Family Medicine Board Review · Hematology/Vascular · Case-Based · AAFP 2025
Venous Thromboembolism: DVT & PE
Pretest probability tools, D-dimer cutoffs, imaging algorithms, pregnancy-specific pathways, outpatient-vs-inpatient PE risk stratification, and the full anticoagulation selection/duration framework.
Why VTE Matters
- 3rd most common cause of sudden cardiovascular death (after MI and CVA/stroke)
- 25% of VTE sudden deaths present as the first presentation of VTE
- ⅓ present with PE; ⅔ present with DVT
- 70% of PE cases have a concomitant DVT
Board trap / classic vignette: a patient who collapses suddenly and dies with no prior history — massive PE should always be on the differential for sudden unexplained death, since it can be the very first presentation.
Pathophysiology — Virchow's Triad
1. Venous Stasis
Immobilization, surgery, long travel
2. Endothelial Injury
Trauma, surgery, central venous catheters
3. Hypercoagulability
Inherited: Factor V Leiden, prothrombin mutation
Acquired: cancer, pregnancy, estrogen, antiphospholipid syndrome
Pearl: every VTE risk factor maps onto one (or more) of these three pillars — a useful mental framework for classifying any new risk factor a vignette throws at you.
Risk Factors for VTE (By Odds Ratio)
Strong (OR >10)
Fracture (hip or leg)
Hip or knee replacement
Major general surgery
Major trauma
Spinal cord injury
Moderate (OR 2–9)
Arthroscopic knee surgery
Central venous lines
Chemotherapy
CHF or respiratory failure
Hormone replacement therapy
Malignancy
Oral contraceptive therapy
Paralytic stroke
Pregnancy/postpartum
Previous VTE
Thrombophilia
Weak (OR <2)
Bed rest >3 days
Immobility from sitting (car/air travel)
Increasing age
Laparoscopic surgery
Obesity
Pregnancy/antepartum
Varicose veins
Board trap: pregnancy appears in BOTH moderate (postpartum) and weak (antepartum) categories — the postpartum period carries substantially higher VTE risk than the antepartum period itself. Don't treat "pregnancy" as a single uniform risk tier.
Diagnostic Approach for DVT
Three-step framework: (1) Pretest probability → (2) D-dimer (if appropriate) → (3) Imaging.
Clinical suspicion of DVT → assess pretest probability
↓
Low probability → D-dimer
Negative → DVT excluded
Positive → compression ultrasound
Moderate/high probability → compression ultrasound directly
Positive → DVT confirmed, start anticoagulation
Negative → D-dimer → if positive, repeat US in 7 days; if negative, DVT excluded
Wells' Criteria for DVT
| Criterion | Points |
|---|
| Active cancer (treatment ongoing, within 6 months, or palliative) | 1 |
| Calf swelling >3 cm vs. asymptomatic side (10 cm below tibial tuberosity) | 1 |
| Collateral superficial veins (nonvaricose) | 1 |
| Entire leg edematous | 1 |
| Localized tenderness along the deep venous system | 1 |
| Paralysis, paresis, or recent immobilization of lower extremity | 1 |
| Pitting edema confined to the symptomatic leg | 1 |
| Previously documented DVT | 1 |
| Recently bedridden >3 days or major surgery within 12 weeks | 1 |
| Alternative diagnosis at least as likely as DVT or more likely | −2 |
Score interpretation: Low probability: <0. Moderate: 0–2. High: >2.
Primary Care Rule Criteria (Alternative Tool)
| Criterion | Points |
|---|
| Abnormal D-dimer assay result | 6 |
| Difference in calf circumference ≥3 cm | 2 |
| Absence of leg trauma | 1 |
| Active cancer in past 6 months | 1 |
| Distention of collateral leg veins | 1 |
| Male sex assigned at birth | 1 |
| Surgery in previous month | 1 |
| Use of hormonal contraceptives | 1 |
Score interpretation: range 0–14; ≤3 = very low risk; ≥4 = increased risk.
D-Dimer
- D-dimer is a fibrin degradation product → elevated with active clot formation and breakdown
- Modern assays have >95% sensitivity for VTE — a rule-out test, not a rule-in test
- Standard cutoff: 0.5 µg/mL (500 µg/L)
- Age-adjusted cutoff (age >50): Age × 10 µg/L
Board trap — calculation: a 72-year-old's age-adjusted D-dimer cutoff = 72 × 10 = 720 µg/L — well above the standard 500 threshold. Age-adjustment improves specificity in older adults and reduces unnecessary imaging without increasing missed VTE. Boards may ask you to calculate this directly.
DVT Imaging
- Compression ultrasound — first-line; high sensitivity/specificity for proximal DVT; diagnosis based on inability to fully compress the vein
- Negative proximal ultrasound → repeat in 7 days — proximal scan only assesses the femoral and popliteal veins, so early distal DVT may be missed initially; repeat imaging detects proximal extension if symptoms persist
- Whole-leg ultrasound may overdiagnose distal DVT — many distal DVTs are clinically insignificant and may resolve on their own; can lead to unnecessary anticoagulation and bleeding risk; best avoided in low-risk patients unless symptoms worsen
- When compression US is inconclusive or not feasible → CT venography or MR venography
Board trap: whole-leg ultrasound sounds "more thorough," but it's actually a trap answer in many vignettes — it risks overdiagnosis and overtreatment of clinically insignificant distal clots. The proximal-scan-plus-7-day-repeat strategy is the preferred, better-validated approach.
DVT Teaching Cases
Case 1 — High Pretest Probability
65F, 2-day unilateral calf pain/swelling, bedridden 5 days post-pneumonia hospitalization, calf 4cm larger, localized deep venous tenderness, pitting edema confined to leg, no alternative diagnosis as likely.
Wells score → High pretest probability → Order compression ultrasound directly (DO NOT order D-dimer first).
Case 2 — Moderate Probability, Negative US, Positive D-Dimer
62M, 3 days leg swelling/calf pain, deep venous tenderness, 10-hour car trip 1 week ago, no prior DVT/cancer/surgery.
Moderate probability → US negative → D-dimer positive → NO immediate anticoagulation → repeat compression US in 7 days to detect evolving proximal DVT. If repeat positive → anticoagulate. If repeat negative → DVT ruled out.
Case 3 — Low Risk
28F, mild intermittent calf discomfort, no swelling/redness/warmth/tenderness, no risk factors, fully ambulatory.
Low risk → D-dimer → negative D-dimer excludes DVT (no imaging needed).
Diagnostic Approach for PE
Same three-step framework: Pretest probability → D-dimer (if appropriate) → Imaging.
Clinical suspicion of PE → assess pretest probability
↓
Low probability → apply PERC Rule → if positive, D-dimer → if positive, CTPA
Moderate probability → D-dimer directly → if positive, CTPA
High probability → CTPA directly (skip D-dimer)
Clinical Prediction Rules for PE
| PE Rule-Out Criteria (PERC) | Pts |
|---|
| Age ≥50 | 1 |
| Heart rate ≥100 bpm | 1 |
| Hemoptysis | 1 |
| Hormone use (OCP, estrogen) | 1 |
| O₂ saturation on room air <95% | 1 |
| Prior PE or DVT | 1 |
| Recent surgery or trauma ≤4 weeks | 1 |
| Unilateral leg swelling | 1 |
PERC interpretation: score range 0–6; 0 = >98.5% negative predictive value for ruling out PE — if pretest probability is already low (<15%) AND all PERC criteria are negative, no further workup needed.
| Wells' Criteria for PE | Pts |
|---|
| Clinical signs/symptoms of DVT | 3 |
| PE is #1 diagnosis or equally likely | 3 |
| Heart rate >100 bpm | 1.5 |
| Immobilization ≥3 days or surgery in past 4 weeks | 1.5 |
| Previous PE or DVT | 1.5 |
| Hemoptysis | 1 |
| Malignancy with treatment within 6 months | 1 |
Wells PE interpretation: Low: 0–1. Moderate: 2–6. High: >6. (Alternate simplified cutoff: ≤4 = "PE unlikely.")
| Geneva Score (Revised) | Pts |
|---|
| Heart rate 95+ bpm | 5 |
| Heart rate 75–94 bpm | 3 |
| Pain on lower limb palpation + unilateral edema | 4 |
| Previous DVT or PE | 3 |
| Unilateral lower limb pain | 3 |
| Active malignant condition | 2 |
| Hemoptysis | 2 |
| Surgery or lower limb fracture in past month | 2 |
| Age >65 years | 1 |
Geneva interpretation: range 0–22; <4 = low; 4–10 = moderate; ≥11 = high probability.
PE Imaging
- CTPA = gold standard for diagnosing PE
- PE size ≠ PE severity — small clot + RV strain = high risk; large clot + stable vitals = lower risk. Hemodynamic status matters more than clot size.
- V/Q scan used when CTPA is contraindicated or less optimal:
- Pregnancy
- Contrast allergy
- CKD (GFR <30)
- In pregnancy specifically, assessment begins with a chest x-ray, followed by perfusion and ventilation imaging as needed
Board trap: "PE size ≠ severity" is a favorite exam concept — a hemodynamically unstable patient with a small subsegmental clot is HIGHER risk than a stable patient with a large clot burden. Risk stratification is driven by RV strain/hemodynamics, not clot volume on imaging.
PE Teaching Cases
Case 4 — Low Risk, PERC-Negative
29M, mild non-worsening dyspnea, no risk factors, normal vitals, unremarkable exam.
Wells score 0 → low risk → apply PERC → all criteria negative → no testing indicated.
Case 5 — Moderate Risk
46F, acute dyspnea + pleuritic chest pain, on OCP, HR 104, normal BP/O2 sat.
Wells PE score 4.5 → moderate risk → D-dimer → positive → CTPA.
Case 6 — High Risk, Unstable
72M, acute SOB + lightheadedness, HR 120, BP 85/60, SpO₂ 88%, recent hip surgery, immobile, clear lungs, pale/diaphoretic.
High risk (hemodynamically unstable) → CTPA directly (skip D-dimer given high pretest probability).
Case 7 — Outpatient Disposition Question
78F, controlled DM, acute dyspnea, HR 104, BP 105/65, O₂ sat 92%, CTPA shows segmental PE, fully independent, lives with family, normal troponin/platelets/echo.
Can be considered for outpatient treatment — disposition is based on clinical stability and bleeding risk (see sPESI/CHEST criteria below); no validated DVT-specific outpatient score exists, so overall clinical judgment applies.
VTE in Pregnancy (Hypercoagulable State)
Suspected DVT in Pregnancy
- No validated clinical prediction rules for DVT in pregnancy
- D-dimer is unreliable — physiologically elevated throughout pregnancy
- 1st-line test: whole-leg compression ultrasound
- If ultrasound negative but suspicion remains: serial compression ultrasound or MR venography
Suspected PE in Pregnancy — YEARS Algorithm
- Clinical criteria: signs of DVT, PE is most likely diagnosis, hemoptysis
- No criteria met → PE ruled out if D-dimer <1000 ng/mL
- ≥1 criterion met → PE ruled out if D-dimer <500 ng/mL
- If D-dimer exceeds threshold → CTPA or V/Q scan
- If DVT confirmed on ultrasound → treat as PE, no chest imaging needed
Treatment in pregnancy: LMWH throughout pregnancy + at least 6 weeks postpartum, with a total minimum duration of 3 months. DOACs should be avoided in pregnancy.
Risk Stratification for PE Treatment Setting (Inpatient vs. Outpatient)
1. Assess Safety of Home Management — CHEST Criteria
- Clinically stable with good cardiopulmonary reserve
- No recent bleeding, severe kidney/liver disease, or severe thrombocytopenia (platelets <50 × 10³/µL)
- Patient expected to be adherent to treatment
- Patient feels well enough to be treated at home
- System in place for outpatient follow-up and prompt care access
Suitable for outpatient treatment only if ALL criteria are met.
2. Assess Mortality Risk — Simplified PESI
| Criterion | Points |
|---|
| Age >80 years | 1 |
| History of cancer | 1 |
| History of chronic cardiopulmonary disease | 1 |
| O₂ saturation <90% | 1 |
| Pulse ≥110 bpm | 1 |
| Systolic BP <100 mmHg | 1 |
Score of 0 = low mortality risk (1.1%) — can be considered for outpatient management if social factors allow.
Treatment Phases
1. Initial Management (5–21 days)
Goals: prevent clot extension/embolization, reduce symptoms/complications.
Risk stratify with
sPESI.
DOACs first-line (apixaban, rivaroxaban) — rapid onset,
no parenteral bridge needed.
Bridge required if using
warfarin, dabigatran, or edoxaban.
2. Primary Treatment (3–6 months)
Purpose: clot resolution + recurrence prevention.
ACCP: 3 months; ASH: 3–6 months.
Applies to both provoked and unprovoked VTE.
Cancer-associated VTE: DOAC preferred.
3. Secondary Prevention (Extended)
Indicated for:
first unprovoked VTE, recurrent VTE, VTE provoked by a chronic risk factor.
Consider thrombophilia testing (post-primary treatment) if VTE was provoked by a nonsurgical major transient risk factor, pregnancy/postpartum, or combined OCP use.
Board trap — LMWH/warfarin preference: preferred over DOACs in antiphospholipid antibody syndrome and severe liver disease with coagulopathy. No routine lab monitoring is needed for DOACs.
Aspirin pearl: hold aspirin during anticoagulation if used for cardiovascular disease — no benefit to adding aspirin without another indication. However, in patients with unprovoked VTE who decline anticoagulation for secondary prevention, aspirin is suggested over no aspirin.
Anticoagulant Selection
Renal Function-Based Selection
| Renal Function | Recommendation |
|---|
| CrCl ≥30 | DOAC can be used |
| CrCl 15–29 | Avoid DOAC / adjust LMWH dose |
| CrCl <15 or dialysis | Unfractionated heparin (UFH) + warfarin |
Warfarin rules: start with heparin; overlap ≥5 days AND INR ≥2 for 24 hours before stopping the heparin bridge; target INR 2–3 for both primary treatment and secondary prevention.
Key Agents at a Glance
| Drug | Class | Key Dosing Note |
|---|
| Apixaban (Eliquis) | Factor Xa inhibitor | 10mg BID × 7 days → 5mg BID; secondary prevention 2.5mg BID; no renal adjustment needed (even on dialysis); avoid in Child-Pugh C |
| Rivaroxaban (Xarelto) | Factor Xa inhibitor | 15mg BID with food × 21 days → 20mg daily with food; avoid if CrCl <15 |
| Edoxaban (Savaysa) | Factor Xa inhibitor | Initiate after 5–10 days parenteral anticoagulation; dose by body weight (>60kg vs. ≤60kg) |
| Dabigatran (Pradaxa) | Direct thrombin inhibitor | Initiate after 5–10 days parenteral anticoagulation (bridge required) |
| Enoxaparin (LMWH) | Low-molecular-weight heparin | 1mg/kg SC q12h or 1.5mg/kg SC q24h; dose-adjust if CrCl <30 |
| Warfarin | Vitamin K antagonist | 5mg daily initially; no renal dose adjustment needed; overlap with heparin per rules above |
Exam pearl: apixaban is unique among DOACs in requiring no dose adjustment for renal impairment, even in dialysis patients — a frequently tested distinguishing feature vs. rivaroxaban/edoxaban.
Special Considerations in VTE Treatment
| Situation | Key Recommendation |
|---|
| Acute distal DVT | If no severe symptoms/extension risk factors → consider weekly imaging × 2 weeks instead of immediate anticoagulation; treat if symptoms worsen or thrombus extends |
| Active cancer + acute VTE | DOACs generally preferred over LMWH; consider indefinite secondary prevention |
| Post-thrombotic syndrome | Regular physical activity is the mainstay; compression stockings not routinely recommended (though not harmful, may reduce pain/edema in some) |
| Subsegmental PE | Anticoagulation favored if multiple imaging defects, symptomatic, markedly elevated D-dimer, or proximal DVT present; surveillance may be considered in low-recurrence-risk patients |
| Upper extremity DVT | Treated similarly to lower extremity DVT; if provoked by a functional/necessary central venous catheter, catheter can remain in place during anticoagulation |
| Obesity (BMI >40) | No formal guidelines, but new evidence supports safe use of rivaroxaban and apixaban after shared decision-making |
| Stable cardiovascular disease | Suspend aspirin for secondary VTE prevention for the duration of anticoagulation therapy |
| Pregnancy | LMWH preferred; DOACs avoided (not tested in pregnancy); continue anticoagulation through pregnancy + at least 6 weeks postpartum (minimum total 3 months) |
Take-Home Messages
- Pretest probability first — always the starting point, before D-dimer or imaging
- D-dimer is a rule-out test — high sensitivity, low specificity; don't use it to "rule in" VTE
- DOACs are first-line for most patients
- Special populations need tailored management — pregnancy, cancer, obesity all shift the standard algorithm
- Duration depends on provoked vs. unprovoked VTE classification
- Early mobilization is encouraged