27 Hemostasis and Coagulation Flashcards
Describe the components of normal hemostasis and laboratory evaluation
Hemostasis:
- Bleeding is controlled through clotting: ?
- Clot breakdown = ?
Hemostasis:
- Bleeding is controlled through clot formation (thrombus)
- Eventual clot breakdown (fibrinolysis)
Describe the components of normal hemostasis and laboratory evaluation
Primary Hemostasis:
- Injury to blood vessel exposes ?
- Two things happen to stop flow:
1. ?
2. ?
Primary Hemostasis:
- Injury to blood vessel exposes collagen below endothelium
- Two things happen to stop flow:
1. Vasoconstriction
2. Platelet Plug formation
Primary hemostasis is a procoagulation clot forming process associated with the initiation and formation of the platelet plug
Primary hemostasis is a procoagulation clot forming process associated w
Platelets:
- 3-4um cell fragments
- Thrombocytes
- Primary hemostasis: Adhesion // Aggregation
- Role in 2° hemostasis
Secondary hemostasis also a procoagulation clot forming process and it is associated with the propagation of the clotting process via the intrinsic and extrinsic coagulation cascades.
Describe the components of normal hemostasis and laboratory evaluation
Platelets:
- what are they? ?
- aka ?
- Encourage primary hemostasis via three major processes: ? // ? // ?
- Role in 2° hemostasis
- activated platelets provide an efficient ? for the assembly of the ? of the blood coagulation system, also known as secondary hemostasis.
Platelets:
- what are they? 3-4um cell fragments
- aka Thrombocytes
- Encourage primary hemostasis via three major processes: Activation // Adhesion // Aggregation
- Role in 2° hemostasis
- activated platelets provide an efficient catalytic surface for the assembly of the enzyme complexes of the blood coagulation system, also known as secondary hemostasis.
Platelets, or thrombocytes, are small, colorless cell fragments in our blood that form clots and stop or prevent bleeding.
- made in our bone marrow (contains stem cells that develop into red blood cells, white blood cells, and platelets)
- component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot.
Describe the components of normal hemostasis and laboratory evaluation
Platelet Adhesion:
- ? on platelet binds to ? (soluble glycoprotein) which binds to exposed ?
Activated platelets change ?, express ?, and release ?
Adhesion:
- Glycoprotein Ib/IX on platelet binds to von Willebrand Factor (soluble glycoprotein) which binds to exposed collagen
Activated platelets change shape, express fibrinogen receptors, and release granules
Aggregation
Glycoprotein IIb/IIIa
binds
Fibrinogen (soluble protein) binds Glycoprotein IIb/IIIa
Describe the components of normal hemostasis and laboratory evaluation
Platelet Aggregation:
Glycoprotein ?
binds
? (soluble protein)
binds
?
Platelet Aggregation:
Glycoprotein IIb/IIIa
binds
Fibrinogen (soluble protein)
binds
Glycoprotein IIb/IIIa
Activated glycoprotein IIb/IIIa receptors become receptive to fibrinogen, and when fibrinogen binds to the glycoprotein IIb/IIIa receptors located on two different platelets it builds the cross-links for platelet-to-platelet aggregation. The glycoprotein IIb/IIIa also mediates platelet adhesion and spreading.
Describe the components of normal hemostasis and laboratory evaluation
What glycoprotein is responsible for platelet aggregation?
Activated glycoprotein IIb/IIIa receptors become receptive to fibrinogen, and when fibrinogen binds to the glycoprotein IIb/IIIa receptors located on two different platelets it builds the cross-links for platelet-to-platelet aggregation.
The glycoprotein IIb/IIIa also mediates platelet adhesion and spreading.
Describe the components of normal hemostasis and laboratory evaluation
Lab Evaluation of Primary Hemostasis:
- ? count
- ?
- ? studies
- ? level and function
- ? level
Lab Evaluation of Primary Hemostasis:
- Platelet count (140-400x10^9/L)
- Morphology
- Platelet Aggregation studies
- Von Willebrand Factor level and function
- Fibrinogen level
Describe the components of normal hemostasis and laboratory evaluation
Secondary Hemostasis:
- Triggered by ?
- Results in ?
- Aids in ?
- Three pathways: ?
Secondary Hemostasis:
- Triggered by Tissue Factor (TF) from epithelial cells at the site of injury
- Results in conversion of Fibrinogen to Fibrin -> Fibrin Clot Formation
- Aids in Clot stabilization
- Three pathways:
1. Intrinsic
2. Extrinsic
3. Common
Secondary hemostasis refers to the cascade of enzymatic reactions that ultimately results in the conversion of fibrinogen to fibrin monomers
Secondary hemostasis is triggered by the release of tissue factor from epithelial cells that are exposed to the circulation at the site of vascular injury. Defects in secondary hemostasis decrease fibrin production and reduce the stability of the formed clot.
Describe the components of normal hemostasis and laboratory evaluation
Secondary Hemostasis: Intrinsic Pathway
- Factors involved:
- ? is activated by collagen
- ? needs other mediators (HMWK, Prekallikrein) to be activated
- ? is a source of phospholipid
- Ca2+-PF3-FVII = ? complex - to activate FX in the common pathway
Secondary Hemostasis: Intrinsic Pathway
- Factors involved: XII // XI // IX // VIII (12, 11, 9, 8)
- FXII is activated by collagen
- FXI needs other mediators (HMWK, Prekallikrein) to be activated
- PF3 = Platelet Factor 3 is a source of phospholipid
- Ca2+-PF3-FVII = Tenase complex - to activate FX in the common pathway
This pathway is the longer pathway of secondary hemostasis. It begins with the activation of Factor XII (a zymogen, inactivated serine protease) which becomes Factor XIIA (activated serine protease) after exposure to endothelial collagen
Describe the components of normal hemostasis and laboratory evaluation
Secondary Hemostasis: Extrinsic Pathway
- Factors involved: 2
- ? is released from injured vessel wall
- ? and ? forms a complex to activate FX in the common pathway
- ? complex can activate FIX in the intrinsic pathway
Secondary Hemostasis: Extrinsic Pathway
- Factors involved: TF // FVII
- Tissue Factor (TF) is released from injured vessel wall
- FVIIa and TF forms a complex to activate FX in the common pathway
- FVIIa:TF can activate FIX in the intrinsic pathway
The extrinsic pathway is the shorter pathway of secondary hemostasis.
Once the damage to the vessel is done, the endothelial cells release tissue factor which goes on to activate factor VII to factor VIIa.
Factor VIIa goes on to activate factor X into factor Xa
Describe the components of normal hemostasis and laboratory evaluation
Secondary Hemostasis: Common Pathway
- Factors involved: 4
- ? is activated from both pathways
- ? ? and ? helps with thrombin production
- ? is produced
- ? forms a stable Clot
Secondary Hemostasis: Extrinsic Pathway
- Factors involved: X, V, II, I
- FX is activated from both pathways
- FV Ca+2 and PF3 helps with thrombin production
- Fibrin is produced
- FXIII forms a stable Clot
PF3 = platelet factor 3
Coagulation Cascade
Describe the coagulation cascade in vitro
How does in-vivo differ?
Intrinsic: Collagen activates FXII to FXIIa: 12→11→9→8→10 (common)
Extrinsic: 3 + TF + Ca →7→9 (intrinsic) // 10 (common)
Common: X + FV (5) + Ca → Prothrombin (FII) + Ca + PF3 + FV (5) → Thrombin (FIIa) →Fibrinogen → Fibrin
In vivo, Thrombin (FIIa) activates Factors 5, 7, 8, 11, 13
PF3 = Platelet factor 3
Describe the components of normal hemostasis and laboratory evaluation
Lab Evaluation of Secondary Hemostasis:
- PTT =?
- PT-INR = ?
- ?
- Patient plasma used to measure ? to ?
Lab Evaluation of Secondary Hemostasis:
- PTT =Activated Partial Thromboplastin Time
- PT-INR = Prothrombin Time
- Fibrinogen
- Patient plasma used to measure time (seconds) to clot
If one or more factors are reduced, clotting time is prolonged
Fibrinogen is helpful
PT time (seconds) converted to ratio (INR) for standardization
PTT measures intrinsic (Factors 12,11,9,8) and Common (Factors X, V, II, I) Pathway
PT measures extrinsic (VII) and common (X, V, II, I) pathways
Discuss acquired bleeding disorders and give examples
- Alcohol:
- Liver and Kidney failure
- Cardiopulmonary Bypass
- Some marrow failure syndromes and hematologic disorders
- Acidosis, Hypothermia, Hypocalcemia
- Disseminated Intravascular Coagulopathy (DIC)
Alcohol: interferes with the clotting process in a couple of ways:
- reduces number of platelets in the blood, in part by interfering with blood cell production in the bone marrow.
- It makes the platelets you do have less sticky.
Platelet disorders are the most common cause of bleeding disorder and are usually acquired rather than inherited.
Discuss acquired bleeding disorders and give examples
- Alcohol
- Liver and Kidney failure
- Cardiopulmonary Bypass
- Some marrow failure syndromes and hematologic disorders
- Acidosis, Hypothermia, Hypocalcemia
- Disseminated Intravascular Coagulopathy (DIC)
The liver plays a central role in the clotting process, and acute and chronic liver diseases are invariably associated with coagulation disorders due to multiple causes:
- decreased synthesis of clotting and inhibitor factors,
- decreased clearance of activated factors,
- quantitative and qualitative platelet defects,
- hyperfibrinolysis, and
- accelerated intravascular coagulation
Platelet dysfunction is the main factor responsible for hemorrhagic tendencies in advanced kidney disease. Anemia, dialysis, the accumulation of medications due to poor clearance, and anticoagulation used during dialysis have some role in causing impaired hemostasis in ESRD patients
Platelet disorders are the most common cause of bleeding disorder and are usually acquired rather than inherited.