Pathoma 4.2 Secondary Hemostasis, 4.3 Other Disorders of Hemostasis
Clotting factors released from liver in inactive form, what 3 things can activate them?
1) Exposure to activating substance 2) Phospholipid surface (platelet surface) 3) Calcium
Overactive plasmin (disorder of fibrinolysis) is seen in
1) Radical Prostatectomy: release urokinase, activates plasmin 2) Cirrhosis of liver: reduced production of alpha2-anti-plasmin
DIC labs
1) decreased platelets (using up platelets for plugs everywhere) 2) increased PT/PTT (coag factors used for plugs everywhere) 3) decreased fibrinogen (used up to link platelet plugs everywhere 4) MAHA (shear on microthrombi everywhere) 5) elevated D-dimer
How can you tell anti-FVIII inhibitor vs. Hemophilia A?
Mix patient's blood with normal blood(Mixing study) Hemophilia A: corrects PTT Anti-FVIII inhibitor: does NOT correct PTT
DIC secondary to
Obstetric complication Sepsis Adenocarcinoma Acute promyelocytic leukemia (AML) Rattlesnake bit
What lab test do you use to monitor liver's affect on coagulation: PT or PTT?
PT (II, VII, IX, X) VII has shortest half life
Secondary hemostasis labs
PT/PTT
Why do we give newborns vitamin K?
Vitamin K generated mainly by bacteria in gut, babies don't have this flora yet
Hemophilia A genetic transmission
X-linked (more common in males), but often de novo
Coagulation factor inhibitor
acquired Ab against coagulation factor
What deactivates plasmin
alpha2-anti-plasmin (liver)
How can obstetric complication lead to DIC?
amnion contains Tissue Factor, leaks into maternal circulation, triggers DIC
Why does DIC (coag activation) eventually lead to bleeding?
bleeding (platelets and clotting factors consumed from massive coag cascade activation so cant' clot bleed where you actually need it, e.g. IV sites, mucosal surface)
Most common vWF disease
decreased vWF (autosomal dominant)
Hemophilia A clinicl presentation
deep tissue, joint and post-surgical bleeding
vWF disease treatment?
desmopression (increase vWF release from Weibel-Palade bodies)
Why can large-volume transfusion give you coagulation disorder?
dilutes coagulation factors
How can sepsis lead to DIC?
endotoxin from bacteria walls activates coag cascade mø response (IL, TNF) activates coag cascade
Disorder of fibrinolysis clinical presentation
exactly same as DIC
Why can you get thrombosis in Heparin-Induced Thrombocytopenia (HIT)?
fragments of destroyed platelets may activate remaining platelets, thrombosis
Heparin-Induced Thrombocytopenia (HIT) pathophysiology
heparin forms complexes with platelet factor 4, IgG Ab's against this drug complex
Hemophilia A labs
increased PTT, normal PT decreased FVIII Normal platelet count and bleeding time
vWF disease labs
increased bleeding time (poor platelet adhesion) increased PTT, normal PT Abnormal ristocetin test
Why can long-term antibiotics give you bleeding disorder?
knockout gut flora that produces vitamin K
vWF disease presents with
mild mucosal and skin bleeding (low vWF, poor platelet adhesion)
How can adenocarcinoma lead to DIC?
mucin can activate coag cascade
Why do you have high PTT in vWF disease?
need vWF to stabilize FVIII
Disorder of fibrinolysis
overactive plasmin, excessive cleavage of both fibrinogen (clots) and coagulation factors(!)
DIC definition
pathologic activation of coag cascade
Hemophilia A treatment
recombinant FVIII
Ristocetin test
risotcetin causes platelets to aggregate together missing vWF, can't aggregate with ristocetin
Hemophilia B clinical presentation
same as Hemophilia A
DIC treatment
treat underlying cause give blood products as needed
Most common coagulation disorder
vWF disease
How can rattlesnake lead to DIC?
venom activates coag cascade
DIC leads initially to
widespread microthrombi, ischemia and infraction
Most common coagulation factor inhibitor?
Anti-FVIII
How can AML lead to DIC?
Auer rods can enter circulation trigger coag cascade
Disorder of fibrinolysis treatment
Aminocaproic acid (blocks tPA, plasmin formation)
How can you tell Disorder of fibrinolysis from DIC?
D-Dimer normal (no actual clots, unlike DIC where there's clots everywhere) others same: increased bleeding time, normal platelet count increased PT/PTT (plasmin cleaves coag factors too)
Best screening test for DIC
D-dimer (shows entire coag cascade is activated including the splitting of fibrin, end stage dissolution of clot)
Secondary hemostasis disorders clinical features
Deep tissue bleeding into muscles and joints Rebleeding after surgical/dental proceduers
Hemophilia B genetic deficiency
FIX ("b" is upside down 9)
Hemophilia A genetic deficiency in
FVIII ("a" "8")
