vWF, hemophilia, DIC, antithrombin deficiency, Flashcards
where is vWF synthesized
in vascular endothelium and megakaryocytes
two key functions of vWF
anchors platelet to vessel wall at the site of vascular injury (platelet adhesion)
carries activated factor 8 in plasma
type 1 vWF disease
mild to moderate reduction in amount of vWF produced
type 2 vWF disease
vWF produced doesn’t work well
type 3 vWF disease
severe reduction in amount of vWF produced
what labs are affected by vWF disease?
no change in PT/IN, platelet count, fibrinogen
increase in PTT and bleeding time!
how does DDAVP help with vWF disease (and which type responds best)
its a synthetic ADH that stimulates release of vWF and increases facto 8 activity.
therefore, type 1 responds best and type 3 doesn’t respond at all
DDAVP dose
.3mcg/kg IV. bleeding time improved for 12-24h
SE of DDAVP
vasodilation - HoTN with rapid administration and hyponatremia due to free water retention
cryo contains which factors and can be used for which vWF disease types
contains factors 8, 13, fibrinogen
can be used for type 1, 2, or 3
ffp contains which factors and cab be used for which vWF disease types
clotting factors. can also be used for vWF 1, 2, 3 but there are better alternatives like cryo
purified 8vWF concentrate is used for which disease type
1st line for vWF type 3 disease, decreases risk of transfusion
which of the two hemophilias is more severe
A is more severe than B
what happens to PTT and PT with hemophilia A and B patients?
PTT is prolonged but PT is normal
treatment for hemophilia A
factor 8 concentrate. t1/2 is 8-12h, continue 2-6w past surgery
hemophilia A is a deficiency of which factor
8
hemophilia B is a deficiency of which factor
9
treatment for hemophilia B
factor 9 prothrombin complex, t1/2 18-24h
what is factor 9 prothrombin complex associated with?
thromboembolic compications
which factor is a treatment for both hemophilia a and b and what are the associated risks
recombinant factor 7 (“bypasses” 8 and 9), risk of arterial and venous thromboses.
90-120mcg/kh
recombinant factor 7 is also used for last ditch tx of
bleeding without ID’d cause- 20-40mcg/kg
signs of DIC
ecchymosis, petechiae, mucosal bleeding, bleeding at IV sites,
prolonged PT and PTT
increased D dimer and fibrin split products
decreased fibrinogen and antithrombin
tx of DIC
hypovolemia: IVF
coagulopathy: FFP, platelets, cryo
microvascular thrombosis: IV heparin or LMWH
antithrombin inactivates factors
9, 10, 11, 12 which ultimately leads to thrombin (factor 2a) inhibiton
patients with antithrombin deficiency are unresponsive to
heparin
treatment of antithrombin deficiency includes
antithrombin concentrate, FFP
HIT causes
clot formation
type 1 HIT MOA and cause
HIT inducted platelet aggregation after large heparin dose
how many days after heparin admin does type 1 HIT occur
1-4 days after administration
platelet count during type 1 HIT
<100,000
tx for type 1 HIT
resolves spontaneously even if heparin is continued
type 2 HIT MOA and cause
antiplatelet antibodies (IgG) attack factor 4 immune complex platelet aggregation. occurs after any heparin dose
how many days after heparin admin does type 2 HIT occur
5-14 days
platelet count during type 2 HIT
<50k
treatment for type 2 HIT
decrease heparin and use anticoagulants with direct thrombin inhibition (biialrudin, hiruden, argatroban)
a deficiency of protein C or S can produce
hyper coagulable state
thromboembolism is treated with
heparin then transitioned to warfarin
factor 5 leiden causes resistance to
anticoagulant effects of protein C
is lifelong anticoagulation necessary for someone who has factor 5 leiden
no unless theyre experiencing alot of thrombotic events
patho of sickle cell disease
valine is substituted for glutamic acid on beta globulin chain which alters RBC geometry
describe vaso occlusive criis
sickled cells impair tissue perfusion and create ischemic injury.
tx is analgesics and hydration
hydroxyurea in the setting of vaso occlusive crisis
decreases incidence and severity
describe acute chest syndrome
caused by thrombosis, embolism, infection
common postoperatively, caused by hypoventilation, narcotics, splinting, pain
describe sequestration crisis
occurs when spleen removes RBC’s from circulation at a faster rate than bone marrow produces them
leads to anemia and hemodynamic instability
describe aplastic crisis
RBC with HGBs have short t1/2 so even a small amount of bone marrow suppression can cause anemia. usually r/t viral infection like parvo B19
two co existing diseases that are seen with a patient who has sickle cell
asthma (50%) and pHTN (10%)
describe sickle cell trait
heterozygous, usually does not advance to crisis unless sever hypoxemia occurrsr
