Hemostasis 0502 Flashcards
hemophilia A
factor VIII deficiency
hemophilia B
factor IX deficiency
vit K deficiency
decreased synthesis of factors II, VII, IX, X, protein C, protein S
antithrombin
inhibits thrombin (II) and factors VII, IX, IX, XI, XII (active forms). activated by HEPARIN.
what protects factor XIII?
vWF
protein C
activated by thrombomodulin (from endo cells).
along with protein S, inactivates factor V and VIII.
tissue plasminogen activator (tPA)
converts plasminogen to plasmin.
plasmin
cleaves fibrin mesh (THROMBOLYTIC)
what activates factor XII (intrinsic)?
subendothelial collagen, basement memb, activated plts
*also HMWK
what activates factor VII (extrinsic)?
tissue thromboplastin
what does plasmin do?
- break down fibrin mesh into fibrin degradation products
2. cleave C3 into C3a in complement cascade
what converts prekallikrein to kallikrein?
activated factor XII
what does kallikrein do?
convert high molec weight kininogen (HMWK) to bradykinin
actions of bradykinin
- increase vasodilation
- increase permeability
- increase pain
which cells release pro-aggregation factors?
plts - release TXA2 (decrease bld flow, increase agg)
which cells release anti-aggregation factors?
endo cells - release PGI2 and NO (increase bld flow, decrease agg)
what facilitates plt adhesion?
vWf binds injured endo first.
plt binds to vWf via GpIb receptor.
what facilitates plt aggregation?
plts release ADP which induce expression of GpIIbIIIa receptor.
fibrinogen binds GpIIbIIIa and link plts.
what drug inhibits TXA2 synthesis?
aspirin - inhibits COX, which converts arach acid to TXA2
what drugs inhibit ADP-induced expression of GpIIbIIIa?
ticlodipine and clopidogrel
what inhibits GpIIbIIIa directly?
abciximab
what increases ESR?
infection inflamm dz (temporal arteritis, polymyalgia rheumatica) malignant neoplasm GI dz (UC) pregnancy
*acute phase reactants can cause RBC aggregation and thus, increased ESR
what decreases ESR?
polycythemia sickle cell anemia CHF microcytosis hypofibrinogenemia
what lab is changed in hemophilia A and/or B?
increased PTT
what lab is changed in vit K deficiency?
increased PT and PTT
what lab is changed in Bernard Soulier disease?
decreased PC
increased BT
*GpIb deficiency - plt adhesion
what lab is changed in Glanzmann thrombasthenia?
normal PC
increased BT
no plt clumping on smear
*GpIIbIIIa deficiency - plt aggregation
what lab is changed in idiopathic thrombocytopenic purpura?
decreased PC
increased BT
increased megakaryocytes in BM
*anti-GpIIbIIIa Abs decrease plt survivial
what lab is changed in TTP?
decreased PC
increased BT
schistocytes, increased LDH
cause of TTP
deficiency of ADAMTS13 vWf metalloproteinase - increase in vWf multimers that increase plt aggregation (micro thrombi)
what are the sx of TTP?
- neuro sx
- renal sx
- fever
- thrombocytopenia
- microangiopathic hemolytic anemia
what lab is changed in vWf disease?
PTT increase (due to loss of F VIII protection) BT increase
vWf manifestations
defective plt plug formation (adhesion).
mild mucosal and skin bleeding.
AD inheritance. most common inherited bleeding d/o - mixed plt and coag d/o.
ristocetin test with vWf
normally ristocetin induces plt agg by causing vWf to bind GpIb.
without vWf, plt agg is impaired and test is abn.
tx of vWf
DDAVP (desmopressin) - releases vWf from endo cells
DIC definition
= disseminated intravascular coagulation.
widespread activation of clotting cascade.
leads to deficiency in clotting factors and consequent bleeding state.
mixed plt and coag d/o.
what lab is changed in DIC?
PC decrease (used in microthrombi) BT increase PT increase PTT increase schistocytes D-dimers (fibrin split product) decrease fibrinogen decrease factors V,VIII
causes of DIC
"STOP Making New Thrombi" Sepsis (gm neg) Trauma Obstetric complications acute Pancreatitis Malignancy Nephrotic syndrome Transfusion
factor V Leiden
hereditary thrombosis syndrome leading to hypercoag - most common cause.
production of mutant factor V that CANNOT be degraded by protein C.
prothrombin gene mutation
hereditary thrombosis syndrome leading to hypercoag.
mutation in 3’ untranslated region.
increased gene expression.
increased prothrombin = increased thrombin.
assoc. w/ venous clots.
antithrombin deficiency
hereditary thrombosis syndrome leading to hypercoag.
less increase in PTT after heparin admin.
*ATIII is normally activated by heparin
protein C or S deficiency
hereditary thrombosis syndrome leading to hypercoag.
decreased ability to inactivate factors V, VIII.
thrombotic skin necrosis with warfarin
normally, warfarin initiation leads to temporary deficit in prot C and S (shorter half life) relative to factors II, VII, IX, X.
increased risk in prot C or S deficiency - more severe deficit is seen with warfarin initiation, leading to increased thrombosis in skin (about 1 wk later)
bld transfusion: packed RBCs
increase Hb and O2 carrying capacity.
for acute bld loss, severe anemia.
bld transfusion: plts
increase plt count.
usu given in “6 pack” or more for therapeutic effect.
stops significant bleeding (thrombocytopenia, qualitative plt defects).
bld transfusion: fresh frozen plasma
increase coag factor levels by about 20%.
for DIC, cirrhosis, warfarin OVER-anticoagulation.
bld transfusion: cryoprecipitate
contains fibrinogen, factor VIII, factor XIII, vWF.
to treat coag factor deficiencies involving fibrinogen and factor VIII.
risks of bld transfusion
infection transmission -low.
transfusion rxns.
iron overload.
hypocalcemia -citrate used as anticoagulant but may also chelate calcium (paresthesias).
hyperkalemia -RBCs may lyse in old bld units.
