37 Heritable bleeding disorders Flashcards
What is the platelet receptor for fibrinogen?
What does it do?
Glycoprotein 2β3A.
Platelet activation.
What is the platelet receptor for vWF?
What does it do?
Glycoprotein 1B9.
Platelet adhesion.
How does aspirin act?
Inhibits COX enzymes, inhibiting the formation of thromboxane. Platelets don’t activate.
How does clopidogrel act?
Inhibits ADP receptors on platelets, preventing platelet activation.
How do GIIβ/IIIA antagonists act?
Inhibit fibrinogen binding to platelets.
Which factors are involved in the intrinsic coagulation pathway? (4)
XII.
XI.
IX.
VII.
What initiates the intrinsic coagulation pathway?
Foreign surface.
Which factors are involved in the extrinsic clotting pathway? (2)
VII.
TF.
Which factors are involved in the common coagulation pathway? (4)
X.
V.
II. Thrombin.
Fibrinogen. Fibrin.
What does the APTT measure?
Intrinsic and common pathway function.
What does the prothrombin time measure?
Extrinsic pathway function.
What is the extrinsic pathway activated by?
Tissue factor exposure.
Which anticoagulant factors circulate in the blood? (4)
Protein C.
Protein S.
Anti-thrombin III.
Fibrinolytic system.
Explain the fibrinolytic system.
TPA breaks down plasminogen to plasmin. Plasmin breaks down fibrin.
α2-AP mops up plasmin, protecting clotting pathway.
What are the four types of platelet and vessel wall defects?
Reduced platelet number.
Abnormal platelet function (aspirin).
Abnormal vessel wall (Ehlers-Danlos).
Abnormal platelet-wall interaction (vWD).
Describe the type of bleeding typically seen in platelet/vascular defects. (4)
Petechiae.
Skin and mucous membranes.
Spontaneous.
Immediate and non-recurrent.
Describe the type of bleeding seen in coagulation defects? (4)
Deep haematoma.
Haemarthrosis.
Retroperitoneal.
Prolonged and often recurrent.
What are the three types of von Willebrand disease?
- Decreased amount.
- Normal amount of low molecular weight polymer.
- Absent molecule.
Which coagulation factor acts as a carrier protein for von Willebrand factor?
VIII.
What are the features of von Willebrand disease?
Inheritance?
Variable reduction in FVIII levels.
Mucotaneous, post operative and post-partum bleeding.
Autosomal dominant.
How is vWD treated? (5)
Antifibrinolytics: tranexamic acid. DDAVP. vWF concentrates. Hepatitis vaccination. COCP for menorrhagia.
How does DDAVP work? (vWD Rx).
Increases release of vWF from stores.
Temporary effect that decreased on repeat dosing.
Which hereditary coagulation factor deficiency is common in the Ashkenazi Jew population?
FXI.
Which coagulation factor deficiency does not constitute a bleeding disorder?
FXII.
Which coagulation factor deficiencies lead to a prolonged APTT?
XII.
XI.
IX.
VIII (vWD and haemophilia).
Which coagulation factor deficiency leads to a prolonged PT?
VII.
Which coagulation factor deficiencies lead to a prolonged APTT and PT? (5)
X. V. II. I. XIII.
What are deficiencies seen in Haemophilia?
A: VIII.
B: IX.
How is haemophilia inherited?
X linked recessive.
Expressed in males, carried in females.
Doesn’t get worse through generations.
What are the degrees of severity in haemophilia?
Mild: 6-50%.
Moderate: 1-5%.
Severe: less than 1%
How is haemophilia treated? (5)
Missing protein replacement. DDAVP. Recombinant factor concentrates. Antifibrinolytics. Vaccination against Hep A + B.
What is the major complication of haemophilia treatment?
Treated?
Inhibitor development.
Occurs in A > B.
Results in poor response to treatment.
Rx: eradication of inhibitor through very high dosage.
Name 6 causes of bleeding with normal coagulation screens.
Thrombocytopenia. Platelet abnormalities. vWD. Factor XIII deficiency. Vascular disorder. Disorder of fibrinolysis.
