COVID-19 and Sickle Cell Disease: Two Independent Risk Factors for Venous Thromboembolism.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been widely documented as a multi-systemic illness and associated with an increased incidence of thromboses. Likewise, sickle cell disease (SCD) is a hematologic disease responsible for widespread effects on the vasculature and is also associated with elevated thrombotic risk. In this review, we examine the incidence rates of venous thromboembolism (VTE) in SCD and COVID-19 independently and review the mechanisms of coagulopathy associated with both diseases. We describe the possible associations and commonalities between VTE mechanisms, as both diseases cause widespread inflammation that influences each tenet of Virchow's triad. We also discuss current anticoagulation guideline recommendations for the prevention of VTE events in each of these diseases. We report on current literature to date describing rates of VTE in SCD-COVID-19 patients and outline prospective areas of research to further understand the possible synergistic influence of coagulopathy in these patients. The association between SCD and COVID-19 remains a largely under-researched area of coagulopathy in current hematology and thrombotic literature, and our report lays out potential future prospects in the field.

Acute Limb Ischemia in COVID-19 Patients: A Single University Center Experience.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is currently known to lead to high rates of thrombotic complications. Of those, acute limb ischemia (ALI) was most frequently reported. Several case reports or case series had already described high mortality and amputation rates. The purpose of our study was to highlight the epidemiological, clinical, and management characteristics of coronavirus disease 2019 (COVID-19)-related ALI patients. Methods This was a monocentric, observational, and retrospective study. Records of all patients ≥18 years of age admitted with ALI and a confirmed diagnosis of COVID-19 infection between March 2020 and December 2021 were retrospectively examined. Data collected included demographics, co-morbidities, biological findings, COVID-19 pneumonia and ALI severity, anatomical location of arterial thromboembolism, treatments, and outcomes. Results During the study period, 22 patients with ALI infected with COVID-19 were evaluated. The median age was 67 years (45-88) and 18 (81.8%) were men. The main comorbidities were diabetes mellitus (36.4%), smoking (22.7%), and arterial hypertension (18.2%). All 22 patients were already diagnosed positive for SARS-CoV-2. The median duration between COVID-19 diagnosis and ALI symptom onset was six days (1-13 days). The computed tomography (CT) extent of pulmonary lesions was assessed according to the French Society of Chest Imaging. The ischemic syndrome was classified on Rutherford Stage IIA (30.4%) and IIB (43.5%). Regarding thrombotic locations, ALI had occurred essentially in the lower limbs (95% vs. 5%). A revascularization procedure was performed in 14 patients (63.6%) of the patients, and primary amputation was unavoidable in five patients (22.7%). Three patients (13.6%) did not undergo operative management, two because of their hemodynamic instability and one rejected surgery. We performed 23 revascularization procedures for 14 patients and three primary amputations. Thromboembolectomy (TE) was the technique of choice (92.8%). Below-the-knee (BTK) femoropopliteal bypass was performed in one patient. Selective tibial vessel thrombectomy was performed in four patients (28.6%). The mortality rate was 27.3%. Among survivors, two secondary amputations were needed with a limb salvage rate of 68.2%. Conclusion By the apparent end of the pandemic, our study further supports the increased risk of ALI in COVID-19-positive patients. Moreover, the results affirm the unfavorable outcomes highly impacted by rethrombosis, reinterventions, and consequently high rates of amputations and mortality.

Outcomes of COVID-19 in Adult Males With Hemophilia A: A Propensity Score-Matched Analysis.

Background Hypercoagulability is a major pathologic event in COVID-19. Factor VIII plays an important role in hemostasis, and high levels of factor VIII have been shown to be associated with an increased risk of thrombosis and severe disease. Little is known about the impact of COVID-19 on clinical outcomes in patients with hemophilia A. Methodology Retrospective data of adult male patients with COVID-19 with and without hemophilia A were retrieved from the TriNetX database (Cambridge, USA). The 1:1 propensity score-matching was performed to balance baseline characteristics. Patients were matched for age, race, body mass index, and medical comorbidities. Thirty-day outcomes were assessed. Results We identified 1,758 patients with pre-existing hemophilia A diagnosis prior to COVID-19 diagnosis and 5,191,908 comparators. After 1:1 propensity score matching, groups were balanced on demographics and comorbidities. All-cause mortality rates were similar between the two groups (HR 0.805; 95% CI 0.467-1.389). The frequency of severe infection, ICU admission, and composite thrombotic events did not differ between the groups. Patients with hemophilia A were hospitalized more frequently than those without a history of hemophilia A (19.2% vs. 14.4%; p<0.05). Additionally, gastrointestinal (GI) bleeding and composite bleeding events occurred more frequently in patients with hemophilia A (3.2% vs. 2.2%; p<0.05 and 4.0% vs. 2.8%; p<0.05, respectively). Conclusions The mortality of individuals with hemophilia A due to COVID-19 is comparable to the general population but with higher risks of hospitalization and bleeding.

COVID-19 coagulopathy - what should we treat?

NEW FINDINGS: What is the topic of this review? Overview of the coagulation abnormalities, including elevated D-dimers widely reported with COVID-19, often labelled as COVID coagulopathy. What advances does it highlight? The review highlights the changes in bronchoalveolar haemostasis due to apoptosis of alveolar cells, which contributes to acute lung injury and acute respiratory distress syndrome; the pathophysiological mechanisms, including endothelial dysfunction and damage responsible for thrombosis of pulmonary microcirculation and potential contribution to the hypoxaemia of COVID-19 acute lung injury; and changes in coagulation proteins responsible for the hypercoagulability and increased risk of thrombosis in other venous and arterial beds. The rationale for anticoagulation and fibrinolytic therapies is detailed, and potential confounders that might have led to less than expected improvement in the various randomised controlled trials are considered. ABSTRACT: Coronavirus disease 19 (COVID-19) causes acute lung injury with diffuse alveolar damage, alveolar-capillary barrier disruption, thrombin generation and alveolar fibrin deposition. Clinically, hypoxaemia is associated with preserved lung compliance early in the disease, suggesting the lack of excessive fluid accumulation typical of other lung injuries. Notably, autopsy studies demonstrate infection of the endothelium with extensive capillary thrombosis distinct from the embolic thrombi in pulmonary arteries. The inflammatory thrombosis in pulmonary vasculature secondary to endothelial infection and dysfunction appears to contribute to hypoxaemia. This is associated with elevated D-dimers and acquired hypercoagulability with an increased risk of deep vein thrombosis. Hypercoagulability is secondary to elevated plasma tissue factor levels, von Willebrand factor, fibrinogen, reduced ADAMTS-13 with platelet activation and inhibition of fibrinolysis. Multi-platform randomised controlled studies of systemic therapeutic anticoagulation with unfractionated and low molecular mass heparins demonstrated a survival benefit over standard care with full-dose anticoagulation in patients with non-severe disease who require supplemental oxygen, but not in severe disease requiring ventilatory support. Late intervention and the heterogeneous nature of enrolled patients can potentially explain the apparent lack of benefit in severe disease. Improvement in oxygenation has been demonstrated with intravenous fibrinolytics in small studies. Inhaled anticoagulants, thrombolytic agents and non-specific proteolytic drugs in clinical trials for decreasing alveolar fibrin deposition might benefit early disease. Essentially, COVID-19 is a multi-system disorder with pulmonary vascular inflammatory thrombosis that requires an interdisciplinary approach to combination therapies addressing both inflammation and intravascular thrombosis or alveolar fibrin deposits to improve outcomes.

Pharmacological Management of Saddle Pulmonary Embolism in a High-Risk Patient With COVID-19.

A pulmonary embolism (PE) that is located in the main pulmonary artery is known as a saddle pulmonary embolism. Individuals at high risk who become unstable often require surgical intervention or more aggressive management with thrombolytic therapy. COVID-19 is a known risk factor for a hypercoagulable state and therefore increases the risk of PE and its associated complications. Individuals hospitalized with the COVID-19 virus and who have evidence of right ventricular dysfunction with PE are found to have a significantly higher risk of mortality. We present a case of an individual with several high-risk factors for PE as well as COVID-19 infection and evidence of cardiac strain, making the decision for treatment less clear. He was, however, treated successfully with heparin and enoxaparin alone. Furthermore, our case hadresolving symptoms of COVID-19, highlighting the importance of high clinical suspicion for PE in those diagnosed with COVID-19.

Use of Systemic Anticoagulation in COVID-19: Delving Beyond Theoretical Hypothesis.

Background Studies suggest that COVID-19 infection may induce increased hypercoagulability, leading to thrombotic complications. The high rates of thrombotic complications among patients receiving standard-dose deep venous thrombosis (DVT) prophylaxis have prompted some clinicians to support the empiric increase of anticoagulation (AC) doses used for prophylaxis in patients with COVID-19. At present, the optimal anticoagulant agents, dosages, and duration have not been designated. We conducted a retrospective study to assess for outcomes in patients who received treatment for COVID-19 based on various dosings of AC. Methods This was a single-institution, retrospective cross-sectional study including patients with a positive COVID-19 test who were admitted within the St. Joseph's Health Network from September to November of 2020. The inclusion criteria were men and women aged 18 years or older who had confirmed COVID-19 by polymerase chain reaction (PCR). Medical charts of patients who met the inclusion criteria were audited to obtain information. The patients were separated into three cohorts: those who received DVT prophylactic dose of AC, those who received an intermediate dose of AC, and those who received therapeutic AC. Results A total of 440 patients were included in the study, of whom 236 were Hispanic (50.3%), 131 were Caucasian (27.1%), 47 were African American (10.7%), and 26 were Asian (5.9%). The most common comorbidities were hypertension (273/440 [62.2%]), diabetes 189/440 [43.1%]), and coronary artery disease (60/440 [13.7%]). In the DVT prophylactic dose of AC cohort, there were 215 patients, and the average length of stay was 10.3 days. Eleven patients experienced bleeding events, five patients experienced thrombotic events, 16 patients required mechanical ventilation, and 20 patients died. In the intermediate dose of AC cohort, there were 63 patients, and the average length of stay was 10.3 days. Three patients experienced bleeding events, two patients experienced thrombotic events, seven patients required mechanical invasive ventilation, and 11 patients died. In the therapeutic dose of AC cohort, there were 162 patients, and the average length of stay was 14 days. In this cohort, 19 patients experienced bleeding events, 12 patients experienced thrombotic events, 26 patients required invasive mechanical ventilation, and 29 patients died. Patients who received intermediate dosing of AC also had the lowest risk of thrombotic events (0.05). Patients who received intermediate dosing of AC had the lowest rates of requiring both high-flow nasal cannula (p = 0.0001) and invasive mechanical ventilation (p = 0.031). Patients who received intermediate dosing of AC had a lower rate of bleeding compared to those who received the DVT prophylaxis dose and systemic AC dose (p = 0.037). The DVT prophylactic and intermediate dosing of AC groups had a shorter length of stay in comparison to the systemic AC group (p = 0.0002). Conclusion In comparison to the venous thromboembolism prophylaxis dose and systemic AC dose groups, intermediate dosing of AC had the lowest rates of hemorrhage, mortality, length of stay, and requirement of high-flow nasal cannula or mechanical invasive ventilation. In the systemic dose AC group, there were worse clinical outcomes in terms of length of stay, incidence of bleeding events, requirement of mechanical ventilator use, and rate of mortality.

Exacerbation of Secondary Cold Agglutinin Syndrome in the Setting of SARS-CoV-2.

In this report, we present a case of exacerbation of cold agglutinin syndrome (CAS) potentially due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia. An 83-year-old female with a history of cold agglutinin hemolytic anemia presented with shortness of breath, productive cough, worsening orthopnea, darkening fingers and urine, and jaundice. Laboratory investigations found elevated white blood cells (WBC) and total bilirubin, severely low hemoglobin, and positive direct Coombs test. Moreover, SARS-CoV-2 RNA was also found to be positive in a sample from the nasal swab by reverse transcription-polymerase chain reaction (RT-PCR), indicating exacerbation of CAS secondary to viral coronavirus 2019 (COVID-19) infection. A treatment regime for SARS-CoV-2 consisting of five days of remdesivir and seven days of dexamethasone 6 mg IV was initiated, resulting in significant improvement in the patient's condition.

Acute Mesenteric Ischemia as an Early Complication of COVID-19.

We herein report a case of a 44-year old male patient with coronavirus disease 2019 (COVID-19) who presented with acute mesenteric ischemia. Acute mesenteric ischemia presents with severe abdominal pain, vomiting, and constipation. The case consisted of features typical of acute mesenteric ischemia. The patient underwent laparotomy with resection of a gangrenous segment of the bowel. The radiological features of the injury along with the pathophysiology and management have been discussed.

A Case of COVID-19 Related Coagulopathy Complications and Heparin Resistance.

Mechanisms of COVID-19 coagulopathy have been speculated and are not definitively understood; the current speculation is that there is elaborate crosstalk between the inflammatory and hemostatic systems which contributes to the overall increased thrombotic risk in the setting of COVID-19 resulting in a hypercoagulable state. A few documented reports regarding cases of apparent heparin resistance in patients with COVID-19 with complications of thromboembolic events occurring in the setting of heparin anticoagulation have been described. This phenomenon of heparin resistance has been observed in patients with active, severe COVID-19 infection. However, we describe a unique case of a patient who had recovered from a recent, mild COVID-19 infection that did not require hospitalization and presented with acute limb ischemia and demonstrated heparin resistance. The patient was managed by specialists in vascular surgery, intensivists, cardiologists, hematology, and physical medicine and rehabilitation (PMR). We present the case of a patient who had successfully recovered from COVID-19 yet demonstrated post-COVID-19 complications related to coagulopathy and heparin resistance.

Thrombosis of the Portal Vein and Superior Mesenteric Vein in a Patient With Subclinical COVID-19 Infection.

More than 122 million cases of COVID-19 infection have been documented, and hundreds of thousands are being added every day. Several co-morbidities are associated with COVID-19, among which hypercoagulability has garnered the attention of many doctors and researchers. Most cases of vascular thrombosis are noted in intensive care unit (ICU) patients with serious disease; among these, many cases of deep venous thrombosis and pulmonary embolism have been noted. A few cases of portal vein thrombosis have also been documented in ICU patients with severe COVID-19. Here, we present a case of a portal vein and superior mesenteric vein thrombosis in a patient with subclinical COVID-19 infection. Through this case report, we intend to increase the research horizon and wish to help diagnose co-morbidities associated with COVID-19 at an earlier stage.

Neurological Manifestations of COVID-19 Within the Intensive Care Unit During a Military Deployment for the Early Pandemic Surge in New York City.

Coronavirus disease 2019 (COVID-19) resulted in a worldwide pandemic that at the time of this writing has caused over 400,000 deaths within the United States. During the pandemic surge in New York City, NY, a number of military Medical Corps (MC) and Nurse Corps (NC) providers were mobilized in direct support of critical care capabilities through expansion intensive care units. In the course of the deployment, high rates of neurological-related manifestations associated with COVID-19 infection were directly observed by our military provider teams which will be described and supporting literature highlighted. This is organic information absorbed in real time during the early stages of the pandemic in New York City. The neurological manifestations of COVID-19 varied in presentation and severity. Cerebral vascular injuries documented included strokes, iatrogenic intraparenchymal hemorrhage, hypoxia-related changes and sequelae, as well as acquired diseases secondary to delayed treatment of other primary neurologic disease states. Hypercoagulable and inflammatory markers (d-dimer, C-reactive protein, etc) were commonly elevated, and anticoagulation became a key factor in disease treatment and to help mitigate the downstream neurologic sequelae associated with this disease. Here we present these initial findings to lay the groundwork for more robust clinical studies moving forward.

Budd-Chiari Syndrome: A Case Report of a Rare Presentation of COVID-19.

Coronavirus Disease 2019 (COVID-19) predominantly involves the respiratory system and shows a wide range of severity. There is a growing body of evidence about the occurrence of thromboembolic events in COVID-19. Case Report: We report the case of a 48-year-old female patient who presented with sudden-onset abdominal pain. Physical examination revealed ascites and tender hepatomegaly. Subsequently, abdominal computed tomography was performed which revealed thrombosis in the hepatic vein and inferior vena cava in keeping with Budd-Chiari Syndrome. The patient was started on low-molecular-weight heparin and supportive care. Clinical improvement was observed over the course of the treatment and the patient was discharged after 10 days from the presentation. Thromboembolic events could be the first manifestation of COVID-19. Early recognition of these complications is crucial for prompt management.

COVID-19-Induced Ischemic Infarcts With Normal Coagulation Profile and Excellent Outcome: A Case Report With Highlights on the Thrombotic Diathesis, Recent Transcranial Doppler Findings, and Neuropathology Update.

We present the case of a previously healthy 41-year-old man right-handed man diagnosed with coronavirus disease 2019 (COVID-19) who developed multiple cortical ischemic infarcts. Our patient developed mild neurologic deficits despite the total volume of cerebral ischemic lesions, presumably due to involvement of non-eloquent cortex, the integrity of the collateral circulation due to his youth and good health, and mild COVID-19 disease without any significant pulmonary involvement. We discuss the coagulopathy and direct vascular effects, if any, of COVID-19 disease and compare it to other agents such as the filovirus, ad Ebola. We also outline the recent intriguing findings of vasodilation of the pulmonary vessels and the potential shunting of micro-emboli into the brain, which may explain the formation of embolic ischemic infarcts in even mild disease. Lastly, we discuss the neuropathology of COVID-19 in patients that who have succumbed to the disease and note the striking lack of direct involvement of the cerebral blood vessels.

Isolated Radial Vein Thrombosis: Upper Extremity Deep Vein Thrombosis in a Patient With COVID-19 Infection.

In general, upper extremity deep vein thrombosis (DVT) is less common than lower extremity DVT. Among upper extremity DVT cases, most of them are due to secondary causes like indwelling catheters, cancer, surgery, trauma or immobilization by plaster casts, pregnancy, oral contraceptives, and estrogen. Patients with coronavirus disease 2019 (COVID-19) infection are known to have coagulation dysfunction and a high incidence of DVT, mostly in the lower extremities; however, upper extremity DVT has been rarely reported. We present a rare case of upper extremity DVT in COVID-19 infection. A 56-year-old male with no significant past medical history was admitted with acute respiratory failure due to COVID-19 pneumonia. During hospitalization, he developed right upper extremity swelling, and an ultrasonogram showed right radial vein thrombosis. He was initially started on low molecular weight heparin (LMWH) and was discharged on apixaban. Patients with COVID-19 infection who develop DVT are recommended treatment with a direct oral anticoagulant (DOAC) for three months.

Coagulation Inhibitors in COVID-19 Leading to Compressive Airway Hematoma.

We are focusing on three things for every patient in the hospital with COVID-19, namely dexamethasone, remdesivir and enhanced anticoagulation protocols as this had shown improved mortality. However, the bleeding risk in these patients has not been taken into consideration. In our ICU setting at Rochester General hospital, we have seen too many cases with gastrointestinal bleeding and hemoptysis in COVID-19 patients. In this case, we report bleeding related to central access removal related to coagulation inhibitors that lead to airway compression. The aim of this case is to keep bleeding tendency of COVID-19 patients on the radar and to delineate that it has clear severe consequences just as clotting.

COVID-19-Associated Acute Limb Ischemia in a Patient on Therapeutic Anticoagulation.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been found to cause multiple complications across several organ systems in patterns not typically observed in previous iterations of the virus. Hemostatic mechanisms have been noted to be significantly altered in particular, resulting in a disseminated intravascular coagulation (DIC)-like picture with elements of coagulopathy as well as hypercoagulability. A 65-year-old man with hypertension, hyperlipidemia, prior tobacco use, chronic kidney disease, and diabetes presented from a correctional facility with hypoxia. The diagnosis of COVID-19 was confirmed. With his elevated D-dimer of >7,955 ng/mL (reference: 90-500 ng/mL) in the setting of COVID-19 and hypoxia, he was empirically started on therapeutic anticoagulation with enoxaparin. His oxygen requirements increased, mental status deteriorated, and platelets began falling, raising concern for heparin-induced thrombocytopenia versus DIC. Heparin products were discontinued in favor of a direct oral anticoagulant. He later became obtunded and unable to tolerate oral medications. Fondaparinux was initiated. Two days later, he was found to have acute limb ischemia of the right lower extremity. He underwent surgical thrombectomy but required an above-the-knee amputation the following day. Shortly after he died secondary to hypoxic respiratory failure. This case highlights the derangement of hemostatic mechanisms seen prominently in COVID-19 infection and raises questions as to appropriate anticoagulant choices to adequately prevent thrombosis. Thorough physical exams should be performed on all patients with COVID-19, taking into account this documented hypercoagulability. Further investigation is warranted into the use of heparin products as the anticoagulant of choice in these patients given observed deficiencies of antithrombin III (ATIII).

Coronavirus Disease 2019 (COVID-19)-Associated Thromboembolic Disease: A Report of Three Patients With Pulmonary Embolism.

Coagulopathy and thromboembolic disease, including pulmonary embolism (PE), are reported complications of coronavirus disease 2019 (COVID-19). The mechanism is not fully understood. We present three patients with COVID-19 and concurrent PE.