Venous Thromboembolism
Venous Thromboembolism
References
- Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report — Chest, American College of Chest Physicians (Stevens SM, Woller SC, Kreuziger LB, et al.). Chest 2021;160(6):e545-e608
- Value of assessment of pretest probability of deep-vein thrombosis in clinical management — The Lancet (Wells PS, Anderson DR, Bormanis J, et al.). Lancet 1997;350(9094):1795-1798
- Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer — Annals of Internal Medicine (Wells PS, Anderson DR, Rodger M, et al.). Ann Intern Med 2001;135(2):98-107
- 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS) — European Heart Journal, European Society of Cardiology (Konstantinides SV, Meyer G, Becattini C, et al.). Eur Heart J 2020;41(4):543-603
- Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism — Archives of Internal Medicine (Jimenez D, Aujesky D, Moores L, et al.). Arch Intern Med 2010;170(15):1383-1389
- Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis — New England Journal of Medicine (Wells PS, Anderson DR, Rodger M, et al.). N Engl J Med 2003;349(13):1227-1235
- American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism — Blood Advances, American Society of Hematology (Ortel TL, Neumann I, Ageno W, et al.). Blood Adv 2020;4(19):4693-4738
- American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer — Blood Advances, American Society of Hematology (Lyman GH, Carrier M, Ay C, et al.). Blood Adv 2021;5(4):927-974
- Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH — Journal of Thrombosis and Haemostasis (Khorana AA, Noble S, Lee AYY, et al.). J Thromb Haemost 2018;16(9):1891-1894
- American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia — Blood Advances, American Society of Hematology (Cuker A, Arepally GM, Chong BH, et al.). Blood Adv 2018;2(22):3360-3392
- Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study — BMJ (Rodger MA, Le Gal G, Anderson DR, et al.). BMJ 2017;356:j1065
- Idarucizumab for Dabigatran Reversal - Full Cohort Analysis — New England Journal of Medicine (Pollack CV Jr, Reilly PA, van Ryn J, et al.). N Engl J Med 2017;377(5):431-441
- Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors — New England Journal of Medicine (Connolly SJ, Crowther M, Eikelboom JW, et al.). N Engl J Med 2019;380(14):1326-1335
Clinical Snapshot
Venous thromboembolism (VTE) is a single disease process that manifests as deep vein thrombosis (DVT), pulmonary embolism (PE), or both — a thrombus forming in the deep veins (most often the legs) can embolize through the venous system and lodge in the pulmonary arteries, so DVT and PE are managed as one continuum rather than two separate conditions.[1] The clinical spectrum ranges from an asymptomatic calf-vein clot to a hemodynamically unstable, life-threatening pulmonary embolism, and the core management questions are the same in every case: how likely is this VTE before committing to imaging (pretest probability), how should anticoagulation be started (which agent, and whether a parenteral lead-in is needed), and how long should it continue (a decision driven by whether the event was provoked by a transient risk factor or occurred without one).
Recognize the Condition
The two clinical faces of VTE
Deep vein thrombosis (DVT)
Unilateral leg swelling, pain, warmth, and erythema, with tenderness along the deep venous system. Calf circumference is often measurably larger than the unaffected leg, and collateral (non-varicose) superficial veins may become visible. A massively swollen, painful, cyanotic limb with threatened arterial supply (phlegmasia cerulea dolens) is a limb-threatening emergency, not a routine DVT presentation.
Pulmonary embolism (PE)
Sudden dyspnea, pleuritic chest pain, tachypnea, and tachycardia are the most common findings. Hemoptysis and syncope occur less often but both raise concern for a larger clot burden. Hypotension or overt signs of right ventricular strain indicate a hemodynamically significant PE requiring immediate escalation, not routine outpatient management.
Both DVT and PE can also be entirely asymptomatic, discovered incidentally on imaging obtained for another reason — an incidental finding still requires the same treatment-duration decision-making as a symptomatic one once it is confirmed as a true, clinically relevant clot.
Risk Factors
- Recent major surgery (especially orthopedic, abdominal, or pelvic) or major trauma.
- Immobilization — hospitalization, long-haul travel over 8 hours, paralysis, or a lower-limb cast.
- Active cancer, including ongoing chemotherapy or a cancer diagnosis within the past 6 months.
- Personal history of a prior VTE.
- Pregnancy and the postpartum period.
- Estrogen-containing contraception or hormone therapy.
- Inherited thrombophilia — factor V Leiden, prothrombin gene mutation, protein C or protein S deficiency, antithrombin deficiency.
- Antiphospholipid syndrome.
- Obesity.
- A central venous catheter or transvenous pacemaker/defibrillator lead.
- Inflammatory bowel disease, nephrotic syndrome, and myeloproliferative disorders.
- Age over 65, and a family history of VTE in a first-degree relative.
Red Flags & Refer
Escalate immediately — do not manage any of the following as routine outpatient VTE:
- Hemodynamic instability suggesting massive (high-risk) PE — systolic blood pressure under 90 mmHg, a drop of 40 mmHg or more from baseline, or the need for vasopressor support.
- Cardiac arrest, syncope, or new signs of right ventricular strain in a patient with suspected or confirmed PE.
- Severe hypoxemia or respiratory failure.
- Signs of phlegmasia cerulea dolens — a massively swollen, painful, cyanotic limb with threatened arterial supply — a limb-threatening surgical emergency.
- Active major bleeding in a patient on anticoagulation, or any intracranial, retroperitoneal, or gastrointestinal bleeding.
- Suspected heparin-induced thrombocytopenia — a falling platelet count with new or worsening thrombosis during heparin or LMWH exposure.
- New or worsening VTE symptoms in a patient already on adequate anticoagulation — this is a treatment-failure presentation, not something to manage by simply continuing the current regimen.
Assessment & Diagnosis
Differentiating DVT from its common mimics
| Feature | DVT | Cellulitis | Ruptured Baker (popliteal) cyst | Superficial thrombophlebitis |
|---|---|---|---|---|
| Distribution | Usually unilateral, whole-leg or calf swelling | Unilateral, follows the area of skin infection | Unilateral, calf swelling with a posterior-knee onset | Follows a superficial vein, often a visibly cord-like tender area |
| Skin changes | Warmth, mild erythema, no sharply demarcated border | Warmth, erythema with a well-demarcated, spreading border; fever may be present | Mild erythema possible | Erythema and tenderness directly over the palpable vein |
| Tenderness pattern | Deep, along the venous system | Diffuse over the infected skin | Posterior knee/calf, often sudden onset | Localized to the palpable superficial cord |
| Key distinguishing step | Compression ultrasound | Clinical diagnosis; ultrasound if DVT cannot be excluded clinically | Ultrasound identifies the cyst and excludes DVT (both can coexist) | Ultrasound confirms the superficial location and excludes extension into the deep system |
Pretest probability first
Apply a validated clinical pretest-probability score before ordering any test — Wells' Criteria for DVT or Wells' Criteria for PE, depending on presentation (see the scoring tables below).[2][3] The result determines the next step: a low/unlikely pretest probability combined with a negative D-dimer excludes VTE without imaging, while a higher pretest probability, or a positive D-dimer at any pretest probability, requires imaging.
D-dimer
D-dimer is highly sensitive but not specific — use it only to rule out VTE in patients with a low or "unlikely" pretest probability, never to rule in VTE or as the sole basis for a high-probability patient to skip imaging. Age-adjusted D-dimer thresholds (age × 10 mcg/L, for patients over 50) increase the proportion of older patients who can safely avoid imaging without missing clinically important VTE.
Imaging
Compression ultrasound of the proximal deep veins is the standard test for DVT. CT pulmonary angiography (CTPA) is the standard test for PE; a ventilation-perfusion (V/Q) lung scan is the preferred alternative when CT contrast is contraindicated — significant renal impairment, contrast allergy, or pregnancy (to reduce breast-tissue radiation exposure, although both tests deliver a low fetal dose).
Isolated distal (calf) DVT
A thrombus confined to the calf veins, with mild symptoms and no extension risk factors, does not automatically require anticoagulation — serial compression ultrasound at 1 week, and again at 2 weeks if still not extending, is a reasonable alternative to treatment; anticoagulate if the clot extends on repeat imaging.
Once PE is confirmed: severity stratification
Every confirmed PE needs a severity assessment that is separate from the diagnostic pretest-probability score — it determines admission, monitoring intensity, and thrombolysis candidacy. Hemodynamic instability defines massive (high-risk) PE outright.[4] In hemodynamically stable patients, the simplified Pulmonary Embolism Severity Index (sPESI) identifies patients with a low risk of short-term mortality who are potential candidates for outpatient management; troponin/BNP elevation together with right ventricular dysfunction on imaging identifies an intermediate-risk (submassive) group that needs closer inpatient monitoring even without hemodynamic instability.[5]
Thrombophilia testing
Reserve thrombophilia testing for patients under 40 years of age with recurrent VTE or a strong family history — testing does not change management in most other patients and should never be ordered reflexively after a first unprovoked VTE in an older patient. Time testing carefully: warfarin lowers protein C and protein S, and heparin lowers antithrombin, so results obtained during active anticoagulation can be falsely low.
Wells' Criteria for DVT
| Clinical criterion | Points |
|---|---|
| Active cancer (treatment ongoing, within 6 months, or palliative) | +1 |
| Paralysis, paresis, or recent plaster immobilization of the lower extremity | +1 |
| Recently bedridden ≥3 days, or major surgery within 12 weeks requiring general/regional anesthesia | +1 |
| Localized tenderness along the deep venous system | +1 |
| Entire leg swollen | +1 |
| Calf swelling ≥3 cm larger than the asymptomatic leg (measured 10 cm below the tibial tuberosity) | +1 |
| Pitting edema confined to the symptomatic leg | +1 |
| Collateral superficial (non-varicose) veins | +1 |
| Previously documented DVT | +1 |
| An alternative diagnosis is at least as likely as DVT | −2 |
Score interpretation: 3-tier — 0 points or fewer is low probability, 1–2 points is moderate probability, 3 or more is high probability. The 2-tier "DVT unlikely" (≤1 point) versus "DVT likely" (≥2 points) dichotomization is the version most widely validated for pairing with D-dimer in clinical practice.[6]
Wells' Criteria for PE
| Clinical criterion | Points |
|---|---|
| Clinical signs and symptoms of DVT (leg swelling and pain with palpation of the deep veins) | +3 |
| An alternative diagnosis is less likely than PE | +3 |
| Heart rate over 100 bpm | +1.5 |
| Immobilization for ≥3 days, or surgery in the previous 4 weeks | +1.5 |
| Previous objectively diagnosed DVT or PE | +1.5 |
| Hemoptysis | +1 |
| Malignancy (treatment ongoing, within 6 months, or palliative) | +1 |
Score interpretation: 3-tier — under 2 points is low probability, 2–6 points is moderate probability, over 6 points is high probability. The 2-tier "PE unlikely" (≤4 points) versus "PE likely" (>4 points) dichotomization is the version most widely used in clinical practice for pairing with D-dimer.[3]
Treatment Targets
Deep vein thrombosis
- Prevent pulmonary embolism.
- Prevent thrombus extension.
- Prevent post-thrombotic syndrome.
- Reduce morbidity from the acute event.
Pulmonary embolism
- Prevent death.
- Prevent recurrent thromboembolism.
- Prevent chronic thromboembolic pulmonary hypertension.
Choose Initial Treatment
Hemodynamic triage
Massive/high-risk PE hemodynamic instability changes everything: admit, and proceed directly to the thrombolysis decision rather than routine outpatient anticoagulant selection.
Everyone else most hemodynamically stable patients with DVT or a low/intermediate-risk PE, without severe symptoms, high bleeding risk, or a barrier to reliable follow-up, can be treated entirely as outpatients from diagnosis.
First-line anticoagulant
Apixaban or rivaroxaban both can be started alone, with no parenteral lead-in required, and are the preferred first-line agents for most adults with normal renal function.[1]
Dabigatran or edoxaban use after 5–10 days of a parenteral anticoagulant (LMWH preferred); reserve for when apixaban/rivaroxaban are not suitable or not preferred.
LMWH or warfarin use instead of a DOAC for significant renal impairment, antiphospholipid syndrome (especially triple-positive), pregnancy, or when an unavoidable DOAC drug interaction is present; if warfarin is chosen, overlap with a parenteral anticoagulant for a minimum of 5 days and until the INR is 2 or higher for 24–48 hours.[7]
Duration of anticoagulation
Provoked by a major transient risk factor (surgery) treat for 3 months and stop.
Provoked by a minor transient or a persistent minor risk factor (immobilization, travel, estrogen therapy, inflammatory bowel disease, obesity) 3 months is the minimum; extending beyond 3–6 months is reasonable and should be discussed individually.
Unprovoked, or provoked by a persistent/irreversible major risk factor (active cancer, antiphospholipid syndrome) indefinite anticoagulation should be considered, balanced against bleeding risk and reassessed at least annually.[1]
Cancer-associated thrombosis
Apixaban, edoxaban, or rivaroxaban preferred over LMWH for most patients with cancer-associated VTE.[8]
LMWH preferred over a DOAC specifically for luminal gastrointestinal or genitourinary cancers (higher DOAC-associated GI bleeding risk in this group), a significant drug interaction, or malabsorption.[9]
Continue anticoagulation for as long as the cancer remains active, reassessing periodically rather than stopping at a fixed timepoint.
Non-Pharmacologic Treatment
Deep vein thrombosis
- Early ambulation is preferred over bed rest — it is at least as effective for symptom resolution and does not increase embolization risk.
- Elevate the affected limb while resting to reduce swelling.
- Graduated compression stockings can relieve acute swelling and pain and help symptoms of established post-thrombotic syndrome, but randomized trial evidence does not support their use to prevent post-thrombotic syndrome from developing in the first place. Avoid in patients with peripheral arterial disease.
Pulmonary embolism
- Supplemental oxygen for documented hypoxemia.
- IV fluids for hypotension or volume depletion — use cautiously, since aggressive fluid resuscitation can worsen right ventricular strain.
- Vasopressor support for shock.
- Temporary mechanical cardiopulmonary support (veno-arterial ECMO) can bridge selected patients with refractory shock or cardiac arrest.
Analgesia
- Acetaminophen first, for pain from the acute event.
- Avoid NSAIDs in a patient on anticoagulation — they add gastric and bleeding risk on top of the anticoagulant.
- Opioids can be used short-term if acetaminophen is insufficient.
Procedural and mechanical options
- IVC filter reserve for acute proximal DVT or PE when anticoagulation has failed (recurrent VTE on adequate therapy) or is absolutely contraindicated (active major bleeding). A retrievable filter is preferred over a permanent one, and it should be removed once anticoagulation can be safely resumed.
- Catheter-directed or pharmacomechanical thrombolysis reserve for limb-threatening DVT (phlegmasia cerulea dolens) in a patient with an acceptably low bleeding risk; randomized trial evidence has not shown a reduction in post-thrombotic syndrome for routine iliofemoral DVT, and bleeding complications are higher than with anticoagulation alone, so this is not a routine escalation for ordinary proximal DVT.
Pharmacologic Treatment Options
| Drug / intervention | Role | Dose / use | Important adverse effects | Teaching points |
|---|---|---|---|---|
| Apixaban Preferred | 1st-line DOAC, DVT/PE monotherapy | 10 mg PO BID x7 days, then 5 mg PO BID | Bleeding | No parenteral lead-in needed. Not recommended if ClCr under 15 mL/min; use caution at ClCr 15-29 mL/min. |
| Rivaroxaban Preferred | 1st-line DOAC, DVT/PE monotherapy | 15 mg PO BID x21 days, then 20 mg PO daily with the largest meal of the day | Bleeding | No parenteral lead-in needed; food is required for adequate absorption. Not recommended if ClCr under 30 mL/min. |
| Dabigatran Alternative | DOAC after a parenteral lead-in | 150 mg PO BID (110 mg PO BID if age >=80 or high bleeding risk) after 5-10 days of a parenteral anticoagulant | Bleeding, dyspepsia | Contraindicated if ClCr under 30 mL/min. |
| Edoxaban Alternative | DOAC after a parenteral lead-in | 60 mg PO daily (30 mg PO daily if ClCr 30-50 mL/min, weight <=60 kg, or with a P-glycoprotein inhibitor) after 5-10 days of a parenteral anticoagulant | Bleeding | Not recommended if ClCr under 30 mL/min. |
| Enoxaparin Special situation | Preferred parenteral agent when a DOAC is not appropriate | 1 mg/kg SC Q12H, or 1.5 mg/kg SC once daily | Bleeding, injection-site bruising, rare HIT | Preferred parenteral bridge/monotherapy agent for renal impairment (with dose adjustment), pregnancy, and most cancer-associated VTE. |
| Warfarin Special situation | Vitamin K antagonist when a DOAC is not appropriate | Individualized dose to target INR 2-3, overlapped with a parenteral anticoagulant for a minimum of 5 days and until INR >=2 for 24-48h | Bleeding, skin necrosis (rare) | Preferred over a DOAC for antiphospholipid syndrome (especially triple-positive) and mechanical heart valves. |
| Fondaparinux Alternative | Parenteral alternative, especially with a HIT history | Weight-based once-daily SC dose (5 mg under 50kg, 7.5 mg 50-100kg, 10 mg >100kg) | Bleeding | Avoid if ClCr under 30 mL/min. |
| Alteplase or tenecteplase Special situation | Massive/high-risk PE with an acceptable bleeding risk | Weight-based, single IV bolus (tenecteplase) or 2-hour infusion (alteplase) per institutional protocol | Bleeding, intracranial hemorrhage | Reserve for hemodynamically unstable PE; greatest benefit within 14 days of symptom onset. |
Special Populations
Pregnancy
LMWH is the anticoagulant of choice throughout pregnancy — it does not cross the placenta. Continue a full weight-adjusted treatment dose for the duration of pregnancy. Treat for a minimum of 3 months in total, including at least 6 weeks postpartum. Avoid warfarin — it crosses the placenta and is teratogenic. Avoid DOACs — they are not adequately studied in pregnancy and cross the placenta. Use fondaparinux only if no other agent can be used. Plan delivery around LMWH dosing together with the obstetric team; if delivery must occur within the first month of treatment for acute VTE, discuss a retrievable IVC filter for the period while anticoagulation is held.
Breastfeeding
Warfarin, UFH, and LMWH are all compatible with breastfeeding. DOACs are not recommended during breastfeeding — safety data are insufficient.
Renal impairment
Apixaban and rivaroxaban are not recommended below a ClCr of 15 and 30 mL/min respectively; dabigatran and edoxaban are contraindicated/not recommended below a ClCr of 30 mL/min. LMWH requires dose reduction and anti-Xa monitoring as renal function falls, and unfractionated heparin — with no renal clearance dependence — is preferred once impairment is severe.
Hepatic impairment
Avoid DOACs in significant hepatic impairment or any coagulopathy from liver disease. Warfarin is difficult to titrate reliably in advanced liver disease given baseline coagulopathy; LMWH or UFH under close monitoring is often more practical.
Older adults
Bleeding risk rises with age across every anticoagulant class. Reduce the dabigatran dose to 110 mg PO BID at age 80 or older, or in a younger patient with additional bleeding risk factors. Choose the anticoagulant and dose based on current renal function, not an assumed baseline.
Antiphospholipid syndrome
Avoid DOACs, particularly in triple-positive antiphospholipid syndrome — trial evidence shows a higher rate of thrombotic events with a DOAC than with warfarin in this group. Warfarin (INR 2-3) remains the preferred long-term agent.
Heparin-induced thrombocytopenia (HIT)
Stop all heparin products immediately — including LMWH and heparin flushes — the moment HIT is confirmed or strongly suspected, and start a non-heparin anticoagulant (argatroban, danaparoid, fondaparinux, or bivalirudin) while confirmatory testing is pending; do not wait for laboratory confirmation before acting. Do not start warfarin until the platelet count has substantially recovered (generally to at least 150 x109/L) — starting warfarin during acute HIT can precipitate venous limb gangrene.[10]
Pediatrics
VTE in children is uncommon, and dosing is weight- and age-based with specialist guidance — refer to pediatric hematology rather than extrapolating adult dosing directly.
Monitoring & Follow-Up
Warfarin: check INR daily or every other day during the first week, then every 3 days for a week, then once or twice weekly, then every 2-4 weeks once stable; intervals up to 12 weeks apart are appropriate once results have been consistently stable for an extended period. DOACs: no routine coagulation monitoring is needed, but check renal function at baseline and periodically thereafter — more frequently in older adults, in reduced renal function, or when an interacting drug is added. Heparin/LMWH: monitor platelet count for HIT surveillance, particularly around days 4-14 of exposure in a patient with recent heparin exposure. Every patient: reassess the anticoagulation-duration decision at 3 months, and at least annually thereafter if extended therapy was chosen, weighing updated recurrence risk against bleeding risk (the HERDOO2 rule can help identify women with a first unprovoked VTE who have a low enough recurrence risk to safely stop[11]); ask about symptoms of post-thrombotic syndrome (chronic limb swelling, pain, skin changes) and, after PE, persistent or worsening dyspnea that could indicate chronic thromboembolic pulmonary hypertension; and reinforce adherence at every dispensing, since VTE recurrence after early, unplanned anticoagulant discontinuation is a preventable failure.
Treatment Failure / Next Step
- Recurrent VTE while on anticoagulation: before assuming true treatment failure, confirm adherence, confirm the dose is correct for current weight/renal function, and screen for an interacting drug.
- Confirmed adherent on a DOAC or warfarin with genuine recurrence: switch to therapeutic-dose LMWH, and investigate for an unrecognized malignancy or thrombophilia if this has not already been done.
- Recurrence while already on LMWH: increase the dose by approximately 20-25% and check anti-Xa levels to guide further adjustment.
- Extending or limb-threatening DVT (phlegmasia): urgent evaluation for thrombolysis or thrombectomy.
- Major bleeding on anticoagulation: hold the agent, apply local hemostatic measures, use the appropriate reversal strategy (see Drug Tables), and reassess the net risk-benefit of resuming therapy once the patient is stable.
- Suspected HIT during heparin or LMWH therapy: stop all heparin products immediately and start a non-heparin anticoagulant — act on clinical suspicion rather than waiting for laboratory confirmation.
Common Errors to Avoid
- Starting dabigatran or edoxaban without a 5-10 day parenteral lead-in — unlike apixaban and rivaroxaban, which can be started alone.
- Forgetting that rivaroxaban needs to be taken with the largest meal of the day for adequate absorption, especially during the 15 mg BID loading phase.
- Using a DOAC in a patient with triple-positive antiphospholipid syndrome — warfarin is preferred based on trial evidence of higher DOAC failure in this group.
- Continuing a heparin product after HIT is confirmed or strongly suspected, or starting warfarin before the platelet count has substantially recovered.
- Assuming compression stockings prevent post-thrombotic syndrome — trial evidence does not support this; they help acute symptoms, not PTS prevention.
- Treating every isolated distal (calf) DVT identically to a proximal DVT, rather than considering serial ultrasound surveillance as an alternative to anticoagulation for a non-extensive clot.
- Ordering thrombophilia testing at the wrong time — while on warfarin (which lowers protein C/S) or heparin (which lowers antithrombin) — or in a patient who doesn't meet the age/recurrence/family-history criteria that would actually change management.
- Stopping extended anticoagulation at an arbitrary point without reassessing bleeding risk and recurrence risk together.
- Prescribing an NSAID for VTE-related pain in a patient on anticoagulation instead of acetaminophen.
- Checking vital signs once rather than trending them — hemodynamic instability in PE can evolve over hours.
Clinical Decision Algorithm
Drug Tables
How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.
Treatment of VTE
Direct Factor Xa Inhibitors (DOACs)
Preferred first-line oral anticoagulants for most adults with normal renal function; no routine coagulation monitoring required.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Apixaban | VTE treatment: 10 mg PO BID x7 days, then 5 mg PO BID Extended VTE-recurrence prevention (after 6 months of treatment): 2.5 mg PO BID | Bleeding | Contraindicated with combined strong dual inhibitors of CYP3A4 and P-glycoprotein (e.g., itraconazole, ritonavir) | No parenteral lead-in needed. Not recommended if ClCr under 15 mL/min; use caution at ClCr 15-29 mL/min. |
| Rivaroxaban | VTE treatment, loading phase: 15 mg PO BID x21 days VTE treatment, maintenance: 20 mg PO daily Extended VTE-recurrence prevention (after 6 months of treatment): 10 mg PO daily (20 mg daily if higher recurrence risk) | Bleeding | Contraindicated with combined strong dual inhibitors of CYP3A4 and P-glycoprotein (e.g., itraconazole, ritonavir) | No parenteral lead-in needed. Take with the largest meal of the day, especially during the loading phase, for adequate absorption. Not recommended if ClCr under 30 mL/min. |
| Edoxaban | VTE treatment: 60 mg PO daily after 5-10 days of a parenteral anticoagulant (30 mg PO daily if ClCr 30-50 mL/min, weight <=60 kg, or with a P-glycoprotein inhibitor) | Bleeding | Avoid combined strong inducers of both CYP3A4 and P-glycoprotein (e.g., rifampin); reduce dose with P-glycoprotein inhibitors (e.g., ketoconazole) | Requires a parenteral lead-in, unlike apixaban/rivaroxaban. Not recommended if ClCr under 30 mL/min. |
Direct Thrombin Inhibitor (DOAC)
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Dabigatran | VTE treatment: 150 mg PO BID after 5-10 days of a parenteral anticoagulant (110 mg PO BID if age >=80 years) | Bleeding, dyspepsia | Contraindicated if ClCr under 30 mL/min or with strong P-glycoprotein inhibitors (e.g., quinidine); use caution with other P-glycoprotein-active drugs | Requires a parenteral lead-in. Consider 110 mg BID over age 75 with additional bleeding risk factors (e.g., recent GI bleed, active ulcerative GI disease). |
Low Molecular Weight Heparins
Preferred parenteral anticoagulant when a parenteral agent is needed; dose individualized by body weight, with caution in renal impairment.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Enoxaparin | VTE treatment: 1 mg/kg SC Q12H, or 1.5 mg/kg SC once daily (maximum 180 mg/day) | Bleeding; HIT and osteoporosis are both less common than with UFH | Additive bleeding risk with ASA, other antiplatelet agents, and oral anticoagulants | 1 mg = 100 units. Contraindicated with a history of HIT; use with caution in renal dysfunction. |
| Dalteparin | VTE treatment: 200 units/kg SC once daily (maximum 18,000 units/day), or 100 units/kg SC Q12H if increased bleeding risk Extended cancer-associated VTE treatment: 200 units/kg SC once daily for month 1, then approximately 150 units/kg SC once daily for months 2-6 | Bleeding; HIT and osteoporosis are both less common than with UFH | Additive bleeding risk with ASA, other antiplatelet agents, and oral anticoagulants | Contraindicated with a history of HIT; use with caution in renal dysfunction. |
| Tinzaparin | VTE treatment: 175 units/kg SC once daily | Bleeding; HIT and osteoporosis are both less common than with UFH | Additive bleeding risk with ASA, other antiplatelet agents, and oral anticoagulants | Contraindicated with a history of HIT; use with caution in renal dysfunction. |
Indirect Factor Xa Inhibitor
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Fondaparinux | VTE treatment, under 50 kg: 5 mg SC once daily VTE treatment, 50-100 kg: 7.5 mg SC once daily VTE treatment, >100 kg: 10 mg SC once daily | Bleeding, thrombocytopenia; allergic reactions are rare | Additive bleeding risk with ASA and oral anticoagulants | Use with caution in renal dysfunction. A reasonable non-heparin option with a history of HIT. |
Unfractionated Heparin
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Heparin (UFH) | IV treatment: 80 units/kg bolus, then 18 units/kg/h infusion adjusted to a therapeutic aPTT IV treatment, alternative fixed dosing: 5,000-10,000 unit bolus, then 15,000-20,000 units Q12H adjusted to a therapeutic aPTT SC treatment, fixed weight-based dosing: 333 units/kg SC initial dose, then 250 units/kg SC Q12H | Bleeding, HIT, osteoporosis | Additive bleeding risk with ASA and oral anticoagulants | Preferred over LMWH in severe renal impairment (no renal clearance dependence) and when rapid reversibility is needed. Monitor platelets closely; contraindicated with a history of HIT. |
Vitamin K Antagonist
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Warfarin | Usual dose: 0.5-10 mg PO daily, individualized to a target INR of 2-3 | Bleeding; hair loss and blue/purple toes are uncommon; skin necrosis is rare | Numerous clinically significant interactions - consult a current drug interaction reference before combining any new drug | Overlap with a parenteral anticoagulant for a minimum of 5 days and until the INR is >=2 for 24-48 hours. Monitor INR frequently at initiation, spacing out to every 2-4 weeks once stable. |
Thrombolytics (massive/high-risk PE only)
Reserve for hemodynamically unstable PE with an acceptable bleeding risk; weigh benefit against intracranial hemorrhage risk in every patient.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Alteplase | PE: 100 mg IV over 2 hours | Bleeding, including intracranial hemorrhage | Additive bleeding risk with any concurrent anticoagulant | Not a Health Canada-approved indication for PE; dosing reflects specialty guideline recommendations. Greatest benefit within 14 days of symptom onset. |
| Tenecteplase | PE: Single weight-based IV bolus per institutional protocol | Bleeding, including intracranial hemorrhage | Additive bleeding risk with any concurrent anticoagulant | An alternative thrombolytic to alteplase for massive/high-risk PE. |
Non-heparin anticoagulants for heparin-induced thrombocytopenia
Start immediately on clinical suspicion of HIT - do not wait for laboratory confirmation. Fondaparinux (above) is also a reasonable choice.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Argatroban | HIT, treatment: IV infusion per institutional protocol, adjusted to a therapeutic aPTT | Bleeding | Additive bleeding risk with other anticoagulants/antiplatelet agents | Hepatically cleared - reduce the dose in hepatic impairment. Does not require renal dose adjustment. |
| Danaparoid | HIT, treatment: IV bolus and infusion per institutional protocol, adjusted to anti-Xa levels | Bleeding | Additive bleeding risk with other anticoagulants/antiplatelet agents | Renally cleared - use with caution in renal impairment. Minimal cross-reactivity with heparin antibodies. |
| Bivalirudin | HIT, treatment: IV infusion per institutional protocol, adjusted to a therapeutic aPTT | Bleeding | Additive bleeding risk with other anticoagulants/antiplatelet agents | Short half-life; renally cleared, so reduce the dose in renal impairment. |
Reversal agents
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Idarucizumab | Dabigatran reversal: 5 g IV (two 2.5 g/50 mL boluses given no more than 15 minutes apart) | Headache; hypersensitivity reactions are uncommon | None significant | Reverses dabigatran's anticoagulant effect within minutes. |
| Andexanet alfa | Apixaban or rivaroxaban reversal: Low- or high-dose IV bolus followed by a 120-minute infusion; the specific regimen depends on which factor Xa inhibitor, its dose, and the time since the last dose | Thrombotic events, infusion reactions | Can reduce the anticoagulant effect of any concurrently administered heparin/LMWH product | Consult the product monograph's dosing table to select the correct regimen. |
| Protamine sulfate | UFH reversal: 1 mg IV per 100 units of UFH given in the preceding 2-3 hours (maximum 50 mg per dose, given slowly) Enoxaparin reversal (partial): 1 mg IV per 1 mg enoxaparin if within 8 hours of the last dose (0.5 mg per 1 mg if given later) | Hypotension, bradycardia, rare anaphylactoid reactions (increased risk with fish allergy or prior protamine/NPH insulin exposure) | None significant | Only partially reverses LMWH anti-Xa activity. |
| Vitamin K1 (phytonadione) | Warfarin reversal, major bleeding: 5-10 mg IV, combined with prothrombin complex concentrate per institutional major-bleeding protocol Warfarin reversal, elevated INR without bleeding: Hold warfarin, +/- low-dose oral vitamin K1, per current INR-management guidance | Rare anaphylactoid reaction with IV administration - give slowly | Antagonizes warfarin's anticoagulant effect | Reduces INR more slowly than prothrombin complex concentrate; combine the two for major bleeding requiring immediate reversal. |
Reversal evidence note: full-cohort dabigatran-reversal and factor Xa inhibitor-reversal trial data for idarucizumab and andexanet alfa above.[12][13]
VTE Prophylaxis (Surgical and Medical Patients)
DOACs for post-orthopedic-surgery prophylaxis
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Apixaban | Hip replacement: 2.5 mg PO BID starting 12-24h after surgery, for 32-38 days Knee replacement: 2.5 mg PO BID starting 12-24h after surgery, for 14 days | Bleeding | Contraindicated with combined strong dual inhibitors of CYP3A4 and P-glycoprotein (e.g., itraconazole, ritonavir) | |
| Rivaroxaban | Hip replacement: 10 mg PO daily starting 6-10h after surgery, for 35 days Knee replacement: 10 mg PO daily starting 6-10h after surgery, for 14 days | Bleeding | Contraindicated with combined strong dual inhibitors of CYP3A4 and P-glycoprotein (e.g., itraconazole, ritonavir) | Not recommended in severe renal impairment. |
| Dabigatran | Hip replacement: 110 mg PO 1-4h after surgery, then 220 mg PO daily, for 28-35 days Knee replacement: 110 mg PO 1-4h after surgery, then 220 mg PO daily, for 10 days | Bleeding, dyspepsia | Contraindicated if ClCr under 30 mL/min or with strong P-glycoprotein inhibitors (e.g., quinidine) | Contraindicated if ClCr under 30 mL/min. Consider 150 mg daily over age 75. |
LMWH prophylaxis
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Enoxaparin | General surgery: 40 mg SC once daily Orthopedic surgery: 30 mg SC Q12H | Bleeding, HIT (rare), osteoporosis with long-term use | Additive bleeding risk with ASA and oral anticoagulants | 1 mg = 100 units. Contraindicated with a history of HIT. |
| Dalteparin | General surgery: 2,500 units SC once daily Orthopedic surgery: 5,000 units SC once daily | Bleeding, HIT (rare), osteoporosis with long-term use | Additive bleeding risk with ASA and oral anticoagulants | Contraindicated with a history of HIT. |
| Tinzaparin | General surgery: 3,500 units SC once daily Orthopedic surgery: 50-75 units/kg SC once daily | Bleeding, HIT (rare), osteoporosis with long-term use | Additive bleeding risk with ASA and oral anticoagulants | Contraindicated with a history of HIT. |
Other prophylaxis agents
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Fondaparinux | High-risk orthopedic surgery, >=50 kg: 2.5 mg SC once daily | Bleeding, allergic reactions (rare) | Additive bleeding risk with ASA and oral anticoagulants | Not recommended below 50 kg or with renal dysfunction. |
| Heparin (UFH) | General surgery, moderate risk: 5,000 units SC Q8-12H | Bleeding, HIT, osteoporosis | Additive bleeding risk with ASA and oral anticoagulants | Monitor platelets closely during the first week of therapy. |
| ASA | Extended prophylaxis after hip replacement: 81 mg PO daily for 28 days, started after an initial 5-10 day course of LMWH or a DOAC Extended prophylaxis after knee replacement: 81 mg PO daily for 9 days, started after an initial 5-day course of a DOAC | Bleeding, usually minor (epistaxis); GI intolerance | Additive bleeding risk with other antiplatelet agents and anticoagulants | A step-down option after an initial LMWH/DOAC course, not a stand-alone first-line prophylaxis agent. |
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.