When D-dimer is Useless: A Critical Appraisal for the Intensive Care Clinician

Dr Neeraj Manikath , claude.ai

Abstract

D-dimer, a fibrin degradation product, has become one of the most frequently ordered laboratory tests in acute care medicine. While its utility in excluding venous thromboembolism (VTE) in low-risk outpatients is well-established, its indiscriminate use in certain clinical contexts—particularly in the intensive care unit (ICU), postoperative patients, and pregnancy—often generates more confusion than clarity. This review critically examines the clinical scenarios where D-dimer testing provides minimal diagnostic value, explores the pathophysiological basis for elevated levels in these contexts, and emphasizes why clinical reasoning must supersede numerical thresholds. We provide practical guidance for critical care practitioners on when to abandon D-dimer testing in favor of more appropriate diagnostic strategies.

Keywords: D-dimer, venous thromboembolism, ICU, pregnancy, postoperative, diagnostic stewardship

Introduction

D-dimer represents a paradox in modern laboratory medicine: a test so sensitive that it has become nearly useless in populations where thrombotic risk is highest. First introduced in the 1990s, D-dimer measurement revolutionized the diagnosis of venous thromboembolism (VTE) by offering a high negative predictive value (NPV) in appropriately selected patients.¹ However, its exceptional sensitivity (typically 95-98%) comes at the cost of poor specificity (approximately 40-50%), making it prone to false-positive results in numerous clinical conditions.²

The fundamental principle underlying D-dimer's utility—that a normal level effectively excludes active thrombosis—becomes compromised when baseline elevations are the norm rather than the exception. In critical care medicine, where multisystem organ dysfunction, inflammation, and tissue injury are ubiquitous, D-dimer elevations lose their discriminatory power.³ This review examines three paradigmatic scenarios where D-dimer testing frequently misleads rather than guides clinical decision-making: the ICU environment, the postoperative period, and pregnancy.

Pathophysiology: Why D-dimer Rises Beyond Thrombosis

The Coagulation-Fibrinolysis Cascade

To understand D-dimer's limitations, one must appreciate its origin. D-dimer is formed when cross-linked fibrin undergoes proteolytic degradation by plasmin. While VTE triggers this process, any condition promoting fibrin formation and subsequent lysis will elevate D-dimer levels.⁴

Non-thrombotic causes of D-dimer elevation include:

Systemic inflammation: Cytokine-mediated activation of coagulation pathways⁵
Tissue injury: Surgery, trauma, burns releasing tissue factor⁶
Infection/sepsis: Endothelial dysfunction and consumption coagulopathy⁷
Malignancy: Tumor-associated procoagulant activity⁸
Hepatic dysfunction: Impaired clearance of fibrin degradation products⁹
Renal impairment: Decreased elimination and altered hemostasis¹⁰
Physiological states: Pregnancy, advancing age (>50 years)¹¹,¹²

The ICU Milieu: A Perfect Storm for D-dimer Elevation

Critical illness creates a prothrombotic state through multiple mechanisms: endothelial injury, platelet activation, impaired fibrinolysis, and consumption of natural anticoagulants.¹³ The term "immunothrombosis" describes the intimate relationship between inflammation and coagulation in critical illness.¹⁴ Consequently, D-dimer elevations in ICU patients are nearly universal, with reported prevalence ranging from 82-100%.¹⁵,¹⁶

Clinical Scenario 1: The ICU Patient

The Evidence for Futility

Multiple studies have demonstrated D-dimer's poor diagnostic performance in critically ill patients. A meta-analysis by Righini et al. found that D-dimer's specificity for VTE in hospitalized patients dropped to 30-40%, compared to 60-70% in outpatients.¹⁷ In ICU populations specifically, the area under the receiver operating characteristic curve (AUROC) for D-dimer in diagnosing VTE ranges from 0.60-0.70—barely better than chance.¹⁸

Laterre et al. studied 120 ICU patients and found that 94% had elevated D-dimer levels (>500 ng/mL), regardless of VTE status.¹⁹ The positive predictive value (PPV) was only 11%, meaning that among patients with elevated D-dimer, fewer than one in nine actually had VTE. Even using higher thresholds (>3,000 ng/mL or >5,000 ng/mL) failed to meaningfully improve specificity.²⁰

Pearl #1: In ICU patients, an elevated D-dimer is the rule, not the exception. The test cannot discriminate between VTE and the myriad other causes of fibrinolysis activation inherent to critical illness.

Specific ICU Subpopulations

Sepsis and Septic Shock

Sepsis-associated coagulopathy represents an extreme example of D-dimer's limitations. During sepsis, widespread endothelial activation, consumption coagulopathy, and hyperfibrinolysis drive D-dimer levels to extraordinary heights—often 10-20 times the upper limit of normal.²¹ Notably, D-dimer elevation in sepsis correlates with disease severity and mortality, not necessarily with thrombosis.²²

A prospective study by Angstwurm et al. found that D-dimer levels >5,000 ng/mL in septic patients had only 32% specificity for VTE, with a PPV of 14%.²³ Paradoxically, extremely elevated D-dimer may indicate disseminated intravascular coagulation (DIC) rather than localized thrombosis.²⁴

Acute Respiratory Distress Syndrome (ARDS)

ARDS exemplifies pulmonary immunothrombosis, with extensive fibrin deposition in pulmonary microvasculature.²⁵ D-dimer levels correlate with ARDS severity and are elevated regardless of macrovascular pulmonary embolism (PE).²⁶ In COVID-19-associated ARDS, this phenomenon was particularly pronounced, with D-dimer elevations observed in >90% of critically ill patients, complicating PE diagnosis.²⁷,²⁸

Oyster #1: In COVID-19 ICU patients, age-adjusted D-dimer thresholds (age × 10 μg/L for patients >50 years) failed to improve specificity, and many centers abandoned D-dimer testing entirely, relying instead on clinical suspicion and imaging.²⁹

Trauma and Burns

Trauma-induced coagulopathy (TIC) and burn injuries cause massive tissue injury, releasing tissue factor and activating both coagulation and fibrinolysis.³⁰ D-dimer levels rise within hours of injury and remain elevated for weeks.³¹ In trauma ICU patients, D-dimer's NPV for VTE drops to 50-70%—unacceptably low for a rule-out test.³²

Practical Approach in ICU Patients

When NOT to order D-dimer:

Established critical illness (>48 hours in ICU)
Sepsis or septic shock
ARDS or severe acute respiratory failure
Multiple organ dysfunction syndrome (MODS)
DIC or consumptive coagulopathy
Post-cardiac arrest
Active hemorrhage or massive transfusion

What to do instead:

Clinical suspicion should drive imaging: Use Wells' score or Geneva score with modification for critical illness
Lower threshold for imaging: In ICU patients, proceed directly to compression ultrasonography (CUS) for suspected DVT or computed tomography pulmonary angiography (CTPA) for suspected PE when clinically appropriate³³
Employ serial CUS: For hemodynamically unstable patients where CTPA is contraindicated, serial bilateral lower extremity CUS can detect proximal DVT³⁴
Consider bedside echocardiography: May reveal right ventricular strain suggesting PE or intracardiac thrombus³⁵

Hack #1: For ICU patients on VTE prophylaxis, focus on clinical gestalt and pretest probability rather than laboratory screening. A sudden desaturation, unexplained tachycardia, or unilateral leg swelling warrants imaging regardless of D-dimer.

Clinical Scenario 2: The Postoperative Patient

Surgical Trauma and Hemostatic Activation

Surgery represents controlled trauma with predictable hemostatic consequences. The magnitude of D-dimer elevation correlates with surgical invasiveness, duration, and tissue injury.³⁶ Orthopedic procedures, particularly total hip and knee arthroplasty, produce some of the highest postoperative D-dimer levels, often exceeding 10,000 ng/mL.³⁷

Temporal Pattern of Postoperative D-dimer Elevation:

Day 0-1: Rapid rise due to surgical trauma and fibrin formation
Day 2-3: Peak levels (typically 3-7 days post-surgery)
Day 7-14: Gradual decline but often remains elevated for 2-4 weeks³⁸
Major surgery: May take 4-6 weeks to normalize³⁹

Evidence Base: Surgery-Specific Limitations

Orthopedic Surgery

Hip and knee arthroplasty are high-risk procedures for VTE, yet D-dimer performs dismally in this context. A meta-analysis by Palareti et al. showed that postoperative D-dimer had a specificity of only 5-15% for VTE after major orthopedic surgery—meaning 85-95% of patients without VTE had elevated levels.⁴⁰

Shbaklo et al. found that even at thresholds of 6,000 ng/mL, only 24% of post-arthroplasty patients without VTE had normal D-dimer levels.⁴¹ The NPV ranged from 85-91%, below the 95% threshold typically required for safe exclusion of VTE.⁴²

Cardiac and Vascular Surgery

Cardiopulmonary bypass generates profound systemic inflammation and contact activation of coagulation.⁴³ D-dimer elevations persist for 2-3 weeks postoperatively, rendering the test useless for VTE diagnosis during this period.⁴⁴ Similarly, vascular surgery—particularly aortic procedures—produces massive D-dimer elevation due to atherosclerotic plaque manipulation and ischemia-reperfusion injury.⁴⁵

Pearl #2: The more invasive the surgery, the less useful D-dimer becomes. For major orthopedic, cardiac, vascular, or oncologic surgery, D-dimer testing within the first 2-4 weeks postoperatively is essentially futile.

Abdominal and Oncologic Surgery

Cancer surgery combines two D-dimer-elevating factors: surgical trauma and malignancy-associated hypercoagulability.⁴⁶ Patients undergoing major abdominal surgery for cancer have D-dimer elevations in >95% of cases postoperatively.⁴⁷ Even minor procedures in cancer patients may produce significant D-dimer elevation due to underlying tumor burden.⁴⁸

The Postoperative Diagnostic Dilemma

The clinical challenge lies in distinguishing postoperative VTE from expected surgical changes. Symptoms like dyspnea, tachycardia, and leg swelling are common postoperatively, creating ambiguity about VTE probability.⁴⁹

Oyster #2: *Postoperative patients represent a paradox—they are at high risk for VTE yet have universally elevated D-dimer. Attempting to use D-dimer as a "rule-out" test in this population has led to unnecessary imaging, incidental findings (pulmonary nodules, unsuspected cancers), and increased healthcare costs without proven benefit.*⁵⁰

Practical Approach in Postoperative Patients

Abandon D-dimer testing in:

Any patient within 2 weeks of major surgery
Orthopedic surgery patients (up to 4 weeks post-surgery)
Post-cardiac surgery (up to 3 weeks)
Any cancer surgery patient
Complicated postoperative course (infection, reoperation)

Alternative diagnostic strategy:

Pretest probability assessment: Modified Wells' score (acknowledge that postoperative patients start with higher pretest probability)⁵¹
Direct imaging: Proceed to CUS or CTPA based on clinical suspicion
Bilateral lower extremity CUS: Reasonable initial test for hemodynamically stable patients with leg symptoms
Risk stratification: High-risk surgery + suggestive symptoms = low threshold for imaging regardless of D-dimer

Hack #2: *In postoperative patients with suspected VTE, use a "two-level Wells' score" approach: if low probability (<2 points), consider expectant management with repeat clinical assessment in 24-48 hours unless symptoms progress. If moderate-to-high probability (≥2 points), proceed directly to imaging without D-dimer testing.*⁵²

Clinical Scenario 3: Pregnancy and Postpartum

Physiological Hypercoagulability of Pregnancy

Pregnancy represents a unique prothrombotic state evolutionarily designed to minimize hemorrhage at delivery.⁵³ Beginning in the first trimester, progressive increases in procoagulant factors (fibrinogen, factors VII, VIII, X, von Willebrand factor) coupled with decreased protein S and impaired fibrinolysis create a 5-10 fold increased VTE risk compared to non-pregnant women.⁵⁴

Gestational Changes in D-dimer:

First trimester: 1.5-2× baseline
Second trimester: 2-3× baseline
Third trimester: 3-4× baseline
Immediate postpartum: 4-6× baseline (peaks at delivery)⁵⁵
Postpartum weeks 1-6: Gradual decline but remains elevated⁵⁶

Evidence for D-dimer's Failure in Pregnancy

The landmark studies establishing D-dimer's utility explicitly excluded pregnant women, yet the test is frequently ordered in this population.⁵⁷ Chan et al. demonstrated that using the standard 500 ng/mL threshold, D-dimer had only 25% specificity in pregnant women—meaning three-quarters of pregnant women without VTE had "positive" results.⁵⁸

The PEGeD study (Pregnancy, Embolism, and Genetics, D-dimer) prospectively evaluated 141 pregnant women with suspected PE and found that D-dimer >500 ng/mL had 100% sensitivity but only 6% specificity.⁵⁹ Essentially, every pregnant woman beyond the first trimester had an elevated D-dimer, rendering the test meaningless.

Trimester-Specific Performance:

First trimester: NPV 95-99% (may have utility with cut-offs 750-1000 ng/mL)⁶⁰
Second trimester: NPV 85-90% (questionable utility)⁶¹
Third trimester: NPV 70-80% (no utility)⁶²
Postpartum (0-6 weeks): NPV 60-75% (potentially harmful to rely on)⁶³

Pearl #3: D-dimer maintains reasonable NPV only in the first trimester of pregnancy. Beyond 12-14 weeks gestation, D-dimer testing should be abandoned in favor of objective imaging.

Special Considerations: Preeclampsia, HELLP, and Pregnancy Complications

Pregnancy complications further elevate D-dimer beyond gestational norms:

Preeclampsia: 2-5× additional elevation due to endothelial dysfunction⁶⁴
HELLP syndrome: Consumptive coagulopathy drives extreme elevations⁶⁵
Placental abruption: Massive release of tissue factor⁶⁶
Intrauterine fetal demise: Ongoing fibrinolysis of placental tissue⁶⁷
Postpartum hemorrhage: Consumption and replenishment cycles⁶⁸

Radiation Concerns and Diagnostic Strategy

The reluctance to perform CTPA in pregnancy due to radiation concerns has driven inappropriate D-dimer use. However, the fetal radiation dose from CTPA is minimal (0.003-0.013 mGy), well below teratogenic thresholds, while the maternal breast dose can be reduced by 30-50% with bismuth shielding.⁶⁹

Oyster #3: The risk of missing PE in pregnancy (maternal mortality ~30% if untreated) far exceeds any theoretical radiation risk from diagnostic imaging (fetal cancer risk increase <0.01%).⁷⁰ Using D-dimer to "avoid" imaging in pregnant women is false reassurance that may prove fatal.

Contemporary Guidelines for VTE Diagnosis in Pregnancy

The 2018 European Society of Cardiology (ESC) guidelines recommend:

D-dimer has no role in excluding PE in pregnancy beyond the first trimester⁷¹
Proceed directly to objective testing (compression ultrasonography for suspected DVT, CTPA or V/Q scan for suspected PE)⁷²
Use clinical prediction rules (LEFt rule: Leg symptoms, Edema, First trimester) to guide imaging, not D-dimer⁷³

The American College of Chest Physicians (CHEST) guidelines similarly state that D-dimer should not be used to exclude VTE in pregnancy beyond the first trimester.⁷⁴

Practical Approach in Pregnant and Postpartum Women

When D-dimer may have limited utility:

First trimester (<12 weeks) with low pretest probability
Threshold of 750-1,000 ng/mL (higher than non-pregnant)
Only if negative result will definitively exclude VTE without imaging

When to abandon D-dimer entirely:

Second or third trimester
Any postpartum patient (0-12 weeks)
Pregnancy complications (preeclampsia, HELLP, abruption)
Previous VTE history
Known thrombophilia

Recommended diagnostic pathway:

Suspected DVT: Bilateral lower extremity CUS (no radiation, highly sensitive for proximal DVT)⁷⁵
Suspected PE with positive CUS: Treat for PE without further imaging⁷⁶
Suspected PE with negative CUS: Proceed to CTPA (preferred) or V/Q scan (alternative)⁷⁷
Negative CTPA/V/Q with high clinical suspicion: Consider MR angiography or serial CUS⁷⁸

Hack #3: *For pregnant women with suspected PE, start with bilateral CUS. If positive for DVT (present in 30-40% of pregnancy-associated PE), you've diagnosed VTE and avoided any radiation. If negative, you've localized the diagnostic question and can proceed confidently to CTPA knowing the yield is higher.*⁷⁹

Why Context Matters More Than Numbers: The Pretest Probability Paradigm

The Bayesian Principle

The utility of any diagnostic test depends fundamentally on pretest probability. D-dimer's high sensitivity and negative predictive value make it excellent for excluding disease in low-probability populations but useless in high-probability scenarios.⁸⁰

Bayes' Theorem Applied:

Post-test probability = (Pretest probability × Sensitivity) / [(Pretest probability × Sensitivity) + (1 - Pretest probability) × (1 - Specificity)]

When pretest probability is high (as in ICU patients, postoperative patients, or pregnant women), even a negative D-dimer fails to reduce post-test probability below the threshold for safe exclusion (typically <2%).⁸¹

The Specificity Trap

In populations where 80-95% of individuals have elevated D-dimer regardless of VTE status, the test's specificity approaches zero. This creates several problems:

False reassurance: Clinicians may be inappropriately reassured by a "mildly elevated" D-dimer (<1,000 ng/mL) when VTE is present⁸²
Threshold confusion: Attempting to use higher thresholds (age-adjusted, trimester-adjusted) has not conclusively improved performance⁸³
Overimaging: Elevated D-dimer prompts unnecessary imaging in low-probability patients
Cognitive burden: Clinicians must remember context-specific thresholds, leading to errors⁸⁴

Pearl #4: The question is not "Is the D-dimer elevated?" but rather "Does this D-dimer result change my management?" In ICU, postoperative, and pregnant patients, the answer is almost always "no."

Clinical Gestalt vs. Laboratory Values

Expert clinicians integrate multiple data points—symptoms, signs, risk factors, alternative diagnoses—to generate pretest probability. D-dimer is only useful when it can meaningfully modify this probability.⁸⁵

Validated clinical prediction rules:

Wells' score for DVT/PE: Not validated in ICU or immediate postoperative patients⁸⁶
Geneva score: Similarly limited in hospitalized patients⁸⁷
PERC rule (Pulmonary Embolism Rule-out Criteria): Excludes critical illness, recent surgery, and pregnancy as criteria⁸⁸
LEFt rule (pregnancy): Incorporates gestational age and leg symptoms⁸⁹

The key insight is that these rules were designed for outpatient or emergency department populations, not for the contexts discussed in this review.

Oyster #4: Attempting to apply outpatient-derived clinical prediction rules and D-dimer thresholds to ICU, postoperative, or pregnant patients is a category error—you're using a tool in a population where it was never validated and where biological plausibility suggests it cannot work.

Age-Adjusted D-dimer: A Failed Solution

The Rationale

Recognizing that D-dimer increases with age (approximately 10 ng/mL per year after age 50), age-adjusted thresholds were proposed: D-dimer threshold = Age × 10 ng/mL for patients >50 years.⁹⁰ This adjustment improved specificity from 34% to 46% in the ADJUST-PE study, allowing exclusion of PE without imaging in an additional 12% of patients.⁹¹

Why It Doesn't Solve the Problem

While age-adjustment helps in ambulatory elderly patients, it fails in the contexts discussed here:

Magnitude mismatch: Age increases D-dimer by hundreds of ng/mL; critical illness, surgery, and pregnancy increase it by thousands⁹²
No validation: Age-adjusted thresholds have not been prospectively validated in ICU, postoperative, or pregnant populations⁹³
False security: Using higher thresholds may miss VTE in elderly ICU patients where baseline is already extremely elevated⁹⁴

Hack #4: Age-adjusted D-dimer is a reasonable strategy for elderly outpatients in the emergency department but offers no advantage in ICU, postoperative, or pregnant patients where other factors overwhelm age-related elevations.

Economic and Stewardship Considerations

The Cost of Unnecessary Testing

D-dimer is inexpensive ($10-30 per test), but the downstream consequences of inappropriate testing are substantial:

Unnecessary imaging: CTPA costs $1,000-2,500; bilateral lower extremity venous duplex $300-600⁹⁵
Incidental findings: 20-40% of CTAs reveal incidental findings requiring follow-up⁹⁶
Radiation exposure: CTPA delivers 10-20 mSv, equivalent to 2-3 years of background radiation⁹⁷
Contrast complications: Contrast-induced nephropathy (1-2% in high-risk patients), allergic reactions⁹⁸
False-positive diagnoses: Subsegmental PE detection on CTPA has uncertain clinical significance⁹⁹

A retrospective analysis found that D-dimer testing in hospitalized patients led to CTPA in 42% of cases, with only 8% positive for PE—implying 34% underwent unnecessary imaging.¹⁰⁰

Pearl #5: Diagnostic stewardship means not ordering tests that won't change management or that predictably generate false positives. Reflexive D-dimer ordering in ICU, postoperative, or pregnant patients represents low-value care.

Choosing Wisely Recommendations

The Society of Hospital Medicine's Choosing Wisely campaign specifically recommends:

"Don't order D-dimer to rule out VTE in hospitalized patients without considering pretest probability"¹⁰¹
Implicit in this is avoiding D-dimer in contexts where pretest probability cannot be reliably estimated or where baseline elevations are expected

Alternative Diagnostic Approaches

Imaging-First Strategies

For the populations discussed, proceeding directly to objective testing is often more efficient:

Advantages:

Definitive diagnosis: CTPA and CUS directly visualize thrombus
Alternative diagnoses: Imaging may reveal pneumonia, heart failure, musculoskeletal injury, etc.
Avoids false reassurance: No risk of being misled by inappropriately interpreted D-dimer
Time-efficient: Eliminates a testing step

Disadvantages:

Radiation (CTPA): Significant but often justified given high pretest probability
Contrast exposure: Risk of nephropathy and allergy
Cost: Higher immediate cost but may be offset by avoiding false-positive workups
Availability: Not all centers have 24/7 access to CUS or CTPA

Hack #5: *For ICU patients with suspected PE, consider bedside compression ultrasonography first. If positive for DVT, you've established VTE without moving an unstable patient. If negative but suspicion remains high, echocardiography showing RV strain may support PE diagnosis and guide therapy pending definitive imaging.*¹⁰²

Risk Stratification Without D-dimer

Alternative biomarkers may have utility in specific contexts:

Troponin and BNP/NT-proBNP: Prognostic in PE (identify high-risk patients) but not diagnostic¹⁰³ Fibrinogen: May help distinguish consumptive coagulopathy from isolated VTE¹⁰⁴ Soluble P-selectin: Investigational marker of platelet activation¹⁰⁵ Thrombin generation assays: Research tools not clinically available¹⁰⁶

None of these have replaced D-dimer; rather, the point is that in high-risk populations, clinical assessment and imaging remain the gold standards.

Clinical Pearls and Oysters: Summary

Pearls

In ICU patients, an elevated D-dimer is the rule, not the exception—it cannot discriminate VTE from critical illness
The more invasive the surgery, the less useful D-dimer becomes; for major surgery, wait 2-4 weeks before considering D-dimer
D-dimer maintains reasonable NPV only in the first trimester of pregnancy; beyond 12-14 weeks, abandon D-dimer testing
Always ask: "Does this D-dimer result change my management?" If the answer is "no," don't order it
Diagnostic stewardship means not ordering predictably unhelpful tests; reflexive D-dimer in ICU/postoperative/pregnant patients is low-value care

Oysters

COVID-19 ICU patients had near-universal D-dimer elevation, forcing abandonment of D-dimer-based algorithms
Postoperative patients are paradoxically at high VTE risk yet have universally elevated D-dimer—attempting "rule-out" testing increases imaging and costs without benefit
The risk of missing PE in pregnancy far exceeds radiation risk from CTPA; using D-dimer to "avoid" imaging creates false reassurance that may prove fatal
Applying outpatient-derived prediction rules and D-dimer thresholds to ICU/postoperative/pregnant patients is a category error—the tool doesn't work in populations where it was never validated

Hacks

ICU VTE suspicion: Focus on clinical gestalt—sudden desaturation, unexplained tachycardia, or unilateral leg swelling warrants imaging regardless of D-dimer
Postoperative VTE suspicion: Use "two-level Wells' score"—low probability (<2 points) = watchful waiting; moderate-to-high (≥2 points) = direct imaging without D-dimer
Pregnant VTE suspicion: Start with bilateral CUS (no radiation); if positive for DVT, you've diagnosed VTE; if negative, proceed confidently to CTPA
Age-adjusted D-dimer works in elderly outpatients but offers no advantage when other factors (critical illness, surgery, pregnancy) overwhelm age-related elevations
Unstable ICU patients with PE suspicion: Bedside CUS + echocardiography can establish diagnosis and guide therapy without moving the patient for CTPA**

Practical Algorithm: When to Order (and Not Order) D-dimer

Patient with suspected VTE
         |
         ↓
Is patient in ICU, postoperative (<2-4 wks), or pregnant (>12 wks)?
         |
    YES  |  NO
         |        ↓
         |    Use validated clinical prediction rule
         |    (Wells, Geneva, PERC)
         |        |
         ↓        ↓
    DO NOT    Low probability?
    ORDER         |
    D-DIMER   YES | NO
         |        |    ↓
         |        |  Direct imaging
         |        ↓  (CUS or CTPA)
         |    Order D-dimer
         |        |
         ↓    Negative? → VTE excluded
    Assess    Positive? → Imaging
    clinical
    probability
         |
    Low/Moderate? → Watchful waiting or imaging
    High? → Direct imaging (CUS for DVT, CTPA for PE)

Conclusions and Future Directions

D-dimer remains an invaluable tool for excluding VTE in appropriately selected ambulatory patients with low pretest probability. However, its indiscriminate use in ICU patients, postoperative individuals, and pregnant women generates more confusion than diagnostic clarity. The test's poor specificity in these contexts—often <10-20%—renders it clinically useless and potentially harmful if negative results provide false reassurance.

The fundamental lesson is that context matters more than numbers. A D-dimer of 1,500 ng/mL has vastly different implications for a healthy 30-year-old with acute dyspnea versus a post-cardiac surgery patient in the ICU versus a 36-week pregnant woman with leg swelling. Interpreting laboratory values requires understanding the physiological milieu in which they were measured.

For critical care practitioners, the path forward is clear:

Abandon reflexive D-dimer ordering in ICU, postoperative, and pregnant patients
Rely on clinical assessment and validated prediction rules adapted to the specific population
Lower threshold for objective imaging when VTE is suspected
Embrace diagnostic stewardship—not ordering tests that won't change management

Future research should focus on discovering alternative biomarkers with better specificity in high-risk populations or developing context-specific algorithms that appropriately weight D-dimer in combination with other variables. Until then, seasoned clinical judgment remains superior to biochemical testing in these challenging diagnostic scenarios.

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Epilogue: A Call for Diagnostic Humility

As critical care practitioners navigate increasingly complex diagnostic landscapes, the temptation to rely on laboratory "certainty" grows stronger. Yet D-dimer's story reminds us that no test exists in a vacuum—each must be interpreted within its biological and clinical context.

The seasoned intensivist knows that the numbers on a laboratory report are less important than the patient lying before them: their clinical trajectory, physiological reserve, and the narrative arc of their illness. When D-dimer is useless—and it often is in the ICU, postoperatively, and in pregnancy—we must return to fundamentals: careful history-taking, meticulous physical examination, sound clinical reasoning, and judicious use of definitive imaging.

In an era of algorithm-driven medicine, this review advocates for diagnostic humility and stewardship. Not every test needs to be ordered; not every elevated value requires action. Sometimes, the most sophisticated medical decision is knowing which test not to order.

Final Pearl: The art of medicine lies not in ordering more tests but in ordering the right tests for the right patient at the right time. In ICU, postoperative, and pregnant patients with suspected VTE, D-dimer is rarely the right test.

Disclosure Statement: The authors report no conflicts of interest.

Funding: No external funding was received for this work.

Author Affiliations: Department of Critical Care Medicine and Pulmonary Sciences Division of Thrombosis and Hemostasis [Academic Medical Center]

Correspondence: [Contact details would appear here in actual publication]

Word Count: 9,847 words (excluding references)

Wednesday, October 1, 2025