Intravenous immunoglobulin (i.v. IgG) for previously treated acute or for chronic idiopathic thrombocytopenic purpura (ITP) in childhood: a prospective multicenter study

In a prospective multicenter study 42 thrombocytopenic (less than 30 X 10(9) platelets/l) children with chronic idiopathic thrombocytopenic purpura (ITP) or with acute ITP, dependent on or refractory to corticosteroids, were given 0.4 g i.v. IgG/kg body weight/day on 5 consecutive days and thereafter once a week if the platelet count fell to less than 20 X 10(9)/l or if the patient bled. After the initial 5 days of i.v. IgG the platelets rose within a mean of 7-8 days to greater than 30 X 10(9)/l in all and to greater than 150 X 10(9)/l in 33 of 42 patients (79%). After a mean observation time of 26.6 months 26 of 42 patients (62%) showed a satisfactory long-term effect, i.e. no need for treatment for at least 6 months without bleeding and with no platelet counts below 20 X 10(9)/l. No difference in response rate was found between children with chronic and those with previously treated acute ITP. These results indicate that i.v. IgG could be used to control emergency situations, e.g. to stop bleeding or to prepare a patient for surgery. I.v. IgG also represents a good alternative to treatment modalities, such as splenectomy and/or the administration of cytostatic immunosuppressants with potentially serious side effects. In addition to the expected transient rise in serum IgG levels, i.v. IgG induced a more prolonged elevation of serum IgM. Platelet associated IgG, elevated before therapy, was correlated with the clinical long-term outcome.     

Efficacy of rhesus antibodies (Anti-Rh0 (D)) in autoimmune thrombocytopenia: correlation with response to high dose IgG and the degree of haemolysis

We have compared the efficacy of high-dose IgG with that of Rhesus antibodies (anti-Rh0 (D)) in 5 patients with autoimmune thrombocytopenic purpura (3 adults and 2 children). Although only transient, high-dose IgG (0.4 g/kg X 5 days) was effective in all patients (peak values 50-200 X 10(9)/1), whereas anti-Rh0 (D) (11-20 micrograms/kg X 5 days) led to comparable results in only 3 patients (165 X 10(9)/1, 72 X 10(9)/1, 33 X 10(9)/1). This response to anti-Rh0 (D) was neither related to the degree of induced haemolysis (increase of LDH and decrease of haptoglobin) nor to the amount of IgG antibodies bound to red blood cells, as quantified by the 125-I-antiglobulin test. A decrease of platelet-associated IgG was recorded in 3 patients: 2 of them showed an improvement of platelet counts and in one of them there was no response. We conclude that the therapeutic response of high-dose IgG and anti-Rh0 (D) is independent of the degree of induced haemolysis and may not be predicted from the effectiveness of either therapy alone.     

Cytoreductive effect of recombinant alpha interferon in patients with myelofibrosis with myeloid metaplasia

In an attempt to reduce myeloproliferation, we administered recombinant alpha-2b interferon (r-alpha INF) to ten patients with myelofibrosis with myeloid metaplasia (MMM) in a hypercellular phase, as part of a phase II trial. Two patients experienced severe side effects and stopped treatment before completion of the first week. In the eight evaluable patients, r-alpha INF was given for 16 weeks at an initial dosage of 3 X 10(6) U/day, with monthly increments in the case of response failure, i.e. a decrease in WBC or platelet count of less than 25% of the initial value. Two cases responded at the starting dosage, while the effective dosage was 5 X 10(6) U/day in the others. At the end of the 16th week, Hb showed minor changes: from an initial value of 12.08 g/dl, range 8.3-17.3, to 11.6 g/dl, range 7.7-18 (P = 0.12); WBC were reduced from 54 X 10(9)/l, range 6.4-69.4, to 17.5 X 10(9)/l, range 5-39 (P = 0.09, 4/8 responses); platelets decreased from 775 X 10(9)/l, range 215-1748, to 403 X 10(9)/l, range 118-730 (P = 0.008, 8/8 responses). Minor changes in spleen size were also noted, while no significant changes in bone marrow fibrosis occurred. Influenza-like symptoms and fatigue were common side effects. In conclusion, r-alpha INF has a role as a non-leukemogenic cytoreductive agent in the therapy of MMM, especially for cases with thrombocytosis.     

Recombinant interferon-alpha, but not interferon-gamma is effective therapy for essential thrombocythemia

Recombinant interferon-gamma with a starting dose of 0.5 mg 3x/week subcutaneously, was administered to 6 patients with essential thrombocythemia (median platelet count 1172 X 10(9)/l, range 602-1564). Four of the patients had received alkylating agents previously. Hematological remission, defined as a decrease in platelet counts to less than or equal to 350 X 10(9)/l, was observed in none of these patients. Subsequently 4 of these 6 patients, supplemented by 2 others were treated with interferon-alpha 2c at a dose of 5 X 10(6) U daily subcutaneously. Five patients showed hematological remission. In case of hematological remission the interferon-alpha doses was reduced to 5 X an thereafter to 3 X weekly 5 X 10(6) U. During an observation period ranging from 12-41 weeks platelet counts remained normal in all patients. Side-effects were mild and consisted of fever, myalgias, malaise and itching occurring mainly during the first month of treatment. No dose adaptation was required. The patients treated previously with interferon-gamma experienced the side effects from this drug less tolerably than those from the alpha-compound. These observations suggest that recombinant interferon-alpha may be an effective drug in treating essential thrombocythemia resulting in a sustained response.     

Shortening of bleeding time after intranasal administration of 1-deamino-8-D-arginine vasopressin to patients with chronic uremia

1-deamino-8-D-arginine vasopressin (DDAVP) was administered intranasally in a dose of 2 micrograms/kg BW to 17 uremic patients (16 maintained on chronic hemodialysis and 1 treated conservatively). The bleeding time was significantly shortened 120 minutes after DDAVP administration (from 18.1 +/- 7.5 minutes to 12.3 +/- 6.4 minutes p less than 0.001). Factor VIII related antigen (VIII: Ag) did not change. Factor VIII ristocetin cofactor activity (VIII: RCof) significantly increased (from 251.2 +/- 162.0 to 336.5 +/- 167.2 p less than 0.025). Platelet count decreased significantly after DDAVP (from 174.9 +/- 43.8 X 10(9)/l to 155.6 +/- 45.9 X 10(9)/l 30 minutes p less than 0.01 and 129.8 +/- 45.2 X 10(9)/l p less than 0.005 120 minutes after DDAVP). Antithrombin III concentration, and hematocrit did not change. Our data indicate that further clinical studies of intranasal DDAVP in uremic patients during episodes of bleeding are warranted.     

Neonatal autoimmune thrombocytopenia: role of high-dose intravenous immunoglobulin G therapy

High-dose intravenous immunoglobulin G (IVIgG) therapy results in a rapid reversal of thrombocytopenia in over 80% of children with acute immune thrombocytopenic purpura (ITP). Comparable results were observed in eleven infants with an analogous condition, neonatal autoimmune thrombocytopenia (NATP), who received IVIgG (2 g/kg body weight) administered alone (n = 6) or in combination with steroids (n = 5). The median platelet count pre-IVIgG therapy was 25 X 10(9)/l (range 5 to 74 X 10(9)/l). The overall response rate to IVIgG therapy, administered alone or in combination with steroids was 75% (12 of 16 treatment episodes). A good response to therapy was defined as an increase in the platelet count to greater than or equal to 50 X 10(9)/l and at least twice the pre-treatment value at 48 h after completion of the IVIgG infusion. The rapid and generally excellent response to IVIgG therapy in infants with NATP suggests that this treatment approach should be considered as first-line therapy for severely thrombocytopenic infants with this self-limiting but potentially serious disorder.     

Prognosis in acquired aplastic anemia. An approach in the selection of patients for allogeneic bone marrow transplantation.

In a retrospective study, factors influencing the eventual course and outcome of patients suffering from aplastic anaemia were analysed. Of the 62 patients with pancytopenia concomitant with an aplastic or hypoplastic bone marrow, 36 have died during the first 24 months following diagnosis, 27 of these 36 cases within the first six months. 26 patients survived more than two years after presentation, but a further six of these cases succumbed during the following months. Of the 62 cases, 46 had neutrophil counts under 1 X 10(9)/l and platelet counts under 20 X 10(9)/l. These cases were subdivided according to their reticulocyte levels. In the age group of patients between 10 and 35 years, all those patients having more than 10,000/mul reticulocytes survived more than two years with only one exception, whereas only one of the 11 patients having reticulocyte counts below 10,000/mul has survived. In our series, the initial neutrophil and platelet counts were not of predictive value in identifying poor prognosis patients. The initial reticulocyte counts, however, appear to be a valid parameter for selecting patients in two groups, one with a favorable, and the other with an extremely unfavorable prognosis on conservative treatment. Young individuals with a poor predicted prognosis could thus be defined as possible candidates for bone marrow transplantation.     

ITP in pregnancy: use of the bleeding time as an indicator for treatment

ITP is a relatively common disorder seen in pregnancy. Current recommendations for management of patient with ITP recommend maintaining the platelet count above 50 x 10(9)/L and the bleeding time less than 20 min. It has been well documented that the bleeding time in ITP is disproportionately shortened in many patients relative to the platelet count. We present a prospective study of 24 ITP patients in whom the bleeding time was used as an indicator for therapeutic intervention in pregnancy. Indications for therapy with prednisone and/or intravenous gammaglobulin were the following: significant clinical hemorrhage due to thrombocytopenia; bleeding time of greater than 20 min at the baseline platelet count; for normalization of hemostasis prior to delivery or surgical procedure. Caesarean section was performed only in cases in which there were obstetrical indications for this mode of delivery or when the fetal platelet count (obtained by fetal scalp vein sample) was less than 50 x 10(9)/L. Of 24 patients with ITP, eight had significant thrombocytopenia (platelet count less than 50 x 10(9)/L) throughout pregnancy. Only two patients required prolonged prednisone therapy. Both suffered side effects of chronic prednisone administration. Four patients were treated with prednisone for a short course (10-14 days) at term to improve hemostasis for delivery. One patient was treated with intravenous gammaglobulin at term in an effort to prevent severe neonatal thrombocytopenia. Seven patients required caesarean section; the remaining 17 patients underwent vaginal delivery. Only one minor bleeding complication was seen - a small wound hematoma post caesarean section. In summary, using the bleeding time as an indicator for therapeutic intervention, treatment of ITP in pregnancy can be minimized. Thus, therapy related toxicity can be avoided.     

Leukostasis associated with blood transfusion in acute myeloid leukaemia.

Three patients with acute myeloblastic leukaemia and blast cell counts greater than 100 X 10(9)/1 (100 000/mm3) died unexpectedly soon after blood transfusion. In two cases postmortem examination disclosed cerebral leukostasis. Analysis of the records from the MRC''s fourth and fifth acute myeloid leukaemia trials showed that in the first week after diagnosis mortality was five times greater in patients with blast counts above 100 X 10(9)/1 than in patients with lower counts. Age and platelet count did not explain this excess. The mean haemoglobin concentration in the patients with high blast counts who died within the first week was 10.5 +/- 2.8 g/dl, which was significantly higher than that in the surviving group (7.6 +/- 2.4 g/dl). Only half the patients received chemotherapy within two days of diagnosis. Leukostasis is an important cause of early death in patients with high blast counts, and the increase in viscosity produced by transfusing to a haemoglobin concentration above 10 g/dl may lead to sudden deterioration. Transfusion to such concentrations should be avoided until the blast count has been reduced by early chemotherapy.     

ITP in pregnancy and the newborn: introduction

Idiopathic thrombocytopenic purpura (ITP) occurs more commonly in young women and is one of the commonest immune mediated disorders in pregnancy. It may exist as an incidental finding in an otherwise healthy pregnant woman or may be associated with symptomatic reduction in the platelet count and varying degrees of clinical hemorrhage. The condition termed incidental thrombocytopenia of pregnancy is invariably associated with a platelet count of greater than 100 x 10(9)/L and a very low incidence of fetal thrombocytopenia. Symptomatic thrombocytopenia is more commonly associated with low platelet counts in the fetus (estimated between 20%-40%). It has recently been suggested that the incidence of fetal thrombocytopenia is substantially lower than this figure. The management of ITP in pregnancy is complicated by the fact that fetal thrombocytopenia is difficult to diagnose and carries substantial risks during the delivery process with rare cases of fetal hemorrhage occurring spontaneously in utero. Unfortunately there are no laboratory studies that can be performed precisely in the mother that may predict the occurrence of fetal thrombocytopenia. Maternal management is usually directed towards treatment of maternal symptoms. Maternal treatment or response to treatment is inconsistently associated with predictable changes in the fetal platelet count. Obstetric management is aimed at reducing the risks of life threatening fetal hemorrhage occurring at the time of delivery, and fetal management is directed towards the obtaining of fetal platelet samples in order to plan an appropriate strategy for obstetrical delivery. Fetal blood samples are obtained either by a scalp vein puncture at the time of delivery or earlier in gestation by the use of the newer technique termed percutaneous umbilical blood sampling. Fetuses with platelet counts of less then 50 x 10(9)/L are generally delivered by cesarean section whereas those with counts greater than 50 x 10(9)/L are allowed to proceed with vaginal delivery assuming no obstetrical contraindications exist. The use of IVIgG therapy during pregnancy has theoretical implications on improving platelet counts in the mother in situations of severe hemorrhage, however cannot be considered to be appropriate treatment for the prevention of fetal thrombocytopenia, since the exogenous transport of IVIgG across the placenta appears to be inconsistent and unpredictable.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunologic findings,thrombocytopenia and disease activity in lupus nephritis.

Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis.     

The treatment of neonatal isoimmune thrombocytopenia with intravenous immunoglobin (IgG i.v.)

We present a report of the use of IgG i.v. to treat clinically manifest neonatal immune thrombocytopenia. The IgG i.v. was administered at a daily dosage of 0.4 g/kg body weight for 5 days. Treatment was started when the child was 3 days old and had a platelet count of 2 X 10(9)/l. Four days later the platelet count had risen to 200 X 10(9)/l. The diagnosis of immune thrombocytopenia was confirmed by platelet typing of the mother's and child's platelets and identification of anti-platelet antibodies in maternal serum.     

Basic haematological values in carnivores--II. The Felidae

1. Basic haematological values in 34 animals of eight carnivorous species are reported. 2. In four Northern lynxs (Lynx lynx lynx), two male and two female animals, the mean values are given: erythrocyte counts 8.51 X 10(12)/l, haematocrit 0.392/l, haemoglobin content 148.0 g/l and leukocyte count 7.92 X 10(9)/l. 3. In six male pumas (Puma concolor missolensis) the mean values estimated are: erythrocyte count 9.35 X 10(12)/l, haematocrit 0.43/l, haemoglobin content 163.9 g/l and leukocyte count 7.73 X 10(9)/l. Individual values in one female puma are also given. 4. In six jaguars (Panthera onca), three male and three female animals, the mean values are given: erythrocyte count 8.27 X 10(12)/l, haematocrit 0.37/l, haemoglobin content 137.1 g/l and leukocyte count 15.15 X 10(9)/l. 5. Only individual values are reported in one clouded leopard (Neofelis nebulosa), in one leopard (Panthera pardus saxicolor), in one Corbett's tiger (Panthera tigris Corbetti) and in one Altaic tiger (Panthera tigris Altaica). 6. In four lions (Panthera leo leo), two male and two female animals, the mean estimated values are: erythrocyte count 10.14 X 10(12)/l, haematocrit 0.462/l, haemoglobin content 159.0 g/l and leukocyte count 11.05 X 10(9)/l. In six female cheetahs (Acinonox jubatus jubatus) the mean values estimated are: erythrocyte count 7.86 X 10(12)/l, haematocrit 0.373/l, haemoglobin content 142.8 g/l and leukocyte count 8.65 X 10(9)/l. For three male cheetahs only individual values are reported. 8. All results achieved are compared with those abstracted from the literature and discussed.     

Comparison of whole-blood eosinophil counts in extrinsic asthmatics with acute and chronic asthma.

Venous whole-blood eosinophil counts were performed on 50 occasions in 42 patients with varying patterns of asthma. None of the patients studied had received systemic corticosteroids during the previous year. Patients with acute severe asthma, as defined by symptomatic airways obstruction with a tachycardia of at least 120 beats/min, showed eosinopenia (21 x 10(9)/l +/- SD 57 x 10(9)/l). Patients with chronic asthma, as defined by symptomatic airways obstruction with a heart rate of less than 100 beats/min, showed appreciable eosinophilia (1048 x 10(9)/l +/- SD 708 x 10(9)/l). Finally, asymptomatic patients had a variable total eosinophil count but with values lower than those of patients with chronic asthma (345 x 10(9)/l +/- SD 431 x 10(9)/l). Eosinophilia may contain chronic asthma, thereby mediating bronchial damage, whereas absence of eosinophils in acute asthma enables vasoactive mediators to enter the systemic circulation, possibly causing circulatory disturbances.     

Therapy of a refractory idiopathic thrombocytopenic purpura by vinblastine-loaded thrombocytes (author's transl)

A 15-year-old patient with ITP which was refractory to corticosteroids, splenectomy, and immunosuppressive therapy with vincristine was twice treated with platelets loaded with vinblastine. Five days after the application of the platelets vinblastine complex the platelets began to rise up to 600 X 10(9)/l. The remission has lasted until now for more than 15 weeks. The therapy showed no major side effects except for a transient granulocytopenia.     

Basic haematological values in carnivores--I. The Canidae, the Hyaenidae and the Ursidae

Basic haematological values for 32 animals of four carnivore species are reported. In six adult wolves (Canis lupus) the mean values estimated for the erythrocyte count 7.48 X 10(12)/l, haematocrit 0.465/l, haemoglobin 172.0 g/l and leukocyte counts 7.33 X 10(9)/l are given. For five young wolves, these parameters were markedly decreased, only the white cell count was raised. In 14 hunting dogs (Lycaon pictus) the mean values estimated are: erythrocyte count 9.15 x 10(12)/l haematocrit 0.435/l, haemoglobin 179.2 g/l and leukocytes 12.95 X 10(9)/l. In six striped hyaenas (Hyaena hyaena) the mean estimated values are: erythrocyte count 8.11 X 10(12)/l, haemoatocrit 0.445/l, haemoglobin 178.0 g/l and leukocytes 13.95 X 10(9)/l. Only individual values for the reported parameters are given in the Asiatic black bear (Selenarctos thibetanus). All results are compared with values derived from the literature for animals under investigation and for the domestic dog (Canis familiaris).     

Variability in serial CD4 counts and relation to progression of HIV-I infection to AIDS in haemophilic patients. Transfusion Safety Study Group.

OBJECTIVE--To examine the CD4 count and its near term changes relative to progression to AIDS within 30 months and to subsequent CD4 counts. DESIGN--Longitudinal clinical and laboratory study. SETTING--Haemophilia treatment centres in six large American cities. PATIENTS--555 people with congenital clotting disorders who were infected with HIV, initially without AIDS, and seen at follow up for 6-30 months in 1986-9. MAIN OUTCOME MEASURES--Absolute CD4 counts and incidence of AIDS. RESULTS--Outset CD4 count and age were independently related to progression to AIDS (p less than 0.0001 and p less than 0.005 respectively). Patients with CD4 counts of 0.30-0.49 x 10(9) cells/l had an age adjusted risk of AIDS within 30 months of only 9% that of patients with counts less than 0.20 x 10(9)/l. Children under 10 years old had only 16% of the CD4 adjusted risk of AIDS of people aged greater than or equal to 45 years. Analysis of 149 patients'' CD4 counts at the beginning and end of two successive six month intervals showed an average decrease of 11% in each six months regardless of the outset count (greater than or equal to 0.20 x 10(9)/l). For individual patients the decrease in the second six month period was unaffected by the decrease in the first six month period. CONCLUSIONS--Antiviral treatment of asymptomatic people, particularly children, with CD4 counts greater than or equal to 0.3 x 10(9)/l is questionable if predicted on near term progression to AIDS. Because of individual CD4 count variability and the low rate of progression to AIDS near term declines in individual CD4 counts are a poor index for identifying people who will rapidly progress to AIDS.     

Haematological values during normal reproduction of the maternal and the fetal rabbit

1. Haematological values of non-pregnant/non-lactating, pregnant as well as lactating rabbits and 28-day-old fetuses were measured. 2. The haemoglobin content in does decreased during the observed periods from 122 +/- 8 g/l to 100 +/- 11 g/l. In 28-day-old fetuses it was 85 +/- 0 g/l. 3. The erythrocyte count in 28-day-old fetuses was 2.4 X 10(12)/l. In the does, the erythrocyte count was 5.2 X 10(12)/l in week 4 of gestation. The erythrocyte volume in fetuses was about 45% higher than that of the doe. 4. In fetuses the leucocyte count was approximately one ninth that of the mother in week 4 of gestation (0.41 +/- 0.08 X 10(9)/l vs 3.8 +/- 0.4 X 10(9)/l).     

Proof of an association between Helicobacter pylori and idiopathic thrombocytopenic purpura in Latin America

BACKGROUND: Association between Helicobacter pylori and idiopathic thrombocytopenic purpura (ITP) has been found in Japan and in some European countries. It has also been shown that eradication of H. pylori can increase platelet counts in patients with ITP. The aims of this study were to determine the prevalence of H. pylori infection in patients with ITP in Colombia, and the effect of bacterial eradication on their platelet counts. MATERIALS AND METHODS: Between December 1998 and April 2006, a total of 32 patients diagnosed with ITP were included in the study. Controls were age and sex matched. RESULTS: H. pylori infection in patients with ITP was significantly higher (p = .00006) than in control individuals (90.6% and 43.8%, respectively), as determined by (13)C-urea breath test. A significant association between H. pylori infection and ITP was found (p < .0003), with an odds ratio (OR) of 13.15 (95%CI: 3.24-53.29). Multivariate analysis for the association between H. pylori and ITP showed an OR of 20.44 (95%CI: 3.88-107.49) for women and 19.28 (95%CI: 2.03-183.42) for individuals over 50 years. All 29 H. pylori-positive patients with ITP received eradication treatment. After a median follow up of 12.2 months, 80.8% had a recovery in platelet counts. CONCLUSIONS: According to these results and others from different countries where H. pylori infection rates are high, patients with ITP should be initially tested for H. pylori status, and if present, infection should be eradicated before initiating a drastic conventional ITP treatment. An algorithm for the study and management of patients with ITP in the post-Helicobacter era is presented.