Primary Hemostasis Flashcards
What are the four steps of primary hemostasis?
- Transient vasoconstriction of damaged vessel
- Platelet adhesion to the surface of disrupted vessel
- Platelet de granulation
- Platelet aggregation
What are the two stages of hemostasis and what mediates them?
Primary hemostasis forms a weak platelet plug and mediated by interaction between platelets and vessel wall
Secondary hemostasis stabilizes the platelet plug and mediated by coagulation cascade
What mediates transient vasoconstriction?
Reflex neural stimulation and endothelia release from endothelial cells
How does vWF play a role in platelet adhesion? Where is it derived from?
It binds exposed sub endothelial collagen, platelets bind to it via GpIb receptor. vWF derived from Weibel - palade bodies of endothelial cells and alpha granules of platelets.
What is released during platelet degranulation and what does it do? What drug can affect this process?
ADP which promotes exposure to GpIIb3a receptors on platelets
TXA2 synthesized by cycloxygensase COX which promotes platelet aggregation. Asprin inhibits COX and you can also have a TXA2 deficiency.
How is a platelet plug formed and what stabilizes it?
Platelets aggregate at injury site via Gp2b3a using fibrinogen from plasma as a linking molecule resulting in platelet plug formation. Platelet plug stabilized by coagulation cascade.
What are symptoms of mucosal vs skin bleeding? What is a common sign of thrombocytopenia?
Mucosal bleeding - epistaxis, hemophylis, GI bleeding, hematuria, menorrhagia, intracranial bleeding
Skin bleeding - petichiea, purpura, echymoses, easy bruising.
Petichiae are a sign of thrombocytopenia
What are useful lab studies for primary hemostasis disorders?
Platelet count < 50 leads to symptoms, bleeding time, blood smear, bone marrow biopsy
What are the lab finding in immune thrombocytopenic purpura?
Low platelet count, normal PT/PTT, increased megakaryocyte on bone marrow biopsy
How is immune thrombocytopenic purpura (ITP) treated?
Initial tx is corticosteroids. Children respond well. Adults respond well initially but relapse. IVIG raises platelet count in symptomatic bleeding, but short lived effect. Splenectomy eliminates primary source of antibodies and the site of platelet destruction.
A 5 year old child presents to your clinic with signs of low platelet counts. Upon interview, you find that he had a stomach virus two weeks ago. What do you tell the mother about the cause of his presentation? Which type does he have? When will it resolve?
He has Immune thrombocytopenic purpura which is an autoimmune IgG production against platelet antigens like GpB2b/3a. These autoantibodies are made in the spleen by plasma cells and the platelet-antibody comby is consumed by splenic macrophages. He has the acute form of ITP. Also caused after immunization and will resolve within weeks of presentation.
A 27 yo stay at home 24 week pregnant mom with a history of lupus comes to the clinic with symptoms of low platelet counts. What does she have? Will her offspring have this? Why of why not?
She has chronic form of ITP. her offspring can have short lived thrombocytopenia since IgG can cross the placenta.
What is microangiopathic hemolytic anemia? What two diseases is it seen? What are some clinical findings?
It is pathological formation of platelet micro thrombi in small vessels. Hemolytic anemia and Schistocytes are seen. Two diseases are thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Clinical findings are a. Skin and mucosal bleeding b. Microangiopathic hemolytic anemia c. Fever d. Renal insufficiency (TTP) e. CNS abnormalities ( mostly HUS)
What causes TTP? Which population does it target?
TTP is due to decreased ADAMTS13 which is an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation. There will be large, uncleaved multimers leading to abnormal platelet adhesion resulting in microthrombi. Decreased ADAMtS13 commonly seen in adult females.
What causes HUS? Which population does it target?
HUS is due to endothelial damage by drugs or infection. Classically seen in children with E. Coli O157:H7 dysentery from undercooked beef. E. Coli verotoxin damages endothelial cells resulting in platelet microthrombi.
