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92 Cards in this Set
- Front
- Back
- 3rd side (hint)
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what are the main steps of the clotting process?
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1. platelet plug
2. propagation by the coag cascade 3. termination 4. fibrinolysis |
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What substances generated outside the platelet regulate its function by interacting with platelet membrane receptors?
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collagen
thrombin (med: GP IIb/IIIa blockers) |
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What substances are generated inside the platelets that regulate its function by interacting with platelet membrane receptors?
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ADP
Prostaglandins Seratonin (med: clopidogrel) |
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What substances are generated within the platelet and regulate its function by acting WITHIN the platelet?
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thromboxane A2
(med: ASA blocks) |
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What affect does thromboxane A2 have on vasculature?
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vasoconstriction (and promotes further platelet aggregation)
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What do ADP and seratonin do when released from the platelet following endothelial damage?
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recruit additional platelets
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What are two adhesive substances that are secreted from inside the platelet following endothelial damage that reinforce/stabilize platelet aggregates?
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fibromectin
thrombospondin |
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All procoagulants except ________ are produced in the __________.
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vWF; liver
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What are the vitamin K dependent procoagulants?
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VII, IX, X, and prothrombin
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What two forms is vitamin K foundn in?
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K1 (phytonadione) - a fat-soluble substance found mostly in leafy greens
K2 (menaquinone) - produced by bacteria in the GI tract |
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What are the vitamin K dependent anticoagulants?
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Protein C
Protein S |
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How does vitamin K affect procoagulants?
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it participates in their postribosomal modification
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Which form of vitamin K must warfarin pts be warned about?
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K1 - phytonadione
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What activates the extrinsic clotting pathway?
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tissue factor
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what is the "primary physiologic initiator of clotting"?
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generation or exposure of tissue factor at the wound site
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What does factor X do?
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converts prothrombin --> thrombin
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What does thrombin do?
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converts fibrinogen --> fibrin
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What is the difference between fibrinogen and fibrin?
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fibrinogen is a soluble plasma protein but fibrin is insoluble
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What two substances are involved in termination of clotting?
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antithrombin
TF pathway inhibitor |
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thrombin activates _______ and no longer promotes platelet aggregation of cleavage of fibrinogen.
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Protein C
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What inactivates factors Va and VIIIa?
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Activated protein C (APC) with protein S on phospholipid surfaces
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What inactivates factors IXa, Xa, XIa, XIIa?
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Antithrombin (by forming irreversible complexes)
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What anticoagulant is used in sepsis pts?
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APC (b/c pt clots and uses it up)
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what is the major activator of plasminogen in the extravascular compartment? intravascular?
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extra - urokinase
intravascular - tPA |
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What does a d-dimer measure?
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fibrin degredation products (resulting from plasmin cleaving fibrin, breaking up clot)
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What does turning off COX-1 do?
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can't get sticky platelets and vasoconstriction (decreased thromboxane A2)
also decreased PGs and prostacyclin |
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what are two ways anti-platelet drugs can lead to renal failure?
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by blocking vasodilating PGs
by AIN |
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What 3 drugs cause AIN?
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anti-platelets
nafcillin quinolones |
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Where are antiplatelet drugs metabolized?
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liver
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Does clopidogrel have a reversible or irreversible effect on platelets?
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irreversible
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how does clopidogrel work?
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decreases platelet aggregation by blocking ADP receptors which prevents binding at that site.
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Which antiplatelet drug can cause a flu like illness?
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clopidogrel
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Name the glycoprotein IIb/IIIa receptor antagonists
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abciximab
eptifibatide tirofiban |
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What are the clinical use(s) of GPIIb/IIIa antagonists?
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PCI with stent
ACS |
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How does warfarin work?
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inhibits vitamin K dependent carboxylation of coag factors (II, VII, IX, and X) that are procoagulants
it also inhibits vitamin k dependent carboxylation of protein C and S |
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what occurs is warfarin is taken during the first trimester? second? third?
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1st- hypoplastic nasal bridges
2nd - CNS anomalies 3rd - bleeding issues |
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Which pathway is initially altered by warfarin with therapy initiation?
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extrinsic pathway (depresses factor VII)
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Why must warfarin be overlapped with LMWH or heparain for 5-7days?
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because warfarin also brings down protein C --> leaving a procoagulation state
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Which drugs may make a patient need higher doses of warfarin?
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rifampin
carbamazepine St john's wort (2C9 inducers) |
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What factors may make a patient need LOWER doses of warfarin?
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hepatic impairment
poor nutrition CHF elderly 2C9 inhibitors like cimetidine, amiodarone, and fluconazole |
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What coag factors are assessed by the INR?
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TF
VII II (Prothrombin) V X fibrinogen (extrinsic path and common path) |
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How often should the INR be checked if pt on warfarin?
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q3-4 wks once stable (or more if concominant meds that interfere)
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How do you reverse hemorrhage from warfarin?
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FFP
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Why should IV vitamin K be given slowly?
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can cause dyspnea, CP, and death
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What ABX could alter warfarin metabolism?
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erythromycin
quinolones |
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What drugs decrease absorption of warfarin?
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antacids
bile acid sequestrants |
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What is purple-toe syndrome?
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cholesterol emboli --> chokes off small vessels (often goes to the toes but other organs/areas possible)
usually won't amputate |
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What drug is associated with "purple-toe syndrome"?
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warfarin
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Explain skin necrosis/gangrene associated with warfarin.
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paradoxical thrombosis that occurs in the first few days of administration (probably mediated by rapid reduction in protein C)
probably more common if protein C deficiency usually affects breast, penis, or extremities |
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WHat drug is made from porcine intestinal mucosa and bovine lung?
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heparin
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How does heparin work?
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complexes with antithrombin --> turns it into a rapid inactivator of thrombin (IIa) and Xa (also XIIa, XIa, and IXa)
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Which factor does antithrombin affect the most?
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II
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What factors are assessed by the aPTT?
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XII, VIII, IX, XI
II, V, X (intrinsic and common) |
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Is the aPTT standardized like the INR?
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no
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What is the half-life of heparin?
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30-60min
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For reversal of heparin what is the maximum dose/speed at which protamine can be given?
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No more than 20mg/min
AND no more than 50mg in 10min |
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Who is at increased risk of anaphylaxis from protamine?
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pts who have received it previously
diabetics on NPH |
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What should be given to pt that is hemorrhaging on heparin?
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FFP
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What is the initial dose of FFP?
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15mL/kg
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What needs to be monitored when pt is on heparin?
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aPTT
heparin level (possible) Platelet counts |
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WHat are the risk factors for hemorrhaging on heparin?
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IE
congenital bleeding disorder active ulcerative GI disease Severe HTN post brain/eye/spinal surg use of other anti-coagulants advanced liver disease |
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WHat anti-coagulant may lead to alopecia?
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heparin
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What anti-coagulant may lead to osteoporosis if given for >6mo?
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heparin (but not much with LMWH)
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Why does heparin lead to osteoporosis?
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increases osteoclast number and activity
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What is the difference between HIT Type I and HIT type II?
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HIT I - transient decrease in platelets that has no clinical significance
HITII - more serious |
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What is HIT Type II?
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Heparin binds to platelet factor 4 complex on platelet and IgG responds by tagging it --> removed from system
Some of these patients will clot at the same time (looks like DIC) |
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Which patients is HIT Type II more likely?
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Those on SQ/IV heparin
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Name 3 LMWHs.
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enoxaparin
dalteparin tizaparin |
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How do LMWHs work?
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inactivate factor Xa
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Unlike unfractionate heparin, LMWH does not prolong which test?
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aPTT
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No labs must be monitored with LMWH except in which population? What needs to be monitored?
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pg women; monitor anti-Xa levels 4 hours after SQ injection
(want it 0.5-1.2 U/mL) |
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LMWH dose needs to be adjusted for what?
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creat clearance
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What is the difference between reversal of heparin and reversal of LMWH?
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reversal of LMWH is not as complete
no easy test to see how much FFP/protamine to give |
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What is Tinzaparin
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newer LMWH - fewer indications
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Which anticoag drug may cause injection site pain and hematoma?
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LMWH
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What is fondaparinux?
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a synthetic analog of heparin that binds to antithrombin with higher affinity
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Why can't you get HIT with fondaparinux?
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it doesn't interact with platelet/PF4
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What is the name of the heparin analog that cannot currently be reversed?
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fondaparinux
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How do you monitor anticoagulation with fondiparinux since it doesn't alter the aPTT, PT, or BT?
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anti-Xa assay
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What lab values should be monitored if pt is on Fondaparinux?
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CBC
Creat (not well studied in creat >1.8) Stool occult blood |
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Are heparin, LMWH, and fondaparinux direct or indirect thrombin inhibitors?
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indirect
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Name 2 direct thrombin inhibitors.
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Hirudin
Lepirudin |
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What anti-coag drugs besides fondaparinux cannot be reversed?
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hirudin, lepirudin, and argatroban (the direct thrombin inhibitors)
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How are the direct thrombin inhibitors monitored?
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aPTT
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What drugs are approved for the treatment of HIT Type II?
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lepirudin (Refludan)
argatroban |
direct thrombin inhibitor
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What patients do you want to be careful when using lepirudin?
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renal dysfunction
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Which direct thrombin inhibitor should be used to treat HIT Type II if patient has renal dysfunction?
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argatroban
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Does warfarin cross the placenta?
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yes
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When is fetal teratogenicity from warfarin most likely during gestation?
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6-9wks
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Can nursing mothers be on warfarin?
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yes
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Does heparin cross the placenta?
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no
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What teratogen category is heparin?
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C
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