MLS 431 Heme Final

steroid purpura

purpura that occurs due to steroid use causing thinning of blood vessels, usually occurs on ankle and foot

drug induced vascular purpura

purpura that occurs in patients with functionally adequate platelets due to developing antibodies against vessel wall components due to certain drug use

senile purpura

purpura that occurs in the elderly due to lack of collagen support for blood vessels and loss of subcutaneous fat/elastic fibers

purpura simplex

simple bruising beneath the skin, deemed clinically insignificant

megakaryocyte (MK3)

the 3rd cell stage of the megakaryocytic lineage; it is the largest cell of the bone marrow and the nucleus is intensely lobulated to eventually shed multiple platelets

megakaryoblast (MK1)

the first recognizable cell of the megakaryocytic lineage; has granules within cytoplasm

storage pool diseases

the most common inherited platelet function defect causing impaired platelet aggregation or impaired granule release from platelets

promegakaryocyte (MK2)

the second cell stage of the megakaryocytic lineage; has a very basophilic cytoplasm and nuclear lobularity

glycocalyx

the surface of the platelet membrane which absorbs albumin, fibrinogen, and other plasma proteins from the circulation via endocytosis and stores them within their alpha granules

alpha granules

these granules within a platelet use the SCCS to dump their granule contents that they have synthesized within the platelet

primary hemostasis

this begins when platelets are exposed to subendothelial collagen or subendothelial inflammatory proteins

-hyper extendable skin -hyper mobile joints -joint laxity -fragile tissues -bleeding tendency

what are complications of elher-danlos syndrome?

-storage pool diseases -dense granule deficiencies -alpha granule deficiencies

what are disorders of platelet secretions?

-hyalomere = clear zone around edge of platelet containing other functional platelet components -granulomere = contains alpha granules

what are the 2 distinct areas of the platelet?

reactive and malignant

what are the 2 main types of thrombocytosis we study?

-vWF Ag (tells how much vWF is present) -vWF RCo or vWF Act (tells function of vWF activity or ristocetin co factor activity) -factor VIII activity as this is carried by vWF

what are the 3 basic lab tests used to look for vWF?

1.) acts as a carrier molecule for factor VIII, giving a longer half life 2.) it mediates platelet adhesion to subendothelial collagen 3.) it aids in platelet aggregation (platelet to platelet binding)

what are the 3 functions of vWF?

1.) binds to exposed endothelial collagen to enhance adherence of platelets in primary hemostasis 2.) it cross-links platelets during aggregation 3.) it acts as a carrier molecule for factor VIII

what are the 3 roles of vWF?

1.) coag factor VIII carrier domain 2.) GP Ib/Ix/V binding domain 3.) GP IIb/IIIa binding domain 4.) collagen binding site

what are the 4 functional domains on a vWF molecule that bind to other molecules?

abnormal

what are the PFA(platelet function assay) results of someone with glanzmann thrombasthenia?

no reaction with ADP, epinephrine, collagen, or arachidonic acid normal ristocetin

what are the aggregation results of someone with glanzmann thrombasthenia?

-prostacyclin is secreted by vasculature cells which inhibits the activation of platelets -it secretes nitric oxide which allows vasodilation and inhibits platelet activation -it secretes heparan sulfate which acts as a natural anticoagulant -it secretes TFPI which shuts off the extrinsic pathway by inhibiting factor VII -it contains thrombomodulin and EPCR which are involved in the PC activation pathway and binds to thrombin

what are the anticoagulant properties of the normal vascular?

lifelong mild bleeding with thrombocytopenia and enlarged platelets

what are the clinical manifestations of alpha granule deficiency?

-hemorrhage -platelet dysfunction -thrombosis

what are the clinical manifestations of essential thrombocythemia (ET)?

heterozygotes = normal platelet function with 50% GP activity heterozygotes = -moderate to severe bleeding as platelets cannot adhere -manifests in childhood -decreased PLT count w/ large platelets

what are the clinical manifestations of heterozygotes and homozygotes with BSS?

-TPA (tissue plasminogen activator) -PAI-1 (plasminogen activator inhibitor) inhibits the plasminogen activator -thrombin activatable fibrinolysis inhibitor (TAFI)

what are the fibrinolytic properties of the normal vascular?

-decreased platelet production -accelerated destruction due to platelet use or antibodies destroying platelets -abnormal distribution/sequestration of platelets

what are the main 3 causes of thrombocytopenia?

ADP, epinephrine, collage, arachidonic acid

what are the normal platelet aggregation results for someone with BSS?

easy bruising but no severe bleeding

what are the physical manifestations of dense granule deficiency?

-its made of smooth muscle cells which allow vasoconstriction to maintain blockage of damage site -when subendothelial cells are damaged, they expose collagen, initiating coagulation -when subendothelial cells are damaged, they also secret vWF which binds to collagen to aid in platelet pulling or carries factor VIII -they secrete adhesion molecules which adhere coag factors to platelets -they secrete tissue factor which initiates the extrinsic pathway after endothelium damage

what are the procoagulant properties of the normal vascular?

2A 2B 2M 2N

what are the subtypes of vWD type 2?

sudden onset of malaise, headache, fever, and rash with lesions on feet, elbows, knees, butt, and chest

what are the symptoms of schonlein henoch syndrome?

vWF Ag = low vWF Act = low APTT = normal/slightly prolonged

what are the vWF Ag, ACtivity, and APTT results of someone with type 1 vWD?

vWF Ag = normal/slightly low vWF Act = marked decrease APTT = normal multimers = no HMW or IMW

what are the vWF Ag, vWF Act, APTT, and multimer results of someone with type 2A vWD?

vWF Ag = normal vWF Act = variable APTT = normal multimers = lack of HWM

what are the vWF Ag, vWF Act, APTT, and multimer results of someone with type 2B vWD?

vWF Ag = normal vWF Act = normal multimers = normal FVIII = low

what are the vWF Ag, vWF Act, FVIII levels, and multimer results of someone with type 2N vWD?

vWF Ag = normal vWF Act = decreased multimers = normal (differs from 2A)

what are the vWF Ag, vWF Act, and multimer results of someone with type 2M vWD?

inflammation, exercise, infection, surgery, renal disorders, postsplenectomy

what can cause reactive thrombocytosis?

ADP, ATP, serotonin, calcium, magnesium

what contents do megakaryocytes synthesize?

below 100,000/uL

what defines thrombocytopenia?

-hermansky pudlak syndrome -chediak higashi syndrome -wiskott aldrich syndrome

what diseases are associated with dense granule deficiency?

fibronectin, fibrinogen, factor V, thrombospondin, vWF, B-thrombomodulin, HMWK, PAI, plasminogen

what do alpha granules contain?

-platelet shape -extension of pseudopods -they control upon activation causing a shape change of the platelet to promote secretion of alpha granules

what do microtubules and microfilaments control?

this allows platelet to platelet binding to allow aggregation

what does the GP IIb/IIIa complex do?

it acts as a multifunctional receptor that binds to fibrinogen to generate interplatelet aggregation, as well as vWF and fibronectin IIb and IIa come together upon platelet activation

what does the GP IIb/IIIa platelet receptor do?

binds to subendothelial collagen in regions of low blood flow

what does the GP Ia/IIa platelet receptor do?

-allows platelet adhesion to collagen via vWF -binds to thrombin -is used in regions of high blood flow shear rates to bind vWF to collagen -GP IX aids in maintaining receptor structure

what does the GP Ib/IX/V platelet receptor do?

it mediates platelet adhesion to fibronectin and laminin

what does the GP Ic/IIa platelet receptor do?

allows direct collagen and thrombospondin binding

what does the GP VI platelet receptor do?

phospholipase A2, COX, thromboxane synthase, phospholipase C

what enzymes does the DTS contain?

1/3

what fraction of platelets does the spleen sequester?

it allows collagen-vWF-platelet binding in high sheer flow rates within the blood

what is GP Ib/V/IX involved in?

-no response to epinephrine -decreased response to ADP -normal collagen response

what is the aggregation pattern of someone with ET?

prolonged

what is the bleeding time of someone with glanzmann thrombasthenia?

1.) cell membrane phospholipids are acted on by phospholipase to form arachidonic acid 2.) arachidonic acid is acted upon by COX-1 to form PGG2 3.) PGG2 is acted upon by thromboxane synthase to form thromboxane and peroxidase to form PGH2, PGF2, PGD2, PGE2, PGI2

what is the eicosanoid synthesis pathway?

it stabilizes the membrane, helps maintain fluidity, controls transmembrane travel

what is the function of cholesterol in the plasma membrane of a platelet?

they migrate directly to the plasma to dump calcium into the extracellular area to induce coagulation and activate platelet pathways

what is the function of dense granules?

7-10 days

what is the life span of a resting platelet?

a low platelet count

what is the most common cause of clinically important bleeding?

von Willebrand's disease

what is the most common inherited bleeding disorder?

150-400 x 10^9/L

what is the normal platelet count range?

lowest = O A B highest = AB

what is the order of blood groups from lowest to highest vWF concentration?

normal

what is the platelet count and platelet morphology of someone with glanzmann thrombasthenia?

neutral and polar phospholipids and cholesterol

what is the platelet's plasma membrane made from?

1.) does the patient have a history of mucocutaneous bleeding? 2.) does the patient have family history of mucocutaneous bleeding? 3.) perform laboratory testing as needed

what is the process of diagnosing von Willebrand's disease?

inversely proportional as its formation decreases when adequate platelets are present

what is the relationship between thrombopoietin and plt/megakaryocyte mass?

theres no specific treatment but platelet transfusions can be done, however the patient could develop alloantibodies

what is the treatment of BSS?

-platelet transfusions -hormones for heavy menses -antifibrinolytic drugs to stop fibrinolysis and form clots -factor VIIa to induce coagulation

what is the treatment of glanzmann thrombasthenia?

-polycythemia vera -chronic myelogenous leukemia -myelofibrosis with myeloid metaplasia -thrombocythemia

what myeloproliferative disorders are associated with thrombocytosis?

collagen is exposed to circulation by subendothelial damage, binding to the platelet or vWF in high flow rates to aid in platelet binding

what occurs during platelet adherence?

over 450,000

what platelet count defines thrombocytosis?

abnormal ristocetin as it usually binds to the GP Ib/IX/V receptor, but if this is mutated, ristocetin cannot bind and platelet aggregation becomes abnormal

what would the abnormal platelet aggregation results be for someone with BSS?

reactive thrombocytosis

when platelet overload occurs within the blood but will not reach over 800k/uL and only lasts for a limited amount of time and then returns to normal

neutral sits on outside of platelet on matrix while polar sit inside cellular matrix in bilayer

where do the neutral and polar phospholipids sit on the platelet surface?

surface connected canalicular system (SCCS)

a route for endocytosis that transports an item into the SCCS into the alpha granules; also acts as a route for secretion of alpha granular contents via the glycocalyx

type 2A vWD

a type of type 2 vWD where vWF is more susceptible to proteolysis causing it be to broken down easily into small MW monomers causing a lack of HMWM and decreased vWF activity

hereditary hemorrhagic telangiectasia

a purpura on face, lips, and conjuctiva due to dilated superficial blood vessels that are fragile and prone to rupturing

type 1 vWD

a quantitative deficiency of vWF due to an autosomal mutation that is relatively mild and difficult to diagnose

dense tubular system

a condensed remnant of the rough endoplasmic reticulum that runs parallel to the SCCS and sequesters calcium and enzymes that aid in platelet activation

dense granule deficiency

a deficiency usually caused by a serotonin or nucleotide transport issue that causes abnormal platelet aggregation due to a lack of proper ADP release from dense granules

type 2B vWD

a form of type 2 caused by a rare mutation that increases the affinity of vWF for platelet receptor GP Ib/V/IX causing large vWF multimers to bind to resting platelets

type 2N vWD

a form of type 2 vWD caused by a rare autosomal missense mutation that impairs the factor VIII binding site on vWF causing vWF to be unable to carry factor VIII

type 2M vWD

a form of type 2 vWD where vWF has decreased affinity for platelet receptor binding

thrombopoietin

a hormone formed in the liver that differentiates HSC into the megakaryocyte lineage

von Willebrand's Factor (vWF)

a huge protein that is synthesized within endothelial cells and megakaryocytes and stored in Weibel Palade bodies and alpha granules

essential thrombocythemia

a malignant condition characterized by extremely high platelet counts and uncontrolled platelet production

allergic purpura

a non-thrombocytic purpura that occurs due to allergic manifestations invoked by foods, drugs, the cold, insect bites, and vaccines

elher-danlos syndrome

a purpura disorder caused by a collagen disorder that leads to bleeding due to defects in collagen production, structure, and cross linking

schonlein-henoch syndrome

an anaphylactoid non thrombocytic purpura that occurs usually in boys with transient nephritis, abdominal pain, and purpuric skin lesions

glanzmann thrombasthenia

an autosomal recessive disorder due to a mutation on chromosome 16 causing abnormal platelet primary aggregation caused by a deficiency or abnormality of the GP IIb/IIIa complex

Bernard Soulier Syndrome (BSS)

an autosomal recessive platelet adhesion disorder that affects GP Ib/V/IX and is characterized by large platelets?

alpha granule deficiency

an autosomal recessive storage pool disease characterized where alpha granules are absent from the platelet, making the platelet appear gray

at about 50,000/uL

at what platelet account will bleeding occur?

both

do qualitative or quantitative defects of vWF cause vWD?

it can have both anticoagulant properties and procoagulant properties depending on the environment; the endothelium is smooth to prevent blood cells sticking to vasculature

how does the normal vasculature aid in maintaining hemostasis?

platelet transfusions, cryo transfusions, DDAVP treatment

how is alpha granule deficiency treated?

skin lesions, history of repeated hemorrhage, family history

how is hereditary hemorrhagic telangiectasia diagnosed?

by causing a slight thrombocytopenia and by reacting with a lower concentration of resticetin

how is type 2B vWD differentiated from the other types?

50-80

how many alpha granules are in one platelet?

2-7

how many dense granules are there per platelet?