hema 2 Flashcards
(102 cards)
1
Q
Hemostasis
A
Process of cessation/stopping of bleeding (in the presence of vessel injury) thru clot formation & dissolution
2
Q
Clot dissolution
A
prevents unwanted/excessive clot formation with the help of
circulating INHIBITORS
3
Q
Prothrombotic substance
A
induces production of clot
4
Q
Antithrombotic/fibrinolytic
A
induces blood clot dissolution
5
Q
Antithrombotic/fibrinolytic
A
induces blood clot dissolution
6
Q
Primary hemostasis
A
Vasoconstriction→ Platelet Adhesion→ Platelet Aggregation→ Platelet Secretion
7
Q
Secondary Hemostasis
A
Coagulation → Fibrin Clot Formation → Fibrin Stabilization
8
Q
Inhibitors
A
A substance that retards or stops a process or chemical reaction Inhibit either coagulation or fibrinolysis
9
Q
Thrombus
A
A blood clot that obstructs a blood vessel
10
Q
Embolus
A
A mass (clot) of blood or foreign matter
carried in the circulation Dislodged thrombus
11
Q
Coagulation
A
- Process of forming a FIBRIN CLOT
Clinical significance: - Defected coagulation factors may cause excessive blood clotting
- Disseminated Intravascular Coagulation (DIC)
- Continuous blood clot formation
Treatment: use of anticoagulant (heparin / warfarin) as therapy
- Continuous blood clot formation
12
Q
Fibrinolysis
A
- Enzymatic breakdown of blood clot
- Fibrinolytic factors are activated
when the injured vessel has
developed a stable fibrin clot - Blood clot inside the vessel must be
dissolved to avoid thrombus
13
Q
Arteriosclerosis
A
Abnormal thickening and hardening of the arterial walls, causing loss of elasticity & impaired blood circulation
14
Q
Atherosclerosis
A
A form of arteriosclerosis in which lipids, calcium, cholesterol, and other substances deposit on the inner walls of the arteries
15
Q
Monophyletic
A
- All blood cells are derived from single progenitor cells
- The widely accepted theory
- The Pluripotential hematopoietic stem cell
16
Q
Polyphyletic
A
Suggests that all cell lineages have its own stem cell of where it came from
17
Q
Myeloid progenitor
A
gives rise to the RBCs, platelets, and WBCs (except
lymphocytes) precursors.
18
Q
cytoplasmic fragmentation of megakaryocytes
A
Platelets are formed through this. (platelet precursor) during thrombopoiesis / platelet shedding
19
Q
Lymphoid progenitors
A
gives rise T cell, NK cell, and B cell precursors.
20
Q
Vascular Intima
A
Innermost vascular lining (made out of Simple SECs)
Endothelial Cells (Endothelium) – comprising the epithelium is involved in clotting process by producing and storing clotting components, which will be secreted to activate platelets and coagulation factors.
Supporting the ECs – Internal elastic lamina composed of elastin & collagen (fibroblasts)
Sub-endothelial CT – Veins (Collagen & Fibroblast) / Artery (Collagen,
Fibroblast & Smooth Muscle Cells)
Fibroblasts produce collagen
21
Q
Vascular Intima
A
Innermost vascular lining (made out of Simple SECs)
Endothelial Cells (Endothelium) – comprising the epithelium is involved in clotting process by producing and storing clotting components, which will be secreted to activate platelets and coagulation factors.
Supporting the ECs – Internal elastic lamina composed of elastin & collagen (fibroblasts)
Sub-endothelial CT – Veins (Collagen & Fibroblast) / Artery (Collagen,
Fibroblast & Smooth Muscle Cells)
Fibroblasts produce collagen
22
Q
Vascular Media
A
Middle layer
23
Q
Vascular Adventitia
A
Outermost layer
24
Q
CONNECTIVE TISSUE MATRIX
A
Regulates the permeability of the inner vessel wall
Site where the important substances needed for activation is found (subendothelial collagen)
25
ENDOTHELIUM
Highly active metabolically due to its stored components needed for hemostasis, coagulation, and fibrinolysis.
Involved in clotting process by producing or storing clotting components
Releases prothrombotic components when injured
Releases antithrombotic /fibrinolytic components once healed.
26
NORMAL HEMOSTASIS
PRIMARY (Coagulation)→ SECONDARY (Coagulation)→ FIBRINOLYSIS (Blood Clot Dissolution)
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2 MAJOR PARTS OF PHYSIOLOGIC HEMOSTATIC SYSTEM
CELLULAR COMPONENT
PLASMA PROTEINS
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CELLULAR COMPONENT
Platelets
Endothelial cells
Neutrophils
Monocytes
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PLASMA PROTEINS
Group of plasma proteins which participates in:
* Clot Formation (Coagulation)
* Dissolution of Clots (Fibrinolysis)
* Naturally Occurring Serine Protease
Inhibitions (Anti-Coagulation)
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VASCULAR DAMAGE
Upon injury, the body immediately constricts blood vessel to decrease blood flow Not only the endothelial cells are affected, but also the connective tissue matrix The damaged CT collagen (sub-endothelial) then activates platelets Platelet activation is then followed by adhesion, aggregation, and secretion
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VASOCONSTRICTION
Narrowing of the diameter of blood vessels
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von Willebrand Factor (vWF)
Promotes platelet adhesion
Binds to PLATELET via platelet glycoprotein membrane receptor (GP Ib/IX/V)
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CLINICAL SIGNIFICANCE Bernard-Soulier Syndrome (BSS)
Absent: GP Ib/IX/V platelet membrane receptor Structure: Giant platelet s/ macrothrombocytes Risk: Bleeding tendencies
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CLINICAL SIGNIFICANCE Bernard-Soulier Syndrome (BSS)
Absent: GP Ib/IX/V platelet membrane receptor Structure: Giant platelet s/ macrothrombocytes Risk: Bleeding tendencies
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CLINICAL SIGNIFICANCE vWF Disease
vWF: Absent or Defective
No platelets can attach to subendothelium Risks: Bleeding tendencies
36
Platelet adhesion REVERSIBLE
Platelet binds to NON-PLATELET SURFACES (Sub-endothelial Collagen) Activation → change in structure → exposure of GP Ib/IX/V → vWF linkage to the receptor → which will then link the PLATELET to exposed sub-endothelial COLLAGEN
37
Platelet aggregation IRREVERSIBLE
PLATELET binds to one another (PLATELET ↔ PLATELET)
When platelets are activated → exposure of GP IIb/IIIa receptor → allows binding of FIBRINOGEN (in the presence of calcium) as well as vWF and FIBRONECTIN → which will then allow binding of one platelet to another
38
Fibrinogen (Factor I)
Binds to GP IIb/IIIa receptors on adjacent platelet and joins them together in the presence of IONIZED / ACTIVATED CALCIUM (Ca2+)
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CLINICAL SIGNIFICANCE Glanzmann Thrombasthenia
Absent: GP IIb/IIIa platelet membrane receptor
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CLINICAL SIGNIFICANCE Afibrogenemia
Lack of Fibrinogen (Total absence)
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CLINICAL SIGNIFICANCE Hypofibrogenemia
↓ Levels of normal fibrinogen
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CLINICAL SIGNIFICANCE Dysfibrogenemia
Dysfunctional/Defective fibrinogen
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Risks
Bleeding and compromised platelet aggregation
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PLATELET SECRETION IRREVERSIBLE
Platelets discharged the contents of their granules RODAKS: Occurs during AGGREGATION
HENRY’S: Occurs during the late stage of platelet activation
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Platelet α-granules (Large Molecules)
β-Thromboglobulin Factor V
Factor XI
Protein S Fibrinogen
VWF
Platelet Factor 4 Platelet-Derived Growth Factor
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Platelet Dense Granules (Small Molecules)
Adenosine diphosphate (activates neighboring platelets) Adenosine triphosphate Calcium (helps platelets clump) Serotonin (Vasoconstrictor)
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During Activation
ADP and Ca2+ → Activates → Phospholipase A2
Phospholipase A2 → converts Membrane Phospholipids → into Arachidonic Acid Cyclooxygenase → converts Arachidonic Acid → into Prostaglandin Endoperoxidase
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In Platelet
Prostaglandins with the action of Thromboxane Synthetase → activates
Thromboxane A2
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Thromboxane A2
Caused ionized calcium to be release Promoted platelet aggregation Promotes Vasoconstriction
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Aspirin Acetylation / Aspirin Like Effect
Permanently inactivates CYCLOOXYGENASE Blocks THROMBOXANE A2 production Impairment of PLATELET FUNCTION (Aspirin Effect)
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Platelet Membrane
Key surface for coagulation enzyme-cofactor-substrate complex formation
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Zymogens (Procoagulants)
Inactive form of enzymes
* Pre-Kallikrein
* FXII
* FXI
* FIX
* FX
* FVII
* Prothrombin (FII) * FXIII
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Cofactors
Binds, stabilized,and enhance activity of their respective enzymes / zymogens
* HMWK
* Tissue Factor
* FVIII
* FV
* Protein Z
* Protein S
* Thrombomodulin
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Control protein
Serve the important function of regulating the coagulation process to avoid unnecessary blood clotting
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Fibrinogen substrate
Fibrinogen is the substrate for the enzymatic action of thrombin (the primary enzyme of the coagulation system).
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When a PROCOAGULANT becomes ACTIVATED
A lowercase “a” appears behind the numeral
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become activated in the coagulation process.
Both ZYMOGENS & COFACTORS
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Factor I
Fibrinogen
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Factor II
Prothrombin
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Factor III
Tissue Thromboplastin (crude mixture of TF and Phospholipid)
Tissue factor (in other references)
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Factor IV
Calcium is referred to by its name or chemical symbol NOT by its numeral
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Factor V
Proaccelerin
Labile Factor, Ac globulin
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Factor VI
VI was withdrawn from the naming system and never reassigned because it was known that it is just the activated form of Factor V
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Factor VII
Proceonvertin
Stable Factor, SPCA (1949) serum prothrombin conversion accelerator
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Factor VIII
Antihemophilic Factor
AHG, Antihemophilic Factor A
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Factor IX
Plasma Thromboplastin Component
Christmas Factor, Antihemophilic Factor B
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Factor X
Stuart Factor
Stuart-Prower Factor
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Factor XI
Plasma Thromboplastin Antecedent
PTA, Antihemophilic Factor C
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Factor XII
Hageman factor
Glass or contact factor
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Factor XIII
Fibrin-stabilizing factor
FSF
71
Prekallekrein
Fletcher factor
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HMW Kininogen
Fitzgerald factor
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vWF
Factor VIII –related antigen
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FIBRINOGEN GROUP
I, V, VIII, XIII
Consumed during the process of coagulation Absent in serum
CALCIUM DEPENDENT
Vitamin K
INDEPENDENT
75
PROTHROMBIN GROUP
II, VII, IX, X
Adsorbable & affected by Coumadin (PIVKAS)
CALCIUM AND Vitamin K
DEPENDENT
INHIBITED by Warfarin
76
CONTACT GROUP
XI, XII, PK, HMWK
NOT consumed during the process of coagulation Present in serum
Calcium and vitamin K
INDEPENDENT
Involved in INTRINSIC Coagulation Pathway
77
Intrinsic pathway
* Reaction system that begins with FXII and culminates in fibrin polymerization
* Coagulation experts identified the activation of FXII as the primary step in coagulation because this factor could be found in blood, whereas TF could not. * XII, pre-K, HMWK, XI, IX, VIII, X, V, prothrombin (II), and fibrinogen (I)
* IXa:VIIIa complex in the intrinsic pathway is crucial to the activation of factor X.
Laboratory Test: PT, APTT (measures XII, XI, IX, VIII)
78
Extrinsic Pathway
Extrinsic Pathway
Formation of TF:VIIa has since proven to be the primary in vivo initiation mechanism for coagulation.
TF is NOT PRESENT in blood (released only if there is injury) VII, X, V, prothrombin (II), and fibrinogen (I)
Laboratory Test: PT
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Common pathway
Two pathways have in common: FX, FV, FII (Prothrombin), FI (Fibrinogen)
80
INITIATION
occurs on tissue factor-expressing cells and produces 3% to 5% of the total thrombin generated
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PROPAGATION
occurring on platelets, which produces 95% or more of the total thrombin.
82
Initiation phase
Refers to extrinsic tenase complex formation and generation of small amounts of FXa, FIXa, and thrombin.
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FVIIa
1%-2% - normally present in blood in activated form Mostly needed to be activated by TF
84
Fibroblast & other sub-endothelial cells
Provide TISSUE FACTOR
85
Tissue Factor
Cofactor to FVIIa
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Propagation phase
Reactions occur on the surface of the activated platelet, which now has all the components needed for coagulation
Platelets are activated at the site of injury by both the low-level thrombin generated in the initiation phase and by adhering to exposed collagen.
87
Cofactors of FVa and FVIIIa
Activated by thrombin in the initiation phase bind to platelet membranes and become receptors for FXa and FIXa
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FIXa
Generated in the initiation phase binds to FVIIIa on the platelet membrane to form the intrinsic tenase complex IXa:VIIIa
89
FXa binds to FVa to form the prothrombinase complex
Activates prothrombin and generates a burst of thrombin (produces 95% or more)
90
Thrombin (FIIa)
Cleaves fibrinogen into a fibrin clot
Activates factor XIII to stabilize the clot
Binds to thrombomodulin to activate the protein C control pathway
Activates TAFI to inhibit fibrinolysis.
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FIBRINOLYSIS
FINAL STAGE of hemostatic activation
Fibrin degradation; restoring normal blood flow during vascular repair Systematic, accelerating hydrolysis of fibrin and plasmin
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2 ACTIVATORS OF FIBRINOLYSIS
Tissue Plasminogen Activator (TPA)
Urokinase Plasminogen Activator (UPA)
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PLASMINOGEN
Inactive form of PLASMIN present in circulating blood.
The 2 activators of fibrinolysis activates and converts plasminogen to plasmin Plasmin will then hydrolyze the fibrin clot
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TISSUE PLASMINOGEN ACTIVATOR (TPA)
TPA released from endothelial cells converts Plasminogen to Plasmin. Plasmin breaks down Fibrinogen & Stable Fibrin Clot creating fragments: Fibrin Monomer Degradation Product & Cross-linked Degradation Products (contains D- Dimers)
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UROKINASE PLASMINOGEN ACTIVATOR (UPA)
An intrinsic plasminogen activator secreted by urinary tract epithelial cells, monocytes, and macrophages
Converts Plasminogen to Plasmin
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Fragment X
The central E domain with the two D domains (D-E-D), minus some peptides cleaved by plasmin
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Fragment Y
The E domain after cleavage of one D domain (D-E).
D-E fragments are further digested to individual D & E Domains.
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Fragment XYDE
Produced by digestion of either fibrin or fibrinogen by plasmin
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Fragment D-D (D-Dimer)
Composed of two D domains from separate fibrin molecules (NOT FIBRINOGEN) cross-linked by the action of factor XIIIa
Specific product of digestion of cross-linked fibrin only Marker of thrombosis (stabilized clot) and fibrinolysis (dissolution of stabilized clot)
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Plasminogen Activator Inhibitor-1 (PAI-1)
Principal inhibitor of plasminogen activation, inactivating both TPA and UPA, thus preventing them from converting plasminogen to the active fibrinolytic enzyme plasmin.
101
a2-antipaslmin
Synthesized in the liver and is the primary inhibitor of free plasmin Only a small amount of plasmin is technically present in blood, circulating
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Thrombin Activatable Fibrinolysis Inhibitor
Synthesized in the liver
Activated by the thrombin-thrombomodulin complex Activated TAFI: Functions as an anti-fibrinolytic enzyme
