Venous Thromboemobolism (anticoagulants/thrombolitics) Flashcards

Question

What is the gold standard, invasive, procedure that has adverse effects of allergic rxn, neprhotoxicity, pain, and is the only test available to detect proximal and distal?

Answer 1

Venography

Answer 2

Impedance plethysomography (IPG)

Answer 3

Doppler U/S

Answer 4

Duplex U/S

Answer 5

D-Dimer Test

Answer 6

If non-invasive tests are negative but clinically suspicious of DVT, perform serial testing on days 5-7 and again on days 10-14.

Answer 7

For suspected PE, if non-invasive tests are negative, perform ventilation/perfusion radionuclide scan (V/Q scan) Detects ventilation/perfusion mismatch Reported as normal, low, intermediate/indeterminate, or high probability May need pulmonary angiography if low or intermediate probability and moderate clinical suspicion.

Answer 8

Prevent development of PE Prevent postphlebitic syndrome Reduce mortality Minimize adverse events and cost

Answer 9

``` General Measures Elevation of affected extremity Localized heat/antiembolic exercises (flexion/extension) Reduced activity/bedrest Analgesics for pain Oxygen for pulmonary embolism Pharmacologic treatment ```

Answer 10

Platelet Aggregation inhibitors Anticoagulants Fibrinolytics (Thrombolytics)- clot busters.

Answer 11

``` Aspirin Dipyridamole Clopidogrel (Plavix®) Glycoprotein IIb/IIIa inhibitors- option for substitution or adding for coronary clotting as well. --Abciximab- specific link to PCI --Tirofiban --Eptifbatide ```

Answer 12

Blocks the synthesis of thromboxane A2 from arachidonic acid by inhibiting the enzyme cyclooxygenase. (Irreversible acetylation) Salicylic acid is a reversible inhibitor of prostacyclin formation

Answer 13

Prevention and treatment of MI and ischemic strokes, and TIAs. Analgesic Anti-inflammatory Anti-pyretic

Answer 14

``` Children under age 12- due to reyes syn Breast feeding Hemophilia PUD Known hypersensitivity rxns ```

Answer 15

Bronchospasms | GI hemorrhage

Answer 16

ER dipyridamole in the combination product with aspirin (Aggrenox®) MOA: causes inhibition of phosphodiesterase enzyme that hydrolyses cAMP. Increase cAMP levels result in decreased thromboxane A2 synthesis and thus platelet aggregation. Indications:

Answer 17

Aggrenox® to prevent thrombosis. Licensed indication for prosthetic mechanical valves, in combo with warfarin Alternative to exercise in thallium myocardial perfusion imaging.

Answer 18

Headache- typically self limiting GI Bleed Hypotension

Answer 19

Contraindications Caution in patients w/ hypotension Caution in patients w/serious CAD Combination w/aspirin was not much more effective than aspirin alone in controlled trials.

Answer 20

Blocks ADP-induced platelet-fibrinogen and platelet-platelet binding.

Answer 21

ROA: Oral administration Better absorption when administered w/food Highly protein bound

Answer 22

Prevention of repeat stroke or TIA | Coronary Artery Stinting

Answer 23

Patients w/severe liver dysfunction Patients w/blood disorders such as thrombocytopenia, neutropenia PUD Internal bleeding

Answer 24

Cimetidine Digoxin Theophylline Red clover (herb)

Answer 25

Bleeding N/V/D Thrombocytopenia, NEUTROPENIA, pancytopenia—monitor CBC Nephrotic syndrome, dark colored urine

Answer 26

inhibits activation of the glycoprotein IIb\IIIa receptor on the surface of platelets, which is required for aggregation to occur.

Answer 27

Secondary prevention of cardiovascular and cerebrovascular events. In patients allergic to aspirin

Answer 28

Hemorrhage Abdominal discomfort N/V

Answer 29

Clopidogrel is safer than ticlopidine, and often added to aspirin to obtain better platelet inhibition.

Answer 30

Prototype MOA: Abciximab is an antibody fragment directed towards the glycoprotein IIb/IIIa receptor of platelets. Binding & Blocking the receptor prevents platelet aggregation. ROA: IV

Answer 31

Prevention of ischemic cardiac complications in patients undergoing percutaneous coronary intervention. Short-term prevention of MI in patients w/unstable angina.

Answer 32

``` Contraindications: Active bleeding ADRs Hemorrhage N/V HPOTN ```

Answer 33

Tirofiban & eptifbatide work similarly to abciximab but are peptide fragments. They are potentially antigenic, & should only be used once.

Answer 34

Anticoagulants

Answer 35

Anticoagulants Heparin Enoxaparin (Lovenox®) prototype of low molecular weight heparins

Answer 36

- Heparin binds to antithrombin III and accelerates inactivation of coagulation factors. - Antithrombin III inhibits the binding of fibrinogen to thrombin and hence is an anticoagulant. - Changes antithrombin from slow acting to rapid acting - Heparin binds to thrombin, inhibiting activity - Heparin binds and inhibits Factor Xa which converts prothrombin to thrombin. LMWH complexes with antithrombin III & inactivates Factor Xa but does not bind as well to thrombin.

Answer 37

IV | Sub Q

Answer 38

- DVT, PE (Treatment and Prophylaxis) - Coronary Artery Re-thrombosis after thrombolytic therapy - Heparin can be used in pregnancy since it does not cross the placenta, therefore is ideal to use for pregnancy

Answer 39

- DVT, PE (Treatment and Prophylaxis) - Unstable Angina (LMWH) - MI (LMWH) - Can be used in pregnancy.

Answer 40

- Stable proximal DVT or PE - Normal vital signs - Low bleeding risk - Absence of severe renal insufficiency - Availability of a practical system for administering --LMWH and warfarin, with appropriate monitoring

Answer 41

Hemophilia Thrombocytopenia- monitor CBC and platelet counts PUD

Answer 42

``` Bleeding (< 5%) Risk Factors Increased dose Intermittent vs continuous intravenous administration (Heparin) Recent surgery or trauma Renal failure Age > 70 (older) Concurrent ASA or NSAID use (something that is thinning your blood) ```

Answer 43

If bleeding should occur, reverse with protamine 1mg for every 100U of heparin given in previous 4 hours LMWH anti-Xa activity partially reversed by protamine

Answer 44

Heparin-induced Thrombocytopenia (HIT) HIT associated with arterial or venous thrombosis in 60% of patients Occurs in 3% of UFH treated patients Platelet counts fall 5-15 days after treatment Reductions of > 50% from baseline diagnostic of HIT or platelet counts < 100,000

Answer 45

- deep vein thrombosis - pulmonary embolism - MI, stroke, TIA - end organ damage (adrenal, spleen, gallbladder, renal)

Answer 46

-D/C Unfractionated Heparin usually resolves within 1 week -Can use DTIs (argotroban or lepirudin- comes from leech spit) -Lepirudin: LD 0.4 mg/kg IV, then 0.15 mg/kg/hr IV with dose adjusted to aPTT 1.5 – 2.5 x control. Do not use if CrCl < 60 ml/min -Argatroban: 2 mcg/kg/min IV, then adjust dose to maintain aPTT 1.5 – 3.0 x control. -Can increase the INR -Initiate warfarin once platelets > 100 x 109 -LMWH less likely to cause HIT (< 1%) but high cross-reactivity (~ 90%)

Answer 47

Osteoporosis Seen during use in pregancy (long-term use) Inhibits osteoblast activity (bone formation) Increases osteoclast activity (bone resorption) LMWHs < UH

Answer 48

- Baseline aPTT, PT/INR, and CBC - aPTT or UFH level q 6h until stable (therapeutic x2) then daily - CBC every other day x 14 days until heparin stopped - Signs and symptoms of bleeding

Answer 49

- Baseline aPTT, PT/INR, CBC, and SrCr (added because of contraindication with renal compromised) - CBC between days 3 and 5 (to monitor platelet count) - Anti factor Xa activity

Answer 50

Fondaparinux

Answer 51

- Prevention of deep vein thrombosis following orthopedic surgery - Treatment of DVT/PE - Requires cofactor of Anti-thrombin III for activity - Contraindicated in patients with CrCl< 30ml/min - Subcutaneous injection

Answer 52

Rivaroxaban | Apixaban

Answer 53

- Indicated in prevention of DVT in patients undergoing knee or hip replacement surgery - Stroke and systemic embolism prophylaxis in patients with non-valvular a fib - Oral

Answer 54

- Indicated for DVT prophylaxis in patients post hip and knee replacement - Oral - Not recommended in CrCl < 15mL/min or severe liver failure (Child-Pugh class C)

Answer 55

Dabigatran Agratroban Hirudins Warfrin

Answer 56

Direct Thrombin Inhibitors - Reduce risk of stroke and systemic embolism in patients with non-valvular atrial fibrilation - Direct thrombin inhibitor able to inhibit both free and clot-bound thrombin - Oral - Dosage adjustment for CrCl< 30mL/min

Answer 57

Direct Thrombin Inhibitors - Binds selectively and reversibly to the catalytic site of thrombin, as a competitive inhibitor. - Different from heparin and some other direct thrombin inhibitors in its ability to inhibit clot-bound thrombin. - Short T ½ = 40-50 min, reversible binding - Use: Heparin-induced thrombocytopenia with and without thrombosis, possible use in ischemic stroke, hemodialysis, percutaneous coronary intervention. - No antidote is currently approved.

Answer 58

Direct Thrombin Inhibitors | Derived from the leech, the recombinant derivatives, Desirudin and Lepirudin, inactivate thrombin

Answer 59

- In patients who have had heparin induced thrombocytopenia | - Prophylaxis of DVT in patients undergoing hip and knee replacement.

Answer 60

Active Bleeding | Renal or hepatic impairment

Answer 61

Hemorrhage | Hypersensitivity

Answer 62

``` Direct Thrombin Inhibitors Vitamin K antagonist Block the reduction of vitamin K epoxide the necessary cofactor for the synthesis of clotting factors: II VII IX X ```

Answer 63

Drug interactions-Lots always look up. | Due to working through the P450 system

Answer 64

``` Route of administration- Oral Onset of action Several hours due to the half life needed for the degradation of the clotting factors, which are: VII ~ 6 hours IX ~ 24 hours X ~ 40 hours II ~ 60 hours ```

Answer 65

- Acute MI - Prophylaxis & treatment of DVT - Prophylaxis & treatment of PE - Prophylaxis of embolization in atrial fibrillation - Prophylaxis of embolization in rheumatic disease - Prophylaxis of embolization in patients w/prosthetic heart valves. - Prophylaxis of embolization in patients who have undergone hip or knee replacement.

Answer 66

- Cerebral thrombosis - Peptic Ulcer - Pregnancy- crosses the placenta and is teratogenic, initially sold as rat poison

Answer 67

--Bleeding Treated w/vitamin K administration takes ~ 24 hours for effect (need to regenerate all of the clotting factors) Blood, plasma, etc. --Skin Necrosis- doesn’t happen with every patient but something to monitor.

Answer 68

- Baseline PT/INR (tells how quickly blood is clotting and how well its going to work), aPTT, CBC, LFTs - Yearly CBC - Urinalysis and fecal occult test as needed - PT/INR should be monitored every 2 to 3 days initially until INR in therapeutic range x 2 then spread out (done at a coumadin clinic) - PT/INR as required (no greater than 4 weeks) - Signs and symptoms of bleeding

Answer 69

- Strict compliance - Side effects—Bleeding - Dietary instruction- vitamin K - INR monitoring- important - Physical Activity limitations - Pregnancy Avoidance - Drug Interactions- might mean you adjust the drug you are giving or warfarin. Works as an ibhibitor and inducer, also as being induced and being inhibited.

Answer 70

Alteplase (Activase®) Streptokinase (Streptase®) Anistreplase (Eminase®) Urokinase

Answer 71

- Turn plasminogen to plasmin, which cleaves fibrin, thus lysing thrombi - Clots are more resistant to lysis as they age - Increased local thrombin may occur as the clot dissolves-many times co-administered w/antiplatelet or anticoagulant.

Answer 72

MI—intracoronary if possible | IV—otherwise

Answer 73

- Acute MI - Massive/Submassive PE with hemodynamic compromise - Massive PE without hemodynamic compromise and low-risk of bleeding - Submassive PE in patients intolerable of CV compromise - Heparin treatment failures - Extensive proximal DVT- these are the ones we worry about progressing to PE.

Answer 74

Hemorrhage | Reperfusion arrhythmias- concern primarily when used for coronary problems. Not as concerning if treating PE.

Answer 75

- Recent surgery/trauma within 7 - 10 days (you have a clot you want to keep and these wont let you) - CVA within 2 months - Recent needle puncture of noncompressible vessels (epidural puncture) - Active bleeding - Uncontrolled HTN - Malignancy (patients that will clot a lot so this is not an option anymore) - Pregnancy - CPR (before or during admission, this is brutal don’t administer something to make them bleed out)

Answer 76

Alteplase (Activase) | Streptokinase

Answer 77

T-PAs A serine protease obtained from recombinant DNA. MOA: enzyme that catalyzes the conversion of tissue plasminogen to plasmin in the presence of fibrin. Fibrin specificity produces local fibrinolysis in the area of a recent clot w/limited systemic proteolysis.

Answer 78

Acute MI PE Acute ischemic stroke Do not give this in hemorrhagic stroke

Answer 79

IV administration | Short half life

Answer 80

- Bleeding - Arrhythmias-monitor ECG for arrhythmias associated w/reperfusion. - N/V - Cardiac arrest, stroke, thromboembolism

Answer 81

Derived from culture broths of Group C β-hemolytic streptococci. MOA: Forms a 1:1 complex w/plasminogen to convert to the active enzyme plasmin. Hydolysis fibrin plugs Catalyzes the degradation of fibrinogen 7 clotting factors V & VII.

Answer 82

- Life-threatening DVT - PE - Arterial thromboembolism - Acute MI

Answer 83

N/V Bleeding Antigenic Allergic reactions—Rash, fever, Anaphylactic reactions Therapeutic failure as a result of endogenous antibodies

Answer 84

-Treatment of Acute DVT of the Leg -If objectively confirmed, initiate short-term tx with SC low-molecular-weight heparin (LMWH) or IV unfractionated heparin (UFH) or SC fondaparinux (all Grade 1A) -If high clinical suspicion of DVT, initiate treatment while waiting for diagnostic study results (Grade 1C) -In acute DVT, tx with LMWH, UFH, or fondaparinux for at least 5 days and until the INR is ≥ 2.0 for 24 hours (Grade 1C). -In patients with severe renal failure (CrCl < 30 ml/min), suggest UFH over LMWH(Grade 2C) -Warfarin should be initiated together with antithrombotic agent (the same day) (Grade 1A).

Answer 85

- In selected patients with extensive acute proximal DVT (i.e. iliofemoral DVT, symptoms < 14 d, good functional status, life expectancy of ≥ 1 yr) who have a low risk of bleeding, suggest that catheter-directed thrombolysis (CDT) may be used to reduce acute symptoms and post-thrombotic morbidity if appropriate expertise and resources are available (Grade 2B). - After successful CDT, suggest correction of underlying DVT using balloon angioplasty and stents (Grade 2C). - In selected patients with extensive proximal DVT (symptoms< 14 d, good functional status, life expectancy of ≥ 1 yr) who have a low risk of bleeding, suggest systemic thrombolytic therapy may be used to reduce acute symptoms and post thrombotic morbidity if CDT not available (Grade 2C).

Answer 86

Recommend early ambulation in preference to initial bed rest when this is feasible (Grade 1A).

Answer 87

-For objectively confirmed PE, recommend short-term treatment with: SC LMWH IV UFH SC fondaparinux (all Grade 1A). -In patients with non-massive PE recommend LMWH over UFH (Grade 1A). Massive PE recommend UFH over LMWH (Grade 2C). -Patients with acute PE should also be routinely assessed for treatment with thrombolytic therapy (if massive PE mainly) -For patients in whom there is a high clinical suspicion of PE, recommend treatment with anticoagulants while awaiting the outcome of diagnostic tests (Grade 1C). -Initial treatment should be continued for at least 5 days and until the INR is ≥ 2.0 for at least 24 h (Grade 1C). -Warfarin should be initiated together with antithrombotic agent (the same day) (Grade 1A).

Answer 88

- In selected high-risk patients without hypotension who are judged to have a low risk of bleeding, suggest administration of thrombolytic therapy - The decision to use thrombolytic therapy depends on the clinician’s assessment of PE severity, prognosis, and risk of bleeding. - For the majority of patients with PE, recommend against using thrombolytic therapy

Answer 89

For patients with DVT/PE secondary to a transient (reversible) risk factor, recommend treatment with warfarin for 3 months (Grade 1A).

Answer 90

- For patients with unprovoked DVT/PE, recommend treatment with warfarin for at least 3 months (Grade 1A). - After 3 months of anticoagulant therapy, all patients with unprovoked DVT/PE should be evaluated for the risk/benefit ratio of long-term therapy (Grade 1C). - For patients with a first unprovoked VTE that is a proximal DVT or PE, and in whom risk factors for bleeding are absent and for whom good anticoagulant monitoring is achievable, long-term treatment is recommended (Grade 1A). - For patients with a first isolated distal DVT that is unprovoked, it is suggested that 3 months of anticoagulant therapy is sufficient rather than indefinite therapy (Grade 2B). - For patients with a second episode of unprovoked VTE, long-term treatment is recommended (Grade1A).

Answer 91

- In patients with DVT/PE, recommend that the dose of warfarin be adjusted to maintain a target INR of 2.5 (range, 2.0 to 3.0) for all treatment durations (Grade 1A). - For patients with unprovoked DVT/PE who have a strong preference for less frequent INR testing to monitor their therapy, after the first 3 months of conventional-intensity anticoagulation (INR range, 2.0 to 3.0), recommend low-intensity therapy (range, 1.5 to 1.9) with less frequent INR monitoring over stopping treatment (Grade 1A).

Answer 92

-Without prophylaxis DVT risk is 10 – 40% in medical or general surgical patients and 40 – 60% in orthopedic surgery patients -25 – 33% of these involve proximal veins (these are the bad ones that we end up with PE) 10% of hospital deaths are attributed to PE -PE is the most preventable cause of hospital death The Agency for Healthcare Research and Quality ranked 79 patient safety interventions -#1: “…appropriate use of prophylaxis to prevent VTE in patients at risk.” -Bleeding risk with prophylaxis very low

Answer 93

general surgery patients who are undergoing minor procedures and have no additional VTE risk factors (Caprini score 0-1)

Answer 94

patients who are undergoing a major procedure for benign disease (Caprini score 2)

Answer 95

patients who are undergoing a major procedure for cancer (Caprini score 3-4)

Answer 96

patients with multiple risk factors for VTE (Caprini score >5)

Answer 97

Early Ambulation (Grade 1A)

Answer 98

ES, IPC, Low dose UFH, LMWH (Grade 1A)

Answer 99

IPC, Low dose UFH, LMWH alone or with ES or IPC (Grade 1A)

Answer 100

LMWH, low dose UFH, Factor Xa Inh combined with IPC/ES (Grade 1C)

Answer 101

LMWH, Warfarin (INR 2.5, range 2-3), Factor Xa inh (Grade1A)

Answer 102

LMWH, Warfarin, Factor Xa inh(Grade 1A); +/- IPC (Grade 1B)

Answer 103

Factor Xa inh (Grade 1A), LMWH (Grade 1B), Warfarin (Grade 1B), LDUH (Grade 1B)

Answer 104

LMWH (Grade 1A); IPC or ES if LMWH C/I (Grade 1B)*

Answer 105

General Med-something else going on besides whats goin on (CHF, COPD) or bedrest and > 1 RFs (CA, previous VTE, sepsis, IBD, acute neurologic disease) LDUH, LMWH, or fondaparinux (Grade 1A)

Answer 106

then ES or IPC (Grade 1A) go back to compression devices listed