Deep vein thrombosis resident survival guide
Jump to navigation
Jump to search
| Deep vein thrombosis resident Survival Guide Microchapters |
|---|
| Overview |
| Causes |
| FIRE |
| Diagnosis |
| Treatment |
| Do's |
| Don'ts |
For deep venous thrombosis prevention resident survival guide click here.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vidit Bhargava, M.B.B.S [2]; Rim Halaby, M.D. [3]
Overview
Deep vein thrombosis (DVT) is the formation of a blood clot, also known as thrombus, in a deep vein. The initial diagnostic test for a suspected DVT is either D-dimer or proximal ultrasound depending on the pretest probability of the disease. The treatment of proximal DVT or isolated distal DVT that are selected for anticoagulation therapy includes parental anticoagulation therapy for at least 5 days and until the INR is equal or more than 2 for more than 24 hours, in addition to long term treatment with oral anticoagulation therapy.
Causes
Life Threatening Causes
Deep venous thrombosis can be a life-threatening condition if thromboembolism and subsequent pulmonary embolism occur, and it must be treated as such irrespective of the underlying cause.
Common Causes
FIRE: Focused Initial Rapid Evaluation
A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention.
Complete Diagnostic Approach
Click here for a complete diagnostic approach for DVT
Assessment of the Pre-Test Probability of DVT
Calculation of Wells Score for DVT
| Variables | Score[1] |
| Active cancer with either palliative therapy or treatment that is either ongoing or within the prior 6 months | 1 |
| Patient was recently bedridden for at least 3 days OR Major surgery in the prior 12 weeks necessitating general or regional anesthesia |
1 |
| Recent plaster immobilization, paresis or paralysis of the lower extremities | 1 |
| Tenderness that is localized is the distribution of the deep veins | 1 |
| Leg is entirely swollen | 1 |
| Calf is swollen for 3 cm or move compared to the other calf | 1 |
| Pitting edema in the symptomatic leg | 1 |
| Presence of collateral superficial veins | 1 |
| Previous DVT | 1 |
| There is an alternative diagnosis as likely as DVT | -2 |
Interpretation of Wells Score for DVT
| Score | Pretest probability[1][2] |
| ≥3 | High |
| 1 or 2 | Moderate |
| 0 or less | Low |
Modified Well Score
Complete Diagnostic Approach for First Episode of Suspected Lower Extremity DVT
Low Pretest Probability
Shown below are the different diagnostic approaches to the diagnosis of DVT depending in case of low pre-test probability of the disease.[4]
| The patient has a low pre-test probability for DVT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with one of the following: Highly or moderately sensitive D-dimer test (1st line) Proximal US (2nd line) Whole leg US (less preferred) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| D-dimer (1st line) | Proximal US (2nd line) | Whole leg US (less preferred) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with either: Proximal US (1st line) OR Whole leg US (less preferred) | What is the location of the DVT? | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Proximal US (1st line) | Whole leg US (less preferred) | DVT is excluded | Treat DVT | DVT is excluded | Proximal DVT | Isolated distal DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | Treat DVT | Perform serial US (1st line) OR Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| What is the location of the DVT? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Treat DVT | DVT is excluded | Proximal DVT | Isolated distal DVT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Treat DVT | Perform serial US (1st line) OR Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Moderate Pretest Probability
| The patient has a moderate pre-test probability of DVT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with one of the following: D-dimer test | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Highly sensitive D-dimer test | Proximal US | Whole leg US | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with either: Proximal US OR Whole leg US | Repeat proximal US OR Moderately/highly sensitive D-dimer | Treat DVT | DVT is excluded | Where is the location of the DVT? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Proximal US | Whole leg US | Repeat proximal US within 1 week | Moderately/highly sensitive D-dimer | Proximal DVT | Isolated distal DVT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | Negative | Positive | Negative | Positive | Treat DVT | Perform serial US (1st line) OR Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Repeat proximal US within 1 week | Treat DVT | DVT is excluded | What is the location of the DVT? | DVT is excluded | Treat DVT | DVT is excluded | Repeat proximal US within 1 week | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Proximal DVT | Isolated distal DVT | Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Treat DVT | Treat DVT | Perform serial US (1st line) OR Treat DVT | Treat DVT | Perform serial US (1st line) OR Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
High Pretest Probability
| The patient has a high pre-test probability for DVT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with either: Proximal US OR Whole leg US | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proximal US | Whole leg US | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with ONE of the following: Repeat proximal US Highly sensitive D-dimer Whole leg US Venography (less preferred) | Treat DVT | DVT is excluded | What is the location of the DVT? | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proximal | Distal | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Treat DVT | Perform serial US (1st line) OR Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Repeat proximal US within 1 week | Highly sensitive D-dimer | Whole leg US | Venography | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | Negative | Positive | Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Treat DVT | DVT is excluded | DVT is excluded | Where is the location of the DVT? | DVT is excluded | Treat DVT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Repeat proximal US within 1 week | Whole leg US | Venography (less preferred) | Proximal | Distal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | Negative | Positive | Treat DVT | Perform serial US (1st line) OR Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Treat DVT | DVT is excluded | Where is the location of the DVT? | DVT is excluded | Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proximal | Distal | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Treat DVT | Perform serial US (1st line) OR Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Risk Stratification Not Performed
| Risk stratification was not performed | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with ONE of the following: Proximal US Whole leg US Highly/moderately sensitive D-dimer (less preferred) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proximal US | Whole leg US | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Treat DVT | DVT is excluded | What is the location of the DVT? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with ONE of the following: Highly/moderately sensitive D-dimer (most preferred) Repeat proximal US within 1 week Whole leg US Venography (less preferred) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Highly/moderately sensitive D-dimer (most preferred) | Repeat proximal US within 1 week | Whole leg US | Venography (less preferred) | Proximal | Distal | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | Negative | Positive | Treat DVT | Serial US (1st line) OR Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Repeat proximal US within 1 week OR Venography | DVT is excluded | Treat DVT | DVT is excluded | Treat DVT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Complete Diagnostic Approach for Suspected Recurrent Lower Extremity DVT
Shown below is the diagnostic approach to suspected recurrent DVT. The recommended initial test is either proximal ultrasound (US) or highly sensitive D-dimer tetsing rather than venography, CT venography or MR imagining. Initial D-dimer testing is recommended over proximal US in case there is no prior ultrasound for comparison. Note the following definitions:
- Negative US:
- Normal US, or
- Increase in residual diameter of less than 2 mman, or
- Area of prior noncompressibility with a decreased or stable residual diameter
- Nondiagnostic US:
- Ultrasound that is technically limited, or
- Area of prior noncompressibility with an increment in residual venous diameter of < 4 mm yet ≥ 2 mm, or
- Area of prior noncompressibility in the absence of a previous measurement of the residual diameter
- Positive US:
- New noncompressible segment, or
- Area of prior noncompressibility with an increment in residual venous diameter of ≥ 4 mm[4]
| The patient has recurrent DVT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with one of the following: Proximal US Highly sensitive D-dimer Venography (less preferred) CT venography (less preferred) MR imaging (less preferred) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proximal US | Highly sensitive D-dimer | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Non diagnostic | Positive | Negative | Positive | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with one of the following: Highly/moderately sensitive D-dimer Repeat proximal US within 1 week Venography (less preferred) No further testing (less preferred) | Click here for the diagnostic approach in case of non diagnostic US | Treat OR Venography (less preferred) | DVT is excluded | Proximal US | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Highly/moderately sensitive D-dimer | Repeat US | Venography | No further testing | Negative | Non diagnostic | Positive | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | Negative | Positive | Repeat proximal US within 1 week OR Venography (less preferred) OR No further testing (less preferred) | Click here for the diagnostic approach in case of non diagnostic US | Treat OR Venography (less preferred) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Repeat proximal US within 1 week OR Venography (less preferred) OR No further testing (less preferred) | DVT is excluded | Treat OR Venography (less preferred) | DVT is excluded | Treat DVT | If proximal US is repeated, what is the result? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| If proximal US is repeated, what is the result? | Negative | Positive | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | DVT is excluded | Treat OR Venography (less preferred) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Treat OR Venography (less preferred) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diagnostic Approach for Non Diagnostic Ultrasound
| The patient has a non diagnostic proximal US | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Are prior US results available? | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Yes | No | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Proceed with ONE of the following: Venography (most preferred) Repeat proximal US within 1 week Highly/moderately sensitive D-dimer Treat DVT (less preferred) | Proceed with ONE of the following: Venography (most preferred) Highly sensitive D-dimer Repeat proximal US (less preferred) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Venography (most preferred) | Repeat proximal US within 1 week | Highly/moderately sensitive D-dimer | Treat DVT (less preferred) | Venography (most preferred) | Highly sensitive D-dimer | Repeat proximal US within 1 week (less preferred) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | Negative | Positive | Negative | Positive | Negative | Positive | Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Treat DVT | DVT is excluded | Treat DVT OR Venography (less preferred) | DVT is excluded | Repeat proximal US within 1 week | DVT is excluded | Treat DVT | DVT is excluded | Venography OR Treat DVT (less preferred) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DVT is excluded | Venography (less preferred) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Diagnostic Approach for Venography
| What is the result of the venography? | |||||||||||||||||
| Negative | Positive | ||||||||||||||||
| DVT is excluded | Treat DVT | ||||||||||||||||
Complete Diagnostic Approach for Suspected Upper Extremity DVT
Initial Treatment
Shown below is an algorithm depicting the initial choice of treatment among patients with DVT. Note that the treatment of DVT with parental anticoagulation should be initiated in case of intermediate or high suspicion of suspected DVT even before the diagnostic confirmatory tests are complete. The choice of parental anticoagulation include: low molecular weight heparin (LMWH), fondaparinux, IV unfractionated heparin (UFH) and SC-UFH; however, the administration of LMWH (once daily rather than twice) and fondaparinux is recommended over IV-UFH and SCUFH. Parental anticoagulation therapy should be administered for at least 5 days and until the INR is equal or more than 2 for more than 24 hours.[5]
| Is the DVT proximal or distal? | |||||||||||||||||||||||||||||||||||
| Proximal DVT | Isolated distal DVT | ||||||||||||||||||||||||||||||||||
| Are there any contraindications to anticoagulation? | Does the patient have severe symptoms OR risk factors for the extension of the thrombus? | ||||||||||||||||||||||||||||||||||
| No | Yes | Yes | No | ||||||||||||||||||||||||||||||||
| Begin initial anticoagulation treatment Begin oral anticoagulant as an overlap therapy for the long term treatment | IVC filter Begin conventional course of anticoagulation if the risk of bleeding subsides | Begin initial anticoagulation treatment (if there are no contraindications) Begin oral anticoagulant as an overlap therapy for the long term treatment | Perform serial imaging for 2 weeks | ||||||||||||||||||||||||||||||||
| Does the repeated US demonstrate any extension of the thrombus (with or without extension to the proximal veins) | |||||||||||||||||||||||||||||||||||
| Yes | No | ||||||||||||||||||||||||||||||||||
| Begin initial anticoagulation treatment (if there are no contraindications) Begin oral anticoagulant as an overlap therapy for the long term treatment | No anticoagulation therapy | ||||||||||||||||||||||||||||||||||
Initial Anticoagulation Choices
❑ SC low molecular weight heparin (1st line)
- ❑ Enoxaparin 1.0 mg/kg every 12 hours OR 1.5 mg/kg once daily
- ❑ Tinzaparin 175 U/kg once daily
❑ SC fondaparinux (1st line)
- ❑ 5 mg once daily (if body weight <50 kg)
- ❑ 7.5 mg once daily (if body weight <50-100 kg)
- ❑ 10 mg once daily (if body weight >100 kg)
- ❑ 80 U/kg as bolus, followed by 18 U/kg/h, OR
- ❑ 70 U/kg as bolus, followed by 15 U/kg/h for stroke or cardiac patients[6]
- ❑ Adjust the dosages according to the aPTT
- ❑ 333 U/kg as bolus, followed by 250 U/kg[6]
Long Term Treatment
Shown below is the long term treatment for DVT. Note that not all patients with isolated distal DVT are started on anticoagulation, only those who are started require long term therapy with anticoagulation. Patients who are planned to receive long term therapy with anticoagulation should be assessed regularly for the risks vs benefits of anticoagulation therapy.[7]
| Is the DVT provoked or unprovoked? | |||||||||||||||||||||||||||||||||||||||||||
| Provoked | Unprovoked | ||||||||||||||||||||||||||||||||||||||||||
| What is the predisposing factor? | Is this the first or second episode? | ||||||||||||||||||||||||||||||||||||||||||
| Surgical OR Transient non surgical predisposing factor | Cancer | First episode | Second episode | ||||||||||||||||||||||||||||||||||||||||
| Therapy for 3 months | Extended therapy or until cancer is cured | Is the DVT proximal or distal? | What is the risk of bleeding? | ||||||||||||||||||||||||||||||||||||||||
| Proximal DVT | Isolated distal DVT | Low or moderate risk of bleeding | High risk of bleeding | ||||||||||||||||||||||||||||||||||||||||
| What is the risk of bleeding? | Therapy for 3 months (irrespective of the risk of bleeding) | Extended therapy | Therapy for 3 months | ||||||||||||||||||||||||||||||||||||||||
| Low or moderate | High | ||||||||||||||||||||||||||||||||||||||||||
| Extended therapy | Therapy for 3 months | ||||||||||||||||||||||||||||||||||||||||||
Assessment of Risk of Bleeding
The risk factors of bleeding with anticoagulation therapy are:[5]
- Age > 75 years
- Alcohol abuse
- Anemia
- Antiplatelet therapy
- Cancer
- Comorbidity and reduced functional capacity
- Diabetes
- Frequent falls
- Liver failure
- Metastatic cancer
- Poor anticoagulant control
- Previous bleeding
- Prior stroke
- Recent surgery
- Renal failure
- Thrombocytopenia
Shown below is a table summarizing the risk of bleed based on the number of risk factors. Note that, although the presence of one risk factor signify moderate risk of bleeding, if the single risk factor is severe (such as severe thrombocytopenia or recent major surgery) then the patient is at high risk of bleeding despite the presence of a single risk factor.
| Risk of bleeding | Number of risk factors[5] |
| Low Risk | 0 |
| Moderate Risk | 1 |
| High Risk | ≥2 |
Do's
- Among patients with low pretest probability of DVT, the preferred initial test is D-dimer. However, among those patients who have comorbidities known to increase D-dimer concentration in the absence of a venous thromboembolism, ultrasound is preferred as an initial test.
- Patients with low pretest probability of DVT among whom an ultrasound can not be practically performed, for example due to the presence of a leg cast, or those who have non-diagnostic ultrasound results, CT scan venography, magnetic resonance venography, or magnetic resonance direct thrombus imaging can be considered instead of venography.
- Among patients with moderate pretest probability of DVT, whole leg US might be preferred over proximal US in case there is severe symptoms consistent with calf pain or in case the patients have difficulty returning for the serial US tests. Patients among whom an ultrasound can not be practically performed, for example due to the presence of a leg cast, or those who have non-diagnostic ultrasound results, CT scan venography, magnetic resonance venography, or magnetic resonance direct thrombus imaging can be considered instead of venography.
- Among patients who underwent whole leg ultrasound that revealed isolated distal DVT, consider serial US testing over trearment to check for extension of the thrombus. However, if the pretest probability is high or there is elevated risk of extension or severe symptoms, consider treatment over serial US testing.
- Consider home treatment for DVT among patients with adequate home circumstances, such as availability of family and friends support, phone and transportation to the hospital in case of deterioration.
- Encourage early ambulation in patients with DVT.
- Treat incidentally found asymptomatic DVT just like symptomatic DVT.
- For the long term management of DVT patient:
- Educate the patient about the long term therapy with anticoagulation
- Recommend comopression stockings for 2 years to prevent post-thrombotic syndrome.
- Among patients started on heparin, if the risk of heparin induced thrombocytopenia is more than 1%, monitor platelet count every 2 to 3 days from the 4th until the 14th day of treatment or until the discontinuation of heparin.
- Screen for thrombophilia if this is a first episode of VTE in a patient less than 50 years of age.
Don'ts
References
- ↑ 1.0 1.1 Wells PS, Owen C, Doucette S, Fergusson D, Tran H (2006). "Does this patient have deep vein thrombosis?". JAMA. 295 (2): 199–207. doi:10.1001/jama.295.2.199. PMID 16403932. Review in: Evid Based Med. 2006 Aug;11(4):119 Review in: ACP J Club. 2006 Jul-Aug;145(1):24
- ↑ Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Gray L; et al. (1997). "Value of assessment of pretest probability of deep-vein thrombosis in clinical management". Lancet. 350 (9094): 1795–8. doi:10.1016/S0140-6736(97)08140-3. PMID 9428249.
- ↑ Wells PS, Anderson DR, Rodger M, Forgie M, Kearon C, Dreyer J; et al. (2003). "Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis". N Engl J Med. 349 (13): 1227–35. doi:10.1056/NEJMoa023153. PMID 14507948. Review in: ACP J Club. 2004 May-Jun;140(3):67
- ↑ 4.0 4.1 Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD; et al. (2012). "Diagnosis of DVT: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e351S–418S. doi:10.1378/chest.11-2299. PMC 3278048. PMID 22315267.
- ↑ 5.0 5.1 5.2 {{http://www.wikidoc.org//index.php/Template:Cite_journal{cite journal| author=Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ et al.| title=Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e419S-94S | pmid=22315268 | doi=10.1378/chest.11-2301 | pmc=PMC3278049 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315268 }}
- ↑ 6.0 6.1 Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ; et al. (2012). "Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): e152S–84S. doi:10.1378/chest.11-2295. PMC 3278055. PMID 22315259.
- ↑ Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel (2012). "Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines". Chest. 141 (2 Suppl): 7S–47S. doi:10.1378/chest.1412S3. PMC 3278060. PMID 22315257.