Notes

A powerful model of endogenous wall clocks as well as exterior stimuli figuring out circadian tempos.
The bleeding phenotype of von Willebrand disease (VWD) varies highly between patients and can only partly be explained by von Willebrand factor (VWF) parameters. By cleaving large VWF multimers into smaller, less active multimers, ADAMTS-13 is an important regulator of VWF activity. However, it is unknown what the role of ADAMTS-13 is in individuals with VWD.

We therefore studied how ADAMTS-13 activity is associated with the laboratory and bleeding phenotype in individuals with VWD.

We measured ADAMTS-13 activity using the fluorescence resonance energy transfer substrate VWF 73 assay in 638 individuals with VWD in the nationwide cross-sectional Willebrand in the Netherlands study and in 36 healthy controls. The bleeding phenotype was assessed using the Tosetto bleeding score.

ADAMTS-13 activity was similar in individuals with VWD (109%±20.6%) and controls (110%±19.7%). ADAMTS-13 activity was higher in individuals with VWD with type 3 than those with type 1 (mean difference, 11.8%; 95% confidence interval [CI], 2.9%-20.8%) or type 2 (mean difference, 16.1%; 95% CI, 7.1%-25.1%). ADAMTS-13 activity was not associated with the Tosetto bleeding score (0.1 Tosetto bleeding score increase per 10% ADAMTS-13 increase, 95% CI, -0.2 to 0.3). Furthermore, ADAMTS-13 activity did not differ between individuals with and without a bleeding event during the year preceding blood sampling (mean difference, 1.4%; 95% CI, -2.1% to 4.9%).

ADAMTS-13 activity was highest in individuals with type 3 VWD, but it had only minor associations with VWF parameters. ADAMTS-13 activity does not influence the bleeding phenotype in individuals with VWD.
ADAMTS-13 activity was highest in individuals with type 3 VWD, but it had only minor associations with VWF parameters. ADAMTS-13 activity does not influence the bleeding phenotype in individuals with VWD.
Hemophilia A is an X chromosome-linked bleeding disorder caused by the deficiency of coagulation factor VIII (FVIII). The majority of the Indian population with hemophilia A use plasma-derived clotting factors and, in some instances, fresh frozen plasma and cryoprecipitate. Safer and more efficient treatment options are needed for this group of patients.

To assess the safety of turoctocog alfa, a third-generation recombinant FVIII molecule, for the treatment and prophylaxis of bleeding episodes in previously treated Indian patients with moderate or severe hemophilia A.

This single-country, multicenter, open-label, nonrandomized trial enrolled 60 patients who received prophylactic treatment with turoctocog alfa for 8weeks, which corresponded to a minimum of 20 exposure days. Confirmed development of FVIII inhibitors during the 8-week treatment period was evaluated. Other assessments included frequencies of adverse drug reactions (ARs), serious adverse reactions, drug-related allergic reactions, and infusion reactions during the 12-week period after the first treatment; hemostatic effect of turoctocog alfa for the treatment of bleeding episodes; and total annualized dose of turoctocog alfa administered during the 8-week treatment period.

No incidence of FVIII inhibitors was detected. No safety concerns such as ARs, serious ARs, or drug-related allergic reactions were noted. The hemostatic success rate for the treatment of bleeding episodes with turoctocog alfa was 81.6%.

The trial results demonstrated that turoctocog alfa is a safe treatment option for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with hemophilia A in the Indian population.
The trial results demonstrated that turoctocog alfa is a safe treatment option for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with hemophilia A in the Indian population.
Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder characterized by reduced levels (afibrinogenemia, hypofibrinogenemia) or dysfunctional fibrinogen (dysfibrinogenemia), for which fibrinogen supplementation is the mainstay treatment.

To assess the efficacy and safety of human fibrinogen concentrate (FCH) in patients with CFD.

This was a multicenter, noninterventional, retrospective cohort study with a 12-month prospective follow-up period in the United States and Canada. Individuals with CFD who received FCH for the treatment of bleeding, perioperative hemostasis, or prophylaxis were included. Data were collected retrospectively from medical records and every 3months during the prospective period. Hemostatic efficacy was rated by the investigators as effective or ineffective using a 4-point efficacy scale. Annualized bleeding rate (ABR) was summarized for patients who received FCH for routine prophylaxis.

Twenty-two patients were enrolled. FCH treatment was rated effective in treating ≥97.0% of bleeding events, in the retrospective and prospective periods. FCH was effective for perioperative hemostasis in ≥97.5% of minor and major surgeries across both periods. In patients treated with FCH for routine prophylaxis, the median ABRs for the retrospective and prospective period were 1.4 and 1.3, respectively. One adverse event (AE), thrombosis of the right cephalic vein, was reported as related to FCH treatment and resolved with a short course of anticoagulant. No serious AEs related to FCH or deaths were reported.

In patients with CFD, FCH is a well-tolerated and effective treatment to achieve hemostasis during bleeding events and surgery and associated with infrequent bleeding events when used prophylactically.
In patients with CFD, FCH is a well-tolerated and effective treatment to achieve hemostasis during bleeding events and surgery and associated with infrequent bleeding events when used prophylactically.
Replacement therapy is the most common treatment for reduction of bleeding and control of episodic bleeding in individuals with hemophilia. Despite the proven effectiveness of factor replacement therapy, repeated intravenous administration is a heavy burden to individuals with hemophilia.

To reduce the burden, therapeutic agents that can be subcutaneously administered need to be developed, and an anti-tissue factor pathway inhibitor (TFPI) antibody may be a suitable candidate for this purpose.

MG1113 is an IgG4 monoclonal antibody that binds to Kunitz-2 domain (KD2) of TFPI. Selleck JAK inhibitor To confirm the coagulation potential of MG1113, several tests were conducted using factor VIII (FVIII)- or IX (FIX)-deficient plasma. For the ex vivo spiking test, platelet-poor plasma samples from 14 individuals with hemophilia were spiked with MG1113. The in vivo efficacy was determined using blood loss tests, modified prothrombin time (mPT), and free TFPI quantification after intravenous or subcutaneous administration of MG1113 into hemophilia A (HA)-induced rabbits.
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