Common Coagulopathies Associated With COVID-19 Patients.

The coronavirus disease 2019 (COVID-19) outbreak, which first appeared in the Chinese province of Hubei city of Wuhan, has been spreading internationally since December 2019. The World Health Organization (WHO) declared the coronavirus illness from 2019 to be a pandemic on March 11, 2020. Patients hospitalised with severe coronavirus or comorbid conditions (like cardiovascular disease and obesity) are linked to a worse prognosis. The rise in D-dimer and its relationship to prognosis are the most often documented aberrations in coagulation/fibrinolysis in COVID-19. However, the D-dimer assessment's utility is not limitless. Since the coagulation/fibrinolytic state might occasionally change over a short period of time, routine exams are also advantageous in understanding the relevance of the inquiry. Both thrombotic and hemorrhagic diseases should be taken into consideration, despite the fact that the pathophysiology of disseminated intravascular coagulation (DIC) linked with coronavirus disease 19 differs significantly from that of septic disseminated intravascular coagulation. Coagulation as well as fibrinolysis indicators are used to make the diagnosis of COVID-19 thrombosis, which encompasses both macro- and micro-thrombosis. Compared to bacterial-sepsis-associated coagulopathy/DIC, COVID-19 has a lower prevalence of prolonged prothrombin time, activated partial thromboplastin time, and decreased antithrombin activity. However, the causes of coagulopathy remain poorly understood. Hypoxia, endothelial injury, dysregulated immunological responses mediated by inflammatory cytokines, and lymphocyte cell death are thought to be implicated. While blood loss tends to be rare, it is uncertain if COVID-19 suffers from thrombosis or whether the current recommendations for regular venous thromboembolic dose are appropriate. It is important to decide on the COVID-19 therapy phases. Antiviral therapy, cytokine storm therapy, and thrombosis therapy are the steps. Future advancements are predicted, such as a therapy that combines heparin and nafamostat.

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.

D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

Multisystemic Infarctions in COVID-19: Focus on the Spleen.

The literature suggests that COVID-19 provokes arterial and venous thrombotic events, although the mechanism is still unknown. In this study, we describe patients with confirmed coronavirus infection associated with multisystemic infarction, focusing on splenic infarction. More data are required to elucidate how COVID-19 and thrombotic disease interact and so that preventive and early diagnosis strategies can be developed. LEARNING POINTS: Thrombotic disease as a complication of COVID-19 must be suspected by clinicians, and recognized and monitored by radiologists.Thrombosis is often the initial manifestation of SARS-CoV-2, hence the importance of early diagnosis to avoid complications and reduce morbidity and mortality.

Understanding COVID-19-associated coagulopathy: From PIC to SIC or DIC.

Coagulopathy, characterized by a high D-dimer level, is a common pathological occurrence in coronavirus disease 2019 (COVID-19) and is associated with poor prognosis. Severe cases with COVID-19 is associated with a significantly higher risk of deep vein thrombosis and acute pulmonary embolism. Pulmonary intravascular coagulopathy is the characteristic coagulopathy in COVID-19. Unlike sepsis-induced coagulopathy and disseminated intravascular coagulation, which are manifestations of systemic coagulopathy, pulmonary intravascular coagulopathy is a manifestation of a local coagulation disorder in the lung. The progression from pulmonary intravascular coagulopathy to sepsis-induced coagulopathy or disseminated intravascular coagulation in the context of COVID-19 may indicate that the patient's coagulation dysfunction has progressed from local to systemic. Exploring the associated coagulation disease will aid in the understanding of the pathophysiological mechanisms underlying severe COVID-19.

Heat Stroke Leading to a Fatal Outcome.

Heat stroke (HS) can cause several physiological changes in the body. In its most severe form, it can cause multi-organ failure including encephalopathy, circulatory shock, liver failure, renal failure, disseminated intravascular coagulation, and rhabdomyolysis among others. HS is a preventable condition; however, it can be life-threatening in severe forms. We present a case of HS in a 54-year-old male, with rapidly progressive multi-organ failure and a fatal outcome along with a brief literature review.

SARS-CoV-2 infection results in upregulation of Plasminogen Activator Inhibitor-1 and Neuroserpin in the lungs, and an increase in fibrinolysis inhibitors associated with disease severity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in coagulation activation although it is usually not associated with consumption coagulopathy. D-dimers are also commonly elevated despite systemic hypofibrinolysis. To understand these unusual features of coronavirus disease 2019 (COVID-19) coagulopathy, 64 adult patients with SARS-CoV-2 infection (36 moderate and 28 severe) and 16 controls were studied. We evaluated the repertoire of plasma protease inhibitors (Serpins, Kunitz, Kazal, Cystatin-like) targeting the fibrinolytic system: Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator/Plasminogen Activator Inhibitor-1 complex (t-PA/PAI-1), α-2-Antiplasmin, Plasmin-α2-Antiplasmin Complex, Thrombin-activatable Fibrinolysis Inhibitor (TAFI)/TAFIa, Protease Nexin-1 (PN-1), and Neuroserpin (the main t-PA inhibitor of the central nervous system). Inhibitors of the common (Antithrombin, Thrombin-antithrombin complex, Protein Z [PZ]/PZ inhibitor, Heparin Cofactor II, and α2-Macroglobulin), Protein C ([PC], Protein C inhibitor, and Protein S), contact (Kallistatin, Protease Nexin-2/Amyloid Beta Precursor Protein, and α-1-Antitrypsin), and complement (C1-Inhibitor) pathways, in addition to Factor XIII, Histidine-rich glycoprotein (HRG) and Vaspin were also investigated by enzyme-linked immunosorbent assay. The association of these markers with disease severity was evaluated by logistic regression. Pulmonary expression of PAI-1 and Neuroserpin in the lungs from eight post-mortem cases was assessed by immunohistochemistry. Results show that six patients (10%) developed thrombotic events, and mortality was 11%. There was no significant reduction in plasma anticoagulants, in keeping with a compensated state. However, an increase in fibrinolysis inhibitors (PAI-1, Neuroserpin, PN-1, PAP, and t-PA/PAI-1) was consistently observed, while HRG was reduced. Furthermore, these markers were associated with moderate and/or severe disease. Notably, immunostains demonstrated overexpression of PAI-1 in epithelial cells, macrophages, and endothelial cells of fatal COVID-19, while Neuroserpin was found in intraalveolar macrophages only. These results imply that the lungs in SARS-CoV-2 infection provide anti-fibrinolytic activity resulting in a shift toward a local and systemic hypofibrinolytic state predisposing to (immuno)thrombosis, often in a background of compensated disseminated intravascular coagulation.

A case of disseminated intravascular coagulation following tumour lysis syndrome due to small cell carcinoma of the lung.

A 64-year-old man was diagnosed with small cell lung cancer (SCLC) with multiple bone and liver metastases and bone marrow metastases. Spontaneous tumour lysis syndrome (TLS) was observed before starting chemotherapy with carboplatin, etoposide, and atezolizumab. The tumour further collapsed, and the patient developed disseminated intravascular coagulation (DIC) on day 4 of chemotherapy. The patient was successfully treated with intravenous hydration and rasburicase for TLS and subcutaneous unfractionated heparin for DIC. A large amount of tissue factor may be released in TLS, which could induce DIC. However, to the best of our knowledge, this is the first report of DIC following TLS in a case of SCLC. DIC following TLS in SCLC is a rare but life-threatening oncologic complication. Therefore, clinicians should be aware of this possibility when treating patients with advanced SCLC.

D-dimer testing in clinical practice in the era of COVID-19.

D-dimer is a fragment of crosslinked fibrin resulting from plasmin cleavage of fibrin clots and hence an indirect biomarker of the hemostatic system activation. Early in the coronavirus disease 2019 (COVID-19) pandemic, several studies described coagulation disorders in affected patients, including high D-dimer levels. Consequently, D-dimer has been widely used in not-yet-approved indications. Ruling out pulmonary embolism and deep vein thrombosis in patients with low or intermediate clinical suspicion is the main application of D-dimer. D-dimer is also used to estimate the risk of venous thromboembolism recurrence and is included in the ISTH algorithm for the diagnosis of disseminated intravascular coagulation. Finally, numerous studies identified high D-dimer levels as a biomarker of poor prognosis in hospitalized patients with COVID-19. This report focuses on validated applications of D-dimer testing in patients with and without COVID-19.

Acute Pancreatitis and Disseminated Intravascular Coagulopathy in COVID-19 Infection: A Case Report.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can be a plausible trigger for both disseminated intravascular coagulopathy (DIC) and acute pancreatitis. We present an 85-year-old male patient who presented with altered mental status and tested positive for COVID-19 infection. He was hypoxic with an incremental need for oxygen. He had clinical as well as imaging evidence of acute pancreatitis. Clinical evidence of bleeding was noted and lab findings were suggestive of DIC. Despite aggressive initial management, his clinical status continued to deteriorate and comfort care was sought eventually. This case highlights COVID-19 infection as a possible trigger for acute pancreatitis as well as DIC. It also highlights some of the differences in COVID-19-induced DIC, which fulfills the diagnostic criteria of DIC but has atypical findings.

Hemophagocytic Lymphohistiocytosis Following COVID-19 Infection.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with multiple inflammatory symptoms involving several organ systems, including hematologic manifestations. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome caused by excessive inflammation in the absence of immune regulation. We present the case of a patient with HLH secondary to dysregulated inflammatory response following COVID-19; we also describe the diagnostic and management challenges associated with the condition.

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.

Venovenous Extracorporeal Membrane Oxygenation Support in Patients with COVID-19 Respiratory Failure: A Multicenter Study.

Objective: The COVID -19 pandemic presents a high mortality rate amongst patients who develop severe acute respiratory distress syndrome (ARDS). The purpose of this study was to evaluate the outcomes of venovenous ECMO in COVID-19-related ARDS and identify the patients that benefit the most from this procedure. Methods: Adult COVID-19 patients with severe ARDS requiring VV-ECMO support at four academic insititutions between March and October 2020 were included. Data were collected through retrospective chart reviews. Bivariate and multivariable analysis were performed with the primary outcome of in-hospital mortality. Results: Fifty-one consecutive patients underwent VV-ECMO with a mean age of 50.4 years; 64.7% were male. Survival to hospital discharge was 62.8%. Median ICU and hospitalization duration were 27.4 (IQR:17-37) and 34.5 days (IQR:23-43), respectively. Survivors and non-survivors had a median ECMO cannulation time of 11 days (IQR 8-18) and 17 days (IQR: 12-25). The average post decannulation length of stay was 17.5 days (IQR: 12.4-25) for survivors and 0 days for non-survivors (IQR 0-6 days). Only one non-survivor was able to be decannulated. Clinical characteristics associated with mortality between non-surviors and survivors included increasing age (p=0.0048), hemorrhagic stroke (p=0.0014), and post operative dialysis (p=0.0013)were associated with mortality in a bivariate model and retained statistical significance in a multivariable model. Conclusion: This multicenter study confirms the effectiveness of VV-ECMO in selected critically ill patients with COVID-19-related severe ARDS. The survival of these patients is comparable to non-COVID-19-related ARDS.

Antithrombin as Therapeutic Intervention against Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation: Lessons Learned from COVID-19-Associated Coagulopathy.

Recent research has contributed significantly to our understanding of the pathogenesis of acute disseminated intravascular coagulation. COVID-19 can be considered as a new underlying condition of disseminated intravascular coagulation. In this narrative review, current evidence is presented regarding biomarker differences between sepsis-induced and COVID-19-associated coagulopathies, supporting the importance of acquired antithrombin deficiency in the early differential diagnosis of septic coagulopathy and its potential impact on treatment with endogenous anticoagulants. Establishing new scoring systems for septic coagulopathy in combination with endogenous anticoagulant biomarker activities may allow for the identification of those in the heterogeneous population of sepsis patients who are more likely to benefit from targeted specific treatment interventions.

A Review of the Prevalence of Thromboembolic Complications among Pregnant Women Infected with COVID-19.

Background: Thrombotic conditions triggered by SARS-CoV-2 virus can result in high mortality, especially in pregnant women as they are already in a hypercoagulability state. This thereby leads to excessive inflammation that will increase the risk of thromboembolic (TE) complications. Objective: The aim of this study is to review the prevalence of thromboembolic complications such as deep venous thrombosis, pulmonary embolism, and intervillous thrombosis, and their preventive strategies among pregnant women infected with COVID-19. Method: The articles were retrieved from online databases PubMed and ScienceDirect published from February 2020 to April 2022. Findings: A total of 5249 participants including 5128 pregnant women and 121 placentas from 19 studies were identified for having TE complications after being infected with COVID-19. The types of TE complications that developed within pregnant women were disseminated intravascular coagulation (DIC) (n = 44, 0.86%), unmentioned thromboembolic complications (TE) (n = 14, 0.27%), intervillous thrombosis (IVT) (n = 9, 0.18%), pulmonary embolism (PE) (n = 6, 0.12%), COVID-19 associated coagulopathy (CAC) (n = 5, 0.10%), and deep venous thrombosis (DVT) (n = 2, 0.04%). Whereas the prevalence of TE complications reported from studies focusing on placenta were IVT (n = 27, 22.3%), subchorionic thrombus (SCT) (n = 9, 7.44%), and placental thrombosis (n = 5, 4.13%). Thromboprophylaxis agent used among pregnant women include low molecular weight heparin (LMWH) at prophylactic dose (n = 9). Conclusions: The prevalence of thromboembolic complications among pregnant women infected by COVID-19 is low with DIC being the most common form and placental thrombosis being the least common form of TE complications that occurred within pregnant women infected with COVID-19. Anticoagulation, in particular LMWH (variable dose), is frequently used to prevent TE complications.

Incidence of ischaemic Stroke Following ComirnatyTM Administration: Comparison of Data from ASST GOM Niguarda and FAERS: An International Journal of Medical Toxicology and Drug Experience

Introduction: Although the mechanism of neurological complications after COVID-19 vaccination has not been precisely explained, it could be attributed to the inflammatory state triggered by COVID-19 vaccine as in the course of COVID-19 viral infection. This condition induces disseminated intravascular coagulation (DIC) in combination with vascular endothelial dysfunction, leading to stroke of the large vessels. This hypothesis may be the main cause of DIC, especially in mRNA-based vaccines, whose mechanism involves delivery of the mRNA code of the spike protein to human cells. Cellular synthesis of the spike protein stimulates the immune system to recognize and store it for future attack. Based on this hypothesis, the inflammatory state triggered by the vaccine can be considered the main pathway for neurological complications of COVID-19 vaccine. Objective: The aim of this work is to analyse the incidence of ischaemic stroke risk following administration of the ComirnatyTM vaccine in ASST GOM Niguarda, an Italian hospital based in Milan, and to compare it with data from FAERS database. Methods: The Reporting Odds Ratio (ROR) was calculated in order to evaluate a possible correlation between the risk of ischaemic stroke and Comirnaty™ vaccine administration in the period of January-December 2021. For this purpose, we consulted FAERS public domain database that allows you to search information relating to adverse events reported to the FDA. Results: From reports of adverse events of ComirnatyTM vaccinated patients at ASST GOM Niguarda hospital, it was observed that after administration of this vaccine there is a correlation with the risk of developing ischaemic stroke mainly in over 65 years old patients (OR = 1.26;95% CI 0.17-9.13;z = 0.230;p value = 0.8182) when comparing the data with other vaccines. These data match the data obtained from FAERS (OR: 1.29;95% CI 0.85-1.96;z = 1.205;p value = 0.228), confirming the data collected in ASST GOM Niguarda. Conclusion: The data extrapolated from this analysis conducted at ASST GOM Niguarda mirror those obtained from the FAERS database with a comparable significance index (p value). In conclusion, the possible correlation between ComirnatyTM vaccine administration and the development of ischaemic stroke as an adverse event was confirmed.

Neonatal RSV positive bronchiolitis with fulminant viral septic shock

AimsMain purpose of presenting this clinical case is that RSV BRONCHIOLITIS can present with lobar pneumonia,Fulminant viral septic shock with DIC,pulmonory haemorrhage and asystole. Viral VS Bacterial sepsis- clinically difficult to differentiate.Methods1 month old girl,unwell for 2 days with cough,decrease oral intake, seen by GP in the morning and diagnosed as BRONCHIOLITIS,same day evening presented to the hospital with apnoea in the car arrived at PAU within 3 mins of apnoea.O/E-no HR or breathing,bleeding from nose and mouth,pale looking,mottled, CRT 5 sec.CPR started and connected to monitor showed asystole.Immediate cardiac arrest call was activated.Intubated, cannula inserted, 2 doses of adrenaline given IV,Bolus of normal saline 10mls/kg thrice,partial septic screening done and covered with triple antibiotics amoxycillin,gentamycin and cefotaxime.After 10 mins of resuscitation baby responded. Given vitamin K and transfused with O negative blood and FFP.Blood gas showed mixed metabolic and respiratory acidosis and hence connected to ventilator started on morphine,maintenance fluids,ionotropes,morphine infusion and transferred to tertiary centre. In tertiary centre admitted for 11 days,extubated to CPAP on day 5, weaned to high flow on day 6, RA on day 9. Ionotropes for 1 day,acylovir, vitamin k for 9 and 6 days respectively.Neuroprotective measures followed.ResultsNPA for RSV positive, covid 19 PCR negative, blood c/s,CSF c/s and CSF PCR for bacteria and viruses negative, X ray chest consolidation upper lobes bilateral,CT Angiogram subsegmental consolidation and possible intraparenchymal haemorrhage. Initial Echo pulmonory hypertension and repeat Echo normal.MRI Brain -hypersensitivity in posterior putamina. Deranged coagulation profile.APTT more than 180, PT 16.2, INR 1.4ConclusionRSV positive bronchiolitis with all complications can mimic bacterial sepsis and its clinically difficult to differentiate between viral and bacterial septic shock.As this baby’s blood C/S was negative only positive thing was RSV in NPA, We have to consider this case as RSV BRONCHIOLITIS with fulminant septic shock with pneumonia, DIC, Pulmonory Haemorrhage leading to Asystole.Management of bacterial and viral Septic shock is pretty much the same except in certain cases we may have to use antivirals drugs when indicated.

Thrombotic thrombocytopenic purpura as an acute complication of COVID-19.

Introduction: While disseminated intravascular coagulation (DIC) is a serious complication of COVID-19, a close differential in critically ill patients with thrombocytopenia is Thrombotic thrombocytopenic purpura (TTP). Case Report: We describe the case of a middle-aged lady admitted with COVID-19 pneumonia who developed progressive thrombocytopenia, altered sensorium and renal failure. The absence of coagulation abnormalities alerted to the possibility of TTP, strengthened by presence of schistocytes in peripheral smear. Conclusions: This case highlights the need for high index of suspicion and to pay attention to normal tests as well that might give clues to the diagnosis. New onset thrombocytopenia in COVID-19 need not always indicate DIC. A careful examination of peripheral smear may help diagnosing TTP especially if coagulation profile is normal.

Comparison of acute respiratory distress syndrome in patients with COVID-19 and influenza A (H7N9) virus infection.

OBJECTIVES: We aimed to compared the clinical features of acute respiratory distress syndrome (ARDS) induced by COVID-19 and H7N9 virus infections. METHODS: Clinical data of 100 patients with COVID-19 and 46 patients with H7N9 were retrospectively analyzed. RESULTS: Elevated inflammatory indices and coagulation disorders were more common in COVID-19-ARDS group than in the H7N9-ARDS group. The median interval from illness onset to ARDS development was shorter in H7N9-ARDS. The PaO2/FiO2 level was lower in H7N9-ARDS, whereas the Sepsis-related Organ Failure Assessment score was higher in COVID-19-ARDS. The proportion of patients with disseminated intravascular coagulation and liver injury in COVID-19-ARDS and H7N9-ARDS was 45.5% versus 3.1% and 28.8% versus 50%, respectively (P <0.05). The mean interval from illness onset to death was shorter in H7N9-ARDS. A total of 59.1% patients with H7N9-ARDS died of refractory hypoxemia compared with 28.9% with COVID-19-ARDS (P = 0.014). Patients with COVID-19-ARDS were more likely to die of septic shock and multiple organ dysfunction compared with H7N9-ARDS (71.2% vs 36.4%, P = 0.005). CONCLUSION: Patients with H7N9 were more susceptible to develop severe ARDS and showed a more acute disease course. COVID-19-ARDS was associated with severe inflammatory response and coagulation dysfunction, whereas liver injury was more common in H7N9-ARDS. The main causes of death between patients with the two diseases were different.

Large abdominal hematoma with hemorrhagic shock in a covid-19 patient

The Covid-19 virus infection was constituted into a pandemic in the last two years and it is a very serious problem worldwide, with tens of million cases and deaths all over the world. Most patients have only mild symptoms, but some patients develop severe complications within a short time after infection, such as adult respiratory syndrome (ARDS) or disseminated intravascular coagulation (DIC), the sepsis being followed by organ failure, and death. Among the leading causes of death were the cardio-respiratory problems, most of them related to procoagulation issues. Many patients with SARS-CoV-2 pneumonia developed deep vein thrombosis, even when they have been receiving antithrombotic prophylaxis. There were also cases with hemorrhagic accidents encountered all over the world, part of them necessitating surgical interventions. We present the clinical case of a man, diagnosed with covid-19 infection, which presented suddenly abdominal pain and later on a hemorrhagic shock due to rupture of a branch of an internal artery, because of an overdose of oral anticoagulation. The patient underwent surgical treatment.