Chapter 22 Flashcards
normal hemostasis
Blood usually fluid
Seals broken blood vessels
abnormal hemostasis
Inappropriate clotting: too much
Insufficient clotting: too little
hemostasis
stopping blood flow
mediators of hemostasis
chemicals produced by platelets
mediators of hemostasis is released at an injury to
Start clotting by reacting with blood proteins Help platelets stick together Stimulate wound healing Help platelets stick to vessel wall Constrict blood vessels
requirements for blood clotting process
Presence of platelets produced in the bone
marrow
Von Willebrand factor generated by the
vessel endothelium
Clotting factors synthesized in the liver
using vitamin K
stages of hemostasis
- vessel spasm
- platelet plug formation
- blood coagulation
- fibrin clot
vessel spasm
Constriction – Endothelial Injury initiates – Vascular spasm/ Vascular Vasoconstriction of the smooth muscle in the vessel wall • decreased Blood Flow – Short Lived and Localized
platelet plug formation
– Release of von Willebrand’s Factor
• By Endothelial Cells & Platelets
- adhesion of platelets to exposed collagen fibers
– platelets become activated and secrete Adenosine diphosphate (ADP) (Promotes Aggregation), then attract more platelets
– Result: Platelet Plug (not a clot)
blood coagulation
Two ways to get there • Extrinsic Pathway • Intrinsic Pathway • Ultimately Both end in X Factor to activate Factor Xa - (Common Pathway) – Prothrombin to Thrombin – Fibrinogen to fibrin
without thrombin, what cannot occur?
aggregation
extrinsic pathway
- occurs in the tissues (outside the vessel)
- clotting process to take a chemical shortcut
- takes 10-15 secs, measured by value PT
production of thrombin is low, clot is small
intrinsic pathway
- collagen in blood vessel wall activates
- 5-10 minuets but measured as a PTT lab value
- larger amounts of thrombin, large clot
Factor X (active)
Prothrombin Activator
without it - Cannot clot
Factor V Complex
Prothrombin to Thrombin
without it - cannot clot
conversion of Thrombin (enzyme)
accelerates the
formation of Fibrin threads from Fibrinogen
(Factor I) that creates insoluble blood clot
common pathway of hemostasis
factor X (active) -> factor V complex + calcium -> conversion of prothrombin to thrombin -> converts fibrinogen to fibrin-> fibrin clot; both extrinsic and intrinsic pathways will end up in the common pathway.
clot retraction and dissolution
retraction- actin and myosin contract, pull out the fibrin, serum is squeezed out of the clot, clot shrinks
dissolution- Enzyme Plasmin Digests Clot
alterations of coagulation
vitamin K deficiency, liver disease
vitamin K
Vitamin K is necessary for synthesis and
regulation of components that make a clot
(stored in liver) fat-soluble vitamin (no vitamin K-> you will bleed/ inability to clot)
liver disease
– Causes a broad range of hemostasis disorders -
– Many Coagulation factors made or stored in
liver
– Causes defects in coagulation, fibrinolysis, and
platelet number and function
- ppl w liver disease are very prone to bleeding bc their liver does not make the clotting factors
Thrombocytopenia
platelet count <150,000/mm^3
- <50,000- hemorrhage from minor trauma
- <15,000- spontaneous bleeding
- <10,000- severe bleeding
causes of Thrombocytopenia
Hypersplenism, autoimmune disease,
hypothermia, and viral or bacterial infections
that cause DIC (disseminated intravascular
coagulation)
platelets
live 8–10 days in circulation – Many are stored in the spleen – Released when needed – Normal Value 150,000 - 400,000 *need to know this – Disc-shaped essential for clotting
Hypercoagulability
states are either inherited or acquired
increased platelet function - increase in number, increase in procoagulation and decrease in anticoagulation during an endothelial injury
Inherited hypercoagulation
Usually associated with venous thrombosis;
Deficiency of Protein C or S
factor V Leiden
protein C and S
work together to
inactivate factors Va(cause clot) and
VIIIa(causes clot) (in order to stop the
clot) So if there is not enough C or S clots
are more probable
protein C deficiency
common DVT
Protein S deficiency
risk of ARTERIAL
thrombosis
Factor V Leiden (FVL) (Deficiency)
AKA Activated protein C resistance = Clotting –Genetic mutation of factor V which causes resistance to the action of Protein C (Unable to stop the CLOT!; C would normally stop clot from Continuing)
most common acquired increase in clotting
- Smoking – Disseminated Cancer – Diabetes – Obesity – Can also be related to other Diseases • Polycythemia Vera (too many RBC) • Sickle Cell Disease Most common Female Acquired – Use of Oral Contraceptives
Hypercoagulability due to increased platelet function results in
platelet adhesion,
formation of platelet clots, and disruption of
blood flow.
causes of increased platelet function
disturbances in flow, endothelial
damage, and increased sensitivity of
platelets to factors that cause adhesiveness
and aggregation.
thrombocytopenia
Results from a decrease in platelet production,
increased sequestration of platelets in the
spleen, or decreased platelet survival
can be due drugs (chemo, heparin), idiopathic (cant be identified), immune system/infections, radiation therapy, autoimmune
Von Willebrand Disease
- Defect in vWF (does not allow platelets to aggregate)
– Normal platelet Count with prolonged bleeding
– Affects men and women
– Multiple variants (3 variations)
hemophilia
Most common X-linked genetic disease
Female cases rare
Lack of Clotting Factors prevents stable clot
Hemophilia A >80% of all hemophiliacs (aka
classic, Factor VIII or A)
Hemophilia B aka Christmas Disease (Factor IX)
Disseminated Intravascular Coagulation (DIC)
Complex, acquired disorder: clotting and
hemorrhage simultaneously occur
– Sepsis, cancer, trauma, blood transfusion, shock
Endothelial damage or Tissue Damage is
primary initiator
Results in Clotting that leads to Bleeding
anticoagulant drugs
Heparin
• binds to AT to produce an anticoagulant effect
– Coumadin drugs interfere with vitamin K action of the liver
(oral)
antiplatelet drugs
(inhibits platelet plug formation)
– Aspirin
• Decrease platelet adherence and may increase bleeding
• Clopidogrel (Plavix) - Prevention of platelet
aggregation
Thrombolytic Drugs
– Plasminogen activators are used to lyse thrombi in vivo
antithrombotic therapy - aspirin
– Administration results in irreversible inhibition
of the platelet enzyme cyclooxygenase, which is
needed for proper platelet aggregation
– This reduces the “stickiness” of platelets
– Affects last for the lifetime of the platelets – 7-10
days
– NSAID drugs such as ibuprofen compete for
cycloxygenase and may be used in conjunction
with aspirin
Plavix (clopidogrel)
a specific
inhibitor of ADP-induced platelet
aggregation
