Thromboprophylaxis in patients with abdominal sepsis

Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep venous thrombosis (DVT), are potentially severe complications in surgical patients. PE is considered the leading preventable cause of in-hospital death. Prevention of venous thromboembolism in critical surgical patients is a challenge because of the high risk of venous thromboembolism in these patients.

There is evidence that primary prophylaxis substantially reduces the incidence of VTE without increasing the risk of major bleeding. However the use of pharmacological prophylaxis in low risk patients and in patients with contraindications could be more risky than beneficial. Active bleeding, previous major bleeding episode, untreated bleeding disorder, severe renal or hepatic failure, thrombocytopenia, uncontrolled systemic hypertension, concomitant use of anticoagulants, antiplatelet therapy, or thrombolytic drugs may be considered risk factors for pharmacological prophylaxis. In these patients a careful assessment of risks and benefits is mandatory.

Patients with intra-abdominal infections may be at increased risk of VTE due to their premorbid conditions, surgical intervention, admitting diagnosis of sepsis, and events and exposures in the ICU such as central venous catheterization, invasive tests and procedures, and drugs that potentiate immobility.

The risk of VTE may be determined by patient-specific factors. It is well known that the incidence VTE increases sharply with age. It is very rare in young individuals with a low rate of about 1 per 10,000 annually before the fourth decade of life, rising rapidly after age 45 years, and approaching 5-6 per 1000 annually by age 80. Other risk factors include obesity, smoking status, prior VTE, malignancy, higher Charlson comorbidity score, hormone replacement therapy and inflammatory bowel disease.  The type of surgery is an important determinant of the risk of DVT too.

In the setting of abdominal surgery low-risk procedures include cholecystectomy and appendectomy.  Where as, more extensive abdominal or pelvic surgery, such as small bowel or colonic resections due to bowel perforations are associated with a higher risk of VTE. VTE risk appears to be highest for patients undergoing abdominal or pelvic surgery for cancer such colonic cancer perforations.

It is well known that sepsis is associated with activation of blood coagulation (hypercoagulability), which may contribute to localized venous thromboembolism. A delicate balance exists between anticoagulant and procoagulant mechanisms. Normally the coagulation system comprises the procoagulant mechanisms responsible for the initiation of coagulation and maintenance of normal hemostasis, and the balancing anticoagulant mechanisms that down-regulates the procoagulant arm and prevents widespread thrombosis. The key event underlying tromboembolism is the overwhelming inflammatory host response to the pathogen. It leads to the overexpression of inflammatory mediators, that causes an upregulation of procoagulant mechanisms and simultaneous downregulation of natural anticoagulants inducing platelet activation, production of tissue factor, and increased fibrin turnover, which can all lead to thrombotic complications.

Additional, specific risk factors for the intensive care unit population include also respiratory or cardiac failure, pharmacologic sedation, mechanical ventilation, central venous catheter that should be always considered.

Early and frequent ambulation of hospitalized patients at risk for VTE is an important principle of patient care and represents the first method of thromboprophylaxis.  Mechanical methods of thromboprophylaxis include both graduated compression stockings (GCS), intermittent pneumatic compression (IPC). Although mechanical methods of thromboprophylaxis (GCS and IPC) are attractive options in patients who have a high risk of bleeding, they have not been studied as extensively as pharmacologic thromboprophylaxis has studied.

Low-molecular-weight heparins (LMWHs) are now the pharmacologic agents of first choice for thromboembolism prophylaxis. LMWHs are generated from the chemical depolymerization of unfractioned heparin (UH) and have significantly great activity towards factor Xa than UHs.

Fondaparinux is a synthetic pentasaccharide that selectively inhibits coagulation factor Xa. It has been shown to be highly efficacious in the prevention of DVT among high risk ortopedic patients.  In the setting of abdominal surgery, postoperative fondaparinux is at least as effective and safe as preoperative LMWHs for the prevention of VTE after abdominal surgery. Unlike UFH and LMWH, it has not been associated with heparin-induced thrombocytopenia. In addition, because fondaparinux does not interfere with thrombin binding, it has no negative effect on wound healing.  Because of its long half-life (approximately 18 h), patients whose creatinine clearance is < 30 mL/min may experience an accumulation of fondaparinux and thus may be at greater risk of bleeding.

In patients having intra-abdominal infections who have a contraindication to heparin, we suggest other alternatives to pharmacoprophylaxis such as mechanical prophylactic treatment (graduated compression stockings or intermittent compression devices).

In patients having intra-abdominal infections who undergo a minor procedure such as laparoscopic appendectomy or cholecystectomy, are < 40 years of age, and have no additional risk factors we suggest no specific prophylaxis other than early mobilization.

In patients having intra-abdominal infections who undergo a minor procedure and are > 40 years even with no other risk factors we suggest pharmacoprophylaxis.

In all patients who undergo major operations, we always suggest pharmacoprophylaxis. In patients with sepsis or septic shock (according to Sepsis 3 definitions) we suggest to continue pharmacoprophylaxis until resolution of sepsis.

In high risk septic patients who have a contraindication to receive pharmacoprophylaxis, we suggest mechanical prophylactic treatment, such as graduated compression stockings or intermittent compression devices.

In septic patients with multiple risk factors, we suggest to combine pharmacoprophylaxis with the use mechanical thromboprophylaxis.


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