pulmonory embolism and dvt guidelines 2016

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ANTITHROMBOTIC THERAPY FOR VTE DISEASE : CHEST GUIDELINES 2016

CASEA 44-year-old man is evaluated in follow-up for an episode of unprovoked left proximal leg deep venous thrombosis 3 months ago. Following initial anticoagulation with low-molecular-weight heparin, he began treatment with warfarin. INR testing done every 3 to 4 weeks has shown a stable therapeutic INR. He has mild left leg discomfort after a long day of standing, but it does not limit his activity level. He tolerates warfarin well. Family history is unremarkable, and he takes no other medications.

Which of the following is the most appropriate management?Continue anticoagulation indefinitelyDiscontinue warfarin in another 3 monthsDiscontinue warfarin nowDiscontinue warfarin and perform thrombophilia testing

OBJECTIVESReview of anticoagulantsRecognize subgroups of VTEReview guidelines for duration of therapyUnderstand differences in therapy based on type of VTE

Subgroups of VTE

Cancer-associated vs No cancerProvoked vs UnprovokedProximal vs Distal DVTUpper extremity vs Lower extremity DVT

PROVOKED Reversible cause-surgery , pregnancy , immobilizationIrreversible causes magnancy , indefinite hypercoagulable states UnprovokedUnidentifiable causes

Classification of Anticoagulants

Parental Anticoagulants DosingUFH80 U/kg IV bolus followed by 18 U/kg/hr5000U IV bolus followed by 1000 U/hrEnoxaparin1 mg/kg SQ Q12H1.5 mg/kg SQ QDCrCl < 30: 1 mg/kg SQ Q24HFondaparinux< 50kg: 5mg SQ QD50-100kg: 7.5mg SQ QD> 100kg: 10mg SQ QDUnfractioned Heparin80 U/kg IV bolus followed by 18 U/kg/hr5000U IV bolus followed by 1000 U/hr Enoxaparin1 mg/kg SC 12HCrCl < 30: 1 mg/kg SC 24H Fondaparinux< 50kg: 5mg SC OD50-100kg: 7.5mg SC OD> 100kg: 10mg SC OD

Tinzaparin175 U/kg SC ODCrCl < 30: use with cautionNadroparin171 U/kg SC ODCrCl 30-50: reduce dose by 25-33%CrCl < 30: use with caution

Oral Anticoagulants TherapyVitamin K Antagonist - warfarinStarted on day 1 or 2 of parenteral anticoagulationMaintain overlap for at least 5 days.INR goal = 2-3Many diet, drug, and disease interactionsORNOAC Rivaroxaban, Apixaban, Edoxaban, DabigatranPreferred VTE treatment

RivaroxobanDosingDVT/PE treatment: 15mg BD x 21 days followed by 20mg ODTake with foodExtremes in weight do not influenceDoes not require parenteral anticoagulation prior to initiationReduction in risk of recurrence: 20mg ODRenal and hepatic impairmentCr Cl < 30: avoid useModerate-severe hepatic impairment: avoid use

Discontinuation for surgery or other proceduresStop rivaroxaban at least 24 hours before procedureRestart rivaroxaban after surgery/procedure as soon as adequate hemostasis is establishedSwitching to rivaroxabanFrom warfarin to rivaroxaban: Discontinue warfarin and start rivaroxaban as soon as INR is below 3.0From anticoagulant other than warfarin to rivaroxaban: Start rivaroxaban 0 to 2 hours prior to next scheduled evening administration of the drug and omit administration of the other anticoagulantFrom unfractionated heparin continuous infusion to rivaroxaban: Stop infusion and start rivaroxaban at the same time

APIXABANDosingDVT treatment: 10mg BD x 7 days followed by 5mg BDDoes not require parenteral anticoagulation prior to initiationReduction in risk of recurrence: 2.5mg BD Renal impairmentCrCl < 30: use with cautionNonvalvular atrial fibrillationDecrease dose to 2.5 mg PO BD in patients with any 2 of the following characteristics:Age 80 yearsWeight 60 kgSerum creatinine 1.5 mg/dL

Hepatic impairmentMild : No dosage adjustment requiredModerate/Severe: Not recommendedSurgery/proceduresDiscontinue at least 48 hr before elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding

EDOXABANDVT or PE TreatmentIndicated for treatment in patients who have been initially treated with a parenteral anticoagulant for 5-10 days>60 kg: 60 mg PO OD60 kg: 30 mg PO OD Renal impairment (DVT/PE)>50 mL/min: No dosage adjustment required15-50 mL/min: 30 mg PO ODRenal impairment (NVAF)CrCl >95 mL/min: Do not use; increased ischemic stroke compared with warfarin CrCl >50 to 95 mL/min: No dosage adjustment requiredCrCl 15-50 mL/min: 30 mg PO OD

Hepatic impairmentMild (Child-Pugh A): No dose adjustment requiredModerate-to-severe (Child-Pugh B/C): Not recommended; Transition to edoxabanFrom warfarin or other vitamin K antagonists (VKAs): Discontinue warfarin and start edoxaban when INR 2.5From oral anticoagulants other than warfarin or other VKAs: Discontinue current oral anticoagulant and initiate edoxaban at the time of the next scheduled dose of the previous oral anticoagulantFrom low molecular weight heparin (LMWH): Discontinue LMWH and initiate edoxaban at the time of the next scheduled administration of LMWHFrom unfractionated heparin: Discontinue heparin infusion and initiate edoxaban 4 hr later

DABIGATRANDVT or PE TreatmentIndicated for patients who have been treated with a parenteral anticoagulant for 5-10 daysCrCl >30 mL/min: 150 mg PO BDCrCl 30 mL/min or on dialysis: not indicatedStroke Prophylaxis With Atrial FibrillationPrevention of stroke and systemic embolism associated with nonvalvular atrial fibrillationCrCl >30 mL/min: 150 mg PO BIDCrCl 15-30 mL/min: 75 mg PO BIDCrCl VKA>LMWH DVT/PE and Cancer:

LMWH>VKA>NOAC

Duration of anticoagulantsFour durations of treatment: (1) 4 or 6 weeks; short term (2) 3 months; long term(3) longer than 3 months but still a time-limited course of therapy(usually 6 or 12 months); or (4) extended (also termed indefinite; no scheduled stopping date) therapy

RISK FACTORRATE OF RECURRENCESURGERY3 % AT 5 YEARSNON SURGICAL15 % AT 5 YEARSUNPROVOKED30 % AT 5 YEARSCANCER15 % ANNUAL RISK

Risk Factors for Bleeding on Anticoagulant TherapyAge >65Previous bleedingCancerMetastatic cancerRenal failureLiver failureThrombocytopeniaPrevious strokeDiabetesAnemiaAntiplatelet therapyPoor anticoagulant controlNSAID useLow risk0 risk factorsModerate risk1 risk factorHigh risk2 risk factors

In patients with a proximal & distal DVT of the leg or PE provoked by surgery or non surgical transient risk factor, Treatment with anticoagulation for 3 months is preferred over (i) treatment of a shorter period , (ii) treatment of a longer, time-limited period (eg 6, 12, or 24 months) , or (iii) extended therapy (no scheduled stop date) ..

In patients with a first VTE that is an unprovoked proximal DVT of the leg or PE should have atleast 3 month anticoagulant therapy

(i) low or moderate bleeding risk ,extended anticoagulant therapy > long term (ii) high bleeding risk , long term > extented therapy

In patients with a second unprovoked VTE and who have a (i) low and moderate bleeding risk , extended anticoagulant therapy > long term (ii) high bleeding risk , long term > extented therapy

In patients with DVT of the leg or PE and active cancer (cancer-associated thrombosis) and who do not have a high bleeding risk, recommendation are extended anticoagulant therapy (no scheduled stop date) over 3 months of therapy .

Aspirin for Extended Treatment of VTEIn patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy and do not have a contraindication to aspirin, aspirin over no aspirin to prevent recurrent VTE is suggested

These recommendations are based on two randomized trials. Extended anticoagulant therapy reduce recurrent VTE by more than 80% and Aspirin by 33 % .

Whether and How to Prescribe Anticoagulants to Patients With Isolated Distal DVT Two management options for isolated DVT

1) treat patients with anticoagulant therapy or

2) follow-up US examination (eg, after 1 and 2 weeks, or sooner if there is concern )

Risk factors for extension of distal DVT that would favor anticoagulation over surveillance:(1) D-dimer is positive (2) thrombosis is extensive (eg, >5 cm in length, involves multiple veins, >7 mm in maximum diameter);(3) thrombosis is close to the proximal veins;(4) there is no reversible provoking factor for DVT; (5) active cancer;. (6) history of VTE; and(7) inpatient status.(8) Severe symptoms(9) DVT that are detected using a selective approach to whole-leg US

Surveillance over anticoagulation 1) thrombosis that is confined to the muscular veins of the calf ( soleus, gastrocnemius) to have a lower risk of extension than thrombosis that involves the axial ( ie, true deep; peroneal, tibial ) veins. 2) high bleeding risk 3) whereas distal DVT detected by routine whole-leg US

In patients with acute, isolated, distal DVT of the leg who are managed with serial imaging,

(i) no anticoagulation if the thrombus does not extend

(ii) suggest anticoagulation if the thrombus extends but remains confined to the distal veins or extends into the proximal veins

CDT for Acute DVT of the LegIn patients with acute proximal DVT of the leg, anticoagulant therapy alone over CDT is preferred.

It was based on various randomized trials and cavenent study (Catheter-Directed Venous Thrombolysis in Acute Iliofemoral Vein Thrombosis Study) which shows CDT is associated with an increase in transfusion (twofold), intracranial bleeding (threefold),PE (1.5-fold), and vena caval filter insertion (twofold);

CDT is preferred over anticoagulation in patients having

1) Iliofemoral DVT, 2) Symptoms for 1 year, and 5) low risk of bleeding

Role of IVC Filter for Acute DVT or PE

In patients with acute DVT or PE who are treated with anticoagulants, recommendations are against the use of an IVC filter.

These recommendations are based on PREPIC 1 and PREPIC 2 trial (Prevention du Risque dEmbolie Pulmon

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