Exam 3- antiplatelets and anti-coagulants Flashcards
What are the functions of von-Willebrand Factor? (2)
Substance releases from damaged endothelium which induces platelet adhesion; also stabilizes Factor VIII
Main factor complexes involved in the
a) extrinsic
b) intrinsic
c) central clotting pathways?
a) Tissue Factor / VIIa complex
b) Factor XIII/VI complex
c) V / Xa
How is thrombin activated from prothrombin?
Cleavage by the factor V/Xa complex
How is fibrin activated from fibrinogen?
Cleavage by thrombin
How does thrombin positively feed back and enhance the clotting response?
Further activates the intrinsic pathway (factor VIII/IX)
Which lab tests assess:
a) the extrinsic pathway
b) the intrinsic pathway?
a) prothrombin time (PT)(and INR)
b) activated partial thromboplastin time (APTT)
Bleeding pattern in a failure of a) primary and b) secondary haemostasis?
a) Mucosal bleeding (e.g. GI, retina, epistaxis)
b) Large haematomas e.g. haemarthroses, intracranial
IgA-mediated vasculitis causing polyarthritis and a palpable purpuric rash over buttocks/extensirs?
Henoch-Schonlein purpura
What is the commonest inherited bleeding disorder and what is its inheritance pattern?
von Willebrand disease; usually autosomal dominant
How does von Willebrand disease presennt?
Presents like a platelet disorder- bruising, mucosal bleeding (e.g. post tooth extraction)
Causes of platelet disorders:
a) decreased production (3)
b) excessive destruction/use (2)
c) poor functioning (2)
a) marrow failure, aplastic anaemia, megaloblastic anaemia
b) immune thrombocytopenic purpura, DIC
c) antiplatelet drugs, uraemia
Causes of multiple clotting factor deficiencies (3)
Liver failure
Vit K deficiency/warfarin
DIC
What does an elevated D-dimer suggest?
Active clotting somewhere in the body; feature of DVT/PE and DIC
X-linked inherited conditions with recurrent haemarthroses and soft tissue bleeds
Haemophilias A (factor XIII deficiency) and B (factor IX deficiency)
Why is APTT deranged in the haemophilias?
APTT measures the intrinsic pathway; which is mediated by factors VIII and IX
What is Virchow’s triad?
Stasis
Hypercoagulability
Endothelial injury/dysfunction
Give examples of hereditary thrombophilias? (5)
Factor V Leiden Antithrombin deficiency Protein C deficiency Protein S deficiency Prothrombin 20210
How should hereditary thrombophilias be managed? (3)
Risk minimization
Short term prophylaxis to cover times of known risk e.g. pregnancy, surgery
Long-term anticoagulation if recurrent thromboses
What is interesting about antiphospholipid syndrome?
Predisposes to both arterial and venous thromboses
Risk factors for venous thrombosis (6)
Surgery Immobility Pregnancy, oral contraceptive pill, HRT Age Obesity Varicose veins/venous insufficiency
Main risk factors for arterial thrombosis (4)
Hypertension
Smoking
High cholesterol
Diabetes
Mechanism of action of asprin?
Inhibits COX-1, thereby inhibiting production of thromboxane 2
Mechanism of action of clopidogrel?
ADP receptor antagonists
How long prior to surgery should antiplatelets be stopped?
7-10 days
What are the main indications for anti-coagulant drugs? (3)
Venous thrombosis
Atrial fibrillation
Mechanical heart valves
What are the two types of heparin? What is the difference between these?
Unfractioned (“standard”) heparin
Low molecular weight heparin.
LMWH only inhibits Factor Xa
How does heparin work?
Potentiates anti-thrombin binding to clotting factors
Monitoring of heparin:
a) unfractionated
b) LMWH
a) APTT
b) anti factor Xa assay, but routine monitoring not required
What is the advantage of using standard heparin over LMWH?
Standard heparin can be quickly reversed with protamine sulfate; this only works partially for LMWH
In coagulation what is Vitamin K required for?
The reduced form of Vitamin K is required as a co-factor for the carboxylation of the clotting factors 2, 7, 8 and 9
How does warfarin cause anti-coagulation?
Inhibits the reduction of vitamin K
Why is there a transient pro-coagulant state when warfarin is administered and how is this overcome?
Because levels of protein C and S also drop; heparin is used as bridging anticoagulation until the INR is at least 2.0
Drugs which inhibit factor Xa?
NOACs such as rivaroxoban, apixiban
How is warfarin reversed?
VitK and clotting factors
What complication can be caused by long-term heparin?
Osteoporosis
What is the target INR for recurrent PE?
3.5
Why is prescription of rivaroxoban/dabigatran inappropriate for VTE prophylaxis in patients with artificial heart valves?
Not licensed for this indication
Investigations in von-Willebrand disease? (2)
Prolonged bleeding time
APTT may be prolonged
Intrinsic clotting pathway is mediated by which complex of clotting factors?
VIII/IXa
Extrinsic clotting pathway is mediated by which clotting factors?
TF/VIIa
What is the basis of the thrombophilia in Factor V Leiden?
Protein C is unable to break down this mutant version of Factor V
Prothrombin is otherwise known as…
Factor II
