• no DNA
• no nucleus
• proteins
  • structural
  • granule (stored)
  • glycoprotein
  • enzymes

• thick proteoglycan coat
• ability to form fibrillar bridges between platelet membranes
• distribution of intramembranous particles

• electron dense granules w/ adenine nucleotides, calcium, serotonin
• specific alpha granules w/ GF, fibrinogen, factor V, vWF, fibronectin, PF4, thrombospondin, B-thromboglobulin
• lysosomes- acid hydrolysis
• plasma membrane- PF3 (receptors for clotting factors and aggregating agents)

1. quiescent stem cell stimulated by IL-6 and GCSF to become active
2. activated stem cell cell goes to CFU MK
3. CFU MK stimulated by GM-CSF to produce promegakaryoblast
4. promegokaryoblast stimulated by TOP to become megakaryocyte
5. megakaryocyte cytoplasm fragment to make platelets

• endothelial cells serve as barrier between circulating blood and thrombogenic substances
• examples of products that cause vasodilation and inhibit platelet interaction
  • prostacyclines
  • nitric acid
  • ADPase
  • plasminogen activators

• endothelial cells switch to procoagulant effect
• promote platelet adhesion via
  • selectins
  • integrins
  • vWF
• also cause vasoconstriction

• collagen- strong platelet agonist cause dense granule relase
• glycoprotein IIb/IIIa expressed on platelet surface
• thrombospondin
• fibronectin
• tissue factor (leads to clotting cascade)

1. primary hemostasis
   1. platelet adhesion to vWF
   2. platelet aggregation via fibrinogen with vWF still playing a role
2. secondary hemostasis- fibrin clot formation (via clotting cascade)

• definition- attachment of platelets to any non platelet surface
• primary adhesion- attachment of platelet to  previously nonstimulated platelets to a non platelet surface
• contact- initial attachment of platelets before shape change
• spreading- mnore intimate bonding of platelets to surface involving shape change and granule relase
• secondary adhesion- attachment of previously activated platelets to surface

• strong
  • thrombin
  • collagen
• weak
  • ADP
  • epi

• performed by:
  • pumping bp cuf to 40 mm
  • making a 1 cm cut 1 mm in depth
  • bloting every 30 seconds until bleeding stops
  • normally less than 8 minutes
• evaluate either because:
  • platelets aren't functioning properly
  • thrombocytopenia

• mucosal bleeding
  • petechia
  • easy bruising
  • heavy menstrual period
  • abnormal beelding time
• NOT muscle or joint bleeding

• plasma membrane defects
  • Glanzmann's thromboasthenia
  • Bernard Soulier syndrome
• storage pool disease
  • decrease or absent dense granules
  • lead to diminished or absent second wave aggregation to most agonists
  • ex: Chediak Hegashi
• alpha granule deficineicy (grey platelet deficiency) diminshed response to epi, ADP, collagen
• von Willebrand disease (one disease that deals with problem with clotting cascade and platelet function)

• myeloprolif. disorders
• myelodysplastic syndromes
• dysproteinemias
• AML
• uremia
• acquired von Willebrand's disedase
• acquired storage pool deficiency
• drugs
  • prostacyclin
  • NSAID's
  • aspirin

• ALL with decreased production (all rare)
  • Wiscott Aldrich syndrome
  • Tar baby syndrome
  • May Hegglin anomaly
  • Alport syndrome
  • acquired amegakaryocytic thrombocytopenic purpura (AATP)

• hypoprolif.
  • radiation
  • drugs
  • chemicals
  • infections
  • bone marrow dysfunction- B12 def, invasion by tumor, MDS, MPD, AML

• drugs
• ITP
• TTP
• DIC
• hypersplenism

• produced by liver constantly
  • expansion and maintenance of progenitor leading to more megakaryocytes
  • enhance megakaryocyte maturation
  • in platelets, TPO is internalized and degraded
    • platelet numbers determine available TPO level

• platelets can aggregate together at times even though we see low values in CBC

• decrease production
  • alcohol
  • thiazide diuretics
  • cimetidine
  • phenylbutazone
  • chemotherapy
• shortened platelet survival

• autosensitization of platelts (RARE)
  • trigger by alpha methyl dopa
• hapten penicillin type
  • drug forms hapten on platelet surface
  • Ab produced against haptent
  • platelets destroyed in reticuloendothelial system
• immune complex deposition (MAJOR)
  • composition of drug and Ab deposited on platelet surace
  • most common: quinidine
  • rapid platelet destruction
  • induced heparin thrombocytopenia

• more common with UFH than LMH
• dx
  • Ab detected via ELISA for PF4, heparin
  • platelets very low
• effect- severe thrombotic complications
• tx- must substitute direct thrombin inh.
  • argatroban
  • leipirudin

• H2 blockers
• NSAIDS
• gold salts
• dilantin
• bp meds
• antibiotics

Need 1 week to clear (depot take longer)

With repeat exposre, you could have amnestic response

• severe cutaneous bleeding
• menorrhagia
• gingival bleeding
• intracranial hemorrhage

• thrombocytopenia with otherwise normal CBC and smear
• rule out:
  • no viral infection
  • no SLE or other autoimmune
  • no lymphoprolif. disease
  • no drugs
  • no MDS
  • no congenital or hereditary disorder

• autoAb to platelet membrane Ag
• some can have spontaneous remission
• biggest risk: intracranial hemorrhage

• impaired immune regulation
  • rapid destruction
  • suppression of thrombopoiesis
  • Ab to platelet Ag
  • Ab to mega Ag
  • effect on T lymphoctes

Requires intact RE system

• autoAb to membrane glycoproteins
  • GP IIb/IIIa
  • GP Ib/IX
• nonspecifc findings in other disorders

• history
• phy exam
• CBC
• peripheral smear
• absence of atypical findings or suggestion of other dx, no additional studies warrented
• if over 60 and splenectomy is considered, bone marrow biopsy

• goals: maintain hemostasis, minimize toxicity
• older
  • prednisone
  • splenectomy
  • vinca alkyloids
  • cytotoxic agents
  • danazol
• newer
  • IV Ig
  • lymphoma chemotherapy
  • high dose decadron
  • anti Rh
  • Rituximab