Blood Coagulation and Wound Repair Flashcards
directly binds to and neutralizes Factor IIa
pradaxa
is activated by trauma inside the vascular system, and is activated by platelets, exposed endothelium, chemicals, or collagen. This pathway is slower, but more important.
Intrinsic pathway
(VWF def.) easy bruising
Von Willebrand disease
cause vasoconstriction in primary hemostasis reducing blood flow to the wound
Serotonin and thromboxane A2
Activated by thrombin in presence of Ca2+; stabilizes fibrin clot by covalent cross-linking
Factor XIII
rare disorder in which your blood doesn’t clot normally because it lacks sufficient blood-clotting proteins (clotting factors). If you have it , you may bleed for a longer time after an injury than you would if your blood clotted normally. Also called factor VIII (FVIII) deficiency or classic hemophilia, is a genetic disorder caused by missing or defective factor VIII, a clotting protein.
Hemophilia A
Most coagulation factors are generally _____
serine proteases
fat soluble vitamin needed as a co-factor by enzyme which catalyzes post-translational gamma-carboxylation (GLA residues) of coagulation proteins (Protein S, factors II, VII, IX, and X) and bone proteins matrix GLA protein and osteocalcin. These GLA residues represent calcium binding sites on these proteins.
Vitamin K
is a proteoglycan composed of a protein core and heparin glycosaminoglycan chains; the latter are sulfated oligosaccharide chains composed of repeating diassacharides of an amino sugar and glucuronic/iduronic acid; stored in granules of basophils and mast cells.
Heparin and Mast/basophils
is calculated from a PT result and is used to monitor how well the blood-thinning medication (anticoagulant) warfarin (Coumadin®) is working to prevent blood coagulation
international normalized ratio (INR)
(GpIIb-IIIa def.) frequent nosebleeds
Glanzmann’s thrombasthenia
drugs which inhibit blood coagulation and which are used to treat conditions where clinical conditions make if more likely to observe negative effects due to formation of clots (inadequate flow of blood, irregular heart rate, etc.). Examples, warfarin, xarelto, etc. Prolong bleeding time and can complicate dental surgery.
Blood thinners
used to disrupt the coagulation cascade and prevent clotting; bind to the calcium in the blood. By reducing the amount of calcium, there will be no regulation of the binding and the cascade cannot begin
Citrate
Factor V and VIII are
glycoproteins
site of metabolism of fat soluble vitamin K.
Gut bacteria
Most important coagulation inhibitor, controls activities of thrombin, and factors IXa, Xa, XIa and XIIa (regulatory element)
Antithrombin III
an enzyme that catalyzes the formation of an covalent bond between a free amine group (e.g., protein- or peptide-bound lysine) and the acyl group at the end of the side chain of protein- bound glutamine. Fibrin is the physiological substrate for it in blood coagulation. The reaction also produces a molecule of ammonia. Bonds formed exhibit high resistance to proteolytic degradation (proteolysis)—thus stabilizing the fibrin clot to degradation
Transglutaminase (factor XIII)
Lower INR than recommended range causes
faster blood clotting
Subendothelial cell-surface glycoprotein that acts as a cofactor for factor VII (cofactor)
Factor III Tissue factor
Pro-coagulant in its actions (acts as a vasoconstrictor) with short half-life (30 sec). Produced by activated platelets it stimulates activation of new platelets as well as increases platelet aggregation through increasing expression of the GPIIb/IIIa protein complex on platelet membranes. This same effect is also how ADP stimulates platelet activation. Clopidogrel blocks this action.Works by binding to its receptors (G protein coupled receptor) on platelets. Synthesized by thromboxane-A synthase from prostaglandin H2 in a reaction which also produces equal amounts of 12-Hydroxyheptadecatrienoic acid (12-HHT).
Thromboxane A2 (TXA2)
Mutation that causes production of too much prothrombin; promotes the formation of blood clots
Factor II Mutation
mutations cause hemophilia A
Factor VIII
collagen is remodeled and realigned along tension force lines and cells no longer needed are removed by apoptosis.
Remodeling phase
Protein on the surface of endothelial cells; binds thrombin, which then activates protein C (regulatory element)
Thrombomodulin
Platelets secrete _____ which cause vessels to spasm decreasing blood flow to that area
serotonin
Crosslinking of fibrin is catalyzed by _______ or _________
transglutaminase or factor XIII
bacteria and debris are phagocytosed and removed from the wound site. Factors are released that cause migration and division of cells involved in the inflammatory phase
Inflammatory phase
anuclear cell bodies derived from megakaryocytes which circulate in the vasculature; undergo Adhesion, Activation, and Aggregation during coagulation
Platelets (thrombocytes)
Mutation that causes a rare bleeding disorder due extrinsic factor deficiency
Factor VII Mutation
cell membrane receptor by which cells specifically recognize each other and adhere to each other. ICAM-1 receptor is an example
Cell-cell adhesion receptor
healthy people’s INR should be
1.1 or below
acid-citrate-dextrose plasma
ACD plasma
Inhibitor of plasmin which acts to limit (slow) the rate of plasmin action, e.g., the rate at which fibrin clots are degraded or removed. Hereditary absence of anti-plasmin can lead to hemorrhaging.
Alpha2-anti-plasmin
Liquid phase of unclotted (anti-coagulated) blood (still contains clotting proteins). Cells have been centrifuged away.
Plasma
angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction
Proliferative phase
Prothrombin test evaluates the presence of what?
prothrombin (II), factors X, V, and VII and fibrinogen
cell membrane receptor by which cells specifically recognize cell matrix proteins and adhere to them. Fibronectin receptor is an example. Integrin receptors are more examples.
Cell-matrix adhesion receptor
Activated on surface of activated platelets by tenase complex and by factor VIIa in presence of tissue factor and Ca2+
Factor X
Anti-coagulant in its actions (it inhibits platelet activation and acts as a vasodilator).; produced in endothelial cells, which line the walls of arteries and veins, from prostaglandin H2(PGH2) by the action of the enzyme prostacyclin synthase; has a half-life of 42 seconds, is broken down into 6-keto-PGF1, which is a much weaker vasodilator.
Prostacyclin (PGI2)
chemical compound which sequesters calcium ion and draws it away from coagulation proteins. Acts as an anti-coagulant.
EDTA (chelation of calcium)
competitively inhibits the vitamin K epoxide reductase complex 1 (VKORC1), which is an essential enzyme for activating the vitamin K available in the body; reduces the synthesis of active clotting factors like factors (II, VII, IX, and X
Warfarin
Extrinsic pathway involves which clotting factors
Factor VII
is activated by external trauma that causes blood to escape from the vascular system. This pathway is faster.
extrinsic pathway
Some physiological responses must happen quickly (like coagulation) so enzymes that catalyze those reactions need to be prepared but not active, for that reason a zymogen precursor form is synthesized and stays poised to act but requiring a rapid activation step. Coagulation is based on an enzymatic cascade involving sequential steps of limited proteolysis which activate and mature the structure of individual proteolytic enyzmes. In activating a small amount of initial catalyzing enzyme, this then leads progressively and rapidly to larger activated amounts of subsequently activated proteolytic enzymes ending up with a big amount of product (activated fibrin) required is form a clot and stop blood loss.
Enzymatic cascade
Mutation that significantly reduces the amount of protein in the bloodstream; causes episodes of abnormal bleeding that can be severe
Factor V mutation
Activated by thrombin; factor VIIIa is a cofactor in the activation of factor X by factor IXa (cofactor)
Factor VIII
take citrated plasma and add calcium back and also thromboplastin (combination of phospholipids and tissue factor); used to help detect and diagnose a bleeding disorder or excessive clotting disorder; measure of the integrity of the extrinsic and final common pathways of the coagulation cascade
Prothrombin Test
bleeding disorder caused by defective scrambling of membrane phospholipids
scott’s syndrome
Activated by thrombin; factor Va is a cofactor in the activation of prothrombin by factor Xa (cofactor)
Factor V
Liquid phase of clotted blood after spinning out clot.
Serum
solution of citric acid, sodium citrate and dextrose in water
Acid Citrate Dextrose Solution
complex process in which skin or other tissue repairs itself after injury
wound healing
onset of Warfarin is _____ (fast or slow)
slow
within minutes post-injury, platelets aggregate at the injury site to form a fibrin clot which acts to control bleeding
Hemostasis
x-linked recessive disorder with decreased synthesis of Factor VIII; treated with Factor VIII
Hemophilia A
Associated with subendothelial connective tissue; serves as a bridge between platelet, glycoprotein GPIb/IX and collagen (regulatory element)
von Willebrand factor
directly binds to and neutralizes factor Xa
Xarelto and eloquis
x-linked recessive disorder with decreased synthesis of Factor IX; treated with Factor IX
Hemophilia B (christmas disease)
Cleaved by thrombin to form fibrin clot
Factor 1 (Firbrinogen)
Factor XIII is a
transglutaminase
is a monoamine neurotransmitter. Derived from tryptophan, primarily found in the gastrointestinal tract (GI tract), blood platelets, and the central nervous system. Released upon degranulation of platelets at site of injury. Functions as a smooth muscle constrictor to immediately act to limit the loss of blood volume.
Serotonin or 5-hydroxytryptamine (5-HT)
Acts as a cofactor of protein C; both proteins contain gla residues (regulatory element)
Protein S
____ breaks down fibrin
plasmin
Small serum/plasma protease inhibitor which is produced by the liver. Its activity is increased dramatically by binding to the anticoagulant drug heparin, which enhances the binding of antithrombin to factor IIa (Thrombin) and factor Xa.
Anti-thrombin III
4 stages of wound healing
hemostasis, inflammation, proliferation, and remodeling
decreases blood clotting by blocking an enzyme called vitamin K epoxide reductase that acts to partially reactivate vitamin K after it participates in an oxidation reaction, e.g., carboxylase epoxidase.
Warfarin
_____ binds to vWF at the subendothelial surface to promote strong adhesion to the vessel wall (primary aggregation)
GP2b/3a
Activated to protein Ca by thrombin bound to thrombomodulin; then degrades factors VIIIa and Va (regulatory element)
Protein C
Higher INR than recommended range causes
slow blood clotting
enzymes that catalyze the reaction from inactive plasminogen into active plasmin in the process that breaks down fibrin
tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), kallikrein, and factor XII
Common pathway involves which clotting factors
factors I, II, V, X
The coagulation factors circulate as inactive
zymogens
ADP and thromboxane A2 attract other platelets and make them stick to the growing mass of platelets that are stuck to the collagen in the broken vessel this process is called a ______
platelet plug
Which coagulation factors are dependent on Vitamin K?
Vii, X, II, and IX
____ and _____ attract other platelets and make them stick to the growing mass of platelets that are stuck to the collagen in the broken vessel
ADP and thromboxane A2
Activated by factor XIIa
Factor XI
normally 1/10,000 bone marrow cells are these large multi-lobulated nuclear cells which give rise to platelets. Number can rise dramatically in disease
Megakaryocytes
is stored in dense bodies inside blood platelets and is released upon platelet activation. interacts with a family of receptors found on platelets (P2Y1, P2Y12, and P2X1), which leads to platelet activation. P2Y1 receptors initiate platelet aggregation and shape change as a result of interactions
ADP
Binds to exposed collagen at site of vessel wall injury, activated by high-MW kininogen and kallikrein
Factor XII
Activated on surface of activated platelets by prothrombinase complex
Factor II(Prothrombin)
Activated by factor XIa in presence of Ca2+
Factor IX
at least 9 mutations identified that don’t generally cause health problems; reduce or eliminate a proteins used in intrinsic pathway
Kallikrein mutations
(GpIb def.) bruise easily; heavy or prolonged menstrual periods
Bernard Soulier syndrome
post-translational modification of glutamic acid side chain of specific coagulation proteins which requires Vitamin K and which adds a calcium binding site needed for blood coagulation to proceed.
Gamma-carboxyglutamic acid
clotting cascade. Consists of the cascade of coagulation serine proteases that culminates in cleavage of soluble fibrinogen by thrombin. Thrombin cleavage generates insoluble fibrin that forms a crosslinked fibrin mesh at the site of an injury. Fibrin generation occurs simultaneously to platelet aggregation
secondary hemostasis
T/F: Disease states can not interfere with the wound healing progression
False
Platelets stick to collagen and undergo a release reaction in which the secrete what 3 things?
ADP, serotonin, and thromboxane A2
____ is needed to form proteins used in clotting; important cofactor for formation of carboxyl group
Vitamin K
Intrinsic pathway involves which clotting factors
factors XII, XI, IX, VIII
Both pathways meet and finish the pathway of clot production in what is known as the common pathway.
Common pathway
exposed collagen fibrils represent a site of platelet attachment to initiate blood coagulation.
Tissue Collagen
naturally high affinity binder of Ca ions that functions to hold enzymes onto the surface of the cell membrane
Carboxyglutamate
vasoconstriction and platelet response. Platelet aggregation at the site of injury is mediated by platelet receptors, platelet-derived agonists, platelet-derived adhesive proteins and plasma-derived adhesive proteins
primary hemostasis
Mutation that reduce the amount of coagulation of factor X in bloodstream
Factor X mutation
inhibitor of cyclooxygenase which catalyzes formation of prostaglandin E2 and other prostaglandins and leukotrienes
Aspirin (NSAID)
effective therapeutic INR range for people taking warfarin
2.0 to 3.0
Activated by thrombin in presence of Ca2+
Factor VII
