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Heme / Onc > SM_253b: Platelet Function and Formation > Flashcards

SM_253b: Platelet Function and Formation Flashcards

1
Q

This is a ____

A

Megakaryocyte

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2
Q

Describe megakaryocyte and platelet development

A

Megakaryocyte and platelet development

  1. CFU-GEMM
  2. BFU-Meg
  3. CFU-Meg
  4. Promegakaryoblast
  5. Megakaryoblast
  6. Promegakaryocyte
  7. Megakaryocyte
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3
Q

Describe proplatelet cytoskeletal mechanics

A

Proplatelet cytoskeletal mechanics

  1. Transcriptional amplification
  2. Organelle synthesis
  3. Platelet-specific protein amplification
  4. Microtubules move to cortex
  5. Proplatelet elaboration
  6. Microtubule sliding and tracking of granules / organelles to nascent platelets
  7. End amplification via branching
  8. Proplatelet release
  9. Platelet release
  10. Nuclear material shed (apoptosis)
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4
Q

Platelets are formed from ___

A

Platelets are formed from megakaryocytes in the bone marrow

  • Each megakaryocyte gives rise to mutlple platelets
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5
Q

___ is the principle regulator of thrombopoiesis

A

Thrombopoietin is the principle regulator of thrombopoiesis

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6
Q

Describe platelet lifespan and fate

A

Platelet lifespan and fate

  • 199 megakaryocytes
  • Turnover: 10-14% per day
  • 1.25 x 1012 circulating platelets
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7
Q

Describe causes of thrombocytopenia due to impaired platelet function

A

Thrombocytopenia due to impaired platelet function

  • Congenital: MYH-9 related, Mediterranean / familial, Wiskott-Aldrich
  • Acquired: HIV infection, chemo and radiation therapy, nutritional and alcohol induced, acute or chronic leukemia / stem cell transplant, bone marrow failure (aplastic anemia and others)
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8
Q

When platelet production decreases turnover ____ and number of circulating platelets ____

A

When platelet production decreases turnover decreases and number of circulating platelets decreases

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9
Q

___ causes impaired platelet production

A

Wiskott-Aldrich syndrome causes impaired platelet production

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10
Q

As platelet count increases, platelet survival ____ and fraction removed ____

A

As platelet count increases, platelet survival increases and fraction removed increases

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11
Q

Describe intrinsic pathway of apoptosis

A

Intrinsic pathway of apoptosis

  1. Lack of survival signals, irradiation / DNA damage
  2. Activation of sensors (BH3-only sensors)
  3. Antagonist of Bcl-2
  4. Activation of Bax/Bak channel
  5. Leakage of cytochrome c and other proteins
  6. Activations of caspases
  7. Apoptosis
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12
Q

Describe causes of thrombocytopenia due to increased platelet clearance

A

Thrombocytopenia due to increased platelet clearance

  • Bleeding
  • Thrombosis
  • Consumptive coagulopathy
  • Sepsis
  • Thrombotic thrombocytopenia purpura
  • Immune thrombocytopenia purpura
  • Drugs / heparin-induced thrombocytopenia
  • Splenomegaly: splenic sequestration
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13
Q

In immune thrombocytopenia, turnover ____ and number of circulating platelets ____

A

In immune thrombocytopenia, turnover increases and number of circulating platelets decreases

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14
Q

Platelet life-span is ___ and regulated by ___

A

Platelet life-span is 8-10 days and regulated by intrinsic apoptosis pathway

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15
Q

Platelets help maintain ____

A

Platelets help maintain endothelium

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16
Q
A
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17
Q

Describe platelet function

A

Platelet function

  • Adhere to subendothelium of a damaged blood vessel
  • Recruit additional platelets
  • Provide a surface for blood coagulation to occur
  • Clot maturation
  • Provide growth factors for wound repair
  • Endothelial maintenance function
  • Adjuvant immune function
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18
Q

Describe stages of platelet activation and thrombus formation

A

Stages of platelet activation and thrombus formation

  1. Unstable adhesion
  2. Aggregation
  3. Thrombin generation
  4. Contraction / clotting
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19
Q

Platelet receptor-ligand interactions are involved in ____ and ____

A

Platelet receptor-ligand interactions are involved in translocation and stable adhesion

20
Q

Platelet adhesion involves ____, ____, ____, ____, and ____

A

Platelet adhesion involves GPIa/IIa, GPIX-V, GPIb, GPVI, and vWF

21
Q

Platelet aggregation involves ____, ____, ____, ____, ____, ____, and ____

A

Platelet aggregation involves GPIb, GPIX-V, GPIIb/IIIa, vWF, p-selectin, and fibrinogen

22
Q

Describe contents of delta (dense) granules

A

Delta (dense) granules

  • ADP
  • ATP
  • Serotonin
  • Pyrophosphate
  • Calcium
23
Q

Describe contents of alpha granules

A

Alpha granules

  • Platelet factor 4
  • Beta-thromboglobulin
  • Platelet derived growth factor
  • Fibrinogen
  • Factor V
  • vWF
  • HMWK
24
Q

Lysosomal vesicles contain ____

A

Lysosomal vesicles contain acid hydrolases

25
Q

Thromboxane is derived from ___

A

Thromboxane is derived from arachidonic acid

26
Q

Describe process of platelet recruitment

A

Platelet recruitment

  1. Platelet granules release (ADP)
  2. Thromboxane (TxA2) synthesis
  3. Fibrinogen receptor (GPIIb/IIIa) activated
  4. Platelets bind fibrinogen
27
Q

Membrane phospholipids are distributed by ___

A

Membrane phospholipids are distributed by phospholipid exchange proteins

  • Expression of PS on platelet surface provides sites for anchorage of coagulation factors
  • Flippases, floppases, scramblases
28
Q

Describe features of arterial thrombosis

A

Arterial thrombosis

  • Begins at site of turbulence or endothelial injury
  • Extends retrograde to flow
  • Platelets, tissue factor, fibrin, few RBC, WBC
29
Q

Describe features of venous thrombosis

A

Venous thrombosis

  • Occurs at sites of stasis
  • Extends in direction of flow
  • Contains RBCs, fibrin, and few platelets
  • Leukocytes, NETs, tissue factor, platelets, and microvesicles
30
Q

Summarize platelet function and hemostasis

A

Platelet function and hemostasis

  • Platelets play a key role in hemostasis and thrombus formation
  • Primary hemostasis begins with platelets adhering to the site of endothelial damage to form a platelet plug
  • Interaction of platelets with receptors mediates platelet adhesion and activation
  • Thrombin generation and coagulation cascade occurs on the surface of activated platelets
31
Q

Describe bleeding symptoms of platelet function defects

A

Bleeding symptoms of platelet function defects

  • Typically involves the skin or mucous membranes
  • Easy bruising, petechiae, epistaxis, purpuric mucocutaneous bleeding, gastrointestinal bleeding, GU bleeding, menorrhagia, excess bleeding with minor surgery or dental extraction
32
Q

___, ___, and ___ are tests used to assess qualitative platelet defects

A

Platelet function analysis, platelet aggregation studies, and platelet flow cytometry are tests used to assess qualitative platelet defects

33
Q

Describe causes of acquired platelet function defects

A

Acquired platelet function defects

  • Drugs: aspirin, NSAIDs, others
  • Uremia: metabolic byproducts inhibit platelet function
  • Dysproteinemia: Waldenstrom macroglobulinemia, IgA myeloma, liver disease when fibrin degradation products interfere with platelet-fibrinogen binding
  • Myeloproliferative disorders
  • Cardiopulmonary bypass: causes platelet activation and exhaustion
  • Antiplatelet antibodies interfere with platelet receptors
34
Q

Bernard Soulier syndrome results from ____ defect

A

Bernard Soulier syndrome results from platelet glycoprotein GP Ib/IX (vWF receptor) defect

35
Q

Bernard Soulier syndrome presents with ____

A

Bernard Soulier syndrome presents with symptoms of platelet dysfunction (mucocutaneous bleeding, etc)

36
Q

Describe diagnosis of Bernard Soulier syndrome

A

Bernard Soulier syndrome diagnosis

  • Variable degree of thrombocytopenia
  • Large platelets
  • Abnormal platelet aggregation to ristocetin, normal aggregation with other agonists
  • Platelet flow cytometry with decreased surface expression of the GP Ib/IX complex
37
Q

____ or ____ are used to treat Bernard Soulier syndrome

A

Platelet transfusion and desmopressin are used to treat Bernard Soulier syndrome

38
Q

Glanzmann thrombasthenia results from a ____ that leads to ____

A

Glanzmann thrombasthenia results from a defective GP IIb/IIIa receptor that leads to failure of platelets to bind fibrinogen and aggregate

39
Q

Glanzmann thrombasthenia presents with ____

A

Glanzmann thrombasthenia presents with symptoms of platelet dysfunction (mucocutaneous bleeding, etc)

40
Q

Describe diagnosis of Glanzmann thrombasthenia

A

Glanzmann thrombasthenia diagnosis

  • Platelet aggregation: normal aggregation with ristocetin, global abnormal aggregation with all other agonists
  • Platelet flow cytometry: decreased number of GP IIb/IIIa receptors
41
Q

___ or ___ are used to treat Glanzmann thrombasthenia

A

Platelet transfusion or desmopressin are used to treat Glanzmann thrombasthenia

42
Q

Glanzmann thrombasthenia shows ____ with all agonists except ____

A

Glanzmann thrombasthenia shows global dysfunction with all agonists except ristocetin

43
Q

Dense granule storage pool disorder results from ___

A

Dense granule storage pool disorder results from defects in platelet dense granules

44
Q

Dense granule storage pool disorder is diagnosed via ____ and ____

A

Dense granule storage pool disorder is diagnosed via abnormal platelet aggregation and lack of dense granules on electron microscopy

45
Q

These are ____

A

Platelet granule deficiency

46
Q

This is ___

A

This is Glanzmann thrombasthenia

47
Q

Summarize congenital and acquired platelet defects

A

Congenital and acquired platelet defects

  • Bleeding symptoms in a patient with a normal platelet count indicate qualitative platelet defects
  • Qualitative platelet defects can be caused by defect in platelet receptors or granules
  • Symptoms of qualitative platelet defects are primarily skin and mucocutaneous bleeding

Heme / Onc (41 decks)

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