Comparison of published guidelines for management of coagulopathy and thrombosis in critically ill patients with COVID 19: implications for clinical practice and future investigations

Flaczyk, Adam; Rosovsky, Rachel; Reed, Clay; Bankhead‐Kendall, Brittany; Bittner, Edward A.; Chang, Marvin G.

doi:10.1186/s13054-020-03273-y

Cited by 88 publications

(118 citation statements)

References 10 publications

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“…While prophylaxis- and treatment-related criteria are fairly similar in all available guidelines, criteria for withholding anticoagulation do not fit all. Withholding of prophylactic anticoagulation with LMWH is proposed for platelet count <25 × 10 9 /L, platelet count <30–50 × 10 9 /L, or fibrinogen <1 g/L, while therapeutic anticoagulation should be held only if platelet count <25 × 10 9 /L or fibrinogen <0.5 g/L for the International Society on Thrombosis and Haemostasis – International Guidelines (ISTH-IG) recommendations; while the Scientific and Standardization Committee (SSC)-ISTH, Center for Diseases Control (CDC), and Anticoagulation Forum (ACF) guidelines do not suggest specific thresholds to withhold [ 59 ].…”

Section: Coagulation Markers and Treatment Proposalsmentioning

confidence: 99%

Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review

Robba

Battaglini

Ball

et al. 2021

JCM

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In critically ill patients with acute respiratory distress syndrome (ARDS) coronavirus disease 2019 (COVID-19), a high incidence of thromboembolic and hemorrhagic events is reported. COVID-19 may lead to impairment of the coagulation cascade, with an imbalance in platelet function and the regulatory mechanisms of coagulation and fibrinolysis. Clinical manifestations vary from a rise in laboratory markers and subclinical microthrombi to thromboembolic events, bleeding, and disseminated intravascular coagulation. After an inflammatory trigger, the mechanism for activation of the coagulation cascade in COVID-19 is the tissue factor pathway, which causes endotoxin and tumor necrosis factor-mediated production of interleukins and platelet activation. The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia. The variety of clinical presentations of the coagulopathy confronts the clinician with the difficult questions of whether and how to provide optimal supportive care. In addition to coagulation tests, advanced laboratory tests such as protein C, protein S, antithrombin, tissue factor pathway inhibitors, D-dimers, activated factor Xa, and quantification of specific coagulation factors can be useful, as can thromboelastography or thromboelastometry. Treatment should be tailored, focusing on the estimated risk of bleeding and thrombosis. The aim of this review is to explore the pathophysiology and clinical evidence of coagulation disorders in severe ARDS-related COVID-19 patients.

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Section: Coagulation Markers and Treatment Proposalsmentioning

confidence: 99%

Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review

Robba

Battaglini

Ball

et al. 2021

JCM

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“…A pattern of increased thrombotic risk among adult patients (especially those most greatly affected) has so far emerged, 2 resulting from an inflammatory‐driven endothelial dysfunction and hypercoagulable state, 3,4 and translating into a high rate of multi‐organ macro‐ and micro‐vascular injury, and death 5 . Thus, international societies and multiple national health‐care institutions have offered guidance on how to evaluate for coagulopathy and implement an anticoagulation prophylaxis protocol in patients admitted with a diagnosis of COVID‐19 6‐8 …”

Section: Introductionmentioning

confidence: 99%

“…5 Thus, international societies and multiple national health-care institutions have offered guidance on how to evaluate for coagulopathy and implement an anticoagulation prophylaxis protocol in patients admitted with a diagnosis of COVID-19. [6][7][8] The available evidence concerning COVID-19 pediatric patients draws a reassuring picture in terms of morbidity and mortality, with a low incidence of thrombotic complications (widely unreported in even the most severely affected patients 9,10 ). Nonetheless, the International…”

Section: Introductionmentioning

confidence: 99%

SARS‐COV‐2–associated coagulopathy and thromboembolism prophylaxis in children: A single‐center observational study

Borrello

Giraudo

Bondone

et al. 2021

Journal of Thrombosis and Haemostasis

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Background: Multiple investigators have described an increased incidence of thromboembolic events in SARS-CoV-2-infected individuals. Data concerning hemostatic complications in children hospitalized for COVID-19/multisystem inflammatory syndrome in children (MIS-C) are scant. Objectives: To share our experience in managing SARS-CoV-2-associated pro-coagulant state in hospitalized children. Methods: D-dimer values were recorded at diagnosis in children hospitalized for SARS-CoV-2-related manifestations. In moderately to critically ill patients and MIS-C cases, coagulation and inflammatory markers were checked at multiple time points and median results were compared. Pro-thrombotic risk factors were appraised for each child and thromboprophylaxis was started in selected cases. Results: Thirty-five patients were prospectively enrolled. D-dimer values did not discriminate COVID-19 of differing severity, whereas were markedly different between the COVID-19 and the MIS-C cohorts. In both cohorts, D-dimer and C-reactive protein levels increased upon clinical worsening but were not accompanied by decreased fibrinogen or platelet values, with all parameters returning to normal upon disease resolution. Six patients had multiple thrombotic risk factors and were started on pharmacological thromboprophylaxis. No deaths or thrombotic or bleeding complications occurred. Conclusions: COVID-19 pediatric patients show mildly altered coagulation and inflammatory parameters; on the other hand, MIS-C cases showed laboratory signs of an inflammatory driven pro-coagulant status. Universal anticoagulant prophylaxis in hospitalized children with SARS-CoV-2-related manifestations is not warranted, but may be offered to patients with other pro-thrombotic risk factors in the context of a multi-modal therapeutic approach.

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“…International guidelines also state that once-daily regimens of LMWH may be advantageous over UFH because missed doses may be associated with worse outcomes, will reduce healthcare worker exposure, and conserve personal protective equipment. 13,62 Recommendations and suggestions ( Table 1). 1) In the absence of contraindications, we recommend prophylactic anticoagulation with either LMWH or UFH for all hospitalized COVID-19 patients in LMICs (strong recommendation and moderate quality of evidence).…”

Section: What Type Of Venous Thromboembolism (Vte) Prophylaxismentioning

confidence: 99%

“…A platelet count < 25 × 10 9 /L or fibrinogen < 0.5 g/L constitutes a bleeding risk, warranting holding of standard dose VTE prophylaxis, whereas therapeutic anticoagulation should be withheld if platelet count < 50 × 10 9 /L or fibrinogen < 1.0 g/L. 62 The role of serial hemoglobin monitoring in COVID-19 patients on therapeutic anticoagulation is poorly defined.…”

Section: What Type Of Venous Thromboembolism (Vte) Prophylaxismentioning

confidence: 99%

Pragmatic Recommendations for the Management of Anticoagulation and Venous Thrombotic Disease for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries

Ahmed

Papali

Haile

et al. 2021

The American Journal of Tropical Medicine and Hygiene

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New studies of COVID–19 are constantly updating best practices in clinical care. Often, it is impractical to apply recommendations based on high-income country investigations to resource limited settings in low- and middle-income countries (LMICs). We present a set of pragmatic recommendations for the management of anticoagulation and thrombotic disease for hospitalized patients with COVID-19 in LMICs. In the absence of contraindications, we recommend prophylactic anticoagulation with either low molecular weight heparin (LMWH) or unfractionated heparin (UFH) for all hospitalized COVID-19 patients in LMICs. If available, we recommend LMWH over UFH for venous thromboembolism (VTE) prophylaxis to minimize risk to healthcare workers. We recommend against the use of aspirin for VTE prophylaxis in hospitalized COVID-19 and non–COVID-19 patients in LMICs. Because of limited evidence, we suggest against the use of “enhanced” or “intermediate” prophylaxis in COVID-19 patients in LMICs. Based on current available evidence, we recommend against the initiation of empiric therapeutic anticoagulation without clinical suspicion for VTE. If contraindications exist to chemical prophylaxis, we recommend mechanical prophylaxis with intermittent pneumatic compression (IPC) devices or graduated compression stockings (GCS) for hospitalized COVID-19 patients in LMICs. In LMICs, we recommend initiating therapeutic anticoagulation for hospitalized COVID-19 patients, in accordance with local clinical practice guidelines, if there is high clinical suspicion for VTE, even in the absence of testing. If available, we recommend LMWH over UFH or Direct oral anticoagulants for treatment of VTE in LMICs to minimize risk to healthcare workers. In LMIC settings where continuous intravenous UFH or LMWH are unavailable or not feasible to use, we recommend fixed dose heparin, adjusted to body weight, in hospitalized COVID-19 patients with high clinical suspicion of VTE. We suggest D -dimer measurement, if available and affordable, at the time of admission for risk stratification, or when clinical suspicion for VTE is high. For hospitalized COVID-19 patients in LMICs, based on current available evidence, we make no recommendation on the use of serial D -dimer monitoring for the initiation of therapeutic anticoagulation. For hospitalized COVID-19 patients in LMICs receiving intravenous therapeutic UFH, we recommend serial monitoring of partial thromboplastin time or anti-factor Xa level, based on local laboratory capabilities. For hospitalized COVID-19 patients in LMICs receiving LMWH, we suggest against serial monitoring of anti-factor Xa level. We suggest serial monitoring of platelet counts in patients receiving therapeutic anticoagulation for VTE, to assess risk of bleeding or development of heparin induced thrombocytopenia.

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Comparison of published guidelines for management of coagulopathy and thrombosis in critically ill patients with COVID 19: implications for clinical practice and future investigations

Cited by 88 publications

References 10 publications

Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review

Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review

SARS‐COV‐2–associated coagulopathy and thromboembolism prophylaxis in children: A single‐center observational study

Pragmatic Recommendations for the Management of Anticoagulation and Venous Thrombotic Disease for Hospitalized Patients with COVID-19 in Low- and Middle-Income Countries

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