Factor V & TFPI Flashcards
Revision: indication of mixing studies result:
a) Corrects
b) Not corrects
a) correct:factor deficiency
b) Not: inhibitor
clinical results of fV east Texas:
What doesn’t make sense about the FV results (Coag profile vs sequencing)
Coag profile: FV not deficient: normal [ ]
Sequ: novel mutation in F5 (A-> G: Ser-> Gly)
What keeps FV inactive
the basic & acidic regions in B domain bind = FV inactive
What activates FV
thrombin or FXa cleaves B domain @
- Thrombin: 709, 1018, 1545
- FXa: 709, 1018, (inefficient at cutting 1545)
=> separating|removing basic &|or acidic region = activate FV
What’s TFPI
- Tissue Factor Pathway Inhibitor
- Anticoagulant protein found circulating in plasma
> binds to & inhibits fXa (1st) & TF: fVIIa (2nd) - but at Hi [TFPIa] = inhibits TF:VIIa
How does TFPia bind to fVa
Basic region (TFPIa) binds to acidic region (fV) bc homologous/same sequences
TFPIa + fV => inhibit fXa inhibit prothrombinase complex
fV east Texas has fV-short
a) how this came to be
b) The affect of a shortened FV
a) A->G muteation => novel splice site in exon 13 of F5 gene= cuts out basic region of fVa
b) Resemble FVa (removal of basic domain) but doesn’t clot (like normal fVa) bc acidic region binds to TFPIa = bleeding
describe what is meant when FV East Texas is classified as an indirect, gain of function mutation
- indirect: TFPIa causes bleeding (effect) not fV
- gain of function: TFPI has a longer half life when bound to fV-short
compare & contrast fV East Texas vs fV-Amsterdam
Contrast: in-frame deletion w/in B-domain
Compare: Basic region of fV removed & acidic retained => works the same = bleeding
Symptoms of FV East Texas (note Fv-Amsterdame is similar)
- moderatley severe bleeding disorder
- easy bruising*
- Epistaxis* (nose bleed)
- bleeding after trauma/injury
- Menorrhagia
