A Case Study Using Papaya Leaf Extract to Reverse Chemotherapy-Induced Thrombocytopenia in a GBM Patient

Chemotherapy-induced thrombocytopenia (CIT) is a critical condition in which platelet counts are abnormally reduced following the administration of chemotherapeutic compounds. CIT poses a treatment conundrum to clinicians given the increased risk of spontaneous bleeding, obstacles to surgical management of tumors, and exclusion from clinical trials. Treatment of CIT involves the removal of the offending agent combined with platelet infusion or thrombopoietin agonist treatment. However, due to the autoimmune and infection risks associated with infusions, this treatment is only reserved for patients with critically low platelet counts. One potential solution for patients in the mid to low platelet count range is Carica papaya leaf extract (CPLE). In this case, we report the novel use of CPLE as a method of bolstering platelet counts in a patient presenting with CIT. The patient was initiated on CPLE therapy consisting of 1 tablespoon twice daily with meals. Following CPLE treatment, the patient’s platelet counts rebounded from less than 10,000/µL to 113,000/µL. This clinical vignette supports the use of CPLE in the clinical context of CIT when thrombopoietin agonists are not a viable option. The potential benefits of CPLE as a method for increasing platelet count deserve further exploration, especially as a treatment option for refractory patients or those ill-suited for other traditional thrombocytopenia therapies.

Anesthesia Management of Children With Head and Neck Hemangiomas Associated With the Kasabach–merritt Phenomenon

Background: We reported the anesthesia management of the patients with head and neck hemangiomas associated with the Kasabach–Merritt phenomenon (KMP).Methods: All 12 young patients with KMP involving the head and neck region who admitted in Henan Provincial Hospital for surgery between June 2012 and December 2016 were included in the study. The data during preoperative preparation including platelet infusion and glucocorticoid treatment, anesthetic management and postoperative recovery were were harvested and analysed.Results: Of the 12 patients, the platelet counts were less than 40× 109/L on admission but no gender difference and three of them responded to glucocorticoid treatment extremely well. The patients who did not respond glucocorticoid treatment well and whose platelets <40× 109/L were transfused platelets 12 hours prior to surgery to correct the platelet count to be equal or more than 100 × 109/L. The patients who had pneumonia before surgery had a prolonged hospital stay. All 12 patients had surgical excision successfully. After surgery, the platelet counts were increased rapidly in all patients.Conclusion Careful pre-anesthesia assessment and preparation, and thoughtful anesthesia management are needed for KMP patients to receive surgical excision.

Treatment with Decitabine Followed By Prednisone for Myelodysplatic Syndrome Concomitant with Sjogren's Syndrome

Myelodysplastic Syndrome (MDS) is rarely concomitant with Sjögren's syndrome (SS) with only 9 previously reported cases in the literature. A case of a previously healthy 31-year-old Chinese female presenting with dysplasia affecting all three lineages without blasts excess showed by bone marrow examination is reported. Autoimmune workup revealed positive antinuclear antibodies and Anti-SSA. Lip biopsy revealed findings consistent with SS. A diagnosis of SS associated with MDS of the refractory cytopenia with multilineage dysplasia (RCMD) subtype was established, and decitabine for five days at 20mg/m2 per day was initiated with only slight increase in platelet counts. Four weeks later, another cycle of decitabine for five days at 20mg/m2 per day was performed. Unfortunately, infection occurred, and the patient suffered from thrombocytopenia and leucopenia. Then the patient received the treatment of Biapenem and Vancomycin Hydrochloride along with granulocyte colony stimulating factor followed by platelet infusion for two weeks. Significant clinical and laboratory response was achieved. In hopes of improving both response rates and durability of response, the third cycle of decitabine for five days at 20mg/m2 per day was performed with again an excellent clinical and laboratory response. However the patient refused further cycle of decitabine due to cost consideration, then prednisone at 10mg per day was used as a basic treatment for SS. It was an amazing feat that the patient was in a state of remission for two years. MDS with SS tends to be incurable. Decitabine alone with prednisone may serve as an effective option to those patients. Disclosures No relevant conflicts of interest to declare.

The Immunogenicity of Platelet-Derived FVIII in Hemophilia a Mice with or without Pre-Existing Anti-FVIII Immunity

Recent studies from our group and others have demonstrated that FVIII ectopically targeted to platelets under control of the platelet-specific αIIb promoter (2bF8) can efficiently restore hemostasis in hemophilia A mice even in the presence of high-titer inhibitory antibodies directed against FVIII (inhibitors). Our studies have demonstrated that platelet-targeted FVIII gene therapy can not only correct the hemophilic phenotype, but also induce FVIII-specific immune tolerance. In the platelet gene therapy model, hematopoietic stem cells (HSCs) are ex vivo transduced with lentivirus carrying 2bF8 and transplanted into the recipient. Sufficient preconditioning has to be employed to create space for therapeutic engraftment of the transduced HSCs. It is not clear whether preconditioning affects the potential for an immune response in the context of platelet-derived FVIII. Furthermore, if current efforts to generate platelets in vitro succeed, genetically manipulated platelets containing FVIII may be used therapeutically, as potential transfusion alternative, in hemophilia A patients even with inhibitors. One important question that has not been explored, however, is the immunogenicity of platelet-derived FVIII. To investigate whether platelet-derived FVIII can act as an immunogen in hemophilia A mice, we infused transgenic mouse platelets with a level of platelet-FVIII of 6 mU/108 platelets into naïve FVIIInull mice without any preconditioning weekly for 8 weeks. These platelets were transfused to a level between 20 to 57% of total platelets upon infusion, and all animals survived the tail-clip survival test 13-hours after platelet infusion. The level of platelet-FVIII in the infused animals was 0.11 ± 0.01 mU/108 platelets (n = 6) even one week after infusion. Neither inhibitory nor non-inhibitory anti-FVIII antibodies were detected in the infused mice during the study course (n = 9). All animals developed inhibitors following further challenge with recombinant human FVIII (rhF8) at a dose of 50 U/kg by intravenous injection weekly for 4 weeks, indicating that infusion of platelets containing FVIII does not trigger an immune response in hemophilia A mice. We then explored whether platelets containing FVIII can act as an immunogen in FVIIInull mice with pre-existing anti-FVIII immunity. FVIIInull mice were immunized with rhF8 to induce anti-FVIII antibodies. Four week after the last immunization, 2bF8 transgenic platelets were transfused into rhF8-primed FVIIInull mice (n = 4) weekly for 4 weeks and anti-FVIII antibody titers were monitored. There was not significant augmentation of FVIII-specific antibodies as determined by Bethesda assay for inhibitory antibodies and ELISA assay for total anti-FVIII IgG, indicating that infusion of platelets containing FVIII does not stimulate an anti-FVIII memory response in the inhibitor model. To investigate whether preconditioning affects the anti-FVIII immune response, animals were pre-conditioned with a sub-lethal 660 cGy total body irradiation (TBI) followed by 2bF8 transgenic platelet infusion weekly for 8 weeks. No anti-FVIII antibodies were detected in recipients (n = 6) after 2bF8 transgenic platelet infusion. Following further challenge with rhF8, the inhibitor titer in this group was significantly lower (75 ± 42 BU/ml) than in the naïve FVIIInull mice without preconditioning when the same infusion protocol was employed (270 ± 76 BU/ml), indicating that 660 cGy TBI plus 2bF8 transgenic platelet infusion may suppress anti-FVIII immune response. In conclusion, our data demonstrate that infusion of platelets containing FVIII triggers neither primary nor memory anti-FVIII immune response in hemophilia A mice. Disclosures No relevant conflicts of interest to declare.