Disorders of Clotting Cascade Flashcards
(23 cards)
Defects of which clotting factors may cause prolonged Prothrombin Time?
Factor I, II, V, VII, X
Defects of which clotting factors may cause prolonged Partial Thromboplastin Time?
Factors VIII, IX, X, XI, XII
What is von Willebrand’s factor?
Polymer containing collagen and platelet binding sites which allow the two to adhere together. Fibrinogen adheres to platelets causing aggregation in that area by a positive feedback system.
Which factor in the coagulation cascade is deficient in Haemophilia A?
Factor VIII
What is the epidemiology and genetic link in Haemophilia A?
X linked recessive
Affects 1 in 5000 males
What complication can arise from haematomas in Haemophilia A?
Increased pressure can lead to compartment syndrome and nerve palsies
What would you expect the blood results of a patient with Haemophilia A to show? (APTT, Factor VIII, PT, Bleeding time, vWF)
APTT = Prolonged
Factor VIII = Reduced
PT, bleeding time, vWF = Normal
What is the treatment for bleeding in a patient with Haemophilia A?
Depends how bad the bleed is:
- Mild bleed: Pressure and elevation ± desmopressin (0.3 ug/kg/12hr via IVI over 20 mins)
- Major bleed: Increase Factor VIII levels to 50%
- Life-threatening bleed: Increase Factor VIII levels to 100% by recombinant Factor VIII
What action does desmopressin have to stop bleeding in a patient with Haemophilia A?
Promotes production of vWF
Why is recombinant Factor VIII preferable in patients with Haemophilia A than plasma-derived Factor VIII?
Hep C and HIV infections have historically been associated with plasma-derived Factor VIII so recombinant is much safer
Which factor in the coagulation cascade is deficient in Haemophilia B?
Factor IX
What is the epidemiology and genetic link in Haemophilia B?
X linked recessive
Affects 1 in 30,000 males
True / False - Desmopressin is effective in Haemophilia B?
False. Desmopressin is only effective in Haemophilia A
Describe the different types of von Willebrand’s Disease
Type 1 = Partial deficiency in vWF
Type 2 = Defective vWF
Type 3 = Complete deficiency in vWF
Give 3 functions of von Willebrand’s Factor
- Adheres platelets to exposed sub-endothelium
- Binds platelets together
- Attaches to Factor VIII to stop its destruction in the circulation
What would you expect the blood results of a patient with Haemophilia A to show? (APTT, PT, bleeding time, vWF, Factor VIII, platelets)
APTT = Prolonged PT = Normal Bleeding time = Prolonged vWF = Decreased Factor VIII = Decreased Platelets = Normal
How would you manage a patient with von Willebrand’s Disease?
- Expert help
- Desmopressin in mild bleeding
- vWF with Factor VIII for surgery or major bleeds
- Avoid NSAIDs
Why is Vitamin K required for clotting?
Activation of Factor II, VII, IX, X
What is the role of ‘antithrombin’ in clotting?
It is a ‘natural anticoagulant’. It’s a serine protease inhibitor. Many coagulation components are serine-based and it acts to inhibit these. Especially active against thrombin (Factor II) and Factor Xa
What is the role of Protein C in clotting?
Another ‘natural anticoagulant’. Protein C is activated by thrombin, and the Activated Protein C cleaves Factor V and Factor VIII. Protein C requires a cofactor, Protein S, and these are both Vitamin K dependent.
Why is the activity of Protein C and Protein S markedly reduced in Warfarin therapy?
Both are Vitamin K dependent.
What is the most common inherited thrombophilia?
Factor V Leiden (or Activated Protein C Resistance)
What is Factor V Leiden?
Factor V is normally degraded by Activated Protein C. These patients have an abnormal Factor V (Factor V Leiden) which cannot be so easily degraded by Protein C and thus there is a higher incidence of VTE. Their Factor V is ‘resistant’ to Activated Protein C.
