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Hemostasis: Medical Lab Science Focus
Primary, Secondary Hemostasis, Fibrinolysis; Coagulation Factors + inhibitors; Coag Testing; Coagulopathies
60
Medical
Undergraduate 4
12/08/2022

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Term
Hemostasis
Definition
Process that leads to the cessation of bleeding from a blood vessel
Term
Factors Influencing Hemostasis
Definition
1. Type and degree of vessel damage
2. Ability of vasoconstriction to occur
3. Availability of platelets and their functionality
4. Availability of clotting factors and their functionality
5. Absence of inhibitors and anticoagulants
Term
Hemostatic Mechanisms
Definition
1. Vascular Damage
2. Exposed Subendothelium
3. Platelet Adhesion
4. Platelet Aggregation
5. Platelet Plug Formation
6. Fibrin Stabilization
Initialization #1 and #2
Primary Hemostasis #3,#4,and #5
Secondary Hemostasis #6
Term
Primary Hemostasis
Definition
Vasoconstriction
Rerouting of Blood Flow
Platelet Aggregation
Contact activation of coagulation system (startup of secondary hemostasis)
Term
Platelets in Hemostasis
Definition
Develop Platelet Plug via binding collagen and basement membrane; this binding causes shape change in the plts; promotes plts to bind to one another (Plt aggregation)
Main Functions
1. Maintenance of Vascular integrity
2. Platelt plug formation
3. Stabilization of plt plug; fibrin strands weave around bound plts creates fibrin clot
Term
Platelet Kinetics
Definition
1. Adhesion' adhere collegen take on spiny shape and vWF is absorbed by surface receptors on plt and exposed subendothelial tissue
2. Release; plts dump contents of granaules adid in aggregation process; act as chemical signal
3. Aggregation; plts bind eachother; chemical signal stimulation
4. Stabilization; Addition of interwoven fibrin strands which produce fibrin clot
Term
The Coagulation Cascade
Definition
1. Intrinsic Pathway
2. Extrinsic Pathway
3. Common Pathway
Term
The Extrinsic Pathway
Definition
Tissue Factor interaction with Factor VII (circulating factor) leads to activation of Factor VIIa which catalyzes the reaction of factor X to Xa
Term
Control of the Extrinsic Pathway
Definition
Controlled by Tissue Factor Pathway Inhibitor TFPI; binds and inhibits Factor X; Controls the initiation of the Common Pathway
Term
The Intrinsic Pathway
Definition
Collagen exposure leads to HMWK, Prekallikrien (Fletcher Factor), and Factor XII (Hageman Factor) forming a complex. This complex catalyzes a conversion of factor XII to its active form XIIa which triggers the intrinsic pathway. XIIa triggers conversion XI to XIa (in presence of HMWK). XIA converts Factor IX to IXa in presence of Ca2+. IXa, Ca2+, plt factor, and factor VIII activate Factor X which activates prothrombin to thrombin in the common pathway
Term
The Common Pathway
Definition
Activation of Factor X into Xa. Xa in the presence of factor V (cofactor), Ca2+, and plt factor convert prothrombin to its active form thrombin. Thrombin catalyzes the conversion of frinogen into fibrin monomer. Thrombin also causes conversion of factor XII into XIIa (stabilizing fibrin monomers)
Term
Factor I
Definition
Fibrinogen
Intrinsic, Extrinsic, Common
Term
Factor II
Definition
Prothrombin
Intrinsic, Extrinsic, Common
Vitamin K
Term
Factor III
Definition
Tissue Thromboplastin
Extrinsic
Term
Factor V
Definition
Proaccelerin
Intrinsic, Extrinsic, Common
Term
Factor VII
Definition
Proconvertin
Extrinsic
Vitamin K
Term
Factor VIII
Definition
Antihemophiliac Factor
Intrinsic
Term
Factor IX
Definition
Christmas Factor
Intrinsic
Vitamin K
Term
Factor X
Definition
Stuart-Prower Factor
Intrinsic, Extrinsic, Common
Vitamin K
Term
Factor XI
Definition
Plasma Thromboplastin
Intrinsic
Term
Factor XII
Definition
Hageman/Contact Factor
Intrinsic
Term
Factor XIII
Definition
Fibrin Stabilizing Factor
Intrinsic, Extrinsic, Common
Term
Prekallikrein
Definition
Fletcher Factor
Intrinsic
Term
HMWK
Definition
Fitzgerald Factor
Intrinsic
Term
Fibrinolysis
Definition
Fibrin is broken down and removed from the clot which leads to the complete dissolution of the clot
Term
The Fibrinolytic System
Definition
Plasminogen->Plasmin->Fibrin Clot->D-Dimer
Term
Blood Collection Tube Used in Coagulation Testing
Definition
Sodium Citrate; Light Blue Top; 9:1 blood to anticoagulant ratio
Waste Tube should be used
Term
Prothrombin Time (PT)
Definition
Extrinsic and Common Pathways
Factors I, II, V, VII, X
Coag disorder assessment and therapeutic monitoring of oral anticoagulant (such as Warfarin)
reported as number of seconds needed for a clot to form
Value is converted into International Normalized Ration (INR)
Term
PT Therapeutic Range
Definition
2.0-3.0 INR
INR= (PT of patient/PT of geometric mean of the normal population)^ISI
ISI=International Sensitivity Index (sensitivity of the manufacture reagent)
Term
Activated Partial Thromboplastin Time (APTT)
Definition
Intrinsic and Common Pathway
Factors I, II, V, VIII, IX, X, XI, XII, Prekallikrein, and HMWK
Factor VII and XIII are not assayed in this test
Used to determine therapeutic effectiveness of heparin
Term
Fibrinogen Assay
Definition
Measures Factor I; Determines if there is enough fibrinogen present for normal clotting
Perform when there is a prolonged abnormal PT and/or APTT
Normal Range is 200-400 mg/dL
Levels <100mg/dL associated with free bleeding
Term
D-Dimer Test
Definition
Indicates fibrin has been formed and degraded (fibrinolysis)
Elevated when coagulation is activated
Confirms that thrombin and plasmin have been generated
Dx for DVT and PE
Term
Fibrin/fibrinogen Degradation Products (FDP) Assay
Definition
Detects degradation products of fibrinolysis less specific compared to the D-Dimer test similar to it.
Term
Platelet Function Assay (PFA)
Definition
Aspirin and other drugs falsely prolong platelet function
Term
Mixing Studies
Definition
Performed after unexpected prolonged PT or APTT
If addition of pooled plasma corrects then that means the patient has a factor deficiency. If it is not corrected it means the patient has an inhibitor.
Term
Factor Assays
Definition
Tested on unexpected prolonged Pt or APTT
Performed after mixing studies
Confirmatory test for the mixing study screening test
Test for specific factor deficiencies
Term
Hemophilia A
Definition
Deficiency of Factor VII
Inherited or auto-antibodies produced against VII
Sex-linked inheritance
Term
Hemophilia B
Definition
Deficiency of factor IX.
Sex-linked recessive inheritance
Term
Von Willebrands Disease
Definition
Platelet Disorder; functional defect in vWF. Decrease function of Factor VIII. Impaired platelet adhesion and aggregation. VWD stabilizes factor VIII
Treated with DDAVP raises levels of vWF and factor VIII
Term
Vitamin K Deficiency
Definition
Loss of functionality of vitamin k dependent factors II, VII, IX, X (Known as the Prothrombin group)
Term
Disseminated Intravascular Coagulation (DIC)
Definition
Clotting factors are depleted in the blood due to them being used up.
Term
Bernard-Soulier Syndrome
Definition
Genetic platelet disorder characterized by abnormally larger platelets and a mod decrease in
platelet count. Bleeding
Term
Liver Disease and Coagulation Disorders
Definition
Decrease in vit K dependent factors
Increase in Factor VIII
Prolonged PT
Lack of fibrinogen
Term
Heparin
Definition
IV or subcutaneously
Inhibits Thrombin
Term
Warfarin
Definition
Orally given
Vitamin K antagonist
Term
Lupus Anticoagulant
Definition
Most common
directed towards phospholipids
IgG Antibody
Causes Thrombosis and Abnormal clotting
Term
Coagulation Inhibitors
Definition
most common= anti-factor VIII
acquired hemophilia a
2nd most common= anti-factor IX
acquired hemophilia b
Term
Prolonged PT
Definition
Warfarin
Liver disease
DIC
Vit K deficiency
Cirrhosis
Hepatitis
Inadequate levels factor I, II, V, VII, X
Term
Prolonged aPTT
Definition
Heparin
Liver disease
Vit K Defieciency
Hemophilias
DIC
von Willebrand Disease
Lupus anticoagulant
Inadequate levels factor I, II, V, VIII, IX, X, XI, XII
Term
False Elevation of PT or aPTT
Definition
Blood collection error
Hct >55%
Clotted Specimen
Heparin contamination (aPTT prolonged)
Term
When to perform a Mixing Study?
Definition
No hx of heparin or warfarin therapy
No hx of liver disease
Prolonged PT and/or aPTT
Term
Mixing Studies Test Principles
Definition
Pt needs >405 of each factor to be detected
Pt with inadequate levels <40$ of any factor would be prolonged and then corrected with the addition of pooled normal plasma (collection of 20 donors which adds up to 1005 of each factor)
Term
Mixing Study Mix of pt and pooled normal plasma
Definition
1:1 mix
Term
Lupus Anticoagulant (LA) Testing
Definition
Dilute Russells Viper Venom Time (DRVVT; Help to ID the Abs dependence on phospholipids
Hexagonal Phospholipid Test (HPP) and Platelet neutralization assay; dependence on phospholipids for LA to take effect
Term
Thromboembolism
Definition
Embolism; obstruction of an artery
DVT, PE
Term
Protein C and S
Definition
Protein C is vitamin K dependent also known as factor XIV; inactivates factor Va and VIIIa. Regulatory protein
Protein S is a cofactor of protein C
Mutated S and c means no off switch and excessive coagulation would occur.
Term
APC Resistance nd Factor v Leiden Mutation Testing
Definition
FVL is a mutation that causes increased thromboembolisms
Russells viper venom time RVVT screenin test for FVL; venom activates factor V and X; pts clotting decreases because venom.
Term
Types of VWD
Definition
Type I: most common; loss in VWF expression mild
Type II: Protien is dysfunctional
Type III: Rare; autosomal recessive; no VWF or Factor VIII activity; spontaneous bleeding
Term
Testing for VWD
Definition
PFAs if both EDP and ADP are prolonged thenits possible theres a plt defect, thrombocytopenia (Plt <100), or anemia (<28% hct)
VWF activity assays
Term
New Oral Anticoagulants NOACs
Definition
Dabigatran (Pradaxa); Thrombin inhibitor; TT, dTT, ECA recommended
Apixaban; Factor Xa Inhibitor
Edoxaban; Factor Xa Inhibitor
Rivaroxaban; Factor Xa Inhibitor
Recommended testing for all drugs except Dabigatran= Anti-Xa
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