hematology Flashcards
factor 1
- fibrinogen
factors 2
- prothrombin
factor 3
- tissue factor
intrinsic pathway factors and measurement
- 12, 11, 9, 8
- PTT, ACT
- heparin
extrinsic pathway factors and measurement
- 7
- measured by PT, INR
- warfarin inhibits extrinsic
final common pathway factors
- 10, 5, 2, 1
(think of dollar denominations)
damage to the extrinsic pathway causes release of what
- thromboplastin
what does heparin do
- accelerates the rate at which ATIII neutralizes thrombin and factor Xa
- effects unbound clotting factors
how is heparin metabolized
- by the reticuloendothelial system
what causes heparin resistance
- increased factor VIII
- accelerated clearance of the drug with PE
- ATIII deficiency (give 2 FFP to provide ATIII)
signs of HIT
- sign is a massive drop in platelets
- dose doesn’t matter when it comes to HIT
- associated with IgG antibodies
diagnosing HIT
- serotonin release assays (SRA) is the gold standard
- ELISA testing detects IgG antibodies
protamine sulfate
- heparin antagonist complexes with anionic heparin to form stable salt
- LMWH are not as susceptible to protamine (65%)
- 100 mg / 100 units of heparin
hypersensitivity reactions to protamine
- fish sensitivity
- previous protamine reversal
- protamine containing insulin (NPH)
- previous vasectomy
( pretreat w/ corticosteroid and antihistamine)
low molecular wright heparins
- Dalteparin (Fragmin)
- Enoxaparin (Lovenox)
- Tinzaparin (Innohep)
(dose adjustments with renal patients)
LMWH mechanism of action
- inhibition of factor Xa by antithrombin
- doesn’t effect aPTT or PT much
Fondaparinux (Arixtra)
- specific inhibitor of factor Xa
- ATIII mediated
- not factor IIa effect
- no effect on platelet function
- same risk of hematoma as with LMWH
black box warning for LMWH and Fondaparinux
- use of neuraxial blockade represents a significant risk of epidural hematoma
- wait at least 12 hours
Xa inhibitors
- Rivaroxaban (Xarelto)
- Apixaban (Eliquis)
- Edoxaban (Savaysa)
- hold 1 day prior to surgery w/ normal CrCl
andexanet alpha (andexxa)
- reverses factor Xa inhibitors
- black box warning for thromboembolic events, ischemic events, arrest, death
argatroban
- direct thrombin inhibitor (factor IIa)
- used for prevention and treatment of thrombosis in pts with HIT
- goal is aPTT 1.5-3x baseline
- no reversal
direct thrombin inhibitors (hirudin analogs) names and how they work
- bivalirudin (angiomax)
- lepirudin (refludin)
- from saliva of the medicinal leech
- direct thrombin inhibitor
- binds irreversibly to both circulating and clot bound thrombin
dabigatran (Pradaxa) and its reversal
- oral direct thrombin inhibitor
- Specific antidote: Idarucizumab and Ciraparantag
warfarin
- indirect anticoagulant that alters factors II, VII, IX, X by interfering with vitamin K
- Vit. K is required for this carboxylation
- never give to pregnant people
warfarin reversal
- vitamin K1 but takes up to 24hrs
- oral recommended, IV for emergency (never subQ)
- for immediate hemostatic FFP 10-20 ml/kg
warfarin reversal chart
- 3-5 = hold dose
- 5-9 hold 1-2 doses and may use vitamin K
- > 9 and no bleeding, oral vitamin K
- serious bleeding give vitamin K IV
warfarin perioperative management
- goal INR is 1.5
- hold at least 5 days prior to surgery
- restart based in bleeding risk
- bridge therapy not necessary unless stroke or clot within 3 months
thrombolytic agents
- alteplase
- reteplase
- tenecteplase
- streptokinase
- urokinase
what thrombolytic agents do
t-PA binds to fibrin and plasminogen and converts bound plasminogen to plasmin
- work to break up any kind of clot
thrombolytic agent toxicity
- lysis of fibrin at vascular sites = major risk of hemorrhage
low molecular weight dextran (dextran 40)
- prevent thromboembolism by decreasing blood viscosity (expansion of intravascular volume)
epsilon aminocaporic acid (amicar)
- synthetic monoaminocarboxylic acid
- indirect inhibitor of plasmin’s antiplatelet effects, inhibiting fibrinolysis
- used for excessive bleeding
tranexamic acid (TXA)
- competitive inhibitor of several plasminogen binding sites, leading to inhibition of fibrinolysis and reduced plasmin activity
- bleeding prophylaxis
- avoid with seizures
raplixa (fibrin sealant)
- spray dried fibrin sealant to control bleeding
- purified fibrinogen and thrombin
- dissolved in the blood causing a reaction between fibrinogen and thrombin to form a clot
NovoSeven RT (factor VIIa)
- used for pts with hemophilia A or B or factor VII deficiency
- works in the extrinsic pathway activating factor X, generating thrombin and fibrin
- expensive
- high risk of thromboembolic events
off label uses of NovoSeven RT
- emergent warfarin induced bleeding
- spontaneous intracranial hemorrhage
- massive bleeding
prothrombin complex concentrate names
- kcentra
- FEIBA
- Profilnine SD
Sodium Citrate
- binds free Ca in the blood
sodium citrate toxicity
- presents initially as paresthesia around the mouth or extremities followed by hypotension
factors that promote platelet adhesion
- vonWillebrand’s factor and factor VIII
factors that promote platelet activation
- thrombin (factor IIa combines with thrombin receptor
factors that promote platelet aggregation
- thromboxane-A2 and ADP uncover fibrinogen receptors and factor 1 attaches platelets together
aspirin
- cyclo-oxygenase (COX) inhibitor
- stops the conversion of arachidonic acid to thromboxane A2
NSAIDs
- depression of thromboxane A2 production
thienopyradine ADP- receptor antagonists
- clopidogrel (plavix)
- ticlopidyne (ticlid)
- prasugrel (effient)
- ticagrelor (brilinta)
thienopyridine ADP- receptor antagonists (P2Y12 inhibitors)
- bind selectively to ADP site on platelets preventing fibrinogen-platelet binding
- irreversibly modify receptor
cangrelor (kengreal)
- IV P2Y12 inhibitor
