platelets Flashcards
Anucleate cells derived from megakaryocytes
in the bone marrow
platelets
platelets:
- production
- nl count
- circulation lifespan
- production: GM-CSF, IL-3, IL-6, TPO
- nl count: 150,000- 400,000
- circulate in the inactive state for 7-10 days
Alpha granules:
- fibrinogen
- thrombospondin
- vWF
- Factor V
- Platelet factor 4
- Beta thromboglobulin
- PDGF (platlet derived growth factor)
- P-selectin
- fibrinogen- aggregation
- thrombospondin- aggregation
- vWF- adhesion/aggregation
- Factor V- fibrin clot
- Platelet factor 4- heparin antagonist–promotes fibrin clot
- Beta thromboglobulin- recruits fibroblasts
- PDGF (platlet derived growth factor)- recruits fibroblasts
- P-selectin- adhesion of activated platelets to phagocytes
dense granules
- ADP and ATP
- Serotonin (5-HT)
- calcium
- ADP and ATP- platelet activation and recruitment
- Serotonin (5-HT)- vasoconstriction
- calcium- cofactors for factors forming fibrin clot
lysosomes
are granules that contain hydrolytic enzymes which phagocytose debris
Glycoprotein (GP) Ib (Ib/IX/V):
vWF receptor
Glycoprotein Ia/IIa:
collagen receptor
Glycoprotein IIb/IIIa:
fibrinogen receptor
procoagulant activity (2)
- thrombin receptor
2. phospholipids
P-selectin (activated platelets only)
leucocyte adhesion
bound to the collagen in the subendothelium of the damaged vessel wall, binds to platelets via GPIb complex, acting as a bridge
vWF
in the damaged vessel wall can bind to the platelet via GPIa/IIa
collagen
involved in adhesion for platelets (2)
- vWF
2. collagen
activating agents in platelets (6)
- thromboxane A2
- thrombin
- epinephrine
- ADP
- collagen
- arachidoinic acid
three actions of the activating agents
- enhances cell interaction (GPIIb/IIIa)
- induces platelet shape change and secretion
- phspholipids on plasma membrane activate clotting on the external surface
shape change with platelets
change from discoid to spherical- develop long pseudopods
where do the granules release their contents?
into the canalicular system
in aggregation the platelet-platelet interaction mediated by ______ and promoted by thombospondin
GPIIb/IIIa with fibrinogen
what does ADP and thromboxane A2 do in aggregation?
swelling, membrane adhere and further release reaction
exposure of membrane ___ for coagulation
PL
_____ stimulates vascular smooth muscle cells, hasten healing
PDGF
Clot retraction:
tenase complex
FIXa, VIIIa and X = FXa
clot retraction:
prothrombinase complex
FXa, Va, and II = thrombin
laboratory studies:
- quantitative
- qualitive
- quantitative: platelet count and morphology
2. qualitative: aggregation and PFA100
Anticoagulated whole blood under high sheer rate passes through an aperature with two membranes coated with either collagen/epinephrine or collagen/ADP
PFA-100
PFA-100 affected by
thrombocytopenia and to some degree anemia
PF-100:
- collagen/epi:
- collagen/ ADP:
- collagen/epi: nl<180 sec
2. collagen/ ADP: nl<116 sec
thrombocytopathies
abnormal platelet function
thrombocytopenia
platelet count<150,000
- GPIb (vWF receptor)
- abnormal adhesion/agglutination
- prolonged bleeding time
thrombocytopenia with large platelets
Bernard Soulier disease
- GPIIb/IIIa (fibrinogen receptor)
- abnormal aggregation and PFA-100
- prolonged bleeding time
Glanzmann’s thrombasthenia
acquired thrombocytopathy (3)
- drugs- ASA, NSAID
- renal insufficiency- uremia
- myeloproliferative disorders/ myelodysplastic syndromes
ASA (aspirin) irreversibly, NSAID’s reversibly acetylate and thus inhibit ______, resulting in reduced ________ synthesis and granule release
ASA (aspirin) irreversibly, NSAID’s reversibly acetylate and thus inhibit cyclo-oxygenase, resulting in reduced thromboxane A2 synthesis and granule release
powerful vasoconstrictor and potentiates aggregation
Thromboxane A2
autosomal dominant, large platelets, dohle bodies in the wbc’s
May-Hegglin anomaly -
X-linked recessive, eczema, immune dysfunction
Wiskott-Aldrich syndrome –
autosomal recessive, abnormal hand/wrist, cardiac lesions
Thrombocytopenia with absent radii (TAR) –
autosomal dominant, interstitial nephritis, deafness, large platelets
Epstein’s/Alport syndrome –
stem cell disorder, can also be acquired
Megakaryocytic hypoplasia/aplastic anemia –
acquired thrombocytopenia due to decreased production (4)
- infiltrative process- malignancy
- infectious- viral
- drugs- chemotherapy
- toxins- radiation
acquired thrombocytopenia due to increased destruction (7)
- drugs- heeparin/HIT
- immune thrimbocytopenic purpura/ ITP
- thrombotic thrombocytopenic purpura (TTP)/ hemolytic uremic syd=ndrime (HUS)
- disseminated intravascular coagulation/DIC
- APLA
- HELLP syndrome/pre-eclmapsia
- hyperspenism
auto-immune disorder, antibody:antigen complex on the surface of the platelet which targets it for removal by the RES
Immune thrombocytopenic purpura (ITP):
1.Adults
2.Fever, thrombocytopenia
microangiopathic anemia, acute renal failure, neurologic dysfunction
3. ADAMTS13-destruction or deficiency which leads to ultra large vWF multimers and aggregation of platelets and thrombosis
4. Normal PT/PTT
5. Rx: plasma exchange
Thrombotic thrombocytopenic purpura
- Children
- Diarrhea infection often E. coli strain
- Microangiopathic anemia, thrombocytopenia
severe renal failure - ADAMTS13 – normal
- Normal PT/PTT
- Rx: supportive care
Hemolytic Uremic Syndrome
Disseminated intravascular coagulation:
- Consumptive coagulopathy associated with
- Initiated by
- Clinical –
- Lab –
- Consumptive coagulopathy associated with thrombocytopenia, excessive fibrinolysis and reduced coagulation factors
- Initiated by endotoxin, infections (meningococcemia, etc), tissue factor release, tissue injury, proteases, toxins, malignancy, obstetrical complications
- Clinical – bleeding and thrombosis
- Lab – microangiopathic HA, thrombocytopenia, prolonged PT/PTT, TT, decreased fibrinogen, increased d-dimer
does the extrinsic pathway depend of platelets?
Nope, the extrinsic pathway is only made up of FVII
gray platelet syndrome
there is a decreased or absent number of alpha granules.
Chediak-Higashi syndrome is a
white blood cell disorder due to a failure of phagolysosome formation.
