Blood: 4.1: 1a hemostatsis and bleeding Flashcards
What is hemostasis?
repairing damaged blood vessels
What is a thrombus?
a clot
What is the goal of 1a hemostasis?
formation of a weak platelet plug
What is the goal of 2a hemostasis?
stabilization of platelet plug
What is the first step of 1a hemostasis?
rapid, transient vaso-constriction of the damaged BV (“knee-jerk reaction”)
____ and ____ modulate the first step of 1a hemostasis.
- Neurostimulation
- endothelien- from the endothelial cells
What is the 2nd step of 1a hemostasis?
Von Willebrand factor lines the damaged area by binding to exposed collagen
Why does Von Willebrand factor bind to the damaged vessel?
to allow platelets to bind to them via GPIb receptor
Platelets bind to Von Willebrand factor via ____.
GPIb
Where does Von Willebrand factor come from?
- platelets
- endothelial cells (in the Weible-Palae body)
What do Wible-Pilate bodies contain?
- P-selectin
- Von Willebrand factor
What is the 3rd step of 1a hemostasis?
activation of platelets
What are the 2 mediators platelets secrete to activate themselves?
- ADP
- thromboxane-A2
Thromboxane-A2 is a derivative of ____.
platelet cyclooxygenase
What kind of granule carries ADP?
dense
ADP induces the platelets to express the ____ receptor.
GP2B3A
What does GPIIb/IIIa do?
allows the platelets to aggregate to one another
Thromboxane-A2 (TXA2) does what?
signals additional platelets to aggregate
What is aggregation?
when all the platelets join together at a particular place where initial platelets have adhered
What is adhesion?
platelets binding to subendothelial collagen via Von Willebrand factor
What is the molecule that links platelets to each other?
fibrinogen
Adhesion causes a ____ in platelets and _____, which releases multiple mediators.
shape change; degranulation
Platelets aggregate at site of injury via ____ using ____ as a linking molecule.
GpIIb/IIIa; fibrinogen
What is the result of 1a hemostasis?
formation of a platelet plug
Name the 2 types of general disorders of 1a hemostasis.
- quantitative
- qualitative
1a disorders of hemostasis are usually due to _____.
abnormalities in platelets
When pts have 1a hemostasis platelet disorders, they will classically present with ____ and ____ bleeding.
mucosal and skin
What complication can occur with severe thrombocytopenia?
intracranial bleeding
Name some skin manifestations that can occur in 1a hemostasis defects.
- petechiae
- purpura
- ecchymoses
- easy bruising
If you suspect a 1a hemostasis disorder, what labs should you order?
- platelet count
- bleeding time
- blood smear
- bone marrow biopsy
What is the normal platelet count range?
150,000-400,000
What is a normal bleeding time range?
2-7 minutes
What are we looking for in a bone marrow biopsy?
- megakaryocytes
- present/absent/morphology
What does ITP stand for?
immune thrombocytopenic purpura
What is ITP?
autoimmune production of IgG against platelet antigens (GPIIb/IIIa)
What is the most common cause of thrombocytopenia in children and adults?
ITP
Where are ITP antibodies produced?
plasma cells in the spleen
Where are antibody-marked platelets consumed? What is the result?
- the spleen macrophages
- thrombocytopenia
Who gets the acute form of ITP? When? What is the tx?
- in children
- weeks after viral infection or immunization
- self-limited- resolves w/i a few weeks; support pt if platelet count drops too far
Who gets the chronic form of ITP? What does it cause in pregnant women?
- adult women of child bearing age
- can cross the placenta to give baby transient thrombocytopenia too
What are the common lab findings in ITP?
- low platelet count (less than 50,000)
- normal PT/PTT
- increased megakaryocytes on bone marrow biopsy
How is ITP treated?
- corticosteroids (good in children, only works short-term in adults)
- IVIG (also short-lived effect)
- splenectomy
Why is splenectomy a good treatment for ITP?
bc it removes both the source of the autoantibody and the source of the platelet destruction
What is microangiopthic hemolytic anemia?
pathologic formation of platelet microthrombi in small vessels
How does hemolytic anemia occur in microangiopthic hemolytic anemia? What is the result to the RBC?
- microthrombi in the BVs damage RBCs as they pass thru, resulting in:
- schistocytes
Platelets are ____ in the formation of microthrombi.
consumed
What is a schistocyte? When are they seen?
- a helmet cell (damaged RBC)
- microangiopathic hemolytic anemia, aortic stenosis
What does TTP stand for?
thrombotic thrombocytopenic purpura
What does HUS stand for?
hemolytic uremic syndrome
What is formed in TPP (thrombotic thrombocytopenic purpura)? Why does this occur?
- microthrombi form, allowing abnormal platelet adhesion
- decreased ADAMTS13 enzyme
What does ADAMTS13 do?
cleaves VWF into monomers for degradation, preventing abnormal platelet adhesion
What causes decreased ADAMTS13? What is the most common reason?
- genetic defects
- autoantibodies** most common
Who is the classic pt with decreased ADAMTS13?
adult females
What causes HUS?
drugs or infections
What pathogen is notorious for leading to HUS?
E. coli 0157:H7
Where do the platelet microthrombi occur in HUS and TTP?
- kidneys
- brain/CNS
How does E. coli 0157:H7 cause platelet microthrombi?
it produces an endothelium-damaging verotoxin
E. coli 0157:H7 is commonly contracted from exposure to ____, causing _____.
undercooked beef ; dysentery
What are the common clinical findings in TTP and HUS?
- skin and mucosal bleeding
- microangiopathic hemolytic anemia
- fever
- renal insufficiency
- CNS abnormalities
What is the predominant problem in HUS?
kidney dysfunction
What is the prominent problem in TTP?
CNS dysfunction
What lab findings are common in TTP/HUS?
- thrombocytopenia
- increased bleeding time
- PT/PTT normal
- anemia w/ schistocytes
- increased megakaryocytes
How is TTP treated?
- plasmapheresis
- corticosteroids
What is Bernard-Soulier Syndrome? What causes it?
- impaired platelet adhesion
- a genetic GP1b deficiency causing
What is seen in a blood smear of a pt with Bernard-Soulier syndrome?
- mild thrombocytopenia
- enlarged platelets
What is GP1b?
an adhesion molecule for VWF to attach to the endothelium
Why are the platelets enlarged in Bernard-Soulier syndrome?
platelets released from bone marrow are immature
What is Glanzman thrombastenia? What causes it?
- impaired platelet aggregation
- genetic GIIb/IIIa deficiency
What drug irreversibly inactivates COX?
aspirin
How does inactivating COX prevent platelet aggregation?
- prevents TXA2 from being produced (the molecule that binds platelets together)
What does uremia do?
causes platelet adhesion and aggregation impairment
What causes the “knee jerk” vasoconstriction to start coagulation?
endothelien
What are the s/s of mucosal bleeding in 1a hemostatis disorders?
- epistaxis
- hemoptysis
- GI bleeding
- hematuria
- menorrhagia
Petechiae are a sign of ______.
thrombocytopenia
______ binds exposed subendothelial collagen.
Von Willebrand factor (vWF)
Von Willebrand factor (vWF) binds ______.
exposed subendothelial collagen
Platelets bind _____ using the GPlb receptor.
von Willebrand Factor (vWF)
Platelets bind vWF using the _____ receptor.
GPlb
Platelets aggregate at the site of injury via _____ using fibrinogen as a linking molecule.
GPIIb/IIla
Platelets aggregate at the site of injury via GPIIb/IIla using _____ as a linking molecule.
fibrinogen
What is GPIIb/IIIa?
receptor used to cross-link platelets via fibrinogen
Name a disease associated with chronic ITP.
SLE
Why is IVIG a treatment for ITP?
it’s a distraction- the spleen starts consuming the IVIG instead of the platelets for a while
What does a schistocyte look like?
- an RBC with two pointy ends- a “helmet cell”
What is uremia?
a build up of urea and other nitrogenous wastes in the blood
