Platelets are important non-nucleated blood cells. Besides their role in thrombosis and hemostasis, there has been a growing focus on the immune regulatory function of platelets in recent years. Platelets have the capacity to sense the presence of pathogens and the inflammatory conditions within the body, which enables them to be activated and engage in both the body′s innate and acquired immune responses. Therefore, platelets play a crucial role in the development of various diseases, including cardiovascular and cerebrovascular diseases, autoimmune diseases, and infections, and tumor evasion. This paper mainly reviewed the immune regulatory mechanisms of platelets and their involvement in different diseases.

Hemophilia is a X-linked recessive hereditary bleeding disorders. The patients need to receive replacement treatment with coagulation factors in their whole lives. The medical care of hemophilia depends on the awareness of the medical professionals, patients, and their family members; on the accessibility to the medication for treatment; on the insurance policies, and etc. This article presents the forming process of the medical care for hemophilia in China, including joining the World Federation of Hemophilia(WFH), forming the Hemophilia Treatment Center Collaborative Network of China(HTCCNC), initiating the national hemo-philia registry system, and organizing hemophilia patients associations. In the meantime, the article presents the clinical practice of tiered care system for hemophilia in China, providing reference to the medical professionals and policy makers involving in the care of rare diseases in China.

Hemophilia is an inherited bleeding disorder and a type of rare disease that is hereditary, lifelong and disabling. The establishment of a National Hemophilia Registry is foundational to treating hemophilia. The initial registry of hemophilia in China was first established using the paper form in 1996 and upgraded to online system in 2007. Following the China's Ministry of Health's decision to establish a national hemophilia case information management system in 2009, China has officially established a National Hemophilia Registry based on previous work. More than 200 hospitals have been involved in this work. The National Hemophilia Registry also provides the basis for the study of hemophilia epidemiology, disease characteristics and related policy formulation.

Hemophilia B is a genetic disorder caused by coagulation factor Ⅸ(FⅨ) deficiency, mainly manifesting as joint, muscle and deep tissue bleeding. Hemophilia pseudotumor is a mass formed by soft tissue liquefaction and necrosis caused by repeated bleeding. Most pseudotumors occur in the bone and muscle. We report a case of hemophilia B with pseudotumor formation in the pelvis and abdomen, where lesion location is relatively rare. After active and effective hemostasis, the patient's hematuria symptom gradually improved. This case suggests that early and timely hemostatic treatment is crucial for patients with hemophilia.

Objective:To analyze the clinical manifestation, laboratory examination, treatment and prognosis of congenital factor Ⅺ (FⅪ) deficiency.Methods:The clinical data of 80 patients with congenital FⅪ deficiency in our hospital from September 2006 to October 2020 were analyzed retrospectively.Results:Among the 80 patients, there were 33 males (41.3%) and 47 females (58.8%) , with a median age of 32 (2-66) years. Twenty-eight cases (35.0%) had bleeding events, including 11 cases of spontaneous bleeding (13.8%) , 9 cases of ecchymosis or bleeding after skin trauma (11.3%) , 9 cases of postoperative bleeding (11.3%) . Among the female patients, there were 11 cases of menorrhagia (23.4%) and 1 case of bleeding after vaginal delivery (2.1%) . Laboratory examination were characterized by prolonged activated partial thromboplastin time (APTT) , normal prothrombin time (PT) , and decreased FⅪ activity (FⅪ∶C) . Nine patients (11.3%) were tested for FⅪ gene (F11) with 11 mutations. Twenty-seven patients (33.8%) received fresh frozen plasma (FFP) treatment, 15 patients (18.8%) were received for prophylaxis with no bleeding occurred during and after operation.Conclusion:Most patients with congenital FⅪ deficiency have no or mild bleeding symptoms. There was no significant correlation between FⅪ∶C and the severity of bleeding symptoms, and there was a well consistency between FⅪ∶C and F11 homozygous or heterozygous mutation type. Prophylactic infusion of FFP can effectively reduce the risk of operative bleeding.

Objective:To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency.Methods:Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis.Results:The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time.Conclusion:The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.

Objective:To investigate the clinical type and gene mutations, clinical manifestations, laboratory tests, diagnosis, and fibrinogen replacement therapy of congenital fibrinogen disorders.Methods:Clinical data of 146 patients with congenital fibrinogen disorders diagnosed from April 2000 to November 2020 were retrospectively analyzed.Results:Among the 146 patients, 61 (41.8%) men and 85 (58.2%) women had a median age of 33.5 years at the time of consultation. 34 patients (34.7%) were found to suffer from the disease due to bleeding symptoms, 33 patients (33.7%) due to preoperative examination. 55 patients (56.1%) had at least one bleeding symptom, and 42 patients (42.9%) had no bleeding symptoms. There is a negative correlation between fibrinogen activity concentration and bleeding ISTH-BAT score (rs=-0.412, P=0.001) . A total of 34 gene mutations were detected in 56 patients, of which 84.1% were missense mutations, and 16 new mutations were found. FGA Exon2 and FGG Exon8 mutations accounted for 71.4% of all mutation sites. Patients with afibrinogenemia were younger, with a median age of 2 (1-12) years, an ISTH-BAT score of 4, and patients with dysfibrinogenemia had significantly longer thrombin time (TT) , with a median of 28.5 (19.2-36.6) s. The 1 hour in vivo recovery (IVR) after fibrinogen infusion was (127.19±44.03) %, and the 24 hour IVR was (101.78±43.98) %. In addition to the obvious increase in the concentration of fibrinogen activity, the TT and the prothrombin time (PT) both decreased significantly, and the TT decreased more significantly, with an average decrease of 15.2% compared to the baseline after 24 hours of infusion. Conclusion:Most patients with congenital fibrinogen disorders have mild or no bleeding symptoms. Patients with afibrinogenemia have more severe symptoms. There is a negative correlation between the fibrinogen and the degree of bleeding. Genetic testing is helpful for the diagnosis of disease classification. FIB∶C/FIB∶Ag<0.7 can be used as a basis for clinical diagnosis. The TT can be used as the basis for the diagnosis of dysfibrinogenemia and the effectiveness of fibrinogen infusion.

Objective:To improve the understanding of splenectomy for treating common variable immunodeficiency complicated with cytopenia.Methods:A case of common variable immunodeficiency complicated with cytopenia was reported, and the literature was reviewed.Results:The patient, female, 16 years old, was hospitalized for eight years due to thrombocytopenia; she manifested recurrent thrombocytopenia with leukopenia since adolescence. The patient was diagnosed with common variable immunodeficiency with repeated mild infections, splenomegaly, and significantly reduced plasma immunoglobulin levels. Additionally, splenectomy was performed with adequate immunoglobulin replacement therapy, and the pathology confirmed hypersplenism; her blood cell level returned to normal after surgery.Conclusions:Common variable immunodeficiency has various clinical manifestations and can be complicated with cytopenia. Under the premise of adequate immunoglobulin replacement therapy, splenectomy is a safe and effective treatment for common variable immunodeficiency in patients with recurrent cytopenia.

Objective:To explore the pathogenesis, clinical characteristics, laboratory findings, diagnosis, treatment, and prognosis of congenital factor Ⅶ (FⅦ) deficiency.Methods:Clinical data of 43 patients with congenital FⅦ deficiency diagnosed from April 1999 to September 2019 were retrospectively analyzed.Results:There were 27 females and 16 males. Median age was 16 (1-70) years. Family history was found in 6 cases. There were 29 (67.4%) cases with bleeding symptoms, most common of which were mucocutaneous bleeding (13 cases, 30.2%) , oral bleeding (13 cases, 30.2%) , and epistaxis (9 cases, 20.9%) . Menorrhagia occurred in 11 cases (47.6% of female patients who were in fertile age) . Laboratory findings were characterized by significantly prolonged prothrombin time (PT) , normal partial thromboplastin time (APTT) , and decreased FⅦ activity (FⅦ∶C) . Ten cases received gene mutation analysis and 3 new mutations were found. Fourteen cases (32.6%) were treated with prothrombin complex concentrates (PCC) , 12 (27.9%) with fresh frozen plasma (FFP) , and 3 (7.0%) with human recombinant activated FⅦ (rFⅦa) . Twenty cases (46.5%) with no or mild bleeding symptoms did not receive any replacement therapy. Previous bleeding symptoms recurred in 5 patients (11.6%) , 8 females still had heavy menstrual bleeding, and 9 patients (20.9%) were lost to follow-up.Conclusion:Most patients with congenital FⅦ deficiency have mild or no bleeding symptoms, but have a tendency to excessive bleeding after surgery or trauma. There is no significant correlation between FⅦ∶C and severity of bleeding symptoms. Prophylaxis should be applied in patients with severe bleeding symptoms and rFⅦa is the first choice. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of the disease.

Objective: To analyze the gene mutation spectrum, clinical features, and the factors of disease progression and prognosis in patients with essential thrombocytosis (ET) . Methods: A retrospective analysis was conducted on 178 newly diagnosed ET patients admitted from February 1st, 2009 to November 1st, 2018. Results: Of the 178 patients, 89 were male and 89 female, and the median diagnosis age was 49.5 (3-86) years old. JAK2V617F, CALR and MPL mutations frequencies were 16.45% (1.67%-43.90%) , 40.00% (10.00%-49.15%) and 25.10% (25.00%-40.00%) , respectively. Compared with patients with CALR mutations, patients with JAK2V617F mutation had higher diagnosis age (P=0.035) , higher white blood cell count (P=0.040) , higher hemoglobin concentration (P=0.001) , and lower platelet count (P=0.002) , respectively. Of them, 47 patients (27.01%) developed thrombotic events before diagnosis, and 3 ones (1.72%) experienced thrombotic events after diagnosis. Multivariate analysis revealed age >60 years (P=0.013, OR=4.595, 95%CI 1.382-15.282) and cardiovascular risk factors (CVF) (P<0.001, OR=8.873, 95%CI 2.921-26.955) as risk factors for thrombotic events, CALR mutation (P=0.032, OR=0.126, 95%CI 0.019-0.838) as a protective factor for thrombotic events. Age >60 years (P=0.042, OR=4.045, 95%CI 1.053-15.534) was found to be a risk factor for the overall survival (OS) of ET patients. OS of age ≤60 years and age>60 years were calculated by Kaplan-Meier analysis to be (115.231±1.899) months and (83.291±4.991) months (χ²=6.406, P=0.011) , respectively. Conclusion Age>60 years and CVF were risk factors for thrombotic event. CALR mutation was a protective factor for thrombotic event. Age >60 years was a risk factor for OS in ET patients.