Evidence Basis for Anticoagulant Treatment of DVT
The review of the diagnosis and treatment of deep venous thrombosis
(DVT) by Tovey and Wyatt does not reference the evidence basis for the
standard management by heparins and oral anticoagulants. A careful review
of the literature on this topic reveals that no controlled randomized
trials demonstrate the efficacy or safety of anticoagulants for DVT
The only randomized, placebo-controlled trial used to justify heparin
and vitamin K antagonists as treatment of DVT was reported in 1960 by
Barritt and Jordan. Ironically, the study population consisted of patients
clinically diagnosed with PE and the subset with DVT was not reported.
This study noted that patients who had survived symptomatic PE and then
received anticoagulants had a significantly lower mortality from PE (i.e.,
0/16 with anticoagulants versus 5/19 with placebo, P <0.0007).1
Anticoagulated patients received three days of intravenous heparin
concurrently with oral nicoumalone (Sinthrome), a vitamin K antagonist,
for a total of 14 days of anticoagulation. Patients were kept at strict
bedrest for 10 days for fear of disloging a clot. This is the opposite of
current practice. The clinical PE diagnoses of the investigators were not
confirmed by pulmonary angiograms or lung scans.1
We now know that about 75% of those clinically diagnosed with PE do
not have it.2 Autopsy descriptions of the patients in Barritt and
Jordan's study show that, in four of the five deaths, severe underlying
diseases (e.g., cerebral infarction and cavitary pneumonia with sepsis)
caused the deaths, with PE only appearing as a contributing factor.1
Since the Barritt and Jordan trial, Kakkar and colleagues reported a
trial of DVT patients randomized between heparin, Malayan pit viper venom
(Arvin), Streptokinase, and placebo, resulting in 2/7 deaths in the
heparin group and 0/6 in the placebo group.3 Ott and colleagues reported a
placebo-controlled trial in which 2 patients died of the 12 receiving
heparin and warfarin and 1 of the 11 placebo-treated patients died.4
Nielsen randomized 90 ambulatory patients with DVT into standard heparin
and phenprocoumon versus phenylbutazone (i.e., no anticoagulants). While
on treatment in the anticoagulated group, 2/48 patients died (one of PE),
while 0/42 in the un-anticoagulated group died. About 50% of both groups
had PE by lung perfusion /ventilation scanning, mostly asymptomatic.5
No trials of low molecular weight heparins with unanticoagulated
controls have been reported. The bleeding risk of DVT patients on
anticoagulants is substantial. The treatment of DVT with anticoagulants
should be reconsidered.
1. Barritt DW, Jordan SC. Anticoagulant drugs in the treatment of
pulmonary embolism -- A controlled trial. Lancet. 1960;1:1309-1312.
2. Ginsberg JS. Management of venous thromboembolism. New England Journal
of Medicine. 1996;335(24):1816-1828.
3. Kakkar VV, Flanc C, O'Shea M, Flute P, Howe CT, Clarke MB. Treatment of
deep-vein thrombosis--a random trial. Br J Surg. 1968;55(11):858.
4. Ott P, Eldrup E, Oxholm P. The value of anticoagulant therapy in deep
venous thrombosis in the lower limbs in elderly, mobilized patients. A
double-blind, placebo-controlled investigation with open therapeutic
guidance. Ugeskr Laeger. 1988;150:218-221.
5. Nielsen HK, Husted SE, Krusell LR, et al. Anticoagulant therapy in deep
venous thrombosis. A randomized controlled study. Thrombosis Research.
I lost my license to practice medicine in the United States because I stopped warfarin treatment of an alcoholic with a DVT.
Competing interests: No competing interests