[Essential thrombocythemia: therapy with alpha interferons].
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Antibody Formation↗
Biomedical subjects
L Catani
Publications and source records attributed to L Catani.
Cancer procoagulant in acute non lymphoid leukemia: relationship of enzyme detection to disease activity.
Blast cell extracts from patients with acute non lymphoid leukemia (ANLL) express cancer procoagulant (CP). This factor X (FX) activator is distinct from tissue factor (TF) in that it does not require factor VII (FVII) to trigger blood coagulation, it acts as a cysteine proteinase and is not present in normal mononuclear cells. To assess whether there is any relationship between the presence of CP and the status of the disease, ANLL patients have been studied at diagnosis, during remission, at relapse. The procoagulant activity in either the presence or absence of F VII and sensitivity to cysteine proteinase inhibitors were tested on cell extracts. Immunoreactivity was explored with an anti-CP polyclonal antibody. Data obtained in 91 newly-diagnosed ANLL patients (subtypes M1 to M5, FAB classification) confirmed the presence of CP in M1 to M4 groups (mean +/- SE FVII-independent activity: M1 = 2.1 +/- 0.7 unit/mg; M2 = 5.7 +/- 1.7 unit/mg; M3 = 31.5 +/- 8 unit/mg; M4 = 1.6 +/- 1.2 unit/mg); CP was absent in the M5 type. In eight patients analyzed in a subsequent phase of partial remission, specific activity had dropped from 26.9 +/- 7.8 to 10.5 +/- 4.0 unit/mg. Activity was virtually absent (0-0.05 unit/mg) in the bone marrow of 37 patients studied at complete remission. Bone marrow samples from six subjects tested at different intervals after complete remission were repeatedly negative for CP but became positive 2 to 5 months before relapse. Upon relapse, the FVII independent activity rose to 24.2 +/- 8.2 unit/mg.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Hypercoagulability during L-asparaginase treatment: the effect of antithrombin III supplementation in vivo.
To evaluate the occurrence of hypercoagulability during treatment with L-asparaginase (L-ase), thrombin-antithrombin complex (TAT) and D-dimer levels in plasma were serially measured in 15 consecutive adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma who had recently completed a chemotherapy cycle with cytosine arabinoside and methotrexate. The first eight patients (group A) received i.v. L-ase alone (20,000 U/m2 on alternate days over 10 d); the last seven patients (group B) received, in addition to L-ase, bolus injection of antithrombin concentrate (2000 U) on alternate days for a total of six administrations, beginning with the second L-ase infusion. Increased levels of TAT (P less than 0.05) and D-dimer (P less than 0.01) were observed prior to L-ase, possibly related to inflammation and cytolysis secondary to previous chemotherapy. In patients treated with L-ase alone, further elevation of TAT (P less than 0.05) and persistence of increased D-dimer were observed, associated with marked reduction of the anticoagulant activities of protein C, protein S and antithrombin III. At variance, in patients receiving antithrombin III supplementation there was no increase of TAT and a normalization of D-dimer levels occurred during L-ase treatment. In these patients, mean plasma antithrombin III activity was maintained at levels higher than 70% of normal throughout the treatment. The rate of decline of fibrinogen, factor IX, protein C and protein S was unaffected by antithrombin III supplementation, indicating that hypercoagulability has little if any relevance for the reduction of coagulation factors and inhibitors induced by L-ase treatment. The usefulness of antithrombin III concentrates in preventing thromboembolic complications in patients submitted to L-ase treatment remains to be determined.
Antithrombin III↗
In vivo and in vitro inhibitory effect of alpha-interferon on megakaryocyte colony growth in essential thrombocythaemia.
Megakaryocyte (MK) colony growth of bone marrow mononuclear non-adherent cells was evaluated in 28 patients with essential thrombocythaemia (ET) and in 26 normal controls. The number of MK-colony forming units (CFU-MK per 3 x 10(5) plated cells) was similar in ET (68 +/- 33) and in controls (63 +/- 37), independently of bone marrow accessory cells. On the contrary, the size of the MK colonies was significantly (P less than 0.01) greater in ET patients. Human recombinant alpha-interferon 2a (alpha-IFN), administered to 10 patients at a dose of 3 x 10(6) IU/d s.c. for 11 +/- 3 weeks, was capable of inducing a significant (P less than 0.01) decrease in the number (from 72 +/- 16 to 31 +/- 14) and size of bone marrow CFU-MK, together with a significant reduction of the platelet count (from 1031 +/- 325 to 378 +/- 75 x 10(9)/l). When added in vitro at time 0 to the culture dishes, alpha-IFN inhibited the CFU-MK growth of both normal and ET bone marrow samples, even at very low concentrations (1 and 10 IU/ml). This study demonstrates that alpha-IFN, both in vivo and in vitro, exerts an inhibitory effect on the growth of MK progenitors, which appears to correlate with the clinically documented antiproliferative effect of this cytokine.
Adolescent↗
The inhibitory effect of serum from hairy-cell leukaemia patients on normal progenitor cells may disappear following prolonged treatment with alpha-interferon.
The possibility that serum from hairy-cell leukaemia (HCL) patients at diagnosis may show an inhibitory effect on the in vitro colony growth of normal haemopoietic progenitor cells has been suggested. Several studies have documented the efficacy of alpha-Interferon (alpha-IFN) in inducing a complete restoration of peripheral blood values and, in some cases, a complete clinical remission. In this study we have evaluated the regulatory effect of serum, collected before and after 3 and 12 months of alpha-IFN treatment, from 10 patients with untreated HCL, on the in vitro growth of normal bone marrow CFU-GM, BFU-E and CFU-MK. The effect of conditioned media, prepared from enriched hairy cells (HC) cultured in synthetic medium, on the growth of normal haemopoietic progenitors was also investigated. The results obtained confirm that sera from untreated HCL patients display a variable degree of inhibitory activity in the progenitor cell compartments analysed. Disappearance of the inhibitory activity, particularly evident for the erythroid compartment, was found only in patients who displayed a disappearance of circulating HC and a good haematological response after prolonged (12 months) treatment with alpha-IFN. The possibility that the serum of patients with HCL may contain a haemopoietic inhibitory factor, released by the neoplastic HC population, is suggested.
Adult↗
[Physiopathology, clinical features and therapy of thrombocytopenia].
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Adrenal Cortex Hormones↗
Procoagulant cellular activity (PCA) in the classification of acute leukemia.
The procoagulant cellular activity (PCA) of leukemic cells was evaluated, before and after endotoxin stimulation, in 38 patients with acute leukemia at presentation subdivided according to the FAB classification. In the M4 and M5 subgroups the stimulated leukemic cells showed a significant increase in the production of PCA compared with freshly isolated cells. No evident PCA was documented in M1 and M2 AML as well as in the majority of acute lymphoid leukemias tested, both before and after endotoxin stimulation. The myeloid and lymphoid leukemic cells appear to behave similarly to normal leucocytes, within which only monocyte/macrophages are capable of producing PCA following endotoxin stimulation. These findings suggest that in human leukemic cells the endotoxin-induced production of PCA may be considered a indicator of monocyte/macrophage differentiation and thus represent a valuable diagnostic tool in the classification of acute leukemias.
Acute Disease↗
Depressed fibrinolysis in patients with acute leukaemia.
The fibrinolytic system was studied in 46 patients with acute leukaemia at diagnosis. Untreated patients (with the sole exception of the M3 subgroup) showed an inhibition of fibrinolytic activity, measured by the euglobulin lysis time and area. This inhibition was accompanied by reduced t-PA antigen and t-PA inhibitor activity. No correlation was found between the above-mentioned fibrinolytic parameters and the biochemical haematological values considered, nor with clinical and/or laboratory features of DIC, fever, liver failure. The decrease in immunological plasminogen and functional alpha 2-antiplasmin, showed a significant correlation with the presence of clinical and/or laboratory signs of DIC, as diagnosed on the basis of concomitant increase in fibrin monomers, plasmatic fibrinopeptide A and serum FDP.
Adolescent↗
Human T-lymphocyte-derived megakaryocyte colony-stimulating activity.
Conditioned medium from a T-lymphoblastic cell line (Mo) contains a number of well-characterized hemopoietins. In this paper we demonstrate that Mo cells also release a factor(s) able to stimulate the growth and the differentiation of megakaryocytic progenitors into large-size pure megakaryocytic colonies in plasma clot cultures. Comparison with other sources of human-active hemopoietins shows that Mo-conditioned medium performs better than others, especially for the megakaryocytic lineage. The factor(s) shows strong similarities with human Meg-CSF obtained from a thrombocytopenic patient's plasma, and is distinguishable from the other hemopoietins present in the medium.
Bone Marrow Cells↗
New syndrome: progressive scoliosis by unilateral unsegmented fusion bar, foot deformity, joint laxity, congenital inguinal herniae, peculiar face.
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Consanguinity↗
Human myeloid precursor cells do not possess or produce procoagulant activity (PCA).
The procoagulant cellular activity (PCA) of human myeloid precursor cells was evaluated after fractionation of normal bone marrow cells over a discontinuous albumin density gradient. No PCA was documented in any of the six freshly isolated fractions (F1-F6); significant amounts of PCA were instead produced, after a 4-h endotoxin preincubation, in fractions F1 and F2, which, unlike the other fractions, contained up to 5% monocyte-macrophages. After removal of the latter by plastic adherence, the PCA was abolished. This study shows that PCA can be produced only by monocyte-macrophages upon endotoxin activation, while myeloid precursor cells, at all stages of differentiation, are incapable of PCA. The PCA demonstrated in some human acute myeloid leukemias, other than that of the monoblastic subgroup, appears therefore to be related to the neoplastic transformation rather than to a maturation arrest or to a toxemic stimulation.
Blood Coagulation Factors↗
Procoagulant cellular activity and disseminated intravascular coagulation in acute non-lymphoid leukaemia.
The procoagulant cellular activity (PCA) of intact and lysed leukaemic cells was evaluated at diagnosis in 23 patients with acute non-lymphoid leukaemia (ANLL). The leukaemic cells of all 13 patients having DIC feature (excess of fibrin monomers, serum FDP and plasma fibrino-peptide A) showed a significant (P less than 0.0001) increase of PCA, while a pattern similar to that of normal granulocytes and lymphomonocytes was observed in the remaining 10 patients without evidence of DIC. When the patients were subdivided according to the FAB cytological classification, features of DIC and increased PCA were demonstrated in 3/3 M3 patients, 5/6 M5 patients and only in 5/14 remaining patients. These findings indicate that in ANLL patients: (1) the increased PCA of leukaemic cells is closely related to the occurrence of DIC; (2) the increased PCA seems related to the differentiation line and maturation level of the leukaemic cells.
Acute Disease↗
Familial occurrence of protrusio acetabuli (Otto's disease). Ten members affected in four generations.
It is rare for hereditary forms of primary protrusio acetabuli to be reported, and the mode of transmission is not always clear. The writers present a familial occurrence of this malformation in which the hereditary factor was in accord with the presence of a dominant autosomal gene.
Acetabulum↗
Ascorbic acid for the treatment of chronic refractory idiopathic thrombocytopenic purpura (ITP).
We describe our experience with ascorbic acid in the treatment of chronic refractory ITP. Nine patients, 5 males and 4 females aged 27-74 years, 4 of whom were previously splenectomized, received the drug at a daily dose of 2 grams. After 2-12 months (median 4) of treatment, a partial response was observed in only one patient, while no response was registered in the other eight. Our data, analyzed together with those of the literature, allow us to conclude that ascorbic acid may not be considered a drug of interest in the treatment of chronic refractory ITP.
Adult↗
In vitro inhibition of interferon alpha-2a antiproliferative activity by antibodies developed during treatment for essential thrombocythaemia.
BACKGROUND: Various authors have reported the development of anti-interferon (IFN) antibodies following IFN-alpha treatment for haematological malignancies. So far the methods for detecting these antibodies have not considered the antiproliferative activity of this IFN, which is its most important property in anticancer therapy. METHODS: In this in vitro study we evaluated the ability of anti-IFN alpha-2a neutralising antibodies to inhibit the antiproliferative activity of IFN alpha-2a and lymphoblastoid IFN alpha using megakaryocyte colony growth as the revelatory system. These antibodies were detected in two patients affected by essential thrombocythaemia (ET) who lost their haematological response to IFN alpha-2a, but responded to a subsequent treatment with lymphoblastoid IFN alpha. RESULTS AND CONCLUSION: The results show that the inhibition of megakaryocyte colony growth induced by IFN alpha-2a was totally suppressed in the presence of the two ET patients' sera, whereas the inhibition induced by lymphoblastoid IFN alpha was not significantly affected. These in vitro data demonstrate the high specificity and activity of these antibodies on the antiproliferative effect of IFN alpha-2a.
Adult↗
Reducing the haemorrhagic risk related to splenectomy in patients with severe chronic idiopathic thrombocytopenic purpura.
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Blood Component Transfusion↗
A regimen for antithrombin III substitution in patients with acute lymphoblastic leukemia under treatment with L-asparaginase.
BACKGROUND AND METHODS: Seventeen adult patients with acute lymphoblastic leukemia (ALL) treated with L-asparaginase (20,000 IU/m2 on six alternate days) were infused with antithrombin III (AT III) concentrates (Kybernin P, Behring). Substitution therapy was aimed at increasing the reduced AT III concentration usually found in these patients, since AT III deficiency is thought to be associated with an increased risk of thrombosis. Two schedules of AT III administration, different in dosage, timing and duration were evaluated. The first 7 patients (group A) received a fixed dose of 2,000 U every day for 6 times, starting with the second L-asparaginase (L-ase) infusion, independently of their plasma AT III levels. In the following 10 patients (group B), 20-25 U/Kg b.w. were administered daily for 7 times only when the plasma AT III level was lower than 60% with plasma fibrinogen higher than 100 mg/dl and platelet count higher than 50 x 10(9)/l, or when AT III was below 40%. Thirteen patients who received L-ase without AT III substitution served as controls. RESULTS AND CONCLUSIONS: Both substitution regimens resulted in mean plasma AT III nadir values significantly (p less than 00.1) higher than in the controls. Our data suggest that, in ALL patients receiving L-ase according to the L20 protocol, satisfactory plasma AT III levels may be assured with infusions of 20-25 U/Kg b.w./day for 7-10 days, starting by day 2 of L-ase treatment.
Adult↗
Prompt plasma-exchange treatment and coma reversibility in two patients with thrombotic thrombocytopenic purpura.
We report on the cases of two women with acute thrombotic thrombocytopenic purpura (TTP) whose clinical courses were characterized by the onset of a coma state. Prompt commencement of plasma-exchange (PE) treatment led to complete hematological and neurological remission, which can still be observed without any maintenance therapy. No CNS abnormalities were observed in either patient using brain CT and NMR scans.
Adult↗