Remission Of Thrombocytopenia Research Articles

Intravenous immunoglobulins (IVIg) in childhood immune thrombocytopenia: towards personalized medicine—a narrative review

: In childhood immune thrombocytopenia (ITP), the morbidity is significant due to the risk of bleeding and a reduced health-related quality of life (HRQoL). Current management guidelines indicate that treatment is considered for children with moderate to severe bleeding, or a reduced HRQoL. Intravenous immunoglobulin (IVIg) treatment has been introduced in childhood ITP in 1981. IVIg treatment speeds up the remission of thrombocytopenia in newly diagnosed ITP and reduces bleeding symptoms, but this has the disadvantage of side effects and costs. Some data indicated that IVIg may modulate the late disease outcomes of ITP, but our recent randomized controlled trial (RCT) showed that IVIg does not affect the development of chronic ITP. Overall, 60% of children with newly diagnosed ITP show a sustained response to IVIg. Such a sustained response after IVIg treatment is strongly associated with long-term remission from ITP. Recent molecular and clinical data show that treatment responders could be identified before IVIg is administered. The same molecular and clinical characteristics that identify treatment responders are otherwise associated with a transient, self-limiting ITP disease course, suggesting the identification of a distinct subgroup of ITP patients. Thus, the development of multivariate clinical and molecular prediction scores could allow to individualize treatment decisions, i.e., target IVIg to those who benefit the most. These prediction scores may also be used to design studies aimed at identifying children who benefit from adjunctive or alternative treatments, such as thrombopoietin receptor agonists (TPO-Ra).

Recurrent thrombocytopenia and Lyme disease

Case report We present the case of a 24 year-old man admitted to the Hospital of Infectious Diseases for headache, myalgia, arthralgia and a previous unrepeated episode of moderate fever. Physical examination at the admission revealed a poor general status, loss of appetite, difficulties in maintaining orthostatic position due to the hypotonia of the lower limbs muscles, absence of meningeal irritation syndrome. He denied any tick bites in the past. Lumbar puncture, cranio-cerebral computed tomography were normal, as well as different serology for EBV, Mycoplasma, HIV, syphilis. The most prominent hematologic feature was a severe thrombocytopenia (29,000/cmm). He received ampicillin and dexamethasone and the level of platelets increased progressively to normal during a period of eight days. He was discharged without any complaints, but he returned after 5 days with the same symptoms, and thrombocytopenia (37,000/cmm). A serology test for Borrelia was performed and it was positive revealing the diagnosis of Lyme disease. The complete remission of thrombocytopenia under the same association of drugs was very rapid – in 4 days. He was discharged after having been treated for three weeks with antibiotic and two weeks of corticotherapy. Authors’ details “Gr.T.Popa” University of Medicine and Pharmacy, Iasi, Romania. Hospital of Infectious Diseases, Iasi, Romania.

IDIOPATHIC THROMBOCYTOPENIC PURPURA AND HELICOBACTER PYLORI INFECTION

Introduction: It has recently been reported that a relationship between Idiopathic Thrombocytopenic Purpura (ITP) and Helicobacter Pylori (HP) infection exists in adult series. A link between the eradication of the infection itself and the remission of thrombocytopenia has also been observed. The aim of our study was to assess the prevalence of HP infection in children affected by chronic ITP and to verify the influence of the treatment on platelets counts. Patients and Methods: Our study lasted a minimum of 12 months and involved 31 children (Mean age: 136 months; range: 53-216 months; M/F: 10/20), all affected by chronic ITP. Patients were followed for 12 months: 6 months to assess chronic behaviour of ITP and 6 months for the follow-up. Unsplenectomized patients affected by chronic ITP underwent: Urea Breath Test (UBT), a search for HP antigen in stool samples as well as a search for HP antibodies in serum. In order for a diagnosis of HP infection to be made, two of the 3 results in the above mentioned tests had to be positive. Patients affected by HP infection were randomized into two groups: one group was treated with amoxicilline, claritromicine and omeprazole; the second group did not receive any therapy: Six weeks after the end of treatment patients underwent a UBT to assess their recovery from HP infection. In both groups, treated and untreated, for the 6 months following the diagnosis of chronic ITP, platelet counts were performed weekly (for Platelets <20000/mmcu), every 2-3 weeks (for Platelets between 20000 and 50000/mmcu) and monthly (for Platelets >50000/mmcu). Results: In our study the prevalence of HP infection in patients affected by chronic ITP was 22.5% (7/31 patients). Three of 7 patients were treated (Mean age: 174 months), and the mean platelet count at the onset of ITP was 72000/ mmcu (range 33000-128000/mmcu); 1/3 patients who received treatment did not recover from HP infection. In the 4 untreated patients (Mean age: 143 months) the mean platelet count was 94000/mmcu (range: 63000-124000/mmcu). At the follow-up the platelet count difference between treated and untreated patients and between infected and uninfected patients was not statistically significant. Conclusions: Our preliminary data do not suggest any relationship between ITP and HP infection.

Pentosan polysulfate‐induced thrombocytopenia and thrombosis

Pentosan polysulfate is a low-molecular-weight sulfated polysaccharide used as an antithrombotic drug. We present two patients who developed thrombocytopenia and venous thrombosis during treatment with pentosan polysulfate. The relationship between pentosan polysulfate and thrombocytopenia is supported by platelet aggregation and serotonin release tests. In the light of the literature and our two cases, it appears that pentosan polysulfate alone as standard heparin and low-molecular-weight heparin can induce thrombocytopenia and thrombosis. Platelet counts should therefore be periodically monitored during pentosan polysulfate treatment. In the case of pentosan polysulfate-induced thrombocytopenia, it seems that heparin or low-molecular-weight heparin should not be instituted during the acute phase even if platelet aggregation studies are negative, because of their low sensitivity. After remission of thrombocytopenia, whether or not glycosaminoglycans can be reinstituted, at least temporarily, after antibody had disappeared is still an open question.

Cephalosporin-induced immune cytopenia in the dog: demonstration of erythrocyte-, neutrophil-, and platelet-associated IgG following treatment with cefazedone.

Cephalosporin treatment in man has been associated with a low incidence of hemolytic anemia, thrombocytopenia, and neutropenia; some cases have been shown to be immune-mediated. This triad of blood dyscrasias was also demonstrated in our laboratory in a series of toxicity studies in dogs of two cephalosporin compounds, cefonicid and cefazedone; these studies provided evidence for drug-associated immune hemolytic anemia, based on conventional laboratory tests. To further investigate possible immune mechanisms of the cephalosporin-induced cytopenias, we measured erythrocyte-associated, platelet-associated (PAIgG), and serum antineutrophil IgG over the course of cephalosporin treatment, using highly sensitive 125I-staphylococcal protein A (SPA) assays, as well as the direct antiglobulin test; we compared these findings with the hematologic changes. Intravenous treatment with high doses of cefazedone (540 mg/kg/day, increased to a maximum of 840 mg/kg/day for 4 months or until hematologic effects were evident) resulted in a high incidence of anemia (7/14), thrombocytopenia (11/14), and neutropenia (7/14). Of the affected dogs examined, 6/7 with anemia, 9/9 with thrombocytopenia, and 7/7 with neutropenia showed increased levels of the respective cell-associated antibody, compared with untreated controls. Unaffected dosed animals generally did not show these changes. In 3/3 dogs examined following remission of thrombocytopenia, PAIgG returned to levels comparable with controls; as one of these dogs suffered a relapse, increased PAIgG was again observed. Animals sacrificed during cytopenic episodes showed cytologic and histologic evidence of increased hemophagocytosis. We conclude that antibody-mediated blood cell destruction contributes to all three cephalosporin-induced cytopenias in the dog.

Heparin-Associated Thrombocytopenia

Two hundred eleven consecutive patients treated for acute thromboembolic disease were evaluated prospectively for the incidence of thrombocytopenia while receiving heparin treatment. One hundred patients received beef lung heparin and 111 patients received porcine intestinal mucosal heparin. All patients received a minimum of 4 consecutive days of continuous intravenous heparin, and platelet counts were determined prior to, at least twice weekly, and at the cessation of heparin therapy. Heparin-associated thrombocytopenia was defined as a decline from a normal platelet count (100,000-400,000/mm3) to less than 100,000/mm3 with a return to above 100,000/mm3 after the discontinuation of heparin. Heparin-associated thrombocytopenia developed in 11 patients (5.2% incidence). Ten of the thrombocytopenic patients had received beef lung heparin and one received porcine mucosal heparin. Chi-square analysis of these data was significant (p = 0.007). Plasma from seven of nine thrombocytopenic patients demonstrated a plasma factor compatible with a heparin-sensitive antiplatelet antibody. Heparin-associated thrombocytopenia appeared on days 2 to 10 of therapy. Cessation of heparin resulted in remission of thrombocytopenia within 4 days in all patients. Serial quantitative platelet count determinations are indicated in all patients receiving therapeutic heparinization for the early recognition and resolution of heparin-associated thrombocytopenia.