Fibrinolytic System: DIC Flashcards
Five components of the fibrinolytic system
- Plasminogen
- Plasmin
- Plasminogen activators
- Plasminogen and plasmin inhibitors
- Fibrinogen/fibrin
Five substances in which plasmin is capable of digesting
The fibrinogen group (I, V, VIII, XIII) plus fibrin
What is the general mode of action/function of plasminogen activators?
To convert plasminogen to plasmin
What is the primary plasminogen activator and its source of origin?
Tissue Plasminogen Activator (TPA) and is found in the endothelial cells that line the vessels (fibrinolytic property of the vascular intima)
What is the consequence of a plasminogen activator deficiency?
Thrombosis
What is the general mode of action/function of plasminogen and plasmin inhibitors?
Serves as a check on fibrinolysis by forming an irreversible complex w/ plasminogen or plasmin
What is the primary inhibitor of plasminogen?
Plasminogen Activator Inhibitor 1 (PAI-1)
What is the primary inhibitor of plasmin?
α-2-antiplasmin
What is the consequence of a deficiency in plasminogen?
Thrombosis
What is the consequence of a deficiency in plasmin inhibitors?
Bleeding
This is a substrate in which plasmin acts upon and involves hydrolytic digestion of this by plasmin to form soluble degradation products
Fibrinogen/fibrin
Plasmin has the ability to degrade both fibrinogen and fibrin into a series of well characterized end products known as ____ and ____
- Fibrinogen Degradation Products (FDP)
- Fibrin Degradation Products (FSP)
What are the two early degradation products?
Fragments X and Y
What kind of clotting do fragments X and Y do when fibrin acts on them?
“Slow clotting”
What are the two late degradation products?
Fragments D and E
Fragments D and E have an ____ effect and don’t allow fibrin monomers to line up to form loose bonding
Antipolymerization
What are the final split products generated from one fibrinogen molecule?
2D and 1E
How are degradation products cleared from the body?
?
This is an intermediate degradation product formed when plasmin acts upon fibrin that was transmitted through the action of XIIIa. It is formed because plasmin cannot degrade the cross-linked covalent bonds between the D domains.
D-Dimer
Nomenclature for D-Dimer
DD or D2E
Clinical significance of a positive D-Dimer
Indicates a clot was/is present
Two synonyms for DIC (essay)
- Consumption coagulopathy
- Defibrination syndrome
Seven clinical states associated w/ DIC (essay)
- OB “complications”
- Trauma
- Sepsis
- Intravascular hemolysis
- Liver disease
- Promyelocytic leukemia
- Burn patients
What is the consequence of uncontrolled formation and deposition of fibrin?
Leads to thromboses
Six coagulation components consumed in clotting
I, II, V, VIII, XIII, platelets
What is the consequence of the secondary activation of the fibrinolytic system?
Leads to bleeding
Five coagulation components that are digested by plasmin
I, V, VIII, XIII, fibrin
Clinical presentation of DIC
- Multiple site bleeding
- Epistaxis
- Hematuria
- Oozing from intravascular sites
- Petechiae/purpura
- Renal failure (due to free hemoglobin)
Treatment for DIC
- Treat underlying condition
- FFP and/or platelet txns
- Heparin therapy
- Antifibrinolytic therapy (AMICAR)
Results of CBC w/ DIC
- Schistocytes
- Decreased platelets
Results of a PT and APTT in DIC
Prolonged PT and APTT
Results of a fibrinogen in DIC
Decreased
Results of a platelet count in DIC
Decreased count
Four confirmatory tests for DIC
- Thrombin clotting time (TCT)
- Reptilase test
- FDP/FSP
- D-Dimer
Thrombin clotting time
- Principle
- Expected result
- ?
- Prolonged b/c it takes longer for fibrinogen to form a fibrin clot
Repitlase time
- Principle
- Expected result
- ?
- Prolonged, adding reptilase instead of thrombin to plasma
FDP/FSP
- Principle
- Expected result
- ?
- Positive, more split products and acts as an antithrombin
D-Dimer
- Principle
- Expected result
- ?
- Positive, fibrinogen is influenced by XIII and DDs are left over
Three conditions in which primary fibrinolysis may occur?
- Open heart surgery
- Metastatic prostate cancer
- Lightening strike patients
Blood smear evaluation
- DIC vs. primary fibrinolysis
- DIC: schistocytes
- Primary fibrinolysis: no schistocytes
D-Dimer
- DIC vs. primary fibrinolysis
- DIC: positive
- Primary fibrinolysis: negative
Platelet count
- DIC vs. primary fibrinolysis
- DIC: decreased (consumed in clotting)
- Primary fibrinolysis: Normal
Blood smear
- DIC vs. TTP
- DIC: schistocytes
- TTP: schistocytes
D-Dimer
- DIC vs. TTP
- DIC: positive
- TTP: negative
Platelet count
- DIC vs. TTP
- DIC: decreased
- TTP: decreased
PT
- DIC vs. TTP
- DIC: prolonged
- TTP: usually normal
APTT
- DIC vs. TTP
- DIC: prolonged
- TTP: usually normal
in TTP, microthrombi are deposited through the body in microcirculation composed primarily of ____, not fibrin like in DIC. This is PRIMARY hemostasis.
Platelets
This enzyme is synthesized in the kidney and is secreted mainly by epithelial cells in the urinary tract
Urokinase
Which factor is derived from contact activation
XIIa