Hema-Lec-Hemostasis Flashcards
Complex physiologic process
Hemostasis
Simple physiologic process of hemostasis
Injury—>produces a clot to stop the bleeding—> Confines the clot to the site of injury—>Finally dissolves the clot as the wound heals
absence of a single
plasma procoagulant
Anatomic hemorrhage
Absence of a control protein leads to (5)
thrombosis,
stroke, pulmonary embolism, deep vein thrombosis and cardiovascular events
Continues bleeding
Hemorrhage
Too much clotting
Thrombosis
Major systems of hemostasis
Blood vessels
Platelets
Plasma protein
Major systems of hemostasis purpose
To prevent, predict, diagnose and manage hemostatic disease
For clot formation
Platelets
Helps to avoid excess clot formation
Plasma protein
Hemostasis interaction of
Vasoconstriction
Platelet adhesion and aggregation
Coagulation enzyme activation
Interaction of
Vasoconstriction
Platelet adhesion and aggregation
Coagulation enzyme activation
Purpose
=To stop bleeding
Vasoconstriction is triggered by?
Serotonin
Key cellular elements
Cells of the vascular intima
Extravascular tissue factor (TF) – bearing cells
Platelets
***plasma components are the coagulation and
fibrinolytic proteins and their inhibitors
***plasma components are the?
coagulation and
fibrinolytic proteins and their inhibitors
Blood vessels and platelets response
Primary hemostasis
involves the interaction of vasoconstriction, plate- let adhesion and aggregation, and coagulation enzyme activa- tion to stop bleeding
Hemostasis
The key cellular elements of hemostasis are the?
cells of the vascular intima
extravascular tissue factor (TF)–bearing cells
platelets
refers to the role of blood vessels and platelets in response to a vascular injury, or to the commonplace desquamation of dying or damaged endothelial cells.
Primary hemostasis
Blood vessels contract to seal the wound or reduce the blood flow is called?
vasoconstriction
platelet plug is produced when?
Platelets become activated, adhere to the site of injury, secrete the contents of their gran- ules, and aggregate with other platelets to form a platelet plug.
_____ and _____ comprise the initial, rapid, short-lived response to vessel damage, but to control major bleeding in the long term, the plug must be reinforced by fibrin.
Vasoconstriction and platelet plug formation
Vasoconstriction and platelet plug formation comprise the initial, rapid, short-lived response to vessel damage, but to control major bleeding in the long term, the plug must be reinforced by?
Fibrin
Defects in primary hemostasis that can cause debilitating, sometimes fatal, chronic hemorrhage. (4)
collagen abnormalities, thrombocytopenia, qualitative platelet disorders, or von Willebrand disease
describes the activation of a series of coagulation proteins in the plasma, mostly serine proteases, to form a fibrin clot.
Secondary hemostasis
an enzyme that converts fibrinogen to a localized fibrin clot
thrombin
The final event of hemostasis is?
fibrinolysis, the gradual digestion and removal of the fibrin clot as healing occurs.
Activated by desquamation and small injuries to blood vessels
Primary hemostasis
Involves vascular intima and platelets
Primary hemostasis
Rapid, short-lived response
Primary hemostasis
Procoagulant substances exposed or released by damaged or activated endothelial cells
Primary hemostasis
Activated by large injuries to blood vessels and surrounding tissues
Involves platelets and coagulation system
Delayed, long-term response
The activator, tissue factor, is exposed on cell membranes
Secondary hemostasis
_____ provides the interface between circulating blood and the body tissues.
vascular intima
The innermost lining of blood vessels is a monolayer of metabolically ________
active endothelial cells
ECs play essential roles in?
immune response, vascular permeability, proliferation, and, of course, hemostasis.
______ form a smooth, unbroken surface that eases the fluid passage of blood.
Endothelial cells
An ____________ (basement membrane) and its surrounding layer of connec- tive tissues support the ECs.
elastin-rich internal elastic lamina
In all blood vessels, ________ occupy the connective tissue layer and produce collagen.
fibroblasts
Smooth muscle cells in ______ and _______, but not in the walls of veins, venules, or capillaries, contract during primary hemostasis.
arteries and arterioles
Normally, the intact _________ prevents thrombosis by inhibiting platelet aggregation, preventing coagulation acti- vation and propagation, and enhancing fibrinolysis
vascular endothelium
Innermost Vascular Lining
Endothelial cells (endothelium)
Supporting the Endothelial Cells
Internal elastic lamina composed of elastin and collagen
Subendothelial Connective Tissue
Collagen and fibroblasts in veins
Collagen, fibroblasts, and smooth muscle cells in arteries
a platelet inhibi- tor and a vasodilator, is synthesized through the eicosanoid pathway and prevents unnecessary or undesir- able platelet activation in intact vessels
Prostacyclin
is synthesized in ECs, vascular smooth muscle cells, neutro- phils, and macrophages.
induces smooth muscle relaxation and subsequent vasodilation, inhibits platelet ac- tivation, and promotes angiogenesis and healthy arteri- oles
Nitric oxide
An important EC-produced anticoagulant is ________, which controls activation of the tissue factor pathway, also called the extrinsic coagula- tion pathway.
tissue factor pathway inhibitor (TFPI)
ECs synthesize and express on their surfaces
inhibitors of thrombin formation, _______, facilitated by _________, and _______
thrombomodulin; endothelial protein C receptor (EPCR); heparan sulfate
______ binds protein C, and ______ catalyzes the activation of the protein C pathway
EPCR; thrombomodulin
downregulates coagulation by digesting activated factors V and VIII, thereby
inhibiting thrombin formation
protein C pathway
protein C pathway downregulates coagulation by digesting activated factors ____ and ____, thereby
inhibiting thrombin formation
V and VIII
is a glycosaminoglycan that
enhances the activity of antithrombin, a serine
protease inhibitor.
Heparan sulfate
a serine protease inhibitor.
Antothrombin
manufactured from porcine gut tissues, resembles EC heparan sulfate in its antithrombin activity
pharmaceutical anticoagulant heparin,
pharmaceutical anticoagulant heparin,
manufactured from _______ resembles EC heparan sulfate in its antithrombin
activity
porcine gut tissues
is used extensively as a therapeutic
agent to prevent propagation of he thrombi that cause coronary thrombosis, strokes, deep vein thromboses, and pulmonary emboli
Heparin
ECs secrete _______ from storage sites called Weibel-Palade bodies when activated by vasoactive agents such as thrombin
Von Willebrand factor (VWF)
ECs secrete von Willebrand factor (VWF) from storage sites called _______ when activated by vasoactive agents such as thrombin
Weibel-Palade bodies
ECs secrete and coat themselves with ______, an adhesion molecule that promotes platelet and leukocyte binding
P-selectin
ECs support ______ (secretion of tissue plasminogen activator (TPA))
fibrinolysis
Activates plasminogen to form plasmin
Tissue plasminogen activator (TPA)
thrombus formation
both TPA and plasminogen bind to polymerized fibrin
TPA activates fibrinolysis by?
converting plasminogen to plasmin
from the cytoplasm of bone marrow megakaryocytes
Platelets
Platelets are from the cytoplasm of ______
bone marrow megakaryocytes
PLATELETS size
2 to 3 um in diameter
complex, metabolically active cells that interact
with their environment and initiate and control hemostasis platelets adhere, aggregate, and secrete the contents of their granules (during injury)
Platelets
is the property by which platelets bind nonplatelet surfaces such as subendothelial collagen
Adhesion
platelet adhesion is underscored by bleeding disorders such as
Bernard-Soulier syndrome
What are the platelet factors absent in Bernard-Soulier syndrome
platelet GP Ib/IX/V
Platelets functions (3)
Adhesion
Aggregation
Secretion
What condition where the VWF is missing or defective.
von Willebrand disease
Platelet a-Granules: ______ molecules (7)
Factor V
Factor XI
Protein S
Fibrinogen
VWF
Platelet factor 4 (heparin inhibitor)
Platelet-derived growth factor
Platelet Dense Granules (Dense Bodies) (3)
Adenosine triphosphate
Calcium
Serotonin (vasoconstrictor)
Plasma transports at least ____ procoagulants (COAGULATION FACTORS)
16
Procoagulants is also termed as
Coagulation Factor
_____ are enzymes that circulate in an inactive form called ______
8; zymogens
____ that bind, stabilize, and enhance the activity of their respective enzymes
cofactors
glycoproteins synthesized in the?
Liver
During clotting - procoagulants become
activated and produce a _____
localized thrombus
What are the zymogens? (8)
VII
IX
X
XI
XII
XIII
Prekllikrein
Prothrombin
Cofactors (7)
V
VIII
HMWK
Protein Z
Protein S
Tissue factor
Thrombomodulin
The plasma procoagulants may be serine proteases or cofactors, except for factor _____, which is a transglutaminase
XIII
The plasma procoagulants may be _____ or _____ except for factor XIII, which is a transglutaminase
Serine proteases or cofactors
The plasma procoagulants may be serine proteases or cofactors, except for factor XIII, which is a ?
transglutaminase
Serine proteases are proteolytic enzymes of the trypsin family and include the procoagulants (7)
factor Ila (thrombin)
VIla
IXa
Xa
Xla
XIla
pre-K
Also known as fletcher factor
Pre-kallikrein
is the ultimate substrate of the coagulation pathway
Fibrinogen
is required for the assembly of coagulation complexes on platelet or cell membrane phospholipids
Calcium
Factor I : Name & Function
Fibrinogen
Thrombin substrate, polymerizes to form fibrin
Factor II : Name & Function
Prothrombin
Serine protease
Factor III: Name & Function
Tissue factor
Cofactor
Factor IV: Name & Function
Ionic calcium
Mineral
Factor V: Name & Function
Labile factor
Cofactor
Factor VII: Name & Function
Stable factor
Serine protease
Factor VIII: Name & Function
Antihemophilic factor
Cofactor
Factor VWF: Name & Function
von Willebrand factor
Factor VIII carrier and platelet adhesion
Factor IX: Name & Function
Christmas factor
Serine protease
Factor X: Name & Function
Stuart-Prower factor
Serine protease
Factor XI: Name & Function
Plasma thromboplastin antecedent (PTA)
Serine protease
Factor XII: Name & Function
Hageman factor
Serine Protease
Factor Prekallikrein : Name & Function
Fletcher factor, pre-K
Serine protease
Factor High-molecular- weight kininogen: Name & Function
Fitzgerald factor, HMWK
Cofactor
Factor XIII: Name & Function
Fibrin-stabilizing factor (FSF)
Transglutaminase, transamidase
Platelet factor 3: Name & Function
Phospholipids, phosphatidyl- serine, PF3
Assembly molecule
Other plasma coagulant
Fibrinogen
Factor XIII
Phospholipids
Calcium VWF
is a transmembrane receptor for factor VIlla and is found on extravascular cells such as fibroblasts and smooth muscle cells, but under normal conditions, it is not found on blood vessel ECs.
Tissue factor (factor III)
are soluble plasma proteins. Both are activated by thrombin and inactivated by protein C
Factors V and VIII
Factors V and VIII are soluble plasma proteins. Both are activated by ____ and inactivated by _____
thrombin; protein C
________ is a cofactor to factor XIla and prekallikrein in the intrinsic contact factor complex.
High-molecular-weight kininogen
High-molecular-weight kininogen is a cofactor to factor ____ and _____ in the intrinsic contact factor complex
XIla; prekallikrein
a mechanism for activating coagulation in conditions where foreign objects such as mechanical heart valves or bacterial membranes and/or high levels of inflammation are present
intrinsic contact factor complex
a transmembrane protein constitutively expressed by vascular ECs, is a thrombin cofactor.
Thrombomodulin
Both ______ and _____are cofactors in the regulation and control of coagulation
protein S and protein C
Factor VIII has a molecular mass of 260,000 Daltons and is produced primarily by?
Hepatocytes
_______ and ________ are therefore sex-linked disorders occur- ring almost exclusively in males
Hemophilia A and Hemophilia B
What is the condition for factor VIll deficiency
Hemophilia A
What is the condition for factor IX deficiency
Hemophilia B
______ is a cofactor, but its importance in hemostasis cannot be overstated, as evidenced by the severe bleeding and symptoms associated with hemophilia A
Factor VIII
_______ deteriorates more rapidly than the other coagulation factors in stored blood
Factor VIII
______ is a large multimeric glycoprotein that participates in platelet adhesion and transports the procoagulant factor VIII
VWF
“contact factors”, also called intrinsic accessory pathway proteins, are factors (3)
factor XIl, high-molecular- weight kininogen (HMWK, factor), and prekallikrein (pre-K, Fletcher factor)
Contact factors are AKA
intrinsic accessory pathway proteins
The contact factor complex (HMWK:pre-K.FXII) activates factor _____; factor Xla is an activator of factor _____
XI; IX
True or false: Deficiencies of factor XII, HMWK, or pre-K do not cause clinical bleeding disorders.
True
______ is activated by the contact factor complex and, more significantly, by ______ during coagulation generated from tissue factor activation
Factor XI; thrombin
What do you call the Deficiencies of factor XI
Rosenthal syndrome
Deficiencies of factor XI (Rosenthal syndrome) usually result in?
mild and variable bleeding
cleave fibrinopeptides A and B from the alpha and beta chains of the fibrinogen molecule, triggering spontaneous fibrin polymerization
Thrombin
In addition, thrombin amplifies the coagulation mechanism by activating cofactors?
V, VIII, XI
In addition, thrombin amplifies the coagulation mechanism by activating cofactors V and VIII and factor XI by a?
positive feed- back mechanism
Thrombin can also activate factor?
VIII
is the primary substrate of thrombin
Fibrinogen
essential for platelet aggregation because it links activated platelets through their GP IIb/Illa platelet fibrinogen receptor.
Fibrinogen
an acute phase reactant protein
Fibrinogen
two coagulation pathways were described, both of which activated ________ at the start of a common pathway leading to thrombin generation
factor X
