Chapter 4.1 Primary Hemostasis and Related Bleeding Disorders Flashcards
Distinguish between primary and secondary hemostasis. Describe the crucial interactions/mediators of each stage.
endothelial cells line blood vessels sit on top of basement membrane
damage of tube is repaired by hemostasis (thrombus/clot will form at site of injury)
primary hemostasis: form weak platelet plug- adhesion and aggregation of platelets in place of injury (interaction platelets and vessel wall)
secondary hemostatsis stabilizes the platelet plug; mediated by coagulation cascade
When there is disruption of blood vessel, what is the first step/reaction of primary hemostasis?
What mediates this process (2 things)?
- transient vasoconstriction of damaged vessels (blood vessel will rapidly constrict) sort of knee-jerk reaction, gets damaged and clamps down quickly.
mediated by neural stimulation (neural reflex)
endothelial cells themselves have molecule called endothelin that will be released upon damage and cause quick transient vasoconstriction of damaged factor
What is step 2 of primary hemostasis? Describe the mechanism.
Platelet adhesion to surface of disrupted vessel:
Von willibrand factor binds exposed subendothelial collagen
platelets bind vWF using GP1b receptor
(when endothelial cells disrupted, BM exposed and connective tissue underneath exposed, both contain collagen which allows vWF to bind and vWF acts as a linker molecule for platelets to bind to this region
platelets use GP1B to bind vWF
Where does Von Wilibrand Factor come from?
- platelet itself
- endothelial cells (vast majority of VWF comes from endothelial cell)
within endothelial cell its the Weibel-Palade body that holds VWF.
vWF is derived from Weibel-Palade bodies of endothelial cells and alpha granules of platelets
WP bodies contain P selectin (selectin speed bump) and VWF
What is step 3 of primary hemostasis?
once binding occurs, platelets activated, undergo shape change, and degranulate
Step 3: Platelet degranulation
adhesion to VWF causes shape change which allows for dumping of mediators to move process forward
mediators are ADP (present in dense core granules) promotes exposure of GPIIb/IIIa receptor on platelets
and Thromboxan A2 (TXA2- derivative of platelet cyclooxygenase) promotes platelet aggregation
ADP induces platelets to express another receptor; Gp2b3a which is essential for platelet aggregation (when all platelets join together at spot)
adhesion-platelet binding to area of exposed sub-eendothelial collagen via VWF, aggregation (when platelets aggregate on top of those adhesed platelets
TXA2 is signal for further platelet aggregation
important linker molecule for platelets to aggregate is fibrinogen
Platelet adhesion to VWF causes shape change which allows for dumping of mediators to move process forward. What are the mediators and where do they come from?
mediators are ADP (present in dense core granules) and Thromboxan A2 (TXA2- derivative of platelet cyclooxygenase)
What is the role of ADP and TXA2?
ADP induces platelets to express another receptor; Gp2b3a which is essential for platelet aggregation (when all platelets join together at spot)
TXA2 is signal for further platelet aggregation
What is step 4 of primary hemostasis?
Platelet aggregation
Platelets aggregate at site of injury via GpIIb/IIIa using fibrinogen as a linking molecule
results in formation of platelet plug
important linker molecule for platelets to aggregate is fibrinogen
What will stabilize the weak platelet plug?
coagulation cascade (secondary hemostasis) stabilizes it
When patients have disorders of primary hemostasis they present with classic signs and symptoms, desscribe.
mucosal and skin bleeding
epistaxis (nose bleeding) most common hemoptysis (coughing up blood) GI bleeding hematuria (blood in urine menorrhagia (heavy menstrual bleeding bc endometrial also is mucosal surface)
What is a feared consequence of low platelet count?
intracranial bleeding occurs with severe thrombocytopenia
What are some symptoms of skin bleeding?
varying sizes of bleeding in skin:
petechiae (pin-point bleeding in the skin)
purpura (larger, 3mm or greater)
ecchymoses (approx greater than 1 cm)
easy bruising
What type of bleeding is a sign of thrombocytopenia?
petechiae (pin-point bleeding in the skin) -presents w quantitative disorders
sign of thrombocytopenia and are not usually seen with qualitative disorders
When a patient has a disorder of primary hemostasis with skin and mucosal bleeding, what are some useful laboratory studies?
platelet count - 150,000-400,000/microliter is normal
bleeding time- prick patient, see how long before they stop bleeding (2-7 minutes is normal)
blood smear - look at blood on slide, assess number in rough estimate, assess size of platelets
bone marrow biopsy (megakaryocytes are cells prod. platelets… are there megakaryocytes in bone marrow?)
What is the most common cause of thrombocytopenia in children and adults?
ITP:
Autoimmune production of IgG against platelet antigens (like GPIIb/IIIa)
CPIIb/IIIa (used for cross linking of platelets via fibrinogen)
acute form- children
chronic form
Where are the antibodies (IgG in ITP) produced?
autoantibodies are produced by plasma cells in the spleen
IgG that cause ITP prod. by plasma cells in spleen, goes out into blood, binds platelets, then macrophages in spleen eat the antibody bound platelets
anitbodies made in spleen and platelets bound to antibody are consumed in spleen
(antibody-bound platelets are consumed by splenic macrophages, resulting in thrombocytopenia)
Describe how ITP usually manifests in children.
acute form arises in children
see thrombocytopenia weeks after viral infection or immunization (due to antibody IgG binding platelets and consuming them)
self-limited, usually resolves within weeks of presentation
What will ITP show in labs?
low platelet count (bc platelets are being consumed) often less than 50K/ul
Normal PT/PTT
increase/hyperplasia in megakaryocytes on bone marrow biopsy (bone marrow trying to increase platelets)
What will the labs show in a patient with ITP? (Platelet count? PT/PTT? megakaryocytes?)
low platelet count (bc platelets are being consumed) often less than 50K/ul
Normal PT/PTT
increase/hyperplasia in megakaryocytes on bone marrow biopsy (bone marrow trying to increase platelets)
If you’re worried that intracranial bleeding may occur in a patient with thrombocytopenia, what treatment can you offer?
IVIG can raise platelet count
give Ig (splenic macrophages will eat that Ig instead of the Ig bound to platelets) basically overrun spleen with IVIG so it'll leave the platelets alone
once IVIG consumed, spleen will eat the platelets again so effect is short lived
(do this to help w symptomatic bleeding)
What effect will a splenectomy have for patients with ITP?
eliminates the source of antibody and the site of destruction
performed in refractory cases
What is microangiopathic hemolytic anemia?
microangio-small blood vessels
pathologic formation of platelet microthrombi in small vessels (get abnormal aggregation of platelets), RBC have to pass across that platelet microthrombus which is partially occluding, you get shearing of RBC - you’ve destroyed the RBC = hemolysis
leads to hemolytic anemia
What is microangiopathic hemolytic anemia?
microangio-small blood vessels
pathologic formation of platelet microthrombi in small vessels (get abnormal aggregation of platelets), RBC have to pass across that platelet microthrombus which is partially occluding, you get shearing of RBC - you’ve destroyed the RBC = hemolysis
platelets are consumed in the formation of microthrombi, RBC are “sheared” as they cross microthrombi, resulting in hemolytic anemia with schistocytes
leads to hemolytic anemia
In what two classic disorders is microangiopathic hemolytic anemia seen?
Seen in TTP and HUS
