Journal Watch: Venous Thromboembolism and Portal Vein Thrombosis

| June 1, 2017

Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study.

Lindström S, Germain M, Crous-Bou M, et al. Hum Genet. 2017 May 20. [Epub ahead of print]

Synopsis: Observational studies have shown an association between obesity and venous thromboembolism (VTE) but it is not known if observed associations are causal, due to reverse causation or confounding bias. The authors conducted a Mendelian Randomization study of body mass index (BMI) and VTE. They identified 95 single nucleotide polymorphisms (SNPs) that have been previously associated with BMI and assessed the association between genetically predicted high BMI and VTE leveraging data from a previously conducted GWAS within the INVENT consortium comprising a total of 7507 VTE cases and 52,632 controls of European ancestry. Five BMI SNPs were associated with VTE at P < 0.05, with the strongest association seen for the FTO SNP rs1558902 (OR 1.07, 95% CI 1.02-1.12, P = 0.005). In addition, we observed a significant association between genetically predicted BMI and VTE (OR = 1.59, 95% CI 1.30-1.93 per standard deviation increase in BMI, P = 5.8 × 10-6). They concluded that their study provides evidence for a causal relationship between high BMI and risk of VTE. Reducing obesity levels will likely result in lower incidence in VTE. PMID: 28528403

Assessment of the relationship between body mass index and incidence of venous thromboembolism in hospitalized overweight and obese patients.

Samuel S, Gomez L, Savarraj JP, Bajgur S, Choi HA. Pharmacotherapy. 2017 May 18. [Epub ahead of print]

Synopsis: To assess whether a positive linear association exists between body mass index (BMI) and incidence of venous thromboembolism (VTE) in overweight and obese hospitalized patients, researchers conducted a single-center, retrospective, observational cohort study. The study included a total of 1,452 adults hospitalized between January 1, 2013, and December 31, 2014, who weighed more than 100kg and had a BMI of 25 kg/m2 or greater on admission, and received heparin subcutaneously for VTE prophylaxis. The patients were categorized into four subgroups based on World Health Organization BMI classification: overweight (141 patients), obese class I (305 patients), obese class II (324 patients), and obese class III (682 patients).

The primary outcome was occurrence of VTE in each subgroup; all-cause mortality and length of hospital stay were secondary outcomes. A linear trend test did not show an association between occurrence of VTE and BMI ≥ 25 kg/m2. VTE occurred in seven (5%) of 141 patients in the overweight group, five (2%) of 305 in the obese class I group, eight (3%) of 324 in the class II group and 18 (3%) of 682 in the class III group (p=0.573). In addition, no linear association was noted between all-cause mortality or length of hospital stay and BMI ≥ 25 kg/m2 . Overall mortality was 10% (146/1452 patients). Ten deaths (7%) occurred in the overweight group, 45 (15%) in the obese class I group, 38 (12%) in the obese class II group, and in 53(8%) the obese class III group (p=0.067). The median length of hospital stay was five (interquartile range 3-9) days (p=0.122) for all patients.

The researchers concluded that in overweight and obese hospitalized patients who weighed more than 100kg and had a BMI of 25 kg/m2 or greater, the incidence of VTE did not increase incrementally with increasing severity of obesity. PMID: 28520085

Evaluation of an unfractionated heparin pharmacy dosing protocol for the treatment of venous thromboembolism in nonobese, obese, and severely obese patients.

Hosch LM, Breedlove EY, Scono LE, Knoderer CA. Ann Pharmacother. 2017 May 1:1060028017709819. [Epub ahead of print]

Synopsis: The objective of this study was to evaluate the time and dose required to achieve a therapeutic activated partial thromboplastin time (aPTT) in nonobese, obese, and severely obese patients using a pharmacist-directed heparin dosing protocol.

This was a retrospective cohort study in a single-center community hospital inpatient setting. Adult patients receiving heparin for venous thromboembolism (VTE) treatment from July 1, 2013, to July 31, 2015, were evaluated. Patients were categorized into three groups: nonobese (BMI < 30kg/m2), obese (BMI = 30–39.9kg/m2), and severely obese (BMI ≥ 40kg/m2). Data on height, weight, initial bolus dose, initial infusion rate, time to therapeutic aPTT, and therapeutic infusion rate were collected. Dosing body weight (DBW) was utilized for patients 20 percent over their ideal body weight (IBW). The primary outcome was time to therapeutic aPTT.

Analysis included 298 patients. Median times to therapeutic aPTT (hours:minutes) in the nonobese, obese, and severely obese were 15:00 (interquartile range [IQR] = 8:05-23:21), 15:40 (IQR = 9:22-25:10), and 15:22 (IQR = 7.54-23:40), respectively (P = 0.506). There was no difference in bleeding among the nonobese (14%), obese (13.9%), or severely obese groups (7.9%; P = 0.453). No adverse thrombotic events occurred during hospitalization.

The authors concluded that using a DBW for heparin dosing in patients 20 percent over their IBW resulted in similar times to therapeutic aPTT and adverse events in the nonobese, obese, and severely obese. PMID: 28511582

Who should get extended thromboprophylaxis after bariatric surgery?: A risk assessment tool to guide indications for post-discharge pharmacoprophylaxis.

Aminian A, Andalib A, Khorgami Z, et al. Ann Surg. 2017;265(1):143–150.

Synopsis: The researchers sought to determine the risk factors for 30-day postdischarge venous thromboembolism (VTE) after bariatric surgery and to identify potential indications for extended pharmacoprophylaxis.

From American College of Surgeons-National Surgical Quality Improvement Program, the authors identified 91,963 patients, who underwent elective primary and revisional bariatric surgery between 2007 and 2012. Regression-based techniques were used to create a risk assessment tool to predict risk of postdischarge VTE. The model was validated using the 2013 American College of Surgeons-National Surgical Quality Improvement Program dataset (N = 20,575). Significant risk factors were used to create a user-friendly online risk calculator.

The overall 30-day incidence of postdischarge VTE was 0.29 percent (N = 269). In those experiencing a postdischarge VTE, mortality increased about 28-fold (2.60% vs 0.09%; P < 0.001). Among 45 examined variables, the final risk-assessment model contained 10 categorical variables including congestive heart failure, paraplegia, reoperation, dyspnea at rest, nongastric band surgery, age ≥60 years, male sex, BMI ≥50kg/m2, postoperative hospital stay ≥3 days, and operative time ≥3 hours. The model demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit test, P = 0.71) and discrimination (c-statistic = 0.74). Nearly 2.5 percent of patients had a predicted postdischarge VTE risk >one percent.

The authors concluded that more than 80 percent of post-bariatric surgery VTE events occurred post-discharge. Congestive heart failure, paraplegia, dyspnea at rest, and reoperation are associated with the highest risk of post-discharge VTE. Routine post-discharge pharmacoprophylaxis can be considered for high-risk patients (ie, VTE risk >0.4%). PMID: 28009739

Prevention of venous thromboembolism in patients undergoing bariatric surgery.

Bartlett MA, Mauck KF, Daniels PR. Vasc Health Risk Manag. 2015;11:461–77.

Synopsis: The authors summarize the available evidence after systematic review of the literature regarding approaches to venous thromboembolism (VTE) prevention in bariatric surgery. Identification of risk factors for VTE in the bariatric surgery population, analysis of the effectiveness of methods used for prophylaxis, and an overview of published guidelines are presented. PMID: 26316771

Portal vein thrombosis following laparoscopic sleeve gastrectomy: A rare case report.

Abu Jkeim N, Al Hazmi A, Alawad AA1, Ibrahim R1, Abudames A, Tawfik S, Mansour M. Int J Case Rep Imag. 2015;6(9):556–559.

Synopsis: The authors present the case of a 33-year- old woman who underwent an uncomplicated laparoscopic sleeve gastrectomy for the treatment of morbid obesity, and presented on postoperative day 14 with epigastric pain. Computed tomography revealed left portal vein thrombosis. She promptly improved after initiation of low-molecular weight heparin (LMWH) and was discharged on hospital day five with oral warfarin. They concluded that although uncommon, portal vein thrombosis (PVT) should be included in the differential diagnosis for unexplained abdominal symptoms after laparoscopic sleeve gastrectomy. PMID: 26339157

Portomesenteric venous thrombosis: an early postoperative complication after laparoscopic biliopancreatic diversion.

Cesaretti M, Elghadban H, Scopinaro N, Papadia FS. World J Gastroenterol. 2015 ;21(8):2546–2549.

Synopsis: The number of bariatric operations, as well as the incidence of perioperative complications, has risen sharply in the past 10 years. Perioperative acute portal vein thrombosis is an infrequent and potentially severe postoperative complication that has not yet been reported after biliopancreatic diversion (BPD). Here, the authors present three cases of portal vein thrombosis (PVT) that occurred following BPD treatment for morbid obesity and type 2 diabetes. The thromboses were detected by abdominal ultrasound and computed tomography with intravenous contrast. The portomesenteric venous thromboses in all three cases presented as unexpected abdominal pain several days after discharge from the hospital. The complications occurred despite adequate perioperative prophylaxis and progressed to bowel gangrene in the diabetic patients only. They concluded that these cases demonstrate the occurrence of this rare type of complication, which may be observed by physicians that do not routinely treat bariatric patients. Awareness of this surgical complication will allow for early diagnosis and prompt initiation of adequate therapy. PMID: 25741166

Incidence of deep vein thrombosis and thrombosis of the portal-mesenteric axis after laparoscopic sleeve gastrectomy.

Alsina E, Ruiz-Tovar J, Alpera MR, Ruiz-García JG, Lopez-Perez ME, Ramon-Sanchez JF, Ardoy F. J Laparoendosc Adv Surg Tech A. 2014;24(9):601-5. Epub 2014 Jul 29.

Synopsis: The aim of this prospective observational study was to determine the incidence of deep vein thrombosis (DVT) and portal-splenic-mesenteric vein thrombosis (PSMVT) in the authors’ population undergoing laparoscopic sleeve gastrectomy (LSG) as the bariatric technique, with an anti-thromboembolic dosage scheme of 0.5mg/kg/day 12 hours preoperatively and maintained during 30 days postoperatively.

The study included 100 consecutive patients undergoing LSG between October 2007 and September 2013. To determine the incidence of DVT and PSMVT, all patients undergo contrast-enhanced abdominal computed tomography (CT) and Doppler ultrasonography (US) of both lower limbs on the third postoperative month, whether they were asymptomatic or symptomatic. Contrast-enhanced CT showed one case of PSMVT (1%). Two patients presented DVT in the right leg (2%). All the cases were asymptomatic.

The authors concluded that the incidence of PSMVT and DVT after LSG with a prophylactic low-molecular-weight heparin dose of 0.5mg/kg/day and maintained during 30 days postoperatively is one percent and two percent, respectively. According to these results, a postoperative screening with Doppler US and/or contrast-enhanced CT seems to be unnecessary. PMID: 25072524

Portomesenteric vein thrombosis after laparoscopic sleeve gastrectomy for morbid obesity.

Anewenah LS, Asif M, Francesco R, Ramachandra P. BMJ Case Rep. 2017 Jan 9;2017.

Synopsis: The authors present the case of a 34-year-old woman who underwent an uncomplicated laparoscopic sleeve gastrectomy (LSG) for the treatment of morbid obesity, and presented on postoperative day 13 with Portomesenteric vein thrombosis (PMVT). The patient underwent mechanical thrombectomy and thrombolytic therapy. After two days, patency was restored and the patient was discharged in stable condition. They concluded that a high index of suspicion for PMVT should be considered in patients reporting diffuse abdominal pain after LSG. Owing to its lethality, upon confirmation of PMVT, therapy should begin immediately along with extended anticoagulation therapy on discharge. PMID: 28069786

Portal vein thrombosis following laparoscopic sleeve gastrectomy for morbid obesity.

Rosenberg JM, Tedesco M, Yao DC, Eisenberg D. JSLS. 2012;16(4):639–643.

Synopsis: The authors report the case of a man who presented with portal vein thrombosis after laparoscopic sleeve gastrectomy. A 41-year-old man underwent an uneventful laparoscopic sleeve gastrectomy for the treatment of morbid obesity, and presented on postoperative day 10 with nonfocal abdominal pain, nausea, vomiting, and leukocytosis. Computed tomography revealed portal vein thrombosis, which was found in the setting of Clostridium difficile colitis.

They concluded that portal vein thrombosis may be identified with increasing frequency as the number of laparoscopic bariatric operations continues to increase. A high index of suspicion is necessary to diagnose this rare, but potentially lethal, complication. PMID: 23484577

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