Fiser: Hematology Flashcards
what are three main functions of thrombin?
- converts fibrinogen to fibrin
- activates factor V and VIII
- Activates platelets
what are three factors that are involved in normal anticoagulation?
antithrombin III, protein C and protein S
what are the only two factors not synthesized in the liver?
factor VIII and vWF (made in the endothelium)
function of protein C
degrades factors V and VIII and fibrinogen
function of protein S
cofactor of protein C
what are the vitamin K dependent factors?
II, VII, IX, X and poteins C and S
whats the normal half life of PRBCs and platelets?
PRBCs = 120 days, Plat = 7 days
functions of prostacyclin? where does it come from?
- decreases platelet aggregation and promotes vasodilation
- increases cAMP in platelets
* antagonist to TXA2, comes from endothelium
functions of Thromboxane? where does it come from?
- increases platelet aggregation and promotes vasoconstriction
- triggers release of calcium in platelets to cause platelet-platelet binding and platelet-collagen binding
* from platelets
what is cryoprecipitate?
contains highest concentration of vWF-VIII, has high levels fibrinogen, used in von willebrands disease and hemophilia A (factor VIII deficiency)
what does ddavp do?
causes the release of VIII and vWF
what is the best measurement for liver synthetic function?
PT (prothrombin time)
what does PT (prothrombin time) measure?
II, V, VII, and X, fibrinogen, (best for liver synthetic function)
what does the PTT measure? ( partial thromboplastin tme)
measures most factors EXCEPT VII and XIII so does not pick up factor VII deficiency!
what is the most common congenital bleeding disorder?
von Willbrand’s disease
what are the different types and inheritance patterns of von willebrand’s disease?
type I: AD, MC, reduced quantity of vWF, mild symptoms
type II:AD, defect in vWF molecule itself, vWF doesnt wok well
type III:AR, most severe bleeding but rare, complete vWF deficiency (DDAVP does not work here!- give cryo)
what is the function of vonwillbrands factor?
link Gp1b receptor on platelets to collagen
what do you see on coag profile in vW disease?
PT normal, PTT can be normal or abnormal, bleeding time is long (ristocetin test)
what is hemophilia A and inheritance?
factor VIII deficiency, sex linked recessive
what coag profile do you see in hemophilia A?
prolonged PTT, normal PT (factor VIII deficiency)
tx of hemophilia A bleeding? (hemarthrosis, epistaxis, ICH)
factor VIII concentrate or cryoprecipitate)
What is hemophilia B? inheritance?
factor IX deficiency, sex linked (aka christmas disease)
what coag profile do you see in hemophilia B?
prolonged PTT, normal PT (factor IX deficiency)
tx for hemophilia B bleeding?
FFP or recombinant factor IX
what are the key functions of antithrombin III?
binds and inhibits thrombin
inhibits factors IX, X and XI
what is the MOA of heparin?
activates antithrombin III up to 1000x the normal activity, neutralizes factors Xa and IIa
coag profile of factor VII deficiency?
prolonged PT and normal PTT
what is Glanzmann’s thrombocytopenia?
GIIb/IIIa receptor deficiency, thus platelets cant bind to eachother, tx = platelets
what is benard soulier disease?
Gp1b receptor deficiency on platelets, thus cannot bind to collagen, tx = platelets
how does uremia inhibit platelet function?
seen in BUN >60-80, inhibits release of vWF
1st line treatment for uremia
hemodialysis (then DDAVP for acute reversal, cryo for mod to severe bleeding)
cause of heparin induced thrombocytopenia?
anti-heparin antibodies (IgG heparin-PF4 antibody)
what do you give to someone w HIT for anticoagulation instead?
argatroban (direct thrombin inhibitor)
what is MOA of Plavix?
clopidogrel: ADP receptor antagonist
what is most common congenital hypercoagulability disorder?
factor V leiden
what is factor V leiden? tx?
defect on factor V that causes resistance to activated protein C
tx: heparin or coumadin
in what subgroup does heparin NOT work?
patients w antithrombin III deficiency
what is anti-phospholipid antibody syndrome?
caused by antibodies to phospholipids including cardiolipid and lupus anticoagulant leading to prolonged PTT but are hypercoagulable
how do you diagnose anti-phospholipid antibody syndome?
prolonged PTT and positive Russell viper venom time (false positive RPR test for syphilis)
what is the most common factor causing acquired hypercoagulability?
tobacco
pathophysiology of warfarin induced skin necrosis?
due to short half life of protein C and S, theyre first to decrease compared to procoagulation factors which results in hyperthrombotic state (pts w relative protein C deficiency are esp susceptible)
what is virchows triad?
stasis, endothelial injury, hypercoagulability
MOA and uses: Aminocaproic acid (Amicar)
inhibits fibrinolysis by inhibiting plasmin, procoagulant, used in DIC or persistent bleeding from thrombolytic overdose
MOA warfarin
prevents vitamin K dependent decarboxylation of glutamic residues on vitamin K-dependent factors
MOA apixaban (eliquis)
direct thrombin inhibitor
what are the 3 direct thrombin inhibitors?
dabigatran (pradaxa), apixaban (eliquis), rivaroxaban (xarelto)
MOA protamine
reverses heparin by binding to it
what is half life of heparin?
60-90 minutes
which anticoagulation agent can be used in pregnancy?
heparin does not cross placenta (warfarin does)
what is a potential side effect of protaime?
it cross reacts w NPH insulin or previous protamine exposure, 1% get protamine reaction (hypotension, bradycardia, decreased heart function)
MOA enoxaparin
LMWheparin, binds and activates antithrombin III but neutralizes only factor Xa (heparin neutralizes Xa and IIa)
MOA argatroban
reversible direct thrombin inhibitor, use in pts w HITT
MOA streptokinase
thrombolytic- activates plasminogen, follow fibrinogen levels
MOA urokinase
thrombolytic- activates plasminogen, follow fibrinogen levels
MOA tPA
thrombolytic- activates plasminogen, follow fibrinogen levels
what is ancrod?
malayan pit viper venom, stimulates tPA release
what is Hirudin?
Hirulog from leeches, irreversible direct thrombin inhibitor, the most potent direct inhibitor of thrombin, high risk of bleeding complications
what type of hypersensitivity reaction is ABO incapatability?
type II (antibody mediated)
what is the most common transfusion reaction?
febrile nonhemolytic transfusion reaction
what is febrile nonhemolytic transfusion reaction?
MC transfusion rxn, recipient antibody reaction against donor WBCs (cytokine release)
pathophysiology of transfusion related urticaria?
recipient antibodies against donor plasma proteins (eg peanuts) or IgA in an IgA deficient patient
pathophysiology of transfusion related anaphylaxis?
recipient antibodies against donor IgA in an IgA deficient recipient
what is TRALI?
transfusion related acute lung injury: rare
caused by DONOR antibodies to recipient WBCs, clot in the pulmonary capillaries leading to pulmonary edema <6hours (ARDS)
MCC death from transfusion reaction?
TRALI
how does being cold lead to coagulopathy?
causes slowing of enzyme reactions
what electrolyte disturbance lead to coagulopathy?
hypocalcemia ( Ca required for clotting cascade)
how do blood transfusions lead to hypocalcemia?
citrate is used in stored blood which binds to calcium after the transfusion and causes hypocalcemia
most common bacterial contaminate of blood?
GNR (E coli)
what is the function of urokinase?
convert plasminogen to plasmin
