Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment. 
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Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Lung Neoplasms/drug therapy* ; Thrombocytopenia/chemically induced* ; Antibodies, Monoclonal, Humanized/adverse effects*

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.
Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; SARS-CoV-2 ; COVID-19/complications* ; Thrombocytopenia ; Thrombosis/drug therapy* ; Thrombopoietin/therapeutic use* ; Recombinant Fusion Proteins/therapeutic use*

Immune thrombocytopenia (ITP) is an immune-mediated acquired hemorrhagic autoimmune disease. At present, the first-line therapeutic drugs for ITP include glucocorticoids and intravenous immunoglobulins. However, about 1/3 of the patients had no response to the first-line treatment, or relapsed after dose reduction or withdrawal of glucocorticoids. In recent years, with the gradual deepening of the understanding on the pathogenesis of ITP, the drugs targeting different pathogenesis continually emerge, including immunomodulators, demethylating agents, spleen tyrosine kinase (SYK) inhibitors and neonatal Fc receptor (FcRn) antagonist. However, most of these drugs are in clinical trials. This review summarized briefly the recent advances in the treatment of glucocorticoids resistance and relapsed ITP, so as to provide reference for the clinical treatments.
Infant, Newborn ; Humans ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Glucocorticoids/therapeutic use* ; Thrombocytopenia ; Immunoglobulins, Intravenous/therapeutic use* ; Immunologic Factors/therapeutic use*

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Bortezomib/therapeutic use* ; Glucocorticoids/therapeutic use* ; Rituximab/therapeutic use* ; Purpura, Thrombotic Thrombocytopenic/drug therapy* ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; ADAMTS13 Protein/therapeutic use*

OBJECTIVE: To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of newly diagnosed adult primary immune thrombocytopenia (ITP). METHODS: Eleven male and 23 female patients with the diagnosis of primary ITP in our hospital from November 2018 to October 2019 were enrolled and randomly divided into test group (17 cases) and control group (17 cases), the median age was 52 years old (range: 20-76 years old). The patients in test group were treated with rhTPO 300 IU/(kg·d) combined with glucocorticoid , while the patients in control group were treated with rhTPO (15 000 IU/d) combined with glucocorticoid. Platelet count, platelet increase, as well as the overall response rate were compared. At the same time, the drug tolerance and any adverse drug reactions were observed. RESULTS: The platelet counts and platelet increase of the patients in the test group were significantly higher than those in control group (P<0.05). There was no significant difference in platelet counts and platelet increase between the patients in the test group and control group at day 3, 7 after treatment. There was no significant difference in overall response rates and complete response rates at day 7, 14 between the two groups either. In test group, there were 13 cases received platelet transfusion, while 12 cases in control group. The muscle aches occurred in one patient, and mild aminotransferase increased in another patient in test group which was self-recovery without treatment. CONCLUSION RhTPO 300 U/(kg·d) combined with glucocorticoid could rapidly increase the platelet count with a low incidence of tolerable adverse events compared with conventional dose rhTPO with glucocorticoid.
Adult ; Aged ; Female ; Glucocorticoids/therapeutic use* ; Humans ; Male ; Middle Aged ; Platelet Count ; Platelet Transfusion ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Recombinant Proteins/therapeutic use* ; Thrombopoietin/therapeutic use* ; Young Adult

Primary immune thrombocytopenia (ITP) is a blood system disease mediated by autoimmune mechanism. Currently, the goal of treatment for primary ITP is to keep patients' peripheral platelet count at a safe level to prevent severe bleeding. Recently, avatrombopag and fostamatinib have been approved by the FDA for the treatment of primary ITP in adults, while new drugs such as rozanolixizumab, efgartigimod, PRTX-100, decitabine and atorvastatin have shown efficacy in early clinical trials. This review summarizes the current accepted therapies for the clinical treatment of primary ITP in adults, and briefly discuss the progress of new therapies.
Adult ; Hemorrhage ; Humans ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Splenectomy

OBJECTIVE: To investigate the clinical efficacy of calcitriol combined with sirolimus in the treatment of chronic primary immune thrombocytopenia (cITP) patients. METHODS: A total of 146 adult cITP patients reated in the First Affiliated Hospital of Hebei North University from March 2017 to March 2020 were randomly divided into observation group (73 cases) and control group (73 cases) according to random number table. The control group was treated with oral sirolimus capsule, the observation group was treated with oral calcitriol capsule combined with sirolimus capsule, and the curative effect of the 2 groups was evaluated after continuous treatment for 6 weeks. The changes of World Health Organization (WHO) bleeding grade, laboratory related index, including peripheral blood regulatory T cell (Treg), serum 1,25-dihydroxy-vitamin D RESULTS: The total effective rate of the observation group was 79.5% (58/73), which was significantly higher than 64.4% (47/73) of the control group (P<0.05). The revised WHO bleeding grades after treatment were significantly better than those before treatment in the 2 groups (P<0.05), but the observation group was improved more significantly than the control group (P<0.05). After treatment, platelet count (PLT), peripheral blood Treg cell ratio, and serum 1,25(OH) CONCLUSION The overall efficacy of calcitriol combined with sirolimus in the treatment of cITP in adults is satisfactory, which can effectively alleviate patient's condition, improve the quality of life, further increase the platelet level and decrease the expression of VDR in peripheral blood lymphocyte, the mechanism may be related to increasing the level of serum 1,25(OH)
Calcitriol ; Humans ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Quality of Life ; Sirolimus

OBJECTIVE: To compare the effect of Sheng-Xue-Xiao-Ban Capsule (SXXBC) and indirubin to the peripheral platelets of the Idiopathic thrombocytopenic purpura (ITP) model mouse. METHODS: The ITP mouse model was established by the method of passive immunization. SXXBC and indirubin were used for intervention treatment. Then the hemorrhagic phenomena of ITP mice were observed and the numbers of peripheral platelets, hemoglobin and white blood cells, bone marrow megakaryocytes and their classification and coagulation function were detected and compared. RESULTS: The improvement rate of hemorrhage in SXXBC group was 40% for small dose, 60% for medium dose and 80% for high dose, while the improvement rate of hemorrhage in indirubin group was 30% for small dose, 50% for medium dose and 60% for high dose. There was no statistically significant difference in the improvement rate of hemorrhage between the two groups (P＞0.05). Compared with the model control group, PLT and Hb increased in different doses of SXXBC and indirubin group 4th-8th day after drug intervention (P＜0.05, 0.01). However, there was no significant difference between the different doses of SXXBC group and indirubin group (P＞0.05). Compared with the model control group, the WBC in each group was significantly lower (P＜0.05, 0.01) on the 4th-8th day after drug intervention; However, there was no statistical significance between the two groups of SXXBC and indirubin (P＞0.05). Compared with the model control group, the total number of megakaryocytes in each treatment group were decreased (P＜0.05, P＜0.01), in which the number of primary megakaryocytes in the large and medium dose groups of SXXBC and indirubin were decreased (P＜0.05, 0.01), and the number of juvenile megakaryocytes in the large dose group of SXXBC and indirubin were also decreased (P＜0.05). The number of granular megakaryocytes were decreased in each intervention groups (P＜0.05, 0.01), and the number of thromocytogenic megakaryocyte was increased in the high and medium dose groups of SXXBC and indirubin (P＜0.01). The time of prothrombin was shortened in the high and medium dose groups of SXXBC and indirubin (P＜0.05), and the fibrinogen (FIB) content in the high and medium dose groups of SXXBC was close to that of the normal control group. CONCLUSION Both of the SXXBC and the indirubin standard all show good hemostatic effects. Indirubin shows a positive effect on increasing the peripheral platelet and hemoglobin in ITP model mice, regulating the immune response, reducing the total number of bone marrow megakaryocytes, increasing the thromocytogenic megakaryocyte, and increasing coagulation function.
Animals ; Blood Platelets ; Capsules ; Indoles ; Megakaryocytes ; Mice ; Purpura, Thrombocytopenic, Idiopathic/drug therapy*

OBJECTIVE: To investigatc the curative efficacy of low dose rituximab for glucocorticoid ineffective on dependent ITP patients and its relation with sensitivity to glucocorticoid so as to provide reference basis for rational use of drugs in clinical treatmant. METHODS: Seventy-ninth ITP patients enrolled in this study included the glucocorticoid-ineffective patients (19 cases) and glucocorticoid-dependent patients (60 cases). All ITP patients were treated with regimen consisted of high dose dexamethasone plus low dose rituximab (dexal-methasone 40 mg/d for 4 days per os, ritaximab 100 mg by intravenous infusion at D7, 14, 21 and 28 respectively). The patients after treatment were followed-up for 12 month, and the relation of patients sensitivity to glucocorticoid with therapentic response of rituximab was analyzed. The changes of Treg cell ratio and BAFF, IL-2 and sCD40L levels before and after treatment were detected by flow cytometry and ELISA respectively. RESULTS: The overall response rate (ORR) of patients treated with above- mentioned regemen at 1, 3, 6 and 12 months after treatment was 79.7% (63/79), 69.6% (55/79), 63.3% (50/79) and 60.8% (48/79) respectivcly, out of which the ORR of glucocorticoid ineffective and glucocorticoid-dependent ITP patients treated with above-mentioned regimen at 1, 3, 6 and 12 months after treatment was 47.4% (9/19) vs 90.0% (54/60), 36.8% (7/19) vs 80.0% (48/60), 21.1% (4/19) vs 76.7% (46/60), 21.1% (4/19) vs 73.3% (44/60), and the difference between 2 groups was statistically significant. The detection of T reg cell showed that the T reg cell ratio in glucocorticoid- ineffective and dependent patients at 1, 3, 6 and 12 months after treatment was (1.70±0.43)% vs (3.47±0.72)%, (1.66±0.33)% vs (4.29±0.91)%, (1.71±0.37)% vs (4.44±0.97)%, (3.36±0.54)% vs (4.29±1.04)%, respectively. The detection of cytokines showed that the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-dependent patients at 1 month after treatment significanlly decreased (P＜0.05), the levels of BAFF, IL-2 and sCD40L in plasma of glucocorticoid-ineffective patients although decreased at 1 mouth after treatment, but there was no statistical difference as compared with glucocosticoid-depenment patients. CONCLUSION The treatment of glucocorticoid-dependent ITP patients with rituximab is more effective. The regulatory effect of rituximab on the T-reg cells, BAFF, IL-2 and sCD40L may be one of its mechanisms.
Dexamethasone ; Glucocorticoids ; Humans ; Inosine Triphosphate ; Purpura, Thrombocytopenic, Idiopathic ; drug therapy ; Rituximab ; therapeutic use

Objective: To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) treatment for primary immune thrombocytopenia (ITP) patients during the perioperative period. Methods: Adult ITP patients who were refractory to first-line glucocorticoid therapy and underwent selective surgery were enrolled to be treated with rhTPO at the dosage of 1.5×10(4)U/d subcutaneously during the perioperative period. rhTPO treatment would not be terminated until one of the following conditions occurred: ①Platelet counts met the requirement of surgery; ②Platelet counts were ≥100×10(9)/L; ③Completed the 14 days of therapy. End points of the study were surgery rate, rhTPO therapy response rate, rescue therapy rate and adverse responses. Results: 42 patients were enrolled from Jan. 1, 2016 to Jun. 30, 2018. 14 were male and 28 were female. The median age was 60 (25-73) years old. There were no newly diagnosed patients. 5 patients were persistent and 37 were chronic. 27 patients completed selective surgery. The surgery rate was 64.3% (27/42) . Among them, 13 patients were under local anesthesia and 14 under general anesthesia. Of 42 cases receiving rhTPO therapy. 31 patients achieved responses, The overall response rate was of 73.8%. Among them, 24 patients achieved CR. The CR ratio was 77.4% (24/31) . 7 achieved response. The response ratio was 22.6% (7/31) . 11 patients did not respond to rhTPO therapy. The non-response rate was 26.2% (11/42) . The median time to reach CR was 7 (3-16) days. The median time to reach the peak of platelet counts were 10 (3-21) days. rhTPO was used for a median of 7 (3-14) days. The median platelet counts of patients undergoing surgery before rhTPO therapy, before surgery and at day 7 after surgery were 33 (20-89) ×10(9)/L, 125 (78-245) ×10(9)/L and 72 (30-250) ×10(9)/L, respectively. The median peak of platelet counts was 149 (101-466) ×10(9)/L. No infection, bleeding, thromboembolism and therapy-related adverse responses occurred in the patients. Conclusion: rhTPO for ITP patients during the perioperative period is safe and effective.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Perioperative Period ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic/drug therapy* ; Recombinant Proteins ; Thrombopoietin/therapeutic use*