Intestinal gangrene is a severe event with a poor prognosis in patients with AMI . Early diagnosis and intervention, especially within 12 hours, can reduce the mortality and preserve more viable intestine [16, 17]. However, when intestinal gangrene and peritonitis develop, immediate laparotomy must be performed to achieve curative treatment [18, 19]. Enteral medication is always unavailable in the short critical period after intestine resection. LMWHs are suggested in all patients undergoing revascularization and/or intestine resection during the critical postoperative period . In the current study, patients with postoperative parenteral anticoagulants, especially enoxaparin, had a lower mortality rate after intestinal resection, in spite of the absence of revascularization.
LMWHs are glycosaminoglycans consisting of chains of alternating residues of D-glucosamine and an uronic acid, either gluconic acid or iduronic acid . LMWHs are fragments of unfractionated heparin produced by controlled enzymatic or chemical depolymerization processes that yield chains with a mean molecular weight between 4,000 and 6,000, and the mean molecular weight of enoxaparin is 4,200 . Compared to heparin, LMWHs have more effective anti-Xa activity than anti-IIa activity, a more predictable anticoagulant response, and a lower incidence of heparin induced thrombocytopenia . Enoxaparin also decreases platelet activity through COX1 in patients with coronary artery disease . In patients with hemodialysis, enoxaparin reduces platelet reaction by decreasing the ability of platelets to bind fibrinogen (glycoprotein IIb/IIIa activation) and express P-selectin in response to adenosine diphosphate . Clinically, enoxaparin can be used in patients with atrial fibrillation, pulmonary embolism, and deep vein thrombosis by its antithrombotic activity [25, 26]. Enoxaparin can also be used in patients with unstable angina and non ST-elevation myocardial infarction during the period of percutaneous coronary intervention . The main effect of enoxaparin is its direct antithrombotic activity, as well as indirect antiplatelet activity.
In patients with sepsis, hypercoagulation is induced by impairing both protein C and antithrombin systems . Inappropriate accumulation and activity of platelets contribute to hyperinflammation and microthrombosis . Severe sepsis, classically associated with gram negative bacteria infection, eventually leads to disseminated intravascular coagulation and multiple organ dysfunction syndrome . In patients with mesenteric ischemia, both platelet-endothelial cell interaction and platelet-leukocyte adhesion also contribute to inflammation during intestine ischemia/reperfusion injury . LMWHs may treat or prevent severe hypercoagulation in patients with sepsis [32, 33]. In critically ill, non-bleeding patients with disseminated intravascular coagulation, prophylaxis for venous thromboembolism with prophylactic doses of heparin or LMWHs is recommended .
In the present study, all patients had intestinal gangrene and resection treatment. This implies that all patients may have intestinal microorganism overgrowth, although not all patients had positive bacterial culture from ascites or blood. Sixty-two patients (72.9%) had abnormal WBC count or immature WBC before surgery (data not shown). Seventy-four patients (87.1%) had 2 or more points of sepsis-related organ failure score (SOFA score , data not shown). Most of our patients experienced both AMI and sepsis. Immediate postoperative anticoagulants may prevent recurrent vascular thrombosis/embolism, sepsis-induced hypercoagulation, and inappropriate platelet activity inducing ischemia/reperfusion intestinal injury.
After a short period of critical illness, enteral antiplatelet or anticoagulant is suggested to avoid recurrent ischemia events. Patients with diabetes or hypertension are at high risk of coronary thrombosis and should be treated by antiplatelet therapy . Patients with atrial fibrillation, accounting for one-third of EAMI, should be treated using an anticoagulant [36, 37]. In our study, 34 patients (60.7%) had enteral antiplatelet or anticoagulant in group B. The antiplatelets included clopidogrel and aspirin, and the anticoagulants included warfarin and rivaroxaban.
The risk factors of mortality include advanced age (more than 70 years), diabetes mellitus, use of digoxin and antiplatelet, delayed surgery, existence of shock status, metabolic acidosis, hypoalbuminemia, recent myocardial infarction, previous cardiac surgery, and colon involvement [9, 11, 38, 39]. In-hospital mortality, 30-day mortality, and 90-day mortality were used for analysis in previous studies. In-hospital mortality is too erratic to represent an accurate postoperative interval. For example, a patient who survived at first admission and died within 90 days of postoperative period would be categorized in the survival group. We calculated both 30-day and 90-day mortality. In the present study, preoperative shock status, hypoalbuminemia, elevated ALT, and elevated creatinine represent significant risk factors for both 30-day and 90-day mortalities by univariate analysis. Use of postoperative parenteral anticoagulants revealed significant advantages for both 30-day and 90-day mortalities by multivariate analysis.
A major limitation in this study was the dosage of anticoagulant. Due to the retrospective method employed in this study, dosage control was not achievable. The doses chosen by the physician might be influenced by patients’ serum creatinine levels, blood platelet counts, INR of PT, and perioperative bleeding events. Two patients with postoperative severe bleeding events, intracranial hemorrhage and gastrointestinal bleeding, were in group A. Another study limitation was the periods of parenteral anticoagulant administration and shifting to enteral antiplatelet/anticoagulant. The periods of enoxaparin use were between 1 and 32 days. In group B, 8 patients had a short period of use (less than 3 days) and 5 of them were due to mortality within 3 days after surgery. It was not possible to reach a definite conclusion regarding the optimal beneficial dosage and period based on our research, and thus further study is necessary to shed light on this issue.