Hematology - Hemostasis 2 Flashcards
______ is needed for medium/large vessels.
Fibrin
What cells are key players for secondary hemostasis?
Platelets and fibroblasts
What proteases are involved in secondary hemostasis?
FXIa, FIXa, Fxa, FIIa, and FVIIa
What cofactors are involved in secondary hemostasis?
Tissue factor (FIII), FVa, and FVIIIa
What crosslinkers are involved in secondary hemostasis?
FXIIIa
What activators are involved in secondary hemostasis?
Vitamin K
What inhibitors are involved in secondary hemostasis?
Antithrombin, protein C, and protein S
What is the end result of secondary hemostasis?
Generation of thrombin which forms a crosslinked fibrin clot
Secondary hemostasis is a series of enzymatic reactions involving what three main things?
Coagulation factors, calcium, and Phosphatidylserine on platelets
What does thrombin (FIIa) do?
It cleaves fibrinogen (FI) into fibrin
How does fibrin form the fibrin clot?
It is cross-linked to form the fibrin clot by FXIIIa
What is the extrinsic pathway composed of?
Tissue factor (TF), FVII, and calcium
What is the intrinsic pathway composed of?
FXII, FXI, and FIX, FVIII, calcium, and phosphatidylserine
What is the end result of the intrinsic pathway?
FIXa and cofactor FVIIIa to activate X into Xa
What factors are involved in the common pathway?
Fxa, prothrombin (FII), FXIII (crosslinker), FV, calcium, and phosphatidylserine
What tests assess the functionality of both the intrinsic and common pathways?
Activated partial thromboplastin time (aPTT) and activated coagulation time (ACT)
What test assesses the functionality of the common pathway alone?
Thrombin clot time (TCT)
What tests assess the functionality of both the extrinsic and common pathways?
Prothrombin time (PT) and PIVKA
What is involved in the initiation phase of the cell-based model?
Extrinsic pathway, tissue factor, and the cell surface of fibroblasts
What is involved in the amplification phase of the cell-based model?
Intrinsic factor, thrombin, and the cell surface of the platelet
What cell surface is associated with the propagation phase of the cell-based model?
the platelet
What are the functions of thrombin?
Activation of the intrinsic patway (FXI, FVIII, and FV to make more thrombin), activation of FXIII to crosslink fibrin, cleaves fibrinogen into soluble fibrin, and activation of platelets for more surface for the intrinsic pathway
Which model of secondary hemostasis explains what goes on in the body better?
the cell based model
What can go wrong with secondary hemostasis?
Too few or too many coagulation factors and antagonized or inactive vitamin K
What are the inherited coagulation disorders?
Hemophilia A and B
What coagulation factor is deficient in hemophilia A?
FVIII (8) deficiency
What coagulation factor is deficient in hemophilia B?
FIX (9) deficiency
What are the acquired causes of coagulation disorders?
Anticoagulant rodenticide, DIC, and Liver disease
How does DIC result in a coagulation disorder?
it consumes clotting factors
How does liver disease result in a coagulation disorder?
There is not enough production of clotting factors
How do rodenticides lead to coagulation deficiency?
they antagonize vitamin K - specifically epoxide-reductase enzyme which turns Vitamin K epoxide into Vitamin K quinone
What factors are dependent on vitamin K?
Factors, II, VII, IX, and X
What clinical signs are associated with secondary hemostasis?
Bleeding into body cavities (hemoabdomen and hemothorax), Large bruises/hematomas, joint bleeds (hemarthroses), and prolonged bleeding after surgery and trauma
What screening coagulation assays can be done for secondary hemostasis?
PT, aPTT, +/- TCT/fibrinogen
What in-house test can be done to asses secondary hemostasis?
activated coagulation time
If there is a long PT only, what factor is deficient and what pathway is that associated with?
FVII - extrinsic pathway
If there is a long aPTT only, what factor(s) are deficient and what pathways are associated with that?
FXII, FXI, FIX, and FVIII - Intrinsic pathway
If both PT and aPTT are long, what factor could be deficient, what pathway is that associated with, and could something else be going on?
FX could be deficient so that would mean thecommon pathway is involved. There could also be multiple defects going on
True or False: Hemophilia A only affects males.
True - it is X linked
How are bleeds managed in hemophilia A cases?
transfusions
What physiologic mechanisms are present to keep the extrinsic pathway in check?
Tissue factor pathway inhibitor (TFPI)
What physiologic mechanisms are present to keep factors II and X in the intrinsic and common pathways in check?
Antithrombin
What physiologic mechanisms are present to keep vitamin K in check in the intrinsic and common pathways?
Protein C and S
What therapeutic methods can be used to keep secondary hemostasis in check?
Heparin and warfarin
What toxic methods keep secondary hemostasis in check?
Warfarin-based anticoagulant rodenticides
What does TFPI act on?
TF-FVIIa-Fxa
What does activated protein C, protein S, and thrombomodulin act on?
FVIIIa and Fva
What activates APC and TM?
thrombin
What does antithrombin act on?
thrombin
What does heparin do?
It binds to antithrombin, allowing it to inhibit FII and FXa
What can go wrong with inhibitors?
They are too active, too few, or there are acquired problems with consumption, loss, and decreased production
What is the cause of too active inhibitors?
you are the cause - they are iatrogenic
What can cause consumption of inhibitors?
Sepsis and DIC
What generally can cause loss of inhibitors?
protein-losing disorders
What protein-losing disorders can cause loss of inhibitors?
protein losing enteropathies and protein losing nephropathies
What can cause decreased production of inhibitors?
liver disease
What is tertiary hemostasis?
fibrinolysis to re-establish blood flow through the vessels
What are the cellular players of fibrinolysis?
endothelial cells
What substrate proteins are involved in fibrinolysis?
fibrin
What protease proteins are involved in fibrinolysis?
Tissue plasminogen activator and plasmin
What activator proteins are involved in fibrinolysis?
Activated factor XIIa, bradykinin, and kallikrein
What inhibitor priteins are involved in fibrinolysis?
Thrombin activatable fibrinolysis inhibitor (TAFI), antiplasmin, and plasminogen activator inhibitor (PAI)
What is fibrinolysis?
fibrin clot breakdown by plasmin
What activates plasmin?
tPA
What is the end point of fibrinolysis?
Release of degradation products - D-dimers and fibrinogen degredation product (FDPs)
What are D dimers released from?
cross-linked fibrin
What are the physiologic inhibitors of fibrinolysis?
antiplasmin, plasminogen activator inhibitor, and thrombin activatable fibrinolysis inhibitor
What does antiplasmin do?
inhibits plasmin
What does plasminogen activator inhibitor do?
inhibits tPA
What does thrombin activatable fibrinolysis inhibitor do?
prevents fibrinolysis
What are some therapeutic inhibitors of fibrinolysis?
e-aminocaproic acid and tranexamic acid
What are e-aminocaproic acid and tranexamic acid used to do?
stabalize clots
What can go wrong with fibrinolysis?
excessive activation or inhibition, or acquired defect
What acquired condition can disturb fibrinolysis?
DIC
What is DIC initiated by?
Severe underlying disease - sepsis, severe inflamatory disease, and metastatic cancer
What severe inflammatory diseases can cause DIC?
heat stroke, pancreatitis, and immune-mediated disease like IMHA
What are the two main mechanisms of DIC?
Excessive activation of hemostasis leading to too much thrombin and excessive clotting AND loss of control and restriction of hemostasis
Excessive activation of hemostases leads to consumption of what?
platelets, coagulation factors, and inhibitors
What does loss of control/restriction of hemostasis result in?
Decreased inhibitors and expression of TF by cells that don’t normally express TF all independent of vessel injury
What diagnostic results should tell you that DIC may be going on?
Low platelets, prolonged goagulation time, low to normal fibrinogen, high D-dimer or FDP, and low AT
What should you treat first if you can in DIC patients?
the underlying disease
If you cannot treat the underlying disease in DIC patients, what should you give?
Plasma for the hemorrhagic phase and heparin for the thrombotic phase
