2-10 Exam 12 Hemostasis

Front 1

Define platelets (thrombocytes), blood coagulation, blood clots, and hemostasis

Back 1

Platelets (thrombocytes): small blood cells that aid in the formation of blood clotsBlood coagulation: formation of blood clot, blood clotting cascade Blood clot: consists of platelet plug enmeshed in a network of insoluble fibrin molecules (and trapped red cells). Hemostasis: stoppage of bleeding

Front 2

Appreciate that a careful balance between blood coagulation and blood flow is necessary and that at the time of platelet aggregation and clot formation, the enzyme machinery necessary to dissolve the clot is also being activated.

Back 2

na

Front 3

Know which cell components are involved in hemostasis.

Back 3

Cellular: mostly platelets, also endothelial cells

Prots: coagulation, fibrinolysis (clot dissolution), regulation

Front 4

What are the 3 main processes involved in hemostasis?

Back 4

vasoconstriction
platelet activation
adhesion and aggregation
blood coagulation cascade.

Front 5

Be able to describe how platelets are formed and understand the importance and regulation of thrombopoietin.

Back 5

Platelets made and released by mature Megakaryocytes
Liver makes const amt of thrombopoeitin

Regulation:More platelets in blood = more thrombopoeitin bound to blood and less TP reaches marrow where it would stimulate the production of more platelets.

Front 6

Know the main cellular characteristics of platelets

Back 6

no nucleus, granules

Front 7

Know that the granules contain factors important for platelet activation, aggregation and adhesion. Appreciate the importance of degranulation.

Back 7

Megakaryocytes, once mature, release platelets (up to 5000) into circulation

Activated platelets release factors
- coagulation factors: fibrinogen, factor V,
- platelet activating factors: ADP, thromboxane A2
- aggregation factors: von Willebrand factor
- vasoconstrictor: serotonin.

Front 8

Identify the roles of von Willebrand factor, ADP, thromboxane, fibrinogen, and serotonin. Know that they are excreted by platelets.

Back 8

von Willebrand factor = aggregation factor
ADP = activating factor
thromboxane A2 = activating factor
Fibrinogen = coag factor
Serotonin = vasoconstrictor

Front 9

Understand the difference between platelet adhesion and aggregation. (What is the role of endothelial cells?)

Back 9

Adhesion = stick to endothelial cells
Aggregation = stick to other platelets

Front 10

Understand that the coagulation cascade is a biological amplification cascade; protein components are always present as inactive precursors; the generation of a dense fibrin network is the final product of the coagulation cascade.

Back 10

na: but be able to viz / draw this

Front 11

Know that there is an ____ and ____ pathway (parallel but some interactions! not redundant) and a ____ pathway.

Back 11

intrinsic , extrinsic, common

Front 12

Understand that the factors are numbered by roman numerals, I being ____ and that numbers increase going ____ in the pathway (sort of). Know that “a” means ____ (each factor exists in an inactive and active form).

Back 12

fibrin/fibrinogen (end product), backwards, activated

Front 13

Which pathway is more rapid? Which is more impt physiologically?

Back 13

extrinsic pathway is more rapid and physiologically probably more important then the intrinsic pathway

Front 14

Remember that the ____ ____ is initiated by trauma/injury and is activated by factor ____ bound to ____. Exposure of tissue factor is crucial. It's TF attached to endothelial and vascular cells (not in blood) that makes this an "extrinsic" pathway. For intrinsic, all the factors necessary are in the blood.

Back 14

extrinsic pathway , VIIa, TF (tissue factor)

Front 15

Know that the ____ pathway appears to be implicated in thrombosis and atherosclerosis. Recall that the proteins and cells (platelets) involved are all present in the blood stream. Platelet activation and ____ exposure is essential. Several factors are involved: (list them)

Back 15

Intrinsic, phospholipid, (remember factors XI, IX (Christmas factor), and cofactor VIII.

Front 16

Know that both pathways converge to the common pathway, started by the activation of ____ and____, ____ is converted to ____ which in turn converts ____ to ____. Factor ____ is important to crosslink the fibrin meshwork

Back 16

factor X, factor V, prothrombin (thrombinogen), thrombin, fibrinogen, firbrin, XIII

Front 17

Understand that fibrin, factor XIII and platelets (and other trapped cells) form the hemostatic plug.

Back 17

fibrin, factor XIII and platelets

Front 18

Appreciate that ____ is involved in all pathways.

Back 18

Ca2+

Front 19

Understand the importance of inhibiting the blood clotting cascade and that several inhibitors exist that target different steps in the coagulation cascade. Remember plasmin (inactive form plaminogen) as a representative.

Back 19

Prohibit thrombosis
The major inhibitors are :
Tissue factor pathway inhibitor - Inhibits Xa, VIIa and tissue factor
Antithrombin - inhibits thrombin
Protein C and protein S - destroy factors Va and VIIIa, enhance fibrinolysis
Plasmin (plasminogen) - degrades fibrin, fibrinogen, factors V and VIII

Front 20

Know what heparin is and what it is used for.

Back 20

Heparin is a naturally occurring anticoagulant produced by basophils and mast cells

Front 21

a. Briefly outline the steps involved in the production of platelets

Back 21

i. Stem cell
1. Thrombopoeitin (from liver to bone marrow) acts at myloid precursor
ii. Myloid progenator
iii. Megakaryocyte - multinucleated cell
1. Granule formation
2. Platelets pinched off
iv. Platelets have granules: enzymes, serotonin, thromboxane A2, ADP, etc.
1. Activatioin = degranulation

Front 22

b. How is the production of thrombopoietin regulated?

Back 22

TPO always being produced by liver into blood stream. Based on num of platelets in circ. More platelets in circ = more TPO bound = less TPO gets back to marrow = less platelets made

Front 23

Which pathway is believed to be more important, the extrinsic or intrinsic pathway?

Back 23

extrinsic

Front 24

Which pathway contains elements that are all present in the plasma?

Back 24

intrinsic

Front 25

Which pathway involves tissue factor?

Back 25

extrinsic

Front 26

Which factors are present where the two pathways converge?

Back 26

X and cofactor V

Front 27

What happens after prothrombin forms thrombin?

Back 27

Cleavage of firbrinogen to fibrin and then factor XIII crosslinks platelets to strengthen fibrin net

Front 28

1. Understand the three general causes for bleeding disorders.

Back 28

separate coag from platelet aggregation

-Plasma protein defect: coagulation or anticoagulation protein
-Platelet abnormality
-Defect in platelet-endothelial cell interactions

can't adhere to endothelial cells
can't stick to itself (aggregate)
can't be xlinked by factor 13

Front 29

2. Know the laboratory tests done to evaluate bleeding disorder, what are they and what do they test for?

Back 29

Thrombin time (TT)
final stages of clotting
Adds thrombin and thus tests only the final stages of clotting (fibrin formation from fibrinogen)

Prothrombin Time (PT)
Extrinsic and common pathway
Tissue factor (factor III or thromboplastin) and calcium is added: specific for extrinsic pathway and common pathway

Activated Partial Thromboplastin Time (PTT or aPTT)
intrinsic and common pathway
Adds phospholipid, surface activator, calcium: tests only intrinsic pathway and common pathway

INR-International Normalized Ratio.
= (PTpatient / PTnormal)^ISI

0.8 - 1.2 means that the patient PT is normal.
>1.0 means the clotting time is elevated

Front 30

4. Know the general causes for platelet disorders.

Back 30

Thrombocytopenia = not enuf platelets
a. Decreased production
i. liver failure and decreased thrombopoietin, vitamin B12 or folic acid deficiency, infections, leukemia, variety of hereditary syndromes
b. Increased destruction
i. hypersplenism
c. Drug induced

Thrombocytosis = high platelet counts
a. Primary (essential) myeloproliferative diseases (like cancer).
b. secondary (reactive) (inflammation, surgery, hyposplenism, blood loss)
Defective platelet function - Abnormalities in the vascular blood interface that impairs platelet adhesion
Inherited - weak platelets
Acqured - aspirin therapy

Thrombosis
--injury to vessel's wall (trauma, infection)
--slowing or stagnation of blood flow (which may occur after long periods of sedentary behavior - for example, sitting on a long airplane flight)
--high altitude
--hypercoagulability state (e.g. genetic deficiencies or autoimmune disorders)
--drug induction (COX-2 inhibitors, birth control pill?)

Front 31

o How can increased coagulation cause increased bleeding?

Back 31

Small clots use up small amt of remainig platelets (thrombocytopenia)

Front 32

o What is thrombocytopenia and what could cause it (general causes)?

Back 32

Lack of platelets

Don't make enuf: decr prod: liver failure, decr TPO, vit B12 or folic acid deficiency, infection, leukemia

Front 33

o What are the health problems associated with HIT?

Back 33

Bleeding, micro clots

Front 34

o Define thrombocytosis.

Back 34

High level of platelets caused by cancer (active) or (reactive) surgery, inflammation, hypersplenism, blood loss

Front 35

o What is the difference between thrombosis and embolism?

Back 35

i. Embolism is a detached thrombus

Front 36

1. Realize that pathways intrin/extrin are not indep in-vivo. There is some dependence.

Back 36

na

Front 37

2. Be able to define thrombocytopenia and thrombocytosis. Don’t memorize but be able to recognize potential causes for either syndrome.

Back 37

Thrombocytopenia = not enuf platelets
a. Decreased production
i. liver failure and decreased thrombopoietin, vitamin B12 or folic acid deficiency, infections, leukemia, variety of hereditary syndromes
b. Increased destruction
i. hypersplenism
c. Drug induced
Thrombocytosis = high platelet counts
a. Primary (essential) myeloproliferative diseases (like cancer).
b. secondary (reactive) (inflammation, surgery, hyposplenism, blood loss)

Front 38

3. Be able to briefly define disseminated intravascular coagulation (understand how widespread clotting can cause increased bleeding).

Back 38

a. Widespread clotting uses up all platelets = bleed risk

Front 39

4. Know what vascular bleeding disorders are

Back 39

Abnormalities in the vascular blood interface that impairs platelet adhesion (defect in platelet-endothelial cell interactions)

Front 40

5. Understand that not only platelet ____ but also platelet _____ are important.

Back 40

a. number
b. Function (aggregation and adhesion)

Front 41

6. Be able to define thrombosis and embolism.

Back 41

Thrombosis = clot attached to vessel wall
Embolism = it's mobile!

Front 42

7. Know the causes of hemophilia A, hemophilia B (Christmas disease), and von Willebrand disease.

Back 42

Hemophilia A (factor VIII - deficiency)-hereditary, X-linked

Treatment:
Infusion of factor VIII concentrates
Gene therapy?

Hemophilia B (IX)

Treatment: replacement therapy, infusion factor IX?

Von Willebrand disease (VW factor)
VWF promotes platelet adhesion and is a carrier molecule for factor VIII

Desmopressin (e.g. DDAVP®): synthetic analogue of vasopressin, transiently increases VWF and factor VIII in plasma, for the milder versions.

The drug Alphanate (factor VIII) is used to decrease bleeding in patients who have surgery or other invasive procedures.

Front 43

Which tests would be normal or abnormal in the different disorders? Define the tests.

Back 43

PT PTT TT Platelet Fx Test
HemA N Abn N N
HemB N Abn N N
VonW N ? N Abn