Pathological Effects of SARS-CoV-19 Associated With Hematological Abnormalities (preprint)

The SARS coronavirus 2 (SARS-CoV-2) is the causative agent of the 2019 coronavirus disease (COVID-19) pandemic that has executed 6.9 million people and infected over 765 million. It’s become a major worldwide health alarm and is also known to cause abnormalities in various systems, including the hematologic system. COVID-19 infection primarily affects the lower res-piratory tract and can lead to a cascade of events, including a cytokine storm, intravascular thrombosis, and subsequent complications such as arterial and venous thromboses. COVID-19 can cause thrombocytopenia, lymphopenia, and neutrophilia, which are associated with worse out-comes. Prophylactic anticoagulation is essential to prevent complication and death rate associated with the virus's effect on the coagulation system. It is crucial to recognize these complications early and promptly start therapeutic anticoagulation to improve patient outcomes. While rare, COVID-19-induced disseminated intravascular coagulation exhibits some similarities to DIC induced by sepsis. LDH, D-dimer, ferritin, and CRP biomarker are often increase in serious COVID-19 cases and poor prognosis. Understanding the pathophysiology of the disease and identifying risk factors for adverse outcomes is critical for effective management of COVID-19.

D-Dimer: An International Assessment of the Quality of Laboratory Testing: Implications for D-Dimer Use in the Real World (preprint)

Background: D-dimer assessment has an established role in the exclusion of venous thromboembolism (VTE) in symptomatic outpatients. It is also used in diagnosing disseminated intravascular coagulation (DIC), and more recently in the risk stratification of illness severity in COVID-19. D-dimer assays are neither standardized nor harmonized, use varying methodologies, and different reporting units, resulting in a potential lack of interchangeability between assay results.Objectives: Using large multi-year datasets from an international laboratory quality assurance program, we assessed: (1) common D-Dimer assays in use worldwide (2) differences in analytical performance between different methods and (3) inter-laboratory variability between positive samples.Methods: External proficiency testing results from laboratories participating in the External quality Control for Assays and Tests (ECAT) Foundation were analyzed from 2017 to 2020.Results: Annually, between 578 and 640 laboratories participated in the D-dimer sample surveys. The three commonest assays in use in the last survey of 2020 were the Siemens Innovance D-dimer (42%), the IL HemosIL D-dimer HS 500 (16%), and the Stago Liatest D-dimer Plus (11%) - all automated, quantitative, latex immunoassays expressed in Fibrinogen Equivalent Units (FEU). The highest inter-laboratory variability on the same samples was observed around the typical VTE exclusion threshold of 0.5 mg/L FEU. Lower inter-laboratory variability was observed at values above 0.7 mg/L FEU.Conclusions: Our study provides recent, international performance data on currently used D-Dimer assays and describes the significant variability between assays and across concentrations. We demonstrate that assays are not interchangeable, and using them interchangeably has the potential to result in clinically important errors. There is an urgent need to educate users about this issue and to work towards harmonization of D-dimer results and reporting units.

D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination.

BACKGROUND: Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. METHODS: We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)-heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4-heparin immunoassay. RESULTS: Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4-heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor-blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4-heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. CONCLUSIONS: Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.).

Disseminated Intravascular Coagulation: The Past, Present, and Future Considerations.

Disseminated intravascular coagulation (DIC) has been understood as a consumptive coagulopathy. However, impaired hemostasis is a component of DIC that occurs in a progressive manner. The critical concept of DIC is systemic activation of coagulation with vascular endothelial damage. DIC is the dynamic coagulation/fibrinolysis disorder that can proceed from compensated to decompensated phases, and is not simply impaired hemostasis, a misunderstanding that continues to evoke confusion among clinicians. DIC is a critical step of disease progression that is important to monitor over time. Impaired microcirculation and subsequent organ failure due to pathologic microthrombi formation are the pathophysiologies in sepsis-associated DIC. Impaired hemostasis due to coagulation factor depletion from hemodilution, shock, and hyperfibrinolysis occurs in trauma-associated DIC. Overt-DIC diagnostic criteria have been used clinically for more than 20 years but may not be adequate to detect the compensated phase of DIC, and due to different underlying causes, there is no "one-size-fits-all criteria." Individualized criteria for heterogeneous conditions continue to be proposed to facilitate the diagnosis. We believe that future research will provide therapeutics using new diagnostic criteria. Finally, DIC is also classified as either acute or chronic, and acute DIC results from progressive coagulation activation over a short time and requires urgent management. In this review, we examine the advances in research for DIC.

Evaluation of Potential Adverse Events Following COVID-19 mRNA Vaccination Among Adults Aged 65 Years and Older: A Self-Controlled Study in the U.S. (preprint)

Background Our near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevations in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluations of the potential associations. Methods We conducted self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged 65 years and older. Adjusted incidence rate ratio (IRRs) and 95% confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following booster doses for AMI, PE, ITP, Bells Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri). Results Among 3,360,981 individuals who received 6,388,542 primary series doses and 6,156,100 individuals with monovalent booster doses of either BNT162b2 or mRNA-1273, AE counts were: AMI (3,653 primary series, 16,042 booster), inpatient PE (2,470 primary, 5,085 booster), ITP (1,085 primary, 88 booster), DIC (254 primary), BP (3,268 booster), and Myo/Peri (1,295 booster). The IRR for inpatient PE cases following BNT162b2 primary series and booster was 1.19 (95% CI: 1.03 to 1.38) and 0.86 (95% CI: 0.78 to 0.95), respectively; and for mRNA-1273 primary series and booster, 1.15 (95% CI: 0.94 to 1.41) and 0.87 (95% CI: 0.79 to 0.96), respectively. The IRR for BP following BNT162b2 and mRNA-1273 booster was 1.17 (95% CI: 1.06 to 1.29) and 1.16 (95% CI: 1.05 to 1.29), respectively. Conclusion In these two studies of the U.S. elderly we did not find an increased risk for AMI, ITP, DIC, and Myo/Peri; the results were not consistent for PE; and there was a small elevated risk of BP after exposure to COVID-19 mRNA vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the elderly.

Coagulation Influencing Liberation from Respiratory Support in Patients with Coronavirus Disease 2019: A Retrospective, Observational Study.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) occasionally develop respiratory failure and coagulopathy. We aimed to determine whether coagulation abnormalities at admission and during the course of hospitalization can predict the liberation from respiratory support in critically ill patients with COVID-19 by combining the results of rotational thromboelastometry (ROTEM) with standard laboratory tests. METHODS: This single-center, retrospective, observational study included 31 consecutive adult patients with COVID-19 who were admitted to the intensive care unit (ICU) and who required respiratory support between April 2021 and August 2021. We divided the patients into two groups according to the liberation from respiratory support and analyzed the differences between the groups. RESULTS: There were 20 patients in the liberation group and 11 in the non-liberation group. There were no significant differences in the overt disseminated intravascular coagulation scores or abnormal counts in the ROTEM parameters at admission between groups, although there was a significant difference in the highest score in the ICU. The Sequential Organ Failure Assessment and sepsis-induced coagulopathy scores were significantly different between both groups at admission and at the time when the highest values were reported during the ICU stay. CONCLUSIONS: High sepsis-induced coagulopathy scores at admission to the ICU were found to be useful predictors of difficulties in the liberation from respiratory support in patients with severe COVID-19. However, increased overt disseminated intravascular coagulation scores and abnormal counts in the ROTEM parameters during the ICU stay were associated with difficulties in the liberation from respiratory support.

Antithrombin as Therapeutic Intervention against Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation: Lessons Learned from COVID-19-Associated Coagulopathy.

Recent research has contributed significantly to our understanding of the pathogenesis of acute disseminated intravascular coagulation. COVID-19 can be considered as a new underlying condition of disseminated intravascular coagulation. In this narrative review, current evidence is presented regarding biomarker differences between sepsis-induced and COVID-19-associated coagulopathies, supporting the importance of acquired antithrombin deficiency in the early differential diagnosis of septic coagulopathy and its potential impact on treatment with endogenous anticoagulants. Establishing new scoring systems for septic coagulopathy in combination with endogenous anticoagulant biomarker activities may allow for the identification of those in the heterogeneous population of sepsis patients who are more likely to benefit from targeted specific treatment interventions.

Surveillance of COVID-19 vaccine safety among elderly persons aged 65 years and older (preprint)

Background: Monitoring safety outcomes following COVID-19 vaccination is critical for understanding vaccine safety especially when used in key populations such as elderly persons age 65 years and older who can benefit greatly from vaccination. We present new findings from a nationally representative early warning system that may expand the safety knowledge base to further public trust and inform decision making on vaccine safety by government agencies, healthcare providers, interested stakeholders, and the public. Methods: We evaluated 14 outcomes of interest following COVID-19 vaccination using the US Centers for Medicare & Medicaid Services (CMS) data covering 30,712,101 elderly persons. The CMS data from December 11, 2020 through Jan 15, 2022 included 17,411,342 COVID-19 vaccinees who received a total of 34,639,937 doses. We conducted weekly sequential testing and generated rate ratios (RR) of observed outcome rates compared to historical (or expected) rates prior to COVID-19 vaccination. Findings: Four outcomes met the threshold for a statistical signal following Pfizer-BioNTech vaccination including pulmonary embolism (PE; RR=1.54), acute myocardial infarction (AMI; RR=1.42), disseminated intravascular coagulation (DIC; RR=1.91), and immune thrombocytopenia (ITP; RR=1.44). After further evaluation, only the RR for PE still met the statistical threshold for a signal; however, the RRs for AMI, DIC, and ITP no longer did. No statistical signals were identified following vaccination with either the Moderna or Janssen vaccines. Interpretation: This early warning system is the first to identify temporal associations for PE, AMI, DIC, and ITP following Pfizer-BioNTech vaccination in the elderly. Because an early warning system does not prove that the vaccines cause these outcomes, more robust epidemiologic studies with adjustment for confounding factors, including age and nursing home residency, are underway to further evaluate these signals. FDA strongly believes the potential benefits of COVID-19 vaccination outweigh the potential risks of COVID-19 infection.

Clinical profile of scrub typhus patients during COVID pandemic: A sub-Himalayan single center experience (preprint)

Introduction Scrub typhus is tropical zoonotic disease, commonly presented with multi organ dysfunction and high mortality rate in untreated patients. This study was done to identify clinical features commonly associated with scrub typhus during COVID pandemics, parameters associated with severe scrub typhus and mortality. Methods This retrospective study was done in a tertiary care hospital with a total of 52 admitted scrub typhus positive patients in October 2020 to February 2022. Diagnosis was established by scrub IgM ELISA or Rapid antigen test. The clinical and laboratory data, duration of hospital stay and outcomes were collected. Common clinical and laboratory findings were of descriptive analysis. Factors associated with mortality were analysed using Chi-square test. Results Fever was the most common presenting symptoms on admission (94.2%) followed by respiratory abnormalities (38.46%). Acute kidney injury was the most common organ failure on admission (67.3%), followed by acute liver injury (46.2%) and thrombocytopenia (32.7%). MODS was seen in 46.15%. Of the total, 30.8% were admitted in ICU. Mortality was seen in 7.7% of all patients. On Chi-square analysis, altered mental status and coagulopathy were associated with significant mortality with p value <0.05. Conclusion Scrub typhus can manifest with potentially life-threatening complications such as acute kidney injury, acute liver injury, thrombocytopenia and MODS. The overall case-fatality rate was 7.7%, and presence of altered mental status and coagulopathy were associated with higher mortality. As per literature, COVID has changed few clinical profiles of scrub typhus compared to same center experience before.

Thrombotic thrombocytopenic purpura as an acute complication of COVID-19.

Introduction: While disseminated intravascular coagulation (DIC) is a serious complication of COVID-19, a close differential in critically ill patients with thrombocytopenia is Thrombotic thrombocytopenic purpura (TTP). Case Report: We describe the case of a middle-aged lady admitted with COVID-19 pneumonia who developed progressive thrombocytopenia, altered sensorium and renal failure. The absence of coagulation abnormalities alerted to the possibility of TTP, strengthened by presence of schistocytes in peripheral smear. Conclusions: This case highlights the need for high index of suspicion and to pay attention to normal tests as well that might give clues to the diagnosis. New onset thrombocytopenia in COVID-19 need not always indicate DIC. A careful examination of peripheral smear may help diagnosing TTP especially if coagulation profile is normal.

D-dimers-"Normal" Levels versus Elevated Levels Due to a Range of Conditions, Including "D-dimeritis," Inflammation, Thromboembolism, Disseminated Intravascular Coagulation, and COVID-19.

D-dimers reflect a breakdown product of fibrin. The current narrative review outlines how D-dimers can arise in normal individuals, as well as in patients suffering from a wide range of disease states. D-dimers in normal individuals without evident thrombosis can arise from background fibrinolytic activity in various tissues, including kidney, mammary and salivary glands, which ensures smooth flow of arising fluids where any blood contamination could be immediately lysed. In addition, healthy individuals can also regularly sustain minor injuries, often unbeknown to them, and wound healing follows clot formation in these situations. D-dimers can also arise in anxiety and following exercise, and are also markers of inflammation. Lung inflammation (triggered by microbes or foreign particles) is perhaps also particularly relevant, since the hemostasis system and fibrinolysis help to trap and remove such debris. Lung inflammation in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may contribute to D-dimer levels additive to thrombosis in patients with COVID-19 (coronavirus disease 2019). Indeed, severe COVID-19 can lead to multiple activation events, including inflammation, primary and secondary hemostasis, and fibrinolysis, all of which may contribute to cumulative D-dimer development. Finally, D-dimer testing has also found a role in the diagnosis and triaging of the so-called (COVID-19) vaccine-induced thrombotic thrombocytopenia.

Thrombocytopenia: the good, the bad and the ugly.

New thrombocytopenia may be associated with a variety of conditions and diagnosis can be challenging. Presentation can vary from life-threatening bleeding or thrombosis to an incidental finding in an asymptomatic patient. New thrombocytopenia requires urgent investigation. Investigations are mainly guided by findings from the clinical history, physical examination, full blood count and blood film analysis. Aside from the actively bleeding patient, rare but life-threatening causes of thrombocytopenia must be identified early as they require urgent treatment. These include thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, suspicion of new acute promyelocytic leukaemia, and vaccine-induced prothrombotic immune thrombocytopenia. Here, we discuss how to approach a patient with new thrombocytopenia, along with key differentials not to be missed.

Spontaneous hemothorax in a 10-year-old boy with COVID-19. (preprint)

Spontaneous hemothorax occurs in the absence of trauma or iatrogenic causes. Etiologies of spontaneous hemothorax in children include connective tissue disease, neoplasia and coagulopathy which is associated with thromboembolic events. We present the case of a 10-year-old chronic hemodialysis patient with spontaneous hemothorax with a concurrent COVID 19 infection.

Purpura fulminans due to Streptococcus pneumoniae bacteraemia in an unsplectomised immunocompetent adult without primary hypocomplementaemia.

Invasive pneumococcal disease occurs in high-risk patient population which includes patients with asplenia and primary hypocomplementaemia. Pneumococcal sepsis can rarely cause disseminated intravascular coagulation (DIC) and intravascular thrombosis of small and medium sized vessels called purpura fulminans which is associated with a high mortality rate. We present the case of an immunocompetent woman in her 50s with an intact spleen who presented with septic shock from Streptococcus pneumoniae bacteraemia. Her hospital course rapidly progressed to multiorgan dysfunction, DIC and purpura fulminans. She was treated aggressively with broad spectrum antibiotics, coagulation factor replacement, multiple vasopressor support, renal replacement therapy and mechanical ventilator support. Despite aggressive measures, she succumbed to the multiorgan failure.

An Incidence of Superior Mesenteric Venous Thrombosis in Mild COVID-19 (preprint)

SARS-CoV-2, an etiological agent of COVID-19, has been reported to inflict remarkably diverse manifestations in different subjects across the globe. Though patients with COVID-19 predominantly have fever, respiratory and constitutional symptoms, atypical presentations are becoming increasingly evident. COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilization, and diffuse intravascular coagulation in moderate to severe symptomatic cases. In this case report, we are reporting thromboembolic complications of COVID-19 in a mild symptomatic subject incidentally diagnosed with mesenteric venous occlusion with no abdominal symptoms. Early recognition of the abdominal symptoms, diagnosis, initiation of anticoagulants, and timely surgical intervention may improvise the outcome in a patient with COVID-19 Infection-induced mesenteric thrombosis. Superior mesenteric artery and venous thrombosis may lead to subsequent ischemia necessitating emergency laparotomy. Thus, the usage of low-dose anticoagulants in all the patients of COVID-19 irrespective of the categorization into mild, moderate, and severe COVID-19 disease should be considered.

Acquired Thrombotic Thrombocytopenic Purpura following inactivated COVID 19 vaccines: Two case-reports and a short literature review (preprint)

The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak from December 2019 causing millions of deaths all over the world and the lack of specific treatment for severe forms of coronavirus disease 2019 (COVID-19) has led to vaccines development in record time with emergency use authorization in several countries increasing the risk of vaccine safety issues. Recently, several cases of Thrombotic Thrombocytopenic Purpura (TTP) have been reported following COVID-19 vaccination. TTP represents a life-threatening consumptive coagulopathy requiring urgent diagnosis and prompt treatment. It is a rare disease characterized by thrombocytopenia, microangiopathic hemolytic anemia and ischemic end-organ lesions. It can be either congenital or acquired. Various events such viral infections, medication, pregnancy, malignancies, and vaccinations may cause TTP. Clinicians should consider this diagnosis when evaluating thrombocytopenia in the post-vaccine period. Here, we report two cases of acquired TTP following Sinopharm COVID-19 vaccine (BBIBP-CorV) and Sinovac COVID-19 vaccine (CoronaVac). Diagnosis was based on clinical presentation and confirmed with severe reduction in the activity of von Willebrand factor-cleaving protease ADAMTS-13 and the presence of inhibitory autoantibodies. The two patients were successfully treated with corticosteroids, plasma exchange therapy and rituximab in the acute phase. In the literature, the reported cases of TTP induced by COVID-19 vaccination occurred after Adenoviral Vector DNA- and SARS-CoV-2 mRNA-Based COVID-19 Vaccines. To the best of our knowledge, this is the first report of acquired TTP after inactivated virus COVID-19 vaccines. A short literature review regarding acquired TTP patients following COVID-19 vaccines is also included.

Coagulopathy in pediatric SARS-CoV-2 infection manifested as deep vein thrombosis and pulmonary embolism. (preprint)

Thrombotic complications of SARS-CoV-2 have been increasingly recognized as an important component of COVID-19 in adults; however, they have been less evident in children. We report a case of a teenager with positive SARS‐CoV‐2 RT–PCR and underlying prothrombotic risk factors, including aromatase inhibitor therapy, who developed deep vein thrombosis resulting in pulmonary embolism. Laboratory tests revealed deranged coagulation parameters (high D-dimers and Factor VIII and low antithrombin). The patient required intensive care and was managed with anticoagulants, dexamethasone and antithrombin concentrate. Clinical condition and hemostatic profile gradually improved. A review of the available literature for similar cases is presented.

Sustained right ventricular dysfunction in severe COVID-19: The role of disseminated intravascular coagulation.

BACKGROUND: Acute right ventricular (RV) failure is common in patients hospitalized with COVID-19. Compared to the conventional echocardiographic parameters, right ventricular longitudinal strain (RVLS) is more sensitive and accurate for the diagnosis of RV systolic dysfunction. OBJECTIVE: Our purpose was to investigate the sustained RV dysfunction echo-quantified by RVLS in patients recovered from severe COVID-19. Furthermore, we aimed to assess whether disseminated intravascular coagulation (DIC) has a key role to predict the impaired RV strain. METHODS: Of 198 consecutive COVID-19 patients hospitalized from March 1, 2020, to April 15, 2020, 45 selected patients who survived from severe COVID-19 were enrolled in the study and referred to our echo-lab for transthoracic echocardiography 6-months after discharge. RVLS was calculated as the mean of the strain values of RV free wall. DIC was defined with a validated scoring system: DIC score equal to or more than 5 is compatible with overt-DIC. Categories of acute respiratory distress syndrome (ARDS) were defined based on PaO2 /FiO2 ratio. RESULTS: A total 26 of 45 patients showed impaired RVLS at 6-months' follow-up. DIC score was significantly higher in patients with worse RVLS than in those with better RVLS (4.8 ± .5 vs. 3.6 ± .6, p =.03). Stages of ARDS did not modulate this relationship. Finally, overt-DIC results the only independent predictor of sustained RV dysfunction (OR 1.233, 95% CI 1.041-1.934, p =.043). CONCLUSIONS: Sustained RV impairment frequently occurs in patients recovered from severe COVID-19. DIC plays a key role, resulting in an independent predictor of sustained RV dysfunction.

FDP Fluctuation in Severe COVID-19 is Associated With the Development of Thrombotic or Bleeding Complications and Systemic Coagulopathy (preprint)

Purpose: COVID-19 is sometimes associated with coagulation disorders. In such cases, patients developed elevated D‐dimer and fibrin degradation products (FDP) levels, both of which are associated with high risks of thromboembolic complications and poor prognosis. To date, time course changes of FDP values in COVID-19 patients has not been well evaluated. The aim of this study is to evaluate whether FDP fluctuation in COVID-19 patients are associated with systemic coagulopathy. Methods: We retrospectively analyzed the changes in coagulofibrinolytic markers including FDP in 42 COVID-19-ARDS patients. FDP elevation as the fluctuation was defined as follows: 1) FDP>10μg/mL for the first time after admission and 2) 10μg/mL or more elevation after the improvement of the first or subsequent FDP elevations. Results: FDP elevation was observed a total of 30 times in 21 patients (50%). Marked intravascular coagulofibrinolytic activation occurred at the same time as the FDP elevation (soluble fibrin: SF, 27.0 [14.9–80.0] μg/mL; thrombin-antithrombin complex: TAT, 7.5 [2.9–17.8] μg/L; plasmin-α 2 -plasmin inhibitor complex: PIC, 2.4 [1.4–4.2] μg/mL). FDP was elevated in all patients who met sepsis-induced coagulopathy (SIC) or disseminated intravascular coagulation (DIC) diagnosis criteria. Thrombotic or bleeding complications developed in 12 patients (28.6%) and were significantly correlated with FDP elevation ( OR [odds ratio] 4.50, 95% CI [confidence interval] 1.01–20.11, p = 0.049). However, there were no significant differences in coagulofibrinolytic activities between the patients with and without SIC or DIC. Conclusions: Coagulation activation which can lead to the development of systemic coagulopathy such as DIC occurred with FDP fluctuation in severe COVID-19 patients. However, there is a limit of the application of existing DIC and SIC diagnosis criteria to COVID-19.