Clotting deficiencies

• What is the role of factor V

  To act as a cofactor to increase thrombin production
• What are the roles of Gla domains in clotting

  To localise the site of injury.
• Which factors use Gla domains

  II, VII, VIII, IX, X.
• Describe how Gla domains work

  Gla domains bind to calcium which allows the factor to bind to the phospholipids on the outside of the platelets.
• What is the molecular name for a Gla domain

  Gama carboxyglutamate each domain consists of 10 of these residues.
• How are Gla domains proudced

  From vitamin K dependant carboxylation.
• How do warfarin and dicumarol work

  They prevent the regeneration of Vitamin K so clotting factors cannot bind to the platelets.
• Describe the structure of II a

  Prothrombin has 10 to 12 glutamic acid residues.
• How is prothrombin activated?

  In the presence of vitamin K, the glutamic acid residues are carboxylated to form Gamma carboxyglutamate residues.
• What are the main causes of clotting issues

  Platelets.

  vitamin K.

  Coagulation factors.
• Which type of haemophilia is the most common

  A
• Which type of haemophilia is the most severe

  A
• Which type of haemophilia is rare

  C
• which type of haemophilia is mild

  C
• What causes haemophilia A

  A deficiency of Factor VIII
• What causes haemophilia B

  A deficiency in factor IX
• What causes haemophilia C

  A deficiency in factor XI
• Which pathways does haemophilia directly affect

  intrinsic
• What is christmas disease

  Haemophilia type B
• How is haemophilia A inheritted

  As a sex-linked recessive condition
• What gene codes for Factor VIII

  Xq28
• Why is haemophilia A the most common

  Because the Xq28 gene which codes for Factor VIII is large and so mutates at a high rate
• Briefly describe Factor V [Abreviate factors such as XII a].

  It is activated by factor II a and acts as a cofactor along with calcium for Factor X a in order to produce more factor II a.
• What are the cofactors for Xa to produce IIa

  Va and calcium
• How is Factor V controlled

  By Protein C
• What is Factor V Leiden

  It is a hypercoagulable disorder.
• Describe the pathology of Factor V Leiden

  The Arginine 506 is substituted for glutamine. This makes the activated Factor V resistant to degradation by protein C.
• What is the presentation of Factor V leiden

  Deep vein thrombosis and pulmonary embolism.
• What are the steps in the formation of a platelet plug

  Adhesion. Activation. Aggregation.
• Describe platelet adhesion

  When the platelet's GP1b receptors bind to collagen and the von Willebrand factor [vWF] this triggers a change in shape.

  Collagen and the vWF factors are only exposed if the blood vessel is damaged.
• What are the symptoms for a deficiency in vWF

  Easy bruising.

  Bleeding gums or nose bleeds.

  Heavy bleeding during menstruation or labour.
• How are platelets activate

  Once their GP1b receptors have bound to collagen and the von Willebrand factor.
• Describe the action of activated platelets

  They release granules for vasoconstriction, platelet activation and the clotting cascade.

  They express surface glycoproteins for aggregation and for fibrin to attach.
• Describe the structure of activated platelets

  Granule release.

  Surface glycoproteins.

  Flat and with many pseudopodia.
• What is thrombocytopaenia

  A platelet deficiency
• What is thrombocytosis

  A High platelet count