Pathoma Ch 4 - Hemostasis Flashcards
what are the steps of primary hemostasis?
- transient vasoconstriction 2. platelet adhesion (Gp1b-vWF) 3. platelet degranulation 4. platelet aggregation (GpIIb/IIIa)
what is the first response to endothelial cell injury?
transient vasoconstriction -mediated by neural reflex and endothelin released by endothelial cells
what does vWF bind initially after endothelial cell injury?
subendothelial collagen
platelets bind vWF on subendothelial collagen by which receptor?
GP1b receptor
vWF derived from where?
Weibel-Palade bodies of endothelial cells and from alpha granules of platelets
what does Weibel-Palade bodies contain? where are they?
vWF and P-selectin (found in endothelial cells)
step 3 platelet degranulation releases what mediators?
ADP (dense granules) TXA2 - derivative of platelet cyclooxygenase
what does ADP and TXA2 do?
ADP - promotes exposure of GpIIb/IIIa on platelets TXA2 - promotes platelet aggregation
platelet aggregation via which receptor
GPIIb/IIIa with fibrinogen as linker mlcl
what links platelets together?
fibrinogen links platelets via GpIIb/IIIa
clinical features of disorders of primary hemostasis (platelet disorders)
mucosal and skin bleeding -epistaxis (MC), hemoptysis, GI bleeding, hematuria, menorrhagia -intracranial bleeding if severe thrombocytopenia
what is the different types of skin bleeding
petechiae (1-2mm) 3mm) 1cm)
petechiae are a sign of what?
thrombocytopenia (seen when platelet count is low)
at what level of platelets do you get symptoms?
less than 50,000
MCC of thrombocytopenia in children and adults
ITP - immune thrombocytopenic purpura
what mediates the platelet destrxn in ITP?
anti-platelet IgG -produced by plasma cells in spleen -consumed by splenic macrophages
acute form of ITP?
-seen in children -usu occurs weeks after viral infxn or immunization -self-limited, provide supportive care
chronic form of ITP
-seen in women 20-50 yo -primary (idiopathic) or secondary (SLE) -can see transient thrombocytopenia in fetus, since IgG can cross placenta
Lab findings in ITP?
-low platelet count (
treatment of ITP
- corticosteroids (children respond well; adults can relapse afterwards) 2. IVIG - symptomatic treatment, but short-lived 3. splenectomy - performed in refractory cases
what is curative of ITP?
splenectomy
what is the basic mechanism in microangiopathic hemolytic anemia?
-formation of platelet microthrombi (platelets get consumed) -shearing of RBCs when trying to cross platelet microthrombi -get schistocytes and hemolysis
what are the 2 disorders that you see microangiopathic hemolytic anemia in?
- TTP - thrombotic thrombocytopenia purpura 2. HUS
what causes TTP?
decreased enzyme ADAMTS13 -normally cleaves vWF multimers into smaller monomers -without enzyme, get abnormal platelet adhesion -forms microthrombi
what causes enzyme defect in TTP?
-decreased ADAMTS13 is due to autoantibodies destroying it -can also be genetic (but rare) -seen in adult females (autoimmune)
what is HUS
hemolytic uremic syndrome -get endothelial damage from drugs or infxn -results in platelet microthrombi - shears rbc’s -microangiopathic hemolytic anemia -esp in the kidney (and brain)
what causes HUS and who gets it?
E.coli O157:H7 -usu seen in children after exposure to undercooked beef
what mediates the damage in HUS?
e. coli O157: H7 has a verotoxin that damages endothelium -esp in the kidney
what are the clinical features of TTP-HUS
- skin and mucosal bleeding 2. microangiopathic hemolytic anemia 3. fever 4. renal insufficiency (more common in HUS) 5. CNS abnormalities (more common in TTP)
lab findings in TTP-HUS
- thrombocytopenia (increased bleeding time) 2. normal PT/PTT 3. anemia with schistocytes 4. increased megakaryocytes on BM biopsy
treatment for TTP-HUS
more for TTP 1. plasmapheresis (remove autoAb) 2. corticosteroids (suppress prdxn of autoAb)
Bernard-Soulier Syndrome
genetic GP1b deficiency -platelet adhesion is impaired -mild thrombocytopenia with enlarged platelets
mild thrombocytopenia with enlarged platelets on blood smear?
Bernard-Soulier Syndrome “Big Suckers = Bernard Soulier”
Glanzmann thrombasthenia
genetic GPIIb/IIIa deficiency -platelet aggregation is impaired
aspirin inhibits what and reduces production of what mediator
-irreversibly inhibits COX -inhibits production of TXA2 - impairs plt aggregation
how does uremia affect platelet function?
uremia impairs both platelet adhesion and aggregation
coagulation factors are produced where?
liver (produced in inactive state, require activation)
what is the purpose of coagulation cascade?
to generate thrombin to convert fibrinogen to fibrin -stabilizes platelet plug -forms platelet-fibrin thrombus
what is required to activate coagulation factors?
- exposure to activating substance -tissue thromboplastin activates FVII (extrinsic) -subendothelial collagen activates FXII (intrinsic) 2. phospholipid surface (of platelets) 3. calcium (platelet dense granules)
clinical features of problems with secondary hemostasis (coagulation cascade)?
-deep tissue bleeding into muscles/joints (hemarthrosis) -rebleeding after surgical procedures
what activates extrinsic pathway?
tissue thromboplastin activates factor 7
what activates intrinsic pathway?
subendothelial collagen activates factor 12
how do you monitor intrinsic pathway?
PTT -activated by SEC - subendothelial collagen -used to monitor HEP - heparin activity
how do you monitor extrinsic pathway?
PT -activated by TT - tissue thromboplastin -used to monitor warfarin/coumadin
heparin acts on what? how do you monitor?
acts on intrinsic pathway -monitor with PTT
warfarin acts on what? how do you monitor?
acts on extrinsic pathway -monitor with PT/INR