NIH Treatment Guidelines: Antithrombotic Therapy in Patients With COVID-19

Antithrombotic Therapy in Patients With COVID-19

(Last Updated: February 11, 2021.)

For hospitalized patients with COVID-19, prophylactic dose anticoagulation should be prescribed unless contraindicated (e.g., a patient has active hemorrhage or severe thrombocytopenia) (AIII). Although data supporting this recommendation are limited, a retrospective study showed reduced mortality in patients who received prophylactic anticoagulation, particularly if the patient had a sepsis-induced coagulopathy score ≥4.4 For those without COVID-19, anticoagulant or antiplatelet therapy should not be used to prevent arterial thrombosis outside of the standard of care (AIII). Anticoagulation is routinely used to prevent arterial thromboembolism in patients with heart arrhythmias. Although there are reports of strokes and myocardial infarction in patients with COVID-19, the incidence of these events is unknown.

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D-dimer testing to determine the duration of anticoagulation therapy

Palareti G, Cosmi B, Legnani C, et al.; DULCIS Investigators. D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood. 2014 Jul 10;124(2):196-203.

Full-text for Emory users.

The optimal duration of anticoagulation in patients with venous thromboembolism (VTE) is uncertain. We investigated whether persistently negative D-dimers in patients with vein recanalization or stable thrombotic burden can identify subjects at low recurrence risk. Outpatients with a first VTE (unprovoked or associated with weak risk factors) were eligible after at least 3 months (12 in those with residual thrombosis) of anticoagulation. They received serial D-dimer measurements using commercial assays with predefined age/sex-specific cutoffs and were followed for up to 2 years. Of 1010 patients, anticoagulation was stopped in 528 (52.3%) with persistently negative D-dimer who subsequently experienced 25 recurrences (3.0% pt-y; 95% confidence interval [CI], 2.0-4.4%). Of the remaining 482 patients, 373 resumed anticoagulation and 109 refused it. Recurrent VTE developed in 15 patients (8.8% pt-y; 95% CI, 5.0-14.1) of the latter group and in 4 of the former (0.7% pt-y; 95% CI, 0.2-1.7; hazard ratio = 2.92; 95% CI, 1.87-9.72; P = .0006). Major bleeding occurred in 14 patients (2.3% pt-y; 95% CI, 1.3-3.9) who resumed anticoagulation. Serial D-dimer measurement is suitable in clinical practice for the identification of VTE patients in whom anticoagulation can be safely discontinued. This study was registered at clinicaltrials.gov as #NCT00954395.

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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.

Full-text for Emory users.

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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Extended-duration thromboprophylaxis after CRS/HIPEC

Khan S, et al. Incidence, Risk Factors, and Prevention Strategies for Venous Thromboembolism after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Ann Surg Oncol. 2019 Jul;26(7):2276-2284.

Full-text for Emory users.

“A policy change was made in February 2010 to discharge all patients post-CRS/HIPEC with 14 days of additional pharmacothromboprophylaxis, which consisted of low-molecular-weight heparin in 327 of 447 (73%) cases (Supplemental Figure). The 60-day VTE rate decreased from 10.2 to 4.9% after this policy was instituted (p = 0.10, Fig. 2).”

“This policy is in accordance with established guidelines indicating the need for a total of 4 weeks of pharmacothromboprophylaxis in high-risk patients after abdominal or pelvic surgery for cancer. [2,21] Given that patients have an average length of stay of nearly 2 weeks, discharging them on 14 days of pharmacothromboprophylaxis fulfills this duration.”

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Guidelines for the perioperative management of anticoagulants

One discussion this week focused on the perioperative management of NOACs.


Reference:  DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 -. Record No. 227537, Periprocedural management of patients on long-term anticoagulation; [updated 2018 Oct 10, cited 2018 Oct 12; [about 26 screens]. Emory login required.

Summary: The information below is from DynaMed Plus (2018). To view full information on the topic, click on the citation above.

Vitamin K antagonists in patients undergoing major surgery or procedures

  • Consider continuing vitamin K antagonist (VKA) therapy in patients who require minor dental procedures, minor dermatological procedures, or cataract surgery.
  • In those having a minor dental procedure, consider coadministering an oral hemostatic agent or stopping the VKA 2 to 3 days before the procedure.
  • In those undergoing implantation of a pacemaker or an implantable cardioverter device, consider continuing VKA therapy.
  • In those having a major surgery or procedure, stop VKA therapy 5 days before surgery.
  • Resume VKA therapy 12-24 hours after surgery when there is adequate hemostasis.

Bridging therapy in patients undergoing major surgery or procedures

  • If at low risk for thrombosis, consider omitting bridging therapy.
  • If at moderate risk for thrombosis, assess individual patient- and surgery-related factors when considering bridging therapy.
  • If at high risk for thrombosis consider bridging therapy with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH).
  • For those receiving bridging therapy with UFH, stop UFH 4-6 hours before surgery.
  • For those receiving bridging therapy with therapeutic-dose LMWH, stop LMWH 24 hours before surgery.
  • For those receiving bridging therapy with UFH or therapeutic-dose LMWH and undergoing non-high-bleeding-risk surgery, consider resuming heparin 24 hours after surgery.
  • For those receiving bridging therapy with UFH or therapeutic-dose LMWH and undergoing high-bleeding-risk surgery, consider resuming heparin 48-72 hours after surgery.

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The PAUSE study: Safety of perioperative DOAC management in patients with atrial fibrillation

A discussion during a previous conference included the perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant (DOAC).


Reference: Douketis JD, et al. Perioperative management of patients with atrial fibrillation receiving a direct oral anticoagulant. JAMA Internal Medicine. 2019 Aug 5; doi:10/1001/jamainternmed.2019.2431

Summary: Each year, 1 in 6 patients with AF, or an estimated 6 million patients worldwide, will require perioperative anticoagulant management. When DOAC regimens became available for clinical use in AF, starting in 2010, no studies had been conducted to inform the timing of perioperative DOAC therapy interruption and resumption, whether heparin bridging should be given, and whether preoperative coagulation function testing was needed. Uncertainty about the perioperative management of DOACs may be associated with unsubstantiated practices and increased harm to patients.

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