Efficacy and safety of prophylaxis with BAY 81-8973 in Chinese patients with severe haemophilia A enrolled in the LEOPOLD II trial.

INTRODUCTION: BAY 81-8973 (Kovaltry® ) is a full-length, unmodified recombinant human factor VIII approved in China for prophylaxis and on-demand treatment in patients with haemophilia A. Limited access to FVIII prophylaxis in China has historically led to this population being undertreated. This subanalysis of LEOPOLD II investigated whether the efficacy and safety of BAY 81-8973 varied between Chinese and non-Chinese patients. AIM: To evaluate BAY 81-8973 efficacy and safety in Chinese patients. METHODS: LEOPOLD II enrolled males aged 12-65 years with severe haemophilia A who were receiving on-demand treatment. Patients were randomly assigned to receive BAY 81-8973 as low-dose prophylaxis (20-30 IU/kg twice-weekly), high-dose prophylaxis (30-40 IU/kg 3 times weekly) or on-demand for 1 year. RESULTS: Data were available from 23 Chinese and 57 non-Chinese patients; Chinese patients had a higher prestudy bleeding rate and were more likely to have target joints than non-Chinese patients. 74% of patients were assigned to prophylaxis. Annualized bleeding rates (ABRs) in Chinese and non-Chinese patients receiving prophylaxis were significantly lower compared to patients treated on-demand. Median ABRs for all bleeds in the last 6 months of the study were 2.0 and 1.0 for Chinese and non-Chinese patients, respectively, in the combined prophylaxis groups, and 61.3 and 58.5 in the on-demand group. A treatment-related adverse event occurred in 1 Chinese patient; no patients developed FVIII inhibitors. CONCLUSION: BAY 81-8973 prophylaxis was efficacious and well tolerated in Chinese patients with severe haemophilia A, with ABRs comparable to those in non-Chinese patients receiving prophylaxis.

Decreased immunosuppressive actions of 1α, 25-dihydroxyvitamin D3 in patients with immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease. 1α, 25-dihydroxyvitamin D3 [1,25(OH)2D3] and vitamin D receptor (VDR) play important immune-suppressive roles in immune system. It has been reported that serum 1,25(OH)2D3 were lower in ITP patients. In this study, we evaluated local 1,25(OH)2D3 level and VDR mRNA expression further, and determined whether 1,25(OH)2D3/VDR were correlated with T cell dysfunction in ITP patients. We found that 1,25(OH)2D3/VDR levels were decreased in active ITP patients, and 1,25(OH)2D3 had significant anti-inflammatory effects on ITP patients, including both anti-proliferation of peripheral blood mononuclear cells (PBMCs) and reversing the abnormal T cells polarization. 1,25(OH)2D3 inhibited the differentiation of T helper (Th)1 and Tc1 cells but induced the differentiation of Th2, Tc2 and T regulatory (Treg) cells in ITP patients. However, the percentage of Th17 cells were not affected obviously with 1,25(OH)2D3. In addition, 1,25(OH)2D3 also suppressed pro-inflammatory cytokines (INF-γ and IL-17A) but promoted anti-inflammatory cytokine (IL-10) secretion in ITP patients. In conclusion, decreased 1,25(OH)2D3/VDR might participate in the pathogenesis of ITP, and appropriate supplement of 1,25(OH)2D3 may be a promising treatment.

[Acquired coagulation factor X deficiency: three cases report and literature review].

OBJECTIVE: To deepen the understanding of acquired coagulation factor X (F X) deficiency. METHODS: The clinical data of 3 patients were analyzed and related literature were reviewed. RESULTS: Case 1, a 57-year-old male, secondary to multiple myeloma and amyloidosis, was presented with spontaneous mucous hemorrhage with the level of FX:C 1.8%, which kept unchanged after chemotherapy with melphalan, glucocorticoid, and thalidomide, and died of primary disease progression. Case 2, a 41-year-old male with psoriasis, was presented with cerebral and retinal hemorrhage with the level of FX:C 26.8%. The signs of hemorrhage were alleviated after the supplement of folic acid, vitamin B12, and vitamin K, and transfusion with red blood cells, platelets, and fresh frozen plasma. Case 3, a 63-year-old female, associated with high level of lupus anticoagulant, was presented with repeated ecchymosis and haemarthrosis with the level of FX:C 6.1%, which was refractory to prothrombin complex concentrate, methyprednisolone, azathioprine, and rituximab. CONCLUSION: Acquired FX deficiency is a rare disorder with variable symptoms. The diagnosis relies on history of disease and laboratory test. Currently, there is no standardized treatment. The prognosis of acquired FX deficiency is mainly related to the underlying disease.

Immune thrombocytopenia in the elderly: clinical course in 525 patients from a single center in China.

Immune thrombocytopenia (ITP), often diagnosed in the elderly, is a hematologic disorder induced by autoimmune mechanism. In this retrospective study, we evaluated the clinical features, the risk of bleeding, and the response to treatment in 525 elderly ITP patients (age ≥60 years) diagnosed at our center from 1980 to 2009. There were more females at 60-74 years of age (P = 0.044). The median duration of follow-up was 27 months (range 1-253 months). Ten patients developed thrombosis during treatment of ITP. At diagnosis, 461 patients (87.8 %) had signs of bleeding. The risk of severe bleeding was associated with both platelet count (P < 0.001; odds ratio (OR), 0.973) and age (P = 0.025; OR, 1.039). The cutoff points in the platelet count at which bleeding and severe bleeding would begin to appear were 29.5 × 10(9) and 21.5 × 10(9)/L, respectively. Sixteen of 144 patients (11.1 %) who did not receive any treatment achieved remission spontaneously. The total response rate to treatment was 62.4 % (166/266). The median time to remission was 7 days, and combined use of intravenous immunoglobulin and steroids took effect faster than use of steroids alone (P = 0.001). Fifty-two patients (31.3 %) relapsed during follow-up. Of the 27 patients who died during follow-up, seven deaths were directly attributed to ITP. In conclusion, the response rate has been improved since the last 10 years. ITP is also a self-limited disease to some extent in the elderly, but easy to relapse. This review represents the largest collection of elderly ITP patients in China in a single center.

Retrospective analysis of 472 Chinese children with chronic idiopathic thrombocytopenic purpura: a single center experience.

We retrospectively analyzed the clinical characteristics and management of 472 Chinese children (age 1~14 years) with chronic idiopathic thrombocytopenic purpura (ITP). The distribution of cases by age showed a maximum at 4 years and more patients below 7 years old than between 7 and 14 years old had ITP (337, 71.4% vs. 135, 28.6%). Variable bleeding signs occurred in this series of patients. Steroids therapy was effective for Chinese children with chronic ITP whether as first- or second-line therapy. Traditional Chinese medicine was less effective than steroids.