Hemostasis and Blood Coagulation Flashcards
Hemostasis refers to the process by which _____
active bleeding is stopped.
Hemostasis occurs in four general steps:
○ Constriction/spasm of the damaged blood vessel
○ Formation of a Platelet Plug
○ Blood clot formation via coagulation
○ Reinforcement of clot with Fibrin
Primary hemostasis occurs at the level of the _____
Platelets
Seconday hemostasis occurs at the level of the ______
Coagulation factors
Platelet lifespan
7-10 days
Platelets contain mitochondria, smooth endoplasmic reticulum, and many _____
granules filled with clotting factors and cytokines.
Platelet Granules secrete various substances:
○ Adenosine Diphosphate (ADP)-
○ von Willebrand Factor (vWF)-
○ Fibrinogen-
Adenosine Diphosphate (ADP)- binds to receptors on other platelets, _____
activating/recruiting.
von Willebrand Factor (vWF)- Also secreted by damaged endothelium, binds ____
exposed collagen to platelet surface glycoproteins.
Fibrinogen- Already present in
plasma as well, precursor to ____
Fibrin.
Granule glycoproteins
Glycoprotein Ib-
Glycoprotein IIb/IIIa-
These glycoproteins bind to plasma Thrombospondin and Fibrinogen, which contribute to Platelet Aggregation
Glycoprotein IIb/IIIa-
A cell surface protein that vWF is able to bind, adhering the platelet to the endothelium.
Glycoprotein Ib-
Formation of the platelet plug involves several steps:
1) Endothelial injury
2) Exposure and Adhesion
3) Activation (of platelets)
4) Aggregation (of platelets)
Describe process of platelet plug
See slide 16-19
The platelet plug is fairly _____
unstable
Last step in primary hemostasis
Thrombospondin and Fibrinogen cross-link
together, clumping one platelet to a nearby platelet. (E)
Coagulation via the Coagulation Cascade/Network converts the Platelet Plug into _____
a more stable clot.
Extrinsic Pathway is Activated by the presence of a protein called _____.
Tissue Factor
Tissue Factor binds to _____, activating it
(VIIa); This complex then catalyzes the activation of Factor X.
Factor VII
Intrinsic Pathway is Activated by exposure to _____ located around damaged endothelium.
collagen fibers
there is some cross activation of ____ as well from both pathways.
Factor IX
Ultimately, the end result or goal of both the Intrinsic and Extrinsic Pathways is to activate ______.
Factor X (Xa)
In the Common Pathway, The activated Factors IX (IXa) and VII (VIIa) help to facilitate
the activation of _____
Factor X.
Activated Factor X helps to convert ____ to _____.
Prothrombin; Thrombin
Thrombin facilitates the conversion of the inactive ____ to ____.
Fibrinogen; Fibrin
Once activated, ____ monomers are then stabilized in polymers by ____ and cross-linked together.
Fibrin; Factor XIII
Nearly all clotting factors are formed in the
liver. ____is essential to help these factors to
mature.
Vit K
Vit K is continually _____ in the
intestinal tract by bacteria.
synthesized
Vit K is a key component for the
formation of:
○ Factor II
○ Factor VII
○ Factor IX
○ Factor X
○ Protein S
○ Protein C
T/F TOO MUCH of either bleeding or clotting can be deadly
T
Factors that inhibit Primary Hemostasis (Platelet Aggregation)
○ Smoothness of the undamaged endothelial lining.
○ Mucosal layer of the endothelium (Glycocalyx) repels clotting factors.
○ Prostacyclin and Nitric Oxide released from uninjured endothelium
that vasodilate healthy endothelium and prevent excessive platelet
aggregation.
■ Keep platelet plug localized to injury
Factors that inhibit Secondary Hemostasis (Coagulation Cascade)
○ Protein C
○ Protein S
○ Antithrombin III
Protein ___ is activated by
Thrombin.
C
Activated Protein C, with the help of Protein S, inactivates _____.
Factor VIII and Factor V
_____ is a protein circulating in the plasma and in vascular endothelium, and serves as a coagulation regulator.
Antithrombin III
Enzymatic breakdown of fibrin in blood clots is called
Fibrinolysis
Factors involved in Fibrinolysis
○ Plasminogen: Inactive protein in the plasma.
○ Tissue Plasminogen Activator (tPA): Present in endothelial cells and minimally in the plasma. Activates Plasminogen into
Plasmin
○ Plasmin: Over time, Plasmin in a clot will degragrades fibrin.
Disorders of Primary Hemostasis (Platelets) involve
Low platelet count or some form of platelet dysfunction.
Examples:
○ Thrombocytopenia
○ von Willebrand’s Disease
○ Immune (Idiopathic)
Thrombocytopenic Purpura (ITP)
○ Thrombotic Thrombocytopenic
Purpura (TTP)
○ Hemolytic Uremic Syndrome (HUS)
Disorders of Secondary Hemostasis (Clotting Factors) involve
Factor deficiencies or dysfunctions within the Coagulation Cascade.
Examples:
○ Hemophilia A (VIII)
○ Hemophilia B (IX)
○ Liver Disease-Induced
○ Vitamin K Deficiency
In order to evaluate for these disorders of
hemostasis, we generally order a ____
Coagulation Panel
Coagulation panel items
○ CBC (for the Platelet Count)
■ Additional platelet function tests are
available if required
○ Prothrombin Time (PT/INR)
■ Primary evaluates Extrinsic and
Common Pathways
○ Partial Thromboplastin Time (PTT)
■ Intrinsic and Common Pathways
Hemophilia A is hereditary bleeding disorder that is considered _____
X-Linked Recessive.
Pathophysiology of Hemophilia A
○ Deficiency in Coagulation Factor VIII.
○ Factor IX is unable to activate Factor X, so coagulation is dysfunctional.
Characteristic Signs and Symptoms of hemophilia A
○ Experiencing hemorrhages in deep tissue is characteristic.
○ Spontaneous Hemarthrosis – essentially diagnostic!
■ Most common joints are knees, ankles, and elbows
○ Big spontaneous bleeds occur only in severe disease.
○ Mild disease requires a little trauma.
definitive diagnosis for hemophilia A
Coagulation Factor VIII Assay will show decreased levels.
Treatment for Hemophilia A
○ Repeated hemarthrosis may lead to joint deformities.
○ Avoid any contact sports, Aspirin, and IM injections.
○ IV infusion of Factor VIII concentrate during acute bleed.
■ Severe cases get 2-3 x / wk prophylactically
