BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

OBJECTIVE: To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. METHODS: Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with ⁶⁰Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit⁺ HSC, and p16 and p38 mRNA expression of c-kit⁺ HSC were detected. RESULTS: Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit⁺ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit⁺ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01). CONCLUSION The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.
Humans ; Mice ; Animals ; Thrombopoietin/metabolism* ; Hematopoietic Stem Cells ; Blood Platelets ; Recombinant Proteins/therapeutic use* ; Radiation Injuries ; RNA, Messenger/metabolism*

OBJECTIVE: To compare the effects of artificial liver treatment with double plasma molecular adsorption system(DPMAS) mode and traditional plasma exchange (PE) mode on platelets in patients, and to evaluate the clinical efficacy of recombinent human thrombopoietin (rhTPO) in the treatment of thrombocytopenia. METHODS: A total of fifteen patients undergoing artificial liver with DPMAS model admitted to the Fifth Affiliated Hospital of Guangzhou Medical University from January 2018 to November 2020 were selected and included in the DPMAS group, and another 15 patients receiving PE were selected and included in the PE group. The improvement of clinical symptoms, such as fatigue, jaundice, oliguria, edema, etc. before and after artificial liver treatment was compared between the two groups, and the trend of blood routine (especially platelet), coagulation function and other indexes before and after treatment were compared between the two groups. The use of rhTPO and the number of platelets were recorded during treatment. RESULTS: The improvement rate of clinical symptoms in DPMAS group was 86.67%, which was higher than that in PE group, but the difference was not statistically significant (P>0.05). There was no statistical significance in the outcome of the two groups within 90 days (P>0.05). There was no significant difference in white blood cell (WBC) and hemoglobin (HB) between the two groups after treatment (P>0.05). However, the level of platelet(PLT) in DPMAS group was significantly lower than that before treatment (P < 0.05), and was significantly lower than that in PE group (P < 0.05). After treatment, the international normalized ratio (INR) level in PE group was significantly improved (P < 0.05), but there was no significant difference in the INR level in DPMAS group (P>0.05). The patients in the DPMAS group received an average of (8.2±3.1) doses of rhTPO and (1.5±0.3) IU of platelet transfusions during hospitalization. In DMPAS group, platelets increased significantly after infusion of terbium. CONCLUSION Compared with PE mode, the artificial liver with DPMAS mode can reduce platelet levels in patients, but the application of rhTPO can stimulate platelet regeneration and increase platelet levels in the patients, thereby reducing the risk of bleeding due to platelet hypoplasia.
Blood Platelets ; Humans ; Liver, Artificial ; Plasma Exchange ; Recombinant Proteins ; Thrombocytopenia/therapy* ; Thrombopoietin

OBJECTIVE: To investigate the effect of recombinant human thrombopoietin (rhTPO) on thrombocytopenia (TCP) induced by endotoxin lipopolysaccharide (LPS) in mice. METHODS: Sixty male C57BL/6 mice were divided into normal saline (NS) control group (NS group), sepsis-induced TCP model group (LPS group) and rhTPO treatment group (LPS+rhTPO group) by random number table with 20 mice in each group. Sepsis-induced TCP model was reproduced by one intraperitoneal injection of LPS 30 mg/kg, and the mice in NS group were given the same amount of NS. In LPS+rhTPO group, 2.7 kU/kg rhTPO was subcutaneously injected into mice immediately after intraperitoneal injection of LPS, once every 24 hours. The mice in NS group and LPS group were injected subcutaneously with the same amount of NS. The observation period of each group lasted for 72 hours. The inner canthus blood was harvested before and every 24 hours after modeling, and the platelet count (PLT) was measured by animal blood cell counter. The eyeball blood of mice was harvested at 72 hours after modeling, and the proportion of CD61⁺CD62p⁺ cells in platelet-rich plasma was detected by flow cytometry, by which the platelet activation was reflected. Lung and spleen tissues of mice were harvested, and the positive expression of CD41 was determined by immunohistochemistry, by which the platelet sequestration in organs was reflected. Bone marrow cells from unilateral femur of mice were harvested, and the proportion of CD41⁺CD61⁺ cells was determined by flow cytometry to reflect the proliferation of bone marrow megakaryocytes. RESULTS: There was no significant difference in PLT among the groups before modeling. With the extension of the time after modeling, PLT in LPS group was decreased continuously, and increased slightly at 72 hours, but it was still significantly lower than that in NS group (×10⁹/L: 308.60±21.70 vs. 1 152.72±50.27, P < 0.05); PLT in LPS+rhTPO group was increased continuously with the extension of modeling time, and it was significantly higher at 72 hours than that in LPS group (×10⁹/L: 926.78±48.85 vs. 308.60±21.70, P < 0.05). At 72 hours after modeling, the proportion of CD61⁺CD62p⁺ cells in platelet-rich plasma of LPS group was significantly higher than that of NS group [(25.07±2.55)% vs. (4.17±0.38)%, P < 0.05], while the value in LPS+rhTPO group was significantly lower than that of LPS group [(15.92±1.26)% vs. (25.07±2.55)%, P < 0.05]. The proportion of CD41⁺CD61⁺ cells in bone marrow megakaryocytes of LPS group was significantly higher than that of NS group [(11.84±0.80)% vs. (3.60±0.42)%, P < 0.05], and the proportion of CD41⁺CD61⁺ cells in LPS+rhTPO group was significantly higher than that in LPS group [(30.96±2.49)% vs. (11.84±0.80)%, P < 0.05]. Immunohistochemistry showed that the positive expressions of CD41 in lung and spleen tissues of LPS group increased significantly than NS group [A value: 828.94±119.30 vs. 447.09±16.19 in lung tissue, (280.15±16.71)×10³ vs. (0.65±0.26)×10³ in spleen tissue, both P < 0.05], while the positive expressions of CD41 in lung and spleen tissues of LPS+rhTPO group decreased significantly than LPS group [A value: 542.78±2.95 vs. 828.94±119.30 in lung tissue, (129.40±13.49)×10³ vs. (280.15±16.71)×10³ in spleen tissue, both P < 0.05]. CONCLUSIONS The rhTPO in endotoxin-induced TCP may stimulate the proliferation of bone marrow megakaryocytes, inhibit platelet activation and affect platelet sequestration in organs, so as to increase platelet levels.
Animals ; Blood Platelets ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Platelet Count ; Recombinant Proteins ; Thrombocytopenia ; Thrombopoietin

The main physiological function of megakaryocytes is the production of platelets, whose development, maturation and platelet production are a complex regulatory process, and are involved in many factors. In recent years it was found that the lung is also the main site of megakaryocyte-producing platelets in addition to bone marrow. Based on the findings of recent years, this review summarizes the process of megakaryocyte development, maturation and platelet production, with emphasis on the analyzing the regulatory effects of apoptotic factors, miRNA, thrombopoietin and its receptors, interleukins, transcription factors and their corresponding signal pathways on platelet production. To understand the regulatory mechanism of platelet production can help to understand the pathological mechanism of platelet-related diseases and provide new ideas for the diagnosis and treatment of platelet-related diseases.
Blood Platelets ; Bone Marrow Cells ; Megakaryocytes ; Thrombopoiesis ; Thrombopoietin

Objective: To investigate and analyze the impact on PLT recovery of recombinant human thrombopoietin (rhTPO) in severe aplastic anemia (SAA) patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A retrospective analysis of Hematology Division of General Hospital of Jinan Military Command was conducted in the 85 SAA cases who treated with allo-HSCT from January 2010 to March 2017. According to the administration of medicines for platelets, 85 patients were divided into rhTPO group (n=29), rhIL-11 group (n=27) and blank group (n=29), respectively. The median time of PLT ≥20×10⁹/L, PLT ≥50×10⁹/L, and PLT ≥100×10⁹/L, the numbers of megakaryocytes in marrow smear (25±5) days after transplantation and the quantities of platelet transfusion were analyzed retrospectively. The adverse events of rhTPO and rhIL-11 groups were observed. Results: There were no significant differences in the recovery of granulocytes and PLT ≥20×10⁹/L among the three groups (P>0.05). The time of PLT ≥50×10⁹/L in rhTPO group was shorter than that in blank group [16.5 (11-39) d vs 22 (14-66) d, P<0.05], as well as the time of PLT ≥100×10⁹/L [rhTPO: 23 (12-51) d; rhIL-11: 28 (12-80) d; blank group: 35 (18-86) d, P<0.05]. Platelet transfusions were also less in rhTPO group than in rhIL-11 and blank groups [20 (10-30) U, 30 (10-50) U, 35 (10-70) U, P<0.05]. The counts of megakaryocyte in rhTPO group, rhIL-11 group and blank group were 31.5 (0-200), 12 (0-142) and 11(0-187) (P<0.05), respectively. The difference between rhTPO group and rhIL-11 group was statistically significant (P<0.05), but no difference between rhIL-11 group and blank group (P>0.05). Multivariate analysis showed that rhTPO was an independent factor for platelet recovery [HR=4.01 (95%CI 1.81-9.97), P=0.010]. The rhTPO group had no obvious adverse events. Conclusion: rhTPO can promote platelet recovery of SAA patients after allo-HSCT, reduce platelet transfusion with safety.
Anemia, Aplastic/therapy* ; Blood Platelets ; Hematopoietic Stem Cell Transplantation ; Humans ; Platelet Count ; Recombinant Proteins ; Retrospective Studies ; Thrombopoietin

OBJECTIVETo evaluate the efficacy and safety of high dose dexamethasone combined with recombinant human thrombopoietin (rhTPO) in adults with severe newly diagnosed immune thrombocytopenia (ITP).

METHODSForty-eight adult patients with severe ITP were randomized into two groups, experimental group and control group. The patients in experimental group were given high-dose dexamethasone combined with rhTPO treatment, the patients in control group were given single high-dose dexamethasone treatment. Platelet count, platelet increase, as well as the overall response rate were strictly observed in the process. At the same time, the patient's drug tolerance and any adverse drug reactions were observed.

RESULTSThe platelet counts and platelet increase of the patients in experimental group were significantly higher than that in control group (P<0.05) at day 3, 7, 14, 30. There was no significant difference in overall response rates between the two groups (34.8% vs 36.0%, 56.5% vs 48.0%, P>0.05) at day 3, 7. The overall response rates of experimental group at day 14, 30 were significantly higher than that of control group (91.3% vs 68.0%, 82.6% vs 52.0%, P<0.05). The muscle aches occurred in one patient in experimental group which was self-recovery without special treatment.

CONCLUSIONrhTPO combined with high-dose dexamethasone could rapidly increase the platelet count, reduce the risk of bleeding, and prolonge the effect with a low incidence of tolerable adverse events compared to single high-dose dexamethasone. rhTPO combined with high-dose dexamethasone could be a new therapeutic choice for severe primary ITP.

Adult ; Blood Platelets ; Dexamethasone ; administration & dosage ; therapeutic use ; Humans ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Thrombopoietin ; administration & dosage ; therapeutic use ; Treatment Outcome

No abstract available.
Adult ; Biomarkers, Tumor/genetics ; Bone Marrow/pathology ; Calreticulin/genetics ; Erythropoietin/blood ; Female ; Fusion Proteins, bcr-abl/*genetics ; Hematocrit ; Hemoglobins/analysis ; Humans ; Janus Kinase 2/genetics ; Male ; Middle Aged ; Mutation ; Myeloproliferative Disorders/*diagnosis/genetics ; Polycythemia Vera/*diagnosis/genetics ; Receptors, Thrombopoietin/genetics ; Thrombocythemia, Essential/diagnosis ; World Health Organization

OBJECTIVETo evaluate the impact of recombinant human thrombopoietin (rhTPO) on short-term response of immunosuppressive therapy (IST) in patients with newly diagnosed acquired severe aplastic anemia (SAA).

METHODSThe clinical data of forty adult acquired SAA patients, who treated with IST combined with rhTPO, were retrospective analyzed and the hematologic recovery were compared with patients by the IST alone during the same period. The factors affecting the short-term response were also analyzed.

RESULTSAt 3 months after IST, both the total response rate and CR+GPR rate in rhTPO group were much higher than those in control group (75.0% vs 50.0%, P=0.022; and 17.5% vs 2.5%, P=0.025). At 6 months after IST, there was no difference of total hematologic response rate in rhTPO group and control group (77.5% vs 57.5%, P=0.058), while the CR+GPR rate was still higher in rhTPO group (45.0% vs 22.5%, P=0.033). The median time of platelet transfusion independence was much shorter in rhTPO group [33(0-90) vs 53(0-75) d, P=0.019]. Patients in rhTPO group needed less platelets transfusion support. The median platelet count in rhTPO group was 29(4-95)×10⁹/L at 3 months after IST, which was much higher than that in control group [29(4-95)×10⁹/L, P=0.006]. There was no significant difference regarding overall survival between the two groups (100.0% vs 91.0%, P=0.276).

CONCLUSIONrhTPO is effective in promoting platelet recovery and improving the hematopoietic response for SAA patients with IST.

Anemia, Aplastic ; Blood Platelets ; Humans ; Immunosuppression ; Platelet Count ; Platelet Transfusion ; Recombinant Proteins ; Retrospective Studies ; Thrombopoietin