Week 1: Primary Hemostasis

what are these?

1. smooth EC lining

2. PGI2

3. nitrous oxide

4. heparan sulfate

5. TFPI

6. thrombomodulin

7. EPCR

8. TPA

anticoagulant functions of intact endothelial cells

what are these?

1. vasoconstriction

2. VWF

3. ADAMTS13

4. P-selectin

5. collagen exposed

6. TF exposed

7. PAI-1

8. TAFI

procoagulant functions of damaged endothelial cells

serotonin and thromboxane A2

released by platelets to cause vasoconstriction

adhesion and aggregation: which platelet zone?

peripheral

dense tubular system for contraction and shape maintenance: which platelet zone?

sol-gel

storage and secretion with dense bodies, alpha granules, and lysozomes: which platelet zone?

organelle

components of peripheral zone

1. plasma membrane

2. cytoskeleton

3. phospholipids

4. receptors

platelet factor 3 (PF3)

negatively charged phospholipids on activated platelet surface

glycocalyx

exterior coat of platelets

components of sol-gel zone

1. microtubules and microfilaments

2. dense tubular system

dense tubular system function

1. calcium reservoir

2. synthesis of prostaglandins and thromboxane A2

dense bodies contain what components?

1. non metabolic ADP and ATP

2. calcium

3. serotonin

alpha granule components

1. HMWK

2. fibrinogen

3. Factor V

4. VIII:vWf

5. PF4

dense bodies promote ___________________, while alpha granules promote _____________

platelet aggregation, coagulation

lysozomes

destroy platelets during coagulation

platelet receptor: GP Ia and IIa

adherence of platelets to negative charge

platelet receptor: GP Ib/IX/V

receptor for vWf, adherence to collagen

platelet receptor: GP IIb/IIIa complex

fibrinogen receptor, forms stable platelet plug

platelet receptor: Factor V

holds Va on the platelet surface to activate X

Multiple agonists generated at the site of vascular injury induce platelet activation, which causes ________ receptors to change to a fibrinogen binding-receptive state

GP IIb/IIIa

platelets provided a ___________ charged surface for coagulation

negatively

platelets bind with which factors to activate Factor X?

IX and VIII

platelets bind Factor Xa and Va, increasing ____________ activation

prothrombin

vWf part of the Factor VIII complex plays a role in adhesion with _____________

glycoprotein Ib

coagulation factors contained in platelets

1. fibrinogen

2. vWf

3. V

4. HMWK

5. XIII

prostaglandin 12 synthesis: phospholipids → _____________

arachidonic acid

phospholipase function

converts phospholipids into arachidonic acid

cyclooxygenase function

converts arachidonic acid into PGH2

prostaglandin 12 synthesis: arachidonic acid → ____________

prostaglandins

prostaglandins → _________ → prostaglandin 12

PGH2

aspirin is a _____ inhibitor via acetylation

COX

prostaglandins can have the following 2 end products

1. thromboxane A2 — blood platelets

2. prostaglandin 12 — endothelial cells

thromboxane A2 and prostaglandin 12 have __________ functions

opposite

what is the effect of aspirin on platelets?

no aggregation or secretions

how does clopidogrel (plavix) work?

inhibits ADP receptors on platelets, preventing ADP released from dense granules from binding → reduced platelet aggregation

the platelet function analyzer (PFA) has test cartridges that contain membranes coated with…

collagen/epinephrine or collagen/ADP

how does the PFA measure platelet function?

records the time needed for platelets to occlude the aperture

what does the PFA screen for?

vWf disease and aspirin induced bleeding

the following stimuli are used to detect abnormal platelet aggregation

1. ADP

2. epinephrine

3. collagen

4. ristocetin

5. thrombin

6. arachidonic acid

ristocetin induces spontaneous platelet agglutination in the presence of ________

vWf

platelet aggregation evaluation: platelet rich plasma

1. light absorbance measured

2. aggregation → decreased optical density

platelet aggregation evaluation: whole blood aggregation

impedance is measured

platelet aggregation evaluation: luminance

platelet release reaction is measured by light

agents with a biphasic light pattern

1. ADP

2. epinephrine

3. thrombin

agent with a single wave and a lag phase light pattern

collagen

agent with a monophasic light pattern

ristocetin

agent with a single wave light pattern

arachidonic acid

bernard-soulier disease is the lack of ____________, which is the receptor for _____

protein Ib, vWf

platelets found in bernard-soulier disease

1. large

2. 50-80,000

patients with bernard-soulier disease do not have an aggregation response to ___________, but other agents are normal

ristocetin

is bernard-soulier disease autosomal dominant or recessive?

recessive

the PFA results for patients with bernard-soulier disease is ___________

increased

bernard-soulider disease is a ____________ platelet disorder

qualitative

the following are what type of platelet disorder?

1. von willebrand’s disease

2. glanzmann thrombasthenia

3. storage pool

4. gray platelet

inherited

von willebrand’s disease is a primary defect in the vWf portion of the ____________ molecule

Factor VIII

von Willebrand’s disease is autosomal ____________

dominant

von willebrand’s disease causes a platelet __________ defect, where the PFA is ____________

adhesion, increased

PT and platelets are normal in von willebrand’s disease, while ________ is slightly increased

aPTT

platelet aggregation in von willebrand’s disease is abnormal to __________

ristocetin

is glanzmann thrombasthenia autosomal dominant or recessive?

recessive

glanzmann thrombasthenia is where platelets lack what?

IIb/IIIa

aggregation pattern with glanzmann thrombasthenia

1. abnormal — ADP, epinephrine, collagen

2. normal — ristocetin

storage pool disorders are caused by a ___________ deficiency with no release action

dense body

in storage pool disorders there is a lack of internal _______ accelerator for aggregation

ADP

what disorder fits this description?

1. CR, PLT count and appearance — normal

2. PFA — variable

3. ADP and EPI — no 2nd wave

4. collagen — absent

5. ristocetin — normal

storage pool

gray platelet disorder is an ______________ deficiency

alpha granule

platelet quality with gray platelet disorder

large, agranular, gray

what disorder fits this description?

1. PLT count — normal to low

2. CR — normal

3. PFA — variable

4. impaired aggregation to ADP, EPI, collagen, and thrombin

gray platelet

what disorder fits this description?

1. PLT count — normal

2. PFA — increased

3. ADP — abnormal 2nd wave

4. collagen — abnormal

5. normal primary

defective thromboxane A2

hereditary telangiectasia

1. Lesions of the skin and mucous membranes, usually seen on the face, hands, fingertips, tongue, and lips

2. Thinning of the blood vessel walls

is hereditary telangiectasia autosomal dominant or recessive?

dominant

which disorders are autosomal dominant?

1. von Willebrand’s disease

2. hereditary telangiectasia

ehlers-danlos: defect in _________ adhesive glycoprotein that cross links _________

fibronectin, collagen

purpura simplex: recurrence of __________ on legs and body

bruises

senile purpura: loss of ___________ of vessel wall, most common in elderly and __________

elasticity, women

scurvy

vitamin C deficiency needed for normal collagen formation

amyloidosis

caused by deposits of amyloid on endothelium

thrombocytopenia: increased destruction disorders (immune)

1. ITP acute and chronic

2. neonatal

3. drug

thrombocytopenia: increased destruction disorders (non-immune or acquired)

1. TTP

2. HUS

3. DIC

4. HIT

thrombocytopenia: decreased production disorders

1. megakaryocyte hypoplasia

2. ineffective thrombopoiesis

3. congenital (may-hegglin)

increased splenic sequestration and dilution can cause what to platelets?

lower counts

thrombocytosis disorders

1. primary: myeloproliferative, PV

2. secondary: acute hemorrhage

how do antibiotics affect platelets?

inhibit intrinsic release of platelet ADP

HUS is similar to what other disorder in manifestations and presentation?

TTP

hemolytic uremic syndrome

1. mostly idiopathic

2. gastroenteritis — Shigella, E. coli

3. injures and inflames blood vessels in kidneys → clotting and RBC destruction

what disorder fits this description?

1. PT, aPTT, fibrinogen — normal

2. PLT count — low

3. FDP — normal to increased

4. HGB and HCT — decreased

5. schistocytes

HUS