Comparison of Thrombotic Complications in Critically Ill Patients between COVID-19 and Mers-COV

Background: Several observational studies have reported the rate of thrombotic events in patients infected with coronavirus disease 2019 (COVID-19), with conflicting results 1. The conflicting results could be partially explained by different population critically ill vs non critically ill, different definition of thrombotic events, follow up period was variable, and different prophylaxis that were used. Middle east respiratory syndrome (MERS-COV) is another coronavirus had been initially reported in Saudi Arabia in 2012. A genome scan has shown a 50% similarity between COVID-19 and MERS-COV 2.A common features of covid-19 and MERS-COV including transmissibility, and MERS-COV clinical presentation have been identified 3. However, data about thrombotic complications in patients with MERS-COV are limited. The aim of this study was to compare the rate of thrombotic events between patients with COVID-19 and MERS-COV. Methods: Patients : We included all confirmed COVID-19 patients who were admitted to intensive care unit (ICU) in 3 major hospitals in Saudi Arabia between February and July 2020. We included all confirmed cases of MERS-COV who were admitted to ICU from these centers between March to May 2014. Patients were excluded if they were transferred in or out from one of these three hospital to another hospitals. Data were collected retrospectively from the first day of admission until discharge or death. Outcome: The primary outcome was the rate of venous thromboembolism (VTE). The secondary outcomes were the rate of arterial events, the rate of composite events (venous and arterial) and the rate of bleeding. VTE included all symptomatic or incidentally diagnosed cases of pulmonary embolism (PE), deep vein thrombosis (DVT) and thrombosis in unusual sites (cerebral, mesenteric, portal, splenic, hepatic, and renal veins). All VTEs were confirmed radiographically by appropriate imaging. Screening for VTE in asymptomatic patients was not performed. If more than on type of VTE occurred in the same patient, it was considered one event. Arterial events included cerebrovascular accidents (CVAs), mesenteric ischemia, and limb ischemia and were confirmed by the appropriate imaging modality. Myocardial infarction (MI) was diagnosed based on the suspicion of the attending physician using clinical criteria as well as biomarker elevations or electrocardiographic changes. Composite events were defined as any VTE or arterial event. Bleeding events were classified as major and nonmajor based on the definition of international society of thrombosis and hemostasis (ISTH) 4. Informed consent was waived. Statistical analysis: Characteristics and outcomes were compared between COVID-19 and MERS-COV groups using chi-square test, fisher exact test or t-test. The rates of thrombosis and bleeding are summarized as proportions, with the corresponding 95 % confidence intervals (CI). A P-value less than 0.05 was considered significant. Statistical analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA) Result: After exclusion, 234 COVID-19 and 58 MERS-COV patients were included. The majority of patients with COVID-19 (98%, n=230) and more than (67% ,n =39 ) of those with MERS-COV group received pharmacological prophylaxis. The most frequently prescribed regimen in both groups was enoxaparin (40 mg twice per day). Over a median length of stay in the COVID-19 group of 22 days, the rate of VTE 9.8%(CI; 6.6-14.3) and was 3.4%(CI; 0.95-11.7) in the MESR-COV group over median length of stay of 10 days. The rate of arterial events were 5.9 % (CI;3.6-9.7) and 8.6% (CI;3.7-18.6) in COVID-19 and MERS-COV respectively. Table 1 and 2. Conclusions: To our knowledge, this is the first study compared thrombotic risk between COVID-19 and MERS-COV. We found a similar rate of composite thrombotic events (venous and arterial ) between COVID-19 and MERS-COV with higher rate of venous thrombosis in COVID-19 and higher rate arterial thrombosis in MERS-COV. This may indicate that not only COVID-19 is a prothrombotic disease, but MERS-COV may have similar risk of thrombotic complication . These result needs to be confirmed in a larger studies. References 1- Al-Samkari, H, 2020. Blood, 136(4), Pp.489-500. 2- Lu, R, 2020. The Lancet, 395(10224), Pp.565-574. 3- Petrosillo, N, 2020. Clinical Microbiology And Infection, 26(6), Pp.729-734. 4- Schulman, S, 2005. Journal Of Thrombosis And Haemostasis, 3(4), Pp.692-694. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Vaccine induced thrombotic thrombocytopenia: Insights from blood smear

Vaccine-induced thrombotic thrombocytopenia (VITT) is a thrombotic complication mimicking heparin induced thrombocytopenia (HIT). This very rare but severe thrombotic complication occurs post vaccination against SARS-Cov-2. Diagnosis of VITT remains challenging, but a current consensus report suggests a 10-point guideline for early detection of VITT, which should be confirmed by PF-4 immunoassays. The latter is considered to be the most reliable diagnostic test. We observed platelet aggregates and increased platelet volume in patients with VITT in routine blood smear analyses. These routine blood analytic findings may – together with the clinical presentation – support and speed up the diagnosis of VITT, and may be of particular importance in low-income countries with limited access to PF-4 immunoassays.

Heart failure with reduced ejection fraction due topolycythemia vera

ABSTRACT Polycythemia vera is a rare hematological disorder that can cause heart failure with reduced ejection fraction from chronic micro-vascular ischemia. Appropriately recognizing the underlying cause of cardiomyopathy is essential to decrease morbidity and mortality. Patients can present with elevated troponin level and have patent epicardial coronary arteries on coronary angiogram, hence presenting a diagnostic challenge for health care professionals. Furthermore, the presentation can mimic myocarditis. Herein, we report a case of a 61-year-old female who presented with heart failure due to microvascular thrombotic complication associated with polycythemia vera. Laboratory investigation and coronary angiogram were inconclusive. A high degree of clinical suspicion and utilizing non-invasive techniques, such as cardiac imaging, can describe myocardial pathology and aid with the diagnosis.

Thrombosis and novel hemophilia therapies: the fine line between clotting and bleeding

The availability of novel nonfactor therapeutics is revolutionizing the management of hemophilia in individuals with inhibitory antibodies, as well as making prophylaxis more convenient even in the absence of inhibitors. Unfortunately, the use of these products has been associated with thrombotic events that are not typically seen with factor replacement. These are primarily seen when a patient on a nonfactor therapy experiences breakthrough bleeding and concomitantly receives another hemostatic agent. This video addresses thrombotic complication in 3 nonfactor products: (1) emicizumab, a bispecific antibody that mimics the cofactor activity of factor VIII; (2) fitusiran, an small interfering RNA that knocks down synthesis of antithrombin; and (3) concizumab, an antibody that blocks inhibition of factor Xa by tissue factor pathway inhibitor. The latter 2 agents were developed on the premise that hemostasis in hemophilia could be “rebalanced” by reducing the levels of anticoagulant activity to compensate for the defect in procoagulant activity. Each of these approaches increases peak levels of thrombin achieved in assays on plasma from treated subjects and reduces bleeding rates in individuals with or without inhibitors. However, we do not yet have a good mechanistic model for precisely how these approaches affect hemostasis in vivo. It is not only the total amount of active thrombin produced that determines the effectiveness of hemostasis but also how thrombin generation is regulated. Therefore, it is currently difficult to predict how these new agents will interact with other perturbations or therapeutic manipulations of the coagulation system.

Prolonged Thrombin Time in Asymptomatic Patient with Hypo Dysfibrogememia Tucson

A 61 years female patient with known diagnosis of the breast cancer in remission for more than 10 years has Renaud’s disease. During her work up for lupus and lupus anticoagulant which both were negative a prolonged thrombin time was noted which was done by mistake. She has no history of bleeding or thrombosis and last recent surgery was 5 years ago for spinal stenosis and was uncomplicated. Her clinical examination is normal without evidence of any spontaneous bruises but colder hands. The thrombin time was greater than 125 seconds on two different occasions and correction of it by addition of normal plasma was down to 56 seconds and was thus incomplete. Her prothrombin time and PTT were normal and there was no evidence of FDP or D-Dimers. There was no evidence of circulating heparins. The fibrinogen level was normal. The para proteinmia was excluded by normal serum protein electrophoresis and by immunofixation . Thus it is felt that this patient has dysfibrinogenemia or hypo dysfibrinogenemia without bleeding or thrombotic complication. The literature review shows approximately 55% of dysfibrinogenemia patients do not have bleeding or thrombotic complications.

CLOT STIFFNESS MEASURED BY SEER SONORHEOMETRY AS A MARKER OF POOR PROGNOSIS IN HOSPITALIZED COVID-19 PATIENTS

Background: High incidence of life-threatening thrombotic complications is observed in severely ill COVID-19 patients. D-dimer may help evaluate disease severity and predict outcomes at hospital admission. However, its non-specificity and long analysis times strongly constrain its clinical value. Viscoelastic tests (VET) are widely available rapid point-of-care devices that have been shown to detect a hypercoagulable state (increased clot stiffness and fibrinolysis shutdown) as major contributors of the thrombotic complication in COVID-19. Nevertheless, based on the data obtained so far, definitive conclusions have not been drawn. Objectives: We aim to evaluate the association between VET parameters, standard coagulation tests and inflammation markers assessed in COVID-19 patients at hospital admission with disease severity and outcomes. Patients/Methods: A total of 69 COVID-19 patients requiring hospitalization were included in the study. The pro-inflammatory and pro-thrombotic state was analyzed by a panel of inflammation markers (IL-6, CRP, LDH, ferritin), routine coagulation tests (PT, aPTT, platelet count, fibrinogen, D-dimer) and a SEER sonorheometry VET profile (Quantra System). Results: Inflammatory markers IL-6, CRP, LDH and ferritin were elevated in a high percentage of patients (73.6%, 89.2%, 57.1% and 52.4%), as were coagulation-related parameters such as fibrinogen (81.4%) and D-dimer levels (66.2%). Quantra analysis revealed increased clot stiffness (CS) in 34.8%, particularly due to increased fibrinogen contribution (FCS) in 63.7%. Increased clot stability to lysis (CSL) was observed in 32.4%. Age > 65 years, elevated values of fibrinogen, D-dimer, LDH, increased clot stiffness and resistance to clot lysis were significantly associated with worsening disease. The Quantra FCS parameter showed a particularly high prognostic value in distinguishing patients with severe symptomatology. Conclusion: The global study of hemostasis by the whole blood point-of-care Quantra VET system may be a powerful tool for identifying poor prognosis in COVID-19 patients at hospital admission. In particular, FCS measured by Quantra could be established as a plausible prognostic marker to aid the clinical management of COVID-19 patients.

CLINICAL CASE: THROMBOSIS OF THE RIGHT OVARIAN VEIN WITH SPREAD TO THE INFERIOR VENA CAVA IN THE PUERPERAL WOMAN

Тромбоз правой яичниковой вены с распространением на нижнюю полую вену является крайне редким, но не казуистическим случаем венозного тромбоза во время беременности. В литературе имеются весьма ограниченные описания отдельных клинических случаев данного тромботического осложнения. Цель: привлечь внимание акушер-гинекологов и ангиохирургов к своевременной диагностике, лечению и профилактике тромбозов в период беременности и в послеродовом периоде. Материалы и методы: С целью диагностики данной патологии было проведено полное клинико-лабораторное обследование, ультразвуковое исследование органов брюшной полости и ультразвуковая допплерография нижней полой вены. Результаты: На основании оценки анамнеза, клинико - лабораторных и инструментальных методов обследования установлен диагноз: Тромбоз правой яичниковой вены с распространением на нижнюю полую вену и флотацией головки тромба. Выводы: Метод селективного тромболизиса при тромбозе правой яичниковой вены с распространением на нижнюю полую вену в сочетании с имплантацией кава-фильтра в нижнюю полую вену в ургентной клинической практике действительно показал себя эффективным методом борьбы с осложнениями тромбозов нижней полой вены. Thrombosis of the right ovarian vein with spread to the inferior vena cava is an extremely rare, but not a casuistic case of venous thrombosis during pregnancy. In the literature, there are very limited descriptions of individual clinical cases of this thrombotic complication. Objective: to attract the attention of obstetricians-gynecologists and angiosurgeons to the timely diagnosis, treatment and prevention of thrombosis during pregnancy and in the postpartum period. Materials and methods: In order to diagnose this pathology, a complete clinical and laboratory examination, ultrasound examination of the abdominal organs and ultrasound Dopplerography of the inferior vena cava were performed. Results: Based on the assessment of the anamnesis, clinical-laboratory and instrumental methods of examination, the diagnosis was made: Thrombosis of the right ovarian vein with spread to the inferior vena cava and flotation of the head of the thrombus. Conclusions: The method of selective thrombolysis for right ovarian vein thrombosis with spread to the inferior vena cava in combination with the implantation of a cava filter in the inferior vena cava in urgent clinical practice has really proved to be an effective method of combating complications of inferior vena cava thrombosis.

Granulocytic Expression of CD11b/CD18 and Thrombotic Risk in Patients with Myeloproliferative Neoplasms

Summary Myeloproliferative neoplasms (MPN) are clonal hematological conditions characterized by excessive production of one or more cell lines in the bone marrow. The blood cells produced are often hyperactive in their functions, which could lead to complications in the disorder‘s clinical course. We aimed to define the role of granulocytic CD11b/CD18 expression for the thrombotic risk in MPN patients. We investigated 110 patients with a histologically confirmed diagnosis of a myeloproliferative disease and a control group of 46 healthy volunteers. In the patient group, we found an average expression 4.59 times higher than in the control group. The highest expression was found in a subgroup of patients with polycythemia vera – 71.55% of the patients’ neutrophils. In each subgroup with essential thrombocythemia, myelofibrosis, and chronic myeloid leukemia, the patients with a history of thrombotic complication had a higher expression than the patients without such complications.

Cerebral Venous Sinus Thrombosis (CVST): an emerging complication of SARS CoV-2 infection

Background: During Coronavirus (COVID-19) pandemic, SARS CoV-2 infection has been documented to be associated with thrombotic complications, especially pulmonary embolism, which are triggered by virus binding to ACE-2 receptors and consequent activation of a cascade leading to a hypercoagulable pathway, however Cerebral Venous Sinus Thrombosis (CVST) is emerging as a further thrombotic complication of COVID-19.Case presentation: We report our experience of a patient affected by SARS CoV-2 infection, who presented to our emergency department with neurological symptoms such as confusion and headache and was diagnosed with CVST at imaging exams.Conclusion: As neurological symptoms such as confusion and headache are aspecific and shared with patients affected by SARS CoV-2 infection in absence of CVST, clinicians should be aware of this emerging hematologic complication in order to recognize it as soon as possible and provide the best patient care.