BASIC PRINCIPLES OF HEMOSTASIS Flashcards
Secondary Hemostasis is also known as …
Coagulation
It involves the enzymatic activation of series of plasma proteins in the coagulation system to form a fibrin meshwork.
Secondary hemostasis
Secondary hemostasis involves what in the coagulation system?
It involves the enzymatic activation of series of plasma proteins
Secondary hemostasis involves the enzymatic activation of a series of plasma proteins in what system?
in the coagulation system
Secondary hemostasis involves the enzymatic activation of a series of plasma proteins in the coagulation system to form what?
a fibrin meshwork
What is the event/step 4 in secondary hemostasis?
Fibrin-Platelet plug formation
In this event, coagulation factors interact on platelet surface to produce fibrin; fibrin-platelet plug then forms at site of vessel injury
Step 4: Fibrin-Platelet plug formation
What happens in Fibrin-Platelet plug formation?
Coagulation factors interact on platelet surface to produce fibrin; fibrin-platelet plug then forms at site of vessel injury
Coagulation factors interact on WHAT to produce fibrin?
PLATELET SURFACE
Coagulation factors interact on platelet surface to produce WHAT?
to produce fibrin
This forms at site of vessel injury
Fibrin-platelet plug
Fibrin-platelet plug then forms where?
forms at site of vessel injury
What is the event/step 5 in secondary hemostasis?
Fibrin stabilization
In this event, fibrin clot must be stabilized by Factor XIII
Fibrin stabilization
What happens in FIBRIN STABILIZATION?
Fibrin clot must be stabilized by Factor XIII
What must be stabilized by Factor XIII?
Fibrin clot
Fibrin clot must be stabilized by what factor?
Fibrin clot must be stabilized by Factor XIII
What factors stabilizes fibrin clots?
Factor XIII
What does Factor XIII do?
It stabilizes the fibrin clot
This is a process whereby, on vessel injury, plasma proteins, tissue factors, and calcium interact on the surface of platelets to form a stable fibrin clot.
Coagulation
In coagulation, upon vessel injury, what are the components that interact on the surface of the platelet to form a stable fibrin clot?
- Plasma proteins
- Tissue factors
- Calcium
On vessel injury, plasma proteins, tissue factors, and calcium interact on the surface of platelets to form what?
to form a stable fibrin clot.
Platelets also interact with fibrin to form a stable platelet-fibrin clot.
True or False
TRUE
This is a mechanism consisting of a series of cascading reactions involving development of enzymes from their precursors which will further be converted to their activated state
Coagulation
Coagulation is a mechanism consisting of a series of what?
a series of cascading reactions
Coagulation is a mechanism consisting of a series of cascading reactions involving what?
involving development of enzymes from their precursors which will further be converted to their activated state.
In the development of enzymes, what do you call their precursors?
ZYMOGENS
Zymogens will further be converted to their ACTIVATED STATE called …
Serine proteases
This occurs in the surface of platelet/endothelial cell membrane/PPL & not in fluid phase.
Coagulation
Coagulatio occurs where?
surface of platelet/endothelial cell membrane/PPL (phospholipid)
How many coagulation factors have a roman numeral assigned to them?
I - XIII
What Coagulation Factor is Fibrinogen?
CF I
What is the Biochemistry of Factor I?
Glycoprotein
These factors have GLYCOPROTEIN as their biochemistry
5 + 2 = 7
Factors I, II, V, VII, VIII, IX, X
What coagulatio factors have plasma proteins as their biochemistry?
- Prekallikrein
- High Molecular Weight Kininogen (HMWK)
CF I is described as …
fibrinogen
What Coagulation Factor is Prothrombin?
CF II
CF II is preferrably described as …
Prothrombin
What is the Biochemistry of CF I?
Glycoproteins
What is the biochemistry of CF II?
Glycoproteins
What is the biochemistry of CF II?
Glycoproteins
What is the coagulation factor of the Tissue Factor?
CF III
CF III is preferrably described as …
TISSUE FACTOR
What is the synonym of Tissue Factor/CF III?
Tissue thromboplastin (TF and PPL)
What is the biochemistry of CF III?
Lipoprotein
What coagulation factor is Calcium?
CF IV
CF IV is preferrable described as…
Calcium
What biochemistry does CF IV have?
Metal ion
What coagulation factor is proaccelerin?
CF V
CF V is preferrably described as …
Proaccelerin
What is the synonym for Proaccelerin?
Labile Factor
What factor is the labile factor?
CF V
Labile factor is also called …
proaccelerin
What biochemistry does proaccelerin have?
Glycoprotein
What coagulation factor is ommitted?
CF VI
CF VI is only the activated factor V
True or False
TRUE
What factor is the activated Factor V?
CF VI
What coagulation factor is Proconvertin?
CF VII
CF VII is preferraby described as…
Proconvertin
Activated Factor V is also called …
CF VI
What are the synonyms for CF VII?
- Stable factor
- Serum prothrombin
- Conversion accelerator
Stable factor is also called …
CF VII
conversion accelerator is synonymous to …
Proconvertin
Serum prothrombin is synonymous to what?
CF VII
Tissue thromboplastin is synonymous to what factor?
CF III/Tissue factor
What biochemistry does Proconvertin have?
Glycoprotein
What coagulation factor is Antihemophillic Factor (AHF)?
CF VIII
CF VIII is preferrable described as…
Antihemophilic Factor
What is the synonym of CF VIII?
- Antihemophilic Globulin
- Antihemophilic Factor A
What is the synonym of CF VIII?
- Antihemophilic Globulin
- Antihemophilic Factor A
What biochemistry does Antihemophilic Factor have?
Glycoprotein
What coagulation factor is Plasma Thromboplastin Component (PTC)?
CF IX
CF IX is preferrably described as …
Plasma Thromboplastin Component (PTC)
What are the synonyms of CF IX?
- Antihemophilic Factor B
- Christmas Factor
Antihemophilic Factor B and Christmas Factor are synonyms for what?
CF IX/Plasma Thromboplastin Component (PTC)
What biochemistry does CF IX have?
Glycoprotein
What coagulation factor is Stuart-Prower Factor?
CF X
CF X is preferrably described as …
Stuart-Prower Factor
What are the synonyms for CF X?
- Prower factor
- Stuart Factor
What biochemistry does StuarT-Prower Factor have?
Glycoprotein
Prower Factor and Stuart Factor are synonyms for what?
CF X/Stuart-Prower Factor
What Coagulation Factor is Plasma Thromboplastin Antecedent (PTA)?
CF XI
CF XI is preferrably described as …
Plasma Thromboplastin Antecedent (PTA)
What are the synonyms for CF XI?
- Antihemophilic Factor C
- Rosenthal factor
Antihemophilic Factor C and Rosenthal Factor are synonyms for what factor?
CF XI/Plasma Thromboplastin Antecedent
What biochemistry does CF XI have?
B or gamma globulin
What coagulation factor is Hageman factor (HF)?
CF XII
CF XII is preferrable described as…
Hageman Factor
What are synonyms for CF XII?
- Glass factor
- Contact factor
Glass factor and contact factor are synonyms for what CF?
CF XII/Hageman Factor (HF)
What biochemistry does CF XII have?
Sialoglycoprotein
What CF has a Sialoglycoprotein biochemistry?
CF XII
What CF is Fibrin Stabilizing Factor (FSF)?
CF XIII
CF XIII is preferrably described as…
Fibrin Stabilizing Factor
What are the synonym for CF XIII?
- Laki-Lorand Factor (LLF)
- Fibrinase
Laki-Lorand Factor and Fibrinase are synonyms of what?
CF XIII
What biochemistry does CF XIII have?
- Beta or Gamma Globulin
- Transglutaminase/transamidase
What is the synonym for Prekallikrein?
Fletcher factor
Together with HMWK are part of the kallikrein & kinin systems & their primary function is in these systems
Prekallikrein
HMWK is an abbreviation for …
High Molecular Weight Kininogen
What are the synonyms for HMWK?
- Fitzgerald factor
- Williams factor
- Flaujeac factor
This CF circulates in the plasma together with VWF and is referred to as FACTOR VIII complex
Factor VIII
Factor VIII circulates WHERE AND TOGETHER WITH WHAT ?
Factor VIII circulates in the plasma together with VWF
Factor VIII circulates in the plasma together with VWF and is referred to as WHAT?
FACTOR VIII complex
It is the carrier for Factor VIII
vWF
vWF is the carrier for what factor?
Factor VIII
This factor functions for platelet adhesion
vWF
What is the function of the vWF?
Functions for platelet adhesion
vWF has a higher mol.wt than FVIII
True or False
TRUE
What is the mol. wt of the vWF?
500,000-20,000,000 Daltons to 260,000 Daltons only
Each VWF is a large multimeric protein of 240,000 Daltons subunit each.
True or False
TRUE
Deficiency in AHF or a dysfunctional AHF results in WHAT?
Hemophilia A
Hemophilia A is a result of what?
A deficiency in AHF or a dysfunctional AHF
A deficiency in VWF or a dysfunctional molecule results in what?
VWD
Von Willebrand Disease
VWD is a result of what?
A deficiency in VWF or a dysfunctional molecule
What is the manifesation of VWD and Hemophilia A?
BLEEDING
This is a mineral & play a big role in impt stages of coagulation. Removal of this ion will prevent coagulation.
Factor IV (Calcium)
Factor VIII is also known as
vWF COMPLEX
customary designation for the combination of factor VIII and VWF.
Factor VIII/VWF
binds activated factor IX to form the complex of VIIIa-Ixa which digests and activates factor X.
Factor VIII
procoagulant factor VIII, transported on VWF.
Factor VIII
Factor VIII deficiency is called …
Hemophilia A.
An epitope that is the antigenic target for the VWF immunoassay
VWF:Ag
Factor VIII coagulant activity as measured in a clot-based factor assay
Factor VIII: C
Assays to measure VWF activity
Most VWF activity assays measure the presence of high molecular weight VWF multimers, which are the most active multimers in platelet adhesion.
TRUE OR FALSE
TRUE
This is to distinguish qualitative and quantitative VWF deficiency
assays measure VWF activity, which is compared to VWF: Ag
A quantitative ristocetin cofactor activity; also called VWF activity
VWF:Rco
VWF activity is measured by what?
measured by the ability of ristocetin to cause agglutination of reagent platelets by the patient’s VWF.
This is a collagen binding assay, a second VWF activity assay
VWF:CB
Large multimers bind immobilized target collagen, predominantly what collagen?
Collagen III
It is an automated nephelometric activity assay that employs latex microparticles and monoclonal anti-glycoprotein I-VWF receptor
VWF: Immunoactivity
This is a third method for assaying VWF activity.
VWF: Immunoactivity
This is an activity assay that employs ristocetin-triggered binding of recombinant glycoprotein 1b (GP1b), detected by LIA or CLIA
VWF:GP1bR-
VWF:GP1bR is an activity assay that employs ristocetin-triggered binding of recombinant glycoprotein 1b (GP1b), detected by WHAT?
detected by LIA or CLIA
This is an activity assay that employs recombinant gain-of-function GP1b
VWF:GP1bM
This binds the VWF A1 domain without the need for ristocetin
VWF:GP1bM
The VWF:GP1bM reaction is detected using what?
LIA
RIPA stands for what?
Ristocetin-induced platelet aggregometry
This assay uses ristocetin and patient’s own platelets, in contrast to the VWF-Rco, which uses reagent platelets
RIPA
This assay is modified by using low ristocetin concentrations to identify VWD subtype 2B in which multimers exhibit increased avidity for the platelet receptor site.
RIPA
RIPA is also called
ristocetin response curve
This is a group-consumed during coagulation process, absent in serum but present in plasma
Thrombin-sensitive group/ Fibrinogen group
What is not needed for the synthesis of Thrombin-sensitive group/Fibrinogen group?
Vit K
This group is not adsorbed by BaSO4 or Al(OH)3
Thrombin-sensitive group/ Fibrinogen group
Test used to differentiate factor deficiency from disorder of circulating anticoagulants.
Differential Tests of Activated Partial Thromboplastin Time (DAPTT)
In APTT, if result becomes normal, then there is
Factor deficiency
In APTT, if result is not from factor deficiency, then there is/are
circulating anticoagulants
What is the formula to identify the deficient factor?
Pt’s plasma+ adsorbed plasma (with Factors V &VIII) or Pt’s plasma + serum(with Factors XI &XII),then re-run APTT.
Another modification of APTT which is done by mixing the patient’s plasma with commercially available correcting reagents, Factor VIII and IX reagents.
Differential Partial Thromboplastin Time (DPTT)
What are the commercially available correcting reagents used in DPTT?
Factor VIII and IX reagents
In DPTT, if there is prolonged result, how would you correct it?
PTT is corrected with Factor VIII (Hemophilia A) and PTT is corrected with Factor IX (Hemophilia B)
In DPTT, if there is partially corrected result, what are the reagents used and what type of hemophilia is associated?
both Factor VIII and Factor IX reagents, Hemophilia C
Simple test for the deficiencies in factors of the INTRINSIC and COMMON pathways of coagulation as well as presence of inhibitors to these factors (anticoagulants).
Partial Thromboplastin Time
Partial Thromboplastin Time is a simple test for deficiencies in factors of what pathways?
Intrinsic and Common pathways
Test where standardized foreign surface is introduced(activator)
Activated Partial Thromboplastin Time (APTT)
What is the reference interval for PTT?
40-100 seconds
What are the 2 tests cannot detect deficiencies in Factor XIII & platelets?
PTT and APTT
Tests that are useful in monitoring heparin or I.V. anticoagulant therapy and more sensitive than coagulation time.
PTT and APTT
There is a decrease in inflammation,trauma, stress & pregnancy in thrombin-sensitive group/ Fibrinogen group
True or False
false
INCREASE
There is a decrease in inflammation,trauma, stress & pregnancy in thrombin-sensitive group/ Fibrinogen group
True or False
false
INCREASE
What are the causes of an abnormally shortened result in APTT?
partial clotting of the blood
high levels of Factor III
an activated coagulation system as in DIC
the presence of platelets in the plasma.
What is the reference interval of APTT?
25-35 seconds
It is a test with more sensitive method than the coagulation time of whole blood.
Plasma Recalcification Time
This test may reveal abnormality which is not detectable by the determination of the clotting time of venous blood.
Plasma Recalcification Time
What is the activator used in activated recalcification time?
0.25 M CaCl2
FV & VIII are susceptible to denaturation & reduced in amt in stored plasma
TRUE OR FALSE
TRUE
What is the reference interval for Plasma Recalcification Time?
Less than 50 seconds
This is present in both serum &plasma(not consumed on coagulation)
Prothrombin group/Vit.K dependent group
Fibrinogen group is also called …
Thrombin-sensitive group
Which test has the principle, “the time necessary for fresh blood to form a clot when incubated at 37̊C in the presence of “surface contact” activation”.
Activated Coagulation Time of Whole Blood
Promthrombin group is also called …
Vit. K dependent group
What test measures overall activity of the intrinsic clotting system?
Activated Coagulation Time of Whole Blood
What is the reference interval of Activated Coagulation Time of Whole Blood?
1-2 minutes
Vit.K is needed for the synthesis of prothrombin group/vit. K dependent group
true or false
TRUE
This group can be adsorbed by BaSO4 & Al(OH)3
Prothrombin group/Vit. K dependent group
These drugs cause a functional decrease by producing PIVKAs( proteins induced by Vit K antagonists) & if measured by immunologic test rather than functional test will be present in normal amounts. Stable in stored plasma.
Vit. K def and coumarin drugs w/c compete with Vit.K
Vit. K def and coumarin drugs w/c compete with Vit.K cause what?
a functional decrease
What are the tests for Phase I and II of Coagulation?
The Coagulation Test
- Micro Methods
- Macro Methods
This test is superior for there is less contamination of the plasma with tissue fluids when blood is drawn from a vein.
Macro methods (from Coagulation test)
Vit. K def and coumarin drugs w/c compete with Vit.K cause a functional decrease by producing what?
by producing PIVKAs
Method that has the principle, “the time required for freshly collected blood to form a firm clot in standardized glass tubes at 37̊C.”
Lee-White Method or Whole Blood Clotting Time
PIVKAs stand for?
proteins induced by Vit K antagonists
What is the Reference interval of Lee-White Method or Whole Blood Clotting Time?
5-10 minutes
What method similar to Lee-White method only that more blood sample is tested.
Howell’s Method
This group is stable in stored plasma.
Prothrombin group/Vit. K dependent group
What is the Reference interval of Howell’s Method?
10-15 minutes
It tests the composite action of all plasma factors acting simultaneously.
Coagulation Test
It is a measure of the ability of the blood to clot and is not influenced by the platelet functions other than PF3.
Clotting time
It measures only the time required for the formation of the traces of thrombin sufficient to produce a visible clot.
Clotting time
Vit. K def and coumarin drugs w/c compete with Vit.K cause a functional decrease by producing PIVKAs( proteins induced by Vit K antagonists) & if measured by functional test rather than immunologic test will be present in normal amounts.
TRUE OR FALSE
FALSE
measured by immunologic test rather than functional test
Vit. K def and coumarin drugs w/c compete with Vit.K cause a functional decrease by producing PIVKAs( proteins induced by Vit K antagonists) & if measured by functional test rather than immunologic test will be present in normal amounts.
TRUE OR FALSE
FALSE
measured by immunologic test rather than functional test
What are the 2 Micro Methods used in Coagulation test?
- Slide or Drop Method
- Capillary or Dale and Laidlaw’s Method
“Short draw” specimens ( specimens with smaller volume than the minimum specified by the manufacturer generates what result?
erroneously PROLONGED results
“Short draw” specimens ( specimens with smaller volume than the minimum specified by the manufacturer generates what result?
erroneously PROLONGED results
Admixture with tissue juice will generate what result?
“SHORTENED “ results
This group is not consumed on coagulation & are not dependent on Vit.K for their synthesis.
Contact group
This anticoagulant may be required for specimens for molecular diagnostic testing, such as testing for Factor V Leiden mutation.
EDTA
This gel tubes may be used for molecular diagnosis as specified by the institution
acid citrate dextrose (ACD, yellow closure) and dipotassium EDTA (K2EDTA), white closure)
Contact group is unstable
true or false
false
stable
This anticoagulant suppress in vitro platelet or coagulation activation for specialty assays such as the platelet activation marker platelet factor 4 ( PF4) or the coagulation activation marker thrombin- antithrombin complex (TAT).
Citrate theophylline adenosine dipyridamole (CTAD, blue closure)
This anticoagulant may be necessary to produce accurate platelet counts in cases of platelet satellitosis (satellitism) as substitute for specimens collected in EDTA.
Heparin
This group is not adsorbed out of plasma by BaSO4 & Al(OH)3
Contact group
If samples are left at room temp. for an extended time, what factors are likely to deteriorate?
Factors V &VIII
PK and HMWK also function in fibrinolysis.
True or false
TRUE
What factors and blood component tend to be prematurely activated at refrigerator temp.( 1-6C) and large multimer VWF may be precipitated.
Factors VII & XI, platelets
What type of plasma may be stored at -4 C or lower for at least several weeks w/out loss of most factors?
Platelet Poor Plasma (PPP)
What are the FOUR classifications of Coagulation Factors as to FUNCTION?
SCST
- Serine protease
- Cofactors/Accelerators
- Substrate
- Transglutaminase/Transamidase
Thawing of plasma should be done rapidly in what temp?
37C incubator or water bath
True or False: Thawed plasma cannot be refrozen
True
What factors are involved in enzymes, serine protease?
A-six
kallikrein, IIa, VIIa,IXa,Xa,XIa,XIIa
Table: Prekallikrein, Serine Protease Ia, IXa, Xa, XIa, Factor XIIIa
True or False: Changes in the pH of samples can affect values by shortening clotting time
False.
PROLONGING clotting time
What factors are involved in cofactors/accelerators?
Tissue factor (from the membranes of fibroblasts & smooth muscle cells, Factors Va, VIIIa, HMWK)
What factors are involved in cofactors/accelerators?
Tissue factor (from the membranes of fibroblasts & smooth muscle cells, Factors Va, VIIIa, HMWK)
Table: Factor V (Labile Factor), Factor VIII:C (AHF)
What factors are included in Substrate?
Fibrinogen/Factor I
True or False.
Changes in pH are mediated by the loss of CO2 from the sample. As CO2 is lost, the pH of the sample decreases (acidic).
False. increases (alkalinized)
What factor is included in Transglutaminase/transamidase?
Factor XIII
What factor is included in Transglutaminase/transamidase?
Factor XIII
This solution protect samples against such loss for a period of time. RBC if not exposed to air have a buffering effect, too.
buffered citrate solution in evacuated tubes
Normal samples collected in evacuation tubes & stored unopened at room temp. for as long as how many hours?
6 hours
True or False. In phlebotomy, release the tourniquet as soon as the blood enters the 1st tube( within 1 minute) or the syringe
True
Tubes with blood should be how many percent of the evacuation’s tube volume.
+/ - 10%
True or False. All tubes used for coagulation studies should have non-contact surface
True
This institution recommends 0.105- 0.109 M sodium citrate (3.2%) as anticoagulant
Clinical and Laboratory Standards Institute (CLSI )
What are the THREE classifications of Coagulation Factors by Physical Properties?
FPC
- Fibrinogen/Thrombin sensitive group
- Prothrombin/Vitamin K dependent group
- Contact group
What is the recommended dilution of sodium citrate according to CLSI?
1:10
What is the recommended dilution of sodium citrate according to CLSI?
1:10
What are the Coag factors included in Contact group?
XII, XI, Prekallikrein, HMWK
True or False. Buffering stabilizes pH & increases stability of labile factors.
True
True or False. Samples of patients with high hematocrits contain more plasma.
False. less plasma
Specimens (whole blood)should be centrifuged within how many hour/s after obtaining the sample?
1 hour
After centrifugation, plasma shd. be separated immediately with what kind of pipettes?
plastic or siliconized pipettes
What are the Coag factors included in Fibrinogen/Thrombin-sensitive goup
last factor with a roman numeral; in between last factor
I, V, VIII, XIII
True or False. Only 2/3 of the plasma layer shd be aspirated & stored in a stoppered plastic or siliconized tube.
False. 3/4
True or False. The buffering effect of red cells is lost once the sample is centrifuged and exposed to air.
True
Testing should be done immediately on centrifuged samples or the plasma should be stored at 6C not to exceed 2 hrs.
False. 4C
Plasma should not be frozen if testing can be done within how many hours after collection?
2 hours
What are the coag factors in Prothrombin/Vit. K dependent group?
II, VII, IX, X, PC, PS
What are the coag factors in Prothrombin/Vit. K dependent group?
II, VII, IX, X, PC, PS
They bind, stabilize & enhance the activities of their respective enzymes.
Cofactors/Accelerators
What is an example of a cofactor that triggers the extrinsic pathway.
thromboplastin
Thromboplast is composed of what?
composed of tissue juice & PPL
thrombomodulin, PS, PZ are also cofactors.
tRUE OR FALSE
TRUE
This comes from endothelial cells
& controls PC
Thrombomodulin
Thrombomodulin is fibrinolytic
True or false
FALSE
antifibrinolytic
Thrombomodulin is fibrinolytic
True or false
FALSE
antifibrinolytic
This binds to thrombin & alters its substrate preference.
Thrombomodulin
This catalyzes the formation of covalent bonds between the carboxy terminals of gamma chains from adjacent D domains in the fibrin polymer
Transglutaminase
Transglutaminase catalyzes the formation of covalent bonds between what ?
between the carboxy terminals of gamma chains from adjacent D domains
With the exception of platelet function tests, plasma for coagulation tests should be what type of plasma?
platelet poor/ ordinary plasma
Transglutaminase catalyzes the formation of covalent bonds between the carboxy terminals of gamma chains from adjacent D domains in the what?
in the fibrin polymer.
Transglutaminase catalyzes the formation of covalent bonds between the carboxy terminals of gamma chains from adjacent D domains in the what?
in the fibrin polymer.
What are the FOUR stages in Coagulation?
- Contact Phase
- Activation of the common pathway
- Conversion of prothrombin to thrombin
- Formation of a stable fibrin clot
Prothrombin is what factor?
Factor II
Thrombin is what factor?
Factor IIa
In some books, there are only 3 stages only
What are the THREE stages of Coagulation?
- Thromboplastin generation
- Conversion of prothrombin to thrombin
- Conversion of fibrinogen to a stable fibrin clot by thrombin
This is the phase wherein there is exposure of collagen/subendothelium
Contact Phase
This pathway is activated by the release of Factor III (TF/Tissue Thromboplastin) into the plasma from injured tissues (collagen injury)
Extrinsic Pathway
This is the pathway wherein activation occurs when a vessel is injured, exposing the subendothelial tissues, basement membrane and collagen.
Intrinsic Pathway
This is the pathway wherein activation occurs when a vessel is injured, exposing the subendothelial tissues, basement membrane and collagen.
Intrinsic Pathway
The instrinsic pathway will lead to the activation of what factors?
pH CF
- “contact factors”
- Factor XII
- HMWK
- prekallikrein.
For some tests, centrifugation of samples is at what degrees?
2-4C
plasma double centrifuged to achieve a platelet count of less than 5,000/uL.
platelet free plasma
Required for certain coagulation tests such as for LA where it is optimal for specimens to be frozen.
platelet free plasma
Plasma required for all coagulation testing. It may be frozen.
platelet poor plasma
plasma centrifuged at 50 x g to achieve a platelet count of 200,000/uL.
platelet rich plasma
This is an assembly molecule( membrane) needed in almost all phases of the intrinsic pathway.
Platelet Factor 3
Plasma used for light transmission platelet aggregometry
platelet rich plasma
What platelet factor 3 in particular is an assembly molecule( membrane) needed in almost all phases of the intrinsic pathway?
phosphatidylserine, in particular
Blood prep: 4.5 ml blood +0.5 ml 0.109M sodium citrate. Store in refrigerator not more than 2 hrs.
Patient’s plasma
Blood prep: 2ml of plasma + 0.2 ml adsorbing reagent ( BaSO4/ Al(OH)3. Centrifuge at 3000 rpm for 3 mins. Refrigerated plasma should be used within 2 hrs.
Adsorbed normal plasma
It is called INTRINSIC since most factors here are in the blood.
TRUE OR FALSE
TRUE
It is called INTRINSIC since most factors here are in the blood.
TRUE OR FALSE
TRUE
Blood prep: collect plasma in the usual manner then incubate at 37 C for 24 hrs. Store in aliquots at -20 C.
Aged normal plasma
This pathway starts with the activation of Factor X to Factor Xa by the intrinsic & extrinsic pathways. Then, Factor Xa in the presence of Factor Va,Ca,PPL( prothrombinase complex) activates Protthrombin to Thrombin
COMMON PATHWAY
The common pathway starts with the activation of what?
with the activation of Factor X to Factor Xa
Blood prep: collect serum in the usual manner. Allow to stand at room temp. For 24 hrs. Divide in aliquots and freeze.
Aged normal serum
The common pathway starts with the activation of Factor X to Factor Xa by what?
by the intrinsic & extrinsic pathways.
The common pathway starts with the activation of Factor X to Factor Xa by what?
by the intrinsic & extrinsic pathways.
Blood prep: 9 parts blood + 1 part 3.2% sodium citrate(0.109 M ). Centrifuge at 3000 for 30 mins.
Platelet-poor plasma (ppp)
Blood prep: Mix blood as in PPP. Centrifuge at 1500 rpm for 5 mins.
Platelet-rich plasma (PRP)
What are the acquired hereditary inhibitors?
F I V
Anti-VIII
Anti-IX, anti-X, anti-V, anti-I, anti-XIII and anti-vWF
Factor Xa in the presence of what factors activates Prothrombin to Thrombin?
Factor Va, Ca, PPL (prothrombinase complex)
What is the acquired non-hereditary inhibitor associated with postpartum, autoimmune disorder?
Anti-VIII
What is the acquired non-hereditary inhibitor related to Streptomycin therapy?
Anti-V
They are essential for the assembly of 3 membrane complexes leading to the generation of thrombin.
Vit . K dependent procoagulants
What is the acquired non-hereditary inhibitor related to Isoniazid therapy?
Anti-XIII
Anticoagulant with no clinical manifestation. It neutralizes the PPL reagent in APTT resulting to its prolonged result.
Lupus anticoagulant
Enumerate the Non-hereditary acquired inhibitors
Anti-VIII-postpartum, autoimmune disorder
Acquired vWF disease
Anti-IX
Anti-XI
Anti-V- related to Streptomycin therapy
Anti-XIII- related to Isoniazid therapy
Lupus anticoagulants-no clinical manifestation. It neutralizes the PPL reagent in APTT resulting to its prolonged result.
What is the non-enzymatic cofactor of Vit K dependent procoagulants?
Vit K dependent serine protease
Anticoagulant like PS is also a cofactor in the regulation and control of coagulation. It is a cofactor to Z-dependent protease inhibitor (ZPI)
Protein Z-dependent protease inhibitor- Serpin-
Anticoagulants which is more active when heparin is present.
Protein C Inhibitor- Serpin
In Vit. K dependent procoagulants, this is bound to the negatively charged PPL membranes of activated platelets/TF –bearing cells.
Calcium
Anticoagulant which is a slow reacting thrombin inhibitor which inhhibits Factor XIa and Xa.
Alpha1 Antitrypsin/ Alpha 1 protease inhibitor
Anticoagulant which inactivates Factor XIIa and kallikrein, Factor XIa and plasmin.
C1 inhibitor
Calcium is bound to the positively charged PPL membranes of activated platelets/TF –bearing cells.
TRUE OR FALSE
FALSE
negatively charged
Calcium is bound to the positively charged PPL membranes of activated platelets/TF –bearing cells.
TRUE OR FALSE
FALSE
negatively charged
Anticoagulant which came from endothelial cells, and also expressed on platelets;lipoprotein associated inhibitor(LACI) that inhibits Xa, binds TF:VIIa.The principal regulator of the TF pathway.
Extrinsic Pathway Inhibitor/ Tissue Factor Pathway Inhibitor
Calcium is bound to the negatively charged PPL membranes of what?
of activated platelets/TF –bearing cells.
Anticoagulant that forms complex with thrombin, kallikrein, thus inhibiting their activities.
Alpha 2 Macroglobulin-Serpin
Anticoagulant that inhibits thrombin rapidly in the presence of dermatan sulfate, heparin sulfate, or heparin.
Heparin cofactor II (HC II)- Serpin
major inhibitor of thrombin and Factor Xa.Its activity is enhanced by heparin to 2000x. The mfirst to be identified and the first to be assayed routinely.
Antithrombin III/ antithrombin- a Serpin
In Vit. K dependent procoagulants, what are the composition of each complex?
PIE
- Prothrombinase
- intrinsic tenase
- extrinsic tenase
Anticoagulant that inactivates the clotting cascade by inducing thrombin to activate PC. Produced by endothelial cells.
Thrombomodulin
Anticoagulant which is a vitamin K dependent protein and also produced by the liver. This functions to enhance binding of Protein C to phospholipid surfaces and increase the rate of Factors Va and VIIIa inactivation by Protein C.
Protein S
True or False. When plasma C4bBP increases, additional PS is bound & free PS levels become proportionally decreased, wc may increase risk of thrombosis.PS is also a cofactor of TFPI.
True
This composition of the vit K dependent procoagulant complex is composed of Factor VIIa and TF
extrinsic tenase
Anticoagulant produced by the liver and is a major inhibitor of blood coagulation. This inactivates Factors VIII:C and Va in the presence of cofactor Protein S. a Vit.K dependent protein.
Protein C
This composition of the Vit K dependent procoagulant complex activates FX to Xa wc are components of intrinsic tenase and prothrombinase.
extrinsic tenase
Converts Factor XIII to XIIIa
Procoagulant
Induces platelet activation and aggregation
Procoagulant
Activates cofactor VIII to VIIIa
Procoagulant
Via autocatalysis converts Prothrombin to Thrombin
Procoagulant
Binds antithrombin to inhibit serine proteases
Coagulation Inhibitor
Binds to thrombomodulin to activate protein C (inhibits Va & VIIIa)
Coagulation Inhibitor
Induces cellular chemotaxis
Tissue Repair
Stimulates proliferation of smooth muscle and endothelial cells.
Tissue Repair
This formation marks a critical event in the hemostatic process.
Thrombin formation
This composition of the vit K dependent procoagulant complex is composed Factor IXa and its cofactor Factor VIIIa
intrinsic tenase
This composition of the vit K dependent procoagulant complex activates Factor X to Xa but much more efficiently than TF:VIIa complex
intrinsic tenase
Give the 4 actions of Thrombin (CAEI)
Converts fibrinogen to fibrin
Activates Factor XIII to Factor XIIIa
Enhances the activity of Factors V & VIII
Induces platelet aggregation.
In vivo, the endpoint of coagulation mechanism is what?
stable fibrin clot
In vitro( coagulation tests), the end point detected is
fibrin polymer
This composition of the Vit K dependent procoagulant complex is composed of Factor Xa and its cofactor Factor Va
Prothrombinase
acute phase reactants whose level increases in inflammation, trauma, stress, infections. (FPFV)
Fibrinogen, Prothrombin, Factor VIII, VWF
This happens in the presence of PPL and Ca.
Prothrombinase
Prothrombinase converts what?
prothrombin to thrombin
They absorb, transport and release abundant fibrinogen.
Platelets’ alpha granules
This converts prothrombin to thrombin in a multistep hydrolytic process that releases thrombin and a peptide fragment
Prothrombinase
The primary serine protease of the fibrinolytic system, also becomes covalently bound via lysine moieties
Plasmin
peptide fragment called …
prothrombin fragment 1.2 (F1.2)
This is a marker for thrombin generation.
Prothrombin fragment 1.2 (in plasma)
A serine protease that ultimately hydrolyzes & activates bound plasminogen to initiate fibrinolysis.
TPA (Tissue Plasminogen Activator)
Prothrombin fragment 1.2 in plasma is a marker for what?
marker for thrombin generation
What factor catalyzes the formation of covalent bonds between the carboxy terminal of gamma chain from adjacent D domains?
Factor XIII
When there is thrombin generation, fibrinolysis will follow, then coagulation.
TRUE OR FALSE
FALSE
coagulation will follow, then fibrinolysis
When there is thrombin generation, fibrinolysis will follow, then coagulation.
TRUE OR FALSE
FALSE
coagulation will follow, then fibrinolysis
a plasma protein involved in cell adhesion
fibronectin
They form to provide an insoluble meshwork of fibrin polymers linked by their D domains.
Multiple cross-links
Fibrinogen Structure and Fibrin Formation measurement
340kD, 200-400mg/dL
The alpha granules of platelets transport and release what?
fibrinogen
What transports and releases fibrinogen?
alpha granules of platelets
This molecule is a mirror- image dimer,with each half consisting of 3polypeptide designated as alpha,beta,and gamma united by disulfide bonds
Fibrinogen
Fibrinogen is a molecule that is a mirror- image dimer,with each half consisting of how many polypeptides?
3 polypeptides
factor that has the shortest plasma half-life at 6 hours
Factor VII
The three polypeptides of fibrinogen is designated as what?
designated as alpha,beta,and gamma
Fibrinogen is a molecule is a mirror- image dimer,with each half consisting of 3polypeptide designated as alpha,beta,and gamma united by what?
disulfide bonds.
Factor that is non-Vitamin K dependent and is not affected by dietary Vitamin K deficiency
Factor V
The 6 amino terminal assemble to form a bulky central region called the what?
E domain
The carboxy terminal assemble at the 2 ends of the molecule to form what?
2 D domains.
This cleaves from the protruding amino terminal of fibrinopeptides A &B.
thrombin
Thrombin cleaves from the protruding amino terminal of what?
of fibrinopeptides A &B
An acute phase reactant that frequently becomes elevated in early or mild liver disease
Fibrinogen
. Each of the 2 alpha & beta chains,reducing the overall mol.wt. by 10,000D
True or False
TRUE
The cleaved fibrinogen is called
FIBRIN MONOMER
Factors used to differentiate Liver disease from Vitamin K deficiency
Factors V and VII
The exposed alpha & beta chain ends (E domain) have an immediate affinity for portions of the D domain of neighboring monomers spontaneously polymerizing to form fibrin polymer.
true or false
true
Test that duplicates thrombin time test except that venom of the reptile Bothrops atrox is substituted.
Reptilase time
