Rapid Disappearance of Lupus Anticoagulant in Novel Coronavirus 2019 Patients; Is It the Key to Pandora's Box?

Background: Coronavirus 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with severe hypercoagulable conditions and complex venous thrombosis is common. Several recent studies have reported elevated aPTT in COVID-19 patients with a thrombotic tendency, suggesting that the test results may be due to the presence of lupus anticoagulant (LA). LA, one of the antiphospholipid antibodies, is included in the diagnostic criteria for antiphospholipid syndrome (APS), and these syndromes are characterized by a tendency to thrombosis, so it is important to ascertain the meaning of LA in SARS-COV-2 infection. Here, we would like to investigate the changes in LA and the characteristics of coagulation-related factors in COVID-19 patients who have undergone LA testing. Methods: From March 2020 to June 2021, we conducted a medical record review of clinical information and laboratory data for COVID-19 patients at our hospital. Among the 140 confirmed patients, 110 patients who underwent lupus anticoagulant testing were included in the analysis. We also performed a subgroup analysis of COVID-19 patients who were regularly screened for LA. Results: Most of the patients in our study were mild, with 95 survivors except for the deaths of 15 patients. Lupus anticoagulant was identified in 71.6% of survivors and 40.0% of deaths. In the LA confirmatory test of survivors, DRVVT positive 98.5% and SCT positive 5.9% were found (Fig 1). When comparing coagulation parameters according to LA results in survivors, aPTT, CRP, and fibrinogen were found to be statistically significant (all P < 0.05). LA-positive patients had higher aPTT, CRP, and fibrinogen, and D-dimer was no different from LA-negative patients (Table 1). Of the 67 LA-positive patients, 25 patients did not follow up, and 12 patients were unable to clearly determine the duration of the negative transition. Among the 30 patients who underwent a follow-up LA test, short-term regular follow-up of LA testing was performed on patients from March 2021 to June 2021, and additional subgroup analysis was performed on these patients. All patients were confirmed to be DRVVT positive and had no other anti-phospholipid syndrome (APS)-related antibodies, such as anti-cardiolipin antibodies or anti-beta-2-gylcoprotein. LA disappeared rapidly within 4 weeks in all patients (range: 2-24 days). As the LA test result converted from positive to negative, aPTT decreased with a statistically significant difference (P=0.003, Fig 2). Conclusions: As previously reported, LA was found in a high proportion of COVID-19 patients. This is the first study to confirm that the proportion of LA positivity (71.6%) is high in Korean COVID-19 patients. Most of the LA positivity disappeared within 4 weeks instead of 12 weeks. The association between LA and thrombotic tendency in COVID-19 patients appears to be low. Presumably, the transient appearance of LA, which is rapidly disappearance in survivors at a high rate, may indicate that other autoantibodies due to the activation of the immune response were detected in the LA test, can be considered as a good indicator of prognosis. It is only necessary to note that there is no delay in anticoagulant treatment due to aPTT prolongation in the early stage due to LA. In summary, the clinical significance of high LA positive rates and rapid negative transitions in COVID-19 patients is currently unknown but needs confirmation. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Accidentally discovered high INR in pregnancy unmasks an inherited factor VII (FVII) deficiency that is paradoxically associated with thrombotic tendency

A 32-year-old multiparous obese woman was referred to our center at 37 weeks of twin gestation. She was referred for birth planning following an accidentally discovered high international normalised ratio (INR) in routine preoperative labs. Her history was significant for recurrent pregnancy-associated deep venous thrombosis as well as two early pregnancy losses. Further work-up revealed transaminitis, mild splenomegaly and high lupus anticoagulant titre. A multidisciplinary team of physicians from the high-risk pregnancy, anaesthesiology, haematology, gastroenterology and hepatology departments put a management plan; it culminated into uncomplicated delivery of the patient by repeated caesarian section. The team was also able to figure out the cause of the patient’s high INR that is associated with thrombophilia rather than haemophilia.

Diabetes mellitus and SARS-CoV-2 infection: pathophysiologic mechanisms and implications in management

Introduction: Currently, diabetes mellitus (DM) as well as coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are major public health issues worldwide. Background: It has been suggested that patients with DM are more vulnerable to SARS-CoV-2 infection and suffer from more severe forms of the disease. Methods: A literature search was performed using PubMed, Scopus and Google search engines. Results: Angiotensin converting enzyme-2 (ACE2) is the major receptor of SARS-CoV-2 in the human host. The differential expression of ACE2 in the lungs of patients with DM makes them more susceptible to COVID-19. Additionally, acute or chronic hyperglycemia renders individuals in an immune-suppressive state, with impaired innate and adaptive immunity function, contributing also to the severity of COVID-19 infection among patients with DM. Other factors contributing to a more severe course of COVID-19 include the co-existence of obesity in T2DM; the endothelial inflammation induced by the SARS-CoV-2 infection, which aggravates the endothelial dysfunction observed in both T1DM and T2DM; and the hypercoagulability presented in COVID-19 infection that increases the thrombotic tendency in DM. Conclusion: This review summarizes the pathophysiologic mechanisms underlying the co-existence of both pandemics as well as the current recommendations and future perspectives regarding optimal treatment of inpatients and outpatients with DM in the era of SARS-CoV-2 infection. Notably, the current recommended drugs for the treatment of severe COVID-19, dexamethasone and remdesivir, may cause hyperglycemia, an adverse effect that physicians should bear in mind, when caring for patients with DM and COVID-19.

Impact of activated monocyte and endothelial dysfunction on coagulopathy in Egyptian adult beta thalassemic patients

The mechanism of the well observed hypercoagulability and high incidence of Thromboembolic Events (TE) in β- thalassemia patients has not been fully elucidated. This study aimed to evaluate evaluate the endothelial dysfunction and monocyte activation among adult Egyptian β-thalassemic patients and assess their role in the hypercoagulability and development of TE. A total of 40 adults patients with bthalassemics and 20 healthy age and sex-matched controls were assessed for endothelial dysfunction using serum Von Willebrand Factor Antigen (VWFAg) and for monocytic activation using flow cytometric assessment of CD14 monocyte microparticles and CD11b activated monocytes. The VWF:Ag level was significantly higher among thalassemic patients (P<0.001) and was positively correlated to development of TE (P<0.05). There was no significance difference for CD14 between patients and controls (P>0.5) and CD11b was higher in controls (P=0.004) with no significant correlation between both and TE development (P>0.05). VWF:Ag is increased in thalassemic patients and could be used as a risk factor for thrombosis in these patients, while no identified role of activated monocytes in thrombotic tendency in such patients.

High Prevalence of Acquired Thrombophilia Without Prognosis Value in Patients With Coronavirus Disease 2019

Background Recent literature reports a strong thrombotic tendency in patients hospitalized for a coronavirus disease 2019 (COVID‐19) infection. This characteristic is unusual and seems specific to COVID‐19 infections, especially in their severe form. Viral infections can trigger acquired thrombophilia, which can then lead to thrombotic complications. We investigate for the presence of acquired thrombophilia, which could participate in this phenomenon, and report its prevalence. We also wonder if these thrombophilias participate in the bad prognosis of severe COVID‐19 infections. Methods and Results In 89 consecutive patients hospitalized for COVID‐19 infection, we found a 20% prevalence of PS (protein S) deficiency and a high (ie, 72%) prevalence of antiphospholipid antibodies: mainly lupus anticoagulant. The presence of PS deficiency or antiphospholipid antibodies was not linked with a prolonged activated partial thromboplastin time nor with D‐dimer, fibrinogen, or CRP (C‐reactive protein) concentrations. These coagulation abnormalities are also not linked with thrombotic clinical events occurring during hospitalization nor with mortality. Conclusions We assess a high prevalence of positive tests detecting thrombophilia in COVID‐19 infections. However, in our series, these acquired thrombophilias are not correlated with the severity of the disease nor with the occurrence of thrombotic events. Albeit the strong thrombotic tendency in COVID‐19 infections, the presence of frequent acquired thrombophilia may be part of the inflammation storm of COVID‐19 and should not systematically modify our strategy on prophylactic anticoagulant treatment, which is already revised upwards in this pathological condition. Registration URL: https://www.clini​caltr​ials.gov ; Unique identifier: NCT04335162.

Bilateral Acute Lower Limb Ischemia Secondary to COVID-19

COVID-19 has to date affected over 5 million people worldwide and caused in excess of 300000 deaths. One of the principal finding is that of a thrombotic tendency within the lungs leading to high mortality. There have been increasing number of reports of peripheral arterial thrombosis as well. Most cases of arterial thrombosis is noted in patient in intensive care setting. Here-in we report a case of acute bilateral lower limb arterial thrombosis in a patient recovering at home with mild COVID-19 symptoms, highlighting that patients with milder symptoms may also suffer from prothrombotic state resulting in acute arterial occlusions. Arterial thrombosis should be suspected in these patients despite the absence of predisposing factors.