Myocardial infarction with non-obstructive coronary arteries (MINOCA) complicating myocarditis

Myocarditis can lead to myocardial infarction in the absence of coronary artery obstruction. We report a case of probable myocarditis, complicated by myocardial infarction with non-obstructive coronary arteries. A 19-year-old man presented with chest pain typical of myocarditis. He was a smoker but was otherwise well. Electrocardiogram revealed diffuse ST-elevation and echocardiography revealed a thin, akinetic apex. Troponin-T levels on admission were raised leading to an initial diagnosis of myocarditis being made. However, late gadolinium enhancement study on cardiac magnetic resonance imaging demonstrated transmural enhancement typical of ischaemia. Coronary angiogram was normal, leading to a likely diagnosis of myocardial infarction with non-obstructive coronary arteries. It is important to highlight that coronary assessment remains important when working up for myocarditis, as myocardial infarction with non-obstructive coronary arteries can often complicate myocarditis in cases of normal angiography. Another important lesson was on how cardiac magnetic resonance imaging provided vital evidence to support underlying ischaemia despite normal coronary angiogram, leading to a diagnosis of myocardial infarction with non-obstructive coronary arteries. Myocardial infarction with non-obstructive coronary arteries remains a broad 'umbrella' term and cardiac magnetic resonance imaging, as well as more invasive coronary imaging techniques during angiography, can further assist in its diagnosis. Our case provides a reminder that myocardial infarction with non-obstructive coronary arteries, although increasingly recognised, remains under-diagnosed and can often overlap with peri-myocarditis, highlighting the need to employ multi-modality imaging in guiding management.Copyright © The Author(s) 2021.

factor V leiden mutation detection before astraZeneca vaccine

BacKgrouNd: on the beginning of 2020 the world woke up with a novel coronavirus disease (coVId-19) pandemic caused by sarscoV-2, started in Wuhan, china. several types of vaccine appeared, one of them was astraZeneca (astraZenca, cambridge, uK) vaccine. METHOD(S): This is a single-center retrospective study which included 9 patients who developed DVT after the first dose of AstraZeneca vaccine. they were screened for thrombophilia, including factor V leiden mutation. rEsults: they were found positive for factor V leiden mutation and were treated by Noacs. also, they were advised to delay second dose for 3 months and to shift to another vaccine like sinopharm (china National Pharmaceutical group, Beijing, china). coNclusIoNs: alert should be raised for patients with factor V leiden mutation having a second dose;and for the treatment of the thrombosis condition. Copyright © 2022 EdIZIoNI MINErVa MEdIca.

HYPERCOAGULABLE AND GENETICALLY THROMBOPHILIC PATIENTS WITH CEREBRAL VENOUS THROMBOSIS

Introduction Cerebral venous thrombosis (CVT) may occur due to a number of common etiologies such as thromboembolism, atherosclerotic disease, or small vessel disease. When these are ruled out or considered unlikely, a hypercoagulability workup is performed. We describe a series of 30 patients with CVT and medical and/or genetic basis for the underlying hypercoagulable state and thrombophilia. Methods A retrospective review of all CVT cases treated with venous thrombectomy between June 2016 and August 2021 was performed within our institutional, neuroendovascular database. Results Of the 30 patients identified, 18 were associated with a hypercoagulable state and/or thrombophilia. Underlying illness was present in seven (36.8%) patients due to polycythemia vera, systemic lupus erythematosus, a combination of nephrotic syndrome and morbid obesity, a combination of rheumatoid arthritis and diabetes, chronic rejection of a small bowel transplant further complicated by acute renal failure and ARDS, a combination of diabetes, DVT, and a dyslipidemic state, and Covid-19. Hypercoagulable states were identified in seven (36.8%) patients due to elevated Factor VIII (1/ 7), antiphospholipid syndrome (3/7), and Protein S deficiency (3/7). Genetic thrombophilia was identified in four (16.4%) patients in the form of a heterozygous Factor V mutation in R506Q (2/4), a heterozygous Prothrombin Factor II mutation in G20210A (1/4), and a homozygous 4G/4G promoter Plasminogen Activator inhibitor I deletion mutation (1/4). Overall, no subset of hypercoagulability (I.e. mutation, disease, transient state) nor hypercoagulability overall was predictive of outcome as measured by recanalization, discharge disposition, or reocclusion likelihood. Conclusion The most common cause of hypercoagulability was underlying disease or transient antiphospholipid syndrome/elevated pro-coagulation factor. While we are unable to report hypercoagulability as a predictive variable of outcome in our cohort, we outline the presence of various coagulopathies within this medically refractory, CVT cohort. While CVT may occur due to many common pathologies, in cases where the cause is unknown a hypercoagulability workup my shed light on mitigating factors underlying the thrombosis.

Symptomatic Renal Infarct Secondary to COVID-19 Infection and Concomitantly Positive Antiphospholipid Antibody

COVID-19 infection predisposes patients to a hypercoagulable state. The clinical significance of concomitantly positive antiphospholipid antibodies as a risk factor for thrombus formation is unknown. We report a case of renal infarct secondary to COVID-19 infection with mildly elevated antiphospholipid antibodies. A 71-year- old woman with a history of hypertension, supraventricular tachycardia, resected carcinoid tumor in remission, COVID-19 infection (20 days prior), presented to the hospital with acute onset severe left lower quadrant pain radiating to the left flank for one day. She reported a fever of 101 F. Vital signs were normal in the emergency room. Physical exam showed left costovertebral angle tenderness, otherwise benign abdomen with no guarding or rigidity. Laboratory findings showed normal liver function tests, mildly elevated creatinine at 1.1 mg/dl (baseline 0.8 mg/dl), and leukocytosis (14.2 K/ul). Urinalysis showed no evidence of proteinuria or microscopic hematuria. CT scan of the abdomen demonstrated a large area of patchy hypoattenuation involving the upper pole and interpolar region of the left kidney with adjacent perinephric inflammation representing a sequela of an infarct. Hypercoagulable workup including HIV, hepatitis, ANA, ANCA, complements, B2 glycoprotein, homocysteine, factor V Leiden, anti-thrombin III, protein C, protein S were done. All tests resulted negative except for mildly elevated anticardiolipin antibody, IgM 12.90 MPL (normal 0.00-12.49 MPL). Holter monitor was negative for atrial fibrillation. An echocardiogram did not show any thrombus. Considering her negative tests, renal infarct was believed to be secondary to a hypercoagulable state from COVID-19 infection. Antiphospholipid antibodies repeated 3 months after this admission were mildly elevated. Renal infarction was treated with a heparin infusion and was subsequently transitioned to apixaban. Acute kidney injury resolved with intravenous fluid resuscitation. At a 3-month follow-up, her renal function remained stable with a resolution of symptoms. Renal artery infarct is a possible thrombotic complication of COVID -19. Role of lupus anticoagulant antibodies in increasing this risk warrants further studies.

Pediatric Cerebral Infarction associated with recent SARS-CoV-2 mild infection treated with intravenous thrombolysis and endovascular thrombectomy

Objective: N/A Background: Acute ischemic stroke is a major cause of disability worldwide in adults and children. It is a common disease after middle age but uncommon in the pediatric population. Disabling arterial ischemic strokes due to acute intracranial large vessel occlusion within 3-4 weeks of SARS-CoV-2 (COVID-19) infection have been described. Design/Methods: N/A Results: A 15-year-old boy presented with sudden onset right-sided weakness and expressive aphasia witnessed by mother. He presented within 50 minutes of symptom onset to the regional ER facility. Around 4 weeks ago, patient had mild SARS-Cov-2 infection with flu-like symptoms and mild chest pain that worsened with exertion lasting 3-4 days. Neurological examination revealed diminished fluency, anomia, and right upper extremity drift. Initial non contrast computed tomography (CT) demonstrated hyperdense left middle cerebral artery (MCA) sign with subtle loss of gray/white matter differentiation in the left anterior insula. Aphasia and right-sided weakness worsened as he was coming back from CT 2 hours after symptom onset. Intravenous Tenecteplase was administered. CT angiography of head/neck confirmed left proximal M2 occlusion with no arterial dissection. Patient underwent successful mechanical thrombectomy. Three days later his deficits completely resolved. Transthoracic echocardiography with contrast bubble study was unremarkable. Laboratory workup demonstrated mildly low ATIII, positive Factor V Leiden screen with negative genetic testing, positive SARS coronavirus-2 IgG, mildly low PTT. Remaining coagulopathy workup was unremarkable. Conclusions: To our knowledge this is the first case of large vessel occlusion in a pediatric patient treated successfully with both intravenous thrombolysis and mechanical thrombectomy associated with recent SARS-Cov-2 infection. The AIS etiology in our case remains uncertain as abnormal laboratory findings do not explain this presentation. There is high clinical suspicion of an embolic event as possible explanation, possibly related to SARS-CoV-2 postinfectious stage.

Acquired factor V inhibitor after SARS-CoV-2 disease. Case report

Background: Infections, drugs, surgical procedures, blood transfusions, solid and hematological cancers, and autoimmune disorders are associated with the risk of developing acquired FV inhibitors. Case report presentation: A 66-year-old Caucasian woman presented to the Emergency Department because of recurrent episodes of bowel bleeding from 2 week, and bleeding from the sites of venous sampling. Coagulation tests showed that the platelet count was normal: prolonged prothrombin time (PT): 45.5 seconds, international normalized ratio: 4.03, and activated partial thromboplastin time (aPTT): 165 seconds, aPTT ratio: 5.4. Coagulation factor II (FII), factor X (FX), factor VIII (FVIII), and fibrinogen were normal. The FV activity was 0.2% (range of normality 60-120%). The PT, aPTT, and one-stage coagulation factors assays were performed using an ACL TOP 550 coagulometer, and factor V was determined using a onestage PT-based assay, and factor V-deficient substrate plasma. Anticardiolipin antibodies were negative. Mixing test of patient's plasma with normal pooled plasma revealed the existence of an FV inhibitor, with an activity level of 4.0 Bethesda unit/mL. Three weeks before, the patient had been treated for coronavirus disease 2019 (COVID- 19) at home, with steroids (dexamethasone 6 mg daily for 5 days), enoxaparin 4,000 IU daily, and oxygen. Conclusions: The Authors presented a case report with acquired factor V inhibitor after SARS-CoV2 disease.

ENDOVASCULAR RECONSTRUCTION FOLLOWING IVC AND BILATERAL LOWER EXTREMITY THROMBOSIS IN AN ADOLESCENT

Background: Inferior Vena Cava (IVC) abnormalities are a risk factor for the development of lower extremity deep vein thrombosis (DVT). Abnormalities can be congenital or acquired and include IVC atresia, a rare and lesser known problem for adolescents. Adolescents with IVC atresia are at high risk for DVT's that are often refractory to standard anticoagulation methods, including thrombolysis. Objectives: The purpose of this report is to highlight a young patient with extensive lower extremity DVT in the setting of underlying IVC atresia and describe the complex care required. The patient is a 16-year-old with a history of venous insufficiency who presented with low back pain and lower extremity swelling. Thrombotic risk factors included factor V Leiden heterozygosity, oral contraceptive use, and recent COVID-19 vaccination. An MRI completed by the orthopedist for back pain was concerning for abnormal signal in the IVC as well as an IVC aneurysm. A contrast enhanced CT was obtained and demonstrated atresia of the suprarenal IVC, subacute thrombosis of the infrarenal IVC along with an IVC aneurysm, and subacute thrombosis of the bilateral iliac veins. Design/Method: A retrospective chart review of the patient's initial presentation, imaging, and treatments was conducted along with a review of the literature involving similar cases. Results: Initial treatment was intravenous heparin and t-PA mediated thrombolysis. After overnight thrombolysis, venography revealed significant clot lysis;thus, she was transitioned to subcutaneous enoxaparin and discharged home with therapeutic anti-Xa levels. Follow up imaging 3 days later revealed recurrent thrombosis of the deep veins in both lower extremities. She was readmitted, placed on intravenous heparin, and received catheter directed t-PA thrombolysis. Clot burden was so extensive it was further reduced using Angio jet thrombectomy and balloon angioplasty. Because the recurrent clots were attributed to lack of outflow from the underlying IVC atresia, interventional radiology completed endovascular reconstruction of the IVC. She then transitioned from intravenous heparin to therapeutic enoxaparin, clopidogrel, and aspirin. At three month follow up, imaging was negative for clot and her vasculature was widely patent. Conclusion: Pediatric patients with bilateral lower extremity DVTs are uncommon and underlying IVC abnormalities should be considered in the evaluation. Optimal treatment strategies are evolving and include aggressive anticoagulation and endovascular reconstruction.

Peripheral vascular lesions with the development of hand and foot skin necrosis in a patient with COVID-19: a case report

In the presented case report, 36-year-old female patient, who was hospi talized in the rheumatology department, developed thrombotic microangiopathy and sepsis-related coronavirus disease 2019 (COVID-19). In the department, hereditary thrombophilia was revealed: heterozygous polymorphism in the coagulation factor 5 gene (Factor V Leiden). Livedo reticularis. It is known that in October 2020, the patient had COVID-19 with bilateral pneumonitis on chest computed tomography. On examination, dry gangrene of 1, 2, 4, 5 fingers of the right hand, 2 finger of the left hand, as well as 2, 3, 4, 5 fingers of the right and left feet were diagnosed. Necrosis of the nasal tip. Surgery was performed with amputation of the affected fingers and distal feet with autodermoplasty.

Post-covid-19 hemostatic characteristics of convalescent patients: The bergamo experience

Introduction: Severe COVID-19 patients present with a hypercoagulable state, complement activation and endothelial perturbation, which result from an excessive inflammatory response. Thromboinflammation is one important mechanism underlying the COVID-19-associated coagulopathy and the increased risk of thrombosis. Bergamo city is one of the first and most affected area by SARS-CoV-2 infection in the world. For this reason, since the beginning we were actively involved in recruiting convalescent COVID-19 patients, in a program of selection of candidates for convalescent plasma donation. In a large cohort of convalescent COVID-19 patients, we aimed to characterize markers of coagulation activation and endothelial perturbation, in order to explore whether the COVID-19-related hemostasis activation might persist afterwards and evaluate its possible association with the degree of severity of the previous infection, and/or with demographic characteristics, or anti-SARS-CoV-2 antibody levels. Methods: In 392 convalescent COVID-19 patients (216M/176F, median age: 46 years) plasma levels of fibrinogen, protein C, protein S, factor V, factor VIII, factor XIII, D-dimer, von Willebrand factor (vWF), prothrombin fragment F1+2 were measured at the recruitment, i.e. 1-5 months from recovery. Samples were tested for the anti-SARS-CoV-2 antibodies, including anti-S IgG (Anti-S Ab) and anti-N IgG (Anti-N Ab) antibodies at enrollment and at each scheduled subsequent visits. Results: Levels of fibrinogen, D-dimer, von Willebrand factor, protein S and protein C were significantly higher (p<0.05) in patients who were hospitalized for severe COVID-19 as compared to patients who were treated at home. There was no correlation between levels of coagulation biomarkers and days from end of symptoms. Male gender, age > 40 years, and severe form of COVID-19 were identified as independent predictors of high levels of both anti-S and anti-N Ab (p<0.001). Among hemostatic biomarkers, fibrinogen (p<0.01) and vWF (p<0.05) independently predict high levels of anti-S Ab. In particular, vWF levels positively correlated with anti-S Ab levels (vWFantigen r=0.188;vWF-activity r=0.241 and vWF-RiC of r=0.223, p<0.01). Evaluation of anti-SARS-CoV2 antibody levels at different time points during follow up revealed that 30% of patients displayed high levels of anti-S Ab until more than 8 months from the end of symptoms. Conclusions: Convalescent patients, with a history of severe COVID-19 had a persistent endothelium activation, despite of disease clinical remission even after 9 months from end of symptoms. Furthermore, fibrinogen and vWF levels predicted high levels of Anti-S Ab. Among demographic characteristics, gender, age and severe disease can be predictors of increased antibody response. These findings suggest that inflammation, coagulation and endothelial dysfunction may persist after recovery and may explain the findings of persistent clinical symptoms reported in these patients after healing from COVID-19.

A Case Series of Acquired Factor Inhibitor Following Sars-COV2-Vaccination

[Formula presented] : Autoimmune disorders post viral illness and post vaccination are some of the known complications. COVID 19 is known to cause complement dysregulation and possible reactivation of known autoimmune disorders. New data are emerging on the possible autoimmune reactivation and cases of de novo ITP and vaccine induced immune thrombotic thrombocytopenia are reported. We are presenting two cases of factor deficiencies due to acquired factor inhibitor in patients who had no apparent cause but who had recently received the Moderna COVID-19 vaccine. We hypothesize that just like native COVID 19 infection can be associated with development of acquired inhibitors, so can the COVID 19 vaccination. Cases:An 83 year old Caucasian Male with history of Arrhythmia, Coronary artery disease, H/O heart artery stent and hypertension, had received the second dose of Moderna covid vaccine one month prior to presentation. Presented with new onset headache and noted to have large right sub insular acute intra parenchymal hemorrhage. He was managed conservatively, and this bleed was attributed to his h/o hypertension. Post treatment was discharged to rehab, where he had worsening neurological status and repeat imaging showed slightly expanded size of a parenchymal hemorrhage centered in the right sub insular region and increasing surrounding edema with new tiny right frontal cortical parenchymal hemorrhage. Initial admission labs reveled a prolonged APTT of 70 and PT normal after his readmission from rehab, his PTT remained elevated to 70 and PT became prolonged to 17. PT. APTT mixing studies demonstrated only partial correction of PT and no correction of APTT. All factor levels were normal except Factor IX low at 8% and Factor XI low at 2.4%. Bethesda titer was positive at 11 BU to specific to factor IX. Further work up demonstrated no oncologic or rheumatological etiology for the coagulation inhibitor. The only possible etiology had been his age and patient had received SARS COV2 moderna vaccine. The patient was treated with rituximab, prednisone and cyclophosphamide with improvement in the inhibitor titer. A 77-year-old Caucasian female with history of hypertension, obesity, steroid induced psychosis, and Moderna Covid-19 vaccination four months prior. She presented to the hospital with epigastric pain, hematochezia, hematuria, epistaxis, and significant bruising without trauma. Laboratory studies showed hemoglobin drop from baseline of 13.8 to 11.8 to 8.2 g/dL. Significant coagulopathy, with elevated PT 130 sec, PTT 108.7. All factor levels were normal except Factor X levels low at <2%. Mixing study of the prolonged prothrombin time mainly demonstrates an inhibitory pattern, with incomplete correction. (1:1 mix PT 22.7 sec;normal 9.4-12.5 sec). Bethesda titers could not be demonstrated. No neoplastic or rheumatologic etiology of her inhibitor was found. She was given cryoprecipitate and vitamin K with no improvement in her coagulation studies. She received factor X infusion for 3 doses 2500 units during day 3 of her hospitalization. She was treated with prednisone and weekly rituximab with complete normalization of her Factor X levels at 132%. Discussion:Acquired inhibitors to coagulation factors are rare disorders that can be related to infections, malignancy, autoimmune conditions, and pregnancy and sometimes seen spontaneously in older individuals. There have been several individual case reports of acquired coagulation inhibitors with COVID 19 infection including inhibitors to III, Factor XI, Factor V and Thrombin. To our knowledge there have been no acquired inhibitors described to the COVID vaccine however, it would seem conceptually possible. Acquired factor deficiencies should be suspected when a patient presents with no previous history of bleeding, use of anticoagulation and unexplained prolonged prothrombin, and activated partial thromboplastin time. It is vital to have high index of suspicious for prompt recognition as it can have a high mortality. Treatment would involve resuscitation and eradic ting the inhibitor with immunosuppression. It would be interesting to follow this patient long term for any relapse. In the above mentioned cases, no other etiologies could be attributed to the abnormal coagulopathy and could be related to the SARS-COV-2 vaccine. Disclosures: No relevant conflicts of interest to declare.

Gaisbock in 2021

Case Report The purpose of the study is to explore the possible diagnosis of Gaisbock in a patient with long-standing erythrocytosis and hypertension. Methods Used Case Study Summary of Results A 40-year-old Caucasian man with obesity was admitted with recurrent leg swelling and increasing oxygen requirements two weeks after hospitalization with COVID-19 pneumonia. Upon review of the patient's history, he was found to have untreated hypertension over several medical encounters and an erythrocytosis spanning ten years. Recent medical history included a diagnosis of deep vein thrombosis (DVT) in the same leg two and a half months prior and was treated with Xarelto. The patient reported a history of low testosterone for 12 years. However, he had not used any testosterone supplementation for the last nine months. He reported daytime fatigue, frequent bouts of nighttime awakenings, and frequent snoring. The patient never had a sleep study or used a CPAP. The patient used half a can of chewing tobacco daily for thirteen years, and he smoked one pack per day for ten years but quit 12 years ago. He worked strenuous jobs in the construction industry most of his life. On this admission, the patient's lab work was notable for hemoglobin of 18.7 gm/dL (13.7-17.5) and a normal erythropoietin level of 5.7 MIU/mL (2.6-18.5) without thrombocytosis or leukocytosis and a positive factor V Leiden mutation. His blood pressure was 132/91 mmHg. On review of previous records, the patient was found to have consistently elevated hemoglobin The patient had a stocky, ruddy appearance without hepatosplenomegaly. Conclusion Erythrocytosis can be categorized as primary, secondary, or relative. Patients with relative erythrocytosis have a decreased plasma volume with a relative increase in hemoglobin. Additionally, elevated hemoglobin levels have been associated with hypertension. Gaisbock's syndrome, first described in 1905, is characterized by hypertension and erythrocytosis without splenomegaly, leukocytosis, or thrombocytosis. It is associated with mild obesity, elevated blood pressure, and increased blood viscosity, which may explain why these patients often develop cardiovascular complications. Patients with relative erythrocytosis are at a higher risk for thromboembolic complications. In this case, Gaisbock's syndrome was suspected because the patient had had a stocky, plethoric appearance with persistently elevated hemoglobin and blood pressure with a normal erythropoietin level. Gaisbock's syndrome establishes a relationship between benign erythrocytosis, hypertension, and an increased risk for cardiovascular events. (Table Presented).

A case of dvt and pe and cardiac arrest in a patient with factor v leiden mutation and covid

Introduction Heterozygous Factor V Leiden (FVL) mutation is the most common inherited thrombophilia, most common in people of Northern European descent and in some Middle Eastern population. It increases risk of developing a deep venous thrombosis (DVT) by 5-to 7-fold, and is considered a weak risk factor, and most people never develop blood clots. Case report 19-year-old woman presented with left lower quadrant abdominal pain, left groin pain, chest tightness and shortness of breath that had started 1 week prior to presentation. Patient had tested positive for COVID-19 six months but had only minor symptoms and recovered without needing treatment. She had completed 2nd dose of Moderna Covid vaccine two weeks ago and had been using oral contraceptive pills (OCP) for two years. Family history was significant for a paternal uncle with history of blood clots. Physical exam revealed swelling and erythema in left lower extremity up to groin area. Doppler ultrasound showed an acute DVT in the left external iliac vein, common femoral vein, deep femoral vein, superficial femoral vein, and proximal popliteal vein. Spiral computed tomography imaging of chest showed pulmonary emboli (PE) in the segmental branches of the pulmonary arteries with mild dilation of the right ventricle. Cardiac echogram (TTE) showed intact right ventricular function. Patient underwent mechanical aspiration thrombectomy with extirpation of DVT, but the procedure was complicated by PEA arrest requiring CPR for about 50-60 mins. During episode, bedside TTE showed evidence of right ventricular dilation and RV strain concerning for a massive PE. She was cannulated for V-A ECMO then underwent therapeutic hypothermia, and was successfully decannulated after six days. Patient eventually recovered and was neurologically intact. She was discharged home on warfarin and aspirin. Hypercoagulable work-up was remarkable for heterozygous FVL mutation R506Q. Both her father and mother were found to have heterozygous FVL mutation and her sister was found to have homozygous FVL mutation. Discussion People with FVL have additional risk factors that contribute to the development of DVT, and FVL alone does not increase the risk of developing arterial thrombosis, heart attacks and strokes. DVTs in heterozygous FVL population are considered provoked DVTs requiring anti-coagulation for a definite period, like that in general population. Curiously, patients with severe COVID-19 infection requiring ventilator support were found to have factor V levels high above the normal reference range and were found to have elevated risk for blood clots. Use of OCPs, and perhaps a recent COVID infection, although mostly asymptomatic, might have contributed to hypercoagulability in our patient. FVL mutation is not considered a contraindication to having COVID vaccination and patients with hereditary clotting disorders are recommended to have the vaccine.

SARS-CoV-2 infection, hypercoagulability and hereditary thrombophilia factors

Coronavirus disease (COVID-19) is a potentially fatal infectious disease caused by the SARS-CoV-2 virus, a virus of zoonotic origin (1). It has been observed that clinical manifestations of SARS-CoV-2 infection range from asymptomatic disease to severe viral pneumonia accompanied by severe respiratory failure and may result in death (2). The most common initial symptoms of COVID-19 disease are fever, cough, and fatigue. Transmission primarily occurs through direct contact or droplets spread from an infected person (1). The binding of a receptor expressed by host cells is the first step of viral infection. Lung epithelial cells are thought to be the primary target of the virus. Most of the used drugs are drugs used in the treatment of other diseases, and their effectiveness in the treatment of COVID-19 is still at the research level. Specific anti-infection drugs are under development for potential treatment in humans (1). Veklury (Remdesivir) is the first treatment for COVID-19 to receive FDA approval. It is used in adults and pediatric patients [12 years and older and at least 40 kilograms] for the treatment of COVID-19 requiring hospitalization (3). The treatment of COVID-19 in our country is carried out by the recommendations of the Ministry of Health's Guide 'COVID-19 (SARS-CoV-2 infection)' prepared by the recommendations of the Coronavirus Science Council and updated by the developments (4). All of the drugs recommended in the manual are used under the approval of the Ministry of Health within the framework of non-indication drug use. In this pandemic, where new waves are constantly coming, scientists have succeeded in developing a large number of COVID-19 vaccine types in a short time as a result of intensive studies. The mRNA-based Pfizer-BioNTech COVID-19 vaccine is the first FDA-approved vaccine [23.08.2021] (5). The information about the COVID-19 disease, which is spreading rapidly around the world, is increasing with new researches day by day. Thrombophilia is a hypercoagulable condition that predisposes patients to thrombosis. It is a multifactorial condition that can result from genetic factors, acquired factors, or a combination of both. The prothrombin gene (F2), factor V Leiden (F5), and PAI-1 are important biomarkers of thrombophilia. Patients with multiple gene defects have a high risk of thrombosis (6). It is known that thromboembolic events can develop in patients with COVID-19 and the incidence of death increases accordingly. Studies have shown that VTE can be induced in patients with COVID-19 and severe pneumonia, and the incidence of VTE in COVID-19 patients hospitalized in the intensive care unit due to severe pneumonia has been reported to be high (7). The risk of thrombosis and arterial and venous thromboembolic complications seen in 30% of hospitalized subjects due to Novel Coronavirus pneumonia has been reported in many studies, which can be explained by the prolonged inflammatory response, decreased physical activity during infection, and reduced oxygen levels in the circulation (6). Thrombotic and microangiopathic effects of the SARS-CoV-2 virus have been reported in COVID-19 patients (8). Circulatory disorders in the toes of COVID-19 patients are also reported as 'Covid toe (acro ischemia)' (9). Although it is reported that the disease progresses more severely in the elderly, patients with sub-diseases, and smoking history, it is also observed that the clinical course is severe and patient losses are experienced in young patients who do not have any underlying disease. The mechanisms of the development of thromboembolic events are the binding of the virus to the ACE-2 receptor and/or direct endothelial damage, activation of inflammatory and microthrombotic pathways as a result of endothelial damage by complement activation as in sepsis, and stasis due to hospitalization and immobility (10). DIC clinic may develop in patients with severe clinical course. The pathophysiology of DIC is reported to be complex and multifactorial, involving the interaction between the hemostatic system and components of the innate immune response to the infecting pathogen (11). However, there is no comprehensive research on inherited thrombophilia factors that may affect the hemostatic system. Severe clinical course in young patients, a similar clinical course in individuals from the same family even though they are in different cities, elderly patients recovering from the clinic safely and being discharged, VTE in different locations in COVID-19 patients, microangiopathic thrombus, etc. monitoring of the findings, the use of anticoagulants due to their positive contributions in treatment are included in the observations in this process. In the light of all this information, it is aimed to examine and reveal the possible relationship between the genetic variations evaluated in the thrombophilia panel and COVID-19 and presented with the literature data findings and recent studies. Gralinski et al. suggested that PAI-1 plays a protective role against infection in the viral pathogenesis studies of SARS-coronavirus disease (12). In another study, no statistically significant difference in thrombophilia polymorphic biomarkers between the severely ill COVID-19 group and the healthy population was found (6). Various studies that will provide new information on the subject are also actively continuing. In conclusion, thrombosis is frequently seen in severe COVID-19 patients. Essentially, the determination of the thrombophilia profile can assist in determining bleeding risk, mortality, ARDS incidence, and admission to the ICU. Latent genetic risk factors for thrombotic events may affect the outcome of COVID-19. Therefore, the identification of these factors may be useful for understanding the various COVID-19 outcomes and assessing COVID-19 patients' risk of thrombosis, severe disease, and vaccination policies.

Outcomes of Patients with Budd-Chiari Syndrome and Factors Predicting the Need for TIPS & Liver Transplantation - a Single-Center Long-Term Experience

Background: Budd-Chiari Syndrome (BCS) is a complex thrombotic disorder caused due to obstruction of hepatic venous outflow involving anywhere from small hepatic venules to the entrance of inferior vena cava into the right atrium. This leads to venous stasis and ischemic injury of hepatic parenchyma and sinusoids, with the risk of liver failure. The prognosis of patients with BCS had improved significantly with long-term anticoagulation and measures like Trans-Jugular-Intrahepatic-Porto-Systemic shunt (TIPS) and liver transplantation. We report the outcomes of patients who follow in our hematology practice and describe the factors predicting the need for TIPS/Liver Transplant. Methods: After appropriate Investigational Review Board permission, we identified patients with a history of BCS following in our thrombosis clinical practice from the year 2010 onwards. We evaluated their laboratory, demographic, anticoagulation data, Model of End-stage Liver Disease (MELD) score, Child-Pugh (CP) score at diagnosis or when earliest available, and other relevant clinical information as outlined. Descriptive statistics with medians, quartiles, frequencies, and percentages are reported. Further, we compared the two categories of patients who needed TIPS/Liver transplants versus those who did not. SAS version 9.4 was used for analysis. For continuous variables, a univariate nonparametric Mann-Whitney test was used. The Fisher's Exact Test was used to associate each variable with the need for TIPS/Liver Transplant. Results: Our study included 23 patients with baseline characteristics, including median age of 36 years (11-59 years), 91% whites, 61% females, 44% smokers, 61% obese(median BMI 29.9 kg/m 2), 6 of 14 women on oral contraceptive pills, 22% with thrombosis history, 17% with stroke history, median hemoglobin 13.4 gm/dL(8.9-20 gm/dL), white blood cell count 9,400/L (3,050-31,500/L), platelet count 294,000/L(14,000-767,000/L), serum creatinine 0.87 mg/L (0.55-2.52 mg/dL), total protein 6.3 gm/dL (5.2-8.8 gm/dL), Bilirubin 2.1 mg/dL(0.1-20.2 mg/dL), Aspartate Aminotransferase (AST) 61 U/L(16-1037 U/L), Alanine Aminotransferase (ALT) 43U/L(18-1694 U/L), MELD score 15 (range 7-38), CP score 9 (5-14), 74% with cirrhosis, 82% with ascites at one point, 57% with myeloproliferative neoplasm (MPN), 4.3% with Paroxysmal Nocturnal Hemoglobinuria (PNH), 17% with Antiphospholipid antibodies positive (APS), 13% had positive antinuclear antibodies, 35% needed TIPS and 44% required liver transplantation. 57% with Janus Kinase (JAK2) V617F mutation (1 patient with a low variant allele frequency of 1%), 1 patient (4.3%) had Calreticulin (CALR) mutation positive MPN, 91% remained on long-term anticoagulation with 40% using warfarin, 35% apixaban, 9% Enoxaparin or Rivaroxaban for long-term anticoagulation, 13% developed heparin-induced thrombocytopenia (HIT). 8.7% had developed BCS after Ad26.COV2.S vaccine to prevent SARS-CoV-2 infection. Excluding the patients with missing variables, 5 of 12 had Protein C deficiency, 3 or 10 had Protein S deficiency, 8 of 20 with Antithrombin (AT) deficiency, 4 of 14 with heterozygous factor V Leiden mutation, 0 of 10 with prothrombin gene mutation, 1 of 13 with hyper-homocysteinemia. 35% had gastrointestinal bleeding though 65% of patients had evidence of varices by endoscopy. When the group needing TIPS/Liver transplant/died is compared to those who did not, they had higher bilirubin, MELD, PC score, AT deficiency, cirrhosis, ascites, and JAK2 mutation (p-value significant: Table 1). With a median follow-up of 90 months, overall survival was not statistically significant between the two groups (Figure 1). Two patients (8.7%) died out of a total of 23. Conclusions: Our data indicate that in patients with BCS, neoplasms (61%), particularly MPN (57%), are very commonly diagnosed. Compared to the historical data in patients with BCS with dismal prognosis (60-80% six-month mortality rate), the overall survival had significantly improved, likely due to supportive measures like TIPS/Liver transplant and long-ter anticoagulation. Outside the established variables like CP and MELD, lower antithrombin activity and positive JAK2 mutation status also predicted a higher TIPS/Liver transplant need. [Formula presented] Disclosures: Bhatt: Partnership for health analytic research, LLC: Consultancy;Abbvie: Consultancy, Research Funding;Jazz: Research Funding;Incyte: Consultancy, Research Funding;Pfizer: Research Funding;Tolero Pharmaceuticals, Inc: Research Funding;National Marrow Donor Program: Research Funding;Abbvie: Consultancy, Research Funding;Genentech: Consultancy;Servier Pharmaceuticals LLC: Consultancy;Rigel: Consultancy. Gundabolu: BioMarin Pharmaceuticals: Consultancy;Blueprint Medicines: Consultancy;Bristol-Myers Squibb Company: Consultancy;Pfizer: Research Funding;Samus Therapeutics: Research Funding.

Inherited Thrombophilias Are Associated with an Increased Risk of COVID-19 Associated Venous Thromboembolism: A Prospective Population-Based Cohort Study

Background: COVID-19 is associated with high rates of venous thromboembolism (VTE). The impact of common inherited thrombophilias on the development of COVID-19-associated VTE (COVID-19 VTE) is not well understood. Objective: To determine if the presence of inherited thrombophilias modifies the risk of COVID-19 VTE or COVID-19 mortality. Methods: Prospective population-based cohort study evaluating adult participants of the UK Biobank diagnosed with COVID-19 between November 2019 and May 2021. Individuals were of European descent and aged between 45 and 69 at recruitment to UK Biobank. We evaluated six single nucleotide polymorphisms including rs6025 (Factor V Leiden mutation) and rs1799963 (Prothrombin mutation) in addition to two polygenic risk scores (PRS-VTE and PRS-ABO). A genome-wide association study was performed for associations with COVID-19 VTE. COVID-19 VTE was defined using International Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for VTE following COVID-19 diagnosis. COVID-19 mortality was defined using ICD-10 codes for COVID-19 on the death certificate. Results: Demographic and clinical characteristics are shown in Table 1. Of the 13 712 COVID-19 positive individuals included in the analysis, the median age was 54 years and 52.5% were female. There were 197 (1.4%) cases of COVID-19 VTE and 890 (6.5%) died due to COVID-19. The rs6025 variant, synonymous with FVL, was associated with a 1.8-fold risk of COVID-19 VTE (95% CI 1.040-2.931) (Table 2). The risk of COVID-VTE was also increased with rs2066865 (OR 1.345;95% CI 1.074-1.675) and the PRS-VTE (OR 1.262;95% CI 1.081-1.468) (Table 2). COVID-19 VTE was associated with increased COVID-19 mortality (OR 2.731;95% CI 1.885-3.901) but this study found no association between the studied inherited thrombophilias and COVID-19 mortality (Table 2). On genome-wide analysis, two novel SNPs, rs4975019 and rs2875853, located on chromosomes 4 and 16 respectively, were associated with an increased occurrence of COVID-19 VTE. Conclusions: These data demonstrate that several inherited thrombophilias increase the risk of COVID-19 VTE and suggest that two novel SNPs are associated with COVID-19 VTE. These results suggest that certain inherited thrombophilias may assist in characterising a subgroup of COVID-19 patients at higher risk of thrombotic events who require individualised antithrombotic therapy. Future prospective studies are required to evaluate inherited thrombophilias in this patient cohort. [Formula presented] Disclosures: No relevant conflicts of interest to declare.