Primary Hemostasis Vessels and Platelets

a mechanism by which the body is protected from excess bleeding after an injury and keeps blood fluid under normal conditions

what is hemostasis?

there will be excess bleeding, clotting—excess clotting causes more health problems than does bleeding

what happens if the system of hemostasis fails?

• primary coagulation

• secondary coagulation

what does coagulation depend on?

• vascular integrity

• platelets

  • form a primary, temporary plug

what is primary coagulation?

• plasma coagulation factors

  • make fibrin that spreads over platelet plug

    • strengthens the plug

what is secondary coagulation?

fibrin lysing system to reestablish blood flow after healing and inhibitors to coagulation to prevent excess clot formation

what is blood fluidity dependent upon?

• lumen

• smooth endothelial cell lining

• extracellular matrix

what is the vascular structure comprised of?

• basement membrane for support

• smooth muscle cells

• fibroblasts and collagen

what is the extracellular matrix comprised of?

a barrier between blood and other tissue—also allows transport of nutrients and cells

what is the function of vessels?

• constriction

• release of substances to initiate other aspects of coagulation

• serves as the template for clotting

• allows collagen in extracelllular matrix and outer wall of vessel to be exposed to platelets and contact activation factors for intrinsic clotting scheme

what is the role of vessels in coagulation?

damaged vessel constricts to reduce blood flow—diminishes amount of blood lost

how do vessels constrict?

• collagen

• Von Willebrand factor

• includes tissue thromboplastin

  • also called tissue factor or factor III

what substances are released by the vessels during coagulation?

• platelets

• external factors

• drugs

what are factors affecting vascular integrity?

decreased numbers may allow red cells to escape—cause petechiae

how do platelets affect vascular integrity?

• pupura

• petechiae

what are symptoms of vascular disorders?

a tourniquet test—blood pressure cuff to 90 mm mercury for 5 minutes—count petechiae

what is the test for vascular disorders?

more than 20 petechiae are present in 3 square centimeter area

when is the tourniquet test positive?

• cytoplasmic or cellular fragments

• produced in bone marrow

• 5-10 days life span

• derived from megakaryocytes

• normal range 150,000-450,000/mm³

• 33% reserved in spleen

what is the overview of platelets?

telangiectasia

what is an inherited vascular disorder?

a rare condition producing abnormal connective tissue and poor support

what is telangiectasia?

may damage endothelial cells or connective tissue

what characterizes an acquired vascular disorder?

megakaryocytes arise from multi-potential stem cell under the influence of CSF-MEG and thrombopoietin

what is the origin of platelets?

lobulated nucleus; increased cytoplasm

what characterizes promegakaryocytes?

• can double DNA without cell division

  • called endomitosis

• cytoplasm fragments into platelets

what characterizes megakaryocytes?

megakaryocyte extends filament through endothelial cells in marrow sinus and releases platelets directly into blood

how are platelets released?

circulate for 5-10 days before the spleen destroys them

what is the lifespan of the 66% of platelets that do not migrate to the spleen?

• platelet plasma membrane

• platelet cytoskeleton

• surface connected canalicular system

• dense tubular system

• granules

what comprises the platelet ultrastructure?

a bilayer composed of proteins and lipids

what is the platelet plasma membrane?

phospholipids that provide basic structure and cholesterol that engages in stability, fluidity, and transmembraneous passageway

what is the platelet bilayer primarily composed of?

outer region of the platelet

where is the receptor/transmitter region located?

glycocalyx—contains factors for adhesion and aggregation

what does the receptor/transmitter region have?

allows platelet to adhere to collagen

what is the function of GP la/lla?

allows platelet to bind to vWF

what is the function of GP lb/IX/V?

allows binding to fibrinogen and vWF

what is the function of GP llb/llla?

surface to which plasma factors adhere

what does the platelet cell membrane provide?

the barrier and regulates metabolic function

what does the plasma membrane of platelets act as?

• circumferential bundle of microtubules

• move inward on activation to enable expression of alpha granules

• microfilaments

what comprises the platelet cytoskeleton?

• maintains the platelet’s discoid shape

• parallels the plane of the outer surface of platelet and resides just within although not touching the plasma membrane

what is the function of the circumferential bundles of microtubules of the platelet cytoskeleton?

between microtubules and plasma membrane

where are microfilaments located?

actin

what are microfilaments composed of?

anchors the plasma membrane glycoproteins

what is the function of actin within the microfilaments?

to store additional quantities of hemostatic proteins found in the glycocalyx

what does the surface connected canalicular system enable the platelet?

enhanced interaction of the platelet with its environment, increasing access to the platelet interior and increasing egress of platelet release products

what does the surface connected canalicular system allow?

twists like a sponge throughout the platelet

where is the surface connected canalicular system located?

dense tubular system

what is known as the “Control Center” for platelet activation?

sequesters Ca²⁺ and bears enzymes that support platelet activation

what is the function of the dense tubular system?

mitochondria and glycogen—responsible for metabolic activity

what do granules consist of?

• dense granules

• alpha granules

what are the two major types of granules?

2-7 per platelet

how many dense granules are there?

migrate to plasma membrane and release contents directly into plasma upon activation—contain ADP, ATP, Ca²⁺, serotonin

what is the function of dense granules?

50-80 per platelet

how many alpha granules are there?

when activated, alpha granules fuse the SCCS and their contents are released—factor V, fibrinogen, vWF, plasma coagulation factors such as HMWK

what is the function of alpha granules?

• adhesion

• shape change

• aggregation

• secretion

what are the 4 main functions of platelets?

endothelial growth factor to heal endothelial cells to maintain vascular integrity

what do platelets release?

exposed collagen and release of vWF—vWF binds to platelet surface via glycoprotein lb to make the platelet adhere reversibly to the vessel wall

what does injury to the vessel wall cause?

due to exposure to collagen and ADP secreted by platelet—changes from discoid to a spiny sphere with pseudopods

how do platelets change shape?

glycoprotein llb-llla on the platelet surface to form a bridge between sticky pseudopods

what does fibrinogen bind to?

arachidonic acid

what is cleaved from the platelet membrane when it binds to ADP?

the formation of thromboxane A₂ (TXA₂)

what does the arachidonic acid stimulate?

microfilaments inside the platelet to centralize organelles

what does TXA₂ activate?

adhesion and aggregation

what does platelet secretion occur during?

ADP is released from the dense granules of platelet organelles through the SCCS—causes more shape change and much more aggregation (secondary aggregation)—produces an irreversible plug

what occurs during platelet secretion?

clot formation

what is the final step of platelet stabilization?

fibrin produced by plasma clotting factors reinforces the irreversible platelet plug to stop bleeding

how are clots formed?

• platelet count

• bleeding time

• platelet aggregation

what are the tests for platelets?

a platelet count below 10,000/µL

what can cause spontaneous bleeding?

platelet count as well as vascular integrity

what is checked with bleeding time?

shallow cut is made in forearm and time is measured regarding the amount of time it takes for site to stop bleeding when constant pressure is applied

what is the bleeding time procedure?

platelet function test

what largely replaced the bleeding time test?

determines the aggregating ability of the platelets

what is the purpose of the platelet aggregation test?

• aggregating agents are added to platelets

• as plug is formed, plasma clears

  • optical density is graphed against time

what is the procedure of the platelet aggregation test?

• due to autoantibody to platelet

• fairly common

• may be acute or chronic

  • acute is usually observed in children following an infection

    • esp. viral

  • chronic is often observed in women of child-bearing years

what characterizes idiopathic thrombocytopenia purpura (ITP)?

• age is 2-6 years

• platelet count is <20,000/µL

• petechiae are common

• following a viral infection

• antibody is produced against viral antigens bind to the platelet surface causing destruction of platelet

what characterizes acute ITP?

• 20-40 year olds

• onset is gradual

• platelet count is 30,000-80,000/µL

• antibody production is such the antibody attaches to the platelets

  • antibody-platelet complex is removed by RES cells

what characterizes chronic ITP?

haptens that elicit an antibody response

what do drugs act as?

• thrombotic thrombocytopenia purpura

• hemolytic uremic syndrome

• disseminated intravascular coagulation

what are the three most common causes of increased platelet destruction due to non-immune destruction?

• thrombocytopenia

• platelet fragments

• neurologic symptoms

• renal disease caused by micro-thrombi of platelets

• treat with plasma exchange

what characterizes thrombotic thrombocytopenia purpura?

accumulation of ultra-large von Willebrand Factor multimers

what is the development of TTP directly related to?

A disintegrin and metalloprotease with thromobspondin type 1 motif, member 13 (ADAMTS-13)

what normally cleaves ULVWF multimers into smaller VWF multimers?

the UVWF binds to platelet GP lb and GP llb/llla—increased adhesion and aggregation and forms hyaline thrombi

what happens in the absence of ADAMTS-13?

decreased platelet count and RBC fragmentation

what is the laboratory findings of a peripheral smear of TTP?

decreased haptoglobin; hemosiduria, hemoglobinuria; increased lactic dehydrogenase and bilirubin

what typical signs of intravascular hemolysis does TTP exhibit?

normal PT, PTT, fibrinogen, fibrin split products, and D-Dimer; helps differentiate from DIC

what is the coagulation findings of TTP?

plasma exchange and corticosteroids

what is the treatment of TTP?

only in children following an infection

where is hemolytic uremic syndrome (HUS) found?

Salmonella or E. coli infections—toxins enter bloodstream, attach to renal endothelial cells, which become damaged

• release ULVWF multimers

• hyaline thrombi in renal vaculature

• renal failure, thrombocytopenia

what does HUS usually follow?

• neurological symptoms usually not present

• thrombocytopenia usually not as severe

  • platelet consumption usually occurring in kidneys

how is TTP differentiated from HUS?

• clotting occurs throughout the body

  • caused by activation of the coagulation cascade

  • thrombi composed of platelets and fibrinogen

• platelets and coagulation proteins are used up

• coagulation results:

  • increased PT, PTT, FSP, and D-Dimer

  • decreased platelet count, fibrinogen

what is disseminated intravascular coagulation (DIC)?

• adhesion defects

• aggregation defects

• secretion defects

what are the three types of qualitative platelet disorders?

• Von Willebrand’s disease

• Bernard-Soulier disease

what are the most common platelet adhesion disorders?

low, absent, or defective VII:vWF—defective platelet adhesion

what causes Von Willebrand’s Disease?

defective glycoprotein lb—unable to bind vWF, patients exhibit hemorrhage characteristics

what causes Bernard-Soulier Disease?

defective glycoprotein llb/llla—defective ability to bind fibrinogen and form bridges for aggregation

what causes Glanzmann’s?

• storage pool defects

• alpha granules

  • storage site for coagulation proteins

• dense granules

  • storage site for ADP, ATP, CA

  • bleeding is mild and usually limited to bruising

what are the secretion defects?