Management of Nonvariceal Upper Gastrointestinal Bleeding

Barkun AN, Almadi M, Kuipers EJ, et al. Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group. Ann Intern Med. 2019 Dec 3;171(11):805-822.

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Preendoscopic management: The group suggests using a Glasgow Blatchford score of 1 or less to identify patients at very low risk for rebleeding, who may not require hospitalization. In patients without cardiovascular disease, the suggested hemoglobin threshold for blood transfusion is less than 80 g/L, with a higher threshold for those with cardiovascular disease.

Endoscopic management: The group suggests that patients with acute UGIB undergo endoscopy within 24 hours of presentation. Thermocoagulation and sclerosant injection are recommended, and clips are suggested, for endoscopic therapy in patients with high-risk stigmata. Use of TC-325 (hemostatic powder) was suggested as temporizing therapy, but not as sole treatment, in patients with actively bleeding ulcers.

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Thrombolysis for acute deep vein thrombosis

Watson L, Broderick C, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Database Syst Rev. 2016 Nov 10;11(11):CD002783.

Main results: Seventeen RCTs with 1103 participants were included. These studies differed in the both thrombolytic agent used and in the technique used to deliver it. Systemic, loco-regional and catheter-directed thrombolysis (CDT) were all included. Fourteen studies were rated as low risk of bias and three studies were rated as high risk of bias. We combined the results as any (all) thrombolysis compared to standard anticoagulation. Complete clot lysis occurred significantly more often in the treatment group at early follow-up (RR 4.91; 95% CI 1.66 to 14.53, P = 0.004) and at intermediate follow-up (RR 2.44; 95% CI 1.40 to 4.27, P = 0.002; moderate quality evidence). A similar effect was seen for any degree of improvement in venous patency. Up to five years after treatment significantly less PTS occurred in those receiving thrombolysis (RR 0.66, 95% CI 0.53 to 0.81; P < 0.0001; moderate quality evidence). This reduction in PTS was still observed at late follow-up (beyond five years), in two studies (RR 0.58, 95% CI 0.45 to 0.77; P < 0.0001; moderate quality evidence). Leg ulceration was reduced although the data were limited by small numbers (RR 0.87; 95% CI 0.16 to 4.73, P = 0.87). Those receiving thrombolysis had increased bleeding complications (RR 2.23; 95% CI 1.41 to 3.52, P = 0.0006; moderate quality evidence). Three strokes occurred in the treatment group, all in trials conducted pre-1990, and none in the control group. There was no significant effect on mortality detected at either early or intermediate follow-up. Data on the occurrence of pulmonary embolism (PE) and recurrent DVT were inconclusive. Systemic thrombolysis and CDT had similar levels of effectiveness. Studies of CDT included two trials in femoral and iliofemoral DVT, and results from these are consistent with those from trials of systemic thrombolysis in DVT at other levels of occlusion.

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Periprocedural bridging anticoagulation

Rechenmacher SJ, Fang JC. Bridging Anticoagulation: Primum Non Nocere. J Am Coll Cardiol. 2015 Sep 22;66(12):1392-403.

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Conclusions: Periprocedural anticoagulation management is a common clinical dilemma with limited evidence (but 1 notable randomized trial) to guide our practices. Although bridging anticoagulation may be necessary for those patients at highest risk for TE, for most patients it produces excessive bleeding, longer length of hospital stay, and other significant morbidities, while providing no clear prevention of TE. Unfortunately, contemporary clinical practice, as noted in physician surveys, continues to favor interruption of OAC and the use of bridging anticoagulation. While awaiting the results of additional randomized trials, physicians should carefully reconsider the practice of routine bridging and whether periprocedural anticoagulation interruption is even necessary.

Central Illustration. Bridging Anticoagulation: Algorithms for Periprocedural Interrupting and Bridging Anticoagulation. Decision trees for periprocedural interruption of chronic oral anticoagulation (top) and for periprocedural bridging anticoagulation (bottom). OAC = oral anticoagulation.

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Systemic Thrombolysis for Pulmonary Embolism

Tapson VF, Friedman O. Systemic Thrombolysis for Pulmonary Embolism: Who and How. Tech Vasc Interv Radiol. 2017 Sep;20(3):162-174.

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PE screenshot

“For several decades, clinicians and clinical trialists have worked toward a more aggressive, yet safe solution for patients with intermediate-risk PE. Standard-dose thrombolysis, low-dose systemic thrombolysis, and catheter-based therapy which includes a number of devices and techniques, with or without low-dose thrombolytic therapy, have offered potential solutions and this area has continued to evolve. On the basis of heterogeneity within the category of intermediate-risk as well as within the high-risk group of patients, we will focus on the use of systemic thrombolysis in carefully selected high- and intermediate-risk patients. In certain circumstances when the need for aggressive therapy is urgent and the bleeding risk is acceptable, this is an appropriate approach, and often the best one.”

More PubMed results on systemic thrombolysis.

Article of interest: COVID-19 associated hyperviscosity: a link between inflammation and thrombophilia?

Maier CL, Truong AD, Auld SC, Polly DM, Tanksley CL, Duncan A. COVID-19 associated hyperviscosity: a link between inflammation and thrombophilia? Lancet. 2020 May 25:S0140-6736(20)31209-5. Epub ahead of print.

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“The 15 patients had plasma viscosity exceeding 95% of normal, as determined by traditional capillary viscometry, ranging from 1·9–4·2 centipoise (cP; normal range 1·4–1·8). Notably, the four patients with plasma viscosity above 3·5 cP had a documented thrombotic complication: one patient had pulmonary embolism, one patient had limb ischaemia and suspected pulmonary embolism, and two patients had CRRT-related clotting. Plasma viscosity and Sequential Organ Failure Assessment scores, a measure of illness severity, were strongly correlated (Pearson’s r=0·841, R2=0·7072, p<0·001; appendix).”

Emory doctors study link between thickness of blood, clotting and inflammation in COVID-19 patients.

Infection rates of different CVC insertion sites

Arvaniti K, et al. Cumulative Evidence of Randomized Controlled and Observational Studies onCatheter-Related Infection Risk of Central Venous Catheter Insertion Site in ICU Patients: A Pairwise and Network Meta-Analysis. Crit Care Med. 2017 Apr;45(4):e437-e448.

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Data Synthesis: Twenty studies were included; 11 were observational, seven were randomized controlled trials for other outcomes, and two were randomized controlled trials for sites. We evaluated 18,554 central venous catheters: 9,331 from observational studies, 5,482 from randomized controlled trials for other outcomes, and 3,741 from randomized controlled trials for sites. Colonization risk was higher for internal jugular (relative risk, 2.25 [95% CI, 1.84-2.75]; I2 = 0%) and femoral (relative risk, 2.92 [95% CI, 2.11-4.04]; I2 = 24%), compared with subclavian. Catheter-related bloodstream infection risk was comparable for internal jugular and subclavian, higher for femoral than subclavian (relative risk, 2.44 [95% CI, 1.25-4.75]; I2 = 61%), and lower for internal jugular than femoral (relative risk, 0.55 [95% CI, 0.34-0.89]; I2 = 61%). When observational studies that did not control for baseline characteristics were excluded, catheter-related bloodstream infection risk was comparable between the sites.

Conclusions: In ICU patients, internal jugular and subclavian may, similarly, decrease catheter-related bloodstream infection risk, when compared with femoral. Subclavian could be suggested as the most appropriate site, whenever colonization risk is considered and not, otherwise, contraindicated. Current evidence on catheter-related bloodstream infection femoral risk, compared with the other sites, is inconclusive.

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Heparin-induced thrombocytopenia (HIT): The use of platelet transfusion

One of the topics of discussion this week was the utilization of platelet transfusions in patients with heparin-induced thrombocytopenia.

Goel R, et al. Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality. Blood. 2015 Feb 26;125(9):1470-6.

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While platelets are primary mediators of hemostasis, there is emerging evidence to show that they may also mediate pathologic thrombogenesis. Little data are available on risks and benefits associated with platelet transfusions in thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT) and immune thrombocytopenic purpura (ITP). This study utilized the Nationwide Inpatient Sample to evaluate the current in-hospital platelet transfusion practices and their association with arterial/venous thrombosis, acute myocardial infarction (AMI), stroke, and in-hospital mortality over 5 years (2007-2011). Age and gender-adjusted odds ratios (adjOR) associated with platelet transfusions were calculated. There were 10 624 hospitalizations with TTP; 6332 with HIT and 79 980 with ITP. Platelet transfusions were reported in 10.1% TTP, 7.1% HIT, and 25.8% ITP admissions. Platelet transfusions in TTP were associated with higher odds of arterial thrombosis (adjOR = 5.8, 95%CI = 1.3-26.6), AMI (adjOR = 2.0, 95%CI = 1.2-3.3) and mortality (adjOR = 2.0,95%CI = 1.3-3.0), but not venous thrombosis. Platelet transfusions in HIT were associated with higher odds of arterial thrombosis (adjOR = 3.4, 95%CI = 1.2-9.5) and mortality (adjOR = 5.2, 95%CI = 2.6-10.5) but not venous thrombosis. Except for AMI, all relationships remained significant after adjusting for clinical severity and acuity. No associations were significant for ITP. Platelet transfusions are associated with higher odds of arterial thrombosis and mortality among TTP and HIT patients.

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Epidurals, DVTs, and chemical prophylaxis in the setting of oncologic surgery

One discussion this week involved preoperative epidurals and chemical prophylaxis.

Reference: Manguso N, et al. The impact of epidural analgesia on the rate of thromboembolism without chemical thromboprophylaxis in major oncologic surgery. The American Surgeon. 2018 Jun 1;84(6):851-855.

Summary: General surgery patients are at a particularly high risk of developing deep vein thrombosis (DVT) without prophylaxis and some data suggest their risk increases 2-fold if an underlying malignancy is present. A meta-analysis by Leonardi et al (2007) found that without chemical prophylaxis, the rate of DVT is as high as 35%, which drops to 12% if a patient receives chemical prophylaxis.

Although the use of chemical prophylaxis to reduce the risk of thromboembolic events has been validated in numerous studies, these drugs increase the risk of bleeding. Risk of bleeding in the setting of epidural analgesia may put the patient at risk for the potentially catastrophic complication of epidural hematoma which may lead to long-term paralysis.

Manguso et al (2018) evaluated the rate of thromboembolic events in cancer patients undergoing major oncologic abdominal and/or pelvic surgery who had a preoperative epidural catheter (EC) placed for postoperative pain control.

The aim of this study was to evaluate the need for chemical thromboprophylaxis in patients undergoing major abdominal or pelvic oncologic surgery with preoperative EC placement for postoperative pain control. Of the 285 patients for whom data were collected over this five-year period, the rates of above knee and below-knee DVTs were 3.2 and 5.2%, respectively. These patients were all asymptomatic and had no serious adverse events occur secondary to the identified thromboses.

A secondary finding was that 2.5% of patients had above-knee DVT before undergoing surgery; thus, it is important to consider the patient’s risk factors for DVT and screen preoperatively if there is concern.

Our data suggest that patients undergoing major open operations with epidural analgesia have low rates of DVT and may obviate the need for chemical prophylaxis. However, larger studies are required to determine the overall effects of epidural analgesia on the development of DVTs postoperatively.