Platelets - Siegel Flashcards
What leads to platelet release from the megakaryocyte
fragmentation of megakaryocyte cytoplasm
Do platelets have a DNA or nucleus?
NO
What sorts of proteins are found in platelets?
structural, granule, glycoproteins, enzymes
How do platelets join together?
form fibrillar bridges between platelet membranes
What sort of coat do platelets have?
thick proteoglycan coat
What are the dense granules in the platelet?
the energy source
- store ATP, ADP, Ca, serotonin, Mg
What do the alpha granules of platelets contain
vWF, factor V, VWF
What proteins serve to keep the vessel walls dilated? (4)
prostacycline, nitric acid, ADPase, plaminogen activator
what do endothelial cells secrete with vessel wall injury?
procoagulants
- selectins
- integrins
- vWF
- promote platelet adhesion and vasoconstriction
What are subendothelial substances that are released with vessel wall injury
collagen, glycoprotein IIb/IIIa on platelet surface, thrombospondin, fibronectin, tissue factor
What are strong platelet agonists
thrombin and collagen
What are weak agonists for platelets
ADP and epinephrine
What does an elevated bleeding time mean
platelets aren’t function properly or thrombocytopenia
Mucosal bleeding
platelet defects
- easy bruising
- heavy menstrual periods
- abnormal period times
What does von Willebrands disease affect
platelet function and coagulopathy
What are causes of hypoproliferation in thrombocytopenia
radiation, drugs, chemicals, infections, bone marrow dysfunction
What are causes of increased desctruction in thrombocytopenia
drug induced, DIC
What is TPO
mediator of platelet production, produced in liver
What is the effect of TPO on megakaryocytes
more platelet production due to increased maturation
What is the effect of TPO on platelets circulating
platelets just absorb the TPO and they are degraded
What are drugs that lead to a decreased production of platelets
alcohol, thiazide diuretics, cimetidine, chemotherapy
What are three mechanisms that lead to a decreased survival of platelets
autosensitization of platelets
- hapten penicillin type
- immune complex deposition
Heparin induced thrombocytopenia
UFG can lead to platelets dropping to very low levels
- can lead to bleeding and thrombotic complications - low platelets but they’re bound together
- need direct thrombin inhibitors
Immune thrombocytopenia purpura
- low platelet count
- menorrhagia
- cutaneous bleeding
- intracranial hemmorhage
- no viral infection, no drugs, no congenital
What causes ITP
autoantibodies to platelet membrane antigens
What is the biggest risk of ITP
intracranial hemmorhage
What is the pathophysiology of ITP
rapid destruction of the spleen and liver
- suppression of TPO
- platelets are barely lasting
What are the autoantibodies targeting in ITP
GP IIb/IIIa and GP Ib/IX
What age group is acute ITP found in?
2-6 yo, usually after a viral infection
Thrombocytopenic purpura
thrombocytopenia, CNS symptoms, renal failure
What is the mechanism of action for thrombocytopenic purpura
antibody blocks the function of VWF cleaving
- no cleaving = increased platelet adhesion without activating coagulation cascade
What is therapy for TTP
removal of antibody and clearance of multimers
- plasma exchange
- steroids
What is the lifespan of a platelet
8 days
What holds the platelet plug together
fibrin wraps around to hold the platelet plug
What promotes platelet adhesion?
VWF - protein that plays an important role in clotting cascade and physiological adhesion of platelets to subendothelial membrane
What does prostacycline do
leads to vasodilation to make clotting less likely
What is the role of collagen with platelets?
strong platelet agonist that causes dense granule release
what is glycoprotein IIb/IIIa
antigens expressed on the platelet surface that helps platelets bind together
What is the role of thrombospondin and fibronectin
help activate platelets
What are examples of mucosal bleeding due to decreased platelet numbers
nose bleeds, easy bruising, heavy menstrual bleeding
A 25 yo woman presents to office complaining of easy bruising and petechiae but feels well otherwise. platelet count is 10,000 but her Hgb is 12.8 and Hct is 39 and WBC is 5.5
normal HgB, Hct, and WBC but LOW platelet count
- most likely diagnosis is immune thrombocytopenia
What is happening with TTP
not associated with clotting time
- collection of large VWF multimers, platelets are coming together forming platelet only clots
- using up platelets faster than the bone marrow can use them
A 45 yo woman presents with profound fatigue, fevers, and confusion. A CBC reveals a markedly diminished platelet count and the lab test saw schiztocytes. What would you want to check?
- check the peripheral smear
- check PT/PTT - checking intrinsic and extrinsic system
- draw blood cultures
- check LDH (hemolysis)
What are the common symptoms of TTP
low platelets, fever, don’t feel well, renal failure, CNS symptoms
What is the mechanism of TTP
- Ab blocks function of vWF cleaving protein ADAMTS-13
- increased level of high molecular vWF multimers
- increased platelet adhesion without activating coagulation cascade
What is the role of ADAMTS-13?
it cleaves Vwf and if you have antibodies against it then you can have TTP
What is the therapy for TTP?
removal of antibody and clearance of multimers
- plasma exchange
When would an in-vitro platelet aggregation study be helpful?
A patient has normal platelet count and bleeds excessively after a biopsy
- figure out what the problem is if you have a normal platelet count
How is a bleeding time study conducted?
pumping BP cuff to 40 mm, making a 1 cm cut 1 mm in depth, blotting q 30 sec until bleeding stops
What is a normal bleeding time?
less than equal to 8 minutes
Where is TPO produced
liver
What does TPO affect
platelets and megakaryocytes and promegakaryoctes in the bone marrow
What happens when TPO binds to progenitor cells?
expansion and maintenance of progenitor cells which leads to more megakaryocytes production
What happens when TPO binds magakaryocytes
enhancement of megakaryocyte maturation which leads to increased platelet production
What happens when TPO binds to platelets
- internalized and degraded within the cytoplasm
- doesn’t affect function or activity
- platelet numbers determine available TPO level
What do storage pool diseases result in
inherited causes of platelet dysfunction
- decrease or absence of dense granules
heparin inducted thrombocytopenia
- antibody reaction that leads to reduced platelet count
- platelets start clotting
- Elisa test to determine the Ab test
What type of heparin is more likely to cause HIT
unfractionated heparin
preeclampasia
- hypertension
- platelet levels can drop
- especially after 30 weeks
HELLP syndrome
- hemolysis
- elevated bilirubin
- elevated liver enzymes
- low platelets
Neonatal alloimmune thrombocytopenia
- fetal inheritance of platelet isoantigens not present in the mother
- comes from the dad
- well infant with very low platelet count
- intracranial bleeding of the baby
What is the treatment for neonatal alloimmune thrombocytopenia
infusion of washed maternal platelets
