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Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis

BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g1340 (Published 10 March 2014) Cite this as: BMJ 2014;348:g1340

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Re: Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis

We read with great interest the research by Geersing et al. concluding that a D-dimer test can contribute as a predictor to rule out deep vein thrombosis by its negative result.[1] This finding makes us think that another disease condition, acute intestinal obstruction (AIO), might be associated with the plasma level of D-dimer to judge whether intestinal necrosis is present or not.

According to our experience, AIO patients with confirmed intestinal necrosis were usually accompanied with preoperatively raised plasma D-dimer level. Some AIO patients, with consistently atypical symptom and signs but gradually increasing plasma D-dimer during the conservative therapy, were also finally proved to have intestinal necrosis. Additionally, we observed that plasma D-dimer level was not only associated with intestinal obstruction but also morbidity and mortality.

Intestinal necrosis is accepted as an independent prognostic factor of AIO.[2] However, sometimes, the signs of peritonitis induced by intestinal necrosis are occult and hard to determine on laparotomy in a timely fashion. Therefore, if negative plasma D-dimer could rule out intestinal necrosis based on a continuous monitoring, prolonged conservative therapy can be given to some selective patients and unnecessary laparotomies can be avoided. On the other hand, early detection of intestinal necrosis by plasma D-dimer monitoring might limit the severe complications subsequent to intensive peritonitis and systemic infection.

D-dimer is a fibrin degradation product present in the blood after fibrinolysis of a blood clot. At the initial stage of intestinal necrosis, thrombosis occurs in the microvessels of the involved intestinal wall, and then mesenteric venous thrombosis (MVT), even portal vein thrombosis in some particular cases. It’s the reason why plasma D-dimer is able to reflect the intestinal necrosis of AIO patients. In animal experiments, the plasma D-dimer level increased along with the prolongation of intestinal ischemia duration.[3,4] However, the intestinal ischemia-reperfusion was also presented as increased plasma D-dimer due to the histologically confirmed intravascular fibrin deposition.[5] Hence, short-lasting intestinal ischemia might lead to positive D-dimer result but false positive assessment of intestinal necrosis. It’s a limitation which impairs the specificity of plasma D-dimer diagnosing the intestinal strangulation or necrosis. In clinical reports, although registered patients were few, D-dimer at admission was raised in all five MVT patients tested.[6] Among nine patients with acute thromboembolic occlusion of the superior mesenteric artery, the plasma D-dimer level was significantly higher than that of patients with only simple intestinal obstruction.[7] In eight intestinal necrosis patients, there was a higher D-dimer level than in the cases with reversible ischemia or simple intestinal obstruction, in despite of not being statistically significant.[8] It implies that plasma D-dimer probably has a dose-response correlation between necrotic and pre-necrotic conditions.

In a short, we think that plasma D-dimer might be helpful in detecting or monitoring intestinal necrosis among AIO patients by ruling out MVT or not. However, current available clinical evidence is quite scarce, with a lack of epidemiological studies. Large scale studies or pooling individual data studies are required to confirm plasma D-dimer as a factor in detecting intestinal necrosis.

Acknowledgement
National Natural Science Foundation of China (No. 81372344 and 81301866).

References
[1] Geersing GJ, Zuithoff NP, Kearon C, Anderson DR, Ten Cate-Hoek AJ, Elf JL, et al. Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis. BMJ 2014;348:g1340.
[2] Chen XZ, Wei T, Jiang K, Yang K, Zhang B, Chen ZX, et al. Etiological factors and mortality of acute intestinal obstruction: a review of 705 cases. Zhong Xi Yi Jie He Xue Bao 2008;6:1010-6.
[3] Altinyollar H, Boyabatli M, Berberoğlu U. D-dimer as a marker for early diagnosis of acute mesenteric ischemia. Thromb Res 2006;117:463-7.
[4] Zeybek N, Yildiz F, Kenar L, Peker Y, Kurt B, Cetin T, et al. D-dimer levels in the prediction of the degree of intestinal necrosis of etrangulated hernias in rats. Dig Dis Sci 2008;53:1832-6.
[5] Schoots IG, Levi M, Roossink EH, Bijlsma PB, van Gulik TM. Local intravascular coagulation and fibrin deposition on intestinal ischemia-reperfusion in rats. Surgery 2003;133:411-9.
[6] Acosta S, Alhadad A, Svensson P, Ekberg O. Epidemiology, risk and prognostic factors in mesenteric venous thrombosis. Br J Surg 2008;95:1245-51.
[7] Acosta S, Nilsson TK, Björck M. D-dimer testing in patients with suspected acute thromboembolic occlusion of the superior mesenteric artery. Br J Surg 2004;91:991-4.
[8] Bogusevicius A1, Grinkevicius A, Maleckas A, Pundzius J. The role of D-dimer in the diagnosis of strangulated small-bowel obstruction. Medicina (Kaunas) 2007;43:850-4.

Competing interests: No competing interests

18 March 2014
Xin-Zu Chen
Gastrointestinal Surgeon
Rui Wang, Jian-Kun Hu
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China.
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Guo Xue Xiang 37, Chengdu 610041, Sichuan Province, China.