- Recombinant Factor VIII Fc Fusion Protein for First-time Immune Tolerance Induction: Final Results of the verITI-8 Study. [Journal Article]Blood. 2023 Feb 03 [Online ahead of print]Blood
- Inhibitor development remains a major challenge in factor VIII (FVIII) replacement therapy. verITI-8 is the first prospective study of a recombinant factor VIII Fc fusion protein (efmoroctocog alfa; rFVIIIFc) for first-time immune tolerance induction (ITI) in males with severe hemophilia A and high-titer inhibitors (historical peak ≥5 Bethesda units [BU]/mL). In this single-arm, open-label, multi…
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- Role of L-Arginine on the Expression of Coagulation Factor VIII Gene. [Journal Article]Altern Ther Health Med. 2023 Feb 03 [Online ahead of print]AT
- CONCLUSIONS: A1 and A2 domain genes had promoter function and could initiate the transcription and expression of CAT gene, but A3, C1 and C2 domain genes could not. Moreover, L-arginine can significantly enhance transcription and expression of human coagulation factor VIII via A2 domain.
- Prolonged Elevations of Factor VIII and von Willebrand Factor Antigen After Multisystem Inflammatory Syndrome in Children (MIS-C). [Journal Article]J Pediatr Hematol Oncol. 2022 Oct 24 [Online ahead of print]JP
- Multisystem Inflammatory Syndrome in Children (MIS-C) is a late systemic inflammatory response to a recent mild or asymptomatic coronavirus disease of 2019 infection. The pathophysiology is incompletely understood but it often features significant coagulopathy along with cardiac and endothelial dysfunction. Endothelial inflammation has been primarily described in acute coronavirus disease of 2019…
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- Fatal acquired coagulation factor V deficiency after hepatectomy for advanced hepatocellular carcinoma as a possible immune checkpoint inhibitor-related adverse event: a case report. [Journal Article]Surg Case Rep. 2023 Feb 02; 9(1):16.SC
- CONCLUSIONS: Severe acquired coagulopathy should be recognized as a possible life-threatening IrAE when using atezolizumab and bevacizumab for HCC.
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- Macrophage Galactose Lectin Contributes to the Regulation of FVIII (Factor VIII) Clearance in Mice. [Journal Article]Arterioscler Thromb Vasc Biol. 2023 Feb 02 [Online ahead of print]AT
- CONCLUSIONS: Cumulatively, these findings demonstrate that MGL plays an important role in regulating macrophage-mediated clearance of both VWF-bound FVIII and free-FVIII in vivo. We propose that this novel FVIII clearance pathway may be of particular clinical importance in patients with type 2N or type 3 Von Willebrand disease.
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- Complement protein C3a enhances adaptive immune responses towards FVIII products. [Journal Article]Haematologica. 2023 Feb 02 [Online ahead of print]H
- The most serious complication in hemophilia A (HA) treatment is the development of factor (F)VIII inhibitors or anti-drug antibodies (ADA) occurring in 25-35% of patients with severe HA. The immunological mechanisms underlying the development of ADA against FVIII products have not been completely understood yet. Immunological danger signals associated with events such as infection or surgery have…
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- Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A. [Clinical Trial, Phase III]N Engl J Med. 2023 Jan 26; 388(4):310-318.NEJM
- CONCLUSIONS: In patients with severe hemophilia A, once-weekly efanesoctocog alfa provided superior bleeding prevention to prestudy prophylaxis, normal to near-normal factor VIII activity, and improvements in physical health, pain, and joint health. (Funded by Sanofi and Sobi; XTEND-1 ClinicalTrials.gov number, NCT04161495.).
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- Decrease in in vivo coagulant potential of emicizumab in a patient with hemophilia A and inhibitor complicated with infectious mononucleosis. [Clinical Trial, Phase II]Blood Coagul Fibrinolysis. 2023 Mar 01; 34(2):122-128.BC
- Emicizumab prophylaxis significantly reduces bleeding episodes in patients with hemophilia A (PwHA). There is little information on coagulant potentials in emicizumab-treated PwHA with infection, however. We encountered an emicizumab-treated PwHA with inhibitor, complicated with Epstein-Barr virus-associated infectious mononucleosis (IM) in phase 1/2 study (ACE001JP/ACE002JP). Although it was a t…
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- Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study. [Journal Article]Lancet Haematol. 2023 Jan 27 [Online ahead of print]LH
- CONCLUSIONS: These data show efficacy and a favourable safety profile of emicizumab in people with non-severe haemophilia A without FVIII inhibitors who warrant prophylaxis, confirming emicizumab as a valuable treatment option in this population.
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- [NEW INNOVATIONS IN THE TREATMENT OF HEMOPHILIA]. [Review]Harefuah. 2023 Jan; 162(1):47-51.H
- Hemophilia is a congenital bleeding disorder with a deficiency of coagulation factor 8 or 9 (hemophilia A or B, respectively) and a tendency for recurrent bleeding, especially into muscles and joints, which may cause orthopedic damage and necessitate joint replacement surgeries at a young age. In recent years, there has been a huge breakthrough in the treatment of hemophilia. Until recently, the …
- The combination of emicizumab and recombinant factor VIII in plasma: Which assays can we use for accurate measurement? [Journal Article]Int J Lab Hematol. 2023 Jan 29 [Online ahead of print]IJ
- CONCLUSIONS: Modified OSA and human FX CSA could not distinguish between rFVIII or emicizumab. The presence of both emicizumab and rFVIII increased thrombin generation to normal levels compared to each drug alone. Bovine FX CSA can be used to accurately determine FVIII activity of rFVIII in plasma which also contains emicizumab.
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- Hemorrhagic and thrombotic adverse events associated with emicizumab and extended half-life factor VIII replacement drugs: EudraVigilance data of 2021. [Journal Article]J Thromb Haemost. 2023 Jan 16 [Online ahead of print]JT
- CONCLUSIONS: The analysis of 2021 EudraVigilance reports shows a lower reporting rate of hemorrhagic ADR vs a higher reporting rate of thrombotic ADR for emicizumab than for EHL FVIII products. These signals stress the importance of monitoring novel drugs in hemophilia, particularly when administered in association with bypassing agents.
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- Identification and antioxidative mechanism of novel mitochondria-targeted MFG-E8 polypeptides in virtual screening and in vitro study. [Journal Article]J Dairy Sci. 2023 Jan 27 [Online ahead of print]JD
- Milk fat globule-EGF factor VIII (MFG-E8) has been identified as an important source of bioactive peptides, which may exert a pivotal role in regulating biologic redox equilibrium. However, the composition of MFG-E8 polypeptides and their mechanisms on mitigating sarcopenia remain unknown. The aim of this study was to identify the composition of MFG-E8 polypeptides and its effects against oxidati…
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- G2 checkpoint targeting via Wee1 inhibition radiosensitizes EGFRvIII-positive glioblastoma cells. [Journal Article]
- CONCLUSIONS: We conclude that the inhibition of Wee1 is an effective targeting approach for the radiosensitization of both EGFRvIII- and EGFRvIII+ GBM cells and may therefore represent a promising new therapeutic option to increase response to radiotherapy.
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- Patients with multiple myeloma and monoclonal gammopathy of undetermined significance have variably increased thrombin generation and different sensitivity to the anticoagulant effect of activated protein C. [Journal Article]Thromb Res. 2023 Jan 23; 223:44-52.TR
- CONCLUSIONS: Hypercoagulability was observed in MM and even in MGUS cases with very low monoclonal protein concentration. In MM patients, APC had no effect on TG, but it attenuated TG in MGUS patients.
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- Protein S Deficiency with Recurrent Deep Vein Thrombosis and Post Thrombotic Syndrome: A Case Report. [Case Reports]JNMA J Nepal Med Assoc. 2022 Oct 01; 60(254):892-894.JJ
- Protein S is a vitamin K-dependent protein that acts as a break in secondary hemostasis by inactivating activated factor V and activated factor VIII. We report a case of a 40 years old male who had the first episode of deep vein thrombosis of the left lower limb 10 years back, which despite treatment, reoccurred 3 months later in the bilateral lower limb. Thrombophilic screening showed severe pro…
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- SARS-CoV-2 infection predicts larger infarct volume in patients with acute ischemic stroke. [Journal Article]
- CONCLUSIONS: SARS-CoV-2 infection seems to play a major role in endothelium activation and infarct volume extension during AIS.
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- Therapeutic potential of fetal liver cells transplantation in hemophilia A mice. [Journal Article]Haematologica. 2023 Jan 26 [Online ahead of print]H
- Hemophilia A (HA) cell therapy approaches in pediatric individuals require suitable factor (F)VIII-producing cells for stable engraftment. Liver sinusoidal endothelial cells (LSEC) and hematopoietic stem cells (HSC) have been demonstrated to be suitable for the treatment of adult HA-mice. However, after transplantation in busulfan (BU)-conditioned newborn mice, adult LSEC/HSC cannot efficiently e…
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- Acquired Hemophilia A In Adults: A Multicenter Study from Turkey. [Journal Article]Indian J Hematol Blood Transfus. 2023 Jan; 39(1):107-115.IJ
- Acquired hemophilia A (AHA) is a rare disease caused by autoantibodies inhibiting factor VIII (FVIII) activity. Although the conditionis usually idiopathic, there may be other underlying diseases. Treatment consists of two steps: treatment of acute bleeding and immunosuppression. In this multicenter study, we aimed to demonstrate the clinical characteristics, management details, and survival of A…
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- Little discrepancy between one-stage and chromogenic factor VIII (FVIII)/IX assays in a large international cohort of persons with nonsevere hemophilia A and B. [Journal Article]J Thromb Haemost. 2022 Dec 22 [Online ahead of print]JT
- CONCLUSIONS: Little assay discrepancy was observed despite the presence of mutations previously associated with discrepancy, suggesting that the presence and magnitude of assay discrepancy are largely determined by laboratory variables.
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- Acute obstetric coagulopathy during postpartum hemorrhage is caused by hyperfibrinolysis and dysfibrinogenemia: an observational cohort study. [Journal Article]J Thromb Haemost. 2022 Dec 22 [Online ahead of print]JT
- CONCLUSIONS: Clinically significant hemostatic impairment is uncommon during PPH, but a subgroup of women have a distinct and severe coagulopathy characterized by hyperfibrinolysis, low fibrinogen, and dysfibrinogenemia associated with poor fetal outcomes.
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- Different inhibitor incidence for individual factor VIII concentrates in 1076 previously untreated patients with severe hemophilia A: data from the PedNet cohort. [Letter]J Thromb Haemost. 2022 Dec 22 [Online ahead of print]JT
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- Evaluation of the procoagulant state in chronic immune thrombocytopenia before and after eltrombopag treatment-a prospective cohort study. [Journal Article]J Thromb Haemost. 2022 Dec 22 [Online ahead of print]JT
- CONCLUSIONS: Patients with ITP in this study were in a hypercoagulable state, with preactivated platelets, increased thrombin generation potential, and increased levels of factor VIII and von Willebrand factor. Eltrombopag treatment further increased plasma thrombin generation potential but no other hemostatic parameters.
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- The effect of a next generation factor VIII mimetic bispecific antibody (Mim8) on assays of factor VIII activity and thrombin generation. [Journal Article]J Thromb Haemost. 2023 Jan 02 [Online ahead of print]JT
- CONCLUSIONS: APTT-based assays are sensitive to Mim8 and should not be performed in the presence of the drug. Chromogenic assays containing human proteins or hybrid human/bovine proteins demonstrated variable sensitivity to Mim8. Bovine only chromogenic assays were largely insensitive to the presence of Mim8. Thrombin generation normalized at increased Mim8 concentrations. Modified one-stage and chromogenic assays could be used to quantify the Mim8 concentration in plasma.
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- Pre-existing anti-factor VIII immunity alters therapeutic platelet-targeted factor VIII engraftment following busulfan conditioning through cytotoxic CD8 T cells. [Journal Article]J Thromb Haemost. 2022 Dec 22 [Online ahead of print]JT
- CONCLUSIONS: Pre-existng immunity can alter the engraftment of 2bF8Tg-Sca-1+ cells through the cytotoxic CD8 T-cell-mediated pathway. Sufficient eradication of FVIII-primed CD8 T cells is critical for the success of platelet gene therapy in hemophilia A with inhibitors.
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- A prospective, multicenter, open-label phase III study of emicizumab prophylaxis in patients with acquired hemophilia A. [Journal Article]J Thromb Haemost. 2022 Dec 22 [Online ahead of print]JT
- CONCLUSIONS: These results suggest that emicizumab prophylaxis with the tested dosing regimen and completion criteria may have a favorable benefit-risk profile in PwAHA.
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- Challenges in the management of women with type 2B von Willebrand disease during pregnancy and the postpartum period: evidence from literature and data from an international registry and physicians' survey-communication from the Scientific and Standardization Committees of the International Society on Thrombosis and Haemostasis. [Journal Article]J Thromb Haemost. 2023 Jan; 21(1):154-163.JT
- CONCLUSIONS: We conclude that an international consensus and guidance are critically required for better care and improved outcomes in this patient cohort.
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- Gene therapy for hemophilia: looking beyond factor expression. [Review]Exp Biol Med (Maywood). 2022 Dec; 247(24):2223-2232.EB
- Hemophilia A (factor VIII [FVIII] deficiency) and hemophilia B (factor IX [FIX] deficiency) are the X-linked recessive bleeding disorders that clinically manifest with recurrent bleeding, predominantly into muscles and joints. In its severe presentation, when factor activity is less than 1% of normal, hemophilia presents with spontaneous musculoskeletal bleeds and may progress to debilitating chr…
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- Small intestinal angiosarcoma on clinical presentation, diagnosis, management and prognosis: A case report and review of the literature. [Case Reports]
- CONCLUSIONS: Angiosarcoma should be considered for unexplained melena and abdominal pain, especially in older men and patients with a history of radiation exposure. Prompt treatment, including surgery and adjuvant chemotherapy, is essential to prolonging patient survival.
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- Factor assay in victims of snake bite: Experience from a tertiary care institute in South India. [Journal Article]
- CONCLUSIONS: Early detection and treatment of envenomation remains the cornerstone of managing snake venom-induced consumptive coagulopathy. Anti-snake venom plays a major role in the reversal of coagulopathy. Blood and blood products would be useful when coagulopathy does not revert by ASV alone. Evidence-based transfusion can be implemented and cryoprecipitate may be used as many of the patients had factor XIII and fibrinogen deficiency as part of venom-induced coagulopathy. To improve patient management and thereby the outcome of patients CMEs and training programs for the treating physicians also has to be implemented so that guidelines are formulated and followed.
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