Thrombophilia and haemophilia

Question 1

haemostatic disorders have a tendency to bleed

whereas thrombophilias have a

Answer 1

tendency to clot

Question 2

Haemophilia A

what chromosome and factor

symptoms

Answer 2

inherited lack of factor * carried on the X chromosome

intrinsic clothing cascade

patients present with haemarthrosis , spontaneous bleeding or prolonged bleeding after surgery

Question 3

treatment of Haemophilia A

Answer 3

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.

Question 4

haemophilia B also known as Christmas disease is characterised by what

Answer 4

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.

Question 5

VonWillebrands disease
VWD is the by far most common inherited coagulopathy

where is this factor found

Answer 5

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

Question 6

symptoms of VWD

Answer 6

Presentation is variable but includes epistaxis, menorrhagia or bleeding after surgery. Treatment involves desmopressin and factor VIII.

Question 7

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

Answer 7

Clotting can also be effected by hypocalcaemia, hypothermia and by dilution for example my massive blood transfusion.

Question 8

commonly seen thrombophilias

Answer 8

Factor V Leiden, Protein C and S deficiency, Prothrombin mutation, and Antithrombin (AT) deficiencies.

They are generally Autosomal dominant and have reduced penetrance.

Question 9

Venous Thrombosis – VTE is a pan-ethnic disorder with incidence increasing with age. The three predisposing influences are

Answer 9

endothelial injury, stasis and hypercoagulability (Virchov’s triad.)

Question 10

Factor V Leiden Mutation

Answer 10

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.

Question 11

Prothrombin Mutation caused by

Answer 11

caused by a point mutation substituting Guanidine for Adensoine at position 20210 in the PT Gene.

Question 12

Protein S deficiency

Answer 12

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.

Question 13

Antithrombin deficiency

what drug increases the activity of AT

Answer 13

heparin

Question 14

thrombosis

Answer 14

clot formation inside BV

Question 15

embolism

Answer 15

lodging of blockage causing piece of material ( embolus ) inside a blood vessel
commonly blood clots, fat, bubble , air , foreign matter

Question 16

Antithrombin

what factors is it the primary inhibitor of

Answer 16

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

Question 17

protein c function

Answer 17

regulates blood clots

acts on factor 8 a and factor 5a

Question 18

prothrombin time PT (INR)

Answer 18

measures the activity of the extrinsic and common coagulation pathways
often expressed as INR
prolonged PT ( or INR) indicates a factor 8 deficiency

Question 19

activated partial thromboplastin time (APTT)

Answer 19

measures the activity of the intrinsic pathway and common pathways of coagulation
prolonged APTT indicates a deficiency in factor 12,11,9,8

Question 20

what gene is factor 8 on

Answer 20

X chromsome - Xq28

Question 21

what gene is vWF on

Answer 21

chromsome 12

Question 22

factor 8 Is made in the liver cells

where is vWF made

Answer 22

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

Question 23

factor V leiden

Answer 23

type of thrombophilia

leading to hyper coagulable state

Question 24

protein c deficiency inactivates what factors

Answer 24

5 8

Question 25

protein s deficiency causes what

Answer 25

caofactors of protein c defficient

Question 26

desmopressin (DDAVP)( mild vasoconstrictor ) normally treats diabetes and bedwetting ( nocturnal enuresis) can treat what

Answer 26

haemophilia A and vWF but is severe replace the clotting factors via injection

releases vWF/F8 complexes from the endothelium

Question 27

thrombophilia - Disorder of the blood that predisposes to thrombosis

Answer 27

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.

Question 28

if you are on combined oral contraceptive pill what happens

Answer 28

oestrogen affects blood clotting by increasing plasma fibrinogen and the activity of coagulation factors ( factor 8, 10, antithrombin III and inhibitors of coagulation