Protein S deficiency causing arterial ischemic stroke during pregnancy is uncommon. Delay or omission of treatment with perfusion therapies may worsen outcomes for both the mother and the fetus. In this paper, we report a case of an early pregnant woman with protein S deficiency and multiple history of chronic cerebrovascular disease who underwent successful thrombolysis and mechanical thrombectomy. The patient is a 35-year-old woman, eight weeks pregnant, with a history of protein S deficiency and chronic cerebrovascular disease, presenting with rightsided weakness and aphasia. Initial National Institutes of Health Stroke Scale was 10 with cranial magnetic resonance imaging findings of acute infarcts on the left caudate, lentiform nucleus, insula, and frontal lobe with a large vessel occlusion on the proximal M1 segment of the left middle cerebral artery. Intravenous thrombolysis and mechanical thrombectomy were performed with complete recanalization. The patient improved and delivered without any complications after 8 months. Protein S deficiency can contribute to arterial thrombosis including ischemic stroke. Arterial ischemic stroke and large vessel occlusion can cause significant disability if not treated appropriately. Reperfusion therapies in pregnant women show favorable outcomes and should be performed if the benefits outweigh the risks.

Humans ; China ; Consensus ; Purpura, Thrombocytopenic, Idiopathic/therapy* ; Thrombocytopenia/therapy* ; Thromboembolism/therapy*

Objective:b> To determine the efficacy of eltrombopag for primary immune thrombocytopenia (ITP) in adults and the predictive factors for treatment-free response (TFR) . Methods:b> Clinical data of adults with ITP who received eltrombopag from June 14, 2013 to May 31, 2021 in the Hematology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University Medical College were retrospectively analyzed. The initial dose of eltrombopag was 25 mg/d, and the maximum dose was 75 mg/d; the dose was adjusted to maintain the platelet count to within 50-150×10(9)/L. Treatment was discontinued according either to the protocol, on the patient's wishes or doctor's judgment (prescription medication), or based on clinical trials. The efficacy of eltrombopag and factors for TFR among patients who achieved complete response and those who discontinued treatment were analyzed. Results:b> Overall, 106 patients with ITP (33 men and 73 women) were included in the study. The median age of patients was 50 (18-89) years. There were 2, 10, and 94 cases of newly diagnosed, persistent, and chronic ITP, respectively. The complete response rate was 44.3% (47/106), the response rate was 34.0% (36/106), and the overall response rate was 78.3% (83/106). Meanwhile, 83 patients who responded to treatment discontinued eltrombopag; of these, 81 patients were evaluated. Additionally, 17 patients (21.0%) achieved TFR. The median follow-up duration of patients who achieved TFR was 126 (30-170) weeks. The recurrence rate was 17.6% (3/17), and the relapse-free survival rate was 76.5%. The results of univariate analysis revealed that non-recurrence after discontinuation of other treatments for ITP (P=0.001), and platelet count and eltrombopag dose of ≥100×10(9)/L (P=0.007) and ≤25 mg/d (P=0.031), respectively, upon discontinuation of eltrombopag were predictors of TFR; these effects were attributed to prolonged effective duration of eltrombopag. Multivariate analysis showed that there was a correlation between non-recurrence and prolonged effective duration after discontinuation of other treatments for ITP (P=0.002) . Conclusion:b> Eltrombopag is effective for patients with ITP as it can result in TFR. Predictors for TFR include non-recurrence after discontinuation of concomitant ITP treatment, and platelet count and eltrombopag dose of ≥100 × 10(9)/L and ≤25 mg/d upon discontinuation of treatment, respectively.
Male ; Humans ; Adult ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Purpura, Thrombocytopenic, Idiopathic/diagnosis* ; Retrospective Studies ; Treatment Outcome ; China/epidemiology* ; Benzoates/therapeutic use*

Objective:b> To evaluate the clinical effects of low- and intermediate-dose factor Ⅷ (F Ⅷ) prophylaxis in Chinese adult patients with severe hemophilia A. Methods:b> Thirty adult patients with severe hemophilia A who received low- (n=20) /intermediate-dose (n=10) F Ⅷ prophylaxis at Nanjing Drum Tower Hospital affiliated with Nanjing University Medical College were included in the study. The annual bleeding rate (ABR), annual joint bleeding rate (AJBR), number of target joints, functional independence score of hemophilia (FISH), quality of life score, and health status score (SF-36) before and after preventive treatment were retrospectively analyzed and compared. Results:b> The median follow-up was 48 months. Compared with on-demand treatment, low- and intermediate-dose prophylaxis significantly reduced ABR, AJBR, and the number of target joints (P<0.05) ; the improvement in the intermediate-dose prophylaxis group was better than that in the low-dose prophylaxis group (P<0.05). Compared with on-demand treatment, the FISH score, quality of life score, and SF-36 score significantly improved in both groups (P<0.05), but there was no significant difference between the two groups (P>0.05) . Conclusion:b> In Chinese adults with severe hemophilia A, low- and intermediate-dose prophylaxis can significantly reduce bleeding frequency, delay the progression of joint lesions, and improve the quality of life of patients as compared with on-demand treatment. The improvement in clinical bleeding was better with intermediate-dose prophylaxis than low-dose prophylaxis.
Humans ; Hemophilia A/drug therapy* ; Factor VIII/therapeutic use* ; Quality of Life ; Retrospective Studies ; Hemarthrosis/prevention & control* ; Hemorrhage/drug therapy*

Objective:b> To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods:b> Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results:b> The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions:b> The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.
Female ; Pregnancy ; Humans ; Adult ; Blood Component Transfusion ; Plasma ; Purpura, Thrombotic Thrombocytopenic/therapy* ; Mutation ; Purpura, Thrombocytopenic, Idiopathic ; ADAMTS13 Protein/therapeutic use*

OBJECTIVE: To retrospectively analyze the clinical phenotypes and genetic variants in two Chinese pedigrees affected with Hereditary hypofibrinemia (IFD) and explore their molecular pathogenesis. METHODS: Two probands and their pedigree members were admitted to the First Affiliated Hospital of Wenzhou Medical University on March 30, 2021 and May 27, 2021, respectively. Clinical phenotypes of the probands were collected, and blood clotting indexes of the probands and their pedigree members were determined. Variants of the FGA, FGB and FGG genes were analyzed by Sanger sequencing, and candidate variants were verified by sequence comparison. Bioinformatic software was used to analyze the conservation of the amino acids and pathogenicity of the proteins. Alteration in protein structure and intermolecular force before and after the variant was analyzed by simulating the protein model. RESULTS: Proband 1, a 18-year-old male, had significantly low plasma fibrinogen activity (Fg:C) and plasma fibrinogen antigen (Fg:Ag), respectively at 0.80 g/L and 1.00 g/L. Proband 2, a 43-year-old male, had slightly low Fg:C and Fg:Ag at 1.35 g/L and 1.30 g/L, respectively. The Fg:C and Fg:Ag of proband 1's father, proband 2's father and son were also below the normal level. Genetic testing showed that proband 1 had harbored a heterozygous missense variant of c.688T>G (p.Phe230Val) in exon 7 of the FGG gene, which was inherited from his father. Proband 2, his father and son all had harbored a heterozygous variant of c.2516A>C (p.Asn839Thr) in exon 6 of the FGA gene. Homology analysis showed that the Phe230 and Asn839 residues were highly conserved among homologous species. Bioinformatic analysis predicted that both p.Phe230Val and p.Asn839Thr were pathogenic variants. CONCLUSION Analysis of protein simulation model showed that the p.Asn839Thr variant has changed the hydrogen bo`nd between the amino acids, thus affecting the stability of the protein structure. The heterozygous missense variants of p.Phe230Val and p.Asn839Thr probably underlay the IFD in the two pedigrees.
Humans ; Male ; Amino Acids ; East Asian People ; Exons ; Pedigree ; Retrospective Studies ; Afibrinogenemia/genetics* ; Mutation, Missense ; Fibrinogen/genetics*

OBJECTIVE: To screen better promoters and provide more powerful tools for basic research and gene therapy of hemophilia. METHODS: Bioinformatics methods were used to analyze the promoters expressing housekeeping genes with high abundance, so as to select potential candidate promoters. The GFP reporter gene vector was constructed, and the packaging efficiency of the novel promoter was investigated with EF1 α promoter as control, and the transcription and activities of the reporter gene were investigated too. The activity of the candidate promoter was investigated by loading F9 gene. RESULTS: The most potential RPS6 promoter was obtained by screening. There was no difference in lentiviral packaging between EF1 α-LV and RPS6-LV, and their virus titer were consistent. In 293T cells, the transduction efficiency and mean fluorescence intensity of RPS6pro-LV and EF1 αpro-LV were proportional to the lentiviral dose. The transfection efficiency of both promoters in different types of cells was in the following order: 293T>HEL>MSC; Compared with EF1 αpro-LV, RPS6pro-LV could obtain a higher fluorescence intensity in MSC cells, and RPS6pro-LV was more stable in long-term cultured HEL cells infected with two lentiviruses respectively. The results of RT-qPCR, Western blot and FIX activity (FIX∶C) detection of K562 cell culture supernatant showed that FIX expression in the EF1 α-F9 and RPS6-F9 groups was higher than that in the unloaded control group, and there was no significant difference in FIX expression between the EF1 α-F9 and RPS6-F9 groups. CONCLUSION After screening and optimization, a promoter was obtained, which can be widely used for exogenous gene expression. The high stability and viability of the promoter were confirmed by long-term culture and active gene expression, which providing a powerful tool for basic research and clinical gene therapy of hemophilia.
Humans ; Transduction, Genetic ; Genetic Vectors ; Hemophilia A/genetics* ; Transfection ; Blood Coagulation Factors/genetics* ; Lentivirus/genetics*

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*

Systemic lupus erythematosus (SLE) complicated with acquired hemophilia A (AHA) is a rare condition with frequently delayed diagnosis and a high mortality rate, so it is necessary to strengthen the understanding of this disease. In this study, the characteristics and treatment in 1 case of SLE complicated by AHA is reported and analyzed, and a literature review is conducted. The patient was a 29-year-old young female with a 10-year history of SLE, the main clinical manifestation was severe abdominal bleeding. Laboratory tests revealed that the activated partial thromboplastin time (APTT) was notably prolonged (118.20 s), and the coagulation factor VIII activity (FVIII꞉C) was extremely decreased (0.20%) with high-titer of factor VIII (FVIII) inhibitor (31.2 BU/mL). After treating with high-dose glucocorticoid, immunoglobulin, cyclophosphamide, rituximab, blood transfusion, and intravenous infusion of human coagulation FVIII, the coagulation function and coagulation FVIII꞉C were improved, and FVIII inhibitor was negative without serious adverse reactions. During the next 5-year follow-up, the patient's condition was stable and no bleeding occurred. In the case of coagulation dysfunction in SLE, especially with isolated APTT prolongation, AHA should be screened. When the therapeutic effects of glucocorticoid combined with immunosuppressants are not desirable, rituximab could be introduced.
Female ; Humans ; Adult ; Hemophilia A/therapy* ; Rituximab ; Glucocorticoids ; Factor VIII ; Lupus Erythematosus, Systemic/complications* ; Hemorrhage/complications*