hematology & infectious disease Flashcards
initial thrombus formation steps?
plt adhesion > shape change (flat), ADP TXA2 granule release > recruitemnt > aggregation.
vascular injury response (3)?
- vasoconstriction
- plt adhesion
- thrombin generation
intrinisic pathway?
collagen + prekallikrein + HMW kininogen + 12
activate 11
activate 9
add 8
activate 10
add 5
2
1 (fibrin)
extrinisic pathway?
tissue factor + 7
10 add 5
2
1
how is thrombin key to coagulation?
2 (thrombin) activate 1a to 1, 5 and 8, activates plt
what does fibrin actually do?
plt plug to bind plt via Gp2BA
normal anticoagulation (3)?
- AT3 antithorombin 3; binds and inhibits 2 (thrombin), 9, 10, and 11
activated by heparin - protein C: degrades 5 and 8 and fibrinogen (1)
- protein S: protein C cofactor
normal fibrinolysis (2)
- tissue plasminogen activator (TPA) released from endothelium and converts plasminogen to plasmin
- plasmin: degrades 5, 8, fibrinogen, and fibrin
* alpha 2 antiplasmin: inhibitor of plasmin (released from endothelium)
factor with shortest half life?
7
whose activity is lose in stored blood but not FFP?
due to lability….
5 and 8.
which factor not synth’d in liver?
8 with vonWillebrand factor.
Vit K factors?
2, 7, 9, 10, C, S
Vit K vs FFP onset?
Vit K 12 hours (IV), FFP is immediate
half life RBC, plt, PMN?
RBC 120 days, plt 7 days, PMN 1-2 days.
function of prostacyclin PGI2?
from endothelium. PREVENT CLOT.
decrease plt aggregation, promote vasodilation (antagonizes TXA2) increases cAMP in plt
function of thromboxane TXA2?
from platelets. INCREASE CLOT.
increase plt aggregation, promote vasoconstriction.
triggers Ca release in plt. exposes Gp2B3A-R and causes plt-plt bind, plt-collagen (GpIb-R).
cryoprecipitate contents?
vWF-8 and fibrinogen.
indication for cryoprecipitate?
von Willebrand’s disease, hemophilia A (8), low fibrinogen.
FFP contents?
ALL coagulation factors, C, S, AT-3**.
DDAVP and conjugated estrogen effect on clotting
cause release of 8 and vWF from endothelium.
prothrombin time measures?
extrinsic pathway… 2, 5, 7, 10, fibrinogen.
best to see liver synthetic function
partial thromboplastin time measures?
measures intrinsic (cannot see 7 and 13 fibrin stabilizing factor).
70-90 AC
activated clotting time goal
150-200 routine AC
>480 for bypass.
vWB disease AD vs AR?
Type 3 is AR. Type 1 and 2 are AD.
vWF role?
GpIb-R on plt link to GpIb on collagen*.
Type I vWB disease?
mild bleeding, most common*
issue: reduced vWF
treat: recomb 8-vWF, DDVP, cryo.
Type 2 vWB disease?
issue: defect in vWF molecule; doesn’t work
treat: recomb 8-vWF, cryo, DDAVP.
Type 3 vWB disease?
AR. rare. complete deficiency.
treat: recomb 8-vWF, cryo (DDAVP won’t work).
DDAVP
desmopressin; stim release of vWF from endothelium.
use in uremic pts 2/2 ESRD as well
use in Hemophilia A and vWB disease
hemophilia A deficiency?
- sex linked recessive.
how does hemophilia A present?
hemarthrosis.
coag abnormality in hemophilia A?
PTT prolonged, PT normal
newborns with hemophilia A?
might be OK because factor 8 crosses placenta.
if bleeding, hemophilia A? how to treat.
ice/immobilize (if joint) +++ factor 8 concentrate, or cryoprecipitate.
hemophilia B deficiency?
- sex linked recessive.
how to preop 8 and 9 levels in hemophilia pre and postoperatively?
100% preop.
A/8: 80-100% for 2 wks after OR.
B/9: 30-40% 2-3 days after OR.
coag abnormality in hemophilia B?
PTT prolonged
PT normal
treat hemophilia B bleeding?
recombinant 9 or FFP.
factor 7 deficiency bleeding? how to treat.
prolonged PT
normal PTT
treat wiht recombinant 7 or FFP.
acquired thrombocytopenia Rx-related etiology?
heparin
H2 blockers famotidine.
glanzmann’s thrombocytopenia
G2B3A-R deficiency on plt
cannot bind together via fibrin
treat: plt
Bernard Soulier thrombocytopenia?
Gp1b-R deficiency on plt.
treat: plt
what level of uremia causes plt dysfxn
BUN > 60-80.
inhibits by inhibiting release of vWF.
treat: HD, DDAVP for acute reversal, cryo (if bleeding)
HIT Ab
IgG heparin-PF4 Ab causing plt destruction.
HIT pathogenesis
plt die… causing plt aggregation and thrombosis***
HIT 1 vs 2
1: non-immune (don’t treat)
2: IgG Abx - Factor 4
clinical manifestation of HIT?
plt < 100 but >20, plt drop > 50% from admission, thrombosis on heparin.
WHITE clot. ALL WITHIN 5-10 DAYS OF EXPOSURE.
how to dx HIT?
ELISA for Ab’s, SRA (serotonin release assay).
treat HIT?
stop heparin, start argatroban (direct 2 inhibitor); don’t give plt
DIC lab abnormalities
thrombocytopenia
low fibrinogen
high fibrin split products (high D dimer)
prolonged PT
prolonged PTT
DIC etiology
intiated by tissue factor. but multifactorial (treat the cause).
ASA MOA?
inhibit COX, decrease TXA2.
when to stop ASA and plavix and coumadin?
7 days preop.
plavix/clopidogrel MOA?
ADP-R antagonist.
what if new stent (need plavix) and need to go to OR?
bridge with eptifibatide (integrilin) Gp2B3A inhbitor
plt goal for periop?
50K preop
20K postop
bleeding issues after prostate surgery?
release of UROKINASE can activate plasminogen causing thrombolysis.
treat: amicar (inhibit fibirnolysis by inhibiting plasmin)
factor V leiden MC what?
MC congenital hypercoagulability d/o
resistance to activated protein C (defect is on factor V)
how to treat Factor V leiden?
heparin, warfarin
how to treat hyperhomocysteinemia?
folic acid, B12.
G20210A
prothrombin gene defect causing hypercoagulability
treat: AC
protein C/S deficiency tx?
AC.n
antithrombin 3 deficiency?
hypercoagulable.
heparin doesn’t work…
treat: recombinant AT-3 concentrate, FFP, warfarin
Polycythemia vera treat?
keep Hct < 48, plt < 400 before OR
treat: phlebotomy, ASA, hydroxyurea
APLS
antiphospholipid antibody syndrome .
ass’d SLE
PTT prolonged but HYPERCOAGULABLE
Ab to phospholipids: cardiolipin (mitochondria) and lupus anticoagulant (cell membrane)
dx APLS?
PTT prolonged, not better with FFP
positive Russell viper venom time
false positive RPR test for syphilis
treat APLS?
heparin, warfarin