Trauma-induced innate immune activation and disseminated intravascular coagulation.

Dysregulated innate immunity participates in the pathomechanisms of disseminated intravascular coagulation (DIC) in trauma-induced coagulopathy. Accidental and regulated cell deaths and neutrophil extracellular traps release damage-associated molecular patterns (DAMPs), such as histones, nuclear and mitochondrial DNA, and high-mobility group box 1, into circulation immediately after trauma. DAMP-induced inflammation activation releases tissue factor-bearing procoagulant extracellular vesicles through gasdermin D-mediated pore formation and plasma membrane rupture by regulated cell death. DAMPs also evoke systemic inflammation, platelet, coagulation activation, and impaired fibrinolysis associated with endothelial injury, leading to the dysfunction of anticoagulation systems, which are the main pathophysiological mechanisms of DIC. All these processes induce systemic thrombin generation in vivo, not restricted to the injury sites immediately after trauma. Thrombin generation at the site of injury stops bleeding and maintains homeostasis. However, DIC associated with endothelial injury generates massive thrombin, enhancing protease-activated, receptor-mediated bidirectional interplays between inflammation and coagulation, aggravating the diverse actions of thrombin and disturbing homeostasis. Insufficiently regulated thrombin causes disseminated microvascular thrombosis, resulting in tissue hypoxia due to reduced oxygen delivery, and mitochondrial dysfunction due to DAMPs causes tissue dysoxia. In addition, DAMP-induced calcium influx and overload, as well as neutrophil activation, play a role in endothelial cell injury. Tissue hypoxia and cytotoxicity result in multiple organ dysfunction in DIC after trauma. Controls against dysregulated innate immunity evoking systemic inflammation, thrombin generation, and cytotoxicity are key issues in improving the prognosis of DIC in trauma-induced coagulopathy.

Recurrent upper extremity arterial thrombosis preceding a diagnosis of COVID-19.

Arterial thrombosis occurs when there is endothelial damage in the setting of hypercoagulability and arterial blood stasis. COVID-19 has been theorized to cause both endothelial damage and promote hypercoagulability by causing an imbalance of clotting factors. In many studies, there have been a large proportion of COVID-19 patients that suffered a thromboembolic event, in both the venous and arterial systems. Our patient, who did not have a significant past medical history, presented with a recurrent brachial artery occlusion despite medical and surgical management, and subsequently tested positive for COVID-19 late in his admission. In conclusion, there is high suspicion that there is a relationship between COVID-19 infection and recurrent arterial thrombosis.

Hepatitis A virus infection is complicated by both pancytopenia and autoimmune hemolytic anemia (AIHA).

Introduction: Hepatitis A infection affects liver tissue primarily and might have some extrahepatic manifestations. Hematologically, the extrahepatic manifestations include aplastic anemia, red cell aplasia, and thrombocytopenia. There were reports about pancytopenia among patients with Hepatitis A infections, however, its association with autoimmune hemolytic anemia is rare as in our case. Case presentation: A 30-year-old male visited the emergency room with tiredness, unmeasured fever, and jaundice. He also mentioned that recently he had anorexia and weight loss without night sweating. Initial laboratory findings showed pancytopenia and marked elevation of AST and ALT. Direct Coombs and IgM anti-Hepatitis A virus were positive. Consequently, he was diagnosed with HAV complicated by both pancytopenia and AIHA and treated with prednisone (1 mg/kg) leading to significant improvement in his anemia. Discussion: This report describes a case of acute viral hepatitis A complicated with severe autoimmune hemolytic anemia and pancytopenia, which was successfully treated by high dose (1 mg/kg/day) prednisolone therapy. Conclusion: This case represents a rare case in the literature review that can increase the awareness of the wide range of complications of HAV and its association with pancytopenia and AIHA.

The Impact of COVID-19 On Comorbidities: A Review Of Recent Updates For Combating It.

Coronavirus disease is caused by the SARS-CoV-2 virus. The virus first appeared in Wuhan (China) in December 2019 and has spread globally. Till now, it affected 269 million people with 5.3 million deaths in 224 countries and territories. With the emergence of variants like Omicron, the COVID-19 cases grew exponentially, with thousands of deaths. The general symptoms of COVID-19 include fever, sore throat, cough, lung infections, and, in severe cases, acute respiratory distress syndrome, sepsis, and death. SARS-CoV-2 predominantly affects the lung, but it can also affect other organs such as the brain, heart, and gastrointestinal system. It is observed that 75 % of hospitalized COVID-19 patients have at least one COVID-19 associated comorbidity. The most common reported comorbidities are hypertension, NDs, diabetes, cancer, endothelial dysfunction, and CVDs. Moreover, older and pre-existing polypharmacy patients have worsened COVID-19 associated complications. SARS-CoV-2 also results in the hypercoagulability issues like gangrene, stroke, pulmonary embolism, and other associated complications. This review aims to provide the latest information on the impact of the COVID-19 on pre-existing comorbidities such as CVDs, NDs, COPD, and other complications. This review will help us to understand the current scenario of COVID-19 and comorbidities; thus, it will play an important role in the management and decision-making efforts to tackle such complications.

Higher mortality of hospitalized haematologic patients with COVID-19 compared to non-haematologic is driven by thrombotic complications and development of ARDS: An age-matched cohorts study.

BACKGROUND AND OBJECTIVES: The characteristics of COVID-19 in haematologic patients compared to non-haematologic patients have seldom been analyzed. Our aim was to analyze whether there are differences in clinical characteristics and outcome of haematologic patients with COVID-19 as compared to non-haematologic. PATIENTS AND METHODS: Retrospective cohort study in 2 University hospitals of patients admitted with laboratory-confirmed COVID-19 included in the SEMICOVID19 database. The cohort with underlying haematologic disease was compared to a cohort of age and date-of-COVID-19-matched controls without haematologic disease (1:2). RESULTS: 71 cases and 142 controls were included from March-May 2020.Twenty (28.1%) had received recent chemotherapy. Twelve (16.9%) were stem cell transplant recipients (SCT). Eleven (15.5%) were neutropenic concurrently with COVID-19 diagnosis.Haematologic patients presented ARDS (58.5 vs 20.7%, p = 0.0001), thrombotic complications (15.7 vs 2.1%, p = 0.002), DIC (5.7 vs 0.0%, p = 0.011), heart failure (14.3 vs 4.9%, p = 0.029) and required ICU admission (15.5 vs 2.8%, p = 0.001), MV (14.1% vs 2.1%, p 0.001), steroid (64.8 vs 33.1%, p = 0.0001), tocilizumab (33.8 vs 8.5%, p = 0.0001) or anakinra treatment (9.9% vs 0%, p = 0.0001) more often. In-hospital mortality was significantly higher (38.0% vs 18.3%, p = 0.002). CONCLUSIONS: Our results suggest COVID-19 has worse outcomes in haematologic patients than in non-haematologic, independently of age, and that the development of ARDS and thrombotic complications drive the higher in-hospital mortality.

Cirrhosis and COVID-19: Diffuse venous thrombosis and its clinical implication.

A 60-year-old woman with Hepatitis C infection, cirrhosis, recurrent hepatic hydrothorax, and hepatocellular carcinoma was hospitalized with Coronavirus disease-2019 (COVID-19). After her initial discharge, she was re-admitted three weeks later with decompensated liver disease. Imaging revealed extensive thrombosis in the portal vein, superior mesenteric vein, splenic vein and bilateral brachial veins. Given the acute onset and extent of the thrombosis, the patient received therapeutic anticoagulation despite elevated prothrombin time/ international normalized ratio, thrombocytopenia and low fibrinogen. Cirrhotic patients with COVID-19 maybe at high risk of thrombosis, which can present with significant hepatic decompensation.

Fatal Spontaneous Intercostal Artery Bleeding During Catheter Ablation for Atrial Fibrillation.

Serious adverse events such as hemothorax are rarely seen in catheter ablation for atrial fibrillation. A recent case report discussed hemothorax from injury of the intercostal artery during atrial fibrillation ablation. Our case presents a patient with spontaneous bleeding from the intercostal artery that led to hemothorax, disseminated intravascular coagulation, and death. (Level of Difficulty: Intermediate.).

Reproductive health crisis during waves one and two of the COVID-19 pandemic in India: Incidence and deaths from severe maternal complications in more than 202,000 hospital births.

BACKGROUND: The SARS-CoV-2 pandemic in India has adversely affected many aspects of population health. We need detailed evidence of the impact on reproductive health in India so that lessons can be learnt. METHODS: Hospital-based repeated monthly survey of nine severe maternal complications and death in 15 hospitals across five states in India covering a total of 202,986 hospital births, December-2018 through to May-2021. We calculated incidence rates (with 95% confidence intervals (CIs)) per 1000 hospital births, case-fatality and rate ratios (RR) with 95% CIs. Linear regression was used to examine the association between the Government Response Stringency Index (GRSI) for India and changes in hospital births, incidence and case-fatality. FINDINGS: There was a significant decrease in hospital births per month during the pandemic period with a 4.8% decrease per 10% increase in the GRSI scores (p < 0.001). The overall incidence of severe complications in the pandemic period was not significantly different from the pre-pandemic period, but hospital admissions from septic abortion was 56% higher (RR=1.56; 95% CI=1.22-1.99; p < 0.001). The overall case-fatality of complications increased by 23% (RR=1.23; 95% CI=1.03-1.46; p = 0.022) and remained high across the different phases of the pandemic with a notable significant increase in deaths from heart failure in pregnancy. INTERPRETATION: Our study supports the legitimacy of the calls made to maintain sexual and reproductive health services as essential services during the pandemic. Lessons learnt should be used to avert the ongoing reproductive health crisis while India plans to manage a third wave of the pandemic. FUNDING: The MaatHRI platform and this study are funded by a Medical Research Council Career Development Award to MN (Ref:MR/P022030/1). The funder has no role in the study design, data collection, analysis, or writing the paper.

Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality. METHODS: We evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk. FINDINGS: Of 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38-0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17-4.37), p = 0.015. INTERPRETATION: Outpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk. FUNDING: No funding was obtained for this study.

A Journey Across Oceans With a Heavy Heart: Rare Presentation of a Pediatric Malignancy.

Myeloid sarcoma, due to extramedullary deposition of myeloblasts, is one of the rare presentations in acute myeloid leukemia. We present an extremely rare case of a 5-year-old boy with cardiac myeloid sarcoma. Noninvasive mode of diagnosis, timely initiation of chemotherapy and meticulous supportive care are the keys to successful outcome. (Level of Difficulty: Intermediate.).

Visceral leishmaniasis associated with macrophage activation syndrome: Case report and literature review.

BACKGROUND: The combination of visceral leishmaniasis (VL) and macrophage activation syndrome (MAS) makes the diagnosis difficult due to their similar clinical presentation, with a poor prognosis especially since the treatment is still poorly codified.We report the case of a 17-month-old female patient from Berkane, presenting for a 3 months history of anarchic fever with anemic syndrome made up of pallor and hemorrhagic syndrome made up of epistaxis. Physical examination revealed a temperature of 39 ° C, lower limbsedema, paleness of skin and mucous membranes, gingival petechiae, bleached hair, and hepatosplenomegaly. CASE PRESENTATION: The complete blood count showed pancytopenia with deep aregenerative normochromic normocytic anemia at 3 g/dL, leukocytes were at 4860/mm 3 with neutropenia at 680/mm 3 and thrombocytopenia at 12.000/mm3, the blood smear was without abnormality. These anomalies were associated with a hypoalbunemia, hypertriglyceridemia, hyperferritinemia, lactate dehydrogenase (LDH) level was at 337 IU/L, low prothrombin time (PT) at 56 % and fibrinogen level at 1 g/L. The direct Coombs test was positive. Examination of the myelogram revealed the presence of leishmania bodies and figures of hemophagocytosis. A diagnosis of visceral leishmaniasis associated with MAS was made.The patient was put on liposomal amphotericin B and corticosteroid therapy with good clinical and biological evolution and good therapeutic tolerance. CONCLUSION: The association of VL and MAS remains rare and should be evoked even in non-endemic areas since late diagnosis worsens the prognosis and may even be responsible for the death of patients despite an aggressive treatment.

Successful management of a lung cancer patient harbouring both EGFR mutation and EML4-ALK fusion gene with disseminated intravascular coagulation.

Lung cancer patients harbouring driver oncogene alterations are markedly responsive to molecular target agents, such as epidermal growth factor receptor (EGFR), tyrosine kinase inhibitor (TKI), and echinoderm microtubule-associated protein like 4 - anaplastic lymphoma kinase (EML4-ALK)-TKI. We encountered an exceptionally rare case, harbouring both EGFR mutation and EML4-ALK fusion gene, and suffering from severe disseminated intravascular coagulation. In this case report, we present two notable points. First, our patient was successfully treated with a third-generation EGFR-TKI, osimertinib. Second, osimertinib could manage severe conditions, such as disseminated intravascular coagulation. Third-generation EGFR-TKIs may be a viable option for patients harbouring both EGFR mutations and EML4-ALK fusion genes, even in severe conditions.

COVID-19 and stroke: A review.

COVID-19 patients have presented with a wide range of neurological disorders, among which stroke is the most devastating. We have reviewed current studies, case series, and case reports with a focus on COVID-19 patients complicated with stroke, and presented the current understanding of stroke in this patient population. As evidenced by increased D-dimer, fibrinogen, factor VIII and von Willebrand factor, SARS-CoV-2 infection induces coagulopathy, disrupts endothelial function, and promotes hypercoagulative state. Collectively, it predisposes patients to cerebrovascular events. Additionally, due to the unprecedented strain on the healthcare system, stroke care has been inevitably compromised. The underlying mechanism between COVID-19 and stroke warrants further study, so does the development of an effective therapeutic or preventive intervention.

Coagulopathies in novel coronavirus (SARS-CoV-2) pandemic: Emerging evidence for hematologists.

The coronavirus disease (COVID-19), which is also known as acute respiratory syndrome coronavirus-2 (SARS-CoV2) is a transmissible disease, has phenotypes varying from asymptomatic to Acute Respiratory Distress Syndrome (ARDS) or multiple organ dysfunction syndrome (MODS) and ultimately death in certain cases. Coagulation disorders are being frequently reported amongst these patients and the pathogenesis is still not completely understood. Proposed mechanisms for these coagulopathies comprise a hypercoagulable state with micro- and/or macro-thrombosis in the vessels. A number of changes have been reported or proposed in circulating prothrombotic factors in COVID-19 patients and includes elevation in both factor VIII and fibrinogen, circulating prothrombotic microparticles and hyperviscosity. The COVID-19 patients are showing varied coagulopathies and are at high risk for venous thromboembolism (VTE) which demands an early intervention. This paper reviews the evolving data regarding the evaluation and managing of coagulopathies in patients with COVID-19.

Cytomegalovirus pancreatitis in an immunocompetent patient.

Cytomegalovirus (CMV) is a double-stranded DNA virus, which infects a large portion of the adult population. In immunocompetent patients, it typically is asymptomatic or manifests as mild and self-limiting flu-like illness symptoms, whereas in immunocompromised patients, CMV can cause significant disease. Herein we report an unusual case of CMV pancreatitis in an immunocompetent 75-year-old female. Patient developed severe significant pancreatic necrosis that failed non-operative management, and ultimately underwent pancreatic necrosectomy. Later on, she developed three spontaneous gastric perforations. The first two perforations were managed operatively, but after the third perforation family decided not to undergo another operation. The CMV pancreatitis diagnosis was based on pancreatic histopathology and confirms by a prompt response to ganciclovir. Patient was promptly started on intravenous (IV) ganciclovir which resulted in clinical recovery and she remained asymptomatic more than one-year post op. This is a rare case of CMV pancreatitis with gastric perforations in an immunocompetent patient. High degree of suspicion and appropriate treatment are important for such clinical scenarios.

Kasabach-Merritt-like phenomenon in a massive uterine leiomyoma presenting with chronic disseminated intravascular coagulation: A case report.

Kasabach-Merritt phenomenon is a process where the presence of vascular irregularity within a Kaposiform hemangioendothelioma or tufted angioma leads to constitutive coagulation factor activation and the development of chronic disseminated intravascular coagulation (DIC). A similar phenomenon has been seen in other tumors but has rarely been described. A 42-year-old woman presented to the hospital following the development of worsening easy bruising and bleeding. She was ultimately found to have a massive uterine fibroid that led to constitutive coagulation cascade activation and subsequent chronic DIC. Following resection, she had complete resolution of DIC and made a full recovery. Although rare, the development of unexplained chronic DIC in a woman should prompt evaluation for the presence of massive uterine fibroids.

Coronavirus disease 2019 and cardiovascular system: A narrative review.

At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management.

COVID-19 for the Cardiologist: Basic Virology, Epidemiology, Cardiac Manifestations, and Potential Therapeutic Strategies.

Coronavirus disease-2019 (COVID-19), a contagious disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has reached pandemic status. As it spreads across the world, it has overwhelmed health care systems, strangled the global economy, and led to a devastating loss of life. Widespread efforts from regulators, clinicians, and scientists are driving a rapid expansion of knowledge of the SARS-CoV-2 virus and COVID-19. The authors review the most current data, with a focus on the basic understanding of the mechanism(s) of disease and translation to the clinical syndrome and potential therapeutics. The authors discuss the basic virology, epidemiology, clinical manifestation, multiorgan consequences, and outcomes. With a focus on cardiovascular complications, they propose several mechanisms of injury. The virology and potential mechanism of injury form the basis for a discussion of potential disease-modifying therapies.

Surgical treatment of adolescent idiopathic scoliosis: Complications.

Despite the fact that spinal surgeries for adolescent idiopathic scoliosis (AIS) result in good outcomes for most patients, they are not without complications either medically or surgically. Neurologic injury represents the most severe complication and is, as such, the most feared. Further complications include dural tears, peripheral neuropathy, surgical-site infections, implant-related issues, thromboembolic events, visual loss, pseudarthrosis, Crankshaft phenomenon, flatback phenomenon, proximal junctional kyphosis, and mortality. It is vital that all spine surgeons to be fully conversant with the possible complications and the proper responses for each of them.