Primary Hemostasis and Related Bleeding Disorders Flashcards
By what process are blood vessels repaired?
Hemostasis
What is primary hemostasis?
Formation of a weak platelet plug and is mediated by interaction
What is secondary hemostasis?
Stabilization of the platelet plug and is mediated by coagulation cascade
What are the 4 steps of primary hemostasis?
Transient vessel vasoconstriction, platelet adhesion to surface of disrupted blood vessel, platelet degranulation, platelet aggregation
What are the two mediators of transient vessel vasoconstriction in primary hemostasis?
Endothelin released by endothelium and neural stimulation
Describe the process of platelet adhesion
Von Willebrand factor binds exposed subendothelial collagen. Platelets bind vWF using the GPIb receptor.
In order of importance, where does Von Willebrand factor come from?
Weibel-Paladie bodies of endothelial cells and Alpha-granules of platelets.
What process does plate adhesion induce.
Adhesion induces platelet degranulation and the release of ADP and TXA2.
Describe platelet degranulation and the release of associated mediators
Adhesion causes platelets to change shape and release ADP which promotes exposure of GIIb/IIIa receptor. Platelets also release TXA2 which promotes further platelet aggregation.
Where do ADP and TXA2 come from, respectively?
Platelet dense granules and platelet cyclooxygenase.
Describe the process of platelet aggregation
Platelets aggregate by GPIIb/IIIa receptor crosslinking via fibrinogen forming the platelet plug. Coagulation cascade eventually strengthens this weak plug.
Clinical Symptoms of disorders in primary hemostasis
Mucosal bleeding, epistaxis, hemoptysis, GI bleeding, hematuria, menorrhagia.
When is intracranial bleeding highly probable?
With severe thrombocytopenia
Symptoms of skin bleeding and sizes
Petechiae 1-2 mm, purpura >3 mm, ecchymoses >1 cm
Are petechiae commonly seen with quantitative or qualitative disorders?
Quantitative disorders
4 Useful laboratory studies and their normal findings
Platelet count 150-400K/uL, Bleeding time 2-7 mins, Blood smear to assess number/size of platelets, Bone marrow biopsy to asses megakaryocytes
What is Immune Thrombocytopenic Purpura?
Autoimmune production of IgG against platelet antigens such as GPIIb/IIIa
Describe the process of ITP
Spleen produces auto Abs against platelet antigen (GPIIb/IIIa), spleen macrophages consume platelet-IgG complex causing thrombocytopenia
Describe acute and chronic ITP
Acute - often arises in children weeks after viral infections/immunizations, self-limiting; Chronic - most commonly found in women of childbearing age, may be primary or secondary.
What is the concern of pregnant women who have ITP?
IgG Abs to platelet antigens can cross the placenta and cause the offspring to have transient thrombocytopenia
3 Laboratory findings in ITP
Platelet count <50K/uL, Normal PT/PTT, Increased megakaryocytes in bone marrow
Tx for ITP
Corticosteroids, IVIG competes with platelet-IgG complex so that spleen only consumes IgG, Splenectomy - removes site of Ab production and platelet-IgG consumption
What is Microangiopathic Hemolytic Anemia?
Pathologic formation of platelet microthrombi in small vessels (uangiopathic) which shear RBCs forming schistocytes (hemolytic)
In which two conditions is microangiopathic hemolytic anemia observed?
Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)
Describe pathology of TTP
ADAMTS13 deficiency (either autoAb or genetic) cannot cleave VWF multimers resulting in abnormal platelet adhesion and uthrombi.
Describe pathology of HUS
E. coli O157:H7 releases veratoxin which causes systemic endothelial damage, resulting in platelet microthromi and RBC shearing
Clinical findings of TTP and HUS
Skin/mucosal bleeding, uangiopathic hemolytic anemia, fever
- Renal Insufficiency (More common in HUS)
- CNS abnormalities (More common in TTP)
What does TTP and HUS stand for?
Thrombotic Thrombocytopenic Purpura and Hemolytic-Uremic Syndrome
Laboratory findings for TTP and HUS
Thrombocytopenia, increased bleeding time, Normal PT/PTT, Anemia w/ schistocytes, Increased megakaryocytes on BM biopsy (Body responds to thrombocytopenia by increase MK activity)
TTP and HUS Tx
Plasmapheresis (to remove Abs) and corticosteroids (to reduce production of Ab)
What is Bernard-Soulier syndrome?
Genetic GPIb deficiency and therefore impaired platelet adhesion, mild thrombocytopenia because platelets get destroyed, enlarged platelets (platelets released as immature) BS = “Big suckers”
What is Glanzmann thrombasthenia?
Genetic GPIIb/IIIa deficiency; platelet aggregation is impaired
Explain the mechanism of aspirin
Irreversibly inactivates COX resulting in low TXA2. Impairs platelet aggregation.
How does uremia cause platelet dysfunction?
Adhesion and aggregation are impaired by nitrogenous waste products which build up during kidney failure
