Coagulation Part I Flashcards
What 2 things does endothelial cell wall injury cause?
- platelet activation
2. coagulation
What will platelets do upon activation?
form a platelet plug (primary hemostasis) as the primary defense against a tear, but they have to be reenforced by coagulation (secondary hemostasis).
What are the two systems of secondary hemostasis that lead to FIBRIN formation?
- intrinsic system
2. extrinsic system
Where do the extrinsic and intrinsic pathways meet in the coagulation cascade?
at the formation of factor X (10)= start of the combined pathway.
What single factor makes up the intrinsic pathway?
Factor VII (7).
What 4 factors make up the extrinsic pathway?
Factors XII (12), XI (11), IX (9), VIII (8)
What 5 factors make up the common pathway?
Factors X (10), V (5), prothrombin, which is converted to thrombin, and then it converts fibrinogen into fibrin!
What factor is not really active in the coagulation cascade?
Factor XII (12). So a person with a factor 12 deficiency will not have any clinical problems (despite the coagulation test done outside of the body indicating that it should be a problem) since it really has no role in blood clotting, when inside the body :)
What is the role of factor XIII (13)?
It is activated by thrombin to cross-link fibrin, forming a stable clot over the platelet plug.
Will a person with factor 13 deficiency be detected by the standard tests (PT or PTT)?
NO. So in this case the person would have a clinical problem, but the coagulation tests would not detect it.
What are the two clotting tests used?
- partial thromboplastin time (PTT)= intrinsic pathway
2. prothrombin time (PT)= extrinsic pathway
What type of surface does the PTT test require to initiate coagulation in the intrinsic system?
negative surface
What initiates the PT test in the extrinsic system?
tissue factor
**If a patient has a prolonged PTT, but a normal PT in what system would you find the defect?
intrinsic system
What is the international normalized ratio (INR)?
gives a value that can be interpreted internationally based on the clotting times of the prothrombin time (PT).
What are the most common bleeding disorders?
Coumadin and heparin overdoses followed by thrombocytopenia, liver disease, and surgical complications.
What is Coumadin (Warfarin)?
blocks the utilization of vitamin K on the vitamin K dependent coagulation factors.
What are the vitamin K dependent coagulation factors?
10, 9, 7, and 2 (prothrombin). All of these proteins are synthesized in the liver, but are not biologically active. Vitamin K allows the carboxylation of glutamine residues to form Gla residue (biologically active).
What could cause a greater than expected response to Coumadin (increased INR or increased PT time)?
- overdose
- suppression of GI flora ability to synthesize vitamin K by antibiotics (low vitamin K and thus more unopposed Coumadin= greater coagulation effect).
- malabsorption of vitamin K
What could cause a lower than expected response to Coumadin (decreased INR or decreased PT time)?
- increased ingestion of leafy vegetables, broccoli, liver, kale (increases vitamin K ).
- genetic variation and hereditary warfarin resistance.
What should you do in the case of Coumadin overdose?
discontinue use and can also give vitamin K, fresh frozen plasma, or prothrombin complex concentrates.
What is Heparin?
negatively charged (anionic) glycosaminoglycan (straight chain of mucopolysaccharides) that binds to and activates ANTITHROMBIN, which leads to inactivation of thrombin and factor 10a, as well as factors 9, 11, and 12.
How do we manage heparin overdose?
withhold heparin (short half life) or give protamine sulfate (not effective for low molecular weight heparins).
What is low molecular weight heparin?
affects thrombin and factor 10a, and has longer half life. Can also be given subcutaneously, thus can be given in outpatient setting. The problem is that there is not a good way to monitor levels, and thus overdose becomes an issue.
How do we monitor heparin dose?
partial thromboplastin time (PTT)
What are the global effects of liver disease?
- thrombocytopenia (low platelets) due to alcoholism or hypersplenism (uses platelets)
- decreased synthesis of coagulation factors
- DIC
- accelerated fibrinolysis
dysfibrinogenemia