Ch4 - 1) Primary Hemostasis and Bleeding Related Disorders Flashcards
What is hemostatsis?
Damage to the wall is repaired by hemostasis,
Hemostasis involves the formation of?
a thrombus (clot) at the site of vessel injury
Hemostasis stages?
primary and secondary.
Primary hemostasis?
forms a weak platelet plug
Primary hemostasis is mediated by?
interaction between platelets and the vessel wall
Secondary hemostasis?
stabilizes the platelet plug
Secondary hemostasis is mediated by?
the coagulation cascade.
What is Step 1 in secondary hemostasis?
Transient vasoconstriction of damaged vessel
How is Step 1 in secondary hemostasis mediated?
by reflex neural stimulation and endothelin release from endothelial cells
What is Step 2 in secondary hemostasis?
Platelet adhesion to the surface of disrupted vessel
In step 2 of secondary hemostasis, how does platelet adhesion occur?
Von Willebrand factor (vWF) binds exposed subendothelial collagen,
How do platelets bind to vWF?
via the GPIb receptor
vWF is derived from?
the Weibel-Palade bodies of endothelial cells and a-granules of platelets.
What is Step 3 in secondary hemostasis?
Platelet degranulation
In step 3 of secondary hemostasis what does Adhesion induce?
shape change in platelets and degranulation with release of multiple mediators
What are the mediators released in step 3 of secondary hemostasis?
ADP and TXA
What is the role of ADP in step 3 of secondary hemostasis?
it is released from platelet dense granules; promotes exposure of GPIIb/IIIa receptor on platelets.
What is the role of TXA in step 3 of secondary hemostasis?
it is synthesized by platelet cyclooxygenase (COX) and released; promotes platelet aggregation
What is step 4 in secondary hemostasis?
Step 4?Platelet aggregation
Where and how do Platelets aggregate in step 4 of secondary hemostasis?
at the site of injury via GPIIb/IIIa using fibrinogen (from plasma) as a linking molecule;
What does platelet aggregation result in?
formation of platelet plug
Platelet plug?
It is weak; coagulation cascade (secondary hemostasis) stabilizes it.
What are disorders of primary hemostasis usually due to?
Usually due to abnormalities in platelets;
Disorders of primary hemostasis are divided into?
quantitative or qualitative disorders
What are some Clinical features for disorders of primary hemostasis?
mucosal and skin bleeding.
What is the most common overall symptom in mucosal bleeding?
epistaxis
What are symptoms of mucosal bleeding?
epistaxis, hemoptysis, GI bleeding, hematuria, and menorrhagia. Intracranial bleeding occurs with severe thrombocytopenia.
What are the symptoms of skin bleeding?
include petechiae (1-2 mm), ecchymoses (> 3 mm), purpura (> 1 cm), and easy bruising;
Petechiae are a sign of what?
thrombocytopenia and are not usually seen with qualitative disorders.
What are some useful laboratory studies for disorders of primary hemostasis?
platelet count, bleeding time, blood smear, bone marrow biopsy
Platelet count
normal 150-400 K/pL; < 50 K/pL leads to symptoms,
Bleeding time
normal 2-7 minutes; prolonged with quantitative and qualitative platelet disorders
Blood smear
used to assess number and size of platelets
Bone marrow biopsy
used to assess megakaryocytes, which produce platelets
What is immune thrombocytopenic purpura?
(ITP) is an autoimmune production of IgG against platelet antigens (GPIIb/IIIa)
What is the most common cause of thrombocytopenia in children and adults?
immune thrombocytopenic purpura
In ITP what results in thrombocytopenia?
Antibody-bound platelets are consumed by splenic macrophages
ITP is divided into?
acute and chronic forms
Acute form of ITP?
arises in children weeks after a viral infection or immunization;selflimited, usually resolving within weeks of presentation
Chronic form of ITP?
arises in adults, usually women of chilbearing age. May be primary or secondary (e.g SLE).
What is the risk involved in chronic ITP?
May cause short-lived thrombocytopenia in offspring since antiplatelet IgG can cross the placenta.
laboratory findings for ITP include
decreased platelet count, often < 50 K/pL, Normal PT/FTT, Coagulation factors are not affected. increased megakaryocytes on bone marrow biopsy
What is the Initial treatment for ITP?
corticosteroids.
How will children and adults respond to the initial treatment for ITP?
Children respond well; adults may show early response, but often relapse.
In addition to corticosteroids what else is used in the treatment of ITP?
IVIG is used to raise the platelet count in symptomatic bleeding, but its effect is short-lived,
What is a permenant solution for patients with ITP?
Splenectomy eliminates the primary source of antibody and the site of platelet destruction (performed in refractory cases).
What is microangiopathic hemolytic anemia?
Pathologic formation of plateletmicrothrombin small vessels
How are plateletmicrothrombin formed and what is the result?
Platelets are consumed in the formation of microthrombi sheering the RBCs as they cross microthrombi, resulting in hemolytic anemiawith schistocytes
What is microangiopathic hemolytic anemia seen in?
thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)
What is TTP due to?
decreased ADAMTS13 which is an enzyme that normally cleaves vWF multimers into smaller monomers for eventual degradation.
How does TTP lead to microangiopathic hemolytic anemia?
- Large, uncleaved multimers lead to abnormal platelet adhesion, resulting in microthrombi.
Decreased ADAMTS13 is usually due what?
an acquired autoantibody;
TTP is most commonly seen in?
adult females
HUS is due to?
Hemolytic uremic syndrome is due to endothelial damage by drugs or infection.
HUS is classically seen in?
children with E coli G157;H7 dysentery, which results from exposure to undercooked beef
How is E Coli related to microangiopathic hemolytic anemia?
E coli verotoxin damages endothelial cells resulting in platelet microthrombi
The clinical findings for HUS and TTP include
Skin and mucosal bleeding, Microangiopathic hemolytic anemia, Fever, Renal insufficiency, CNS abnormalities
Renal insufficiency is more common in HUS or TTP?
HUS ? thrombi involve vessels of the kidney
CNS abnormalities are more common in HUS or TTP?
TTP ? Thrombi involve vessels of the CNS
Laboratory findings for microangiopathic hemolytic anemia include?
Thrombocytopenia with increased bleeding time Normal PT/PTT (coagulation cascade is not activated), anemia with schistocytes, increased megakaryocytes on bone marrow biopsy
Treatment for microangiopathic hemolytic anemia?
involves plasmapheresis and corticosteroids, particularly in TTP.
What are the qualitative platelet disorders?
bernard-soulier, Glanzmann thrombasthenia, asprin, uremia
Bernard-Soulier syndrome
is due to a genetic GPIb deficiency; platelet adhesion is impaired.
In Bernard-Soulier what lab test are you interested in?
Blood smear which shows mild thrombocytopenia with enlarged platelets.
Glanzmann thrombasthenia is due to?
a genetic GPIIb/IIIa deficiency; platelet aggregation is impaired.
Aspirin and microangiopathic hemolytic anemia?
it irreversibly inactivates cyclooxygenase; lack of TXA, impairs aggregation.
Uremia and microangiopathic hemolytic anemia
disrupts platelet function; both adhesion and aggregation are impaired.
