Bleeding and Thrombosis Flashcards
What is required for blood clotting?
Abnormal surface
Activator
How does an abnormal surface trigger platelet adhesion?
Von Willebrand factor
Exposed sub-endothelial collagen
Physiological activator
What do platelets have on their surfaces?
Cell surface receptors - molecules released by damaged sites (activation)
Platelet glycoproteins - binding
What is the role of platelets in homeostasis?
Adhere
Activation
Aggregation
Phospholipid surface for coagulation
What is required for binding to Von Willebrand factor?
Glycoprotein 1b
What is needed for a platelet to adhere?
(vWF)
Glycoprotein 1a and 1b
What is required for platelets to activate?
ADP
Epinephrine
COX
What is required for platelets to aggregate?
Thromboxane A2
What is required for platelets to coagulate?
Phospholipid membrane
Scramblase
What is the sequence of scab formation?
Primary homeostatic platelet plug
Fibrin formation
What is deficient in haemophilia B?
Factor IX
What is deficient in haemophilia A?
Factor VIII
Outline the blood clotting cascade
Intrinsic + extrinsic = X–> Xa
Prothrombin to Thrombin
Fibrinogen to Fibrin
What are the natural anti-coagulants?
TFPI (Xa and VIIa)
Protein C and Protein S
Antithrombin
Outline the process of Fibrinolysis
Endothelial cells secrete u/t-PA (plasminogen activator)
Activate plasminogen –> Plasmin
Plasmin breaks down clot
How is fibrinolysis inhibited?
Plasminogen inhibitors
Plasmin inhibitors
What is required for clot formation?
Platelets
von Willebrand factor
Coagulation factors
What is the role of platelets canaliculi?
Allow it to secrete molecules onto its own surface (excretion of alpha and dense granule)
What is the role of scramblase?
“flip” phospholipid membrane to the outside surface for adhesion
What is necessary for the clotting process to begin in the platelet?
Thrombin
ADP
Epinephrine to contact platelets
Aspirin inhibits what to act as an antithrombotic?
COX (cyclo-oxygenase)
conversion of Arachadonic acid to Thromboxane A2
How do Clopidogrel/Ticagrelor work?
Prevent activation - Thrombin/ADP/Epinephrine binding to the platelet
How does Fibrin reach the site of injury?
Fibrinogen binds to platelets, platelets carry it to the injury to then cleave it
What is the intrinsic pathway of clotting?
(extrinsic activates Thrombin) Thrombin activates XI XIa converts IX > IXa to form more X > Xa Xa activates Prothrombin Thrombin cleaves Fibrinogen > Fibrin
What is the extrinsic pathway for clotting?
Factor VII binds to tissue factor to form activate Factor X to Xa
Xa activates Prothrombin
Thrombin converts Fibrinogen –> Fibrin
How does TFPI work?
“deactivates” Factor X and VII
How does activated protein C and protein S work?
Deactivates VIII and V
How does antithrombin work?
Deactivates: Thrombin IX VIII XI X
What is D-dimer?
Fibrin degradation (breakdown) product
How does Warfarin work?
Inhibits vitamin K factors (1972) X, IX, VII, II
How do Abciximab/Tirofiban work?
Prevent Glycoprotein IIb/IIIa work
prevents binding of fibrinogen
How does heparin work?
Inhibit thrombin and activated Xa
How do DOACs Rivaroxaban, Apixaban work?
Stop activated Xa
