4.2 CHESNEY Platelets Flashcards Preview

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Flashcards in 4.2 CHESNEY Platelets Deck (18):
1

Platelet Production

-Endomitotic replication: DNA rep in the absense of nuclear or cytoplasm division

-one meg makes 2,00-5,000 plts taks about 5 days

-platelets last for about 10 days

2

Storage of Platelets

~1/3 of plts are sequestered in the Spleen

-Losing spleen will cause an increase in plts b/c they have no where to go

-Over time the plt count will normalize

3

Platelet structure

-Dense granules: nucleotides (ADP), Ca and serotonin

-Alpha granule: PDGF, fibrinogen, vWF, fibronectin, beta-thromboglobulin (heparin agonist) and thrmobospondin

-Contents of the granules is released from the platelet, not used w/n the platelet

-Dense tubular system: Ca storage, responsible for Ca release w/n the platelet during activation

-Open-canalicular system: invagination of surface area into cell

-Submembranous filaments: made of actin and myosin, responsible for contraction of platelets

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4

Primary Hemostatic Plug

-ADP: released from dense granule, happens rather fast, pro-aggregation

-Thromboxane A2 also induces more platelet act and aggregation, syn by platelets, takes more time for release

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5

Platelet Aggregation

-Platelets use IIb/IIIa to bind to fibrinogen which links platelets to each other and responsible for aggregation of platelets

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6

Activation of Platelets 

2 things lead to platelet activation:

-Mobilization of Ca from the dense tubular system

-Increase in ADP levels (high cAMP levels turn the cell off)

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7

Clotting System

-Platelet is surface area where a lot of the clotting system will happen

-cofactor VIII is located on the surface and binds, XI and together they activate X

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8

Platelet Receptors

-Platelets have several surface receptors

-Thrombin is the most potent activator of platelets

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9

Metabolic cascades: Endothelial cells vs Platelets

-Platelets make TXA2 which inhibits cAMP production and activates the platelet

-Endothelial cells make Prostacyclin, inhibits platelet, vasodilator and favors cAMP production in platelets

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10

Testing if Platelets work

-Platelet aggregometry, measures the fall in light absorbance in platelet rich-plasma as platelets aggregate

-Initial aggregation is caused by an external agen, the secondary response by aggregating agents released from the platelets themselves.

-External agents: ADP, collagen, ristocetin, arachidonic acid and adrenaline

-Patients on aspirin: will see initial clotting b/c of external factors, but will not continue b/c platelets are inactivated

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11

Causes of Thrombocytopenia

-Failure of production

-increased consumption: bleeding, DIC

-sequestration: spleen, alcoholics, portal hypertension

-dilution

12

Selective megakaryocyte depression

-drug tox

-viral infection

-congenital mutation of c-MPL receptor

-congenital absent radii

-May-Hegglin anomaly

-Wiscott-Aldrich syndrome

13

Increased destruction-Immune

-Autoimmune-idiopathic, SLE, CLL/lymphoma (most common ones)

-Infection-H pylori, HIV, other viral malaria

-Post transfusion

-Feto-maternal alloimmune thrombocytopenia

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14

Drug induced destruction

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15

TPO

-Binds receptors on Megs and platelets

-If platelets are high in circulation, they will bind up TPO and will prevent them from binding Megs and activating them

-If low platelets TPO will bind Megs and lead to platelet production

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16

Treatment for Chronic ITP

-Corticosteroids: 80% respond to high dose, take off and plts fall

-High dose IVIg

-Immunosuppression

-Rituximab 50% response

-Thrombopoietin receptor agonist (romiplastim)

-Splenectomy

-IV anti-D immunoglobin

-Role of platelet transfusion: dont do unless extreme circumstances call for, body will just break down

-Stem cell transplant: drastic measure

17

Increased Destruction-Non Immune

-DIC and TTP

18

Causes of Reactive Thrombocytosis

-Acute trauma, surgery, blood loss, chronic iron def

-Splenectomy for hemolytic anemia

-Infections: osteomyelitis, TB

-Inflammaotry disease; rheumatoid arthritis, chronic ulcerative colitis, vasculitis

-Malignancy: carcinoma, Hodgkin's Disease