platelets + disorders (4 stars)

Question 1

precursor: megakaryocyte
no nucleus (like RBC)
lifespan: 8-10 days
many glycoprotein receptors
contain granules filled with signaling substances

Answer 1

platelets

Question 2

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

Answer 2

von Willebrand Factor

Question 3

unable to stabilize CF 8 →↑ PTT

no platelet adhesion to wall or platelets → ↑ bleeding time

Answer 3

von Willebrand disease

like hemophilia A

Question 4

antiplatelet drugs

Answer 4

aspirin
ADP R inhibitors
glycoprotein 2b/3a inhibitors

Question 5

platelet disorder presentation

Answer 5

platelet: microhemorrhages (mucous membranes, epistaxis, petechiae, purpura - larger hemorrhage under skin)
vs
coagulopathy: macrohemorrhages

Question 6

↑ bleeding time

normal PT/INR and PTT

Answer 6

platelet disorder

Question 7

platelet disorders: ↑ bleeding time

Answer 7

immune thrombocytopenia (ITP)
thombotic thrombocytopenic purpura (TTP) - HUS
Bernard-Soulier syndrome
Glanzmann thrombasthenia

Question 8

auto-antibodies bind to Gp2b/3a on platelet surface → immune system destroys platelets
↓ PLT →↑ megakaryocytes on BM

Answer 8

immune thrombocytopenia (ITP)

Question 9

treatment of immune thrombocytopenia (ITP)

Answer 9

steroids
IVIG
splenectomy: 1/3 PLT are normally stored in spleen → allows more PLT to be in circulation

Question 10

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)

Answer 10

thrombocytopenic purpura (TTP)

Question 11

triad of hemolytic uremic syndrome - HUS

pentad of TTP

Answer 11

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

Question 12

HUS-TTP presentation

Answer 12

Nasty Fever Torched His Kidneys
TTP:
Neuro sx
Fever
HUS:
Thrombocytopenia
Hemolytic anemia
Kidney failure: uremia

Question 13

child with E. coli O157:H7 infection

Answer 13

hemolytic uremic syndrome

Question 14

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)

Answer 14

Bernard-Soulier syndrome (rare)

Question 15

defect in Gp2b/3a → abnormal PLT aggregation
NORMAL PLT count
↑ bleeding time: no aggregation

Answer 15

Glanzmann thrombasthenia

Question 16

additional causes of thrombocytopenia (↓ PLT)

Answer 16

heparin-induced thrombocytopenia

aplastic anemia

Question 17

mixed platelet + coagulation

disorders

Answer 17

von willebrand disease

DIC

Question 18

mixed bleeding disorder:
defect of von Willebrand factor: no stabilization of CF 8 → ↑ PTT
no binding to subendothelial collagen + Gp1b →↑ bleeding time

Answer 18

von willebrand disease:

most common inherited bleeding disorder

Question 19

treatment of von willebrand disease

Answer 19

DDAVP: desmopressin (synthetic form of ADH) - ↑ release of vWF in endothelial cells

Question 20

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

Answer 20

DIC

Question 21

causes of DIC

Answer 21

STOP Making Thrombi
Sepsis: G- usually
Trauma
Obstetric: amniotic fluid embolism, abrupto placentae (postpartum hemorrhage + gum bleeding - think DIC)
Pancreatitis (acute)
Malignancy
Transfusion

Question 22

chronic (genetic) platelet disroders

Answer 22

von willebrand disease
bernard-soulier syndrome
glandmann’s thrombasthenia
ITP