Cardiovascular

Deep vein thrombosis: outpatient diagnosis and anticoagulation

Clinical Overview and When to Suspect DVT

— Stasis: immobilization, long-haul travel >4–6 h, recent hospitalization, paresis, obesity

— Endothelial injury: surgery (especially orthopedic hip/knee), trauma, indwelling catheter, prior DVT

— Hypercoagulability: malignancy (occult or known), estrogen (OCP, HRT, pregnancy/postpartum), inherited thrombophilia (factor V Leiden, prothrombin G20210A, protein C/S or antithrombin deficiency), antiphospholipid syndrome, nephrotic syndrome, IBD, COVID-19

— Unilateral leg swelling, calf pain, warmth, erythema, or new dilated superficial veins

— Post-op patient calling with calf tenderness 1–3 weeks after orthopedic or pelvic surgery

— Cancer patient on chemotherapy with new arm or leg swelling

— Pregnant or postpartum patient with left leg swelling (left iliac vein compressed by right iliac artery — May-Thurner anatomy amplified in pregnancy)

— Major transient provocation (surgery, trauma, hospitalization ≥3 days within 90 days): 3 months

— Unprovoked or persistent risk (active cancer, antiphospholipid): extended/indefinite

Board pearl: A Step 3 stem describing a patient 2 weeks post knee arthroplasty with unilateral calf swelling who is hemodynamically stable is the prototypical outpatient DVT case — your job is to risk-stratify with Wells, not to admit reflexively.

Definition: Thrombus formation in a deep vein, most commonly in the lower extremity (popliteal, femoral, iliac) but also upper extremity (axillary, subclavian) in patients with central catheters or effort thrombosis.

Epidemiology: ~1–2 per 1000 adults/year in the US; risk rises sharply after age 60. Roughly half of untreated proximal DVTs embolize to the lungs.

Virchow's triad — the trigger framework:

When to suspect in clinic:

Provoked vs. unprovoked matters early because it drives duration of anticoagulation:

Presentation Patterns and Key History

— Unilateral leg swelling (>3 cm calf circumference difference measured 10 cm below tibial tuberosity)

— Dull aching or cramping calf or thigh pain, worse with standing/walking

— Warmth, erythema, palpable cord along a deep vein

— Pitting edema confined to the symptomatic limb

— Recent surgery, trauma, hospitalization, immobilization, long travel

— Cancer history, weight loss, new screening lapses (occult malignancy hides here)

— Estrogen exposure: OCPs, HRT, fertility treatment, pregnancy, postpartum status

— Personal or family history of VTE, miscarriage, stroke under 50 (antiphospholipid clues)

— Prior DVT/PE and prior anticoagulation duration

— Bleeding history, GI bleed, intracranial bleed, falls, alcohol use, NSAID/antiplatelet use — these drive anticoagulant choice and duration

— Renal and hepatic comorbidities (drug selection)

— Pregnancy intention or current pregnancy (DOACs contraindicated)

Key distinction: Bilateral leg swelling is rarely DVT — think heart failure, cirrhosis, nephrotic syndrome, or pelvic mass causing bilateral venous compression. Unilateral asymmetry is the DVT signature.

Step 3 management: Document Wells score components explicitly in the chart — it is both a clinical and medicolegal anchor for choosing D-dimer vs. immediate ultrasound.

Classic lower-extremity DVT:

Iliofemoral DVT: entire leg swollen, thigh pain, sometimes blue/dusky discoloration — risk of phlegmasia cerulea dolens (limb-threatening).

Upper-extremity DVT: arm swelling, heaviness, dilated chest wall collaterals; ask about central line, pacemaker, recent PICC, or repetitive overhead activity (Paget-Schroetter effort thrombosis in young athletes).

Asymptomatic presentations: PE may be the first clue — sudden dyspnea, pleuritic chest pain, syncope, or unexplained tachycardia in a high-risk patient.

Targeted history must capture:

Red flags for PE coexistence: dyspnea at rest, pleuritic pain, hemoptysis, syncope, HR >100, SpO2 <94% — these patients leave the outpatient pathway.

Physical Exam Findings and Hemodynamic Assessment

— Compare limbs side-by-side; measure calf circumference 10 cm below tibial tuberosity — >3 cm difference is a Wells criterion

— Look for pitting edema, erythema, dilated superficial collaterals, skin discoloration

— In iliofemoral DVT: pale, swollen limb (phlegmasia alba dolens) or cyanotic, painful limb with compromised arterial inflow (phlegmasia cerulea dolens — surgical/IR emergency)

— Warmth over affected calf or thigh

— Tenderness along the deep venous system (popliteal fossa, medial thigh)

— Palpable cord — firm, tender vein

— Pulses should be intact in uncomplicated DVT; diminished pulses suggest phlegmasia or alternative arterial disease

— Vitals: HR, BP, RR, SpO2, temperature

— Tachycardia, hypotension, hypoxia, or syncope → assume coexisting PE → do NOT manage as outpatient → ED transfer, CT pulmonary angiography, risk-stratify for thrombolysis

— Look for elevated JVP, parasternal heave, accentuated P2, right-sided S3 — signs of RV strain from PE

— Ecchymoses, petechiae, fundoscopic hemorrhages

— Stool guaiac if GI symptoms or anemia

— Neurologic baseline (falls, prior stroke)

Board pearl: A normal exam does NOT rule out DVT — up to 50% of patients with proven DVT have minimal findings. The Wells score + D-dimer pathway exists precisely because the exam is unreliable.

Step 3 management: If the patient is hemodynamically stable, ambulatory, and has reliable follow-up, outpatient workup and treatment are the standard of care — admission is not required for uncomplicated DVT.

Inspection:

Palpation:

Homans sign (calf pain with passive dorsiflexion): historically taught but poor sensitivity and specificity — do not rely on it.

Hemodynamic and systemic assessment — the outpatient gating question:

Skin signs of chronic venous disease vs. acute DVT: hemosiderin staining, lipodermatosclerosis, healed ulcers suggest chronic venous insufficiency or post-thrombotic syndrome from prior DVT — context for recurrence risk.

Bleeding-risk exam before anticoagulation:

Diagnostic Workup — Initial Labs, Wells Score, and D-dimer

— Active cancer (+1), paralysis/recent immobilization (+1), bedridden ≥3 days or major surgery within 12 wk (+1), localized tenderness along deep veins (+1), entire leg swollen (+1), calf swelling >3 cm vs. asymptomatic side (+1), pitting edema in symptomatic leg (+1), collateral superficial veins (+1), prior documented DVT (+1), alternative diagnosis as likely or more likely (−2)

— DVT unlikely: ≤1 point

— DVT likely: ≥2 points

— Unlikely (≤1) → high-sensitivity D-dimer

— Negative → DVT excluded, no imaging, no anticoagulation

— Positive → compression ultrasound

— Likely (≥2) → go directly to compression ultrasound (skip D-dimer; it lacks specificity at this pretest probability)

— Elevated in pregnancy, age >50, malignancy, infection, recent surgery, hospitalization — low specificity

— Use age-adjusted cutoff in patients >50: age × 10 ng/mL (FEU)

— Highly sensitive ELISA or immunoturbidimetric assays only — qualitative bedside assays are insufficient

— CBC (platelets, baseline Hgb)

— CMP — creatinine and CrCl drive DOAC dosing and choice

— LFTs — hepatic impairment alters DOAC and warfarin choice

— PT/INR and aPTT — baseline for warfarin or if heparin needed

— Pregnancy test in reproductive-age women (DOACs contraindicated)

— Consider HIV, hepatitis serologies if relevant to long-term planning

Key distinction: D-dimer is a rule-out test in low-pretest-probability patients only. Ordering D-dimer in a Wells-likely patient wastes time and can falsely reassure when negative.

Board pearl: Age-adjusted D-dimer cutoff in a 72-year-old = 720 ng/mL FEU — a value of 600 is negative and rules out DVT in a low-probability patient.

Step 1 — Apply the Wells DVT score (the gateway to the algorithm):

Step 2 — Branch on the score:

D-dimer caveats:

Baseline labs before starting anticoagulation:

Diagnostic Workup — Compression Ultrasound and Advanced Imaging

— Proximal (2-point) compression US: evaluates common femoral and popliteal veins — fast, high sensitivity for proximal DVT (>95%)

— Whole-leg US: also images calf veins — detects isolated distal DVT but operator-dependent

— Diagnostic criterion: non-compressibility of the vein with probe pressure (the single most reliable sign); Doppler augments by showing absent or abnormal flow

— Echogenic intraluminal material is supportive but not required

— Positive proximal US → diagnosis confirmed, start anticoagulation

— Negative proximal US + Wells likely or positive D-dimer → repeat US in 5–7 days to catch propagating calf thrombi, OR proceed to whole-leg US

— Negative whole-leg US → DVT excluded

— Options: anticoagulate (especially if symptomatic, large thrombus, persistent risk factor, prior VTE, cancer) or surveillance US in 1–2 weeks for propagation

— Propagation rate ~15% — many guidelines prefer treating symptomatic patients

— Suspected iliac or IVC thrombus (entire leg swelling, pregnancy, postpartum, abdominal/pelvic mass): CT venography or MR venography

— Upper-extremity DVT: ultrasound of subclavian/axillary; if non-diagnostic due to clavicle shadowing, CT or MR venography

— Suspected May-Thurner syndrome in young woman with left iliofemoral DVT: MR/CT venography after acute treatment

Step 3 management: Schedule the repeat ultrasound in 5–7 days before the patient leaves the clinic if the initial proximal US is negative but suspicion remains — failure to arrange follow-up imaging is a documented malpractice pattern.

Board pearl: Non-compressibility — not Doppler flow — is the gold-standard ultrasound finding for acute DVT.

Compression ultrasound with Doppler — the confirmatory test:

Algorithm after initial US:

Isolated distal (calf) DVT — management nuance:

When ultrasound is inadequate:

Concurrent PE workup: if any cardiopulmonary symptoms — CT pulmonary angiography; V/Q scan if contrast contraindicated (renal failure, pregnancy).

Risk Stratification and Outpatient vs. Inpatient Triage

— Hemodynamically stable, no signs of PE compromise (SpO2 ≥94%, HR <110, SBP ≥100)

— No phlegmasia, no severe pain

— Low bleeding risk (no recent bleed, no severe thrombocytopenia, no active ulcer)

— Adequate renal function (CrCl >30 for most DOACs)

— Reliable patient — can take meds, attend follow-up, access pharmacy

— No pregnancy (DOACs contraindicated — bridge to LMWH outpatient is still possible if stable)

— Adequate social support, telephone access, transportation

— Massive iliofemoral DVT or phlegmasia → IR consult for catheter-directed thrombolysis

— Coexisting PE with RV strain, troponin elevation, or hemodynamic instability

— Active bleeding or very high bleeding risk requiring observation

— Severe renal failure (CrCl <30) requiring tailored heparin

— Pregnancy with iliofemoral or extensive clot

— Inability to arrange outpatient anticoagulation logistics (uninsured + DOAC cost, no pharmacy access)

— Major transient (surgery >30 min, hospitalization ≥3 days, major trauma, c-section within 90 days): 3 months

— Minor transient (estrogen therapy, pregnancy, leg injury with reduced mobility ≥3 days, flight >8 h): 3 months

— Unprovoked: at least 3 months, then reassess for extended therapy

— Active cancer or antiphospholipid syndrome: extended/indefinite

CCS pearl: On CCS, the outpatient DVT case typically wants you to: confirm dx with US, start a DOAC, schedule a 2-week follow-up, counsel on bleeding precautions, and avoid unnecessary admission orders — admitting a stable DVT loses points.

Board pearl: Even with confirmed proximal DVT, early ambulation is encouraged — bedrest does not reduce PE risk and worsens outcomes.

Most DVTs are managed entirely as outpatients. Hospitalization is reserved for specific high-risk features.

Criteria favoring outpatient management:

Criteria favoring admission:

Provoked vs. unprovoked classification at diagnosis — determines duration:

HAS-BLED or similar bleed-risk assessment guides extended-therapy decisions, not initial treatment.

Pharmacotherapy — First-Line Anticoagulation

— Apixaban: 10 mg BID × 7 days, then 5 mg BID. No parenteral lead-in. Preferred when bleeding risk is a concern (lowest GI bleeding among DOACs).

— Rivaroxaban: 15 mg BID × 21 days, then 20 mg daily with food. No lead-in. Take with food for absorption.

— Dabigatran: 5–10 days of parenteral lead-in (LMWH) then 150 mg BID. Reversal: idarucizumab.

— Edoxaban: 5–10 days of LMWH lead-in then 60 mg daily (30 mg if CrCl 15–50 or weight ≤60 kg).

— First-line in pregnancy, active cancer (though DOACs increasingly preferred), and severe renal dysfunction adjustments needed

— Required as lead-in for dabigatran/edoxaban

— Reserved for mechanical valves, antiphospholipid syndrome (triple-positive), severe renal impairment, cost barriers

— Always overlap with LMWH for ≥5 days AND until INR ≥2 for 24 h — warfarin alone is initially procoagulant (protein C/S drop faster than factors II, VII, IX, X)

— Target INR 2.0–3.0

— Apixaban or rivaroxaban are now first-line (non-GI/GU cancers); edoxaban also acceptable

— LMWH preferred for luminal GI cancers (bleeding risk) and GU cancers with bleeding

— Bleeding precautions: soft toothbrush, avoid NSAIDs/aspirin unless indicated, fall prevention

— Drug interactions: strong CYP3A4/P-gp inducers (rifampin, phenytoin, carbamazepine, St. John's wort) reduce DOAC levels

— Adherence is critical — DOACs have short half-lives; missed doses raise recurrence risk

Step 3 management: Apixaban 10 mg BID × 7 days → 5 mg BID is the most board-tested outpatient DVT regimen. Memorize the load and the step-down.

Board pearl: Triple-positive antiphospholipid syndrome = warfarin, not DOAC.

DOACs are first-line for most non-cancer, non-pregnant outpatients (ACCP/CHEST 2021, ASH 2020):

LMWH (enoxaparin 1 mg/kg SC q12h or 1.5 mg/kg daily):

Warfarin:

Cancer-associated VTE:

Antiphospholipid syndrome (especially triple-positive): warfarin — DOACs increase recurrent thrombosis risk.

Counseling at start:

Procedural Therapy and Expanded Pharmacology

— Indications: iliofemoral DVT with phlegmasia cerulea dolens, limb-threatening ischemia, or massive iliofemoral DVT in young patients with low bleeding risk and symptoms <14 days

— ATTRACT trial: routine CDT did not reduce post-thrombotic syndrome overall, but subgroups with iliofemoral DVT had reduced moderate-to-severe PTS

— Performed by IR; requires hospitalization, intensive monitoring

— Only indication: acute proximal DVT with absolute contraindication to anticoagulation (active major bleeding, recent CNS hemorrhage)

— Retrievable filters must be removed when anticoagulation can be resumed — un-retrieved filters cause long-term complications (filter thrombosis, migration, fracture)

— Not indicated for "extra protection" alongside anticoagulation

— Reversal agents:

— Dabigatran → idarucizumab

— Apixaban/rivaroxaban → andexanet alfa (or 4-factor PCC if unavailable)

— Warfarin → 4-factor PCC + IV vitamin K for major bleeding; oral vitamin K for INR >10 without bleeding

— LMWH → protamine (partial reversal)

— Renal dosing thresholds:

— Apixaban: standard dose unless ≥2 of: age ≥80, weight ≤60 kg, Cr ≥1.5 (then 2.5 mg BID for AFib, but 5 mg BID is retained for VTE)

— Rivaroxaban: avoid if CrCl <15; caution 15–30

— Dabigatran: avoid if CrCl <30

— Edoxaban: avoid if CrCl >95 (paradoxically less effective) and if <15

— Drug interactions: azoles, HIV protease inhibitors, amiodarone, verapamil increase DOAC levels; rifampin/anticonvulsants decrease them.

Board pearl: IVC filter for a patient with acute DVT and intracranial hemorrhage 2 weeks ago is the textbook indication — and the filter must be retrieved once anticoagulation can resume.

Key distinction: Retrievable ≠ removed. A retained "temporary" filter is a Step 3 transitions-of-care error.

Catheter-directed thrombolysis (CDT) / pharmacomechanical thrombectomy:

Systemic thrombolysis (alteplase): rarely used for isolated DVT — reserved for limb-threatening clot when CDT unavailable.

IVC filter:

Surgical thrombectomy: rare, reserved for phlegmasia when thrombolysis fails or is contraindicated.

Expanded anticoagulant pharmacology details:

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher bleeding risk, polypharmacy, falls, cognitive issues

— Apixaban preferred — lowest major bleeding among DOACs, especially GI bleeding

— Avoid rivaroxaban in patients with high GI bleed risk (higher GI bleeding rate)

— Reassess fall risk, vision, medication adherence at each visit

— Adjust apixaban to 2.5 mg BID only if treating AFib with ≥2 criteria (age ≥80, wt ≤60 kg, Cr ≥1.5) — for VTE treatment, full dose is retained

— Use age-adjusted D-dimer cutoff to avoid unnecessary imaging

— CrCl 30–50: all DOACs generally acceptable with attention to dosing

— CrCl 15–30: apixaban preferred (least renal clearance, ~27%); avoid dabigatran; rivaroxaban and edoxaban with caution

— CrCl <15 or dialysis: warfarin is traditional standard; apixaban is increasingly used off-label but data limited — consult nephrology and pharmacy

— LMWH dosing requires anti-Xa monitoring if CrCl <30; UFH is preferred in severe renal failure for acute treatment

— Child-Pugh A: DOACs acceptable

— Child-Pugh B: avoid rivaroxaban; apixaban with caution; consider LMWH or warfarin (though warfarin difficult with baseline coagulopathy)

— Child-Pugh C: avoid all DOACs; LMWH preferred with anti-Xa monitoring

— Active hepatitis with elevated transaminases >3× ULN: avoid DOACs

— Avoid concurrent NSAIDs, aspirin (unless ASCVD-mandated), SSRIs increase bleeding risk

— Review every medication at start — DOACs interact with antifungals, anticonvulsants, HIV meds, amiodarone

Step 3 management: A 78-year-old woman with a new proximal DVT and CrCl 38 → apixaban 10 mg BID × 7 days, then 5 mg BID, hold concurrent ibuprofen, switch to acetaminophen, schedule 2-week follow-up with CBC.

Board pearl: Among DOACs, apixaban has the lowest GI and overall major bleeding rates — the default choice in elderly or bleed-prone patients.

Elderly (age ≥75):

Renal impairment:

Hepatic impairment:

Drug-drug interactions in elderly:

Special Populations — Pregnancy, Postpartum, and Pediatrics

— Hypercoagulable state throughout pregnancy and up to 6 weeks postpartum

— Left leg predominance (compression by gravid uterus + right iliac artery)

— D-dimer is unreliable — physiologically elevated; do not use to rule out DVT in pregnancy

— Compression ultrasound is first-line; if iliac vein suspected, MR venography (no gadolinium ideally) or limited Doppler

— LMWH is the agent of choice (enoxaparin 1 mg/kg SC BID) — does not cross placenta

— DOACs and warfarin are contraindicated (warfarin teratogenic, especially weeks 6–12; DOACs cross placenta, fetal effects unknown)

— UFH acceptable peripartum (short half-life, reversible)

— Hold LMWH 24 h before scheduled delivery or neuraxial anesthesia (12 h for prophylactic dose)

— Resume 4–6 h postpartum if hemostasis secure; continue for ≥6 weeks postpartum and ≥3 months total

— Breastfeeding: LMWH and warfarin compatible; DOACs not recommended (limited data)

— Most pediatric DVTs are associated with central venous catheters, malignancy, congenital heart disease, or inflammatory disease

— LMWH is standard; DOACs increasingly approved (rivaroxaban, dabigatran have pediatric indications)

— Duration similar to adults (3 months for provoked, longer if persistent risk)

— Hematology consultation for thrombophilia workup is warranted in unprovoked pediatric VTE

— Stop estrogen-containing OCPs/HRT at diagnosis

— Progestin-only methods acceptable

— Future pregnancies: prophylactic or therapeutic LMWH depending on history and thrombophilia

Key distinction: Pregnancy → LMWH always; never DOAC, never warfarin antepartum.

Step 3 management: Pregnant patient with confirmed DVT → enoxaparin 1 mg/kg SC BID, OB and hematology consult, plan to bridge to UFH or hold LMWH 24 h before delivery, continue ≥6 weeks postpartum.

Pregnancy — VTE is a leading cause of maternal mortality:

Anticoagulation in pregnancy:

Postpartum: highest VTE risk in first 6 weeks; threshold for imaging should be low.

Pediatrics:

Hormonal therapy and VTE:

Complications and Adverse Outcomes

— Occurs in ~30–50% of untreated proximal DVTs

— Symptoms: dyspnea, pleuritic pain, hemoptysis, syncope, tachycardia, hypoxia

— Workup: CT pulmonary angiography; echocardiogram for RV strain; troponin/BNP for risk stratification

— Treatment: same anticoagulation as DVT; thrombolysis for massive/submassive PE with hemodynamic compromise

— Develops in 20–50% of patients after proximal DVT, typically within 2 years

— Symptoms: chronic leg pain, heaviness, swelling, hyperpigmentation, varicosities, venous ulcers

— Villalta score quantifies severity

— Prevention: adequate anticoagulation, early ambulation; graduated compression stockings (30–40 mmHg) — evidence mixed but commonly recommended for symptomatic relief

— Treatment: compression, leg elevation, weight loss, wound care for ulcers

— Risk highest in first 6–12 months after stopping anticoagulation

— Unprovoked DVT: ~10%/year recurrence after stopping

— Cancer-associated: even higher

— D-dimer measured 1 month after stopping anticoagulation can help stratify recurrence risk in unprovoked DVT (HERDOO2 rule in women)

— Major bleeding ~2–3%/year on anticoagulation

— GI most common with rivaroxaban, dabigatran; intracranial highest with warfarin

— Manage with reversal agents (see chunk 8), transfusion, source control

— 5–10 days after heparin exposure (sooner with prior exposure)

— Platelet drop >50% + new thrombosis = HIT

— Stop all heparin (including LMWH), start argatroban or fondaparinux, do NOT transfuse platelets

— Confirmatory: serotonin release assay; screening: 4T score + anti-PF4 antibody ELISA

Board pearl: Compression stockings do not prevent PTS in landmark trials (SOX) but remain recommended for symptom relief — the distinction matters for board questions.

Key distinction: Falling platelets on heparin = HIT until proven otherwise; never transfuse platelets in HIT.

Pulmonary embolism:

Post-thrombotic syndrome (PTS):

Recurrent VTE:

Bleeding complications:

Heparin-induced thrombocytopenia (HIT):

Phlegmasia cerulea dolens: limb-threatening — IR thrombectomy/thrombolysis emergently.

When to Escalate Care — ED, ICU, and Specialist Consultation

— Hemodynamic instability (HR >110, SBP <100, syncope)

— Hypoxia (SpO2 <94% on room air) or new dyspnea

— Chest pain, hemoptysis suggesting PE

— Phlegmasia (severely swollen, painful, cyanotic, or pale limb)

— Active bleeding on anticoagulation

— Suspected massive iliofemoral DVT in a young patient with significant symptoms (CDT candidate)

— Pregnancy with suspected DVT requiring urgent imaging

— Severe renal failure complicating drug choice

— Massive PE with shock, RV failure, or need for systemic thrombolysis/ECMO

— Major bleeding requiring reversal and transfusion

— Phlegmasia with limb ischemia post-thrombectomy

— Hematology: unprovoked VTE in patient <50, recurrent VTE, antiphospholipid syndrome, thrombophilia evaluation, HIT, pregnancy-associated VTE planning, anticoagulation failure

— Interventional radiology: iliofemoral DVT for catheter-directed thrombolysis, IVC filter placement/retrieval

— Vascular surgery: phlegmasia, thrombectomy, May-Thurner stenting

— OB/maternal-fetal medicine: pregnant patients

— Oncology: cancer-associated VTE management coordination

— Do not test during acute thrombosis or while on anticoagulation — results unreliable

— Indications: unprovoked VTE in young patient, recurrent VTE, unusual site (cerebral, splanchnic), strong family history, obstetric losses

— Tests: factor V Leiden, prothrombin G20210A, protein C/S, antithrombin, antiphospholipid antibodies (lupus anticoagulant, anti-cardiolipin, anti-β2 glycoprotein I — repeat in 12 weeks if positive)

— Antiphospholipid antibody testing changes management (warfarin over DOAC) — most clinically useful

— Age-appropriate cancer screening up to date (mammogram, colonoscopy, Pap, low-dose CT for smokers, PSA discussion)

— Extensive imaging not routinely recommended (SOME trial: no benefit)

Step 3 management: Unprovoked DVT in a 62-year-old with no recent colonoscopy → ensure age-appropriate cancer screening is current, not pan-scan.

Send to ED immediately:

ICU criteria:

Consultations:

Thrombophilia workup — when and what:

Occult malignancy screening:

Key Differentials — Other Venous and Vascular Causes

— Tender, palpable cord along a superficial vein (often great saphenous), erythema, mild swelling

— Ultrasound: clot in superficial vein, deep system patent

— Treatment: NSAIDs, warm compresses; if ≥5 cm clot, within 3 cm of saphenofemoral junction, or extensive → fondaparinux 2.5 mg SC daily × 45 days (CALISTO trial) due to risk of progression to DVT

— Migratory thrombophlebitis (Trousseau sign) → search for occult malignancy, especially pancreatic

— Bilateral or unilateral, chronic edema, hyperpigmentation, venous stasis dermatitis, medial ankle ulcers

— Improves with elevation

— Treatment: compression, leg elevation, weight management

— Six P's: pain, pallor, pulselessness, poikilothermia, paresthesias, paralysis

— Cold, pale, pulseless limb — distinct from DVT

— Surgical/IR emergency

Key distinction: Superficial phlebitis above the knee within 3 cm of saphenofemoral junction is treated as a DVT — close to deep system, high progression risk.

Board pearl: Trousseau sign of malignancy = migratory superficial thrombophlebitis in different anatomic locations — classic pancreatic adenocarcinoma association.

Superficial thrombophlebitis:

Chronic venous insufficiency:

Post-thrombotic syndrome: previous DVT, chronic symptoms — distinct from acute DVT recurrence; if doubt, ultrasound to assess for new clot vs. chronic changes

Varicose veins / saphenofemoral reflux: dilated tortuous superficial veins, aching, no acute swelling

May-Thurner syndrome: left iliac vein compression by right iliac artery → recurrent left iliofemoral DVT in young women; treat acute DVT, then evaluate for stenting

Paget-Schroetter (effort thrombosis): young, athletic patient with repetitive overhead activity → upper-extremity DVT from thoracic outlet anatomy; treat with anticoagulation + thrombolysis + first rib resection in selected cases

Peripheral arterial disease / acute arterial occlusion:

IVC thrombosis: bilateral lower extremity swelling, distended abdominal wall veins, often in malignancy or hypercoagulability

Key Differentials — Non-Vascular Mimics of Unilateral Leg Swelling

— Warm, erythematous, tender — but typically with fever, leukocytosis, defined erythema borders, often a portal of entry

— Can coexist with DVT

— Treatment: antibiotics covering streptococci and MRSA when indicated

— "Pseudothrombophlebitis" — sudden calf pain and swelling in patient with RA or knee OA

— Ultrasound differentiates: cystic structure in popliteal fossa, sometimes with fluid tracking into calf

— Treatment: rest, NSAIDs, intra-articular steroid if RA flare

— Acute pain during exercise, ecchymosis appearing later

— Ultrasound shows muscle tear/hematoma, no venous thrombosis

— Painless, chronic, non-pitting edema, positive Stemmer sign (cannot pinch dorsal foot skin)

— Causes: prior lymph node dissection, radiation, filariasis (international travel), congenital

— Severe pain out of proportion, pain with passive stretch, tense compartment, paresthesias

— Surgical emergency — fasciotomy

— Dihydropyridine CCBs (amlodipine), thiazolidinediones, gabapentin/pregabalin — usually bilateral but can be asymmetric

Step 3 management: Patient with unilateral leg swelling and fever — get ultrasound AND examine for cellulitis. Both can coexist; don't anchor on one diagnosis.

Key distinction: Lymphedema is non-pitting with positive Stemmer sign; DVT and venous insufficiency are pitting.

Cellulitis:

Baker (popliteal) cyst — ruptured:

Calf muscle hematoma / strain / "tennis leg":

Lymphedema:

Compartment syndrome:

Trauma / fracture / hematoma: history of injury, ecchymosis, point tenderness, radiographs as needed

Drug-induced edema:

Heart failure, cirrhosis, nephrotic syndrome: usually bilateral but worth excluding

Pelvic or abdominal mass compressing iliac vein: ovarian, uterine, lymphoma — workup with CT

Septic thrombophlebitis (Lemierre disease in neck, septic pelvic vein thrombophlebitis postpartum): fever + clot + persistent bacteremia despite antibiotics → anticoagulation + prolonged antibiotics

Secondary Prevention, Duration of Anticoagulation, and Long-Term Plan

— Major transient provocation (surgery ≥30 min, hospitalization ≥3 days, major trauma, c-section): 3 months, then stop

— Minor transient (OCPs, pregnancy, leg injury with reduced mobility, long flight): 3 months

— Unprovoked first VTE: ≥3 months, then reassess for extended therapy; many patients continue indefinitely with reduced-dose DOAC

— Recurrent unprovoked VTE: indefinite anticoagulation

— Active cancer: as long as cancer is active or being treated

— Antiphospholipid syndrome (especially triple-positive): indefinite warfarin

— Severe thrombophilia (antithrombin deficiency, homozygous factor V Leiden): consider indefinite

— Apixaban 2.5 mg BID or rivaroxaban 10 mg daily after initial 6 months — reduced-dose extended therapy preserves efficacy with lower bleeding (AMPLIFY-EXT, EINSTEIN-CHOICE)

— Reassess annually: bleed risk, fall risk, patient preference, life expectancy

— HERDOO2 rule (women): if ≤1 of (Hyperpigmentation/Edema/Redness, D-dimer ≥250 off anticoagulation, Obesity BMI ≥30, Older age ≥65) → safe to stop

— DASH score (mixed sex): D-dimer, Age, Sex, Hormonal therapy

— Smoking cessation

— Weight loss if obese

— Stop estrogen-containing contraception/HRT — switch to progestin-only, copper IUD, or non-hormonal methods

— Hydration and mobilization during long travel; consider prophylactic compression stockings for high-risk travelers

— 30–40 mmHg knee-high for symptomatic relief of edema and PTS prevention attempts

— Daily wear during ambulation

Board pearl: Provoked by major transient factor → stop at 3 months. Unprovoked → at least 3 months, then strongly consider extended low-dose DOAC.

Step 3 management: Discontinuing anticoagulation requires a conversation: shared decision-making about recurrence (~10%/yr unprovoked) vs. bleeding (~1–2%/yr) — document the discussion.

Duration decisions are the single highest-yield Step 3 anchor for DVT:

Extended therapy dosing:

Tools to support stopping in unprovoked DVT:

Lifestyle and modifiable risk:

Compression stockings:

Follow-Up, Monitoring Parameters, and Counseling

— Phone or in-person within 3–7 days of diagnosis: confirm med initiation, adherence, no bleeding, no worsening symptoms

— 2-week clinic visit: symptom resolution, bleeding check, CBC, basic metabolic panel

— 1-month visit: review labs, reassess provoking factors, confirm med adherence

— 3-month visit: decision point — stop, continue, or switch to reduced-dose extended therapy

— Thereafter every 3–6 months if on extended anticoagulation

— DOACs: annual CBC, CMP (CrCl, LFTs); no routine drug-level monitoring

— Warfarin: INR weekly until stable, then every 4 weeks; target 2.0–3.0

— LMWH: anti-Xa monitoring only if pregnancy, obesity (BMI >40), renal impairment (CrCl <30), pediatrics

— Symptom check: leg swelling trajectory, new dyspnea, bleeding signs

— Bleeding precautions: avoid contact sports, use soft toothbrush and electric razor, fall-proof the home

— Medication adherence — DOACs have short half-lives; missing doses raises recurrence quickly

— Avoid NSAIDs; use acetaminophen for pain

— Report melena, hematuria, severe headache, syncope, prolonged bleeding immediately

— Drug interactions: notify all providers (dentist, surgeon) before procedures

— Procedure planning: most DOACs held 24–48 h before low-bleed procedures, 48–72 h before high-bleed (longer if renal impairment); resume 24 h after hemostasis

— Travel: hydrate, ambulate every 1–2 h, consider compression stockings on flights >4 h

— Early ambulation from day 1

— Compression stockings 30–40 mmHg for symptom relief

— Physical therapy if significant deconditioning

— Weight loss, smoking cessation referrals

CCS pearl: Order CBC and CMP at 2 weeks and 1 month, schedule 3-month follow-up to decide on duration, and counsel on bleeding precautions — these orders earn full credit on a CCS DVT case.

Board pearl: A patient stable on apixaban at 3 months with an unprovoked DVT → step down to 2.5 mg BID for extended prevention.

Initial outpatient follow-up cadence:

Monitoring parameters by drug:

Counseling checklist:

Rehabilitation:

Ethical, Legal, and Patient Safety Considerations

— Discuss bleeding risk (major bleed ~2–3%/yr, intracranial ~0.3–0.5%/yr) vs. recurrence risk

— Document the conversation; patient autonomy includes the right to decline anticoagulation after understanding consequences

— In refusing patients, document risks discussed and consider IVC filter only if recurrent VTE despite refusal (controversial — generally not recommended for refusal alone)

— Hospital discharge: ensure first DOAC dose given before discharge or filled at bedside pharmacy; confirm patient can afford the drug (apixaban/rivaroxaban can cost >$500/month uninsured — use patient assistance programs, copay cards, or warfarin if cost-prohibitive)

— Communicate to PCP within 48 h: diagnosis, drug, duration plan, follow-up appointments, pending studies

— IVC filter retrieval must be explicitly scheduled — un-retrieved filters are a sentinel patient-safety event and a malpractice risk

— Bridge clarity: if warfarin started, who manages INRs? Anticoagulation clinic referral is best practice

— HIT with thrombosis: report to pharmacy/quality if hospital-acquired

— Anticoagulant-related major bleeding: root-cause analysis if preventable (dosing error, missed drug interaction)

— Falls and anticoagulation: assess fall risk in elderly; PT referral, home safety evaluation

— Occupational hazards: contact sports, heavy machinery — counsel on bleeding risk

— Women of childbearing age on warfarin or DOAC: discuss teratogenicity; offer contraception (progestin-only or non-hormonal); plan pregnancy with switch to LMWH preconception

— Standardized protocols, dose-checking software, patient education materials

— Joint Commission anticoagulation core measures

Step 3 management: A 70-year-old discharged on apixaban without insurance coverage → switch to warfarin with anticoagulation clinic enrollment to ensure adherence — cost-related nonadherence is a documented preventable harm.

Key distinction: "Retrievable" IVC filter ≠ retrieved. Schedule the removal at insertion.

Informed consent for anticoagulation:

Shared decision-making at 3 months: stopping vs. extended therapy — high-stakes decision; use decision aids, document patient values

Transitions of care — a known DVT failure point:

Mandatory reporting and legal triggers:

Driving and occupational safety:

Pregnancy and reproductive counseling:

Patient safety in anticoagulation clinics:

High-Yield Associations and Rapid-Fire Clinical Facts

Board pearl: Memorize apixaban 10/5 and rivaroxaban 15/20 dosing — these are nearly guaranteed Step 3 stems.

Wells DVT score: ≥2 = likely → ultrasound; ≤1 = unlikely → D-dimer

Age-adjusted D-dimer: age × 10 ng/mL FEU for patients >50

Apixaban VTE dosing: 10 mg BID × 7 days → 5 mg BID; extended = 2.5 mg BID

Rivaroxaban VTE dosing: 15 mg BID × 21 days → 20 mg daily with food; extended = 10 mg daily

Dabigatran/edoxaban: require 5–10 day LMWH lead-in

Warfarin: overlap with LMWH ≥5 days AND until INR ≥2 × 24 h

Pregnancy: LMWH only (enoxaparin 1 mg/kg BID); never DOAC or warfarin

Antiphospholipid syndrome (triple-positive): warfarin, not DOAC

Cancer-associated VTE: apixaban/rivaroxaban first-line (non-GI/GU); LMWH for luminal GI/GU cancers

IVC filter: only for absolute contraindication to anticoagulation in acute proximal DVT

HIT: platelets drop >50% at 5–10 days on heparin → stop heparin, start argatroban; never transfuse platelets

Trousseau sign: migratory superficial thrombophlebitis → occult malignancy (classically pancreatic adenocarcinoma)

May-Thurner: left iliofemoral DVT in young women — compression of left iliac vein by right iliac artery

Paget-Schroetter: upper-extremity DVT in young athletes (effort thrombosis) → anticoagulation + thrombolysis + first rib resection

Phlegmasia cerulea dolens: painful, swollen, cyanotic limb → IR emergency

Post-thrombotic syndrome: chronic limb pain/swelling/hyperpigmentation after DVT — 20–50%

Reversal agents: dabigatran → idarucizumab; apixaban/rivaroxaban → andexanet alfa or 4F-PCC; warfarin → 4F-PCC + IV vitamin K

DOAC contraindications: pregnancy, mechanical valves, triple-positive APS, severe hepatic disease, severe renal impairment (variable)

Non-compressibility on ultrasound = diagnostic for DVT

Provoked transient (surgery, trauma, hospitalization): 3 months

Unprovoked: ≥3 months, consider extended

Cancer-associated: as long as cancer active

Recurrent unprovoked or APS: indefinite

HERDOO2 rule: identifies low-risk women who can stop anticoagulation after unprovoked DVT

Compression stockings (SOX trial): did NOT prevent PTS, but recommended for symptoms

SOME trial: extensive cancer screening not warranted in unprovoked VTE — age-appropriate screening only

Board Question Stem Patterns

— 58-year-old, unilateral leg swelling 2 weeks after long flight, US confirms proximal DVT, CrCl 75, no comorbidities

— Answer: apixaban 10 mg BID × 7 days, then 5 mg BID × 3 months

— 28-year-old G2P1 at 24 weeks with left leg swelling and confirmed femoral DVT

— Answer: enoxaparin 1 mg/kg SC q12h; not warfarin, not DOAC

— 32-year-old woman with recurrent DVTs, history of fetal loss, positive lupus anticoagulant + anti-cardiolipin + anti-β2 GPI on two occasions

— Answer: warfarin INR 2–3, NOT a DOAC (TRAPS trial — rivaroxaban inferior in triple-positive APS)

— Day 7 of UFH for DVT, platelets drop from 220 to 80, new clot

— Answer: stop heparin, start argatroban; send anti-PF4 antibody and serotonin release assay

— 65-year-old with DVT 1 week after hip replacement; provoked

— Answer: 3 months total, then stop

— Patient finishing 3 months of apixaban for unprovoked proximal DVT, low bleed risk

— Answer: continue apixaban 2.5 mg BID indefinitely (extended therapy)

— Patient with acute proximal DVT and intracranial hemorrhage 5 days ago

— Answer: retrievable IVC filter; plan retrieval when anticoagulation safe

— Patient with colon cancer and new DVT

— Answer: LMWH (luminal GI cancer with bleeding risk) or apixaban if low GI bleed risk

— 45-year-old with calf pain, Wells = 1, D-dimer 320 ng/mL (negative)

— Answer: no further testing, DVT excluded

— Wells = 3, US negative for proximal DVT

— Answer: repeat ultrasound in 5–7 days OR whole-leg US

— 60-year-old with migratory superficial thrombophlebitis, weight loss

— Answer: workup for pancreatic adenocarcinoma

Step 3 management: Recognize the pattern, choose the drug, set the duration, schedule the follow-up — that quartet wins almost every DVT vignette.

Stem 1 — Outpatient DVT, choose first-line drug:

Stem 2 — Pregnancy:

Stem 3 — Antiphospholipid syndrome:

Stem 4 — HIT:

Stem 5 — Duration:

Stem 6 — Unprovoked at 3 months:

Stem 7 — IVC filter:

Stem 8 — Cancer-associated VTE:

Stem 9 — Wells unlikely + D-dimer:

Stem 10 — Wells likely + ultrasound:

Stem 11 — Trousseau sign:

One-Line Recap

Confirmed proximal DVT in a stable, ambulatory adult is an outpatient diagnosis — risk-stratify with Wells, confirm with compression ultrasound, start a DOAC (apixaban 10 mg BID × 7 days → 5 mg BID is the default), individualize duration based on provoking factors, and schedule structured follow-up.

Board pearl: The single most testable DVT regimen on Step 3 is apixaban 10 mg BID × 7 days → 5 mg BID for an outpatient proximal DVT — with a 3-month checkpoint to decide on extended low-dose therapy.

Step 3 management: Confirm, treat, counsel, follow up, and reassess at 3 months — outpatient DVT is a longitudinal management story, not a single decision point.

Diagnosis: Wells ≤1 → D-dimer (age-adjusted in >50); Wells ≥2 → compression ultrasound directly. Non-compressibility is the diagnostic finding.

First-line treatment: Apixaban or rivaroxaban for most outpatients; LMWH for pregnancy; warfarin for triple-positive antiphospholipid syndrome and mechanical valves; LMWH or DOAC for cancer-associated VTE (LMWH preferred for luminal GI/GU cancers).

Duration anchors: Major transient provocation = 3 months; unprovoked = ≥3 months then consider extended low-dose DOAC (apixaban 2.5 mg BID or rivaroxaban 10 mg daily); recurrent unprovoked or APS = indefinite; active cancer = while active.

Escalation triggers: Hemodynamic instability, hypoxia, phlegmasia, massive iliofemoral DVT, active bleeding, severe renal failure, or coexisting PE with RV strain — these leave the outpatient pathway.

Patient safety wins: Schedule the repeat US if initial is negative but suspicion high, retrieve every "retrievable" IVC filter, communicate with the PCP within 48 hours of diagnosis, address drug cost barriers proactively, and never transfuse platelets in suspected HIT.