Hemostasis Flashcards
MODERN CONCEPT OF BLOOD COAGULATION
Cascade or “Waterfall” Hypothesis
MODERN CONCEPT OF BLOOD COAGULATION STAGES
STAGE 1 : Generation of thromboplastin activity (“intrinsic” and “extrinsic”)
STAGE 2 : Conversion of prothrombin to thrombin by “thromboplastin” in the presence of calcium
CONTACT GROUP
Includes:
Prekallikrein
Kallikrein
Factor XII
Factor XI
PROTHROMBIN (VITAMIN K DEPENDENT) GROUP
Includes:
Factor II, VII, IX, and X
Synthesized in the liver with Vitamin K as Co-Factor
PROTHROMBIN
is needed to carboxylate glutamate of the vitamin K dependent factors
Vitamin K
FIBRINOGEN GROUP
Includes :
Factor I, V, VIII, and XIII
Highest molecular weights of all factors
Most labile
Consumed in coagulation
FIBRINOGEN GROUP
Act as substrates for plasmin
FIBRINOGEN GROUP
FIBRINOGEN GROUP
All are found in the alpha granules of platelets EXCEPT __ and ___
Factor XIII (platelet cytoplasm) Factor VIII:C
A globulin (MW 341,000)
FACTOR I - Fibrinogen
FACTOR I - Fibrinogen NV
NV: 200-500mg/dL
FACTOR I - Fibrinogen Strengthened by Factor
Strengthened by Factor XIII
Stable protein of alpha globulin type (MW 63,000)
FACTOR II - Prothrombin
Related to Factor VII
FACTOR II - Prothrombin
A powerful proteolytic enzyme
Potent platelet aggregating substance
MW = 40,000
THROMBIN
The _ is the amount that will coagulate 1mL of standard fibrinogen solution in 15 seconds at 28C
THROMBIN UNIT
Protein intermediate between beta and gamma globulin
FACTOR V - Proaccelerin
Labile, deteriorating rapidly in oxalated plasma and even in frozen (-20C) specimens
FACTOR V - Proaccelerin
Not destroyed or consumed in the clotting process
Appears to be a beta globulin
FACTOR VII - Proconvertin
In-vivo survival after transfusion = 50% is lost within 8-12H More stable in FFP stored in -30 to -70C
FACTOR VIII – Antihemophilic Factor
The entire molecule as it circulates in the plasma
Composed of VIII:C and VIII:vWF portions which is not covalently bound
VIII/vWF
Portion capable of binding to endothelium and supporting normal platelet adhesion and function. Tested by the bleeding time
VIII:vWF
Portion acting in intrinsic system as cofactor to factor Ixa.
Tested by PTT
VIII:C
Antigenic property of procoagulant portion as measured by monoclonal immunologiocal techniques
VIIIC:Ag
Factor VIII related antigen
Large vWF portion and measured by immunologic techniques of Laurell rocket or immunoradiometric assay using heterologous antibodies
VIIIR:Ag
Ristocetin (antibiotic) cofactor activity
Required for platelet aggregation studies
VIIIR:RCo
Stable protein factor
Not consumed during clotting
Not destroyed by ageing
No significant loss in blood and plasma stored at 4C X 2W
Adsorbed by aluminum hydroxide and barium sulfate
FACTOR IX – Plasma Thromboplastin Component
Stable a-globulin protein factor
Activity related to Factor VII
FACTOR X – Stuart-Prower Factor
B-globulin protein factor
Activity related to Factor VII
FACTOR XI – Plasma Thromboplastin Antecedent
Stable globulin
Adsorbed into powdered glass, Celite, or bentonite (negatively charged)
Activity is accelerated by Fletcher (Prekallikrein) and Fitzgerald factor (HMWK)
FACTOR XII – Hageman Factor
Thrombin splits 4 arginyl-glycine bonds of fibrinogen to produce two peptides A, two peptides B and a fibrin monomer
FACTOR XIII – Fibrinase
Fine clot is produced from further polymerization
Fine clot is soluble in 5M urea and 1% monochloroacetic acid
FACTOR XIII – Fibrinase
FACTOR XIIa
Initiates the
Initiates
Initiates
intrinsic coagulation system
fibrinolysis
kinin and complement systems
KALLIKREIN Perpetuates _ activation and its own production Initiates the _ Initiates _&_ Directly activates \_\_
Factor XII
kinin system
fibrinolytic and complement systems
Factor IX
Most important
Found in plasma and serum
Acts on thrombin to form metathrombin
ANTITHROMBIN III
ANTITHROMBIN III Made up of:
Alpha 2 globulin
Alpha 2 macroglobulin (Heparin cofactor)
Alpha 2 antitrypsin
ATIII-deficiency
Thromboembolism and liver disease
ALPHA2 MACROGLOBULIN Inhibits _ but not completely Protect its bound enzymes against other circulating antithrombins Inhibits _ by inhibiting plasmin Inhibits _
thrombin
fibrinolysis
kallikrein
ALPHA1 ANTITRYPSIN
Potent inhibitor of _
Inactivates_ and _
Factor Xia
plasmin and thrombin
C’1 ESTERASE INHIBITOR
Inhibitor of _ and _
Inhibits _ _ and _
fibrinolysis and coagulation
Factor XIIa, XIIf and XIa
Vitamin K dependent
Potent inhibitors of coagulation
Destroys Factors Va and VIIIa
PROTEIN C and S
_ is the cofactor of Protein C
Protein S
C:S complex enhances fibrinolysis by activating __ __
plasminogen activators
an enzyme that cleaves fibrinogen, fibrin, and other coagulation factors (ie. _ and _ )
PLASMIN
VIII and V
Present in the blood are large amounts of alpha globulins with antiplasmin activity
INHIBITORS OF PLASMINOLYSIS
INHIBITORS OF PLASMINOLYSIS
Two types:
Immediate acting
Slow acting
Inhibitors of Plaminogen activators : _ and _
EACA and Tranexamic acid
Fine chromatin
Abundant cytoplasm
MEGAKARYOBLAST
(+) globules
Many polyribosomes
DMS first appears
PROMEGAKARYOCYTE
Marginated chromatin
Multinucleation
MEGAKARYOCYTE
Coagulation factors, permeability factors, PDGF (smooth muscle cell proliferation), fibrinogen, B-thromboglobulin and PF4 (heparin inhibition), and Factor Va
ALPHA GRANULES
Adenosine and guanosine di- and triphosphates, calcium, magnesium, serotonin
DENSE BODIES
Platelet Factors: PF-1 : Absorbed to \_\_ PF-2 : A _ _ PF-3 : Involved in intrinsic cascade acting as prothrombin activator by catalyzing the reactions between Factors _ _ and _ PF-4: Inhibitor of _ and _ like activity
factor 5 - thrombin accelerator - Xa, V, and calcium - heparin and Factor XIII
PLATELET SYSTEM
Subdivided into 4 major zones under the electron microscope:
PERIPHERAL ZONE
SUBMEMBRANE AREA
SOL-GEL ZONE
ORGANELLE ZONE
PERIPHERAL ZONE
– Glycocalyx and Plasma Membrane
SUBMEMBRANE AREA
– Filaments
SOL-GEL ZONE
– Microtubular
Blood vessels and tissues injured; bleeding begins through _ and _
__ of the injured vessels
The torn endothelium__ and curls up
_ _ are released from damaged tissues
transected and injured vessels
Nervous vasoconstriction
retracts
Thromboplastic substances
Plasma flows over the damaged tissues – __is activated and triggers the activation of the intrinsic system; __ activates tissue thromboplastic substances and activates the extrinsic system
Factor XII
Factor VII
The activated _ thromboplastin(s) in the presence of calcium then interacts with _ and _ , forming definitive thromboplastin which converts prothrombin to thrombin
extrinsic
Factor V and X
In the meantime, _ adhere to damaged endothelium; _ from extrinsic pathway and _ adhere with the platelets adhering to __, causing aggregation to a plug
platelets
thrombin
ADP
subendothelial collagen
In the meantime, the intrinsic mechanism is activated _ _
Fibrinogen Fibrin
Fibrin absorbs excess thrombin and the remainder is neutralized by _
The _ so produced between and on the framework of the platelet plug polymerizes and contracts, thus effectively anchoring the platelet plug and sealing the defect of the vessel
_ grows over the plug and clot within the lumen is dissolved for _
increased thrombin
antithrombins
fibrin latticework
Endothelium
recanalization
