DVT Flashcards
S/sx of PE
Dyspea
Pleuritic Pain
Cough
Criteria for hemodynamically unstable PE
SBP <90 mm Hg for a period >15 mins
Requires vasopressors or inotropic support
NOT explained by other causes
Criteria for hemodynamically stable PE
Does not meet criteria for unstable PE
Unstable PE has a higher chance of death from obstructive shock
Clinical S/sx of DVT
Non-specific, pain, edema, swelling
Unprovoked DVT
No identifiable cause or provoking event
Higher risk of VTE (venous thromboembolism)
Provoked DVT
Caused by a known event
Surgery, major trauma, estrogen therapy, prolonged immobility
RFs for VTE
Age >40 Long auto/plane trips Malignancy Previous DVT or stroke CHF Lower extremity fxs Spinal cord trauma Inherited hypercoagulable factors Obesity Immobilization Major surgery Serious infection/sepsis Acute AMI Burns Vasculitis Thrombocytosis Pregnancy/postpartum Trauma Cigarette smoking
Diagnostic approach for DVT
D-dimer (sensitivity varies) DVT-specific: Compression u/s Serial testing PE-specific: ECG CT chest V/Q scanning Pulmonary angiography
D-dimer details
Low positive predictive value
Assays differ in sensitivity and units of measure
>500 mg/mL
Positive tests require further evaluation
Measures the amount of fibrin
What is the other name for minimum duration therapy
Long-term therapy
3 mos
What is the other term for extended anticoagulation therapy?
Implies indefinite therapy
Duration of therapy for DVT/PE provoked by proximal surgery
3 mos
Duration of therapy for DVT/PE provoked by nonsurgical transient risk factor- proximal
3 mos
Duration of therapy for unprovoked DVT/PT
3 mos
Duration of therapy for VTE association with active cancer (until resolution or CI to therapy)
Extended anticoag therapy
Duration of therapy for second unprovoked VTE
Extended anticoag therapy
Duration of therapy for first VTE and one interited hypercoagulable RF
Extended anticoag therapy
How is decision making made for duration of anticoagulation?
Decision requires individualization based on pt preferences and assessment of the pt’s added risk of recurrent VTE and risk of bleeding
Deciding to d/c anticoag therapy factors
Risk of bleeding
Pt sex (males 75% increase risk of recurrence)
D-dimer level (measure 1 mo after d/cing therapy)
-Pos D-dimer result 50% risk of recurrence
Non-pharmacologic therapies
Leg elevations
Ambulation
Fitted graduated compression stockings (CHEST does not recommend for post-thrombotic syndrome)
IVC- only recommended in situations due to CI anticoagulation
Catheter embolectomy/local thrombolytic therapy
Surgical embolectomy
Outpatient tx
Hemodynamically stable
Low risk of bleeding
Renal function stable
Home environment
Inpatient tx
Massive DVT
High risk of bleeding
Comorbid conditions/other factors that warrant in-hospital care
Pulmonary embolism
Traditional tx of VTE
Initial therapy bridging therapy
Unfractionated heparin OR
LMWH- 5 to 7 days OR until INR is therapy
Warfarin: 3 mos to lifetime
MOA of unfractionated heparin (UFH)
Indirectly inactivates thrombin and factor Xa by activating antithrombin
Monitoring for UFH
aPTT, anti-factor Xa, platelets
Therapeutic aPTT is typically 2-3x prolongation of aPTT
Side effects of UFH
Bleeding
Thrombocytopenia (HIT)
Osteoporosis
Elevation of transaminases
Prophylaxis dosing of UFH
Trying to prevent a clot when one already hasn’t happened
5000 units subQ BID-TID daily usually in abdomen
Renal impairment is usually twice a day
Regular tx with UFH
Use weight-based nomograms with continuous infusion
Draw an initial PTT then dose based on nomogram
Then, after six hours, draw another one and use the nomogram
Limitations of UFH
Poor bioavailability at low doses
Dose-dependent clearance
Variable anticoagulant response
Reduced activity in the vicinity of platelet-rich thrombi
Reversal of UFH
D/c (short 1/2 life) and/or protamine sulfate
Protamine sulfate neutralizes the heparin molecule
Dose of protamine sulfate
1 mg IV neutralizes 100 units of heparin
UFH short 1/2 life/IV/drip/general only calculate the amount of heparin given in last 2-2.5 hrs
Max dose of protamine sulfate
50 mg
Excessive protamine may worsen bleeding
Place of UFH in therapy
Overlap therapy bridging 5-7 days until warfarin reaches steady-state and the INR is at least 2.0 for at least 24 hrs.
What drug is considered a LMWH?
Enoxaparin (Lovenox)
Pros of LMWH
Less chance of thrombocytopenia
No monitoring for coagulation
MOA of enoxaparin (LMWH)
Accelerate factor Xa inhibition by antithrombin but are too short to convert thrombin by antithrombin
Monitoring for enoxaparin (LMWH)
No coagulation monitoring required, serum creatinine, platelets
May measure anti-Xa levels if needed 3-4 hrs after giving the dose
Procedure for checking for HIT
Platelet count at baseline, between days 3 and 5 repeat
D/c if platelets <100,000 cell/mm cubed
Direct thrombin inhibitor can be utilized for tx
Cross-reactivity with heparin and other LMWH
After true HIT occurs, we can never use these agents again
Side effects of LMWH (enoxaparin)
Bleeding
Less concerned with HIT and osteoporosis
Prophylaxis dose of LMWH (enoxaparin)
40 mg subq daily or 30 mg subq bid (certain surgical procedures- hips and knees)
Renal adjustment: CrCl <30 mL/min = 30 mg subq daily
Tx VTE for LMWH (enoxaparin)
1 mg/kg subq bid (dosed on ABW) or 1.5 mg/kg subq daily
Renal adjustment: CrCl <30 mL/min = 1 mg/kg subq daily
Inpatient DVT dosing
1 mg/kg subq bid OR
1.5 mg/kg subq daily
Renal adustment: CrCl <30 mL/min 1 mg/kg subq daily
Outpatient DVT dosing
1 mg/kg subq bid
Renal adjustment: CrCl <30 mL/min 1 mg/kg subq daily
Inpatient PE dosing
1 mg/kg subq bid OR
1.5 mg/kg subq daily
Renal adjustment: CrCl <30 mL/min 1 mg/kg subq daily
Advantages of LMWH
Better bioavailability and longer half-life Dose-independent clearance Predictable anticoagulant response Lower risk of HIT Lower risk of osteoporosis
Reversal of LMWH
No true antidote
Protamine can be used off-label
Active bleed may also require FFP
LMWH place in therapy
Overlap therapy bridging 5-7 days until warfarin reaches steady stead and the INR is at least 2.0 for at least 24 hrs
Preferred over UFH due to ease of administration and may be utilized in outpatient therapy
CHEST guidelines: “Cancer associated therapy”. LMWH over warfarin and the newer anticoagulants
Pentasaccharide MOA
Binds only to antithrombin, catalyzes factor Xa inhibitors by antithrombin and does not enhance the rate of thrombin inhibition
Does not cause HIT
Monitoring of pantasaccharide
Platelets, serum creatinine (CIed in renal impairment), no coagulation monitoring needed
Since thrombin is not inhibited, no effect on aPTT
SEs of pentasaccharide
Bleeding
No cross-reactivity of fondaparinux with HIT antibodies
What is another name for pentasaccharide?
Fondaparinux (Arixtra)
Pentasaccharide prophylaxis
Adults greater than or equal to 50 kg: 2.5 mg subq once daily
Renal adjustment: CrCl <30 mL/min is contraindicated
Pentasaccharide (fondaparinux) rversal
No antidote, FFPs, bleeding emergency
Place of pentasaccharide (fondaparinux) in therapy
Overlap therapy bridging 5-7 days until warfarin reaches steady state and the INR is at least 2.0 for 24 hrs
Effective tx option for HIT
Utilized in high-risk ortho pts
What is an example of a vit K antagonist?
warfarin (Coumadin)
MOA of warfarin
Interferes with synthesis of the vit K-dependent clotting proteins, prothrombin (factor II), factors VII, IX, and X. Along with proteins C and S.
Monitoring for warfarin
PT, INR
What is a nl INR range on warfarin?
INR range 2-3 nl (2.5-3.5 mechanical heart valves)
Initial INR reflects depletion of factor VII, depletion of factor II takes several days
Why do we use bridging therapy?
As depletion of protein C occurs and with a slow onset of anticoag effect, pts develop increased hypercoagulability during the first few days
Frequency of INR monitoring in warfarin
Initial: INR checked daily for days 1-4, then monitored as needed until INR is greater than or equal to 2 for 24hrs then weekly until stable
Maintenance: Typically every 3-4 wks if stable, with dose changes, new medications added, recheck INR in 7-14 days
Many factors can affect the INR, monitor appropriately
SEs of warfarin
Bleeding Mild: epistaxis or hematuria Severe: retroperitoneal or GI bleeding Life-threatening: intracranial bleeding Skin necrosis: rare complication typically seen in 1st 2-5 days Fetal abnormalities- crosses placenta Tx of choice of VTE in pregnancy is LMWH
Initiation dose of warfarin
Adults (18-70 yrs): 5-10 mg once daily for 1-4 days
Geriatrics (>70 yrs): 2.5-5 mg once daily for 1-4 days
His rule: <65: 5 mg, >65: 2.5 mg
Maintenance dose for warfarin
Adults: 5 mg (range 1-20 mg) once daily, based on INR
Geriatrics: 2.5 mg (range 1-20 mg) once daily, based on INR
Maintenance adjustments are typically based on dosing algorithms
Drug interactions with warfarin that cause increased INR
Metronidazole Bactrim/septra Cipro Levo Fluconazole Amiodarone
Drug interactions with warfarin that cause decreased INR
Rifampin
Carbamazapine
Phenytoin
OTC drugs that increase risk of bleeding with warfarin
NSAIDs ASA Ginger Gingko biloba Garlic
Foods that have high interactions with warfarin
Broccoli (cooked) Brussels sprouts Cabbage (raw) Canola oil Endive (raw) Kale Lettuce (gourmet) Liver Parsley Silver beet (cooked) Soybean oil (mayo) Spinach
Foods that have a moderate interaction with warfarin
Abalone Asparagus Avocado Beans (snap) Cabbage (cooked) Cheese (blue) Margarine Olive oil Peas Pickle, dill Red cabbage
Pt education for warfarin
Drug knowlege Administration of dose ID of SEs Awareness of drug, food, and herbal meds Importance of monitoring S/Sx of bleeding Pregnancy precautions Verbal instruction must be supplemented with written materials Want to take it in the afternoon or evening Do not give refills easily
Reversal of warfarin
Vit K (oral/injection), prothrombin complex concentrate (PCC), FFPs, and recombinant factor VIIa
vit K dose with INR 5-9/no bleeding
2.5-5 mg oral x 1 dose
vit K dose with INR >10/No bleeding
5-10 mg oral x 1 dose
vt K dose with INR >10/bleeding
5-10 mg IV (slow infusion) or PCC +/- FFP
vit K dose with major bleeding
10 mg IV (slow infusion) or PCC +/- FFP
What are names of NOACs?
dabigatran
rivaroxaban
apixaban
edoxaban
What is still the standard of care for a mechanical heart valve?
VKA
Which NOAC(s) requires 5-10 days of parental therapy (not the same as bridging)?
Dabigatran
Edoxaban
SEs of NOACs
Bleeding
Less intracranial bleeding than VKA but more GI bleeding
Dyspepsia in dabigatran
DIs in NOACs
Low potential, P-glycoprotein based (lovastatin and simvastatin), CYP3A4
CIs for NOACs
Pregnancy
Reversal of NOACs
Praxabind (idirucizumab)
3-factor prothrombin complex concentrate (3-F PCC)
4-factor prothrombin complex concentrate (4-F PCC)
FFP
Contain all blood factors found in plasma
Disadvantage: volume/thawing, and infectious dz/transfusion rxn
Clinical pearls for NOACs
Surgery stop them 1-2 days prior to procedure
Dialysis removes 60% of dabigatran from circulation in pts
Rivaroxaban/apixaban/edoxaban NOT considered dialyzable
Increased incidence of MI associated with dabigatran
Dabigatran has a tartaric acid core/capsule is unable to be opened
Apixaban associated with less GI bleeds than other NOACs
CHEST guidelines
Risk reduction for recurrent VTE appears to be similar between NOACs and VKA.
Pts with VTE and CA have a lower recurrent rate of VTE with LMWH compared to VKA.
Risk reduction for recurrent VTE with different NOACs has not been compared but appears to be similar to all of the NOACs.
Based on less bleeding and greater convenience, NOACs are preferred to VKA for initial and long-term tx in pt with CI and CA.
What drug should you give in CA?
LMWH
Recent diagnosis, extensive VTE, metastatic CA, N/V with chemo
What drug should you give in pregnancy?
LMWH
What drug should you give for compliance
VKA/NOACs
Frequent monitoring of INR/detect issues with VKA
NOACs dosing less complex
If you miss a NOAC, won’t be covered. If you miss warfarin, you’ll still be partially covered
Which drugs are given once daily?
Rivaroxaban
Edoxaban
VKA
Edoxaban is CIed in pts with CrCl >95 mL/min
Which drugs should be given when parenteral therapy must be avoided?
Rivaroxaban
Apixaban
Which drugs should be given with renal dz and/or CrCl <30 mL/min?
VKA
What drugs should be given with liver dz and coagulopathy?
LMWH
Which drugs should be given with dyspepsia/hx of GI bleed?
VKA
Apixaban
If you are concerned about a reversal agent, which drugs should you use?
VKA
UFH
Dabigatran
