Chapter 4 - Haemodynamic disorders Flashcards
What are the three natural anti-coagulants and how do they work?
(1) The protein C system generates active protein C that inactivates cofactors V and VIII
(2) Antithrombin - activated antithrombin causes proteolysis of active factors IX, X, and XI, and thrombin.
(3) Plasmin - cleaves fibrin
What stage in the formation of a thrombus is an important target of the currently used antithrombotic medications?
Platelet aggregation. This crucial step requires binding of platelets by fibrinogen molecules, which attach to platelets at the GPIIb/IIIa receptor.
- Aspirin inhibits synthesis of thromboxane A2.
- Clopidogrel inhibit ADP-mediated structural alterations in the GPIIb/IIIa receptor, preventing binding of fibrinogen to this receptor.
- Direct GPIIb/IIIa inhibitors are also available.
What are the major differences between a myocardial and a cerebral infarct?
A myocardial infarct typically features coagulative necrosis, which heals by fibrosis and leaves behind a fibrous scar. In contrast, a cerebral infarct is typically liquefactive necrosis, in which dead tissue is digested without being replaced by fibrosis, leaving behind a cystic, cavitary lesion.
What are the two major triggers of DIC?
The two major triggers of DIC are release of tissue factor and endothelial injury.
Common sources of tissue factor include major trauma to tissues, the placenta in obstetric complications, mucus released by adenocarcinomas, bacterial endotoxins
Common triggers of endothelial injury include Microorganisms (e.g., meningococci, rickettsiae), temperature extremes (e.g., heatstroke, burns), and antigen-antibody complexes (e.g., systemic lupus erythematosus)
What induces the conformation change of GpIIb-IIIa receptors to promote platelet aggregation?
ADP
What is contained in Dense granules of platelets?
ADP ATP ionised calcium serotonin epinephrine
What is contained in platelet alpha granules?
Fibrinogen Coagulation factor V vWF Fibronectin Platelet factor 4 PDGF Transforming growth factor Beta
Receptors on activated platelets that form bridging cross-links with fibrinogen, leading to platelet aggregation
Glycoprotein IIb/IIIa
What receptor is important for platelet adhesion to the ECM with vWF?
Glycoprotein Ib
What deficiency is involved with Bernard-Soulier syndrome?
Gp1b
important for platelet adhesion
What deficiency is involved with Glanzmann thrombasthenia?
Glycoprotein IIb-IIIa
Concomitant activation of ___ promotes fibrin deposition, cementing the platelet plug in place
Thrombin
The prothrombin time (PT) assay assesses the function of which proteins
Those in the extrinsic pathway: factors 7, 10, 5, 2 (prothrombin) and fibrinogen
The partial thromboplastin time (PTT) assay screens the function of which proteins
Those in the intrinsic pathway (12, 11, 9, 8, 10, 5, 2 and fibrinogen)
Based on the effects of various factors deficiencies in humans, it is believed that in vivo, what is the most important activator of factor IX?
Factor VIIa/tissue factor complex
