Platelets Flashcards
primary job of platelet
hemostasis
stops the blood loss
which component of the cell is essential for hemostasis
cell membrane
covered with glycoproteins, coagulation factors, and phospholipids
IIb/IIIa protein
essential glycoprotein
once activated, binds to the fibrin to connect one platelet to others
forms stable clot
once activated they stick together
granules in platelet fxn
have vasoactive substances
causes vasoconstriction
histamine, ADP, platelet factor 4
activated platelet
degranulates, amplifies the coagulation response
platelet function once vessel injury occurs
- to adhere to defect in vessel wall when complexed with vWF
- release vasoconstrictors and chemicals that cause platelet aggregation (clumping)
- initiate and propagate the coagulation
coagulation factors are ____ form in blood
inactive
remain this way until they are activated by another factor in cascade
then they go on to activate the next one
coagulation cascade
highly complex chain ran activated by exposure of sub endothelial tissue OR release of tissue factor
(extrinsic or intrinsic)
common coagulation pathway
where they extrinsic and intrinsic pathways merge
- activation of factor 10 (X) –> 10a
- Xa cleaves prothrombin into thrombin
- thrombin cleaves fibrinogen to fibrin
fibrin
binds platelets and connects them to ea. other to stabilize the clot
endothelial cells
vasodilators that line blood vessels
produce vasorelaxors: NO, ADP-ase, prostacyclin
when damaged, stops producing these cells triggering vWF expression
also expresses tissue factor
vonWillebrand’s factor
binds platelets from bloodstream to vessel wall
grabs platelet from circulation and causes degranulation
site where platelet and coagulation factors interact
carrier protein for factor Viii
blood clot is formed bc of which process
coagulation cascade + platelet activation
made up of meshwork of fibrin threads with platelets trapping RBC and WBC
requirements for adequate hemostasis
- integrity of small vessels
- adequate # and fxn of platelets
- normal # and fxn of coagulation factors
- normal amount of inhibitors
opposition of coagulation
occurs bc we don’t want the clot to be too big (dampens cascade)
coagulation inhibitors and fibrinolysis
coagulation inhibitors
natural anticoagulants
protein C, protein S, anti thrombin III
inactive coagulation factors, stopping process
deficiencies lead to hyper coagulable state (more likely to form clots)
fibrinolysis
breaks up the clot
plasminogen is activated to make plasmin, which lyses fibrin and breaks up clot
what activates plasminogen ?
release of t-PA baby endothelial cells
can be artificially done in stroke, MI
activation occurs at same time as activation of coagulation cascade
what tests do we use to evaluate coagulation process
- platelet count
- PTT
- PT
platelet count
part of CBC
quantitive number of platelets
PTT
partial thromboplastin time
measures first phase of coagulation
used to monitor dosages of UNFRACTIONATED heparin
PT
prothrombin time
measures time of combined second and third phases of coagulation
monitors warfarin dosage and liver dysfunction
Thrombocytosis
excesss of platelets (above 400,000 - get worried when its more like 700k)
increases viscosity
secondary thrombocytosis
excessive platelets that occur secondary to cytokine processes (infection or impending sepsis )
this is most common
may also be bc of iron deficiency, autoimmune, malignant
essential thromocytosis
occurs less commonly
don’t know why but when work up must exclude everything else
thrombocytopenia
platelet deficiency
<100,000
often found with petechial bleeding
may also prevent with clotting (may cause clotting to activate too)
6 main etiologies of thrombocytopenia
- bone marrow injury or disease causing damage to megakaryocytic (CXT, XT, alcohol) or medications (thiazide diuretics, PCN, cephalosporins, NSAIDS, H2 blockers, estrogen)
- infiltration of bone marrow by cancer cells (leukemia or metastases) – will affect multiple lines
- anitplatelet antibody destroys platelets in peripheral vessels (3 subtypes)
- splenic sequestration of larger # than usual (enlarged spleen - liver disease, CML, mono)
- failure of stimulation of thrombopoeisis hormones
- abnormal platelet FUNCTION
subtypes of anti platelet Abs in peripheral vessels
immune thrombocytopenia purpura
heparin induced thrombocytopenia
thrombotic thrombocytopenia purpura
immune thrombocytopenia purpura
ITP
IgG Abs to platelets cause them to be tagged and trapped in the spleen
Pediatric ITP - 1-6, male, occurs acutely after viral infection, resolves spontaneously
Adult ITP- females, 30s-40s, occurs insidiously, req. treatment (steroid)
heparin induced thrombocytopenia
autoantibody to heparin and platelet factor 4
only occurs in pts on heparin
causes activation of platelet and its destruction at same time
paradoxical arterial venues clot formation
clots in larger arteries AND veins
thrombotic thrombocytopenia purpura
TTP
adult females (20-50)
can be associated with infection, high levels of estrogen (Birth control)
lack of an enzyme that cleaves vWF in molecules causing platelets to be consumed and activated (less numbers of free ones in blood)
splenic sequestration of platelets when?
can occur anytime the spleen is enlarged
i.e. liver disease, CML , mono
more platelets are in the spleen than are in the blood
why is it uncommon to see hormone failure as a cause of thrombocytopenia?
bc thrompoeitin can be stimulated by the bone marrow, liver, muscles or nervous tissue while erythopoeitin can only be activated by the kidneys
petechiae
small breaks in the capillaries cause pin point size hemorrhages in the skin and mucous membranes
coagulation factor deficiencies
hereditary and rare
- vonWillebrand’s dx
- hemophilia
extensive and severe bleeding following minor trauma
von Willebrand’s dx
autosomal dominant
cells don’t express the vWF on their cells so they are unable to attach to the platelet and clot
will also have lower factor 8 levels
excessive bleeding in SubQ tissues and skin after injury
hemophilia
x linked recessive
PRIMARILY effects males
episodes of hemorrhage in joints and internal organs
Hemophilia A- factor 8 def.
Hemophilia B- factor 9 def.
hemarthroses will cause pain and deformity
these deficiencies cause bleeding deeper in the soft tissue
hematoma are large and palpable
coagulation factors
unable to get bleeding to stop but eventually it does
platelet disorder
get bleeding to stop but only for a short amount of time
coagulation deficiency
clot can still form but it isn’t held together
disseminated intravascular coagulation
condition where body creates and dissolves clots at the same time – widespread intravascular clot formation and fibrinolysis
this will use all the clotting factors and platelets supplied so can be terrible bc eventually can’t clot at all (consumptive coagulopathy)
large and widespread clotting and bleeding issue
caused by
- dx ass. with shock and tissue necrosis
- overwhelming bacterial infections (esp. gram - endotoxin that turns on coagulation)
inherited clotting disorders/thrombophilias
- factor V lieden
- anti thrombin III deficiency
- Protein C and Protein S deficiency
factor V leiden
most common
genetic mutation in Factor V that causes it to be resistant to inactivation
once activated it stays activated for a long time and clots form
anti-thrombin III def.
unable to inhibit thrombin
hypercoagulabilty caused by increase in fibrin
Protein C and Protein S def.
inability to inactivate factors Va and VIIIa
longer activation of 5 and 8 and hypoercoagulable state
