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Inhibitors develop in many patients with hemophilia who receive recombinant factor VIII. Prophylaxis with emicizumab, an antibody that functionally replaces factor VIII in the clotting pathway, reduced the rate of bleeding events among patients with hemophilia with inhibitors.

The authors examined the incidence of thromboembolic events associated with off-label use of rFVIIa in patients with bleeding problems. Coronary arterial thrombotic events and abnormal clotting among older patients were more common with rFVIIa than with placebo. Recombinant activated coagulation factor VII (rFVIIa) (NovoSeven, Novo Nordisk) is approved for the treatment of bleeding in patients with hemophilia A or B who have inhibiting antibodies to coagulation factor VIII or IX. Indications have been broadened to include the treatment of episodes of bleeding and the prevention of episodes of bleeding related to surgical or invasive procedures in patients with congenital and acquired hemophilia, factor VII deficiency, or Glanzmann's thrombasthenia (the last indication is approved only in Europe). The mechanism of action of rFVIIa may offer the potential for its use in preventing or treating severe or life-threatening bleeding . . .

Diffuse alveolar hemorrhage (DAH) is a life-threatening pulmonary complication in patients with hematologic malignancies or systemic autoimmune disorders. Pathologic findings show pulmonary capillaritis, bland hemorrhage, diffuse alveolar damage, and hemosiderin-laden macrophages, but in the majority of cases, pathogenesis remains unclear. Despite the severity and high mortality, the current treatment options for DAH remain empirical. Systemic treatment to control inflammatory activity including high-dose corticosteroids, cyclophosphamide, and rituximab and supportive care have been applied, but largely unsuccessful in critical cases. Activated recombinant factor VII (FVIIa) can achieve rapid local hemostasis and has been administered either systemically or intrapulmonary for the treatment of DAH. However, there is no randomized controlled study to evaluate the efficacy and safety, and the use of FVIIa for DAH remains open to debate. This review discusses the pathogenesis, diverse etiologies causing DAH, diagnosis, and treatments focusing on hemostasis using FVIIa. In addition, the risks and benefits of the off-label use of FVIIa in pediatric patients will be discussed in detail.

In a previous phase 2 placebo-controlled trial, recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcome in patients with intracerebral hemorrhage. Those findings were not reproduced in this phase 3 trial, in which rFVIIa reduced hematoma growth but did not improve clinical outcomes. In this phase 3 trial, recombinant activated factor VII (rFVIIa) reduced hematoma growth but did not improve clinical outcomes in patients with intracerebral hemorrhage. Intracerebral hemorrhage is the most devastating form of stroke. Approximately 40% of patients with intracerebral hemorrhage die within 30 days, and the majority of survivors are left with severe disability. 1 , 2 Hematoma growth occurs in up to 70% of patients who have intracerebral hemorrhage documented by computed tomographic (CT) scanning performed within 3 hours after the onset of symptoms. 3 , 4 Furthermore, hemorrhage expansion is an independent determinant of death and disability. 4 In addition to intracerebral-hemorrhage growth, other predictors of poor outcome include age, baseline volume of the hemorrhage, Glasgow Coma Scale score, intraventricular hemorrhage, and infratentorial location. 5 There is no . . .

Sequential combination bypass therapy (SCBT) is an effective treatment option for haemophilia patients with inhibitors; however, its safety, efficacy, and cost have largely have yet to be systematically evaluated. To address this question, we retrospectively analyzed the medical records of 14 haemophilia patients with high titer inhibitors who underwent surgery. The patients with high inhibitors were treated with two SCBT regimens by optimizing doses of the recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC). The effectiveness and safety of the two SCBT regimens were evaluated. In addition, rFVIIa and PCC factor consumption and costs were also compared. The median age of the 14 patients was 30.00 (27.25–42.75) years. They all underwent major surgeries, with 85.71% (12/14) was orthopedic surgeries related to hemophilic arthropathy. Four patients were treated using regimen 1 and ten with regimen 2. Results showed that regimen 2 exhibited a higher haemostatic efficiency (90% vs. 75% intraoperative and 90% vs. 50% postoperative) and a 28.0% reduction in economic costs (863,604.68 RMB vs. 621,756.62 RMB). All patients after surgery had no prothrombin time extension, 7.14% had fibrinogen and platelet count decreases, and 57.14% had D-dimer increases that returned to baseline within 5–7 days after SCBT. The study shows that regimen 2 as an optimized SCBT regimen is an efficient approach to secure haemostasis for haemophilia patients with high titer inhibitors in the perioperative period, rather than regimen 1. The findings can help design future clinical studies and provide more reliable data and implementation advice.

Background. Pulmonary hemorrhage (PH) leads to acute and catastrophic deterioration in neonates, and there is no curative treatment available. Off-label use of recombinant Factor VIIa (rFVIIa) is a promising treatment to control bleeding. The aim of this study was to investigate the efficacy and safety of rFVIIa in neonatal massive PH. Methods. We used rFVIIa for PH in our neonatology unit during October 2022. We compared demographic and prognostic data of neonates with PH, for two years prior to and following this time point. Intravenous rFVIIa (50-90 μg/kg/dose) was administered to patients with life-threatening PH that was unresponsive to conventional therapies including surfactant administration, vitamin K treatment, blood product transfusion, increasing airway pressure, high frequency ventilation, and endotracheal adrenaline. Potential side effects, such as thromboembolism, were monitored for one week. Results. We present 16 neonates (7 females; 14 preterm) treated with rFVIIa in addition to conventional treatments and compared their clinical outcomes with the rFVIIa-untreated group (n=21). Median (interquartile range [IQR]) birth weight (960 [775-2377] vs 910 [710-1360] g, p=0.20) and gestational age (29 [27-32] vs 27 [27-29] weeks, p=0.25) did not significantly differ between the groups. Median (IQR) postnatal day of PH occurrence was 7.5 (3-15) in the rFVIIa-treated group and 3 (1.5-6) in the rFVIIa-untreated group (p=0.019). Overall, six neonates died of PH complications in the intervention group. All neonates responded to rFVIIa to varying degrees (cessation of bleeding, n=11; reduced bleeding, n=5). A second dose was required in three. No thromboembolism was observed during the treatment period. Death attributable to PH [6 (37%) vs 16 (76%), p=0.042] and overall mortality (7 [43%] vs 18 [86%], p

Acute blood loss in trauma requires quick identification and action to restore circulating volume and save the patient. Massive transfusion protocols (MTPs) have become standard at Trauma Centers, in order to rapidly deliver blood products to bleeding patients. This literature review presents current standards of transfusion ratios, as well as insights into adjuncts during massive transfusions. PubMED was searched for articles from 2005 to 2020 on MTPs, the article were assessed for single vs. multi-institutional, mechanism of injury, type of MTP, timing in which blood products should be administered, timing of delivery of blood products to trauma bay, pre-hospital treatment and adjuncts, and outcomes. Eleven studies addressed transfusion ratios. Seven studies looked at timing of blood products. Nine studies addressed MTP pre-hospital treatment and adjuncts. Prior to 2015, studies supported the benefits of a balanced transfusion ratio, which was then confirmed by the PROPPR randomized controlled trial. The shorter the time to blood product delivery the better the outcomes. New advances in technology have allowed us to measure different patterns of coagulation, allowing more individualized approaches to the bleeding patient. Current massive transfusion protocols should utilize between 1:1:1 and 1:1:2 ratios of the 3 main products; plasma, platelets, and red blood cells. Massive transfusion protocols are effective in decreasing mortality. Better resuscitation efforts were seen when blood products were readily available in the trauma bay when the patient arrived and the faster the replacement of blood, the better the outcomes.

In this randomized trial, treatment of patients with intracerebral hemorrhage with recombinant activated factor VII (rFVIIa) within four hours after the onset of bleeding reduced the growth of the hematoma and the rates of disability and mortality (90-day mortality was 18 percent with rFVIIa and 29 percent with placebo). Serious thromboembolic adverse events were more common among patients treated with rFVIIa than among those who received placebo. Despite the higher rates of some complications, early treatment with rFVIIa improved functional outcomes and survival among patients with intracerebral hemorrhage. Intracerebral hemorrhage is one of the most disabling forms of stroke. More than one third of patients with this disorder die within one month after the onset of symptoms, and only 20 percent regain functional independence. 1 There is currently no effective treatment for intracerebral hemorrhage. 2 The volume of the hematoma is a critical determinant of mortality and functional outcome after intracerebral hemorrhage, 3 , 4 and early hematoma growth is an important cause of neurologic deterioration. 5 – 8 An increase in volume of more than 33 percent is detectable on repeated computed tomography (CT) in 38 percent of patients initially scanned within three . . .

We describe a 67-year-old patient with hemophilia A and inhibitors (PwHA-I) receiving emicizumab prophylaxis who underwent surgical treatment for pseudoaneurysm. He was treated with a bolus infusion of recombinant factor VIIa (rFVIIa; 79 μg/kg) immediately before surgery, and a second dose of rFVIIa after an initial treatment on day 1. A third rFVIIa bolus was infused 17 h after the second dose on day 2, and the treatment was continued every 24 h on day 3 and day 4. Treatment with rFVIIa was discontinued on day 4. No perioperative bleeding or thrombotic events were observed. Coagulation potentials at 8 h after rFVIIa administration determined by clot waveform analysis (CWA) and thrombin generation assay (TGA) were within near-normal ranges, and results at 17 h after rFVIIa administration showed coagulation function comparable to that in the patient without rFVIIa. Our experimental data suggest that the coagulation potential in FVIII-deficient plasma spiked with both 0.28 µg/mL (11.2 μg/kg) rFVIIa and emicizumab was equivalent to or greater than that spiked with 2.2 µg/mL (90 μg/kg) rFVIIa alone. Thus, administration of rFVIIa every 8 h may be feasible for managing perioperative treatment in emicizumab-treated PwHA-I.

BackgroundFactor VII deficiency is considered a contraindication to neuraxial anesthesia due to the risk of an epidural hematoma.Case ReportA 32 year old G1P0 parturient with severe factor VII deficiency presented for an anesthesiology consultation at 32 weeks gestation. Initial coagulation studies were significant for an elevated INR (2.0) and a low factor VII level of 6%. After interdisciplinary discussion, it was decided that neuraxial analgesia could be offered if her coagulation studies corrected after administration of recombinant activated factor VII (rFVIIa). The patient presented at 36 weeks gestation for a rFVIIa challenge. She received 22 mcg/kg rFVIIa and coagulation studies were analyzed 20 minutes later which showed complete correction of the coagulopathy. The patient presented to the hospital at 39 weeks and 3 days for delivery, received 2 mg rFVIIa and 20 minutes later, successfully received an epidural catheter. Her INR was monitored every 3 hours during her labor course and rFVIIa was given if the INR was 1.3 or greater. She required three additional doses over 22 hours. No bleeding or thrombotic events occurred, and the patient was discharged home without complications.ConclusionThis case highlights the safe management of an epidural catheter in a parturient with severe factor VII deficiency.