Abnormal immunothrombosis and lupus anticoagulant in a catastrophic COVID-19 recalling Asherson's syndrome.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a complex disease with many clinicopathological aspects, including abnormal immunothrombosis, and the full comprehension of its pathogenetic mechanisms is urgently required. METHODS/RESULTS: By means of a multidisciplinary approach, we here report a catastrophic COVID-19 in a 44-year-old Philippine male patient, discovered lupus anticoagulant (LAC)-positive shortly before death, occurred 8 days after hospitalization in a clinical scenario refractory to standard high acuity care recalling Asherson's syndrome (catastrophic antiphospholipid syndrome). CONCLUSION: A parallelism between this severe form of COVID-19 and Asherson's syndrome can be so drawn. Both the diseases in fact exhibit hypercytokinemia, thrombotic microangiopathy, disseminated intravascular coagulation and multiple organ failure, they show a relationship with viral infections, and they are burdened by a high mortality rate. A genetic predisposition to develop these two overlapping conditions may be supposed.

Lupus Anticoagulant Single Positivity During the Acute Phase of COVID-19 Is Not Associated With Venous Thromboembolism or In-Hospital Mortality.

OBJECTIVE: The clinical relevance of antiphospholipid antibodies (aPLs) in COVID-19 is controversial. This study was undertaken to investigate the prevalence and prognostic value of conventional and nonconventional aPLs in patients with COVID-19. METHODS: This was a multicenter, prospective observational study in a French cohort of patients hospitalized with suspected COVID-19. RESULTS: Two hundred forty-nine patients were hospitalized with suspected COVID-19, in whom COVID-19 was confirmed in 154 and not confirmed in 95. We found a significant increase in lupus anticoagulant (LAC) positivity among patients with COVID-19 compared to patients without COVID-19 (60.9% versus 23.7%; P < 0.001), while prevalence of conventional aPLs (IgG and IgM anti-ß2 -glycoprotein I and IgG and IgM anticardiolipin isotypes) and nonconventional aPLs (IgA isotype of anticardiolipin, IgA isotype of anti-ß2 -glycoprotein I, IgG and IgM isotypes of anti-phosphatidylserine/prothrombin, and IgG and IgM isotypes of antiprothrombin) was low in both groups. Patients with COVID-19 who were positive for LAC, as compared to patients with COVID-19 who were negative for LAC, had higher levels of fibrinogen (median 6.0 gm/liter [interquartile range 5.0-7.0] versus 5.3 gm/liter [interquartile range 4.3-6.4]; P = 0.028) and C-reactive protein (CRP) (median 115.5 mg/liter [interquartile range 66.0-204.8] versus 91.8 mg/liter [interquartile range 27.0-155.1]; P = 0.019). Univariate analysis did not show any association between LAC positivity and higher risks of venous thromboembolism (VTE) (odds ratio 1.02 [95% confidence interval 0.44-2.43], P = 0.95) or in-hospital mortality (odds ratio 1.80 [95% confidence interval 0.70-5.05], P = 0.24). With and without adjustment for CRP level, age, and sex, Kaplan-Meier survival curves according to LAC positivity confirmed the absence of an association with VTE or in-hospital mortality (unadjusted P = 0.64 and P = 0.26, respectively; adjusted hazard ratio 1.13 [95% confidence interval 0.48-2.60] and 1.80 [95% confidence interval 0.67-5.01], respectively). CONCLUSION: Patients with COVID-19 have an increased prevalence of LAC positivity associated with biologic markers of inflammation. However, LAC positivity at the time of hospital admission is not associated with VTE risk and/or in-hospital mortality.

Failure of Anticoagulation to Prevent Stroke in Context of Lupus-Associated Anti-Phospholipid Syndrome and Mild COVID-19.

Hypercoagulability and virally-mediated vascular inflammation have become well-recognized features of the SARS-CoV-2 virus infection, COVID-19. Of growing concern is the apparent ineffectiveness of therapeutic anticoagulation in preventing thromboembolic events among some at-risk patient subtypes with COVID-19. We present a 43-year-old female with a history of seropositive-antiphospholipid syndrome and systemic lupus erythematosus who developed an acute ischemic stroke in the setting of mild COVID-19 infection despite adherence to chronic systemic anticoagulation. The clinical significance of SARS-CoV-2-mediated endothelial cell dysfunction and its potential to cause macrovascular events in spite of full anticoagulation warrants further investigation and likely represents another disease-defining pathology of COVID-19.

Acquired factor V inhibitor in the setting of coronavirus disease 2019 infection.

Factor V inhibitors are a rare cause of life-threatening bleeding. We present a case of an acquired factor V inhibitor likely caused by coronavirus disease 2019 infection. Bleeding was manifested by severe anemia requiring frequent red-cell transfusion, left psoas muscle hematoma, and left retroperitoneal cavity hematoma. Factor V activity was less than 1% and the factor V inhibitor titer was 31.6 Bethesda units. Severe acute respiratory syndrome coronavirus 2 RNA testing of the nasopharynx was positive 2 weeks before presentation and continued to be positive for 30 days. The patient failed treatment with intravenous immunoglobulin and dexamethasone. Three cycles of plasmapheresis with fresh frozen plasma replacement resulted in correction of the bleeding and laboratory coagulopathy. This is the first reported case of a factor V inhibitor in a coronavirus disease 2019 patient and suggests that plasmapheresis may be a successful treatment strategy.

Lupus anticoagulant and mortality in patients hospitalized for COVID-19.

Coronavirus disease 2019 (COVID-19) is characterized by a procoagulant state that can lead to fatal thromboembolic events. Several studies have documented a high prevalence of lupus anticoagulant that may at least partially explain the procoagulant profile of COVID-19. However, the association between lupus anticoagulant and thrombotic complications in COVID-19 is controversial and no study has specifically evaluated the impact of lupus anticoagulant on mortality. The aim of our study was to investigate the association between lupus anticoagulant and mortality in a large group of 192 consecutive patients hospitalized for COVID-19. Lupus anticoagulant was found in 95 patients (49.5%). No difference in the percentage of patients with lupus anticoagulant was observed between 130 survivors and 62 non-survivors (47.7 versus 53,2%; p = 0.4745). When the combined outcome of death or need for mechanical ventilation in survivors was taken into account, the difference in the prevalence of patients with lupus anticoagulant between the patients with the combined outcome (n = 76) and survivors who did not require mechanical ventilation (n = 116) was not significant (52.6% versus 47.4%; p = 0.4806). In multivariate analysis predictors of mortality or need for mechanical ventilation in survivors were obesity, low oxygen saturation and elevated troponin levels measured on admission. In conclusion, our study did not show any association of lupus anticoagulant with mortality and with need for mechanical ventilation in survivors. The role of obesity, low SaO2 and elevated troponin levels as predictors of a worse prognosis in patients hospitalized for COVID-19 was confirmed.

An 89-Year-Old Man with COVID-19-Associated Coagulopathy Presenting with a Prolonged Partial Thromboplastin Time, Lupus Anticoagulant, and a High Titer of Factor VIII Inhibitor.

BACKGROUND Coagulation abnormalities are frequently encountered in patients with coronavirus disease 2019 (COVID-19), especially in those with more severe disease. These hematologic abnormalities are suspected to occur in the context of underlying immune dysregulation and endothelial dysfunction. Elevated D-dimer levels, COVID-19-associated coagulopathy (CAC), disseminated intravascular coagulation (DIC), and positive lupus anticoagulants are the most common findings to date. Current guidelines suggest that all patients with COVID-19 should receive pharmacologic thromboprophylaxis. CASE REPORT An 89-year-old man with a medical history of hypertension, type 2 diabetes, and advanced prostate cancer in remission presented with generalized weakness. At our center, a reverse transcription-polymerase chain reaction test was positive for severe acute respiratory syndrome coronavirus 2, but the patient did not have symptoms of COVID-19. He was also found to have a prolonged activated partial thromboplastin time, secondary to both a high titer of factor VIII inhibitor and a lupus anticoagulant. He eventually developed respiratory compromise, during which his disease manifested as a bleeding rather than a prothrombotic state. CONCLUSIONS This report highlights the importance of a comprehensive evaluation of prolonged partial thromboplastin time, rather than making an assumption based on a positive lupus anticoagulant result. In the case presented, the concomitant factor VIII inhibitor caused the patient to have a greater bleeding tendency. It is imperative that physicians balance the risk of bleeding and clotting in patients with COVID-19 because patients seem to have varying presentations based on disease severity and level of immune dysregulation.

COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of haemostasis and clot waveform analysis.

Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic response to the SARS-CoV-2 infection. Overlapping syndromes of COVID-19 associated coagulopathy with consumptive coagulopathy and microangiopathy can be seen in critically ill patients as well. Blood was collected from 12 Intensive Care Unit (ICU) patients with severe COVID-19 who were on either mechanical ventilation or on high flow oxygen with a PaO2/FiO2 ratio of <300 mmHg. Laboratory tests were performed for parameters of haemostasis, clot waveform analysis and anti-phospholipid antibodies. CWA parameters were raised with elevated aPTT median Min1 (clot velocity) 9.3%/s (IQR 7.1-9.9%/s), elevated PT median Min1 10.3%/s (IQR 7.1-11.1%/s), elevated aPTT median Min2 (clot acceleration) 1.5%/s2 (IQR 1.0-1.6%/s2), elevated PT median Min2 5.2%/s2 (3.6-5.7%/s2), elevated aPTT median Max2 (clot deceleration) 1.3%/s2 (IQR 0.8-1.4%/s2) elevated PT median Max2 3.8%/s2 (IQR 2.6-4.2%/s2), increased aPTT median Delta change (decreased light transmission due to increased clot formation) 87.8% (IQR 70.2-91.8%) and PT median Delta change 33.0%. This together with raised median Factor VIII levels of 262.5%, hyperfibrinogenemia (median fibrinogen levels 7.5 g/L), increased median von Willebrand factor antigen levels 320% and elevated median D-dimer levels 1.7 µg/dl support the diagnosis of COVID-19 associated coagulopathy. A lupus anticoagulant was present in 50% of patients. Our laboratory findings further support the view that severe SARS-CoV-2 infection is associated with a state of hypercoagulability.

A Peculiar Case of Small Bowel Stricture in a Coronavirus Disease 2019 Patient with Congenital Adhesion Band and Superior Mesenteric Vein Thrombosis.

BACKGROUND: There is increasing evidence supporting coronavirus disease 2019 (COVID-19)-related coagulopathy. In the available literature, only 2 cases of superior mesenteric vein thrombosis have been described. METHODS: We present a peculiar case of high-grade small bowel obstruction in a patient with COVID-19 infection. RESULTS: Exploratory laparotomy revealed a congenital adhesion band with associated focal bowel ischemia contributed by superior mesenteric vein thrombosis and positive lupus anticoagulant. CONCLUSIONS: It is important to consider the rare differential of mesenteric vein thrombosis and its related sequelae of mesenteric ischemia in a patient with COVID-19 who presents with abdominal pain.

A 31-Year-Old Man with COVID-19-Associated Empyema and Lupus Anticoagulant.

BACKGROUND COVID-19 was declared a pandemic in March 2020 in the United States. It has been associated with high mortality and morbidity all over the world. COVID-19 can cause a significant inflammatory response leading to coagulopathy and this hypercoagulable state has been associated with worse clinical outcomes in these patients. The published data regarding the presence of lupus anticoagulant in critically ill COVID-19-positive patients is limited and indicates varying conclusions so far. CASE REPORT Here, we present a case of a 31-year-old man who was admitted to the hospital with COVID-19 pneumonia, complicated with superadded bacterial empyema and required video-assisted thoracoscopic surgery with decortication. This patient also had prolonged prothrombin time on preoperative labs, which was not corrected with mixing study. Further workup detected positive lupus anticoagulant and anti-cardiolipin IgM along with alteration in other coagulation factor levels. The patient was treated with fresh frozen plasma and vitamin K before surgical intervention. He had an uneventful surgical course. He received prophylactic-dose low molecular weight heparin for venous thromboembolism prophylaxis and did not experience any thrombotic events while hospitalized. CONCLUSIONS COVID-19 infection creates a prothrombotic state in affected patients. The formation of micro-thrombotic emboli results in significantly increased mortality and morbidity. Routine anticoagulation with low molecular weight heparin can prevent thrombotic events and thus can improve patient outcomes. In patients with elevated prothrombin time, lupus anticoagulant/anti-cardiolipin antibody-positivity should be suspected, and anticoagulation prophylaxis should be continued perioperatively for better outcomes.

Bilateral Acute Cardioembolic Limb Ischemia After Coronavirus Disease 2019 Pneumonia in a Lung Transplant Recipient: A Case Report.

Very few cases of lung transplant patients affected by coronavirus disease 2019 (COVID-19) have been reported to date. A 31-year-old patient who underwent bilateral lung transplantation for cystic fibrosis in 2012 was admitted for severe acute lower limb pain. He had a confirmed exposure to COVID-19 and a 3-week history of upper respiratory tract infection. Whole-body computed tomography (CT) angiography revealed an occlusion of the 2 common femoral arteries. CT angiography detected an intracardiac thrombus in the left ventricle. Chest CT angiography showed ground-glass opacities consistent with COVID-19. A bilateral femoral surgical embolectomy using Fogarty catheter was successfully performed. Specific reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 performed on an extracted thrombus was negative, but IgM antibodies specific for COVID-19 were detected. Cardiac magnetic resonance imaging demonstrated a subendocardial and almost transmural late gadolinium enhancement in the mid and distal inferolateral and inferior wall segments, consistent with a nonrecent myocardial infarction and an apical centimetric thrombus adjacent to the lesion. Thrombophilia laboratory tests found the presence of a positive lupus anticoagulant. Treatment with low-molecular-weight heparin and aspirin was prescribed. On day 13, the patient was discharged from the hospital. This case underlines the need to be vigilant with respect to the thrombotic complications of COVID-19 and raises the issue of thrombosis prevention in COVID-19 patients.