Inherited thrombophilias
Reading File
Finding Sources
Finding Sources
Searching PubMed
"Thrombophilia"[MeSH Terms]
Searching the Web
ASH guidelines thrombophilia testing inherited thrombophilia 2023
Reading File
Reading File
Reading Web Page
https://ashpublications.org/bloodadvances/article/7/22/7101/…
Inherited thrombophilias
Inherited thrombophilia refers to genetic conditions that increase the tendency to develop venous thromboembolism (VTE), especially deep-vein thrombosis (DVT) and pulmonary embolism (PE). Events often occur in young adulthood, may cluster in families, and commonly require an additional trigger such as surgery, immobilization, pregnancy, estrogen exposure, or illness. - Goldman-Cecil Medicine, p. 1804
Main disorders
| Disorder | Mechanism | Relative clinical risk |
|---|---|---|
| Factor V Leiden (FVL) | Factor V is resistant to inactivation by activated protein C | Most common inherited thrombophilia in people of European ancestry; modest risk when heterozygous, much higher when homozygous |
| Prothrombin G20210A mutation | Increased prothrombin production, leading to greater thrombin generation | Common, generally lower risk than natural-anticoagulant deficiencies |
| Antithrombin deficiency | Reduced inhibition of thrombin and factor Xa | Uncommon but high-risk |
| Protein C deficiency | Reduced degradation of activated factors Va and VIIIa | Uncommon but high-risk |
| Protein S deficiency | Reduced protein C cofactor activity | Uncommon but high-risk |
Factor V Leiden and prothrombin G20210A are considered lower-risk inherited thrombophilias, while antithrombin, protein C, and protein S deficiencies carry higher thrombotic risk. - Goldman-Cecil Medicine, p. 1804
Clinical clues
Consider an inherited cause when there is:
- VTE before age 40-50
- Recurrent VTE
- Strong family history of unprovoked VTE
- Thrombosis at an unusual venous site, such as cerebral or splanchnic veins
- VTE with only a minor provoking factor
- Warfarin-induced skin necrosis or neonatal purpura fulminans, which point particularly toward severe protein C or protein S deficiency. - Goldman-Cecil Medicine, p. 1804
These disorders are mainly associated with venous, rather than arterial, thrombosis.
Testing
A standard inherited-thrombophilia panel includes:
- Factor V Leiden mutation
- Prothrombin G20210A mutation
- Antithrombin activity
- Protein C activity
- Protein S testing
Testing is generally not recommended after VTE clearly provoked by major surgery, trauma, or prolonged immobilization, unless the result would alter management. - Tietz Textbook of Laboratory Medicine, inherited thrombophilia section
Important testing limitations:
- Do not measure protein C, protein S, or antithrombin during an acute clot or while results may be altered by anticoagulants.
- Warfarin lowers protein C and protein S.
- Heparin and acute thrombosis can affect antithrombin testing.
- Pregnancy and estrogen exposure can lower protein S.
- Genetic FVL and prothrombin testing are not affected by anticoagulant therapy.
- Antiphospholipid syndrome is acquired, not inherited, but may need separate testing in appropriate cases.
The 2023 ASH testing guideline recommends against indiscriminate testing, including screening the general population before combined oral contraceptive use. It supports selective testing when a result could change prophylaxis, hormone decisions, or anticoagulation duration.
Management principles
- Treat an acute DVT/PE with standard anticoagulation.
- The presence of an inherited thrombophilia alone does not automatically mean lifelong anticoagulation.
- Decisions on extended anticoagulation depend more on whether the event was unprovoked or recurrent, bleeding risk, clot site, and patient preferences.
- Use preventive anticoagulation in selected high-risk settings, such as major surgery, prolonged immobilization, and sometimes pregnancy or postpartum.
- Avoid or carefully assess estrogen-containing contraception or hormone therapy in individuals with prior VTE or high-risk thrombophilia.
- Test relatives selectively, mainly when there is a known familial antithrombin, protein C, or protein S deficiency and the result would affect prevention decisions.
A recent systematic review and meta-analysis on VTE risk in hereditary thrombophilia is available as PMID 39167180.
Wells score in PE
Reading File
Finding Sources
Searching PubMed
"Pulmonary Embolism"[MeSH Terms] AND Wells
Searching the Web
Wells score pulmonary embolism criteria points guideline
Wells score for suspected pulmonary embolism
| Clinical feature | Points |
|---|---|
| Clinical signs of DVT: leg swelling and pain on palpation of deep veins | 3 |
| PE is more likely than an alternative diagnosis | 3 |
| Heart rate >100/min | 1.5 |
| Immobilization for >3 days or surgery in past 4 weeks | 1.5 |
| Previous DVT or PE | 1.5 |
| Hemoptysis | 1 |
| Malignancy: active treatment, treated within 6 months, or palliative | 1 |
Two-level interpretation
- PE likely: >4
- PE unlikely: ≤4
For the usual diagnostic pathway, PE-unlikely patients undergo D-dimer testing, while PE-likely patients generally need prompt imaging, usually CTPA if appropriate. See the NICE PE pathway.
Three-level interpretation
- Low probability: <2
- Moderate probability: 2-6
- High probability: >6
Memory aid: DVT signs, Diagnosis more likely, Tachycardia, Immobilization/surgery, Previous VTE, Hemoptysis, Malignancy.
The score estimates pretest probability only. It does not by itself rule in or rule out PE.
Pulmonary embolism severity index
Reading File
Finding Sources
Searching PubMed
"Pulmonary Embolism"[MeSH Terms] AND "severity index"
Searching the Web
Pulmonary Embolism Severity Index PESI score points risk class guideline
Reading File
Reading Web Page
https://www.ncbi.nlm.nih.gov/books/NBK611959/table/fm.s1.t10
Pulmonary Embolism Severity Index (PESI)
PESI estimates 30-day mortality in patients with confirmed acute pulmonary embolism. It helps identify low-risk patients who may be suitable for early discharge or outpatient treatment after clinical assessment.
Original PESI score
| Variable | Points |
|---|---|
| Age | Age in years |
| Male sex | +10 |
| Cancer | +30 |
| Heart failure | +10 |
| Chronic lung disease | +10 |
| Pulse ≥110/min | +20 |
| Systolic BP <100 mmHg | +30 |
| Respiratory rate ≥30/min | +20 |
| Temperature <36°C | +20 |
| Altered mental status | +60 |
| Oxygen saturation <90% | +20 |
Cancer generally includes active cancer, cancer treated within the previous 6 months, or recurrent/metastatic disease.
PESI risk classes
| Class | Total score | Approximate 30-day mortality | Risk |
|---|---|---|---|
| I | ≤65 | ~1% | Very low |
| II | 66-85 | ~1-3% | Low |
| III | 86-105 | ~3-7% | Intermediate |
| IV | 106-125 | ~4-11% | High |
| V | >125 | ~10-25% | Very high |
- Classes I-II are conventionally considered low risk.
- Classes III-V require more cautious inpatient assessment and treatment planning.
- Hemodynamic instability, shock, or persistent hypotension overrides a low PESI score and indicates high-risk PE.
Simplified PESI (sPESI)
Assign 1 point each:
- Age >80 years
- History of cancer
- Chronic cardiopulmonary disease, such as heart failure or chronic lung disease
- Heart rate ≥110/min
- Systolic BP <100 mmHg
- Oxygen saturation <90%
| sPESI | Interpretation |
|---|---|
| 0 | Low risk |
| ≥1 | Higher risk |
PESI/sPESI are prognostic tools, not diagnostic scores. Unlike the Wells score, they should be applied after PE has been diagnosed or is strongly established, alongside blood pressure, right-ventricular function on echo/CT, and cardiac biomarkers. The score incorporates demographic factors, comorbidity, and cardiopulmonary findings. - Murray & Nadel's Textbook of Respiratory Medicine, risk stratification section
A current NIH-hosted PESI table provides the full scoring criteria.
This is a shared conversation. Sign in to Orris to start your own chat.