Acute limb ischemia and antithrombotic therapy in COVID-19 patients

Galyfos G, et al. Acute limb ischemia among patients with COVID-19 infection. J Vasc Surg. 2022 Jan;75(1):326-342. doi: 10.1016/j.jvs.2021.07.222. Epub 2021 Aug 12.

Results: In total, 34 studies (19 case reports and 15 case series/cohort studies) including a total of 540 patients (199 patients were eligible for analysis) were evaluated. All studies were published in 2020. Mean age of patients was 61.6 years (range, 39-84 years; data from 32 studies) and 78.4% of patients were of male gender (data from 32 studies). There was a low incidence of comorbidities: arterial hypertension, 49% (29 studies); diabetes mellitus, 29.6% (29 studies); dyslipidemia, 20.5% (27 studies); chronic obstructive pulmonary disease, 8.5% (26 studies); coronary disease, 8.3% (26 studies); and chronic renal disease, 7.6% (28 studies). Medical treatment was selected as first-line treatment for 41.8% of cases. Pooled mortality rate among 34 studies reached 31.4% (95% confidence interval [CI], 25.4%%-37.7%). Pooled amputation rate among 34 studies reached 23.2% (95% CI, 17.3%-29.7%). Pooled clinical improvement rate among 28 studies reached 66.6% (95% CI, 55.4%%-76.9%). Pooled reoperation rate among 29 studies reached 10.5% (95% CI, 5.7%%-16.7%). Medical treatment was associated with a higher death risk compared with any intervention (odds ratio, 4.04; 95% CI, 1.075-15.197; P = .045) although amputation risk was not different between the two strategies (odds ratio, 0.977; 95% CI, 0.070-13.600; P = .986) (data from 31 studies).

Conclusions: SARS-CoV-2 infection is associated with a high risk for thrombotic complications, including ALI. COVID-associated ALI presents in patients with a low incidence of comorbidities, and it is associated with a high mortality and amputation risk. Conservative treatment seems to have a higher mortality risk compared with any intervention, although amputation risk is similar.

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Mesenteric ischemia caused by heparin-induced thrombocytopenia

Ahmed M, et al. Mesenteric Ischemia Caused by Heparin-induced Thrombocytopenia: A Case Report. Cureus. 2019 Jan 16;11(1):e3900.

“The incidence of HIT incidence is 0.1% – 5% in patients receiving heparin with 35% – 50% of those patients developing thrombosis. It should always be suspected in patients receiving heparin who develop a new onset thrombocytopenia with platelet counts are less than 150,000, or there is a drop of 50% or more in the platelet count, venous or arterial thrombosis, skin necrosis at the site of the injection, and if the patient develops acute systemic reactions after intravenous (IV) administration of heparin (fever, chills, tachycardia, hypertension, dyspnea, cardiopulmonary arrest). Antibody formation typically requires four or more days of exposure to heparin and presents with a dropping platelet count within five to 14 days. HIT is subdivided into two subtypes: HIT Type I (none immune and usually resolves spontaneously in few days) and HIT Type II which is immune-mediated (immunoglobulin G (IgG) antibody against heparin-platelet factor 4 (PF4) complex) resulting in excessive thrombin generation that leads to venous or arterial thrombosis [5].

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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.

Full-text for Emory users.

Recommendations: 

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.