Platelets Flashcards
What are the major components of plats
Plasma membrane with lots proteins invaginated canalicular system
microtubles
Granles: alpha and dense are key
How do plats get around the blood and in what state?
Inactive state
- Adhesion to vessel endothelium till find a break in vessel
- Secreation of granules
- Aggretation to each other
What tethers Platelts to collagen once plateltes stick to tear in vessel?
Platelet–GPIb–vWF–Collagen
What happens when a platelet gets activated?
undergoes biochemical and physical changes
You see plates squeeze all granules to center
then podocyte processes reach out to surroundings
What are inside our Dense or Delta plat granules?
ADP, ATP, Seratonin (key for vasoconstriction) and Calcuim
What is inside the Alpha granules
Fibrinogen, factor V
Thrombosponsin
*****PDGE, PF4 and TG-B which are all key in atherosclerotis pathogenesis (how clotting contributes to this disease)
There are receptors on the surface of platelets that once activated will induce activity of phospholipase A inside the platet… what does this result in?
PL-A cleaves phospholipids to arachadonic acid
this is the key precursor to prostaglandins and thromboxanes
Arachadoinc Acid —-> PGG2 and PGH2
via Cyclooxygenase (inhibted by aspirin and COX inhibitors)
PGG2 and PGH2—> TXA2 and TXAb
Via thromboxane synthase
What is the role of thromboxanse and where do they come from
from AA inside plats
fnx to make membranes fuse and dump contnets out of cell
What two paths does PGG2 or PGH2
thromboxane synthase—> to TxB2 = platelet stimulation
OR
Prostacyclin synthast –> PGI2 = Plate INHIBTION
How to platelets adhere to one another?
Plat–GPIIIa/GPIIb —–FIBRINOGEN—-GPIIIa/GPIIb—–Plat
What is characteristic of Quantitative platelet disorders?
Decreased Platelet count
Prolongued bleeding time
What is characteristic of Qualitative Plat disorders?
Normal plat cound
Prolounged bleed time
von-Willebrands disease is what type of disorder?
Cofactor abnormality of platelets
Ehlers Danlos, Scury and Pseudoxanthoma elastiucm are all expamples of
Substrate abnormalities
What do we see in von Willebrand Disease
(whats missing, what test confirms it, what happens to bleed time)
Decreased vWF acitivty and antigen
Abnormal Ristocetin aggregation
Prolongued beelding time
What do we see in Bernar Soulie syndrome (insufficiency of GPIb)
normal vWF activity
Abnormal Ristocetin aggregation
Prolonged bleed time
What do we see when there are collagen abnormalities
normal vWF activity and antigen
Normal Ristocetin aggregation
Prolongued bleed time
phospholipase, cyclooxygenase and thromboxane synthase disorders are all what types of defects?
Defects of secreation: Prostaglandin defects
If a platet is missing granules, what type of defect is this?
storage pool defect
Membrane changes like Glanzmanns thrombasthenia and Peniccillin/carbenicillin are what type of defects
defects of aggregation
What are two types of defects seen with Increased Destruction of platelets?
Increased utlization: DIC, TTP and abnormal valves
Immunological destruciton: Idiopathic TTP, Lupus, Drugs
4 yo girl comes to the office with purpura on her trunk and legs. She has prominent bleeding from an IV site. She has a viral infection last week and has no prior hx of bleeding
Acute ITP; often proceeded by viral syndrome
How is chronic ITP differnt from acute ITP
chronic: bleeding is less prominent and often discovered incidentally. Plats are usually low and pt has long hx of bruising
3: 1 (F:M)
What are some different characteristics of ITP antibodies
Platelet specific, restricted heterogeneity, Antigenic heterogeneity (GPIb, GPIIb) and site of produciton (spleen or BM)
What do we need to make a dx of ITP
- Evidence for immune thrombocytolysis
- thrombocytopenia—Normal or incresase megakaryocytes—antiplat antibody - Absence of other causes of thrombocytopenia (like lupus or DIC)
- Absence of splenomegaly
What do we tx those dx with ITP with?
- corticosteroids (see 70% respond w/ high relapse rate)
- Splenectomy (50% response and low relapse, remove source of antiB prodcution)
- Immunosuppresive agents
18 yo girl, bilateral rash on ankles for 3 days, petichae and has progressively increased
feels fine, no recent illness on birth control, active and in high school
LMP: 3 weeks ago w/ moderate bleeds for 5 days changed out every 6 hrs
neg for lymphadenopathy, normal vitals
normal coagulation times and CBC below
– WBC =7.0 (normal 4-10) with normal differential
– Hemoglobin = 11.9 (normal 11.2-15.4)
– Platelet count = 6 (normal 150-350)
next step?
Peripheral blood smear
Get peripheral blood smear for girl with petichae and CBC of
– WBC =7.0 (normal 4-10) with normal differential
– Hemoglobin = 11.9 (normal 11.2-15.4)
– Platelet count = 6 (normal 150-350)
What are some differentials you should include in workup
IMmune thrombocytopenia: autoimmune syndormes, drugs, infections
DIC: unlikley bc no prolongued bleeds
TTP: no hemotonizing, so prbly not
Hematologic malignancy: not likley bc nothing going on with WBC and no lymphadenopathy
Your pt is dx with ITP, what do you treat her with
prednisone and IVIg
Pt has hx of ITP managed for 10 yrs with prednisone and IVIg.
Decreased tolerance to running (marathon runner) and gtes tired. Uses aspirin 4-5x week for ankle pain and ibuprofen for mentral pain prn.
Vegetarian but eats fish and has increased menorrhagia over past two months
PE: slight tachy, thin conjunctival pallor, no rash but bruising.
– WBC = 5.2 (normal 4-10) with normal differential
– Hemoglobin = 8.1 (normal 11.2- 15.4)
– Platelet count = 216 (normal 150- 350)
– MCV = 70 (normal 80-100)
Normal coag times
Microcytic hemochromatic
Iron deficiency anemia
What studies could you use to confirm a dx of iron deficency anemia?
– Ferritin
– Iron (transferrin) saturation
– Total iron binding capacity
– Reticulocyte count
MCV Decreased
RDW: incresed
Iron sat% Decreased
Ferritin: Decreased
BM irone: Decreased
Fe defiency anemia
MCV: low or normal
RDW: normal
IRon Sat%: Decreased/normal
Ferritin: Increased/normal
BM Iron: increased
Anemia of Chronic Disease
MCV: decreased
RDW: increased/normal
IRon Sat%: increased
Ferritin: BIG increase
BM Iron: Big increase
Thalassemias
MCV: decreased
RDW: increased
IRon Sat%: increased/normal
Ferritin: increase
BM Iron: increase
Sideroblastic anemia
Further evaluation of the patient’s bleeding includes:
– Von Willebrand’s antigen = 90% (nml 60-130)
– Von Willebrand’s activity = 110% (nml 60-130)
– Factor VIII activity =95% (nml 65-140)
– Von Willebrand multimers = normal distribution
– Thrombin time = 13 seconds (nml 12-14 sec)
– Platelet function assay- prolongation on collagen/epinephrine cartridge >300 sec (nml <180); normal on collagen/ADP cartridge
what caused this?
d. decreased platelet aggregation due to reduce formation of thromboxane A2 : from aspirin use
Mechanism of aspirin
Decreaes plat aggregatiob via COX-1 inhibiton
see decreased thromboxane formation which is responsible for platelet aggregation via mediation of GPIIB/IIIA
cause mucocutaneous bleeding including petechiae and mucosal bleeding (epistaxis, gingival bleeding, menorrhagia)
Defects of primary hemostasis (formation of platelet plug)
Disorders that affect primary hemostasis include
qualitative and quantitative platelet defects, vW disease, and disorders of the endothelium
is a diagnosis of exclusion, requiring lab testing to evaluate for other causes of bleeding
ITP
