scholarly journals Low serum iron levels are associated with elevated plasma levels of coagulation factor VIII and pulmonary emboli/deep venous thromboses in replicate cohorts of patients with hereditary haemorrhagic telangiectasia

Thorax ◽  
2011 ◽  
Vol 67 (4) ◽  
pp. 328-333 ◽  
Author(s):  
John A Livesey ◽  
Richard A Manning ◽  
John H Meek ◽  
James E Jackson ◽  
Elena Kulinskaya ◽  
...  
Keyword(s):  
Factor Viii ◽  
Plasma Levels ◽  
Serum Iron ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Pulmonary Emboli ◽  
Elevated Plasma ◽  
Venous Thromboses ◽  
Low Serum

scholarly journals Hypercoagulability in hereditary hemorrhagic telangiectasia with epilepsy

2015 ◽  
Vol 6 (03) ◽  
pp. 407-409 ◽  
Author(s):  
Josef Finsterer ◽  
Ernst Sehnal
Keyword(s):  
Venous Thrombosis ◽  
Factor Viii ◽  
Plasma Levels ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Intestinal Bleeding ◽  
Recurrent Bleeding ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Recurrent Epistaxis

ABSTRACTRecent data indicate that in patients with hereditary hemorrhagic teleangiectasia (HHT), low iron levels due to inadequate replacement after hemorrhagic iron losses are associated with elevated factor-VIII plasma levels and consecutively increased risk of venous thrombo-embolism. Here, we report a patient with HHT, low iron levels, elevated factor-VIII, and recurrent venous thrombo-embolism. A 64-year-old multimorbid Serbian gipsy was diagnosed with HHT at age 62 years. He had a history of recurrent epistaxis, teleangiectasias on the lips, renal and pulmonary arterio-venous malformations, and a family history positive for HHT. He had experienced recurrent venous thrombosis (mesenteric vein thrombosis, portal venous thrombosis, deep venous thrombosis), insufficiently treated with phenprocoumon during 16 months and gastro-intestinal bleeding. Blood tests revealed sideropenia and elevated plasma levels of coagulation factor-VIII. His history was positive for diabetes, arterial hypertension, hyperlipidemia, smoking, cerebral abscess, recurrent ischemic stroke, recurrent ileus, peripheral arterial occluding disease, polyneuropathy, mild renal insufficiency, and epilepsy. Following recent findings, hypercoagulability was attributed to the sideropenia-induced elevation of coagulation factor-VIII. In conclusion, HHT may be associated with hypercoagulability due to elevated factor-VIII associated with low serum iron levels from recurrent bleeding. Iron substitution may prevent HHT patients from hypercoagulability.

scholarly journals Mice deficient in the anti-haemophilic coagulation factor VIII show increased von Willebrand factor plasma levels

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0183590 ◽  
Author(s):  
Klytaimnistra Kiouptsi ◽  
Alexandra Grill ◽  
Amrit Mann ◽  
Mareike Döhrmann ◽  
Maren Lillich ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Plasma Levels ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Von Willebrand ◽  
Willebrand Factor

Is coagulation factor VIII a useful marker for colorectal carcinoma?

2012 ◽  
Vol 27 (1) ◽  
pp. 20-26
Author(s):  
Vera S. Schellerer ◽  
Larissa Mueller-Bergh ◽  
Susanne Merkel ◽  
Robert Zimmermann ◽  
Dominik R. Weiss ◽  
...  
Keyword(s):  
Pilot Study ◽  
Colorectal Carcinoma ◽  
Factor Viii ◽  
Plasma Levels ◽  
Coagulation Factor ◽  
Coagulation Factor Viii ◽  
Uicc Stage ◽  
Tumor Characteristics ◽  
Thromboembolic Events ◽  
Normal Ranges

Background and Objective Increased thromboembolic events are well known in patients suffering from malignant diseases. In the following pilot study, we investigated the usefulness of coagulation factor VIII (FVIII) as a possible prognostic marker in patients with colorectal carcinoma (CRC). Methods Plasma FVIII levels were measured in 79 patients with CRC, correlated with tumor characteristics, and compared with normal ranges of blood group (BG) 0 and BG A/AB/B and with 19 control patients. Results In CRC patients mean FVIII levels were elevated compared with controls (BG 0: p=0.283, BG A/AB/B: p=0.001) and normal ranges. Interestingly, mean FVIII levels varied significantly in different blood groups (p=0.002). UICC stage I CRC patients presented with mean FVIII plasma levels within normal ranges, whereas UICC stage II-IV CRC patients presented with elevated FVIII plasma levels. In BG A/AB/B a significantly elevated FVIII level was found in G2 compared with G1 tumors (p< 0.001). Patients with elevated carcinoembryonic antigen also showed significantly elevated FVIII levels (p=0.050). FVIII levels at time of surgery did not correlate with survival within the first 2 years following surgery. Conclusion In this pilot study, we demonstrated that FVIII plasma levels are elevated in patients with CRC and affected by T-stage and differentiation of the tumor. Whether FVIII is a clinical useful marker needs to be tested in a larger cohort.

Influence of anticoagulant therapy with vitamin K antagonists on plasma levels of coagulation factor VIII

2010 ◽  
Vol 126 (3) ◽  
pp. 243-245 ◽  
Author(s):  
Serena Maria Passamonti ◽  
Paolo Bucciarelli ◽  
Rossella Bader ◽  
Ida Martinelli
Keyword(s):  
Factor Viii ◽  
Anticoagulant Therapy ◽  
Vitamin K ◽  
Plasma Levels ◽  
Vitamin K Antagonists ◽  
Coagulation Factor ◽  
Coagulation Factor Viii

LDL receptor cooperates with LDL receptor–related protein in regulating plasma levels of coagulation factor VIII in vivo

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 906-912 ◽  
Author(s):  
Niels Bovenschen ◽  
Koen Mertens ◽  
Lihui Hu ◽  
Louis M. Havekes ◽  
Bart J. M. van Vlijmen
Keyword(s):  
Ligand Binding ◽  
Factor Viii ◽  
Plasma Levels ◽  
Dominant Role ◽  
Ldl Receptor ◽  
Coagulation Factor ◽  
Plasma Lipoproteins ◽  
Coagulation Factor Viii ◽  
Related Protein

Abstract Low-density lipoprotein (LDL) receptor (LDLR) and LDLR-related protein (LRP) are members of the LDLR family of endocytic receptors. LRP recognizes a wide spectrum of structurally and functionally unrelated ligands, including coagulation factor VIII (FVIII). In contrast, the ligand specificity of LDLR is restricted to apolipoproteins E and B-100. Ligand binding to the LDLR family is inhibited by receptor-associated protein (RAP). We have previously reported that, apart from LRP, other RAP-sensitive mechanisms contribute to the regulation of FVIII in vivo. In the present study, we showed that the extracellular ligand-binding domain of LDLR interacts with FVIII in vitro and that binding was inhibited by RAP. The physiologic relevance of the FVIII–LDLR interaction was addressed using mouse models of LDLR or hepatic LRP deficiency. In the absence of hepatic LRP, LDLR played a dominant role in the regulation and clearance of FVIII in vivo. Furthermore, FVIII clearance was accelerated after adenovirus-mediated gene transfer of LDLR. The role of LDLR in FVIII catabolism was not secondary to increased plasma lipoproteins or to changes in lipoprotein profiles. We propose that LDLR acts in concert with LRP in regulating plasma levels of FVIII in vivo. This represents a previously unrecognized link between LDLR and hemostasis.

scholarly journals Inhibition of human coagulation factor VIII by monoclonal antibodies. Mapping of functional epitopes with the use of recombinant factor VIII fragments

1989 ◽  
Vol 263 (1) ◽  
pp. 187-194 ◽  
Author(s):  
A Leyte ◽  
K Mertens ◽  
B Distel ◽  
R F Evers ◽  
M J M De Keyzer-Nellen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Factor Viii ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Procoagulant Activity ◽  
Coagulation Factor Viii ◽  
Coagulation Cascade ◽  
Restriction Enzyme Digestion ◽  
Proteolytic Activation

The epitopes of four monoclonal antibodies against coagulation Factor VIII were mapped with the use of recombinant DNA techniques. Full-length Factor VIII cDNA and parts thereof were inserted into the vector pSP64, permitting transcription in vitro with the use of a promoter specific for SP6 RNA polymerase. Factor VIII DNA inserts were truncated from their 3′-ends by selective restriction-enzyme digestion and used as templates for ‘run-off’ mRNA synthesis. Translation in vitro with rabbit reticulocyte lysate provided defined radiolabelled Factor VIII fragments for immunoprecipitation studies. Two antibodies are shown to be directed against epitopes on the 90 kDa chain of Factor VIII, between residues 712 and 741. The 80 kDa chain appeared to contain the epitopes of the other two antibodies, within the sequences 1649-1778 and 1779-1840 respectively. The effect of antibody binding to these sequences was evaluated at two distinct levels within the coagulation cascade. Both Factor VIII procoagulant activity and Factor VIII cofactor function in Factor Xa generation were neutralized upon binding to the region 1779-1840. The antibodies recognizing the region 713-740 or 1649-1778, though interfering with Factor VIII procoagulant activity, did not inhibit in Factor Xa generation. These findings demonstrate that antibodies that virtually inhibit Factor VIII in coagulation in vitro are not necessarily directed against epitopes involved in Factor VIII cofactor function. Inhibition of procoagulant activity rather than of cofactor function itself may be explained by interference in proteolytic activation of Factor VIII. This hypothesis is in agreement with the localization of the epitopes in the proximity of thrombin-cleavage or Factor Xa-cleavage sites.

scholarly journals Characterization and visualization of murine coagulation factor VIII-producing cells in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morisada Hayakawa ◽  
Asuka Sakata ◽  
Hiroko Hayakawa ◽  
Hikari Matsumoto ◽  
Takafumi Hiramoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Factor Viii ◽  
Fluorescent Protein ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Genetically Engineered ◽  
Coagulation Factor Viii ◽  
Liver Sinusoidal Endothelial Cells ◽  
Genetically Engineered Mice

AbstractCoagulation factors are produced from hepatocytes, whereas production of coagulation factor VIII (FVIII) from primary tissues and cell species is still controversial. Here, we tried to characterize primary FVIII-producing organ and cell species using genetically engineered mice, in which enhanced green fluorescent protein (EGFP) was expressed instead of the F8 gene. EGFP-positive FVIII-producing cells existed only in thin sinusoidal layer of the liver and characterized as CD31high, CD146high, and lymphatic vascular endothelial hyaluronan receptor 1 (Lyve1)+. EGFP-positive cells can be clearly distinguished from lymphatic endothelial cells in the expression profile of the podoplanin− and C-type lectin-like receptor-2 (CLEC-2)+. In embryogenesis, EGFP-positive cells began to emerge at E14.5 and subsequently increased according to liver maturation. Furthermore, plasma FVIII could be abolished by crossing F8 conditional deficient mice with Lyve1-Cre mice. In conclusion, in mice, FVIII is only produced from endothelial cells exhibiting CD31high, CD146high, Lyve1+, CLEC-2+, and podoplanin− in liver sinusoidal endothelial cells.

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