How to recognize and manage COVID-19-associated coagulopathy

Abstract COVID-19 is frequently associated with abnormalities on coagulation testing and a coagulopathy driven by inflammation, intravascular coagulation activation, and microvascular thrombosis. Elevated D-dimer is the most common finding and is a predictor of adverse outcomes including thrombosis, critical illness, and death. Although COVID-19-associated coagulopathy has some similarities to disseminated intravascular coagulation, the platelet count is usually preserved, coagulation times are usually normal or minimally prolonged, and thrombosis is more common than bleeding, at least in noncritically ill patients. Bleeding is uncommon but may be a significant problem in critically ill patients, including those who may develop a consumptive coagulopathy with frank disseminated intravascular coagulation and those on extracorporeal membrane oxygenation. Blood product support to correct coagulopathy is reserved for bleeding patients or those requiring invasive procedures. Current recommendations suggest that all hospitalized patients should receive at least a prophylactic dose of anticoagulation. Results from a multiplatform randomized clinical trial suggest that therapeutically dosed anticoagulation may improve outcomes, including the need for organ support and mortality in moderately ill patients but not in those requiring critical care. The results of ongoing trials evaluating the impact of different antithrombotic strategies (therapeutic agents and intensity) on COVID-19 outcomes are eagerly awaited and are expected to have important implications for patient management. We also discuss COVID-19 vaccine-associated cytopenias and bleeding as well as vaccine-induced thrombotic thrombocytopenia, in which thrombosis is associated with thrombocytopenia, elevated D-dimer, and, frequently, hypofibrinogenemia.

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False-Positive D-Dimer Result in a Patient With Castleman Disease

Archives of Pathology & Laboratory Medicine ◽

10.5858/2004-128-328-fdriap ◽

2004 ◽

Vol 128 (3) ◽

pp. 328-331

Author(s):

Kimberly Mugler ◽

Jerry B. Lefkowitz

Keyword(s):

Western Blot ◽

Disseminated Intravascular Coagulation ◽

False Positive ◽

Degradation Products ◽

False Negative ◽

Castleman Disease ◽

Laboratory Findings ◽

Intravascular Coagulation ◽

Immunodeficiency Virus ◽

D Dimer

Abstract In suspected cases of disseminated intravascular coagulation, concurrent elevation of both fibrin(ogen) degradation products (FDPs) and D-dimer levels aids in confirming the diagnosis. This pattern of results reflects the action of plasmin proteolysis of cross-linked fibrin polymers as well as fibrinogen. We report the case of a patient with human immunodeficiency virus (HIV) and Castleman disease who presented with a high-positive D-dimer level and a negative FDP level in the course of a workup for disseminated intravascular coagulation. This finding suggested the possibility of either a false-positive D-dimer or a false-negative FDP level. To investigate the former, a Western blot was performed on the patient's serum to determine the presence of the D-dimer. No D-dimer band was visualized on the Western blot, confirming the false-positive nature of the D-dimer result. Insufficient quantity of patient serum, however, prevented further investigation into the etiology of this result. The false-positive D-dimer result is likely attributable to interference caused by the patient's Castleman disease–associated monoclonal gammopathy, a phenomenon that has been reported in other immunoassays. As the development of lymphoproliferative disorders is especially common within the HIV population, and hypergammaglobulinemia in Castleman disease is particularly common, clinicians should be aware of this phenomenon when the laboratory findings do not fit the clinical picture. Although it is rare, recognition of potential paraprotein interference in immunoassays will help avoid undertreatment or overtreatment of patients based on erroneous laboratory results.

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Disseminated intravascular coagulation at diagnosis is a strong predictor for thrombosis in acute myeloid leukemia

Blood ◽

10.1182/blood-2016-02-701094 ◽

2016 ◽

Vol 128 (14) ◽

pp. 1854-1861 ◽

Cited By ~ 26

Author(s):

Eduard J. Libourel ◽

Clara P. W. Klerk ◽

Yvette van Norden ◽

Moniek P. M. de Maat ◽

Marieke J. Kruip ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Disseminated Intravascular Coagulation ◽

Arterial Thrombosis ◽

Myeloid Leukemia ◽

Strong Predictor ◽

Newly Diagnosed ◽

Intravascular Coagulation ◽

Key Points ◽

D Dimer ◽

Acute Myeloid

Key Points A high D-dimer level strongly predicts symptomatic venous and arterial thrombosis in newly diagnosed AML. Thrombosis occurs in up to 10% of patients with newly diagnosed AML.

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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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Significance of Decreased Plasma D-Dimer Levels following Lipopolysaccharide-Induced Disseminated Intravascular Coagulation in Rats

International Journal of Hematology ◽

10.1532/ijh97.03168 ◽

2004 ◽

Vol 79 (4) ◽

pp. 394-399 ◽

Cited By ~ 6

Author(s):

Hidesaku Asakura ◽

Yoko Sano ◽

Mika Omote ◽

Tomotaka Yoshida ◽

Yasuo Ontachi ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Intravascular Coagulation ◽

D Dimer

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Molecular Testing of SARS-CoV-2 Infection from Blood Samples in Disseminated Intravascular Coagulation (DIC) and Elevated D-Dimer Levels

Clinical Laboratory ◽

10.7754/clin.lab.2020.200704 ◽

2021 ◽

Vol 67 (01/2021) ◽

Author(s):

Raluca Dumache ◽

Ecaterina Daescu ◽

Veronica Ciocan ◽

Camelia Mureşan ◽

Cut Talida ◽

...

Keyword(s):

Disseminated Intravascular Coagulation ◽

Molecular Testing ◽

Blood Samples ◽

Intravascular Coagulation ◽

D Dimer

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Significant Correlations between Tissue Factor and Thrombin Markers in Trauma and Septic Patients with Disseminated Intravascular Coagulation

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615025 ◽

1998 ◽

Vol 79 (06) ◽

pp. 1111-1115 ◽

Cited By ~ 96

Author(s):

Satoshi Nanzaki ◽

Shigeyuki Sasaki ◽

Osamu Kemmotsu ◽

Satoshi Gando

Keyword(s):

Tissue Factor ◽

Disseminated Intravascular Coagulation ◽

Thrombin Generation ◽

Trauma Patients ◽

Elevated Plasma ◽

Antigen Concentration ◽

Intravascular Coagulation ◽

Factor Antigen ◽

D Dimer

SummaryTo determine the role of plasma tissue factor on disseminated intravascular coagulation (DIC) in trauma and septic patients, and also to investigate the relationships between tissue factor and various thrombin markers, we made a prospective cohort study. Forty trauma patients and 20 patients with sepsis were classified into subgroups according to the complication of DIC. Plasma tissue factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2), thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after admission. The levels of plasma tissue factor in the DIC group were more elevated than those of the non-DIC group in both the trauma and the septic patients. In patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC group showed markedly higher values than those in the control patients (135 ± 8 pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D-dimer were observed in the DIC patients, however, no such correlations were found in the non-DIC patients. These results suggest that elevated plasma tissue factor in patients with trauma and sepsis gives rise to thrombin generation, followed by intravascular coagulation.

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