Antithrombotic treatment of below knee deep venous thrombosis
Date First Published:
May 2, 2002
Last Updated:
September 20, 2005
Report by:
Kerstin Hogg, Clinical Research Fellow (Manchester Royal Infirmary)
Search checked by:
Andrew Ashton, Manchester Royal Infirmary
Three-Part Question:
In [a patient with a below knee venous thrombosis], is [warfarinisation necessary] to prevent [a pulmonary embolus]?
Clinical Scenario:
A 50 year old man attends the emergency department with a plethoric, swollen left calf. Ultrasound examination reveals a posterior tibial vein thrombosis. You are unsure what the risk of a pulmonary embolus is, or whether he should be anticoagulated.
Search Strategy:
Using MEDLINE OVID interphase 1966 – September week 1 2005
Search Details:
({DVT.mp or exp venous thrombosis or deep vein thrombosis.mp} AND {below knee.mp or calf.mp or popliteal.mp or exp popliteal vein or fibular.mp or peroneal.mp or posterior tibial.mp } AND {therapy.mp or exp therapeutics or treatment.mp or exp heparin or exp heparin, low-molecular-weight or heparin.mp or exp warfarin or warfarin.mp or exp coumarins or coumarin.mp }) limited to human and English language.
Outcome:
695 papers were found. 13 addressed the question. Some studies included other patients with PE or thigh DVTs – only the patients with calf thrombosis are described.
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Calf deep venous thrombosis. A wolf in sheep's clothing. Philbrick JT, Becker DM. 1988, USA | All studies of sufficient quality identified from literature search over years 1944 to 1986. | Literature review | Incidence PE | 6/163 patients receiving no anticoagulation (Strength of evidence weak). 9/208 patients receiving a range of anticoagulation (0/32 in only study with strong evidence, all other studies weak) | |
| Relationship between deep vein thrombosis in the calf and fatal pulmonary embolism. Giachino A. 1988, Canada | 152 patients who died in Ottawa hospitals over a 5 year period, with PE listed as the cause of death | Retrospective study | Source of thrombosis in fatal pulmonary emboli | 82 had no post mortem examination. 23 post mortems confirmed PE as the cause of death, and identified the source of the embolus. 3/23 post mortems revealed the calf veins as the source of the thrombi | No controlling of post mortem procedures – unclear if all legs veins thoroughly examined Only 23/152 considered to die from PE actually had a PM and had the source of the embolus confirmed |
| Lower extremity calf thrombosis: to treat or not to treat? Lohr JM, Kerr TM, Lutter KS et al. 1991, USA | 75 patients with ultrasound diagnosed calf thrombosis Treatment left to physician's discretion |
Prospective study with follow-up serial ultrasound examination | Thrombosis propagation | 15% propagated to involve the popliteal or larger veins. A further 17% propagated within the calf veins | Publication bias – all of these patients may have been included in the study by Pelligrini V et al. No information regarding the length of follow-up, or the effect of varying therapies |
| Embolic complications of calf thrombosis following total hip arthroplasty. Pellegrini VD Jr, Langhans MJ, Totterman S et al. 1993, USA | 25 patient with isolated calf DVT and 12 patients with superficial or muscular calf thrombosis, diagnosed by venography on post-operative screening of total-hip arthroplasty patients Only 12 calf DVTs and 1 superficial/muscular calf thrombosis were anticoagulated |
Prospective study following-up at 6, 12, 24 and 52 weeks | Incidence of PE | 4/13 untreated calf DVT patients were diagnosed with PE. 0/1 treated calf DVT patient and none of the superficial/muscular calf thrombosis developed PE | Two of the PEs were diagnosed on the strength of sudden collapse and cardiac arrest – no post mortem carried out |
| Incidence and fate in a randomised, controlled trial of anticoagulation versus no anticoagulation. Nielsen HK, Husted SE, Krusell LR et al. 1994, Denmark | 15 patients with venographically diagnosed calf DVTs | Prospective study | VQ scan result at presentation | 5/15 had positive VQ scans | No information regarding exact criteria for diagnosing PE from VQ scan alone – probable over-estimation of incidence VQ scans were performed at 10 and 60 days, however no information regarding the breakdown of subsequent PEs between proximal and isolated calf DVT groups |
| Calf vein thrombi are not a benign finding. Lohr JM, James KV, Deschmukh RM et al. 1995, USA | 192 patients with ultrasound diagnosed below knee DVTs, Treatment left to physicians discretion | Prospective study with serial ultrasound for 4 weeks | Thrombus propagation | 53/139 thrombi propagated | Publishing bias – the cohort appears to include all of the patients included in the previous Lohr study (see study in this table) Paper does not establish rate of PE |
| The value of duplex ultrasound in the follow-up of acute calf vein thrombosis. O'Shaughnessy AM, Fitzgerald DE. 1997, Ireland | 50 patients with ultrasound diagnosed DVTs, 43 treated with anticoagulation and 7 without | Prospective study, using repeat ultrasound at one week, one month, six months and one year | 'Outcome' of isolated calf thrombosis | 3 patients presented initially with a 'positive' VQ scan. One fatal PE within the first month | Venography not used to diagnose initial calf DVT Apparently, no attempts were made to actively seek the diagnosis of PE throughout the follow-up period No adequate description of the positive VQ scans 10 patients lost to follow-up at 6 months No account taken of the effect of treatment |
| Clinically important pulmonary emboli: does calf vein US alter outcomes? Gottlieb RH, Widjaja J, Mehra S et al. 1999, USA | 238 patients with ultrasound diagnosed below knee DVTs | Retrospective study | Incidence of diagnosed PE's | 2/56 patients not receiving anticoagulant therapy had PE | Patients were not identified using venography Retrospective study, therefore unable to detect silent PEs or those that did not present to medical services One PE diagnosed on strength of high probability VQ scan alone. No description of frequency of follow-up ultrasound scans Therapy at the discretion of physician No information regarding anticoagulant therapy for patient with extension to thigh DVT 28 patients were not followed for the full 6 months as they died |
| Incidence of extension into thigh DVT | 1/227 receiving anticoagulant therapy had documented extension to thigh DVT | ||||
| Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf Pinede L, Ninet J, Duhaut P et al, 2001, France | 105 patients with calf DVTs treated for 6 weeks with warfarin, 92 patients with calf DVTs treated for 12 weeks with warfarin | Prospective study | Incidence of PE | 1/197 (patient from 12 week warfarin group) had documented PE | Diagnosis did not always use venography No information regarding which symptoms would prompt investigations for PE Method's description implies that a VQ scan result of intermediate probability would diagnose PE – no information as to how this PE was diagnosed |
| Therapy of isolated calf muscle vein thrombosis with low-molecular-weight heparin. Schwarz T, Schmidt B, Beyer J et al. 2001, Germany | 84 patients with isolated calf muscle thrombosis. 52 received LMWH for 10 days, 32 received no anticoagulation | Prospective cohort with serial ultrasound examinations | Progression to deep veins of calf | Study discontinued as 8/32 non-anticoagulated patients progressed to deep veins thrombosis, compared to 0/52 anticoagulated patients | Gold standard venography not used VQ scan results interpreted in isolation |
| PE | |||||
| Incidence and natural history of below-knee deep venous thrombosis in high-risk trauma patients. Sharpe RP, Gupta R, Gracias VH, et al. 2002, USA | 85 trauma patients with below knee DVTs | Prospective cohort | Thrombus propagation | 4/85 thrombi propagated proximally | Gold standard investigations not applied for DVT or PE |
| PE | 1/85 did not propagate but had a PE | ||||
| Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. Lagerstedt CI, Olsson CG, Fagher BO, Oqvist BW, Albrechtsson U. 1985, Sweden | 52 patients admitted to medical ward with venogram confirmed below knee DVT 24 randomised to warfarin therapy, 28 randomised to no warfarin therapy |
RCT | 90 day incidence of recurrent DVT or PE | Warfarin group, no patient had recurrence. 5 patients had proximal extension of deep vein thrombosis and one had symptomatic PE. | Gold standard not used to diagnose PE. 5 more patients had abnormal VQ scans at 90 days, but whether they had PE remains unclear. |
| Short-term natural history of isolated gastrocnemius and soleal vein thrombosis. Macdonald PS, Kahn SR, Miller N, Obrand D. 2003, Canada | 120 patients with isolated gastrocnemius or soleus muscle vein thrombosis. No patient anticoagulated. 69% inpatients. | Prospective cohort study with duplex scans at 5, 9, 14, 30 and 90 days. | Thrombus propagation | Complete resolution in 46%. Thrombus extension in 16.3%. 3% extended to level of popliteal vein or above. 90% of thrombus extensions occurred within 2 weeks. | Only 65% were followed up to 3 months. No details are available for the deaths of 22 patients. Outcomes did not include PE. |
Author Commentary:
All of these studies could have been more thorough in their diagnostic criteria and/or follow-up.
Bottom Line:
Despite the flaws in almost all of these studies, it is clear that pulmonary emboli DO result from below knee thrombi. All patients with calf thrombosis should receive oral anticoagulation.
References:
- Philbrick JT, Becker DM.. Calf deep venous thrombosis. A wolf in sheep's clothing.
- Giachino A.. Relationship between deep vein thrombosis in the calf and fatal pulmonary embolism.
- Lohr JM, Kerr TM, Lutter KS et al.. Lower extremity calf thrombosis: to treat or not to treat?
- Pellegrini VD Jr, Langhans MJ, Totterman S et al.. Embolic complications of calf thrombosis following total hip arthroplasty.
- Nielsen HK, Husted SE, Krusell LR et al.. Incidence and fate in a randomised, controlled trial of anticoagulation versus no anticoagulation.
- Lohr JM, James KV, Deschmukh RM et al.. Calf vein thrombi are not a benign finding.
- O'Shaughnessy AM, Fitzgerald DE.. The value of duplex ultrasound in the follow-up of acute calf vein thrombosis.
- Gottlieb RH, Widjaja J, Mehra S et al.. Clinically important pulmonary emboli: does calf vein US alter outcomes?
- Pinede L, Ninet J, Duhaut P et al,. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf
- Schwarz T, Schmidt B, Beyer J et al.. Therapy of isolated calf muscle vein thrombosis with low-molecular-weight heparin.
- Sharpe RP, Gupta R, Gracias VH, et al.. Incidence and natural history of below-knee deep venous thrombosis in high-risk trauma patients.
- Lagerstedt CI, Olsson CG, Fagher BO, Oqvist BW, Albrechtsson U.. Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis.
- Macdonald PS, Kahn SR, Miller N, Obrand D.. Short-term natural history of isolated gastrocnemius and soleal vein thrombosis.