COVID-19 and its implications for thrombosis and anticoagulation

Abstract Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC). The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness. The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur. The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations. Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested. COVID-19–associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC. Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated. Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported. If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.

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Impairments of haemostasis and therapeutic management in patients with COVID-19

Bulgarian Cardiology ◽

10.3897/bgcardio.26.e54113 ◽

2020 ◽

Vol 26 (2) ◽

pp. 40-45

Author(s):

Zheina Cherneva ◽

Radostina Cherneva

Keyword(s):

Degradation Products ◽

Multiorgan Failure ◽

Pulmonary Inflammation ◽

Current Data ◽

Target Organ ◽

Thromboembolic Prophylaxis ◽

Disseminated Intravascular Coagulopathy ◽

Viral Illness ◽

Intravascular Coagulopathy ◽

D Dimer

The lack of prior immunity to SARS-CoV-2 coronavirus (COVID-19) infection has led to pandemic, where there is no certain management, regarding the complications of this viral illness. The lungs are the target organ for COVID-19 and patients develop acute lung injury that may progress to respiratory and multiorgan failure. Recent data shows the presence of diffuse bilateral pulmonary inflammation in COVID-19 infection. It is associated with a specific pulmonary vasculopathy, defined as pulmonary intravascular coagulopathy (PIC) that is distinct from disseminated intravascular coagulopathy (DIC). The coagulopathy in the early stages of COVID-19 is characterized by initial elevation of D-dimer and fibrin/fibrinogen degradation products, while abnormalities in prothrombin time, partial thromboplastin time and platelet counts are uncommon. That is why screening of D-dimer and fibrinogen levels, are mandatory. COVID-19-associated coagulopathy should be treated, following the guidelines for thromboembolic prophylaxis. Although D-dimer is a marker of mortality, current data does not show routine application of anticoagulants, unless otherwise clinically indicated. Bleeding in COVID-19 is uncommon, even when a laboratory constellation for DIC is present. However, if it occurs, standard guidelines for DIC management should be followed.

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COVID-19 Associated Coagulopathy and Implications for its Treatment

Acta Medica Bulgarica ◽

10.2478/amb-2020-0035 ◽

2020 ◽

Vol 47 (3) ◽

pp. 48-52

Author(s):

Zh. Cherneva ◽

R. Cherneva

Keyword(s):

Degradation Products ◽

Multiorgan Failure ◽

Pulmonary Inflammation ◽

Early Screening ◽

Thromboembolic Prophylaxis ◽

Standard Management ◽

Viral Illness ◽

Intravascular Coagulopathy ◽

Inflammatory Changes ◽

D Dimer

AbstractThe SARS-CoV-2 coronavirus (COVID-19) pandemic is due to lack of prior immunity and there is no certain management, regarding the complications of this viral illness. The target organ for COVID-19 infection are the lungs. Patients may develop acute lung injury that can be complicated by acute respiratory failure, as well as multiorgan failure. The pathophysiology of COVID-19 infection is characterized with inflammatory changes, associated with coagulopathy. Recent data suggests diffuse bilateral pulmonary inflammation observed in COVID-19 infection that is related to a novel pulmonary-specific vasculopathy, defined as pulmonary intravascular coagulopathy (PIC), distinct from disseminated intravascular coagulopathy (DIC). The coagulopathy associated with COVID-19 is distinguished by initial elevation of D-dimer and fibrin/fibrinogen degradation products. Abnormalities in prothrombin time (PT), partial thromboplastin time (APTT) and platelet counts are not common in the early stages of the infection. This suggests the early screening measurement of D-dimer and fibrinogen. The implications for COVID-19-associated-coagulopathy is the established thromboembolic prophylaxis and standard management for sepsis-induced coagulopathy or DIC. High levels of D-dimer are a marker of higher mortality risk. However, current studies do not show the common use of full therapeutical doses of anticoagulants, unless there are other clinical indications. Bleeding in COVID-19 infection is uncommon, even when a laboratory constellation for DIC is present. However, if it occurs, standard guidelines for DIC management should be followed.

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D-dimer kit with a High FDP/D-Dimer Ratio is Useful for Diagnosing Thrombotic Diseases

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211070584 ◽

2022 ◽

Vol 28 ◽

pp. 107602962110705

Author(s):

Nozomi Ikeda ◽

Hideo Wada ◽

Yuhuko Ichikawa ◽

Minoru Ezaki ◽

Motoko Tanaka ◽

...

Keyword(s):

Venous Thromboembolism ◽

Critically Ill ◽

Disseminated Intravascular Coagulation ◽

Critically Ill Patients ◽

Degradation Products ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Peripheral Arterial ◽

Thrombotic Diseases ◽

D Dimer

Introduction Although D-dimer is a useful biomarker of thrombosis, there are many D-dimer kits, with high and low fibrinogen and fibrin degradation products (FDP)/ D-dimer ratios. Methods Plasma D-dimer levels were measured using three different kits in critically ill patients to examine the usefulness of such measurements for detecting the thrombotic diseases and determining the correlation with the FDP and FDP/D-dimer ratio. Results Although three D-dimer kits showed marked utility for diagnosing disseminated intravascular coagulation (DIC) and peripheral arterial and venous thromboembolism (PAVTE), the D-dimer levels determined using the three kits varied among diseases. Indeed, one D-dimer kit showed a high FDP/D-dimer ratio, and another kit showed a low FDP/D-dimer ratio. D-dimer kit with low FDP/D-dimer ratio tended to have high cut-off values and low specificity for diagnosing DIC and PAVTE. In D-dimer kit with high FDP/D-dimer ratio, FDP/D-dimer ratios in patients with thrombosis was significantly higher than that in patients without thrombosis. Conclusion All three D-dimer kits show utility for detecting thrombotic diseases. However, the D-dimer levels determined using the kits varied due to differences in the FDP/D-dimer ratio. In combination with the FDP level, a D-dimer kit with a high FDP/D-dimer ratio may be useful.

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The Impact of COVID-19 Disease on Platelets and Coagulation

Pathobiology ◽

10.1159/000512007 ◽

2020 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Geoffrey D. Wool ◽

Jonathan L. Miller

Keyword(s):

Degradation Products ◽

Severe Bleeding ◽

Bleeding Events ◽

Current State ◽

Venous Thromboembolic Events ◽

Venous Thromboembolic ◽

Intravascular Coagulopathy ◽

Vascular Beds ◽

The Impact ◽

D Dimer

Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.

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Extrapulmonary Manifestations of COVID-19: A Call to Extra Vigilance and Tribute to Dr Li Wenliang

Western Journal of Medical and Biomedical Sciences ◽

10.46912/wjmbs.5 ◽

2020 ◽

Vol 1 (1) ◽

pp. xi-xiv ◽

Cited By ~ 1

Author(s):

AM Onoja ◽

GTA Jombo ◽

AT Onoja ◽

AI Nwannadi ◽

IH Aba

Keyword(s):

Degradation Products ◽

Clinical Manifestations ◽

Fulminant Myocarditis ◽

Severe Thrombocytopenia ◽

Disseminated Intravascular Coagulopathy ◽

Course Of Disease ◽

Fibrin Degradation Products ◽

Intravascular Coagulopathy ◽

Life Threatening ◽

D Dimer

COVID-19 pandemic has covered all continents and virtually all countries of the world infecting millions of people with several hundred thousands of death. It was first brought to the attention of a Chinese ophthalmologist Dr Li Wenliang. The disease which was first believed to be solely associated with the lungs and respiratory system has now shown that the spectrum of organ involvement of the disease is much larger than earlier believed. While lung and pulmonary features still account for a much larger presentation of the disease, other clinical manifestations such as fulminant myocarditis, arteriovenous thromboembolism, disseminated intravascular coagulopathy, intracerebral haemorrhage, diarrhea, hypoxic encephalopathy, septicaemia and detection of SARS-CoV-2 particles in stool, saliva and semen of infected individuals are also becoming less infrequent. Haematologic manifestations of hypercoagulable blood are commonly reported among hospitalized COVID‐19 patients. An elevated D‐Dimer, that is rising in the course of disease may signifies disease deterioration. Prolonged PT and aPTT and increased fibrin degradation products with severe thrombocytopenia have been associated with life-threatening disseminated intravascular coagulation (DIC). Physicians should therefore be on a watch out for these features in the management of patients and be ready to spot out other new surprises by the disease. This should be through deepening of curiosity by health personnel in the assessment and management of patients to spot out early surprises of COVID-19 to strengthen the sustenance of the ongoing control of the pandemic

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Acute coagulation disorder in a critically ill patient – A case report

Journal of the Intensive Care Society ◽

10.1177/1751143718761847 ◽

2018 ◽

Vol 20 (1) ◽

pp. 86-89 ◽

Cited By ~ 2

Author(s):

Agnes Oberhuber ◽

Benedikt Treml ◽

Dietmar Fries ◽

Ingo H Lorenz ◽

Friesenecker Barbara ◽

...

Keyword(s):

Critically Ill ◽

Prothrombin Complex Concentrate ◽

Multiorgan Failure ◽

Artery Bypass ◽

Activated Partial Thromboplastin Time ◽

Critically Ill Patient ◽

Severe Bleeding ◽

Coagulation Disorder ◽

Bypass Grafting ◽

Thrombin Time

A 79-year-old critically ill woman presented with remarkable prolongation of activated partial thromboplastin time and thrombin time combined with high levels of anti-factor IIa activity 26 days after coronary artery bypass grafting. Coagulation disorder was associated with severe bleeding. Cause of coagulopathy was accidental administration of argatroban in an unknown dosage. Clearance of argatroban was significantly prolonged because of a liver function disorder related to septic multiorgan failure. Argatroban reversal was performed with prothrombin complex concentrate.

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A Novel Method for the Rapid Purification of Human and Rat Fibrin(OGEN) Degradation Products in High Yields

10.1055/s-0038-1665826 ◽

1979 ◽

Author(s):

W. Nieuwenhuizen ◽

I. A. M. van Ruijven-Vermeer ◽

F. Haverkate ◽

G. Timan

Keyword(s):

Degradation Products ◽

Complete Separation ◽

Purification Method ◽

Amino Terminal ◽

Novel Method ◽

Rapid Purification ◽

The One ◽

High Yields ◽

Size Heterogeneity ◽

D Dimer

A novel method will be described for the preparation and purification of fibrin(ogen) degradation products in high yields. The high yields are due to two factors. on the one hand an improved preparation method in which the size heterogeneity of the degradation products D is strongly reduced by plasmin digestion at well-controlled calcium concentrations. At calcium concentrations of 2mM exclusively D fragments, M.W.= 93-000 (Dcate) were formed; in the presence of 1OmM EGTA only fragments M.W.= 80.000 (D EGTA) were formed as described. on the other hand a new purification method, which includes Sephadex G-200 filtration to purify the D:E complexes and separation of the D and E fragments by a 16 hrs. preparative isoelectric focussing. The latter step gives a complete separation of D (fragments) (pH = 6.5) and E fragments (at pH = 4.5) without any overlap, thus allowing a nearly 100% recovery in this step. The overall recoveries are around 75% of the theoretical values. These recoveries are superior to those of existing procedures. Moreover the conditions of this purification procedure are very mild and probably do not affect the native configuration of the products. Amino-terminal amino acids of human Dcate, D EGTA and D-dimer are identical i.e. val, asx and ser. in the ratgly, asx and ser were found. E 1% for rat Dcate=17-8 for rat D EGTA=16.2 and for rat D- dimer=l8.3. for the corresponding human fragments, these values were all 20.0 ± 0.2.

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