New directions to develop therapies for people with hemophilia.

Introduction: The past few decades have seen a tremendous advancement in the management of hemophilia. Whether it is improved methods to attenuate critical viruses, recombinant bioengineering with decreased immunogenicity, extended half-life replacement therapies to mitigate the burden of repeated infusion treatments, novel nonreplacement products to avoid the drawback of inhibitor development with its attractive subcutaneous administration and then the introduction of gene therapy, the management has trodden a long way.

Areas Covered: This expert review describes the progress in the treatment of hemophilia over the years.

A single-arm, long-term efficacy and safety study of subcutaneous romiplostim in children with immune thrombocytopenia.

Romiplostim is a thrombopoietin (TPO) receptor agonist approved for children and adults with immune thrombocytopenia (ITP) for ≥6 months, recommended as second-line treatment. This phase 3b, single-arm, multicenter study investigated long-term efficacy and safety of romiplostim in children ≥1 to <18 years old with ≥6 months' ITP duration and platelet counts ≤30 × 109/L. Children received weekly subcutaneous romiplostim (1 μg/kg titrated to 10 μg/kg) to maintain platelets within 50 to 200 × 109/L.

Assessment of romiplostim immunogenicity in pediatric patients in clinical trials and in a global postmarketing registry.

Development of first-generation thrombopoietins (TPOs) was halted due to antibodies that neutralized endogenous TPO, causing protracted thrombocytopenia in some patients. The second-generation TPO receptor agonist romiplostim, having no homology to TPO, was developed to circumvent potential immunogenicity. We examined the development of binding and neutralizing antibodies to romiplostim and TPO among pediatric patients with primary immune thrombocytopenia (ITP) in 5 clinical trials and a global postmarketing registry.

SARS-CoV-2 vaccination and ITP in patients with de novo or preexisting ITP.

Cases of de novo immune thrombocytopenia (ITP), including a fatality, following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] ×109/L approximately 1 week postvaccination.

Severe, Refractory Immune Thrombocytopenia Occurring After SARS-CoV-2 Vaccine.

The rollout of the SARS-CoV-2 vaccine is underway, and millions have already been vaccinated. At least 25 reports of "immune thrombocytopenia" (ITP) or "thrombocytopenia" following the Moderna or Pfizer vaccine have been added to the Vaccine Adverse Event Reporting System (VAERS) in the US. ITP is a rare but known complication of several vaccinations.

Clinical overview and practical considerations for optimizing romiplostim therapy in patients with immune thrombocytopenia.

The fundamental treatment goal for patients with immune thrombocytopenia (ITP) is reduced or ameliorated bleeding. Although various treatment options exist for the management of ITP, recent advances have led to the approval of three thrombopoietin receptor agonists (TPO-RAs; romiplostim, eltrombopag, and avatrombopag) in the United States and European Union. Current treatment guidelines for ITP indicate that medical therapy is preferred over surgical therapy and support the use of TPO-RAs as early as 3 months after disease onset.

Efficacy of rFVIIIFc versus Emicizumab for the Treatment of Patients with Hemophilia A without Inhibitors: Matching-Adjusted Indirect Comparison of A-LONG and HAVEN Trials.

Purpose: Primary prophylaxis, using factor VIII replacement, is the recognized standard of care for severe hemophilia A. Recombinant factor VIII-Fc fusion protein (rFVIIIFc) and emicizumab, a humanized, bispecific antibody, are approved for routine prophylaxis of bleeding episodes in severe hemophilia A. These products have different mechanisms of action, methods of administration and treatment schedules.

Fostamatinib is an effective second-line therapy in patients with immune thrombocytopenia.

Fostamatinib demonstrated efficacy in phase 3 trials of adults with immune thrombocytopenia (ITP). Post hoc analysis compared patients who received fostamatinib as second-line therapy (after steroids ± immunoglobulins) versus third-or-later-line therapy (after ≥2 prior lines of therapy including a second-line agent). Platelet responses ≥50 000/µl were observed in 25/32 (78%) second-line and 54/113 (48%) third-or-later-line patients.

The Need for Comprehensive Care for Persons with Chronic Immune Thrombocytopenic Purpura.

Chronic platelet disorders (CPD), including chronic immune thrombocytopenic purpura (cITP), thrombotic thrombocytopenic purpura (TTP) and platelet function disorders are among the most common bleeding disorders and are associated with morbidity and mortality. The clinical phenotype and complexity of cITP is much like that of hemophilia. In cITP and hemophilia, bleeding is problematic for many, complicating employability, insurability and overall quality-of-life (QoL).

Romiplostim treatment for children with immune thrombocytopenia: Results of an integrated database of five clinical trials.

Background: Treatment for chronic immune thrombocytopenia (cITP) in children is largely limited to immunosuppressive agents. Thrombopoietin receptor agonists (TRAs) have been used to treat cITP in adults for over a decade. The objective of this integrated analysis was to examine the safety and efficacy of the TRA romiplostim in children with ITP.

Factor VIII replacement is still the standard of care in haemophilia A.

Prophylactic factor VIII (FVIII) has dramatically improved haemophilia A treatment, preventing joint bleeding and halting the deterioration of joint status. FVIII products with an extended plasma half-life further improve patients' quality of life and increase therapeutic adherence. New licensed classes of non-replacement products include prophylactic emicizumab, which is administered subcutaneously up to every 4 weeks.

Long-term treatment with romiplostim and treatment-free platelet responses in children with chronic immune thrombocytopenia.

Children with immune thrombocytopenia for ≥6 months completing a romiplostim study received weekly subcutaneous romiplostim (1-10 μg/kg targeting platelet counts of 50-200×10/L) in this extension to examine romiplostim's long-term safety and efficacy. Sixty-five children received romiplostim for a median of 2.6 years (range: 0.

An Outbreak of Synthetic Cannabinoid-Associated Coagulopathy in Illinois.

Background: In March and April 2018, more than 150 patients presented to hospitals in Illinois with coagulopathy and bleeding diathesis. Area physicians and public health organizations identified an association between coagulopathy and synthetic cannabinoid use. Preliminary tests of patient serum samples and drug samples revealed that brodifacoum, an anticoagulant, was the likely adulterant.

Hemophilia Management via Data Collection and Reporting: Initial Findings from the Comprehensive Care Sustainability Collaborative.

Background: Despite being a rare disorder, hemophilia represents a significant driver of health care resource utilization and requires expert hematologic and multidisciplinary services to achieve optimal outcomes. Since their inception nearly 40 years ago, hemophilia treatment centers (HTCs) have served as centers of excellence in providing the intensive care and ancillary services necessary for this unique patient base; however, the full capabilities of these centers may be underused in the current framework of managed care, largely because of a lack of communication and information shared between payers and HTC stakeholders.

Program Description: In an effort to enact tangible change toward improving the quality of care for bleeding disorders, the National Hemophilia Foundation developed an ongoing initiative among 18 leading clinicians and managed care decision makers called the Comprehensive Care Sustainability Collaborative (CCSC).

Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study.

Background: The thrombopoietin receptor agonist romiplostim could be an effective treatment in symptomatic children with persistent or chronic immune thrombocytopenia. We aimed to assess whether romiplostim is safe and effective in children with immune thrombocytopenia of more than 6 months' duration.

Methods: In this phase 3 double-blind study, eligible participants were children with immune thrombocytopenia aged 1 year to 17 years and mean platelet counts 30 × 10(9)/L or less (mean of two measurements during the screening period) with no single count greater than 35 × 10(9)/L, and were recruited from 27 sites in the USA, Canada, and Australia.

Hospitalizations in pediatric patients with immune thrombocytopenia in the United States.

To examine utilization and outcomes in pediatric immune thrombocytopenia (ITP) hospitalizations, we used ICD-9 code 287.31 to identify hospitalizations in patients with ITP in the 2009 HCUP KID, an all-payer sample of pediatric hospitalizations from US community hospitals. Diagnosis and procedure codes were used to estimate rates of ITP-related procedures, comorbidity prevalence, costs, length of stay (LOS), and mortality.

Romiplostim as a treatment for immune thrombocytopenia: a review.

"Immune thrombocytopenia" (ITP) is an autoimmune disorder that leads to peripheral destruction, as well as a decreased production of platelets. ITP most commonly presents as mild mucocutaneous bleeding. Though it is rare, the leading cause of mortality in persons with ITP is intracranial hemorrhage and those that do not respond to therapy are at increased risk.

Dental procedures in 24 patients with chronic immune thrombocytopenia in prospective clinical studies of eltrombopag.

Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by chronically low peripheral blood platelet counts. Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that increases platelet production. This report examines peri-procedural platelet counts and bleeding complications among chronic ITP patients requiring dental procedures while participating in clinical studies with eltrombopag.