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J B Bussel

Publications and source records attributed to J B Bussel.

106 records · Page 6Linked to original sources
PubMed1984

The use and mechanism of action of intravenous immunoglobulin in the treatment of immune haematologic disease.

In summary, intravenous gammaglobulin appears to be a very useful treatment of immune haematologic disease. Almost all patients with ITP treated with IVIg will have an increase in their platelet counts lasting at least 2 weeks. Some of these patients will derive long-term benefit from the IVIg and many can maintain their platelet counts by periodic single outpatient infusions. Patients with immune neutropenia are also likely to benefit by IVIg treatment which may be of particular benefit due to its not interfering with phagocyte function. RES blockade is a well-documented mechanism of action immediately after IVIg infusion and platelet antibody synthesis may decrease in some patients; IVIg does not appear to protect platelets from platelet antibodies.

Acute Disease↗
PubMed1984

Modulation of mononuclear phagocyte function by intravenous gamma-globulin.

To assess the effects on mononuclear phagocyte function of i.v. gamma-globulin treatment in idiopathic thrombocytopenic purpura, we examined in vivo and in vitro mononuclear phagocyte function in 11 patients before and after therapy. All patients, both splenectomized and non-splenectomized, demonstrated a prolongation of in vivo clearance of autologous IgG-sensitized erythrocytes (p less than 0.01). Concurrent in vitro assessment of blood monocyte function showed decreased IgG-sensitized erythrocyte (EA) rosette formation (mean +/- SD: 31.6% +/- 8.2 vs 24.5% +/- 9.5; p less than 0.03) and decreased affinity of Fc receptor-specific IgG oligomer binding (9.9 +/- 16.3 vs 1.8 +/- 2.1 X 10(8) M-1; p less than 0.008), but no consistent change in the estimate of the maximum number of binding sites. Phagocytosis of two different EA probes was decreased (EhuA:0.49 +/- 0.26 vs 0.25 +/- 0.14 erythrocyte/monocyte/hr; p less than 0.02, EoxA: 1.76 +/- 0.66 vs 1.27 +/- 0.67 erythrocyte/monocyte/hr, p less than 0.05). The change in in vivo mononuclear phagocyte system clearance was significantly correlated with the change in the association constant for oligomer binding (r = 0.98, p less than 0.05). These data demonstrate that i.v. gamma-globulin infusions induce alterations of mononuclear phagocyte function that are not dependent on the presence of autologous serum containing infusate. The change in apparent Fc receptor affinity rather than receptor number may reflect an altered Fc receptor population with different binding properties.

Adolescent↗
PubMed1983

Intravenous use of gammaglobulin in the treatment of chronic immune thrombocytopenic purpura as a means to defer splenectomy.

Intravenous gammaglobulin was used to treat 12 children with chronic immune thrombocytopenic purpura in order to avoid splenectomy. The average rise in platelet count with initial treatment was 226,000/microliters. Currently, one patient is in remission, four patients maintain platelet counts greater than 40,000/microliters without treatment, four patients maintain platelet counts greater than 40,000/microliters with single maintenance infusions of IV IgG at four- or 10-week intervals; three patients did not respond to treatment. In nine of 12 patients, splenectomy was avoided or at least postponed. In responding patients, we were able to discontinue immunosuppressive medication. Platelet count rises with initial IV IgG therapy were correlated with both platelet antibody levels and with a better long-term outcome. Toxicity was minimal.

Adolescent↗
PubMed1983

Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura.

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.

Adolescent↗
PubMedDate not supplied

Fetal alloimmune thrombocytopenia: consensus and controversy.

Fetal and neonatal alloimmune thrombocytopenia (AIT) is a serious disease that can affect subsequent siblings to an even greater degree than a first affected child. The devastating outcome of antenatal intracranial hemorrhage (ICH) is not uncommon. Great strides have been made in the antenatal diagnosis and treatment of this disease. This article reviews our knowledge of the laboratory diagnosis of AIT during pregnancy, the pitfalls in this diagnosis, the natural history of AIT during pregnancy, and the collected series of the management of fetal AIT in both Europe and the United States. Discrepancies in outcome between European and American studies exist. Reasons for these discrepancies are highlighted, including differences in populations studied, differences in management, and differences in the definition of response to treatment. Intravenous immune globulin appears to be efficacious in increasing the fetal platelet count and decreasing the occurrence of ICH.

Antigens, Human Platelet↗
PubMedDate not supplied

Combined plasma exchange and intravenous gammaglobulin in the treatment of patients with refractory immune thrombocytopenic purpura.

Plasma exchange (PE) and intravenous gammaglobulin (IVGG) are potentially effective therapies in immune thrombocytopenic purpura (ITP). In this study, eight patients refractory to IVGG and to prednisone were treated with a protocol of combined PE and IVGG therapy using a single PE on each of 3 consecutive days, followed by 2 consecutive days of IVGG at 1 g per kg. Four of the eight patients responded to the combined therapy with a mean peak platelet count of 132,000 per microliter (range, 74,000 to 225,000/microliter). Responses lasted approximately 2 weeks. These four patients were among the five who had initially responded to IVGG before becoming refractory; none of the three patients without an initial response to IVGG responded to the combined therapy. Age, duration of disease, and splenectomy status did not appear to be related to response to the combined therapy. Two patients began maintenance treatment (1 PE followed by 1 g/kg IVGG on the same day), but both became unresponsive after three treatments. PE combined with IVGG may be a useful treatment for some patients with refractory ITP who have uncontrollable bleeding or require major surgery. The development of resistance to IVGG effect may be mediated by an increase in the level of antiplatelet antibodies. PE, by lowering antiplatelet antibody levels, may then allow IVGG infusion to be effective again in elevating the platelet count.

Adolescent↗
PubMedDate not supplied

Intravenous gammaglobulin in the prophylaxis of late sepsis in very-low-birth-weight infants: preliminary results of a randomized, double-blind, placebo-controlled trial.

The efficacy of intravenous immunoglobulin (IVIG) as prophylaxis for late sepsis was evaluated in a placebo-controlled, randomized, double-blind trial involving 240 infants of very low birth weight (less than 1,300 g). Each infant received a total of five doses of either IVIG (1 g/d) or an albumin placebo. The first four doses were administered between days 1 and 5 of life, and the last dose was administered on day 15 or shortly thereafter. Preliminary analysis of data available for 126 patients showed that in the first 30 days, sepsis developed in nine of 61 patients given IVIG and in 16 of 65 given placebo (one-tailed P = .065). At 70 days, the number who developed sepsis was similar in the two groups: 20 for those who received IVIG vs. 23 for those who received placebo. When patients with coagulase-negative staphylococcal infections were deleted from the totals, the results were essentially the same, i.e., three of 61 who received IVIG vs. nine of 65 who received placebo (one-tailed P = .041), developed sepsis during the first 30 days and 12 of 61 vs. 13 of 65, respectively, had developed sepsis at 70 days. In the IVIG group, the median peak level of serum IgG at day 7 was 1,700 mg/dL and the IgG levels were significantly greater than those in the placebo group for days 7-42. These data suggest that infusions of IVIG at the doses and dosing intervals used in this study may be effective in decreasing the incidence of late-onset sepsis during the first month of life in infants of very low birth weight.

Bacterial Infections↗
PubMedDate not supplied

Safety and efficacy of low-dose intravenous immune globulin (IVIG) treatment for infants and children with immune thrombocytopenic purpura. Low-Dose IVIG Study Group.

PURPOSE: This report presents pooled data from two multicenter studies conducted to assess the efficacy, safety, and tolerance of lower-dose intravenous immune globulin (IVIG) regimens of 250 mg/kg/day, 400 mg/kg/day, and 500 mg/kg/day for 2 days, compared to an established higher-dose regimen of 1 g/kg/day for 2 days, in children with immune thrombocytopenic purpura (ITP). PATIENTS AND METHODS: A total of 24 children received IVIG (Gammar i.v.). In Study 1, 10 centers enrolled 12 children between 5 and 12 years old who received IVIG at either 400 mg/kg/day or 1 g/kg/day for 2 days. In Study 2, five centers enrolled 12 infants and children younger than 5 years old who received IVIG at 250 mg/kg/day or 500 mg/kg/day for 2 days. Both studies were prospective and randomized. RESULTS: IVIG treatment was effective (platelets increased at least 30,000/cu mm over baseline) in 94% (16 of 17) of the evaluable patients in the low-dosage group. Platelet increases occurred rapidly: by 48 hours, total platelet counts ranged from 32,000/cu mm to 256,000/cu mm, and peak platelet counts reached 38,000/cu mm to 551,000/cu mm. Adverse events (AEs) were most often mild, lasted less than 3 hours, and were usually those typically associated with immunoglobulin administration-headache, nausea, vomiting, and fever. There were two serious AEs-an anaphylactoid reaction in one patient in the 400 mg/kg group and aseptic meningitis in one patient in the 1 g/kg high-dosage group. Both patients recovered without sequelae and were responders. Although the incidence of AEs varied by dosage groups, this difference was not significant. However, the incidence of AEs was affected by age. AEs were significantly lower in patients younger than 5 years of age. CONCLUSIONS: In this small, randomized trial, low-dose IVIG in 2-day regimens of 250, 400, or 500 mg/kg/day rapidly reversed thrombocytopenia just as effectively as 1 g/kg/day in infants and young children with ITP. Lower-dosage regimens are safe and well-tolerated; the incidence of AEs is lower in children younger than 5 years of age.

Child↗
PubMedDate not supplied

BRa (HPA-5b) incompatibility may cause thrombocytopenia in neonates of mothers with immune thrombocytopenic purpura.

PURPOSE: The association of anti-Br(a) immunoglobulin G (IgG) platelet alloantibodies with the development of thrombocytopenia in neonates of mothers with autoimmune thrombocytopenic purpura (ITP) is reported. METHODS: Between March 1994 and July 1997, 28 consecutive pregnant women with ITP seen at New York Hospital were screened for platelet-reactive antiglycoprotein (glycoprotein [GP] IIb/IIIa, Ib/IX, and Ia/IIa) antibodies. RESULTS: The sera from 6 of these 28 women contained IgG alloantibodies to GP Ia/IIa directed against the Br(a) (HPA-5b) antigen. Only three families each had at least one Br(a)+ and at least one Br(a)- infant. Platelet typing in these families revealed that the mothers were Br(b/b) (Br(a)-) and the fathers were Br(a/b) (Br(a)+). Platelet counts < 100,000/microl occurred only in 2 of the 3 infants who were Br(a)+. The platelet counts were significantly lower in the three Bra+ infants compared to the five Br(a)- infants (p = 0.038). CONCLUSION: Platelet alloimmunization with anti-Br(a) can cause neonatal thrombocytopenia in infants of mothers with ITP. Platelet antibody testing in the pregnant women with ITP is recommended.

Antigens, Human Platelet↗
PubMedDate not supplied

Hematologic toxicity of sodium valproate.

PURPOSE: Sodium valproate is a commonly used anticonvulsant in the management of childhood refractory epilepsy with good response rates and acceptable toxicity. Hepatotoxicity is the most widely recognized toxicity. With the use of higher drug levels to achieve adequate seizure control, hematologic toxicity is being increasingly encountered, and the pediatric hematologist is consulted for these problems in the pre- or perioperative setting. The purpose of this article is to characterize the various hematologic toxicities encountered in a clinical setting and to provide guidelines to assist in the management of these patients. METHODS: A literature review was undertaken to identify the hematologic toxicities of valproate used as monotherapy or polytherapy. Key words used in the search were valproate, hematology, and bleeding. RESULTS: Valproate can cause direct bone marrow suppression leading to aplastic anemia or peripheral cytopenia affecting one or more cell lines. Occasional fatal bone marrow failure, myelodysplasia, and a clinical picture resembling acute promyelocytic leukemia have also been seen. Thrombocytopenia, macrocytosis, neutropenia, and pure red cell aplasia can occur but are not reported to be life-threatening. A bleeding diathesis associated with valproate use may include thrombocytopenia, abnormal platelet function, and acquired von Willebrand disease type I. CONCLUSIONS: Hematologic toxicities of valproate are common, vary in onset and severity, are recurrent, transient, or persistent, and usually occur with a serum valproate level greater than 100 microg/mL. In most situations, even when highly clinically significant, they can be reversed with dosage reduction; drug discontinuation is rarely required. Potential adverse effects such as thrombocytopenia and leukopenia are easily detected by laboratory monitoring, which should be continued indefinitely at least on a quarterly basis. Caution for elective surgery is advised; preoperative coagulation studies should be done, including platelet function studies and von Willebrand factor levels. Perioperative use of DDAVP to increase von Willebrand factor levels and improve platelet function is appropriate in some cases.

Anticonvulsants↗
PubMedDate not supplied

Uses of intravenous gammaglobulin in immune hematologic disease.

In summary, for intravenous gammaglobulin use of ITP in children and adults, it is clear that intravenous gammaglobulin is an effective way to increase the platelet count acutely and this will be faster than or as fast as any other therapy. However, there is no proven curative effect of IV gammaglobulin. Its use in situations requiring a rapid increase in the platelet count seems secure as does its use in children with chronic ITP. The latter however and the treatment of HIV-ITP may find IVIG treatment largely replaced in the future by IV Anti-D(10) which is currently experimental. The use of a viral inactivated form of IVIG currently seems mandatory to avoid post-transmission hepatitis.

Adult↗