exam 5 review for hematology platelets and coagulation cascade

we gonna get goooood!

Define Hemostasis

The process that maintains flowing blood in a fluid state and prevents loss of blood from sites of vascular injury

Primary Hemostasis

Formation of platelets plug

Physiological role and definition of the vascular intima

Innermost tunic (layer) of a vessel/ vein or artery. It provides a smooth barrier between circulating blood and body tissues

Describe the innermost lining of the vascular intima

Monolayer of endothelial cells

Describe the capillary composition

It consists of a layer of endothelial cells on a basement membrane and is surrounded by pericytes, there are no smooth muscle or fibroblasts

Because the vascular intima functions to promote coagulation and anticoagulation. describe its coagulation properties when it is intact and damaged

Intact - endothelial cells make anticoagulant properties

Damaged - endothelial cells make procoagulant properties

What is the main function of platelets in secondary hemostasis? Briefly describe how fibrin clot is formed

Provide cofactors and a reaction surface to allow coagulation cascade to occur. Incorporation of fibrin & coagulation factors to form the secondary hemostatic plug (fibrin clot)

Procoagulant properties And their results

Vasoconstriction- minimizes escaped blood

Secretes Collagen- binds and activates platelets

Secretes von Willebrand’s factor- required for platelet adhesion

Secretes P-Selectin- promotes platelet and WBC binding

Anticoagulant properties

Normal negatively charged surface.

Synthesizes heparan sulfate

Synthesizes Thrombomodulin.

Synthesizes PGI2 (Prostacyclin)

Synthesizes Tissue Plasminogen Activator (TPA)

Synthesizes Tissue Factor Pathway Inhibitor (TFPI)

Synthesized Nitric oxide

When endothelial cells synthesize heparin sulfate, is it anti or pro coagulant? what does it do?

Anticoagulant property, which enhances antithrombin activity - preventing creation of fibrin

The synthesis of the anticoagulant thrombomodulin from the endothelial cells would result in?

The activation of the protein C pathway

The synthesis of the anticoagulant property Prostacylicn (PGI2) by endothelial cells would lead to

trigger vasodilation (widening of the veins), which then inhibits the aggregation of platelets

The activation of the fibrinolytic system is triggered by the synthesis of what anticoagulant property?

Tissue Plasminogen Activator (TPA)

Activation of the Extrinsic Pathway would be controlled by the

synthesis of Tissue Factor Pathway Inhibitor (TFPI) by endothelial cells

Function of nitric oxide

inhibits platelet activation

Initialization is composed of which mechanisms?

Vascular damage and exposure of subendothelium

Primary Hemostasis is associated with what mechanism?

Platelets adhesion and platelet aggregation

Arteries and arterioles blood flow

Carry blood away from heart to capillaries

Veins and venules blood flow

Return blood from the tissues BACK to the heart

Which structure is the smallest out of all of them, microscopic and has the fewest elements?

Capillaries

Maturation time from blast stage to platelet formation is

5 days

normal circulation life of a platelet is

8 to 10 days

platelets are removed or destroyed by

macrophages in the liver and spleen, or by active use

Circulated platelets distributed between the spleen and the blood, how much are ALWAYS in the spleen?

one third of circulated platelets

avg diameter of platelets 

2.5 microns 

average number of platelets is

140,000-450,000 cmm

The glycocalyx, part of the peripheral zone of a platelet is best described as

the outer membrane surface, rich in glycoproteins, which serve as membrane receptors. These glycoproteins provide surface for soluble plasma coagulation (coag) factors to adhere to. 

• contains ABO and HLA antigens 

The protein expressed on activated platelets is ? and describe what it does and how it is involved in plt aggregation

The 23BA protein is expressed on activated platelets, when bound with fibrinogen, it can bind to other platelets so they can aggregate

Understand and explain the process of GP (glycoprotein) pathway in primary hemostasis

______

Organelle zone consists of

alpha, dense, glycogen, and lysosome granules

Dense granules are what? what are dense granules made of?

release contents directly to plasma membrane upon activation; made of calcium, ADP, ATP, and serotonin which are important for providing energy for the rest of platelet activation

what do alpha granules do?

fuse OCs, participate in adhesion and aggregation and support plasma coagulation

What do alpha granules contain?

Fibrinogen, von Willebrand factor, platelet-derived growth factor (PDGF), and other proteins essential for coagulation and healing (ie Factors V, XI, Protein S)

Component of organelle zone: lysosome function

digests debris

In primary hemostasis, what functions are included?

all the answer choices are correct

Structural zone (aka. Sol-gel zone) – a system of membranes running throughout the cytoplasm; it includes

• Open Canalicular System (OCS) – a pore system
  that provides direct communication between
  intracellular and extracellular compartments; allows
  granule contents to be moved to surface, & plasma &
  coag factors to enter into plt. (where some coag.
  factors get concentrated.)

• . Dense Tubular System (DTS) - closed internal
  membrane system (sER remnant) that pumps Ca to trigger microtubular-controlled changes in plt.
  shape that occurs once plt. is activated. DTS is
  made of phospholipids, which support
  prostaglandin synthesis.

Structural zone, explain what it is and what it does

It is a microtubular/microfilamentous cytoskeleton –
provide an active means of platelet contraction
to squeeze the contents of the cytoplasmic granules.

• contains actin (contractile in plts. and muscle) which
  supports plt. shape & allows for its shape change
  from discoid to spiny once activated.

The first response to vascular injury is always, then is followed by

vasoconstriction, then platelet activation to promote adhesion and aggregation (mediated by fibrinogen +vWF) to form the platelet plug, a temporary “bandaid” over vessel wall

The second phase of hemostasis (secondary hemostasis) after the platelet plug is formed would be the coagulation cascade, briefly explain how thrombin is used?

Thrombin released to convert fibrinogen to fibrin, the fibrin strands then “net” over the platelets and trap blood cells to form a blood clot.

The last phase, occurring in secondary hemostasis after the blood clot is formed is when

plasmin is released, which cleaves fibrin strands, leading to fibrinolysis and clot degradation

Intrinsic pathway is initiated by the activation of what factor?

Hageman factor (factor XII)

The exposure of the negatively charged subendothelial tissue, which contains collagen, if associated with which pathway of the coagulation cascade?

Intrinsic pathway

Describe the start of the intrinsic pathway 

Factor XII is attracted to negatively charged endothelial tissue of damaged blood vessel. Negative polarity allows it to activate XII by making the molecule expose its active serine center- activating it from XII to XIIa

What is the method used to test the intrinsic pathway

activated partial thromboplastin time (APTT)

The extrinsic pathway is tested by

PT (prothrombin time test)

In the intrinsic pathway, how is XIIa involved in the production of the thrombin inhibitor bradykinin?

Prekallikrein reacts with activated XIIa and a cofactor (high molecular weight kininogen) to make kallikrein

Then kallikrein reacts with kininogen to form bradykinin

Plasmin in the intrinsic pathway is produced how?

Plasminogen (zymogen) is enzymatically cleaved by XIIa to an active form of plasmin, which will initiate clot dissolution reactions (aka plasmin breaks down blood clot)

the 4 products of XIIa reactions

Prekallikrein , plasminogen , factor XI to XIa, activation of complement cascade

Factor I is

fibrinogen

Factor II is 

prothrombin

Factor III is 

tissue thromboplastin

Factor IV is

plasma calcium

Factor V

Labile factor

Factor VII is

Stable factor 

Factor VIII is

antihemophilic factor

Factor IX is

Christmas factor

Factor X is

Stuart-Prower factor

Factor XI is

Plasma thromboplastin Antecedent (PTA)

Factor XII is

Hageman factor

Pre-K factor is

Prekallikrein - Fletcher factor

Factor XIII

Fibrin stabilizing factor (FSF)

HMWK factor is

high molecular weight kininogen - Fitzgerald factor

XI is one of the products of XIIa, how?

Factor XIIa enzymatically activates factor XI (PTA) to yield XIa, which then continues the cascade

Patients deficient in factor XII tend to develop

pulmonary embolisms (PE) and other thrombotic disorders, instead of pro-longed bleeding, because without factor XII, there’s very little option for triggering fibrinolysis

The ONLY coagulation deficiency in which patients develop clots instead of bleeding is the lack of

factor XII

deficiency in factor VIII (antihemophilic factor) leads to what disease

Hemophilia A

Hemophilia B is caused by 

deficiency in factor IX (Christmas factor)

Hemophilia C is caused by a lack of

factor XI (PTA, plasma thromboplastin antecedent)

The “contact factor'“ complex is composed of 

XIIa, HMWK, and Prekallikrein

Factor XI of coagulation cascade

Inactive zymogen that is activated as XIa

Hemophilia C

Deficiency of factor XI

vitamin K factors

2,7,9,10, C,S,Z

NR of fibrinogen

200-400 mg/dL

Fibrinogen is made in

Liver

What is Factor XI (PTA) activated by?

contact factors, thrombin, and XIIa

Factor VII (stable factor) is activated by what in the extrinsic pathway? What else does it activate?

• endothelial cells release TF (tissue factors) to activate it

• upon contact with Ca2+ and TF3 forms complex (VIIa/Ca/TF3) activates factor X to Xa

• also activates factor IX in intrinsic pathway

Prothrombin (factor II) is vitamin K dependent, and the vitamin K factors associated with it in the coagulation cascade are?

factors II, VII, IX, X,

The deficiency in factor XI leads to what disorder?

hemophilia

End goal of primary Hemostasis

Platelet clot through adhesion,

Dense granules contain what? and what is their importance?

ADP, ATP, Serotonin, and Calcium; they are essential for providing energy for the rest of platelet activation process

Alpha granule contain

fibrinogen, factor V, facto XI, protein S, Platelet derived growth factor (PDGF), vWF 

End goal of secondary Hemostasis

Formation of fibrin to hold the clot in place

Fibrinogen (has the highest plasma concentration of any clotting factor), aggregates and stabilizes platelets by binding to the platelets’ 

Gp2b3a receptor

Congenital hypo- or afibrinogenemia will cause what?

severe bleeding caused by failure to form fibrin clots

D- dimers in the fibrinogen strand are caused by

double bounded bands from factor XIII, fibrin stabilizing factor

What factors are dependent on thrombin for activation?

factors V, VIII, XI, and XIII, as well as fibrinogen. It also activates platelets and Protein C

What factor acts as a mediator for platelet activation? how does it do that?

Factor IV (ionic calcium) as it helps bind vitamin K dependent coagulation factors (2, 7, 9, 10, C, S) to phospholipids such as TF3 and PF3