Disorders of hemostasis fall into two main categories:
1. Inappropriate formation of clots (thrombosis)
2. Failure of blood to clot (bleeding)
In bone marrow, ______ fragment into platlets
Megakaryocytes
The liver, kidney, bone marrow, and smooth muscles all release ______, which stimulates the production of bone marrow.
Thrombopoietin (made mostly in liver)
Normal platelet number is __________ of blood
150,000 - 400,000/ microliter of blood
about 1/3 stored in spleen
How many days to platelets circulate?
8-10 days
True/False: Platelets have a small nucleus
False: NO NUCLEUS
Glycoprotein llb/lla bind to ______ and acts to connect platelets together to form a platelet plug.
fibrinogen
____ and ____ within the platelet cell membrane helps in clot retraction.
Actin and Myosin
Alpha granules on the outside of platelets contain f____, c____ ____, and p_____, which aid in platlet aggregation, blood coagulation and initial phase vessel repair.
fibrinogen, coagulation factors, and plasminogen
____ granules are found inside platelets, which hold ADP, ATP, calcium ions, serotonin, and histamine which facilitate platelet adhesion and vasoconstriction.
Dense granules
Where are most clotting factors made?
Inside the liver
Vitamin ____ is needed for synthesis of factor VII, IX, and X; as well as prothrombin and protein C.
Vitamin K
How do blood vessels, themselves, prevent and control blood clot formation?
Lined w/ endothelial tissue that prevents clotting factors from interacting w/ underlying collagen and sub-endothelial extracellular matrix. Swift blood flow and the fact that coagulation factors exist in nonactive form also contribute.
When endothelial cells are injured they synthesize ______ which aids in platelet adhesion and formation of platelet plug.
von Willebrand Factor (vWF)
List the 5 stages of hemostasis:
1. vessel spasm
2. Loss of endothelial integrety, primary platlet plug
3. activation of coagulation cascade
4. clot retraction
5. fibrinolysis
Smaller vessels release a vasoconstrictor prostaglandin called (TXA2)
thromboxane A
Vessel spasm at the beginning of hemostasis lasts how long?
Less than 1 minute
vWF is produced both by ___ and ____.
megakaryotes and endothelial cells
The combined actions of ADP and TXA2 lead to the expansion of the enlarging platelet aggregate, which is called _____
Primary hemostatic platelet plug
*plug soft, not stable, still reversible.
How is the primary platlet plug converted to a definitive clot?
Via the coagulation pathway which leads to fibrinogen being converted to fibrin--> forms a meshwork that cements plug components together.
Intrinsic pathway of coagulation begins in:
begins in circulation, initiated by Factor XII
RELATIVELY SLOW
Assessed w/ Partial Thromboplastin Time (PTT)
Extrinsic pathway of coagulation is activated by:
Activated by cellular lipoprotein called tissue factor that is exposed when endothelium is injured
Faster process
assessed via prothrombin time (PT)
Both pathways lead to the activation of Factor X which leads to the conversion of:
conversion of prothrombin to thrombin
which converts fibrinogen to fibrin
Clot retraction requires a large amount of _____ and failure of clot retraction is indicative of a low ____ count.
Platelet(s)
Plasminogen is normally present in the blood, when converted to it's active form, Plasmin, it serves what purpose?
Digestion of fibrin strands of the clot and certain clotting factors (fibrinogen, V, VIII, and XII)
Excess Plasmin is quickly deactivate by what?
Alpha 2 antiplasmin which limits fibrinolytic process to local clot rather than entire circulation
Antithrombin III as well as protein C and S, all serve what purpose?
Regulate blood coagulation
They act as anticoagulants by inactivating some cotting factors
Hypercoagulability States
exaggerated form of hemostasis that predisposes thrombosis and blood vessel occlusion
What are the two forms of hypercoaguability states?
1. increased platelet function
2. Accelerated activity of clotting system
Increase in turbulence and increased platelet numbers causes which type of thrombi?
Arterial thrombi
Stasis if flow and decrease in anticoagulation factors cause whicg type of thrombi?
Venous thrombi
True/false: Arterial thrombi are composed largely of platelet aggregates and fibrin complexes.
False. Only platelet aggregates! VENOUS thrombi include fibrin complexes
What are the two main causes of increased platelet function?
Bleeding disorders are caused by defects associated with p_____, c____ ____, and v____ integrity.
platelets, coagulation factor, vessel integrity
1. Inadequate platelet production (bone marrow disfunction)
2. Excess platelet destruction (thrombocytopenia)
3. Abnormal platlet function (thrombocytoparhia)
4. Defects in von Willbrand Factor
All cause a decrease in plug formation, leading to bleeding disorders
Thrombocytopenia:
less than 100,000 platelets/microliter of blood
common bleeding from skin/mucous membranes
Purpura and peteciae
The following are all signs of what disorder?
1. Decreased platelet production
2. Decreased platelet survival
3. Excessive pooling of platlets in spleen
4. Dilution from massive blood/plasma transfusions
Thrombocytopenia
Name at least 5 conditions that can lead to decreased platelet production:
congenital-or-acquired anemia
leukemia
bone marrow depression
HIV
cytomegalovirus (suppress megakaryote production)
Quinidine is a medication taken for heart arrhythmias. It can also cause what complication?
Reduced platelet survival--> Thrombocytopenia
A type of hapten, also sulfa-containing antibiotics
Thrombocytopathia (defective platelet function) is common in ______.
Uremia (presumably because of un-excreted waste products)
What is the most common cause of Thrombocytopathia?
a. Smoking
b. Quinidine (haptens)
c. Radiation
d. Aspirin (NSAID's)
True/False: Factor VIII is made by the liverand endothelial cells. von Willenbrand Factor is made by megakaryocytes and endothelial cells.
TRUE!
What is the connection between Factor VIII and von Willebrand Factor?
von Willebrand Factor serves as a carrier for Factor VIII
Each is synthesized separately, then circulate the plasma as a unit
Which is more common, Hemphilia A or von Willebrand disease?
von Willebrand Disease
Hemophilia A is a (vWB/Factor VIII) deficiency that affects 1 in 5000 male live births. It is an X-linked recessive disorder.
Hemophilia A--Factor VIII deficiency
With Hemophilia A, bleeding commonly occurs in what areas of the body?
soft tissues, GIT, various joints
Intracranial hemorrhage is also possible--death
This bleeding disorder in an autosomal dominant disorderwith over 20 different mutations. Spontaneous bleeding is commonly seen from the nose, mouth, GIT, with excessive menstrual flow.
von Willebrand disease
This bleeding disorder shows a prolonged bleeding time in the presence of a normal platelet count.
von Willenbrand disease
What are some causes of Vitamin K deficiency, and what does this deficiency cause?
caused by treatment w/ broad spectrum antibiotics and in newborns not yet exposed to intestinal flora
clotting factors remain in inactive forms due to a lack of Vitamin K
True/false: In persons with bleeding disorders caused by vascular defects, the platelet count and coagulation factor tests are normal.
True!
Scurvy
Vitamin C deficiency (vascular disorder)
Disseminated Intravascular Coagulation (DIC)
a paradox of both excessive coagulation and excessive bleeding
massive activation of clotting scheme leads to fibrin deposition and formation of clots throughout microcirculation (arterioles and capillaries)
Thrombi block vessels, resulting in tissue ischemia and hemolytic anemia as RBC fragment trying to squeeze through narrow vessels
The depletion of platelets and coagulation factors leads to diffuse bleeding all over the body
Disseminated Intravascula Coagulation can be caused by both coagulation pathways. It is not a primary disease, but is a complication of different disorders: