Thrombophilia and haemophilia Flashcards
haemostatic disorders have a tendency to bleed
whereas thrombophilias have a
tendency to clot
Haemophilia A
what chromosome and factor
symptoms
inherited lack of factor * carried on the X chromosome
intrinsic clothing cascade
patients present with haemarthrosis , spontaneous bleeding or prolonged bleeding after surgery
treatment of Haemophilia A
Treatment is infusion of recombinant FVIII or desmopressin.(you will need to look up how this works!) 30% of Haemophillia A is spontaneous and associated with no family history. Female carriers of Haemophilia A typically have Factor VIII levels less than 50% of normal.
haemophilia B also known as Christmas disease is characterised by what
lack of factor 9
Treatment is with recombinant factor IX.
Female carriers of Haemophilia B typically have Factor IX levels less than 50% of normal.
VonWillebrands disease
VWD is the by far most common inherited coagulopathy
where is this factor found
Von Willebrands factor is found in the endothelium, and binds to platelet membranes (GP 1b) and has an important role in platelet adhesion. It is also found in the plasma also serves to maintain levels of Factor VIII
autosomal dom or recessive
symptoms of VWD
Presentation is variable but includes epistaxis, menorrhagia or bleeding after surgery. Treatment involves desmopressin and factor VIII.
Acquired coagulopathy
Autoimmune Haemophilia can develop due to antibodies to factor VIII. Liver disease can cause coagulopathy as clotting factors are normally synthesised in the liver. Biliary obstruction can cause coagulopathy as Vitamin K (fat soluble) is not absorbed leading to deficiency of the Vitamin K dependent clotting factors.
what other things can affect the clotting cascade
Clotting can also be effected by hypocalcaemia, hypothermia and by dilution for example my massive blood transfusion.
commonly seen thrombophilias
Factor V Leiden, Protein C and S deficiency, Prothrombin mutation, and Antithrombin (AT) deficiencies.
They are generally Autosomal dominant and have reduced penetrance.
Venous Thrombosis – VTE is a pan-ethnic disorder with incidence increasing with age. The three predisposing influences are
endothelial injury, stasis and hypercoagulability (Virchov’s triad.)
Factor V Leiden Mutation
Activated Factor V is a cofactor of Factor X (thrombin.) It is normally inactivated by Protein C. The FVL mutation removes the preferred site for activated protein C proteolysis on factor V.
Prothrombin Mutation caused by
caused by a point mutation substituting Guanidine for Adensoine at position 20210 in the PT Gene.
Protein S deficiency
PS requires C3-binding protein to provide a further source of PS when functional levels are reduced. Quantitative and functional reductions in PC & PS have also been discovered. Furthermore, reductions in PS also occur when C3-binding protein increases, such as during pregnancy.
Antithrombin deficiency
what drug increases the activity of AT
heparin
thrombosis
clot formation inside BV
embolism
lodging of blockage causing piece of material ( embolus ) inside a blood vessel
commonly blood clots, fat, bubble , air , foreign matter
Antithrombin
what factors is it the primary inhibitor of
substance that limits the blood ability to clot and the primary inhibitor of thrombin , factor 10a and 9a that are required for the generation of thrombin
protein c function
regulates blood clots
acts on factor 8 a and factor 5a
prothrombin time PT (INR)
measures the activity of the extrinsic and common coagulation pathways
often expressed as INR
prolonged PT ( or INR) indicates a factor 8 deficiency
activated partial thromboplastin time (APTT)
measures the activity of the intrinsic pathway and common pathways of coagulation
prolonged APTT indicates a deficiency in factor 12,11,9,8
what gene is factor 8 on
X chromsome - Xq28
what gene is vWF on
chromsome 12
factor 8 Is made in the liver cells
where is vWF made
endothelial cells
whole factors 8 and vWF complex formed
If deficiency in either one then complex won’t be formed so if no 8 then just a vWF complex and vv
factor V leiden
type of thrombophilia
leading to hyper coagulable state
protein c deficiency inactivates what factors
5 8
protein s deficiency causes what
caofactors of protein c defficient
desmopressin (DDAVP)( mild vasoconstrictor ) normally treats diabetes and bedwetting ( nocturnal enuresis) can treat what
haemophilia A and vWF but is severe replace the clotting factors via injection
releases vWF/F8 complexes from the endothelium
thrombophilia - Disorder of the blood that predisposes to thrombosis
Congenital:
Type I is severe deficiency of inhibitors
Rare
Type II less severe elevation of coagulation factors
Common
Acquired
Bed rest, tissue damage, antiphospholipid antibodies
Thromobus may propagate, resolve, become organized or embolize.
if you are on combined oral contraceptive pill what happens
oestrogen affects blood clotting by increasing plasma fibrinogen and the activity of coagulation factors ( factor 8, 10, antithrombin III and inhibitors of coagulation
