The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China
in December 2019 has led to an ongoing global pandemic with more than 8.5 million
cases and 460,000 deaths worldwide.[1] Early reports from Wuhan, China, where the pandemic is believed to have originated,
highlighted abnormal coagulation studies in patients, including elevated levels of
D-dimer and fibrinogen, prolonged prothrombin time (PT), and mild thrombocytopenia.[2]
[3]
[4] Severe coronavirus disease-2019 (COVID-19) is associated with pulmonary microvascular
thrombosis, and arterial and venous thromboembolism that has been termed COVID-associated
coagulopathy (CAC).[5]
[6] The pathophysiology of CAC is incompletely understood, but includes upregulation
of proinflammatory cytokines that promote immunothrombosis and endothelial dysfunction
leading to widespread micro- and macrovascular thrombosis.[7]
[8]
[9]
[10] These thromboembolic events are particularly prevalent in critically ill patients
(35–45%), even when compared with other critically ill patients with non-COVID-19
diagnoses (5–15%).[11] Although initial reports from China included patients who were not on thromboprophylaxis,
the use of heparin thromboprophylaxis was shown to decrease mortality, especially
in subsets of patients with higher D-dimer levels.[12]
[13] Furthermore, studies from Europe have demonstrated high venous thromboembolism (VTE)
rates despite the use of pharmacologic thromboprophylaxis.[5]
Given the concern for the heightened thrombotic risk and the contribution of the ensuing
hypercoagulable state to the considerable morbidity and mortality of severe COVID-19,
the role of anticoagulation beyond standard thromboprophylaxis for hospitalized medical
patients has been raised. Currently, several drugs targeting the thromboinflammatory
pathway in COVID-19 patients are under investigation, including parenteral and oral
antithrombotics, antiplatelet, and fibrinolytic agents.[14]
Notably, several clinical trials are currently underway to examine the role of higher
than standard dose thromboprophylaxis and even therapeutic intensity anticoagulation
prophylaxis in patients with COVID-19 (e.g., NCT04359277, NCT04345848, and NCT04344756).
However, in the absence of randomized clinical trial data, numerous professional societies
have published interim consensus recommendations to guide clinicians based on expert
consensus and observational data ([Table 1]).[15]
[16]
[17]
[18]
[19]
[20] These documents universally recommend standard prophylactic doses of low molecular
weight heparin (LMWH) or subcutaneous unfractionated heparin (UFH) for all hospitalized
patients with COVID-19. In addition, monitoring of coagulation parameters, including
platelet count, PT, D-dimer, and fibrinogen, are encouraged. The American Society
of Hematology guidelines published in May 2020 specifies that therapeutic anticoagulation
is not required unless documented indications such as VTE or atrial fibrillation are
present.[17] A notable specified exception is presumed VTE, such as acute respiratory decompensation
in intubated patients with clinical and laboratory findings that are suggestive of
VTE, when radiographic confirmation is not feasible. Epidemiologic data are currently
lacking for postdischarge rates of VTE in COVID-19 patients, although factors including
the hypercoaguable state of COVID-19, comorbidities, advanced age, and prolonged hospitalization
may put these patients at higher risk.[21] Of note, three of the existing guidelines recommend postdischarge thromboprophylaxis
([Table 1]).[16]
[17]
[20]
Table 1
Current societal guidance
Source
|
Recommendation
|
Date Published
|
International Society on Thrombosis and Haemostasis[18]
|
Monitor: Platelet count, PT, D-dimer and fibrinogen
|
March 25, 2020
|
Prophylactic LMWH should be considered in all patients who require hospitalization
for COVID-19 infection unless contraindicated (active bleeding, platelet < 25 × 109/L; monitoring advised in severe renal impairment)
|
American Society of Hematology[17]
|
Monitor: Platelet count, PT/aPTT, D-dimer, and fibrinogen
|
May 18, 2020
|
Prophylactic dose LMWH is recommended for all hospitalized COVID-19 patients despite
abnormal coagulation tests in the absence of active bleeding, and held only if platelet < 25 × 109/L, or fibrinogen less than 0.5 g/L
Therapeutic anticoagulation is not required unless VTE or atrial fibrillation is documented
Empiric therapeutic anticoagulation may be considered in the following cases when
imaging cannot be performed: intubated patients who develop sudden clinical and laboratory
findings highly consistent with PE, patients with physical findings of thrombosis
(i.e., superficial thrombophlebitis, cyanosis, thrombosis of dialysis filters/catheters/tubing),
or patients with respiratory failure with very high D-dimer and fibrinogen and in
which other causes have not been identified
All patients with COVID-19 who are started on empiric therapeutic anticoagulation
for presumed or documented PE should be given a minimum course of 3 months of the
therapeutic regimen
It is reasonable to consider extended thromboprophylaxis after discharge using a regulatory-approved
regimen (e.g., betrixaban 160 mg on day 1 followed by 80 mg once daily for 35–42 days
or rivaroxaban 10 mg daily for 31–39 days). Any decision to use postdischarge thromboprophylaxis
should consider the individual patient's VTE risk factors, including reduced mobility
and bleeding risk as well as feasibility
The use of LMWH or UFH in hospitalized critically ill patients should be considered
because of the shorter half-life and fewer drug–drug interactions compared with direct
oral anticoagulants and potential antiviral therapies
|
American College of Cardiology[16]
|
For hospitalized patients with COVID-19 and not in DIC or in suspected/confirmed DIC
but not overtly bleeding, prophylactic doses of anticoagulation can be administered
to prevent VTE with enoxaparin 40 mg daily or similar LMWH regimen (e.g., dalteparin
5000 U daily), or UFH 5000 U SC BID or TID for renal dysfunction. There is insufficient
data to consider routine therapeutic or intermediate-dose parenteral anticoagulation
with UFH or LMWH
For patients with moderate or severe COVID-19 and an indication for dual antiplatelet
therapy (e.g., PCI within the past 3 months or recent myocardial infarction) and with
suspected/confirmed DIC without overt bleeding, in the absence of evidence, decisions
for antiplatelet therapy need to be individualized. In general, it is reasonable to
continue dual antiplatelet therapy if platelet > 50,000, reduce to single antiplatelet
therapy if 25,000 < platelet < 50,000, and discontinue if platelet < 25,000
For patients with presentations concerning for STEMI and COVID-19, clinicians should
weigh the risks and severity of STEMI presentation with that of potential COVID-19
severity in the patient, as well as risk of COVID-19 to the individual clinicians
and to the health care system at large to inform decisions on primary percutaneous
coronary intervention or fibrinolytic therapy
Special attention should be also given to drug–drug interactions between antiplatelet
agents or anticoagulants, i.e., DOAC, and COVID-19 investigational therapies
Pharmacological prophylaxis for up to 45 days postdischarge should be considered if
there is elevated risk for thrombotic events (prior VTE, active cancer, major cardiopulmonary
disease) without high bleeding risk
|
April 15, 2020
|
World Health Organization[19]
|
Use pharmacological prophylaxis (LMWH [preferred if available] or heparin 5000 U SC
BID) in adolescents and adults without contraindications. For those with contraindications,
use mechanical prophylaxis (intermittent pneumatic compression devices)
|
March 13, 2020
|
National Institutes of Health[26]
|
Monitor: In nonhospitalized patients with COVID-19, there are currently no data to
support the measurement of coagulation markers (e.g., D-dimers, prothrombin time,
platelet count, fibrinogen)
In hospitalized patients with COVID-19, hematologic and coagulation parameters are
commonly measured, although there are currently insufficient data to recommend for
or against using this data to guide management decisions
|
May 12, 2020
|
Patients who are receiving anticoagulant or antiplatelet therapies for underlying
conditions should continue these medications if they receive a diagnosis of COVID-19
Any time anticoagulant or antiplatelet therapy is being used consideration must be
given to potential drug–drug interactions with other concomitant drugs.
Venous thromboembolism prophylaxis and screening:
Hospitalized adults with COVID-19 should receive VTE prophylaxis per the standard
of care for other hospitalized adults
LMWH or UFH may be preferred in hospitalized, critically ill patients because of their
shorter half-lives, ability to be administered intravenously or subcutaneously, and
fewer drug–drug interactions compared with oral anticoagulants
There are currently insufficient data to recommend for or against the use of thrombolytics
or increasing anticoagulant doses for VTE prophylaxis in hospitalized COVID-19 patients
outside the setting of a clinical trial
Patients with COVID-19 who experience an incident thromboembolic event or who are
highly suspected to have thromboembolic disease at a time when imaging is not possible
should be managed with therapeutic doses of anticoagulant therapy as per the standard
of care for patients without COVID-19
Patients with COVID-19 who require extracorporeal membrane oxygenation or continuous
renal replacement therapy or who have thrombosis of catheters or extracorporeal filters
should be treated with antithrombotic therapy per the standard institutional protocols
for those without COVID-19
Hospitalized patients with COVID-19 should not routinely be discharged on VTE prophylaxis,
however, using Food and Drug Administration-approved regimens, extended VTE prophylaxis
can be considered in patients who are at low risk for bleeding and high risk for VTE
as per protocols for patients without COVID-19
|
Spanish Society of Cardiology[15]
|
Monitor: It is proposed to monitor the proinflammatory and hemostatic parameters every
24–48 hours including C-reactive protein, D-dimer, IL-6, ferritin, and absolute lymphocyte
count
|
April 22, 2020
|
Prophylactic LMWH (enoxaparin 40 mg/24 h or bemiparin 3500 U/24 h) should be considered
in all patients who require hospitalization for COVID-19 infection unless contraindicated
(active bleeding, platelet < 20 × 109/L), with weight-adjusted doses for patients with a body mass index > 35 or renal
impairment
If the patient does not have refractory respiratory insufficiency (PaO2/FiO2 < 200 or SaO2/FiO2 < 300), does not have a high risk of thromboembolism (determined by 2 or more of
the following proinflammatory parameters, CRP > 15, D-dimer > 3× ULN, IL-6 > 40, ferritin > 1000,
and/or lymphocytopenia < 800) and does not have a history of prior VTE or ischemic
vascular disease, prophylactic LMWH should be used
If the patient has refractory respiratory insufficiency but does not have high risk
features (criteria noted above), intermediate dose LMWH (enoxaparin 1 mg/kg/24 h or
bemiparin 5000 U/24 h) is recommended
If the patient has refractory respiratory insufficiency and high-risk features (criteria
noted above) or a high suspicion for VTE, high-dose LMWH (enoxaparin 1 mg/kg/12 h
or bemiparin 175 U/kg/24 h) is recommended
If the diagnosis of VTE is established, LMWH should be administered at therapeutic
doses
Hospitalized patients who are receiving anticoagulant therapies for underlying conditions
should continue these medications if stable and do not meet criteria for severe disease
or may be transitioned to LMWH if they receive a diagnosis of COVID-19 (with adjustments
for renal insufficiency)
It is considered prudent to prolong the use of LMWH in prophylactic doses for 7–10
days after discharge
In patients with an acute STEMI, even though primary angioplasty is the preferred
reperfusion strategy, fibrinolysis can be considered for infected patients with a
poor clinical situation that makes transfer difficult or who have a low bleeding risk
and symptoms of evolution < 3 hours
If it is considered essential to use any of the antiviral treatments that interact
with clopidogrel or ticagrelor, then it would be reasonable to prescribe prasugrel
|
Abbreviations: aPTT, activated partial thromboplastin time; BID, two times a day;
COVID-19, coronavirus disease-2019; CRP, C-reactive protein; DIC, disseminated intravascular
coagulation; DOAC, direct oral anticoagulant; IL, interleukin; LMWH, low molecular
weight heparin; PCI, percutaneous coronary intervention; PE, pulmonary embolism; PT,
prothrombin time; STEMI, ST-elevation myocardial infarction; TID, three times a day;
UFH, unfractionated heparin; ULN, upper limit of normal; VTE, venous thromboembolism.
Until more evidence-based guidelines for thromboprophylaxis are available, individual
medical institutions have created their own institutional algorithms, presumably based
on local individual expertise and consensus, as well as interim professional society
and governmental recommendations.[21]
[22] To assess the alignment of these institutional recommendations with published guidance
from national and international professional societies and health authorities, we
obtained local written algorithms from 15 large U.S. institutions across 11 U.S. states
([Table 2]). Written treatment algorithms from these institutions were obtained by searching
publicly available online algorithms or via a unique educational initiative, “Hematology
and Oncology Inter-Institutional Collaborative Videoconferencing Learning,” that brings
together hematology and oncology fellowship trainees, faculty, and program leadership
from these 15 institutions to share important updates and institutional best practices
at the participating institutions.
Table 2
Institutional algorithms
Institution
|
Risk stratification
|
Hospitalized
|
Outpatient
|
Date published
|
Low/Intermediate risk
|
High risk
|
ICU
|
University of Michigan,
Ann Arbor, MI
|
Wells & VTE-BLEED scores
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency
|
If elevated Wells for DVT/PE and low VTE-BLEED (< 2) → therapeutic a/c UFH, Enoxaparin
1 mg/kg SC BID or DOACs
If elevated Wells, but elevated VTE-BLEED, consider imaging and prophylactic a/c vs.
therapeutic a/c depending on findings
|
If Wells score low and high risk of bleeding → thromboprophylaxis
If VTE-BLEED low (< 2), regardless of Wells score → VTE treatment with UFH w/ goal
anti-Xa depending on case
If elevated Well's and VTE-BLEED → consider imaging and prophylactic a/c vs. therapeutic
a/c depending on findings
|
If on therapeutic a/c, upon discharge continue LMWH, UFH, or DOAC treatment for 1–2
months
|
April 3, 2020
|
New York Presbyterian Hospital/
Weil Cornell/, Columbia
NY, NY
|
Clinical signs/symptoms
Troponin
BNP
D-dimer
SIC score
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
If confirmed PE/DVT, treat with therapeutic anticoagulation and consider thrombolysis
or systemic fibrinolysis if refractory hypoxemia or ongoing clinical instability
If high clinical suspicion for PE/DVT, defined by hemodynamic instability and parameters
listed, consider further imaging such as TTE to evaluate RV strain or venous Doppler
ultrasonography, and treat with therapeutic anticoagulation if evidence of RV strain
or DVT
|
|
April 7, 2020
|
Johns Hopkins University Hospital,
Baltimore, MD
|
Fibrinogen > 500 mg/dL
D-dimer > 2 mg/L
Chromogenic Factor VIII activity > 250 IU/dL
Platelet > 350 k/μL
High risk characteristics: Pregnancy, active malignancy, prior VTE, sickle cell disease,
known thrombophilia
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
|
Enoxaparin 30 mg SC BID or
Heparin 7500 SC TID (with adjustments for BMI or renal insufficiency)
|
Recommended for patients with ARDS, heavily sedated, and at high risk of VTE/PE:
Enoxaparin 30 mg SC BID or
Heparin 7500 SC TID (with adjustments for BMI or renal insufficiency)
|
|
April 13, 2020
|
University of North Carolina,
Chapel Hill, NC
|
D-dimer > 2,500 ng/ml (10× ULN per UNC assay)
|
IF D-dimer < 2,500 ng/mL and no clinical suspicion or radiographic evidence of DVT/PE
→ Enoxaparin 30 mg SC BID (with adjustment for BMI) or UFH 5,000 units TID
IF D-dimer > 2,500 ng/mL and no clinical suspicion or radiographic evidence of DVT/PE
→ Enoxaparin 0.5 mg/kg SC BID (with adjustment for BMI) or UFH with 60 u/kg bolus
and goal anti-Xa 0.3–0.7
If confirmed DVT/PE, prior condition requiring therapeutic a/c, high clinical suspicion
or renal failure with recurrent clotting of dialysis tubing enoxaparin 1.0 mg/kg SC
BID (with adjustment for BMI) or UFH with 80 u/kg bolus and goal anti-Xa 0.3–0.7
|
Apixaban 2.5 mg PO BID or rivaroxaban 10 mg daily for 30 days postdischarge or until
mobile
|
April 13, 2020
|
Massachusetts General Hospital,
Boston, MA
|
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
If confirmed or high clinical suspicion for PE/DVT, treat with therapeutic anticoagulation
with LMWH or UFH
|
|
April 14, 2020
|
Loyola University Medical Center,
Chicago, IL
|
D-dimer > 5× ULN
SIC ≧ 4
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
|
Enoxaparin 0.6 mg/kg SC BID or low dose UFH nomogram
|
Refer to risk category
|
Continue thromboprophylaxis or a/c treatment at same dose as inpatient or apixaban
2.5 mg BID for 1 month postdischarge
|
April 15, 2020
|
Moffitt Cancer Center/ University of South Florida,
Tampa, FL
|
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
If confirmed or high clinical suspicion for PE/DVT, treat with therapeutic anticoagulation
with LMWH or UFH
|
|
April 15, 2020
|
Mount Sinai Hospital,
NY, NY
|
↑ O2 requirement
↑ D-dimer
↑ Cr
↑ CRP
|
Enoxaparin 40mg SC daily or
apixaban 2.5–5 mg PO BID
|
Enoxaparin 1 mg/kg SC Q12H or apixaban 5 mg PO BID or
UFH w/ standard VTE target
|
UFH w/ standard VTE target or
enoxaparin SC 1 mg/kg SC BID
|
Consider treatment dose a/c, apixaban 5 mg PO BID for 2 weeks postdischarge for patients
on therapeutic a/c while inpatient
|
April 15, 2020
|
Yale New Haven Health System,
New Haven, CT
|
D-dimer ≧ 5 mg/L
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
If confirmed or high clinical suspicion for PE/DVT, treat with therapeutic anticoagulation
with LMWH, UFH, or DOAC
|
If mechanically vented/on ECMO AND D-dimer ≧ 5 mg/L → Enoxaparin 0.5 mg/kg SC BID
or apixaban (UFH for CrCl < 30 mL/min)
|
|
April 20, 2020
|
Beth Israel Deaconess Medical Center,
Boston, MA
|
D-dimer < 1,500 ng/mL
TEG c/w hypercoagulability
High suspicion of thromboembolism
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
If confirmed or high clinical suspicion for PE/DVT, treat with therapeutic anticoagulation
with LMWH or UFH
|
Enoxaparin 40 mg SC BID or
Heparin 7500 SC TID;
Consider therapeutic a/c w/ UFH, enoxaparin 1 mg/kg SC BID or DOACs if severe hypoxemic
respiratory failure AND markers;
Consider fibrinolytic salvage therapy with P:F < 100 consistently
|
Continuation after
discharge can be considered in patients expected to have a period of prolonged immobility,
provided they are not at high bleeding risk
|
April 21, 2020
|
Emory University,
Atlanta, GA
|
D-dimer ≧ 3000 ng/mL
(6× ULN per Emory Univ assay)
|
IF D-dimer < 3,000 ng/mL and no clinical suspicion or radiographic evidence of DVT/PE
→ Level 1: LMWH 0.5 mg/kg/day (with adjustments for BMI or UFH for renal insufficiency)
IF D-dimer ≧ 3,000 ng/mL and no clinical suspicion or radiographic evidence of DVT/PE
→ Level 2: LMWH 1 mg/kg/day or heparin gtt low-standard with no bolus if renal insufficiency
IF known or suspected VTE, or otherwise unexplained increase in oxygen requirement,
dead space, or organ failure (e.g., AKI, MSOF) with concern for microvascular thrombi
→ Level 3: LMWH 1 mg/kg/BID or heparin gtt high-standard with bolus if renal insufficiency
|
Recommended extended prophylaxis depending on inpatient therapy:
Level 1: 7 days of continued prophylaxis with LMWH or DOAC (preferred)
Level 2: Continue treatment for 4–6 weeks with LMWH or DOAC (preferred)
Level 3: Continue treatment for 3 months for provoked VTE with treatment-dose LMWH,
warfarin, or DOAC (preferred)
|
April 21, 2020
|
Vanderbilt University Medical Center,
Nashville, TN
|
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
If confirmed or high clinical suspicion for PE/DVT, treat with therapeutic anticoagulation
with LMWH or UFH
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
If confirmed or high clinical suspicion for PE/DVT, treat with therapeutic anticoagulation
with LMWH or UFH
|
|
April 22, 2020
|
University of Alabama at Birmingham Hospital,
Birmingham, AL
|
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
If confirmed or high clinical suspicion for PE/DVT, treat with therapeutic anticoagulation
with LMWH or UFH
|
|
May 1, 2020
|
University of Pennsylvania,
Philadelphia, PA
|
Sick = Clinical deterioration,
High risk of ICU transfer: ≥6 LPM O2, signs of organ failure
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
|
If “sick” and low risk of bleeding, consider intermediate dosing with LMWH 0.5 mg/kg
BID or therapeutic dosing with LMWH 1 mg/kg SC BID (with adjustments for BMI or UFH
for renal insufficiency)
If “sick” and high risk of bleeding, consider standard or intermediate dosing
|
Extended prophylaxis should be strongly considered in patients with low bleeding risk
with betrixaban 160 mg PO × 1 followed by 80 mg PO daily for 35–42 days, rivaroxaban
10 mg daily for 45 days from discharge, or enoxaparin 40 mg SC daily for 28 days from
discharge
|
May 1, 2020
|
Cleveland Clinic Medical Center,
Cleveland, OH
|
D-dimer > 3,000 ng/mL (6× ULN)
|
Enoxaparin 40 mg SC daily (with adjustments for BMI or UFH for renal insufficiency)
|
If D-dimer > 3,000 ng/mL, perform POCUS:
IF negative → Enoxaparin 40 mg SC BID (with adjustments for BMI or UFH for renal insufficiency)
IF positive or high clinical suspicion → IV Heparin per DVT/PE nomogram or enoxaparin
1 mg/kg SC BID
|
Refer to risk category
|
Patients with persistently elevated D-dimer (greater than 2× ULN) may benefit from
extended prophylaxis or treatment
|
May 14, 2020
|
Abbreviations: AKI, acute kidney injury; ARDS, acute respiratory distress syndrome;
BID, two times a day; BMI, body mass index; BNP, B-type natriuretic peptide; CrCl,
creatinine clearance; CRP, C-reactive protein; DOAC, direct oral anticoagulant; DVT,
deep vein thrombosis; ICU, intensive care unit; LMWH, low molecular weight heparin;
MSOF, multisystem organ failure; PE, pulmonary embolism; PO, orally; RV, right ventricular;
TID, three times a day; TTE, transthoracic echocardiogram; UFH, unfractionated heparin;
ULN, upper limit of normal; VTE, venous thromboembolism.
Of the 15 centers, 4 institutional algorithms (Massachusetts General Hospital, Moffit
Cancer Center/University of South Florida, University of Alabama, and Vanderbilt University
Medical Center) are generally consistent with evidence-based thromboprophylaxis recommendations
in non-COVID-19 populations, that is, enoxaparin 40 mg subcutaneous daily (with adjustments
for body mass index or renal insufficiency). Numerous laboratory and clinical parameters
are recommended to risk-stratify hospitalized COVID-19 patients into intermediate
or higher risk. Eight of the 15 institutions recommend using D-dimer thresholds to
risk-stratify hospitalized COVID-19 patients into intermediate or higher risk, with
different cutoffs recommended. For such “higher risk populations,” anticoagulation
strategies vary across the institutions. In 8 centers, use of an “intermediate” dose
of LMWH (0.4–0.6 mg/kg two times daily) is advised for this population. An additional
4 institutions advise full-dose anticoagulation with heparins (LMWH or UFH, three
institutions) or direct oral anticoagulants (DOACs) (apixaban, one institution). Although
bleeding has not been raised as a major concern in hospitalized patients with COVID-19,
one institution (University of Michigan) recommends using clinical prediction rules
to estimate a patient's thrombotic (Wells score) and bleeding (VTE-BLEED score) risks
to guide individualized decisions regarding empiric use of high-dose or therapeutic
anticoagulation. Almost all algorithms agree that for situations with a high clinical
suspicion for VTE without confirmatory imaging, therapeutic anticoagulation with LMWH,
UFH, or DOAC is recommended. One institution (Beth Israel Deaconess Medical Center),
mentions consideration of empiric fibrinolysis for salvage therapy in severe and persistent
hypoxia. Extended-duration thromboprophylaxis following hospitalization, especially
in critically ill patients, has been shown to be effective in reducing VTE incidence
in certain high-risk populations[23]
[24]; however, data specifically for COVID-19 patients are not yet available.[25] Notably, among the 15 institutional protocols presented here, 8 include guidance
on postdischarge outpatient thromboprophylaxis, recommending LMWH or DOACs for 1 to
3 months in selected higher risk subgroups.
The COVID-19 pandemic has pressurized the medical community to make medical decisions
and recommendations based on limited anecdotal, observational, and in some cases,
a complete absence of evidence.[26] The observed increased risk for VTE has led institutional experts across the world
and North America to create a variety of algorithms to guide anticoagulant use in
this population, extrapolating from general experience from other subsets of patients
with VTE. Here, we have collated guidelines from 15 U.S. institutions to: (1) allow
comparison of similarities and differences in practice recommendations; (2) allow
critical analysis of advantages and disadvantages of strategies proposed; and (3)
allow other institutions both in the United States and abroad to strategize their
preferred approach while awaiting more robust evidence. The wide disparity in institutional
recommendations highlights the existing equipoise regarding antithrombotic management
in patients with COVID-19, the lack of a true standard of care, and the need for data
from robust, randomized prospective clinical trials to guide clinical practice.