SM_253b: Platelet Function and Formation Flashcards
This is a ____

Megakaryocyte

Describe megakaryocyte and platelet development
Megakaryocyte and platelet development
- CFU-GEMM
- BFU-Meg
- CFU-Meg
- Promegakaryoblast
- Megakaryoblast
- Promegakaryocyte
- Megakaryocyte

Describe proplatelet cytoskeletal mechanics
Proplatelet cytoskeletal mechanics
- Transcriptional amplification
- Organelle synthesis
- Platelet-specific protein amplification
- Microtubules move to cortex
- Proplatelet elaboration
- Microtubule sliding and tracking of granules / organelles to nascent platelets
- End amplification via branching
- Proplatelet release
- Platelet release
- Nuclear material shed (apoptosis)

Platelets are formed from ___
Platelets are formed from megakaryocytes in the bone marrow
- Each megakaryocyte gives rise to mutlple platelets
___ is the principle regulator of thrombopoiesis
Thrombopoietin is the principle regulator of thrombopoiesis
Describe platelet lifespan and fate
Platelet lifespan and fate
- 199 megakaryocytes
- Turnover: 10-14% per day
- 1.25 x 1012 circulating platelets

Describe causes of thrombocytopenia due to impaired platelet function
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)
When platelet production decreases turnover ____ and number of circulating platelets ____
When platelet production decreases turnover decreases and number of circulating platelets decreases

___ causes impaired platelet production
Wiskott-Aldrich syndrome causes impaired platelet production
As platelet count increases, platelet survival ____ and fraction removed ____
As platelet count increases, platelet survival increases and fraction removed increases

Describe intrinsic pathway of apoptosis
Intrinsic pathway of apoptosis
- Lack of survival signals, irradiation / DNA damage
- Activation of sensors (BH3-only sensors)
- Antagonist of Bcl-2
- Activation of Bax/Bak channel
- Leakage of cytochrome c and other proteins
- Activations of caspases
- Apoptosis

Describe causes of thrombocytopenia due to increased platelet clearance
Thrombocytopenia due to increased platelet clearance
- Bleeding
- Thrombosis
- Consumptive coagulopathy
- Sepsis
- Thrombotic thrombocytopenia purpura
- Immune thrombocytopenia purpura
- Drugs / heparin-induced thrombocytopenia
- Splenomegaly: splenic sequestration
In immune thrombocytopenia, turnover ____ and number of circulating platelets ____
In immune thrombocytopenia, turnover increases and number of circulating platelets decreases

Platelet life-span is ___ and regulated by ___
Platelet life-span is 8-10 days and regulated by intrinsic apoptosis pathway
Platelets help maintain ____
Platelets help maintain endothelium
Describe platelet function
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
Describe stages of platelet activation and thrombus formation
Stages of platelet activation and thrombus formation
- Unstable adhesion
- Aggregation
- Thrombin generation
- Contraction / clotting

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

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

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

Describe contents of delta (dense) granules
Delta (dense) granules
- ADP
- ATP
- Serotonin
- Pyrophosphate
- Calcium
Describe contents of alpha granules
Alpha granules
- Platelet factor 4
- Beta-thromboglobulin
- Platelet derived growth factor
- Fibrinogen
- Factor V
- vWF
- HMWK
Lysosomal vesicles contain ____
Lysosomal vesicles contain acid hydrolases
Thromboxane is derived from ___
Thromboxane is derived from arachidonic acid

Describe process of platelet recruitment
Platelet recruitment
- Platelet granules release (ADP)
- Thromboxane (TxA2) synthesis
- Fibrinogen receptor (GPIIb/IIIa) activated
- Platelets bind fibrinogen

Membrane phospholipids are distributed by ___
Membrane phospholipids are distributed by phospholipid exchange proteins
- Expression of PS on platelet surface provides sites for anchorage of coagulation factors
- Flippases, floppases, scramblases

Describe features of arterial thrombosis
Arterial thrombosis
- Begins at site of turbulence or endothelial injury
- Extends retrograde to flow
- Platelets, tissue factor, fibrin, few RBC, WBC

Describe features of venous thrombosis
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

Summarize platelet function and hemostasis
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
Describe bleeding symptoms of platelet function defects
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
___, ___, and ___ are tests used to assess qualitative platelet defects
Platelet function analysis, platelet aggregation studies, and platelet flow cytometry are tests used to assess qualitative platelet defects
Describe causes of acquired platelet function defects
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
Bernard Soulier syndrome results from ____ defect
Bernard Soulier syndrome results from platelet glycoprotein GP Ib/IX (vWF receptor) defect

Bernard Soulier syndrome presents with ____
Bernard Soulier syndrome presents with symptoms of platelet dysfunction (mucocutaneous bleeding, etc)
Describe diagnosis of Bernard Soulier syndrome
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
____ or ____ are used to treat Bernard Soulier syndrome
Platelet transfusion and desmopressin are used to treat Bernard Soulier syndrome
Glanzmann thrombasthenia results from a ____ that leads to ____
Glanzmann thrombasthenia results from a defective GP IIb/IIIa receptor that leads to failure of platelets to bind fibrinogen and aggregate

Glanzmann thrombasthenia presents with ____
Glanzmann thrombasthenia presents with symptoms of platelet dysfunction (mucocutaneous bleeding, etc)
Describe diagnosis of Glanzmann thrombasthenia
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
___ or ___ are used to treat Glanzmann thrombasthenia
Platelet transfusion or desmopressin are used to treat Glanzmann thrombasthenia
Glanzmann thrombasthenia shows ____ with all agonists except ____
Glanzmann thrombasthenia shows global dysfunction with all agonists except ristocetin
Dense granule storage pool disorder results from ___
Dense granule storage pool disorder results from defects in platelet dense granules
Dense granule storage pool disorder is diagnosed via ____ and ____
Dense granule storage pool disorder is diagnosed via abnormal platelet aggregation and lack of dense granules on electron microscopy
These are ____
Platelet granule deficiency

This is ___

This is Glanzmann thrombasthenia

Summarize congenital and acquired platelet defects
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