Platelets Flashcards

1
Q

How are platelets made? What are they? Location? Life span?

A
  • Megakaryocyte cytoplasm elongation (pro-platelets); elongations gain granules and cytoskeleton then bud off megakaryocyte
  • No nucleus and very grainy cytoplasm
  • 1/3 in spleen at any time
  • 8-12 day life span
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2
Q

TPO

A

(thrombopoietin)
- Made in liver (dec if liver disease) then binds receptors on mega surface –> JAK-STAT path –> proliferation and platelet formation
- When low platelet count normally have inc TPO to try to compensate BUT exception is in immune thrombocytopenia purpura when there are dec platelets and dec TPO

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3
Q

TPO Mimetic Drugs (2)

A

romiplostim and eltrombopag

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4
Q

Platelet Granules + Contents

A

More alpha than dense

  • Alpha - VWF, fibrinogen, thrombospondin, fibronectin (adhesion) + Factor V, PAI-1 (coagulation factors) + platelet factor 4, PDGF, TGF-beta (growth factors)
  • Dense - Ca++, serotonin, ADP, ATP (dense granules require greater activation for release)
  • Lysosomes - acid hydrolases
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5
Q

What prevents platelet plug formation in normal state?

A
  • Endothelial-derived factors
    -
    Endothelial prostacyclin PGI2 (made from same COX path as TXA2), NO (vasodilate and prevent aggregation of platelets)
  • Adenosine disphosphatase (or CD30) hydrolyzes trace ADP (ADP normally inc aggregation)
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6
Q

Primary Hemostasis Steps

A
  • formation of platelet plug-
  • 1- INJURY
  • 2- Initiation/Adhesion - exposure to collagen and VWF from Weible-Palade bodies under endothelium –> platelet mono-layer
  • 3 - Activation - now that platelets adhere, binding to receptors on platelet membrane –> activated membrane phospholipids –> AA –> TXA2 production and granules now released
  • 4- Extension - ADP and TXA2 released from active platelets in plug bind additional platelets thru G protein receptors to recruit them (platelets aggregate via fibrinogen - GPIIbIIIa)
  • 5- Stabilization - concomitant activation of thrombin stabilizes the platelet plug w/ fibrin
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7
Q

What receptors do collagen, VWF and fibrin bind to?

A
  • Collagen - GP-Ia/IIa or GP-VI on platelets
  • VWF binds collagen and then binds GP-Ib or GP-V or GP-IX on platelets
  • Fibrin binds GPIIb/IIIa
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8
Q

R v L Sided Hemostasis

A
  • L - high flow rate so few red cells incorporated; platelets more important; clots made of platelets, VWF, fibrin
    • When high flow/ high sheer collagen alone cannot hold platelets so VWF-GPIb needed
    • “White clots”
  • R - low flow rates so coagulation components readily available; less dep on platelets; clots made of fibrin, white cells and red cells
    • When low flow, VWF not needed (collagen - GPIaIIa is sufficient)
    • “Red clots”
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9
Q

How does platelet dysfunction present clinically?

A
  • Petechiae, purpura ecchymosis, nose bleeds, GI/GU bleed, oral bleeding (“mucocutaneous bleeding”)
  • Normally bleed in lower extremities first b/c inc pressure from gravity
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10
Q

Bleeding Time v Closure Time

A
  • Bleeding Time - use BP cuff and make small incision; time how long until stop bleeding (operator dependent - not used often)
  • Closure Time - blood sample thru capillary tube w/ high shear rate (tube contains collagen and ADP or collagen and epinephrine)
    • If normal in both … normal
    • If epi prolonged but ADP normal … drug-induced
    • If both prolonged … platelet problem
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11
Q

Platelet Aggregometry

A
  • put plasma in cuvettes then add diff platelet aggregating agents to ea and mea light transmittance (more aggregation means more light transmittance)
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12
Q

VerifyNow

A
  • meas resistance to anti-platelet meds; put whole blood from pt on a med in chamber w/ platelet agonists and fibrinogen beads and meas light transmittance change
    • If still aggregate then drug not that effective
    • ARU (aspirin reaction units) - use AA agonist
    • PRU (p2y12 reaction units) - use ADP as agonist
    • PAU (platelet aggregation units) - thrombin analog agonist
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13
Q

Platelet Works

A
  • meas baseline light transmittance of pts blood then add agonist and remeasure (used by anesthesia to determine if platelets are being adequately inhibited)
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14
Q

Thromboelastography

A
  • measures coagulation
  • blood sample in cuvette is rotated to simulate venous flow then measure resistance in cuvette which reflects clot formation
  • Tests coagulation and platelets function
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15
Q

Glanzmann’s thromboasthenia

A
  • GP IIbIIIa def (no aggregation w/ fibrin)
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16
Q

Bernard-Soulier

A
  • GPIb defect (no VWF binding - adhesion)
17
Q

Reasons for Acquired Platelet Dysfunction (7)

A
  • Aspirin - irreversibly accetylates COX –> block TXA2 (affects all platelets made in its 5 day half-life for the whole existence of that platelet)
  • Ibuprofen/naproxen block COX reversibly so effects subside rapidly after stopping drug
  • PCNs (esp ticarcillin)
  • Omega 3 fatty acids -compete w/ AA for COX –> les TXA2
  • Thienopyridine and anti-IIbIIIa drugs
  • Renal failure
  • Bypass for surgery - dilution and activates platelets/ some granule release
18
Q

Thrombocytopenia (definition and categories)

A
  • “Thrombocytopenia” - results from dec production or inc destruction of platelets
    • <150,000 / microL
    • 150,000 - 100,000 no risk
    • 100,000 - 50,000 bleeding/closure time inc
    • < 50,000 inc risk surgical hemorrhage
    • < 20-10,000 spont hemorrhage
  • Dec Production (**see dec or abnormal megakaryocytes on bone marrow biopsy)
    • Aplastic anemia and other bone marrow disorders
    • Radiation/ chemo damage to bone marrow
    • Marrow infiltration - leukemia, cancer, fibrosis, infection of marrow
  • Inc Destruction Non-Immune (**see ample or inc megakaryocytes - comp)
    • DIC - thrombin is platelet agonist
    • Sepsis - endotoxin aggregates platelets
  • Inc Destruction Immune - Related
19
Q

ITP

A
  • (immune thrombocytopenia purpura)
  • Acute - usually seen in kids after viral illness; present w/ bruising and bleeding but self-limited (2-6 wks); antigen-ab complex binds platelets
  • Chronic - present at 20-40 yo; insidious onset of bruising/bleeding; not self-limited
  • Anti-platelet antibodies bind surface of platelet then splenic macrophages bind antibody –> phagocytosis and destruction
  • SO… treatment includes steroids (impair phagocytosis), splenectomy, IVIG to bind macrophages instead rituximab (dec # B cells)
    -
    May have suppression of thrombopoiesis too - give TPO analogs
20
Q

TTP/HUS

A
  • Both involve thrombocytopenia + microangiopathic hemolytic anemia (platelet/VWF thrombi form in small vessels - depletes platelets) + fever
  • TTP - more brain involvement (weakness, visual prob, reduced mentation or reduced consciousness, headache, seizure, coma)
    • ADAMTS-13 deficiency or IgG attack –> does not cleave VWF –> larger VWF better at aggregation
  • HUS - more kidney involvement (creat >2, proteinuria, hematuria)
    • From preceding bacterial infection
  • Both - schistocytes and elevated LDH from hemolysis
  • Tx for TTP, daily plasma exchange (replace missing ADAMTS-13 and removes antibodies to it) + steroids and rituximab
21
Q

HITT (types 1 and 2)

A

(heparin-induced thrombocytopenia and thrombosis)

  • Type I - benign; after IV heparin started; gradual inc platelets
  • Type II - moderate thrombocytopenia and often thromboembolic events; 5-10 days after starting heparin
  • Antigen = PF4–> immune complexes –> Fc of platelet binds immune complex –> platelet activation
  • AND Antibodies also bind heparin sulfate on endothelial surface –> endo damage and tissue factor generation
  • Platelet act + tissue factor –> pro-thrombic state
  • Dx - anti-heparin-PDF antibody assay and 4-T Score (probability of having HITT)
22
Q

3 Reasons for Thrombocytosis

A
  • May act as acute phase reactant - so inc in bacterial abscess, osteomyelitis, RA, post-op
  • Myeloproliferative syndromes cause in platelets
  • Rebound thrombocytosis after splenectomy - give aspirin post-op
23
Q

4 T Score

A

Thrombocytopenia > 50%, 50-30%, <30% dec

Timing of Platelet Dec - more points if clear onset 5-10 days after heparin (or 1 day heparin exposure 100 days b/f)

Thrombosis + other prob

Other Causes not Evident - more points if no other causes