Treatment trends and risks of corticosteroid use in adult primary immune thrombocytopenia: a claims database study in Japan.

Recent trends in the treatment of primary immune thrombocytopenia (ITP) were investigated using a claims database that included data from 16,161 Japanese patients with ITP collected from April 2014 to August 2022. Of the 4144 adult patients analyzed, 1276 received corticosteroids. The mean and median durations of corticosteroid use were 115.

[Recent topics in the pathophysiology and treatment of immune thrombocytopenic purpura].

Increased and impaired platelet productions via immunological abnormalities are the main pathophysiological mechanisms of primary immune thrombocytopenia (ITP). Recent studies have revealed that platelet removal from circulation involves not only Fc receptor-mediated phagocytosis of immunoglobulin G autoantibodies-bound platelets but also complement-dependent mechanism and platelet glycoprotein desialylation. Understanding the molecular mechanism of ITP pathophysiology has helped develop many novel molecular targeted drugs, and recent clinical trials have shown their effectiveness.

FNAIT pathogenesis determined by serial analysis of three subsequent pregnancies of a woman with severe fetal and neonatal alloimmune thrombocytopenia (FNAIT) with anti-HPA-4b and anti-HPA-5b alloantibodies in the first sibling.

Background: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is caused by anti-HPA alloantibody, and anti-HPA-4b is the most common cause in Japanese. Anti-HPA-5b is frequently detected in pregnant women, but it is still controversial whether anti-HPA-5b causes severe FNAIT.

Case Presentation: A Japanese woman with anti-HPA-4b and anti-HPA-5b alloantibodies delivered a baby with severe FNAIT who was both HPA-4b and HPA-5b incompatible.

Progress in pathophysiological understanding and treatment of thrombocytopenia.

Immune thrombocytopenia (ITP), thrombotic thrombocytopenic purpura (TTP), and vaccine-induced immune thrombotic thrombocytopenia (VITT) all have "thrombocytopenia" in their name, and all but congenital TTP are caused by immune mechanisms, but these conditions are quite different in their clinical features and pathophysiology. This review series covers recent progress in pathophysiology and treatment of these diseases, as well as a recent epoch-making clinical trial of induced pluripotent stem cells (iPSC)-derived platelets for patients with thrombocytopenia.

Increased cleavage of von Willebrand factor by ADAMTS13 may contribute strongly to acquired von Willebrand syndrome development in patients with essential thrombocythemia.

Background: Patients with essential thrombocythemia (ET) often experience bleeding associated with acquired von Willebrand syndrome (AVWS) when the platelet count is markedly increased.

Objective: We investigated whether von Willebrand factor (VWF) degradation is enhanced in patients with ET.

Methods: Seventy patients with ET underwent VWF multimer (VWFM) analysis and measurement of VWF-related parameters.

Development of an Automated Chemiluminescent Enzyme Immunoassay for Measuring Thrombopoietin in Human Plasma.

Plasma thrombopoietin (TPO) measurements help distinguish between different types of thrombocytopenia but are not feasible in routine clinical practice. We developed a fully automated quantitative chemiluminescent enzyme immunoassay (CLEIA) for measuring TPO (TPO-CLEIA), which is a one-step sandwich-type assay. This assay utilizes a mouse monoclonal capture antibody, which has the neutralizing epitope of the interaction between TPO and the TPO receptor, and a newly generated rabbit monoclonal detector antibody.

Autoimmune-mediated thrombocytopenia after allogeneic hematopoietic stem cell transplantation: significance of detecting reticulated platelets and glycoprotein-specific platelet autoantibodies.

Autoimmune hematological disorders are rare complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of immune thrombocytopenia (ITP) is challenging, especially after allo-HSCT, because various complications such as graft-versus-host disease, disease relapse, viral infection, thrombotic microangiopathy, and drug side effects can also cause thrombocytopenia. Assessment of reticulated platelets (RP) and plasma thrombopoietin (TPO) levels may be useful to distinguish between ITP and hypoplastic thrombocytopenia.

[Reference guide for the treatment of adult idiopathic thrombocytopenic purpura].

The treatment strategy of adult idiopathic thrombocytopenic purpura (ITP) in Japan had consisted of corticosteroids as the first-line option, splenectomy as the second-line option, and others as the third-line option, respectively, for a long time. However, thrombopoietin receptor agonists (TPO-RAs) have been widely adopted recently for corticosteroid-resistant ITP, and indications for rituximab have been extended to adult ITP in Japan, suggesting that ITP treatment is dramatically changing. In the "Reference guide for adult ITP treatments in Japan" revised in 2019, TPO-RAs and rituximab are equally recommended as second-line treatments alongside splenectomy.

Risk factors for skin, mucosal, and organ bleeding in adults with primary ITP: a nationwide study in Japan.

Bleeding manifestations in primary immune thrombocytopenia (ITP) range from skin petechiae to life-threatening intracranial hemorrhage (ICH). However, the relation between these various bleeding manifestations and the platelet count in ITP remains poorly characterized. Using a nationwide database of patients with ITP during the years 2005 to 2014 (10 years) in Japan, we analyzed 19 415 adult patients newly diagnosed with ITP, including 222 with ICH.

Reevaluation of platelet function in chronic immune thrombocytopenia: impacts of platelet size, platelet-associated anti-αIIbβ3 antibodies and thrombopoietin receptor agonists.

Platelet function of immune thrombocytopenia (ITP) has been controversial because of methodological problems associated with low platelet counts. In this study, we evaluated platelet function in 21 patients with chronic ITP (cITP) using the recently developed flow cytometry (FCM)-based platelet aggregation assay (FCA) along with a PAC1/CD62P assay. Since ITP platelets are larger than controls, whole platelets (whole gating method) and size-adjusted platelets (size-adjusted method) were analysed in the PAC1/CD62P via FCM.

Distinct effects of daratumumab on indirect and direct antiglobulin tests: a new method employing 0.01 mol/L dithiothreitol for negating the daratumumab interference with preserving K antigenicity (Osaka method).

Background: There is an increasing demand for daratumumab (DARA), an immunoglobulin (Ig)G1κ monoclonal antibody (MoAb) that recognizes CD38, to manage relapsed or refractory multiple myeloma (MM) patients. However, DARA leads to positive and panreactive agglutination reactions in indirect antiglobulin tests (IATs) in vitro (the DARA interference). In addition, effects of DARA on red blood cells (RBCs) in vivo remains elusive.

Protease-activated receptor-4 (PAR4) variant influences on platelet reactivity induced by PAR4-activating peptide through altered Ca mobilization and ERK phosphorylation in healthy Japanese subjects.

Background: Thrombin belongs to the most potent platelet agonists and activates human platelets through GPIbα and two protease activated receptors (PARs), PAR1 and PAR4. However, the details of thrombin receptor system, especially the role of PAR4 on human platelet activation is still not clear.

Objectives: We found a significant difference in PAR4-activating peptide (PAR4-AP)-induced, but not PAR1-AP, platelet aggregation between healthy Japanese subjects.

Immature platelet fraction (IPF) as a predictive value for thrombopoietic recovery after allogeneic stem cell transplantation.

We consecutively examined the utility of measurements of percentage of immature platelet fraction (IPF%) and absolute IPF number (A-IPF) in predicting thrombopoietic recovery in 15 adult patients who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT). Four patients were excluded from the evaluation due to insufficient data. Platelet count and IPF were measured by Sysmex XN-1000 (XN), a newer generation analyzer.

[Autoimmune bullous disease and Hashimoto's disease complicated by acquired hemophilia A].

A 67-year-old man was admitted with a 1-month history of spontaneous hematoma in his right back and severe anemia. He had suffered from rashes with blisters involving both legs for 10 years, which had shown worsening and extended to his entire body concurrently with the hematoma. APTT was markedly prolonged to 119 seconds, and Factor VIII:C and FVIII inhibitor levels were less than 1% and 153.

Human CalDAG-GEFI deficiency increases bleeding and delays αIIbβ3 activation.

Affinity regulation of integrin αIIbβ3 for fibrinogen by inside-out signaling plays a critical role in hemostasis. Calcium and diacylglycerol (DAG)-regulated guanine nucleotide exchange factor I (CalDAG-GEFI) was identified as a Rap1-activating molecule, and its role in inside-out αIIbβ3 activation was established in CalDAG-GEFI-deficient mice. However, little information regarding CalDAG-GEFI in human platelets is available.