hemostasis and thrombosis Flashcards
What is the platelet membrane consist of and how is it important in coagulation?
it contains phospholipids and when released forms AA that metabolized to Thromboxane A2 (platelet aggregation) they also express receptors P selectin that is necessary for endothelial adhesion
How are platelets activated?
by exposure to collagen, platelet activating factor (PAF), thrombin, vWF and others
What are the granules secreted by platelets?
Factor V, XIII, heparin neutralizer (platelet factor 4 PF4), growth factors for growing more platelets and inflammatory cells, serotonin and histamine, calcium needed for coagulation cascade, ADP needed for platelet aggregation
What facilitates the aggregation and stabilization of platelets?
thromboxane A2, ADP, Fibrinogen and ADP causes changes in Gp IIb-IIIa and fibrinogen to form a bridge between platelets
What does the endothelium have to assist in clotting?
secretes endothelin that causes vasoconstriction
synthesizes Factor III thromboplastin (activates extrinsic)
produces vWF that binds platelets to collagen when exposed to endothelial cells
Coagulation Cascade
- *most clotting factors are synthesized in liver and they circulate in the blood in an inactive form; **activation of many clotting factors need Ca ant platelet phospholipids
- *intrinsic cascade is activated by factor XII by exposure to collagen
- *extrinsic pathway activated by factor III by tissue injury
What stimulates plasmin?
Factor XIIa and endothelial t-PA
What does Protein C inactivate and what disease is caused with protein C resistance?
inactivates Va and VIIIa; mutation to the factor V gene; will cause hyper coagulability states
Protein C and S do not allow deactivation of what factors?
Va and VIIIa
problems with platelets
thrombocytosis: too many
caused by recovery from iron deficiency anemia, secondary to inflammation response and myeloproliferative disorders
thrombocytopenia: too few
liver problems (thrombopoietin)
bone marrow problems
or problems involving destruction of platelets
Heparin Induced Thrombocytopenia
heparin binds to platelet protein PF4 hapten and IgG antibodies bind to the heparin PF4 complex that causes platelet to aggregate, and destroys platelets; this binding also causes endothelial damage
What gene is effected in hemophilias?
X-linked recessive gene
What factor is affected with Hemophilia A and B?
A-factor VIII
B-factor IX
What clotting factor is effected in von Willebrand Disease? What is the result?
VIII is carried on vW so when vW is decreased the factor VIII is no longer circulating as long and decrease in VIII being circulated
When is DIC most likely to occur?
after sepsis, obstetric complications, malignancy and trauma