An alternative intermittent eltrombopag dosing protocol for the treatment of chronic immune thrombocytopenia.

Eltrombopag, an oral thrombopoietin receptor agonist, is dosed daily to treat chronic immune thrombocytopenia (ITP). As it has a half-life of 26-35 h in ITP patients and requires patents to abide by strict dietary restrictions that may impair quality of life and reduce compliance, we developed an alternative intermittent (AI) eltrombopag dosing protocol for ITP, with dosing less frequent than once daily. Ten patients were treated with AI dosing for a median of 94 (range: 29-156) weeks, with most patients treated with 2-4 weekly doses for extended durations. During AI dosing, 95%, 84% and 71% of all platelet counts were ≥20 × 109 l-1 , ≥50 × 109 l-1 and ≥100 × 109 l-1 , respectively. Five patients required rescue treatment for thrombocytopenia and World Health Organization grade 1 mucocutaneous bleeding, and there were no thromboembolic events. In summary, intermittently dosed eltrombopag was efficacious in treating chronic ITP in a small cohort, with rates of platelet response and rescue treatment comparable with rates in studies evaluating daily dosing.

[Particular features of erythropoiesis in high altitude and possibilities of applying of hypoxic hypoxia methodology for the patients with hemopoietic suppression].

Conditions of hypoxic hypoxia at 3200 m height exert significant positive changes in hemopoiesis, normalizing erythropoiesis and coagulation system. Hypoxic climate therapy can be regarded as an additional efficient method to the pathogenetic treatment for patient with unpainful aplastic anemia and idiopathic thrombocytopenic purpura. It should be emphasized that patients must be out of immunosuppressive therapy when getting high altitude stationary.

Alternative therapy for persistent childhood immune thrombocytopenic purpura unresponsive to intravenous immunoglobulin.

OBJECTIVE: Presentation of a case illustrating the benefits of traditional Chinese herbal granules for treatment of immune thrombocytopenic purpura in children. CLINICAL FEATURES: A 4-year-old girl presented with persistent immune thrombocytopenic purpura refractory to the first-line conventional treatment of steroids and intravenous immunoglobulin over 7 months. She was brought to the traditional Chinese medical clinic at the Chang Gung Memorial Hospital in 2011 for alternative therapy. She received a modified Chinese herbal formula, Zi-Ying-Jiang-Huo-Tang (Phellodendri Combination), for 6 months and was followed clinically by both a pediatrician and a traditional Chinese medical doctor. The patient had a dramatic improvement in platelet count and entered complete remission after treatment with the traditional Chinese medicine. There was no recurrence of disease or side effects of treatment noted during the 12-month follow-up period. CONCLUSIONS: Our case report suggests that collaborative monitoring of treatments with traditional Chinese medicine may prove beneficial in the management of childhood persistent immune thrombocytopenic purpura. A larger clinical study is warranted for further evaluation of the role of Zi-Ying-Jiang-Huo-Tang in treating immune thrombocytopenic purpura.

Antibody-mediated platelet phagocytosis by human macrophages is inhibited by siRNA specific for sequences in the SH2 tyrosine kinase, Syk.

Immune thrombocytopenia depends upon Fc receptor-mediated phagocytosis that involves signaling through the SH2 tyrosine kinase, Syk. We designed small interfering (siRNA) sequences complementary to Syk coding regions to decrease the expression of Syk in the human macrophage cell line, THP-1. To evaluate the functional effect of siRNA on phagocytosis, we developed a new in vitro assay for antibody-mediated platelet ingestion by THP-1 cells. Incubation of THP-1 cells at 37°C with fluorescence-labeled platelets and anti-platelet antibody promoted ingestion of platelets that could be quantitated by flow cytometry. Transfection of THP-1 cells with Syk-specific siRNA resulted in a reduction in the amount of FcγRII-associated Syk protein. Coincident with decreased Syk expression, we observed inhibition of antibody-mediated platelet ingestion. These results confirm a key role for Syk in antibody-mediated phagocytosis and suggest Syk-specific siRNA as a possible therapeutic candidate for immune thrombocytopenia.

Durability and factors associated with long term response after splenectomy for primary immune thrombocytopenia (ITP) and outcome of relapsed or refractory patients.

Splenectomy is the usual form of therapy for immune thrombocytopena (ITP) after steroid failure. We retrospectively studied the data in adult patients who underwent splenectomy for ITP from July 1996 to June 2008 to evaluate the long term responses, clinical and laboratory factors associated with long term responses and outcome of relapsed or refractory patients. Thirty eight patients, 30 (79%) females, with a median age of 23 years (range 15-69), underwent splenectomy. The procedure was laparoscopic in 28 (73.5%) and open in 10 patients. Splenectomy resulted in a response in 34/38 (89.5%) patients and failed in four (10.5%) patients. After a median follow-up of 58 months (range 7-144), 24 (63%) patients had a maintained response without treatment (platelet count of >50 × 109)/l). Most of the relapses occurred during the first year but two patients had late relapses. There were procedure-related complications in seven (18.0%) patients but no cases of overwhelming sepsis. Only four relapsed or refractory patients had a platelet count below 50 × 109/l at the last follow-up indicating response to alternative therapies. Responsiveness to steroids before the procedure (p = 0.025) along with a platelet count of ≥ 150 × 109/l at 4 weeks (p = < 0.0001) and a highest platelet count of ≥ 400 × 109/l at any time post-splenectomy (p = 0.005), were associated with a long term response in univariate analysis. In conclusion, splenectomy remains an effective treatment for ITP after steroid failure in terms of long term responses, and the majority of relapsed or refractory patients respond to alternative therapies.

Treatment of 37 patients with refractory idiopathic thrombocytopenic purpura by shengxueling.

OBJECTIVE: To explore the clinical effect and possible mechanism of Shengxueling (SXL), a Chinese medical preparation mainly consisting of ginseng saponins, in treating refractory idiopathic thrombocytopenic purpura (ITP). METHODS: The selected 69 patients with ITP were randomly assigned to two groups, the 37 patients in the treated group were treated orally by SXL with the dose for adult as 60 mg twice a day for two weeks. Then when no marked rise of platelet count after that, the dose would be doubled and administered for another two weeks. Then the dose could be gradually reduced to the initiative level in patients who responded to the treatment, and if they did not, the treatment was regarded as ineffective and be terminated. The 32 patients in the control group were treated with ampeptide elemente instead of SXL, 0.4 g each time three times a day in the first two weeks, and, if that was ineffective, 0.2 g would be added each time and 1.8 g would be administered a day for two more weeks. Four weeks' treatment was regarded as one therapeutic course for both groups and the observation lasted for two successive courses in patients showing positive reslonse. RESULTS: In the 37 patients in the treated group, markedly effective was obtained in 7 (19.0%), favorably effective in 15 (40.5%), improved in 5 (13.5%) and ineffective in 10 (27.0%), the total effective rate being 59.5%. The corresponding number in the 32 patients in the control group was 4 (12.5%), 6 (18.8%), 3 (9.4%), 19 (59.4%) and 31.3% respectively. Comparison showed the difference in therapeutic efficacy between the two groups was significant (P<0.05). CONCLUSION: SXL is a safe and effective preparation for treatment of ITP, showing an immediate effect which is obviously superior to that of ampeptide elemente with less adverse effect.

Treatment with liposome-encapsulated clodronate as a new strategic approach in the management of immune thrombocytopenic purpura in a mouse model.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease related to the presence of elevated levels of platelet-associated immunoglobulin, or autoantibodies. In recent years the importance of macrophage Fc gamma receptors in the uptake of platelets in ITP has been confirmed. Although in patients with ITP the platelet destruction occurs in liver and spleen, in this present experimental mouse model the liver was the principal organ of sequestration of sensitized platelets. The uptake in the spleen, bone marrow, lung, and kidneys was negligible and not different from that in control animals. In addition, the trapped platelets did not return to circulation, and new cells derived from the platelet-storage pool or new thrombocytogenesis were necessary to restore the platelet count. The depletion of splenic and hepatic murine macrophages by liposome-encapsulated clodronate (lip-clod) was studied as a new strategy for ITP treatment. Lip-clod inhibits, in a dose-dependent manner, the antibody-induced thrombocytopenia. Moreover, lip-clod treatment rapidly restored (24 hours) the platelet count in thrombocytopenic animals to hematologic safe values, and despite additional antiplatelet antiserum treatment, mice were able to maintain this level of platelets at least up to 48 hours. The bleeding times in lip-clod-treated animals was not different from those in controls, demonstrating that the hemostasis was well controlled in these animals. The results presented in this study demonstrate that lip-clod treatment can be effective in the management of experimental ITP. (Blood. 2000;96:2834-2840)