Characteristics of Coagulation/Fibrinolysis Abnormalities in Serious Corona Virus Disease 2019 (COVID-19) Patients Complicated with Stroke: Case Series

Abstract Background: Not surprisingly, novel coronavirus disease 2019 (COVID-19) patients are frequently complicated with COVID-19 associated coagulopathy (CAC). And cerebrovascular disease is not uncommon during SARS-CoV-2 infection, especially in older patients and severe patients with risk factors. This time we treated six patients with serious COVID-19, of whom two had a stroke during ICU admission. Based on our experience, we report some findings on the relationship between CAC pattern and risk of stroke in patients with serious COVID-19.Case presentation: Two patients who subsequently had a stroke were transferred to our emergency center and underwent veno-venous extracorporeal corporeal membrane oxygenation (V-V ECMO) with unfractionated heparin as an anticoagulant for treatment of severe respiratory failure. In one patient, the platelet count was 5.7 × 104/mm3 on ICU admission, increased to above 10 × 104/mm3 after 5 days. In the other patient, the platelet count progressed to above 10 × 104/mm3 for the observation period of 8 days. Both prothrombin-international normalized ratio and activated partial thromboplastin time remained almost within the normal ranges throughout the 8-day period. In contrast, the levels of fibrin degradation products, D-dimer, and plasmin alfa2-plasmin inhibitor complex remained above the upper limits of the normal ranges throughout the 8-day period, and the levels in both cases increased markedly around the onset of stroke.Discussion: From these findings, we gained a strong impression that the pattern of CAC in stroke patients was not a “suppressed-fibrinolytic type” pattern, but rather an “enhanced-fibrinolytic type” pattern.Conclusions: During the period in which serious COVID-19 patients undergo V-V ECMO, we need to be aware that these patients with CAC may be complicated with stroke not only cerebral infarction, but also cerebral hemorrhage.

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Associations Among Coagulation-Related Variables, Resolution of Disseminated Intravascular Coagulation (DIC), and Mortality in Patients with Sepsis-Induced DIC Treated with Recombinant Human Soluble Thrombomodulin: A Retrospective Observational Study

10.21203/rs.3.rs-558224/v1 ◽

2021 ◽

Author(s):

Chieko Mitaka ◽

Izumi Kawagoe ◽

Daizoh Satoh ◽

Masakazu Hayashida

Keyword(s):

Platelet Count ◽

Observational Study ◽

Disseminated Intravascular Coagulation ◽

Early Phase ◽

Degradation Products ◽

International Normalized Ratio ◽

Soluble Thrombomodulin ◽

Intravascular Coagulation ◽

Before And After ◽

Recombinant Human Soluble Thrombomodulin

Abstract Background: We evaluated associations among coagulation-related variables, resolution of disseminated intravascular coagulation (DIC), and mortality in patients with sepsis-induced DIC treated with recombinant human soluble thrombomodulin (rTM). Methods: We retrospectively investigated patients with sepsis-induced DIC treated with rTM. Changes in coagulation-related variables before and after treatment with rTM were examined. Further, associations between coagulation-related variables and DIC resolution were evaluated. Results: A total of 123 patients were included. The platelet count, prothrombin international normalized ratio (PT-INR), and fibrin/fibrinogen degradation products (FDP) significantly (p < 0.001) improved after rTM administration in survivors (n = 98), but not in nonsurvivors (n = 25). However, the DIC score significantly (p < 0.001) reduced not only in survivors but also in nonsurvivors. PT-INR before rTM was significantly (p = 0.0029) lower in patients attaining than not attaining DIC resolution (n = 87 and 36, respectively). The 28-day mortality was significantly lower in patients attaining than not attaining DIC resolution (11.5% vs. 41.7 %, p = 0.0001).Conclusions: The DIC score significantly reduced after rTM in both survivors and nonsurvivors. rTM might play an important role in improving DIC, especially when treatment with rTM is initiated in the early phase of DIC.

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Effect of Vitamin E on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657264 ◽

1982 ◽

Vol 48 (02) ◽

pp. 235-237 ◽

Cited By ~ 14

Author(s):

T Yoshikawa ◽

Y Furukawa ◽

M Murakami ◽

K Watanabe ◽

M Kondo

Keyword(s):

Platelet Count ◽

Vitamin E ◽

Disseminated Intravascular Coagulation ◽

Fibrinogen Level ◽

Degradation Products ◽

Tocopheryl Acetate ◽

Preventive Effect ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Fibrin Thrombi

SummaryExperimental disseminated intravascular coagulation (DIC) can be induced by 4 hr sustained infusion of endotoxin in a dose of 100 mg/kg in rats. The experimental model of DIC in rats was used to study the preventive effect of vitamin E, α-tocopheryl acetate, against DIC. Before the infusion of endotoxin, 0.01, 0.1, 1.0 or 10.0 mg/kg/day of α-tocopheryl acetate was injected intraperitoneally for 4 successive days. The preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count, and the number of renal glomeruli with fibrin thrombi, in rats treated with 1.0 or 10.0 mg/kg of α-tocopheryl acetate. From these results, it was shown that vitamin E, α-tocopheryl acetate, inhibited endotoxin-induced experimental DIC in rats.

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Effects of Ticlopidine and Aspirin on Endotoxin-Induced Disseminated Intravascular Coagulation in Rats

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657359 ◽

1983 ◽

Vol 49 (03) ◽

pp. 190-192 ◽

Cited By ~ 13

Author(s):

T Yoshikawa ◽

M Murakami ◽

Y Furukawa ◽

S Takemura ◽

M Kondo

Keyword(s):

Platelet Count ◽

Continuous Infusion ◽

Disseminated Intravascular Coagulation ◽

Partial Thromboplastin Time ◽

Fibrinogen Level ◽

Degradation Products ◽

Preventive Effect ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Fibrin Thrombi

SummaryThe effects of ticlopidine and aspirin on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4 hr sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were intraperitoneally injected with ticlopidine at 2.0, 20.0, 50.0, 100.0 or 200.0 mg/kg, or aspirin at 0.03, 0.3, 3.0 or 30.0 mg/kg, followed by the continuous infusion of 100 mg/kg/4 hr of endotoxin. A preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products (FDP), fibrinogen level, prothrombin time, partial thromboplastin time (PTT), platelet count and the number of renal glomeruli with fibrin thrombi, in the rats treated with 20.0, 50.0, 100.0 or mg/kg of ticlopidine. Although a preventive effect was also noted in FDP, PTT, platelet count and the number of glomeruli with thrombi in rats treated with 0.03 or 0.3 mg/kg of aspirin, this agent was less effective than ticlopidine.

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Hyponatremic Unconsciousness as a Presenting Symptom of COVID-19: A Case Series

JOURNAL FOR CLINICAL AND DIAGNOSTIC RESEARCH ◽

10.7860/jcdr/2021/50139.15214 ◽

2021 ◽

Author(s):

Ajay Chauhan ◽

Asmita Gupta ◽

Kari Suguna ◽

Shashikant Shukla ◽

Parul Goyal

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Clinical Symptoms ◽

Virus Disease ◽

Case Series ◽

The Novel ◽

Altered Sensorium ◽

Respiratory Involvement ◽

New Concepts ◽

Novel Coronavirus

The novel Coronavirus Disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection can present with a multitude of clinical symptoms. The virus, disease symptomatology, pathogenesis and complications are being studied and new concepts are evolving rapidly. The current worldwide situation caused by the disease makes it exceedingly important to recognise varied presentations of the disease. Three cases are being discussed hereby, wherein the patients presented with altered sensorium secondary to hyponatremia as the initial and only presentation of SARS-CoV-2 infection, in the absence of fever or any respiratory involvement. Acute symptomatic hyponatremia is an under-recognised presentation with only a few cases reported till date and needs further awareness and understanding.

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Prediction of Early Death in Patients With Sepsis-Associated Coagulation Disorder Treated With Antithrombin Supplementation

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029618797474 ◽

2018 ◽

Vol 24 (9_suppl) ◽

pp. 145S-149S ◽

Cited By ~ 5

Author(s):

Toshiaki Iba ◽

Makoto Arakawa ◽

Yoshifumi Ohchi ◽

Takao Arai ◽

Koichi Sato ◽

...

Keyword(s):

Clinical Trials ◽

High Risk ◽

Sofa Score ◽

Degradation Products ◽

Early Death ◽

Patient Characteristics ◽

International Normalized Ratio ◽

Coagulation Disorder ◽

Fibrin Degradation Products ◽

Hemostatic Markers

For success in clinical trials, eliminating inclusion of patients with irreversible recovery is important. The purpose of this study was to identify the patient population who do not survive for more than 3 days. A total of 449 patients with sepsis suspected of having disseminated intravascular coagulation (DIC) and treated with antithrombin were examined. The patient characteristics, baseline sequential organ failure assessment (SOFA) score, DIC score, and hemostatic markers were retrospectively analyzed in relation to early death (died within 3 days). At the end of day 3, a total of 419 patients had survived and 30 patients had died. A logistic regression analysis revealed a significant association between early death and the baseline prothrombin time-international normalized ratio PT-INR ( P <.05) and the total SOFA score ( P <.01). In contrast, neither the platelet count, fibrinogen/fibrin degradation products, and antithrombin activity nor the DIC score was associated with early death. Although the accuracy for predicting early death defined by either baseline PT-INR of ≥1.57 or total SOFA score of more than 13 was not high enough, that of “high-risk of early death (PT-INR ≥ 1.57 and SOFA score ≥ 13)” was 83.5%. Furthermore, the negative predictive of this category was 96.0%. The baseline SOFA score and PT-INR were associated with early death among patients with sepsis-associated coagulation disorders. Patients who do not meet the “high-risk of early death” criteria were likely to survive for more than 3 days and therefore should be considered for future therapeutic clinical trials.

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Effects of Superoxide Dismutase and Catalase on Disseminated Intravascular Coagulation In Rats

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665331 ◽

1983 ◽

Vol 50 (04) ◽

pp. 869-872 ◽

Cited By ~ 28

Author(s):

T Yoshikawa ◽

M Murakami ◽

N Yoshida ◽

O Seto ◽

M Kondo

Keyword(s):

Superoxide Dismutase ◽

Platelet Count ◽

Disseminated Intravascular Coagulation ◽

Fibrinogen Level ◽

Degradation Products ◽

Preventive Effect ◽

Endotoxin Infusion ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

Fibrin Thrombi

SummaryThe effects of superoxide dismutase (SOD) and catalase on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4 hr sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were subcutaneously injected with SOD at 0.5, 5.0 or 50.0 mg/kg, or catalase at 0.01, 0.1 or 1.0 mg/kg, followed by the continuously infusion of 100 mg/kg/4hr of endotoxin. A preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi, in the rats treated with 50.0 mg/kg of SOD or 1.0 mg/kg of catalase. When 50.0 mg/kg of SOD or 1.0 mg/kg of catalse was injected subcutaneously at 1, 2 or 3 hr after the initiation of the endotoxin-infusion, the protective effect against DIC was noted in all the parameters.

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Clinical features of critically ill patients with COVID-19 infection in China

10.21203/rs.3.rs-16250/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Bo Hu ◽

Dawei Wang ◽

Chang Hu ◽

Ming Hu ◽

Fangfang Zhu ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Clinical Laboratory ◽

Virus Disease ◽

Prolonged Mechanical Ventilation ◽

Univariate Analysis ◽

Management Strategies ◽

Case Series ◽

Hypoxemic Respiratory Failure ◽

Icu Admission

Abstract Importance: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections outbreak in China is now a global issue. There is only a limited understanding of the clinical characteristics of patients with SARS-CoV-2 infections is available.Objective:To describe the characteristics, management strategies, and outcomes of critically ill patients with SARS-CoV-2 infection.Design, Setting, and Patients: This is aretrospective, multi-center case series of 50 critically ill patients with confirmed SARS-CoV-2 infection who were admitted at Zhongnan Hospital of Wuhan University and Wuhan Pulmonary Hospital in Wuhan, China, from January 8 to February 9, 2020.Exposures:Documented Corona Virus Disease, 2019 (COVID-19).Main Outcome Measures: Demographic, clinical, laboratory, imaging data were collected along with management strategies, complications and outcomes of enrolled individuals. Results Fifty critically ill patients with SARS-CoV-2 infections were enrolled. Their median age was 62 (range, 29-92) [IQR,49.5-69.0] years, 68% were male, and 28 (56%) patients had comorbidities, the most common being hypertension. In this cohort, 20(40%) patients survived ,16(32%) patients died, and the rest remained hospitalized. The invasive mechanical ventilator was used in 36(72%) patients with 15(30%) of them requiring prone positioning, and 17(34%) switched to ECMO. The compliance scores of lungs (Cstat)on the day of ICU admission among survivors were higher than those in non-survivors [42.0(18.0-47.0), vs. 19.5(14.0-24.2), p=0.038].The blood IL-6 levels and neutrophils counts at the first day of ICU admission were significantly higher in non-survivors compared to survivors [123.7(85.3-228.8), vs. 20.2(6.8-67.2) ng/ml, p=0.025 for IL-6, and 20.2(6.8-67.2) vs. 4.01(1.99-7.05) × 10⁹/L, p=0.02 for neutrophils counts].The heart rates, PaCO2, lung injury scale (LIS), and positive end-expiratory pressure levels were constantly higher for 10 days in non-survivors than those who survived (p<0.05). The frequency of vasopressor uses and neuromuscular blockers was higher in non-survivors from day 1 to day 10 compared to survivors (p<0.05). In the whole cohort, the most common complications were ARDS (97%), shock (44%), arrhythmia (38%), acute cardiac injury (26%), and acute kidney injury (22%). A secondary bacterial infection was noted in 17(34%) patients. Univariate analysis indicated that lower lung complianceand higher neutrophil counts at the day of ICU admission were related to higher mortality (p-0.03, and 0.04, respectively)ConclusionWe demonstrated that SARS-CoV-2 infection-related critical illness predominantly affected old individuals with comorbidities and characterized by severe hypoxemic respiratory failure, often requiring prolonged mechanical ventilation and rescue therapies. Low lung compliance and persistently elevated PaCO2 indicated poor outcomes.

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Mechanisms Of Coagulopathy After Envenomation By The Eastern Diamondback Rattlesnake

10.1055/s-0038-1652103 ◽

1981 ◽

Author(s):

C S Kitchens ◽

L H S Van Mierop

Keyword(s):

Platelet Count ◽

Degradation Products ◽

Thrombin Time ◽

Agkistrodon Piscivorus ◽

Fibrin Degradation Products ◽

Coagulation Tests ◽

At Iii ◽

Diamondback Rattlesnake ◽

Sistrurus Miliarius ◽

Secondary Activation

All 34 patients seen at this hospital during the 19781980 period who were envenomated by poisonous snakes were studied in a prospective manner with respect to their hemostatic system. Blood was drawn on the patient’s arrival to the emergency room and every 6 h thereafter. Blood was analysed for platelet count; routine coagulation tests; levels of factors II, VIII, IX, XII; clottable fibrinogen; fibrinogen antigen; fibrin degradation products (FDP); plasminogen (PI); antithrombin III (AT III); α2 plasmin inhibitor (API); and plasminogen activator (PA). Twelve of the 34 patients underwent a coagulopathy as described below. These patients included all 10 patients envenomated by the Eastern diamondback rattlesnake (Crotalus adamanteus) and 2 of 17 patients bitten by the pygmy rattlesnake (Sistrurus miliarius). Values of all the above coagulation tests in 15 pygmy rattlesnake and 7 moccasin (Agkistrodon piscivorus) victims were indistinguishable from normal. Patients undergoing coagulopathy rapidly developed noncoagulable blood as defined by a thrombin time (TT) >120 s; blood remained incoagulable for an average of 18 h. The nadir clottable fibrinogen (0 mg/dl), fibrinogen antigen (99 mg/dl), Pl (20% of normal), API (17% of normal), and maximal levels of FDP (1:4096) and PA (20 times normal) were all significantly (p < 0.001) altered when compared with normal values. The platelet count and AT III levels were only midly decreased. Factors II, VIII, IX, and XII were normal. Because venom from the Eastern diamondback rattlesnake does not directly activate Pl, we conclude that the coagulopathy following envenomation by that reptile appears to be due to partial proteolysis of the fibrinogen with secondary activation of Pl by PA released from the endothelium. The resulting defibrination is distinguishable from disseminated intravascular coagulation.

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Clinical and Laboratory Profile of Hospitalized Symptomatic COVID-19 Patients: Case Series Study From the First COVID-19 Center in the UAE

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.632965 ◽

2021 ◽

Vol 11 ◽

Author(s):

Suad Hannawi ◽

Haifa Hannawi ◽

Kashif Bin Naeem ◽

Noha Mousaad Elemam ◽

Mahmood Y. Hachim ◽

...

Keyword(s):

Cardiac Injury ◽

Laboratory Data ◽

Case Series ◽

Kidney Injury ◽

Severe Infection ◽

International Normalized Ratio ◽

Cross Sectional ◽

Icu Admission ◽

Case Series Study ◽

The Mean

IntroductionCOVID-19 is raising with a second wave threatening many countries. Therefore, it is important to understand COVID-19 characteristics across different countries.MethodsThis is a cross-sectional descriptive study of 525 hospitalized symptomatic COVID-19 patients, from the central federal hospital in Dubai-UAE during period of March to August 2020.ResultsUAE’s COVID-19 patients were relatively young; mean (SD) of the age 49(15) years, 130 (25%) were older than 60 and 4 (<1%) were younger than 18 years old. Majority were male(47; 78%). The mean (SD) BMI was 29 (6) kg/m2. While the source of contracting COVID-19 was not known in 369 (70%) of patients, 29 (6%) reported travel to overseas-country and 127 (24%) reported contact with another COVID-19 case/s. At least one comorbidity was present in 284 (54%) of patients and 241 (46%) had none. The most common comorbidities were diabetes (177; 34%) and hypertension (166; 32%). The mean (SD) of symptoms duration was 6 (3) days. The most common symptoms at hospitalization were fever (340; 65%), cough (296; 56%), and shortness of breath (SOB) (243; 46%). Most of the laboratory values were within normal range, but (184; 35%) of patients had lymphopenia, 43 (8%) had neutrophilia, and 116 (22%) had prolong international normalized ratio (INR), and 317 (60%) had high D-dimer. Chest x ray findings of consolidation was present in 334 (64%) of patients and CT scan ground glass appearance was present in 354 (68%). Acute cardiac injury occurred in 124 (24%), acute kidney injury in 111 (21%), liver injury in 101 (19%), ARDS in 155 (30%), acidosis in 118 (22%), and septic shock in 93 (18%). Consequently, 150 (29%) required ICU admission with 103 (20%) needed mechanical ventilation.ConclusionsThe study demonstrated the special profile of COVID-19 in UAE. Patients were young with diabetes and/or hypertension and associated with severe infection as shown by various clinical and laboratory data necessitating ICU admission.

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Anticoagulation in COVID – 19: An Update

The Journal of Critical Care Medicine ◽

10.2478/jccm-2020-0033 ◽

2020 ◽

Vol 6 (4) ◽

pp. 217-223

Author(s):

Nishant R Tiwari ◽

Khalid I Khatib ◽

Subhal B Dixit ◽

Prajay K Rathore ◽

Sameer Melinkeri ◽

...

Keyword(s):

Venous Thromboembolism ◽

Degradation Products ◽

Specific Treatment ◽

Coagulation Parameters ◽

Fibrin Degradation Products ◽

History Of ◽

Unexplored Area ◽

Pneumatic Compression Devices ◽

Novel Coronavirus ◽

Thrombotic Diseases

AbstractThe novel coronavirus disease, 2019 (COVID – 19) evolved as an unprecedented pandemic. The severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2) infection has been associated with significantly deranged coagulation parameters and increased incidence of thrombotic events. Deranged coagulation parameters, such as D-dimers and fibrin degradation products, can indicate a poor prognosis, and their measurement will help stratify the patients according to the disease severity, need of intensive care unit admission, and prediction of the clinical course. Gaps in understanding the natural history of the disease cause difficulties in tailoring therapies and optimizing the management of patients. Lack of specific treatment further complicates this situation. While thrombotic events can cause significant morbidity and mortality in patients, a focused approach to the prevention and treatment of venous thromboembolism (VTE) can, to a great extent, decrease the disease burden caused by thrombotic diseases. Pharmacological prophylactic anticoagulants and mechanical therapies such as pneumatic compression devices can help prevent venous thromboembolism and other thrombotic events. Thrombotic events due to COVID-19, their prevention and management, are the focus of this paper, with the prospect of providing insights into this relatively unexplored area.

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