platelets + disorders (4 stars) Flashcards
precursor: megakaryocyte no nucleus (like RBC) lifespan: 8-10 days many glycoprotein receptors contain granules filled with signaling substances
platelets
several subunits linked by disulfide bonds
made by endothelial cells + megakaryocytes
present in platelets + endothelial cells
coag cascade: complexes with CF 8 to stabilize it
platelet adhesion to vessel wall and other platelets
von Willebrand Factor
unable to stabilize CF 8 →↑ PTT
no platelet adhesion to wall or platelets → ↑ bleeding time
von Willebrand disease
like hemophilia A
antiplatelet drugs
aspirin
ADP R inhibitors
glycoprotein 2b/3a inhibitors
platelet disorder presentation
platelet: microhemorrhages (mucous membranes, epistaxis, petechiae, purpura - larger hemorrhage under skin)
vs
coagulopathy: macrohemorrhages
↑ bleeding time
normal PT/INR and PTT
platelet disorder
platelet disorders: ↑ bleeding time
immune thrombocytopenia (ITP)
thombotic thrombocytopenic purpura (TTP) - HUS
Bernard-Soulier syndrome
Glanzmann thrombasthenia
auto-antibodies bind to Gp2b/3a on platelet surface → immune system destroys platelets
↓ PLT →↑ megakaryocytes on BM
immune thrombocytopenia (ITP)
treatment of immune thrombocytopenia (ITP)
steroids
IVIG
splenectomy: 1/3 PLT are normally stored in spleen → allows more PLT to be in circulation
acute deficiency of metalloprotease ADAMTS 13: usually cleaves vWF multimers into active vWF units
wWF multimers bind to platelets → unregulated platelet aggregation → widespread thrombosis
↓ PLT (none left) → bleeding and purpura
also, activation of coag cascade → excessive fibrin mesh in vessels → microangiopathic hemolytic anemia (shistocytes, ↑LDH)
thrombocytopenic purpura (TTP)
triad of hemolytic uremic syndrome - HUS
pentad of TTP
hemolytic anemia renal insufficiency: uremia ↓ PLTs (none left) add for TTP: neuro sx: confusion, headache, seizure, coma, focal deficit fever
Nasty Fever Torched His Kidneys
HUS-TTP presentation
Nasty Fever Torched His Kidneys TTP: Neuro sx Fever HUS: Thrombocytopenia Hemolytic anemia Kidney failure: uremia
child with E. coli O157:H7 infection
hemolytic uremic syndrome
type of platelet dysfunction
defect of Gp1b: binds platelet to vWF (which is bound to subendothelial collagen)
platelet unbound to collagen → defect in platelet plug
platelets enlarged → remove from circulation (slighlty↓PLT)
Bernard-Soulier syndrome (rare)
defect in Gp2b/3a → abnormal PLT aggregation
NORMAL PLT count
↑ bleeding time: no aggregation
Glanzmann thrombasthenia
additional causes of thrombocytopenia (↓ PLT)
heparin-induced thrombocytopenia
aplastic anemia
mixed platelet + coagulation
disorders
von willebrand disease
DIC
mixed bleeding disorder:
defect of von Willebrand factor: no stabilization of CF 8 → ↑ PTT
no binding to subendothelial collagen + Gp1b →↑ bleeding time
von willebrand disease:
most common inherited bleeding disorder
treatment of von willebrand disease
DDAVP: desmopressin (synthetic form of ADH) - ↑ release of vWF in endothelial cells
widespread activation of clotting → use all PLTs + CFs → then become hypocoaguable → bleeding, multiorgan failure
↓ PLT: ↑ bleeding time
↓ CF: ↑ PTT, PT
↓ fibrinogen (high yield!): used up
↑ fibrin split products (D-dimer): body trying to break clots
microangiopathic anemia: schistocytes
DIC
causes of DIC
STOP Making Thrombi Sepsis: G- usually Trauma Obstetric: amniotic fluid embolism, abrupto placentae (postpartum hemorrhage + gum bleeding - think DIC) Pancreatitis (acute) Malignancy Transfusion
chronic (genetic) platelet disroders
von willebrand disease
bernard-soulier syndrome
glandmann’s thrombasthenia
ITP
