Hemostasis 1 Flashcards
What is primary hemostasis?
the formation of a weak platelet plug
What are the general steps of primary hemostasis?
(1) transient vasoconstriction of the damaged vessel
(2) Platelet adhesion to the surface of the disrupted vessel
(3) platelet degranulation
(4) platelet aggregation
What mediates transient vasoconstriction?
(1) reflex neural stimulation
(2) endothelin release from endothelial cells
Describe platelet adhesion to a damaged vessel in primary hemostasis
vWF binds to exposed subendothelial collagen; the platelets then bind the vWF via GP1b receptor on the platelet surface
Where does vWF come from?
(1) the Weibel-Palade bodies of endothelial cells
(2) alpha-granules of the platelets
Describe platelet degranulation
The adhesion of the platelet induces a shape change in the platelets and degranulation, with the release of multiple mediators, including ADP and TXA2 (thromboxane A2)
Where is ADP released from in platelets? What does it do?
Its released from the dense core granules
It promotes exposure of the GP2b/3a receptors on platelets
Where does TXA2 come from in platelets and what does it do?
It is synthesized from platelet cyclooxygenase, and promotes platelet aggregation
Describe platelet aggregation. What is the end result
Plates aggregate using GP2b/3a receptors, and fibrinogen as a linker molecule. The result is the formation of a weak platelet plug that must be stabilized by the coagulation cascde (secondary hemostasis).
What are the general clinical features of disorders of primary hemostasis?
mucosal and skin bleeding
What is a normal platelet count? Under what value will lead to symptoms?
150-400K/uL
<50K/uL will lead to symptoms
What is a normal bleeding time?
2-7 minutes
What happens to the bleeding time with platelet disorders?
It increases (it is prolonged)
What is the most common cause of thrombocytopenia in children and adults?
Immune Thrombocytopenic Purpura (ITP)
Briefly describe Immune Thrombocytopenic Purpura (ITP)
This is a disease in which autoantibodies (IgG) are produced against platelet antigens (e.g.,GP2b/3c). These antibodies are produced by plasma cells in the spleen, and the antibody-bound platelets are consumed by splenic macrophages –> thrombocytopenia
What are the laboratory findings in ITP?
(1) decreased platelet count (often <50K/uL)
(2) normal PT/PTT (coagulation cascade is not affected)
(3) increased megakaryocytes on bone marrow biopsy
Why do we see an increase in the number of megakaryocytes in ITP?
Because platelets are being destroyed outside the bone marrow (peripheral destruction), the bone marrow will respond by trying to produce more platelets. This leads to hyperplasia of the megakaryocytes.
What is the treatment for ITP?
(1) corticosteroids (initial treatment)
(2) IVIg (intravenous immunoglobulin)
(3) splenectomy (last resprt)
Explain how IVIG works and why it is used.
IVIG is used to raise the platelet count in symptomatic patients, but the effect is short-lived. When you administer IVIG, the splenic macrophages consume the IVIG instead of the antibody that is attached to the platelets, preventing platelet destruction. But once the IVIG is consumed, splenic macrophages will once again consume the platelet-bound IgG
How does splenectomy work?
It works in two ways, by (1) removing the site of auto-antibody production (plasma cells in the spleen); and (2) the site of antibody/platelet destruction (splenic macrophages).
This is only performed as a last resort in refractory cases
What type of infections would someone with a splenectomy be pre-disposed to?
Infections by encapsulated bacteria
What autoimmune disorder is associated with ITP, especially as a secondary cause of ITP?
SLE
What is Bernard-Soulier syndrome?
It is due to a genetic GP1b deficiency, imparing platelet adhesion
How does Bernard-Soulier syndrom present?
Blood smear shows mild thrombocytopenia with enlarged platelets.
(The platelets that are produced are large because they are produced prematurely; mild thrombocytopenia because if GP1b is not functioning, platelets tend not to live as long, and get destroyed)
What is Glanzmann thrombasthenia?
It is due to a genetic GP2b/3a deficiency that results in impaired platelet aggregation.
How does aspirin work?
Aspirin irreversibly inactivates cyclooxygenase. This inhibits TXA2 production; a lack of TXA2 impairs platelet aggregation