hema cram Flashcards
What is the physiologic response to vascular injury?
Limit blood loss
What are the characteristics of hemostasis?
Rapid, localized, well-regulated
Who published a sequence of proteolytic reactions for coagulation?
MacFarland
What begins the coagulation cascade?
Factor XII activation
What substance does Thrombin proteolyze to form a clot?
Fibrinogen
What did patients with Factor XII Deficiency show?
Did not bleed
What is a key feature of the cell-based model of hemostasis?
Cellular elements express TF
Which cells provide a phospholipid surface for coagulation?
Endothelium, Platelets
What does Thrombin convert Fibrinogen into?
Fibrin Clot
What are the two groups of zymogens in the Coagulation System?
Phospholipid-Bound, Surface-Bound
What is the role of Vitamin K in coagulation proteins?
Essential for γ-carboxylation
What does the γ-carboxylation reaction allow coagulation proteins to do?
Bind to phospholipid and cell membranes
What is necessary for proteins FX, FIX, FVII, and FII to function normally?
Carboxylation reaction
What does activated Protein C do?
Inactivates FVa and FVIIIa
What role does Protein S play?
Natural anticoagulant
What is K-dependent and acts as cofactor for APC?
Surface-Bound
What are the proenzymes of the Plasma Kallikrein/Kinin System?
FXII, Prekallikrein, FXI
What are the protein zymogens of the CONTACT SYSTEM?
FXII autoactivation
What common laboratory test uses FXII autoactivation?
Activated Partial Thromboplastin Time (APTT)
What are the types of Urokinase Plasminogen Activator?
ScuPA, TcuPA
Where are these plasminogen activators found?
Endothelium, Neutrophils, Monocytes
What do tPA, ScuPA, and TcuPA do?
Convert Plasminogen to Plasmin
How is tPA produced?
Constitutively
What increases ScuPA levels?
Inflammatory states
What is the major inhibitor of tPA and TcuPA?
Plasminogen Activator Inhibitor-1 (PAI-1)
What can TAFI do to control Plasmin?
Remove lysine residues from Fibrin
What is the active Plasmin molecule?
A potent protease
What does Plasmin do to soluble Fibrinogen?
Produces Fibrinogen Degradation Products
What does Plasmin cleave Fibrinogen into?
An X Fragment
What complex does TFPI form?
FVIIa, TF, FXa
Where is TFPI produced?
Microvascular endothelium
What condition is associated with murine TFPI knockout?
Embryonically lethal
Where is AβPP present?
Platelets and brain
Which factors does AβPP regulate?
XIa, IXa, Xa, VIIa/TF
What does AβPP not inhibit?
Thrombin
What enzyme produces Prostacyclins (PGI2)?
Cyclooxygenase-2
What is the function of PGI2?
Vasodilator, inhibits platelet aggregation
What hormone is involved in controlling hemostasis?
Vasoactive hormones
What are believed to be cerebral anticoagulants?
Prostacyclins, Nitric Oxide, Thrombospondin-5
How do Prostacyclins mediate their actions?
IP Receptors and PPARs
What enzyme do endothelial cells express?
eNOS (NOS3)
What is a significant function of Nitric Oxide?
Potent vasodilator
What does NO inhibit?
Platelet adhesion and aggregation
What does NO activate?
Guanylate Cyclase and cGMP
What do activated platelets produce under shear flow?
NO
What is Thrombospondin-5 also known as?
COMP
What type of protein is COMP?
Extracellular protein
What tissues release COMP?
Cartilage and muscle
Common presentations of Secondary Hemostasis defects?
Ecchymoses, soft tissue, joint bleeds
Types of bleeding tendencies?
Congenital or acquired
What is necessary before laboratory testing for bleeding?
Personal and family history
When are congenital bleeding disorders usually diagnosed?
Early childhood
When might mild bleeding disorders be revealed?
Later in life with hemostatic challenge
What are Routine Coagulation Screening Tests used for?
Identify hemostatic defects
Is it clinically useful to perform coagulation tests on nonbleeding patients?
Not clinically useful
What tests are considered screening coagulation tests?
PT, APTT, Fibrinogen, Thrombin Time, D-Dimers
What is the collection ratio for whole blood in Sodium Citrate?
9:1 Blood:Citrate
How should blood specimens be mixed after collection?
Gently invert 3 to 5 times
What is the transport requirement for the specimen?
Room temperature, within 4 hours
What should be done if testing cannot be performed within 4 hours?
Centrifuge and freeze
Why should separated plasma be platelet free before freezing?
To prevent false low anti-FXa
What is the threshold for platelet count in separated plasma before freezing?
<10 K
What does platelet factor 4 bind to?
Heparin
What is the Fibrin Stabilizing Factor?
XIII
Cellular Component consists mostly of what?
PLATELETS and ENDOTHELIAL CELLS
What does the Large Group of Plasma Proteins participate in?
clot formation
What is vascular integrity BREACHED?
vascular injury
Where is it found?
most tissues and cells
What is the cause of the formation of complexes with FVII?
hemostatic reactions
What results in the formation of complexes with FVII that produce the initiation of hemostatic reactions?
Upregulation of TF
What is the cofactor for FIXa when it is activated?
FVIIIa
What is the most severe clinically recognized bleeding disorder?
Hemophilia A. FV
What is a protein with homology to FVIII?
330-kDa
What is the main substrate of FII?
Thrombin Fibrinogen
What is the principal adhesive molecule for platelet aggregation?
330-kDa
What proteolyzes Fibrinogen?
Thrombin
What is formed when Fibrinogen is proteolyzed by Thrombin?
a FIBRIN MONOMER
What type of FIBRIN CLOT do monomers associate end to end and side to side to form?
polymerized FIBRIN CLOT
What are the most prominent bleeding disorders that occur in patients who survive gestation and birth?
Deficiencies in coagulation Factors VIII and IX
What type of patients have congenital deficiencies of coagulation Factor VII, X, V, and II?
rare
Rare patients who have what type of deficiencies of coagulation Factor VII, X, V, and II usually do not have severe bleeding states?
congenital deficiencies
What is the order structure of the Prothrombinase Complex?
FII (Prothrombin)
What are the components of the Prothrombinase Complex?
phospholipid membranes or cell membranes
What is the Endothelial Protein C Receptor?
EPCR
What does the complex formed by APC+EPCR need to do to allow binding of APC with Protein S to inactivate FVa and
DISSOCIATE
How does APC bind to cell surfaces in a way that orients itself to inactivate?
FVa and FVIIIa
What does the enzyme use to localize its activity to perform its inhibitory function?
receptor
What is in equilibrium between the FREE FORM (40%) and a BOUND FORM (60%)?
Plasma Protein S
How many Receptors on Endothelial Cells bind APC to?
3
What is the PAR?
Protease-Activated Receptor
What may contribute to the anticoagulant function of Activated Protein C by liberating tPA?
Activation of PAR1
What is the inhibitor effect on FIIa Heparin Cofactor II?
4000-fold
What is Factor Xa dependent?
Vitamin K3
What is the causative factor for Types I and II Hereditary Angioedema?
The absence of C1 Inhibitor
What is the most potent inhibitor of the FVIIa-Tissue Factor Vomplex?
Kunitz-Type Serine Protease Inhibitor
Who was the downloader of lOMoARcPSD?
Princess Therese Timbal
What does COMP inhibit?
Thrombin
What are EXPOSED at the site of endothelial cell injury?
Subendothelial Collagen and Von Willebrand Factor
What does the platelet undergo from DISCOID to SPHERICAL?
SHAPE CHANGE
GPIb/IX/V Receptors are binding to what?
vWF
What is followed by platelet Adhesion?
SECRETION
What is the name of the path that releases the contents of Alpha and Dense Granules from Platelets?
the Cyclooxygenase-1 (COX-1) Pathway
What parts of Platelets are released during Secretion?
Alpha and Dense Granules
What causes ACTIVATION TXA2?
vasoconstriction
ACTIVATION TXA2 causes vasoconstriction and ACTIVATES PLATELETS via what?
TXA receptor
What leads to exposure of Phosphatidylserine?
Activation of Platelets
What does Phosphatidylserine begin to produce?
Thrombin
What can be divided into 2 different phases?
secondary Hemostasis
TF PATHWAY is the initiator of what?
coagulation 2.
What is the name of TF PATHWAY?
EXTRINSIC PATHWAY
INTRINSIC PATHWAY amplifies and propagates what?
thrombin generation
What does the TF Pathway begin with on the cell surface?
ENDOTHELIAL INJURY and EXPRESSION OF TF
What is the name of the complex that activates FX to FXa?
Extrinsic Tenase
Extrinsic Tenase activates FX to FXa on the cell surface in the presence of what?
Ca++
What does ASE COMPLEX form?
Thrombin
What is the cell surface of the FXa?
PL
What converts Prothrombin to Thrombin?
PROTHROMBINASE COMPLEX
What is the cell surface of the Intrinsic Pathway?
Ca++
What is the cell surface of FIXa?
PL
What forms the INTRINSIC TENASE?
FIXa
What is the primary pathway of THROMBIN FORMATION?
Intrinsic Pathway
What is the Intrinsic Pathway?
AMPLIFIER AND PROPAGATOR of Thrombin
What is the INITIATOR?
TF Pathway
What would patients with Hemophilia A and B have if they were independent pathways producing Thrombin?
bleeding tendencies
What are the test tubes that assess Thrombin?
Prothrombin Time (PT) and Activated Partial Thromboplastin Time (APTT)
What is the main enzyme in the coagulation system?
Thrombin
What does Thrombin convert Fibrinogen to?
Fibrin Monomers
What does it activate to cross-link fibrin monomers to stabilize the clot?
FXIII to FXIIIa
What are released from platelet membranes?
Phospholipids
What do Phospholipids release from platelet membranes bind to?
Lupus Anticoagulant
How long should the specimen be held at room temperature?
4 hours
What is often encountered in office clinics that send out their specimens to remote reference laboratories for coagulation testing?
Improper sample handling
What part of coagulation testing is crucial for accurate diagnosis and management?
preanalytic
What does PT contain?
tissue Thromboplastin and CaCl2
What are the Coagulation Factors in the Intrinsic Pathway and what other path?
Common Pathway
What does APTT generally assess in the Intrinsic Pathway and Common Pathway?
Coagulation Factors
What type of contact factor is activated in APTT?
PLs
What is the activation of in APTT?
Contact Factors
How many different quantities of PL are available in the APTT reagents?
three
What are the three APTT reagents with different sensitivities for various needs?
a.
What does APTT-FS have the highest amount of?
PL
What is APTT-FS?
-Factor Sensitive
What is the smallest amount of PL?
weak LA
What does APTT-FSL detect?
decreased amounts of coagulation factors and lupus anticoagulant
What is the term for PL?
c. APTT-FSL
What is a common clinical finding?
prolonged APTT
What should further investigation be dictated by if the presenting symptom is the presenting symptom?
a personal and family history of bleeding
What is prolonged in a bleeding patient?
APTT
What should be considered and investigated by measuring FVIII first?
a CONGENITAL BLEEDING DISORDER of INTRINSIC PATHWAY
What is the name of the DISORDER of INTRINSIC PATHWAY?
FIX
Why is Thrombin time not a commonly ordered test?
limited utility
What is added to the patient’s plasma and the clotting time recorded?
Bovine Thrombin
How long should the upper limit of the normal range be adjusted to make TT more sensitive to detect DYSFIBRINOGENEMIA?
25 sec
