Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

Anticoagulant Drugs: Low-Molecular-Weight Heparins

1.3K
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
1.3K
Clot Retraction and Fibrinolysis01:16

Clot Retraction and Fibrinolysis

7.8K
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
7.8K
Extrinsic and Intrinsic Pathways of Hemostasis01:20

Extrinsic and Intrinsic Pathways of Hemostasis

10.7K
Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which...
10.7K
Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants01:18

Anticoagulant Drugs: Vitamin K Antagonists and Direct Oral Anticoagulants

1.6K
Oral anticoagulants are vital tools in preventing and treating blood clotting disorders. This diverse class of medications can be categorized as vitamin K antagonists, exemplified by warfarin, and direct thrombin inhibitors (DTIs), such as dabigatran, as well as factor Xa inhibitors, including rivaroxaban.
Warfarin, a prominent vitamin K antagonist family member, exerts its effect by inhibiting the enzyme VKORC1 (vitamin K epoxide reductase complex 1). By hindering this enzyme, warfarin...
1.6K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

3.0K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
3.0K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

6.2K
Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
6.2K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same authorSame journal

Factor VIII Aurora: A Naturally Occurring Gain of Function FVIII Variant with Enhanced FIXa Affinity.

Blood·2026
Same author

One-stage Assay Factor VIII Activity Reflects AAV-Derived Factor VIII-Enhanced Thrombin Activation and Predicts Phenotype.

Blood·2026
Same author

Neuroepithelial Tumor with AAV Integration after Intracisternal Magna Vector Delivery.

The New England journal of medicine·2026
Same author

Factor IXa and factor X influence factor VIIIa stability and inactivation mechanisms in vitro and in vivo.

Blood·2025
Same author

Blood Coagulation Factor IX: Structure, Function, and Regulation.

IUBMB life·2025
Same author

Loss of factor VIII in zebrafish rebalances antithrombin deficiency but has a limited bleeding diathesis.

Blood advances·2025

Related Experiment Video

Updated: Nov 19, 2025

Helical Organization of Blood Coagulation Factor VIII on Lipid Nanotubes
12:24

Helical Organization of Blood Coagulation Factor VIII on Lipid Nanotubes

Published on: June 3, 2014

12.5K

Activated protein C has a regulatory role in factor VIII function.

Amelia R Wilhelm1,2, Nicole A Parsons3, Benjamin J Samelson-Jones1,2,4

  • 1Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA.

Blood
|January 29, 2021
PubMed
Summary

Activated protein C (APC) regulates factor VIIIa (FVIIIa) in vivo, contrary to previous assumptions. An APC-resistant FVIII variant showed significantly enhanced hemostatic function in hemophilia A mouse models.

More Related Videos

Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
13:08

Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay

Published on: September 9, 2012

19.2K
Tail Vein Transection Bleeding Model in Fully Anesthetized Hemophilia A Mice
08:13

Tail Vein Transection Bleeding Model in Fully Anesthetized Hemophilia A Mice

Published on: September 30, 2021

6.9K

Related Experiment Videos

Last Updated: Nov 19, 2025

Helical Organization of Blood Coagulation Factor VIII on Lipid Nanotubes
12:24

Helical Organization of Blood Coagulation Factor VIII on Lipid Nanotubes

Published on: June 3, 2014

12.5K
Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
13:08

Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay

Published on: September 9, 2012

19.2K
Tail Vein Transection Bleeding Model in Fully Anesthetized Hemophilia A Mice
08:13

Tail Vein Transection Bleeding Model in Fully Anesthetized Hemophilia A Mice

Published on: September 30, 2021

6.9K

Area of Science:

  • Hematology
  • Biochemistry
  • Thrombosis and Hemostasis

Background:

  • Activated factor VIII (FVIIIa) function is regulated by A2-domain dissociation and activated protein C (APC) cleavage.
  • The in vivo role of APC in FVIIIa regulation is largely unexplored, with biochemical studies suggesting a marginal contribution.

Purpose of the Study:

  • To investigate the in vivo contribution of APC to FVIIIa inactivation.
  • To assess the hemostatic function of an APC-resistant FVIII variant in hemophilia A mouse models.

Main Methods:

  • Comparison of wild-type B-domainless FVIII (FVIII-WT) with an APC-resistant FVIII variant (FVIII-QQ) in plasma-based and mouse models.
  • Tail clip and ferric chloride injury assays in hemophilia A (HA) mice, including HA/FV Leiden (FVL) mice with inhibited APC function.

Main Results:

  • FVIII-QQ exhibited expected APC resistance without altered procoagulant function or A2-domain dissociation.
  • FVIII-QQ demonstrated approximately fivefold increased procoagulant function compared to FVIII-WT in HA mice.
  • Enhanced hemostatic function of FVIII-QQ was confirmed to be APC-specific in HA/FVL mice and when APC function was blocked.

Conclusions:

  • APC plays a significant role in the in vivo regulation of FVIIIa.
  • The APC-mediated regulation of FVIIIa offers a potential target for developing novel hemophilia A therapeutics.