The contribution of low density lipoprotein (LDL) receptor-related protein (LRP) to variance of factor VIII (FVIII) levels in plasma was investigated in thrombotic women through analysis of frequent LRP genotypes. The G allele of the LRP -25C/G polymorphism, predicting increased LRP expression, was associated with 15% and 18% mean reductions of FVIII activity and protein levels, respectively. T...

Increased factor VIII (FVIII) levels are a prevalent and independent risk factor for venous thromboembolism (VTE). The low density lipoprotein receptor-related protein 1 (LRP1) has been associated with FVIII catabolism. After a median of 10 years of the first thrombotic episode, we evaluated FVIII activity levels in 75 patients with VTE and high FVIII levels and in 74 healthy controls. Subseque...

The development of antibodies directed against factor VIII (FVIII) represents a major hurdle in the treatment of hemophilia A. Most anti-FVIII antibodies are identified through their ability to inhibit the FVIII procoagulant activity. Many of them, however, do not interfere with the functional properties of FVIII. Antibodies directed against the B domain belong to this latter category. Here, we...

Factor VIII (FVIII) is a large glycoprotein that is challenging to express both in vitro and in vivo. Several studies suggest that high levels of FVIII expression can lead to cellular stress. After gene transfer, transgene expression is restricted to a subset of cells and the increased FVIII load per cell may impact activation of the unfolded protein response. We sought to determine whether inc...

In endothelial cells, von Willebrand factor (VWF) multimers are packaged into tubules that direct biogenesis of elongated Weibel-Palade bodies (WPBs). WPB release results in unfurling of VWF tubules and assembly into strings that serve to recruit platelets. By confocal microscopy, we have previously observed a rounded morphology of WPBs in blood outgrowth endothelial cells transduced to express...

BACKGROUND Elevated factor VIII (FVIII) has been linked with higher risk of vascular events. We aimed to determine the relationship between FVIII and hypertension in patients with acute ischemic stroke. METHODS FVIII levels and transthoracic echocardiogram reports were reviewed in patients with acute ischemic stroke who presented to our stroke center between July 2008 and September 2011. Pres...

Loss of procoagulant factor VIII (FVIII) function results in pathologic bleeding.Noncovalent binding to vonWillebrand factor (VWF) protects FVIII from degradation and rapid clearance from plasma. FVIII levels in patients with vonWillebrand disease (VWD) type 1 or type 3 are generally reduced concomitant with decreased levels of plasma VWF. Patients with VWF mutations interfering with VWF: FVIII...

第VIII因子（FVIII）はトロンビンによってArg372，Arg740，Arg1689を開裂することにより活性化される．野上らは，FVIII A2ドメインにトロンビンによるArg372開裂を制御する部位が存在することを示した．本研究では，Arg372開裂とFVIII A1ドメイン337～372残基の相互作用に着目した．アラニン置換したFVIII変異体（Y346AおよびD347A/D348A/D349A）は，野生型と比較してトロンビンによる活性化ピーク値が約50％，開裂速度が約10～20％に抑制されたことから，FVIII A1ドメイン346～349残基がArg372による活性化を制御するトロンビン結合部位であることを示した．また，FVIII A1ドメイン337～346残基をヒルゲン配列に置換したFVIII変異体では，トロンビンによるFVIII活性化のピーク値とArg372での開裂速...

INTRODUCTION We report a successful case of immune tolerance to factor VIII (FVIII) inhibitor after a major operation. An attempt was made to induce immune tolerance with inhibitor in a haemophilia A patient, who was required to undergo an above-knee amputation. We opted to give high-dose FVIII infusion with no immunosuppression. OUTCOME The highest preoperative FVIII inhibitor level was 5 BU...

Hemophilia A is the most common X-linked bleeding disorder; it is caused by deficiency of coagulation factor VIII (FVIII). Replacement therapy with rFVIII produced from human cell line is a major goal for treating hemophilia patients. We prepared a full-length recombinant FVIII (FVIII-FL), using the pMFG-P140K retroviral vector. The IRES DNA fragment was cloned upstream to the P140K gene, ...