Management of infants of mothers with immune thrombocytopenic purpura.
Explore the source record for details and available documents.
Cerebral Hemorrhage↗
Biomedical subjects
J B Bussel
Publications and source records attributed to J B Bussel.
Analysis of lymphocyte proliferative response subpopulations in very low birth weight infants and during the first 8 weeks of life.
Cell-mediated immunity is not well characterized in very low birth weight infants, and abnormalities may represent a significant vulnerability to infection. This report describes 165 serial studies in 58 infants between 700 and 1300 g birth weight during the first 8 wk of life. Two ml of blood were drawn at 2-wk intervals to measure T cell numbers and subsets and response to phytohemagglutinin (PHA). Overall, lymphocyte proliferation to PHA averaged 17,264 cpm, significantly less than the adult control (23,566 cpm). T cell numbers and subsets were CD3 62% (adult controls 75%), CD4 45% (49%), and CD8 18.6% (27%). Values at birth were lower as all parameters increased for at least the first 4 wk of life: PHA at birth was 15,464 cpm, CD3 48%, CD4 37%, and CD8 13%. Because of the lymphocytosis of premature infants, the absolute numbers of total T cells and subsets were within the normal adult range despite less than 50% of the mononuclear cells at birth being T cells. A study of five infants demonstrated an average of 52% B7+ cells at birth showing that the number of B cells at birth was increased approximately 10-fold over the control number in adults. Clinical correlation showed that the increases in both the % CD8 and the absolute number of CD8+ lymphocytes after birth were correlated with both the occurrence of sepsis and the assessed lymphocyte subsets in a sizeable number of very low birth weight infants serially during the first 8 wk of life including lymphocyte function using isolated mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Maintenance treatment of adults with chronic refractory immune thrombocytopenic purpura using repeated intravenous infusions of gammaglobulin.
Intravenous infusion of gammaglobulin (IVGG) has been extensively used in the treatment of immune thrombocytopenic purpura (ITP) in adults to acutely raise the platelet count but not as a maintenance therapy. This report describes the maintenance treatment of adults with chronic ITP using repeated infusions of 800 to 1,000 mg/kg of IVGG. Sixteen of 40 patients were able to discontinue all therapy after receiving between one and 15 infusions. Five patients achieved remission and 11 other patients became stable without therapy (SWT) maintaining a platelet count greater than 20,000/microL without bleeding. The average quantity of gammaglobulin received for all patients was 606 g per patient. Of the 30 patients who underwent but did not respond to splenectomy, 11 (37%) were able to discontinue all therapy by either achieving remission (5) or becoming SWT (6). None of the five patients who achieved remission did so after only the initial therapy; all first received between one and 12 maintenance infusions. The ten splenectomized patients who were unresponsive to IVGG also failed to subsequently respond to conventional therapy including immunosuppressive agents and androgens. No toxicity of IVGG was seen except for postinfusion headaches. IVGG is an effective although expensive maintenance therapy for adults with ITP and is useful in patients who have not responded to splenectomy.
Adult↗
Autoimmune neutropenia of childhood.
Autoimmune neutropenia (AIN) of infancy is an underreported disease because of its benign nature. In addition, the relative unavailability of neutrophil antibody testing prevents confirmation of suspected diagnoses. Small children do not have life-threatening infections, do not have associated diseases, respond to i.v. gamma globulin with increased neutrophil counts, and tend to improve on their own. Older children with AIN have associated diseases such as hepatitis or Hodgkin's disease, often have other immune cytopenias, and respond poorly to any therapy. Immune deficiency states, especially those of the humoral arms, are associated with development of AIN.
Adrenal Cortex Hormones↗
Intravenous treatment with gammaglobulin in adults with immune thrombocytopenic purpura: review of the literature.
The results of high-dose intravenous gammaglobulin therapy (IVGG) of adults with immune thrombocytopenic purpura (ITP) were reviewed in 28 published reports which included 282 patients. Overall, 64% of the patients responded to IVGG with a peak platelet count greater than 100,000/mm3; 83% had peak platelet counts greater than 50,000/mm3. Unmodified immunoglobulin was superior to modified immunoglobulin; 70% of the patients treated with the former having platelet increases to greater than 100,000/mm3 compared to only 49% of those treated with the latter. More patients were refractory among those who had had ITP for at least 3 years. A higher peak platelet count immediately after IVGG administration was correlated with a longer duration of the platelet response. Patients above the age of 60 tended to have a weaker response to IVGG than did younger patients, and females tended to respond better than males. A pre-IVGG platelet count of less than 10,000/mm3 was not associated with a poor response to IVGG. While there is still no way to reliably predict response prior to therapy in an individual patient, the above information may help in the decision of whether or not treatment with IVGG is likely to be successful. It also suggests that inhibition of antiplatelet antibody production is an important mechanism of IVGG effect at least in some patients.
Age Factors↗
Intravenous immunoglobulin therapy of idiopathic thrombocytopenic purpura in childhood and adolescence.
Intravenous immunoglobulin is not only a dramatic clinical therapy, but it is also extremely interesting in regard to mechanism of action. The high cost of therapy limits its application, yet it appears to be equal to or perhaps slightly more effective than corticosteroids as a treatment of ITP and is far less toxic with prolonged use. The appropriate place for its exact use remains to be determined but probably includes patients urgently requiring rapid platelet increases (in conjunction with steroids), treatment of immunocompromised patients, and treatment of chronic patients, either children to avoid splenectomy or adults with severe disease after splenectomy. Controlled trials to resolve these clinical questions are urgently needed. Existing studies on its mechanisms of actions are very interesting and have furthered our understanding of the pathophysiology of ITP. Although future work may lead to further applications, initial enthusiasm for the use of IVGG in the treatment of other autoimmune diseases with the exception of myasthenia gravis has been limited by subsequent clinical experience.
Acute Disease↗
Blockade of clearance of immune complexes by an anti-Fc gamma receptor monoclonal antibody.
Clearance of immune complexes by the mononuclear phagocyte system is important for maintaining normal host defenses against bacterial and viral assault (1), but also contributes to the pathogenesis of a variety of immune- mediated diseases . For example, removal from the circulation of IgG-coated erythrocytes and platelets by the MPS is the sine qua non of immune-mediated cytopenias (2, 3). On the other hand, abnormally decreased removal by the MPS of smaller, soluble immune complexes may play a role in the pathogenesis of immune complex-mediated tissue damage found in such autoimmune diseases as SLE (4). Although the physicochemical nature and the size of immune complexes can influence rates of clearance and sites of deposition (reviewed in 5), interactions between immune complexes and the MPS in vivo are poorly understood. The inability to directly measure binding or internalization of immune complexes by cells in the liver and spleen has made the analysis of the molecular basis of immune complex clearance very difficult . Receptors for the Fc portion of IgG (FcgammaR) and for complement (CR) undoubtedly play a role in the removal of immune complexes, but the relative importance of these receptors is not known.
Animals↗
Treatment of refractory immune thrombocytopenic purpura with an anti-Fc gamma-receptor antibody.
Explore the source record for details and available documents.
Adult↗
Concurrence of von Willebrand's disease and hemophilia A: implications for carrier detection and prevalence.
Five families with concurrent von Willebrand's disease (VWD) and classic hemophilia (hemophilia A) are described. Three were ascertained through women undergoing hemophilia carrier testing, one through an obligate carrier who also has VWD, and one through the affected father of a hemophiliac. The VWD probands exhibited Type I VWD with reduced Factor VIII-related antigen (VIIIR:Ag) and/or von Willebrand factor on more than one occasion, normal VIIIR:Ag on crossed immunoelectrophoresis, and mild symptoms. No male had both disorders, but two obligate hemophilia carriers also had VWD. Neither was detectable as a carrier by discriminant analysis. Four possible carriers of hemophilia had VWD and would also be classified as noncarriers statistically. These findings suggest that the presence of VWD may invalidate hemophilia carrier testing by conventional methods. The independent entry into the family of the two genes by mating of a hemophilia carrier and a VWD male is documented in two cases and probable in two. The observed frequency of such matings supports the hypothesis that VWD is a common disorder.
Adolescent↗
Immunoglobulin therapy for autoimmune hemolytic anemia.
Explore the source record for details and available documents.
Anemia, Hemolytic, Autoimmune↗
Intravenous treatment of autoimmune hemolytic anemia with very high dose gammaglobulin.
Autoimmune hemolytic anemia (AIHA) has been considered to be unresponsive to intravenous gammaglobulin (IVGG) at the doses that are effective in immune thrombocytopenic purpura and autoimmune neutropenia (usually 2 g/kg total dose). This study reports the use of a higher dose (5 g/kg total dose over 5 days) in four severe cases of AIHA which resulted in a sustained remission in two patients, a transient response in the third, and a failure in the forth patient. These data suggest that larger quantities of IVGG may be needed in this disease, possibly because the reticuloendothelial system appears to be enlarged in AIHA patients.
Adult↗
Intravenous immunoglobulin therapy for the treatment of idiopathic thrombocytopenic purpura.
Intravenous immunoglobulin is not only a very dramatic clinical therapy but also extremely interesting from the point of view of understanding its mechanism of action. The difficulty of delivery and especially the high cost of therapy limits its application; yet it appears to be equal to or perhaps slightly more effective than corticosteroids as a treatment of ITP and is less toxic with prolonged use. The appropriate place for its exact usage remains to be determined, and further controlled trials are urgently needed. Existing studies on its mechanisms of actions are very interesting and have furthered our understanding of the pathophysiology of ITP. Although future work may lead to further applications, initial enthusiasm for the use of IVGG in other autoimmune diseases has been limited by subsequent clinical experience.
Adult↗
Treatment of acute idiopathic thrombocytopenia of childhood with intravenous infusions of gammaglobulin.
Gammaglobulin treatment was given at a dose of 1 gm/kg/day intravenously in 29 patients with acute idiopathic thrombocytopenic purpura: 15 previously untreated, 10 resistant to steroids, and four who were steroid dependent. The average platelet increase in 24 hours was greater than 50,000/microliter; the average peak platelet count was 194,000/microliter. Eighteen of 25 patients required only one infusion; 10 of these 18 never required any additional (maintenance) therapy. Outcome in previously untreated and steroid-resistant patients was identical; however, previously untreated patients required only 1.8 gm/kg total dose of gammaglobulin, whereas steroid-resistant patients received 3.9 gm/kg. Only one steroid-dependent child of the 29 patients still requires maintenance therapy, at 6-week intervals. Toxicity was minimal. Cost was minimized by not admitting patients and by giving treatment in one visit, rather than five.
Acute Disease↗
Intravenous usage of gammaglobulin: humoral immunodeficiency, immune thrombocytopenic purpura, and newer indications.
Intravenous gammaglobulin is effective therapy of ITP and other autoantibody-mediated immune cytopenias. All children as well as adults unresponsive to splenectomy or with known immune deficiency are probably the best candidates for treatment with IVGG. Its major advantage, in addition to its efficacy of treatment and possible remission-inducing effect, is that it has the fewest side effects of any treatment of ITP so that it is the best maintenance therapy of patients when effective. Future uses of IVGG remain to be determined. Premature infants with a high mortality from sepsis and with hypogammaglobulinemia due to termination of pregnancy prior to transplacental antibody transfer may benefit from IVGG. A preliminary study suggested such benefit and also showed safety of IVGG treatment in that there was no impaired immune responsiveness of these prematures at 2 years of age (28). Another potential usage of IVGG involves the treatment of the hypogammaglobulinemia associated with certain types of malignancy. Patients with CLL, especially in the advanced stages, are often hypogammaglobulinemic. Multiple myeloma and Waldenstrom's macroglobulinemia are two other B-cell malignancies associated with antibody production defects which might benefit from antibody replacement therapy. Therapeutic IgG levels may be harder to obtain due to hypercatabolism of immunoglobulin. The issue of immune hyporesponsiveness during intensive chemotherapy is also unexplored. Secondary antibody responses do not seem to be impaired, but primary responses, as tested in numerous immunization studies, are decidedly impaired. Certain protocols, especially those treating high-risk acute leukemias and neuroblastoma during induction therapy are intensive with high rates of sepsis, and may warrant trials of prophylactic IVGG. Similarly, some form of humoral prophylaxis is becoming an important part of the handling of the patient undergoing bone marrow transplantation not only to prevent bacterial sepsis but also to prevent cytomegalovirus (CMV) interstitial pneumonitis. A likely additional usage is gammaglobulin replacement for patients undergoing plasmapheresis, especially if performed multiple times. Finally, the broad spectrum of antibacterial and antiviral antibodies present in the preparations (such as anti-CMV, anti-Group B strep, and antiendotoxin) and the ease and safety of delivery allow the preparations to be used in situations where a hyperimmune preparation might be desired and/or where more than one pathogen is possible. In summary, IVGG is a treatment capable of safely conferring significant benefits to selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Management of idiopathic thrombocytopenic purpura in childhood.
Explore the source record for details and available documents.
Acute Disease↗
Total knee arthroplasty in hemophilia.
Twenty-four total knee arthroplasties were performed in fourteen disabled patients with hemophilia. The average age of the patients at operation was thirty-five years. Twenty-one of the implants that were used were total condylar prostheses. Using The Hospital for Special Surgery knee-rating system after two to nine years of follow-up, the result in fifteen knees was rated as excellent; in six, as good; and in one, as fair. Two patients had a poor result that was attributable to late infection. Pain and function were markedly improved, and the average gain in range of motion was 23 degrees. Postoperative complications, in addition to the infections, included one subcutaneous hematoma, one hemolytic anemia, and one instance of inhibition to Factor VIII. The technical problems in treatment were formidable. Total knee arthroplasty in a hemophiliac can be successful, but it should be performed only with strict hematological supervision. The surgeon should be prepared to treat many potential postoperative complications.
Adult↗
A heparin-like anticoagulant in an 8-month-old boy with acute monoblastic leukemia.
An 8-month-old male with acute monoblastic leukemia died during induction chemotherapy of severe bleeding refractory to repeated infusions of platelets and clotting factors. A heparin effect was suggested by prothrombin time (PT) of 26 seconds, partial thromboplastin time (PTT) of 94 seconds, thrombin time 240 seconds, and reptilase time 18.4 seconds, with a fibrinogen of 88 mg/dl. Both plasma mixed with the patient's urine and the patient's plasma had their thrombin times corrected toward normal by both PF4 and protamine. Synergism of the anticoagulant with antithrombin III was demonstrated not only by enhanced inhibition of thrombin but also by an increased rate of formation of thrombin--antithrombin III complexes in the presence of the anticoagulant, which was eliminated by preincubation with heparinase. Since the anticoagulant activity was not found in the blasts themselves, it is presumed that the anticoagulant is heparin/heparan liberated from the endothelial lining by products of the cell destruction secondary to chemotherapy.
Acute Disease↗
Modulation of mononuclear phagocyte system function and circulating immune complexes by lyophilized concentrates in patients with classic hemophilia.
Infusions of lyophilized antihemophilic factor concentrates in patients with hemophilia were found to affect both circulating immune complexes and in vivo mononuclear phagocyte system function. Following infusion nine patients had simultaneous assessment of serial immune complex levels and mononuclear phagocyte system clearance of IgG-sensitized autologous erythrocytes relative to a previously established baseline. Nine patients also had a separate second sequence, and two a third sequence, of serial immune complex measurements in relation to infusions. The net change in immune complexes over the 2- to 4-hr interval following infusion was consistent in 10 of 11 study pairs (P less than 0.01) despite different antihemophilic factor preparations for each study and different individual patient responses. This change could not be explained by immunochemical rearrangement in infusate and serum since in vitro mixing experiments showed no relationship to in vivo results. Change in mononuclear phagocyte system function showed a strong correlation with change in complexes (r = 0.70; P less than 0.05). It is suggested that infusions of antihemophilic factor can modulate the mononuclear phagocyte system which in turn alters immune complex levels. Both of these effects could potentially influence immune regulation which has been shown to be abnormal in other hemophiliac patient groups.
Adolescent↗