Recombinant factor viia

BACKGROUND: Preclinical bleeding models increase current hemophilia A (HA) knowledge and aid the development of new pharmacological treatments. There are several well-established mouse bleeding models, but limited options are available for rat models despite their high resemblance to human disease process. OBJECTIVE: To provide a comprehensive description of the tail vein transection (TVT) bleeding model in HA rats and examine the correlation between in vivo pharmacological efficacy and global hemostatic assays...

Haemophagocytic syndrome, diffuse alveolar haemorrhage, catastrophic antiphospholipid syndrome and various types of thrombotic microangiopathies are rare conditions with significant morbidity and mortality. A common feature is late diagnosis, which can affect the success of treatment. The aim of this review article is to summarize the basic diagnostic and therapeutic steps of the present subpopulation of critically ill patients.

Recombinant factor VIIa (rFVIIa) has of April 2022 been approved by the European Medicines Agency for treatment of severe postpartum haemorrhage. The extended approval is based on one small open-label, non-blinded randomized trial of 84 women from 2015 showing reduced "second line" treatment, but also increased risk of thromboembolism. Systematic use of tranexamic acid and timely coagulation assessment with thromboelastography/rotational thromboelastometry are not applied. Danish and international societies recommend that rFVIIa is reserved as a last option in severe life-threatening cases of postpartum haemorrhage...

BACKGROUND: Coagulopathy following cardiac surgery is associated with considerable blood product transfusion and high morbidity and mortality. The treatment of coagulopathy following cardiac surgery is challenging, with the replacement of clotting factors being based on transfusion of fresh frozen plasma (FFP). Prothrombin complex concentrate (PCCs) is an alternative method to replace clotting factors and warrants evaluation. PCCs are also an alternative method to treat refractory ongoing bleeding post-cardiac surgery compared to recombinant factor VIIa (rFVIIa) and also warrants evaluation...

INTRODUCTION: Emicizumab is a humanized bispecific monoclonal antibody licensed for patients with severe haemophilia A. Breakthrough bleeding still occurs in patients on emicizumab and can be managed with recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC). Thrombotic events were reported when patients on emicizumab received concomitant aPCC at relatively high doses. We studied the effect of infusing various doses of aPCC to patients on emicizumab. MATERIAL AND METHODS: Nine patients with severe haemophilia A with inhibitors who are on emicizumab were recruited to participate...

OBJECTIVES: RecombinanthumanactivatedfactorVIIahas been usedprophylactically to mitigate requirements for transfusion in liver transplant. We explored its effectiveness andrisks amonglivertransplantrecipients at high risk for massive transfusion. MATERIALS AND METHODS: We performed a retrospective study of recipients who underwent liver transplant from 2012 to 2015. Patients considered at risk for massive transfusion received up to two 20 μg/kg doses of recombinant human activated factor VIIa, with rescue use permitted for other patients...

Diffuse pulmonary haemorrhage is an ominous condition that has a high paediatric mortality rate. Recombinant activated factor VIIa (rFVIIa) is a powerful haemostatic agent which has been used intravenously in life-threatening haemorrhage in variety of conditions in which conventional medical or surgical therapy are unsuccessful. We report off-label successful use of endotracheal rFVIIa for massive life-threatening respiratory haemorrhage following aspiration and cardiopulmonary resuscitation in a 3-month-old infant who was anticoagulated with enoxaparin following corrective cardiac surgery with other comorbidities...

Bernard-Soulier syndrome (BSS) is a rare congenital bleeding disorder of the platelet, and it is mainly inherited as an autosomal recessive trait. It is caused by both qualitative and quantitative deficiency of the platelet membrane glycoprotein (GP) Ib-IX-V receptor complex, thereby causing abnormal platelets adhesion.We report a case of a primigravida in her 20s with history of BSS diagnosed in childhood due to family history. Her preconception period was challenging as she suffered from severe menorrhagia often requiring hospital admission, blood and platelet transfusions...

Mycotic aortic aneurysm is an infective disease of the aorta with high mortality rate despite surgical repair. Recombinant activated factor VIIa (rFVIIa) is approved for the treatment of bleeding in hemophilia and used (off-labeled) in acute bleeding related to the trauma, cardiac surgery, and intracranial bleed. A 38-year female was admitted with abdominal pain, and was subsequently diagnosed with bleeding mycotic aneurysm of the abdominal aorta. She was given rFVIIa and the bleeding stopped successfully. We recommend further evaluation of the role of rFVIIa in bleeding mycotic abdominal aortic aneurysm, as it can bring a novel change in the management of this devastating disease...

Platelet procoagulant mechanisms are emerging to be complex and important to achieving haemostasis. The mechanisms include the release of procoagulant molecules from platelet storage granules, and strong agonist-induced expression of procoagulant phospholipids on the outer platelet membrane for tenase and prothrombinase assembly. The release of dense granule polyphosphate is important to platelet procoagulant function as it promotes the activation of factors XII, XI and V, inhibits tissue factor pathway inhibitor and fibrinolysis, and strengthens fibrin clots...

Paraneoplastic coagulopathies are uncommon in patients with lymphoma. We report the first case of an acquired coagulopathy in a patient with isolated primary central nervous system lymphoma (PCNSL) demonstrating large-cell histology. In our patient, a paraneoplastic factor VII inhibitor significantly delayed a diagnostic lumbar puncture despite fresh frozen plasma and inactivated prothrombin complex concentrate. While her coagulopathy was effectively overcome with recombinant activated factor VIIa and subsequently with lymphoma-directed therapy, her delayed diagnosis likely contributed to a poor outcome...

OBJECTIVE: Activated prothrombin complex concentrate (aPCC) is a bypassing agent indicated to treat bleeds in patients with acquired hemophilia A (AHA). Nevertheless, its efficacy and safety in the real-world setting have not often been addressed. METHODS: We report the experience of Spanish reference centers for coagulation disorders and from acquired hemophilia Spanish Registry (AHASR) from August 2012 to February 2021. Follow-up period of 30 days after aPCC withdrawal...

Introduction: Diffuse alveolar haemorrhage (DAH) is a potentially life-threatening disease, characterized by diffuse accumulation of red blood cells within the alveoli. It can be caused by a variety of disorders. In case DAH results in severe respiratory failure, veno-venous extracorporeal membrane oxygenation (VV-ECMO) can be required. Since VV-ECMO coincides with the need for anticoagulation therapy, this results in a major clinical challenge in DAH patients with hemoptysis. Case presentation: We report a patient case with severe DAH-induced acute respiratory failure and hemoptysis in need for VV-ECMO complicated by life-threatening membrane oxygenator thrombosis...

Introduction Glanzmann's thrombasthenia (GT) is an autosomal recessive disorder of platelets caused by a deficiency in the glycoprotein IIb-IIIa. Bleeding from the skin, mucous membranes, and ecchymosis are symptoms manifested starting in early childhood. There may also be major bleeding conditions as a result of surgical procedures or trauma. The treatment is based on platelet transfusions, antifibrinolytic agents, and recombinant activated factor VII (rFVIIa). Objective To describe the demographic and clinical characteristics as well as the main treatment strategies used during bleeding events or procedures for patients diagnosed with GT that required inpatient attention at a university hospital, a referral center specialized in hemostasis, in the city of Bogota...

BACKGROUND: Acquired Hemophilia A (AHA) is a rare autoimmune disorder associated with the development of autoantibodies against factor VIII (FVIII). Although obtaining hemostatic control through the use of recombinant factor VIIa, activated prothrombin complex concentrate and recombinant porcine FVIII are cornerstones in the clinical management of AHA, these therapies have several disadvantages, including a higher risk for the development of thromboembolic events, unpredictable efficacy and short half-lives...

INTRODUCTION: Acute bleeding leads to significant morbidity and mortality. Recombinant wildtype Factor VIIa (WT FVIIa) had been reported to have some therapeutic effects in some clinical trials, however, its use was associated with thromboembolic events. We sought to develop a novel FVIIa molecule (CT-001) with enhanced activity and lowered thrombogenicity risk. METHODS AND METHODS: CT-001 has 4 N-glycans (T106N/N145/V253N/N322) with terminal sialic acid residues removed to promote active clearance via the asialoglycoprotein receptor, and P10Q/K32E substitutions introduced to its gamma-carboxyglutamic acid (Gla) domain for enhanced phospholipid affinity and activity...

The management of pregnancy and delivery in patients with Glanzmann thrombasthenia requires platelet transfusion and recombinant activated factor VII. We report two successful pregnancies in a single patient and propose a protocol for monitoring and treatment. The urgent need for controlled trials and other epidemiological studies is also underscored.

BACKGROUND: A mainstay of treatment in patients with hemophilia with inhibitors (PWIs) is the use of a recombinant factor VIIa (rFVIIa) bypassing agent. A new rFVIIa product may allow reduced rFVIIa utilization for on-demand treatment of bleeding episodes (BEs). OBJECTIVE: A decision analytic health economic model was developed to compare the utilization and consequent need for bleed-related clinical encounters of 2 rFVIIa products, with the International Nomenclature Name of eptacog alfa (EA) and eptacog beta (EB)...

Acquired hemophilia A (AHA) is a rare disease with a prevalence in Europe of 1.5 per million. This diagnosis is significantly delayed in about one-third of all cases, leading to deferred treatment. The main signs of AHA are spontaneous bleeding seen in about two-thirds of all patients. AHA can be lethal in 20% of all symptomatic cases. This patient population's main standard laboratory finding is a prolonged aPTT (activated prothrombin Time) with otherwise normal coagulation results. In addition, antibodies against FVIII (in Bethesda Units) and a quantitative reduction of FVIII activity are necessary to confirm AHA...

Cerebral haemorrhage is a serious subtype of stroke, with most patients experiencing short-term haematoma enlargement leading to worsening neurological symptoms and death. The main hemostatic agents currently used for cerebral haemorrhage are antifibrinolytics and recombinant coagulation factor VIIa. However, there is no clinical evidence that patients with cerebral haemorrhage can benefit from hemostatic treatment. We provide an overview of the mechanisms of haematoma expansion in cerebral haemorrhage and the progress of research on commonly used hemostatic drugs...