imbalance. The treatment did not influence the percent distribution of T-cell subpopulations. The patients with WM exhibit an alteration in the distribution of the T-cell subsets similar to the MM patients with a T4/T8 ratio of 1.1 +/- 0.1. This imbalance was more pronounced in WM patients with monoclonal B-lymphocytes in peripheral blood (leukaemic phase of WM). The functional significance of the altered T-cell subsets in MM and WM patients remains to be established, though it is probable that such an imbalance plays an important role in regulating these B-cell proliferations.

Chronic granulocytic leukemia: correlation of blastic transformation type with karyotypic evolution.

Abstract: Over a 3-year period, 26 patients with Philadelphia chromosome-positive chronic granulocytic leukemia were studied cytogenetically in both the chronic and blastic transformation phases of the disease; a further three patients were studied only after blastic transformation. Sixteen were considered to have adequate evidence of the type of transformation and form the basis of the report, where chromosome changes have been correlated with the morphological type of blastic transformation. Seven patients developed a myeloblastic transformation, seven a lymphoblastic transformation, and two an erythroblastic transformation. All patients in the myeloid group acquired one or more of the nonrandom changes associated with CGL blastic transformation, viz. +8,i(17q), +19, +22q-. Patients in the lymphoblastic group acquired structural abnormalities, apparently random in nature and usually in a small percentage of cells. The two patients with erythroblastic transformation developed markedly hyperdiploid cells (greater than 50 chromosomes) with both numerical and structural abnormalities. Patients in the lymphoblastic group appeared to have a slightly better prognosis than the myeloid group, whilst the patients with erythroblastic transformation had a very poor prognosis.

Pseudotumor of hemophilia in the orbit: the role of radiotherapy in management.

Abstract: A case of pseudotumor of hemophilia is presented that occurred in the right orbit of a boy with severe factor VIII deficiency and an inhibitor. After a period of observation and conservative management, low-dose radiotherapy (750 rads) and Proplex was used. Eighteen months after radiotherapy significant healing had occurred. The role of radiotherapy in the treatment of hemophilic pseudotumor is reviewed.

The procoagulant effect of zinc on fibrin clot formation.

Abstract: The influence of Zn+2 on fibrin clot formation was investigated by measuring its effect on the clotting times of fibrinogen exposed to thrombin. It was observed with either human or bovine thrombin that 0.01-0.1 mM Zn+2 induced significant reductions of clotting times in a concentration-dependent manner. The procoagulant effect of Zn+2 occurred in the presence of Ca+2 but was inhibited by metal chelating agents. Higher levels of Zn+2 (greater than 0.2 mM final concentration) were required to accelerate thrombin-induced clot formation in the presence of citrate or oxalate. Similarly with oxalated human plasma, greater than 0.2 mM Zn+2 decreased the clotting time. Cations such as Mg+2 and Mn+2 caused little change in clotting times. As an extension of these findings, we examined the effect of Zn+2 on the inhibition of thrombin by antithrombin-III (AT-III). The presence of as little as 0.006 mM Zn+2 in an incubating mixture of thrombin and AT-III severely reduced the inhibitory activity of AT-III towards thrombin. It was observed that the relative intrinsic fluorescence emission of human thrombin decreased upon exposure to Zn+2 but was unaffected by Mg+2 or Mn+2. It is suggested that Zn+2 can form a complex with thrombin, which results in altered reactivity towards fibrinogen and decreased inhibition by AT-III.

High-dose intravenous igg in the management of pregnancy in women with idiopathic thrombocytopenic purpura

Abstract: Idiopathic thrombocytopenic purpura (ITP) may develop during pregnancy or affect later pregnancies, causing serious risks of bleeding to the mother and fetus. High-dose intravenous immunoglobulin (IGIV) has caused an immediate and predictable rise in platelet count during the infusion in both adults and children with chronic or acute ITP. The rapid rise in platelet counts may be important in preparing pregnant women with ITP for surgery or delivery. We report our experience in managing two women at weeks 29 and 37 week of gestation who required splenectomy and/or cesarean section. Both patients demonstrated an increase in platelet counts, underwent surgery without excess bleeding, and had normal infants with normal platelets, and with mild thrombocytopenia at delivery.

Adenosine deaminase (ADA) in leukemia: clinical value of plasma ADA activity and characterization of leukemic cell ADA.

Abstract: Adenosine deaminase (ADA) activity was measured in plasma, erythrocytes, and mononuclear cells from 18 patients with acute and chronic leukemia. High levels of ADA activities were found in plasma, erythrocytes, and mononuclear cells from patients with acute leukemia, especially acute lymphoblastic leukemia, and blastic crisis of chronic myeloid leukemia. Serial determination of plasma ADA activities was done in 9 patients with acute leukemia. All patients untreated or in relapse had an elevation of plasma ADA activity, which decreased to normal or subnormal levels during complete remission. On starch gel electrophoresis, plasma ADA in leukemic patients separated into two bands. The major band showed a mobility identical to that of normal red cells and mononuclear cells, and the minor band corresponded to that of normal plasma ADA. Enzymatic and immunological studies were performed on ADA from leukemic cells of acute myeloid and lymphoblastic leukemia. There were no differences in Michaelis constant for adenosine, thermostability, electrophoretic mobility, immunological reactivity, and specific activity between ADA of leukemic cells and normal mononuclear cells. These results strongly suggest that the increased ADA activity in leukemic cells is caused by an increased synthesis of a structurally normal enzyme and that increased plasma ADA activity in leukemic patients reflects an increment of leukemic cells in bone marrow. Therefore, serial determination of plasma ADA activities seems to provide a good indicator of the total mass of leukemic cells in bone marrow.

Granulopoiesis in patients with congenital neutropenia.

Abstract: Granulopoiesis was investigated in five patients with congenital neutropenia (CN) (one Kostmann type, four benign forms). In semisolid agar culture, the marrow cells of all five patients produced normal numbers of CFU-c (colony-forming unit-culture). The size and classification of colonies were normal. In suspension culture in vitro with exogenous colony-stimulating factor (CSF) generated from omental-conditioned medium (OMCM), the myeloid precursors of all patients could proliferate and differentiate into normal polymorphonuclear neutrophils (PMNs). But in the absence of exogenous CSF, myeloid precursors of the patient with Kostmann-type CN did not proliferate or differentiate into PMNs at all. In the four patients with benign neutropenia, however, PMNs were found even without exogenous CSF similar to normal individuals. These results suggest that patients with CN may have normal granulopoietic stem cells with normal proliferative and differentiating capacity in response to exogenous CSF. When a small amount of normal human serum was added to normal marrow cultures stimulated by exogenous CSF, the colony growth increased in a superadditive manner. The enhancing activity of serum from neutropenic patients differed from that of normal serum. Especially, the addition of serum from the patient with Kostmann type CN to normal marrow cultures did not show this enhancement effect. The sera of patients with benign neutropenia had less enhancement effect than did normal control serum. These findings might be interpreted as showing an imbalance between CSF enhancer and inhibitors in the patients' serum.