DOES THIS PATIENT UNDERGOING GENERAL SURGERY NEED VTE PROPHYLAXIS?
A 32-year-old mother of two comes to the emergency room with abdominal pain and nausea. An ultrasound confirms acute appendicitis, and the general surgeon at your center feels this patient should have an appendectomy within the next 6 hours. He feels she is at low operative risk, since she has no past medical history and is taking no medications, apart from an oral contraceptive pill. The general surgery resident phones you to ask if the patient needs VTE prophylaxis.
Data from studies done more than 20 years ago involving patients who did not routinely receive VTE prophylaxis found that rates of asymptomatic DVT in patients having general surgical procedures were between 15% and 30%, while fatal PE occurred in 0.2% to 0.9% of patients. Current surgical practices, including better perioperative care, rapid postoperative mobilization, and greater use of regional anesthesia have likely reduced these figures. However, general surgery patients are still considered to be at moderate to high risk of VTE. Numerous randomized clinical trials and meta-analyses have shown that VTE prophylaxis with low dose unfractionated heparin (LDUH) or low molecular weight heparin (LMWH) reduces the risk of symptomatic VTE by 40% to 70% in these patients. However, both of these agents—and others currently used for VTE prophylaxis—can increase the risk of postoperative bleeding.
The risk of thrombosis
The type of surgery and the type of anaesthesia are the primary determinants of VTE risk in nonorthopedic surgical patients.
The approximate DVT risk without prophylaxis is based on objectively confirmed rates of DVT in asymptomatic patients who did not receive prophylaxis.
There is a range of DVT risk of approximately 10% to 40% in general surgical patients, depending on the specific procedure, complications, and traditional risk factors.
General anesthesia poses a greater risk of VTE than spinal or epidural anesthesia and the duration of anesthesia irrespective of the type of anesthesia influences VTE risk, with >3.5 hours associated with the highest risk.
Postoperative complications may further increase the risk.
Patients at very low risk of VTE do not require any specific VTE prophylaxis, but should be mobilized postoperatively. All other patients should be evaluated for VTE prophylaxis. Patients at a low risk for bleeding should receive pharmacologic prophylaxis with LDUH, LMWH, or fondaparinux. There have been no trials that directly compare the two most popular dosing regimens of subcutaneous LDUH, 5000 units every 8 hours and 5000 units every 12 hours. A meta-analysis of 51 randomized controlled trials compared LMWH and LDUH in general and abdominal surgery patients, and found that the risk of clinically evident VTE was ~30% lower in the LMWH group. However, this difference disappeared when the analysis was restricted to high-quality (blinded, placebo-controlled) trials. The meta-analysis also failed to show any difference in PE, death from any cause, major bleeding, or wound hematoma between the LMWH and LDUH groups. Our practice is to use the lowest recommended dose of heparin for prophylaxis, to minimize bleeding complications, and reduce the number of injections that a patient must receive. Further, we prefer LMWH as it carries a lower risk of heparin induced thrombocytopenia than LDUH. Parental anticoagulants can be given at various points in the patient’s hospitalization: 0 to 2 hour preop (if the patient does not receive an epidural and does not undergo a very high bleed risk procedure, such as liver resection); the evening of the day of surgery; or the morning after surgery. Timing of administration is dependent on bleeding concerns, and should be a shared decision between all of the patient’s health care providers.
The selective factor Xa inhibitor fondaparinux has also been evaluated for major abdominal surgery. There does not appear to be any significant difference in PE, or nonfatal symptomatic VTE, or death when fondaparinux is compared with LMWH. There was a trend to increased nonfatal major bleeding in the fondaparinux, but there was no demonstrable increase in fatal bleeding or bleeding requiring reoperation.
Direct-acting oral anticoagulants (eg, rivaroxaban and apixaban, factor Xa inhibitors, and dabigatran etexilate, a factor IIa inhibitor) have shown efficacy in VTE prophylaxis as well. These agents are appealing to clinicians and patients, as they are ingested orally, in a fixed dosing schedule. They have not yet been approved for use after nonorthopedic surgery in the United States.
Mechanical VTE prophylaxis is an option in patients with a high risk of bleeding. However, graduated compression stockings (GCS) and intermittent pneumatic compression devices (IPC) are not as effective as pharmacologic prophylaxis, and do not appear to reduce the risk of proximal DVT or symptomatic PE. Though many use them as an “add-on intervention” in general surgery patients who are at particularly high risk of VTE, such as those with cancer, there is little evidence that they add to the protective effect of pharmacologic prophylaxis. If mechanical VTE prophylaxis is used, bleeding risk should be reassessed regularly, and pharmacologic VTE prophylaxis should be started as soon as it is acceptably low.
The risk of VTE appears to be elevated for at least 12 weeks following inpatient surgery. However, the evidence for extended VTE prophylaxis in general surgery is not as robust as in orthopedic surgery. A multicenter, randomized, blinded, placebo-controlled trial studied extended 21-day prophylaxis with bemiparin (a LMWH) in patients who underwent abdominal or pelvic surgery for cancer. The primary outcome was a composite of any DVT (including asymptomatic and distal events), nonfatal PE, and death from any cause. Though the bemiparin group’s had a 24% lower risk of the composite outcome and an 88% lower risk of proximal DVT than the placebo group, neither group had and symptomatic, nonfatal VTE events. The results also showed no difference in bleeding. At this time, it is not recommended that all general surgery patients receive extended VTE prophylaxis. However, cancer patients who are at particularly high risk of VTE should be considered for post discharge prophylaxis for 4 weeks.
A risk assessment does not have to be complicated.
The number of risk factors determines whether a patient is low, moderate, or high risk, not just the surgical procedure itself.
Once a patient exceeds two risk factors, the patient is at least moderate risk.
DOES THIS PATIENT UNDERGOING GYNECOLOGIC OR UROLOGIC SURGERY NEED VTE PROPHYLAXIS?
A 78-year-old man is undergoing a radical prostatectomy for prostate cancer. His past medical history is significant for type 2 diabetes mellitus, peripheral neuropathy, and a below-knee amputation performed 10 years ago. He has no history of bleeding. The urologist asks you if you are aware of any intraoperative or postoperative strategies to reduce this patient’s VTE risk.
There are fewer randomized clinical trials of VTE prophylaxis in gynecologic or urologic surgery. Existing risk assessment models have also not been validated specifically in these patients. However, the rates of DVT, PE, and fatal PE in major gynecologic surgery are similar to those in general surgery. For this reason, VTE prophylaxis recommendations are similar. There is data that cancer, use of hormones and the pregnancy state are associated significantly with thrombosis in gynecologic surgery, and must be considered in risk assessment.
VTE is an important problem in major urologic surgery, with rates of postoperative symptomatic VTE between 1% and 5%. However, there has been only one methodologically rigorous randomized clinical trial in the last 20 years in this area. Again, VTE prophylaxis recommendations are similar to those in general surgery. It is known that open procedures (vs transurethral procedures) and the use of the lithotomy position are associated with increased VTE risk. Communication with the surgeon and the anesthetist can modify these intraoperative factors and help reduce the patient’s VTE risk.
DOES THIS PATIENT UNDERGOING CARDIAC OR VASCULAR SURGERY NEED VTE PROPHYLAXIS?
An 82-year-old woman is undergoing femorodistal bypass for longstanding peripheral arterial disease. She is an ex-smoker, and has a history of hypertension and hyperlipidemia. The patient is currently on aspirin and has been told that she will receive additional blood thinners at the time of her operation to keep her arteries from getting blocked. She has read about deep vein thrombosis, and wonders if she should receive any extra care to prevent this complication of surgery.
There is limited evidence for VTE prophylaxis in vascular surgery patients, with few well-designed randomized clinical trials in this area. Studies have not shown a clear benefit for prophylaxis, with no significant difference in rates of DVT detected by routine ultrasound screening or rates of major bleeding. Why does VTE prophylaxis not appear to have a benefit in vascular surgery patients? One potential reason is that vascular surgery patients frequently receive antithrombotic agents such as intravenous heparin, and antiplatelet agents such as aspirin and clopidogrel, to prevent arterial occlusion after vascular reconstruction. These agents lower the risk of VTE, making routine use of additional anticoagulants redundant (and possibly harmful). However, the methodologic limitations of existing evidence are also a concern; vascular surgery patients do have an increased risk of VTE postoperatively, and these patients were included in validation studies of surgical risk assessment models. At this time, it is recommended that vascular surgery patients should receive pharmacologic VTE prophylaxis in a similar fashion to general surgery patients. Caution should be used with mechanical prophylaxis; GCS and IPC are relatively contraindicated in vascular surgery patients undergoing lower limb bypass.
Computed tomography pulmonary angiography showing emboli in both pulmonary arteries.
There is also limited evidence for VTE prophylaxis in cardiac surgery patients. Like vascular surgery patients, these individuals commonly receive antithrombotic agents such as intravenous heparin, and antiplatelet agents such as aspirin and clopidogrel. Patients who undergo cardiac valve replacement generally receive full-dose anticoagulation postoperatively, making pharmacologic VTE prophylaxis redundant. The incidence of symptomatic VTE after cardiac surgery is thought to range from 0.5% to 1.1%. Patients at highest risk are those on prolonged bed rest, those with prolonged hospitalization before surgery, those with postoperative complications, and those with congestive heart failure. Coronary artery bypass grafting (particularly if done off-pump) carries a higher risk of VTE than valve surgery. The risk of heparin-induced thrombocytopenia (HIT) also influences decision making regarding VTE prophylaxis. Approximately 20% of patients undergoing coronary artery bypass grafting (CABG) who develop a PE are diagnosed with HIT. HIT has been shown to be more common when LDUH is used, versus LMWH. It is uncertain if VTE prophylaxis should be administered to all cardiac surgery patients; however, in CABG patients who do not receive full-dose therapeutic anticoagulation postoperatively most physicians elect to use prophylactic-dose heparin or bilateral mechanical VTE prophylaxis (if the patient has not had saphenous vein grafting). Because the risk of HIT is high in cardiac surgery, LMWH is preferred over LDUH. Attention must, however, be paid to bleeding risk; this risk goes up with concomitant antiplatelet use, older age, renal insufficiency, and longer bypass time. If bleeding is a concern, mechanical VTE prophylaxis is preferred over pharmacologic VTE prophylaxis.
DOES THIS PATIENT UNDERGOING NEUROSURGERY NEED VTE PROPHYLAXIS?
Patients undergoing major neurosurgery are at a moderate risk for VTE, with rates of proximal DVT as high as 5% postoperatively. Those with malignant brain tumors are at particularly high risk. One prospective study of more than 250 patients with gliomas showed that 31% had symptomatic, venographically confirmed DVT within 5 weeks of their surgery. However, a major barrier to optimal VTE prophylaxis in neurosurgery patients is their risk of bleeding. Intracranial bleeding can have devastating clinical consequences, and for this reason, preoperative and early postoperative pharmacologic prophylaxis should be used with caution in craniotomy patients. Rates of intracranial hemorrhage appear to double when postoperative LMWH is compared to mechanical or no VTE prophylaxis (approximately 2%-6% vs 1%-3%). Most of these bleeds occur within the first 2 days after surgery. A reasonable approach that balances the risks of bleeding and thrombosis is to start mechanical VTE prophylaxis with properly fitted IPC at the time of neurosurgery. Perioperative use of IPC is highly effective, reducing the risk of VTE by more than two-thirds. If a careful clinical assessment is stable and postoperative CT scan does not show bleeding at 24 to 48 hours, LMWH or LDUH can be added to further protect the patient from VTE. There is no evidence for extended prophylaxis in neurosurgery patients.
DOES THIS PATIENT UNDERGOING LAPAROSCOPIC OR BARIATRIC SURGERY NEED VTE PROPHYLAXIS?
Laparoscopic surgery is becoming an increasingly popular alternative to conventional open surgical procedures, due to decreased tissue trauma and faster recovery times. However, there are some unique features of laparoscopic surgery that increase thrombosis risk, including longer intraoperative time, the reverse Trendelenburg position, and pneumoperitoneum (which creates venous stasis in the lower extremities). Nevertheless, rates of symptomatic VTE following laparoscopic surgery are lower than in general surgery, less than 0.5% in most series. Rates of asymptomatic VTE are thought to be lower than 1%. For this reason, routine VTE prophylaxis is not recommended in laparoscopic surgery.
Bariatric surgery, which includes Roux-en-Y gastric bypass, gastric banding, vertical-banded gastroplasty, and biliopancreatic diversion, is also a growing field. More than 100,000 bariatric surgeries for morbid obesity are performed in the United States every year. Obesity is a known risk factor for VTE and puts bariatric surgery patients in a unique risk group. Rates of symptomatic VTE vary depending on the study quoted, anywhere from 0.8% to 2.4%. However, there is still insufficient high-quality evidence to make clear recommendations regarding VTE prophylaxis in bariatric surgery. Early ambulation and mechanical prophylaxis (either IPC or GCS) are widely accepted components of postoperative care in bariatric surgery patients. The American College of Chest Physicians’ most recent guidelines also recommend LMWH, LDUH, or fondaparinux be routinely used. Consultation with a pharmacist is important, as patients who are obese who may require higher drug doses.