A retrospective multicenter cohort study of the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19.

BACKGROUND: Patients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19. METHOD: This retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients' minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations. RESULTS: In total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients' minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism. CONCLUSIONS: Measuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results. TRIAL REGISTRATION: The study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.

Cardiac Arrest Due to out-of-Hospital Pulmonary Embolism During Pregnancy: Successful Thrombolysis.

Introduction: Pulmonary embolism (PE) is a rare, severe complication in pregnancy, in which case thrombolysis can be lifesaving but has risks. We aim to highlight actions specific to pregnant women. Case Description: A 24-week pregnant woman developed shortness of breath and experienced sudden cardiac arrest. Cardiopulmonary resuscitation (CPR) was begun immediately in the ambulance and a perimortem caesarean section was performed upon arrival at hospital, but the new-born died. After 55 minutes of CPR, bedside echocardiography revealed right ventricular strain and thrombolysis was given. The uterus was bandaged to minimize blood loss. After massive transfusions and correction of haemostasis, a hysterectomy was performed due to inability of the uterus to contract. After 3 weeks, the patient was discharged in good health and placed on continuous anticoagulant treatment with warfarin. Discussion: Approximately 3% of all out-of-hospital cardiac arrest cases are due to PE. Among the few patients who survive at the scene, thrombolysis can be lifesaving and should be considered in pregnant women with unstable PE. Prompt collaborative diagnostic work-up in the emergency room is necessary. In a pregnant woman with cardiac arrest, a perimortem caesarean section improves the chances of both maternal and fetal survival. Conclusion: Thrombolysis should be considered for patients with PE in pregnancy with the same indications as in a non-pregnant woman. In case of survival, there is profuse bleeding with need for massive transfusions and haemostasis correction. Despite being in very poor condition, the above patient survived and was fully restored to health. LEARNING POINTS: In a young person with a non-shockable rhythm, pulmonary embolism should be kept in mind, especially if they have risk factors for thromboembolism, and pregnant women should be thrombolysed on the same indication as non-pregnant women.In cardiac arrest, a perimortem caesarean section improves the chances of both maternal and fetal survival, but after major surgery one should be prepared for the need for massive transfusions after thrombolysis. Bandaging the uterus might minimize bleeding. Despite 1-hour cardiac arrest with CPR, the patient survived and made a complete recovery.Lifestyle advice with exercise and sun exposure might help avoid rethrombosis and depression in both the short and long term.

[Man diagnosed with Klinefelter syndrome after having a pulmonary embolism]. / Lungembolier ledde slutligen till diagnosen Klinefelters syndrom.

Klinefelter syndrome occurs in approximately 1/700 males, and it is widely undiagnosed. Venous thromboembolism is common in Klinefelter syndrome. In boys or childless men with unprovoked venous thromboembolism, Klinefelter syndrome is an important diagnosis to consider. A thorough somatic examination including the testes is important to raise suspicion of Klinefelter syndrome. This case report describes a man who is diagnosed with Klinefelter syndrome after having a pulmonary embolism. Since there were not any other factors that could explain his venous thromboembolism, his genetic condition was considered to be the underlying cause.

An observational study of intermediate- or high-dose thromboprophylaxis for critically ill COVID-19 patients.

BACKGROUND: Critically ill COVID-19 patients have a high reported incidence of thromboembolic complications and the optimal dose of thromboprophylaxis is not yet determined. The aim of this study was to investigate if 90-day mortality differed between patients treated with intermediate- or high-dose thromboprophylaxis. METHOD: In this retrospective study, all critically ill COVID-19 patients admitted to intensive care from March 6th until July 15th, 2020, were eligible. Patients were categorized into groups according to daily dose of thromboprophylaxis. Dosing was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios of death within 90 days from ICU admission. Multivariable models were adjusted for sex, age, body-mass index, Simplified Acute Physiology Score III, invasive respiratory support, glucocorticoids, and dosing strategy of thromboprophylaxis. RESULTS: A total of 165 patients were included; 92 intermediate- and 73 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. The 90-day mortality was 19.6% in patients with intermediate-dose and 19.2% in patients with high-dose thromboprophylaxis. Multivariable hazard ratio of death within 90 days was 0.74 (95% CI, 0.36-1.53) for the high-dose group compared to intermediate-dose group. Multivariable hazard ratio for thromboembolic events and bleedings within 28 days was 0.93 (95% CI 0.37-2.29) and 0.84 (95% CI 0.28-2.54) for high versus intermediate dose, respectively. CONCLUSIONS: A difference in 90-day mortality between intermediate- and high-dose thromboprophylaxis could neither be confirmed nor rejected due to a small sample size.

The role of ventilatory support for long-term outcomes after critical infection with COVID-19: A prospective cohort study.

OBJECTIVES: The full range of long-term health consequences in intensive care unit (ICU) survivors with COVID-19 is unclear. This study aims to investigate the role of ventilatory support for long-term pulmonary impairment in critically ill patients and further to identify risk factors for prolonged radiological recovery. METHODS: A prospective observational study from a single general hospital, including all with COVID-19 admitted to ICU between March and August 2020, investigating the association between ventilatory support and the extent of residual parenchymal changes on chest computed tomography (CT) scan and measurement of lung volumes at follow-up comparing high-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV) with invasive ventilation. A semi-quantitative score (CT involvement score) based on lobar involvement and a total score for all five lobes was used to estimate residual parenchymal changes. The association was calculated with logistic regression and adjusted for age, sex, smoking, and severity of illness. RESULTS: Among the 187 eligible, 86 had a chest CT scan and 76 a pulmonary function test at the follow-up with a median time of 6 months after ICU discharge. Residual lung changes were seen in 74%. The extent of pulmonary changes was similar regardless of ventilatory support, but patients with invasive ventilation had a lower total lung capacity 84% versus 92% of predicted (p < 0.001). CONCLUSIONS: The majority of ICU-treated patients with COVID-19 had residual lung changes at 6 months of follow-up regardless of ventilator support or not, but the total lung capacity was lower in those treated with invasive ventilation.

High-flow nasal oxygen (HFNO) for patients with Covid-19 outside intensive care units.

INTRODUCTION: High-flow nasal oxygen (HFNO) has traditionally only been used in intensive care units (ICU) especially in acute respiratory distress syndrome (ARDS). METHODS: We studied the use of HFNO at Södersjukhuset, Stockholm, in patients with moderate to severe ARDS related to Covid-19 as well as its benefits both for patients and to offload the ICU. The patients were observed with frequent controls to assess the need of ICU in case of deterioration. RESULTS: We studied 41 patients with HFNO treatment either as primarily treatment (Step-Up) or after stabilizing in the ICU (Step-Down). The average duration for treatment with HFNO was 5.6 days. Of these patients 55% were discharged home or to geriatric rehabilitation and 10% avoided ICU completely. The usage of HFNO saved in total 229 days in the ICU. Mortality was higher among elderly patients, and patients with comorbidities (mainly hypertension and obesity). DISCUSSION AND CONCLUSION: HFNO treatment is feasible and efficient for patients with Covid-19, saving resources in the ICU and offering additional advantages as waken proning and fewer complications compared to traditional ICU care. It requires however frequent controls as deterioration is recurrent.

Long-term consequences in critically ill COVID-19 patients: A prospective cohort study.

BACKGROUND: COVID-19 can cause severe disease with need of treatment in the intensive care unit (ICU) for several weeks. Increased knowledge is needed about the long-term consequences. METHODS: This is a single-center prospective follow-up study of COVID-19 patients admitted to the ICU for respiratory organ support between March and July 2020. Patients with invasive ventilation were compared with those with high-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV) regarding functional outcome and health-related qualify of life. The mean follow-up time was 5 months after ICU discharge and included clinical history, three well-validated questionnaires about health-related quality of life and psychological health, pulmonary function test, 6-minute walk test (6MWT) and work ability. Data were analyzed with multivariable general linear and logistic regression models with 95% confidence intervals. RESULTS: Among 248 ICU patients, 200 patients survived. Of these, 113 patients came for follow-up. Seventy patients (62%) had received invasive ventilation. Most patients reported impaired health-related quality of life. Approximately one-third suffered from post-traumatic stress, anxiety and depression. Twenty-six percent had reduced total lung capacity, 34% had reduced 6MWT and 50% worked fulltime. The outcomes were similar regardless of ventilatory support, but invasive ventilation was associated with more bodily pain (MSD -19, 95% CI: -32 to -5) and <80% total lung capacity (OR 4.1, 95% CI: 1.3-16.5). CONCLUSION: Among survivors of COVID-19 who required respiratory organ support, outcomes 5 months after discharge from ICU were largely similar among those requiring invasive compared to non-invasive ventilation.

Dosing of thromboprophylaxis and mortality in critically ill COVID-19 patients.

BACKGROUND: A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding. METHOD: In this retrospective study, all critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis: low (2500-4500 IU tinzaparin or 2500-5000 IU dalteparin), medium (> 4500 IU but < 175 IU/kilogram, kg, of body weight tinzaparin or > 5000 IU but < 200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥ 200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis. RESULTS: A total of 152 patients were included: 67 received low-, 48 medium-, and 37 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13-0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43-1.83) among those who received medium dose, as compared to those who received low-dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04. CONCLUSIONS: Among critically ill COVID-19 patients with respiratory failure, high-dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses. TRIAL REGISTRATION: Clinicaltrials.gov NCT04412304 June 2, 2020, retrospectively registered.

[Better adherence to guidelines can help avoid unnecessary ultrasound investigations and ER visits]. / Bättre följsamhet till rutiner vid svullet ben kan undvika onödiga akutbesök och undersökningar - Genomgång av utredningar av patienter med misstänkt DVT.

Deep vein thrombosis (DVT) is a common differential diagnosis in patients with a swollen lower limb and the suggested method of investigation with pre-test probability including Wells score and D-dimer is well established. We have conducted a retrospective descriptive directory study to examine how DVT-investigations are being conducted and a retrospective cohort study to compare correctly and incorrectly investigated patients regarding missed DVT and the usage of imaging. Our study has been conducted though chart reviews of 398 patients with suspected DVT at the emergency department (ED) at Södersjukhuset in Stockholm during 2016. A total of 74/398 cases of DVT were verified. More than half of the investigations were not conducted according to the current guidelines. These investigations did not miss any DVTs but did use significantly more imaging (86,2 % vs 49,6 %, p < 0,01). ED admissions could be avoided for approximately one out of three referred patients if stricter diagnostics were conducted by the referring doctor.

d-Dimer and simplified pulmonary embolism severity index in relation to right ventricular function.

BACKGROUND: Right ventricular (RV) involvement in pulmonary embolism (PE) is an ominous sign. The aim of this study was to investigate the extent to which the d-dimer level or simplified PE severity index (sPESI) indicates RV dysfunction in patients with preserved systemic arterial pressure. METHODS: Right ventricular function was studied in 34 consecutive patients with acute nonmassive PE by echocardiography including Doppler tissue imaging within 24 hours after arrival to the hospital. d-Dimer and sPESI were assessed upon arrival. RESULTS: d-Dimer correlated with RV pressure (Rs, 0.60; P < .001) and pulmonary vascular resistance (PVR; Rs, 0.68; P < .0001) and tended to be related to myocardial performance index (MPI; Rs, 0.31; P = .067). Compared to a level less than 3.0 mg/L, patients with d-dimer 3.0 mg/L or higher had lower systolic tricuspid annular velocity (11.3 ± 2.7 vs 13.5 ± 2.7 cm/s; P < .05), a prolonged MPI (0.8 ± 0.3 vs 0.5 ± 0.2; P < .01), increased RV pressure (58 ± 13 vs 37 ± 12 mm Hg; P < .001), and increased PVR (3.3 ± 1.1 vs 1.8 ± 0.4 Woods units; P < .001). Patients in the high-risk sPESI group had higher filling pressure than those in the low risk sPESI group. CONCLUSIONS: In the acute stage of PE, a d-dimer level 3 mg/L or higher may identify nonmassive PE patients with RV dysfunction and thereby help to determine their risk profile. We found no additional value for sPESI in this context.

Echocardiographic evaluation of right ventricular function in patients with acute pulmonary embolism: a study using tricuspid annular motion.

Assessment of right ventricular (RV) function is a challenge due to complex anatomy. We studied systolic and diastolic tricuspid annular excursion and longitudinal RV fractional shortening as geometry-independent measures in patients with acute pulmonary embolism (PE). Forty patients with PE were studied within 24 hours after admission and after 3 months, and compared to 23 healthy subjects used as controls. We recorded tricuspid annular plane systolic (TAPSE) and diastolic (TAPDE) excursion from the four-chamber view and calculated RV fractional shortening as TAPSE/RV diastolic length. The diastolic RV function was defined as the ratio of the amplitude of tricuspid annular plane excursion during atrial systole to total tricuspid annular plane diastolic excursion (atrial/total TAPDE). In the acute stage, the TAPSE was decreased in PE compared to healthy subjects (19 +/- 5 vs. 26 +/- 4 mm, P < 0.001), with greater reduction in patients with increased, compared to normal, RV pressure (16.6 +/- 5 vs. 20.5 +/- 5 mm, P < 0.05). The atrial/total TAPDE was increased in patients compared to healthy subjects (47 +/- 13% vs. 38 +/- 7%, P < 0.001) and normalized during the follow-up. Although the patients were asymptomatic after 3 months, the TAPSE recovered incompletely as compared to healthy subjects (21.4 +/- 4 vs. 26 +/- 4 mm, P < 0.001). Both systolic and diastolic RV function are impaired in acute PE. Diastolic function recovers faster than systolic; therefore, the atrial contribution to RV filling may be a useful measure to follow changes in diastolic function in PE.

The use of D-dimer testing and Wells score in patients with high probability for acute pulmonary embolism.

RATIONALE, AIMS AND OBJECTIVE: To investigate if a combination of Wells pre-test probability score and D-dimer testing could be used as a safe base for making clinical decisions on further investigations for patients with intermediate to high risks of pulmonary embolism (PE). METHODS: One hundred and twenty patients with signs or symptoms of acute PE were investigated with pulmonary angiography (PA) or contrast enhanced computed tomography of the pulmonary arteries (CTPA), D-dimer testing (Tinaquant) and clinical scoring using the Wells pre-test probability score during their first 48 hours at the hospital. Patients were recruited consecutively from emergency departments at two teaching hospitals. RESULTS: The cut-off value of 0.5 mg L(-1) in D-dimer analysis is proved adequate with a negative predictive value (NPV) of 92% in this group of patients with intermediate to high risks. The combination of D-dimer testing and Wells score increases the NPV to 94%. The specificities of both tests were low. CONCLUSION: D-dimer and Wells pre-test probability scores are safe to rule out acute PE even in patients with at least an intermediate risk of PE, but the specificity is low. D-dimer testing had a higher NPV than Wells score and the combination improved the algorithm further. The cut-off level for a high risk of PE measured with the Wells score was four and it seems reasonable to use that cut-off level in future algorithms. In addition, both PA and CTPA can present false positive and negative results difficult to interpret.

Evaluation of Wells score and repeated D-dimer in diagnosing venous thromboembolism.

BACKGROUND: Patients presenting with symptoms suggestive of venous thromboembolism (VTE), i.e., deep vein thrombosis (DVT) and pulmonary embolism (PE), are common at the emergency departments. However, of those, only 15-25% actually have the disease. The aims of this study were to determine (1) if low pre-test probability (PTP) using the Wells score, together with a normal D-dimer, safely excludes VTE in outpatients and (2) if a follow-up D-dimer adds extra information. METHODS: Patients (n=151, 68% women) with suspected VTE, a PTP below 1.5, and a D-dimer test (TinaQuant) below 0.5 mg/L were included in the study and underwent no further diagnostic investigations. Patients (n=177, 54% women) with D-dimer levels of 0.5 mg/L or higher or a PTP of 1.5 or higher were excluded. A follow-up D-dimer test was conducted 3-7 days after the initial hospital visit and further diagnostic investigations were made if test results were abnormal. Patients were studied for 3 months. RESULTS: A follow-up D-dimer test was conducted in 101/151 cases (67%), 13/101 of which revealed elevated D-dimer levels. None of these 13 patients had persistent symptoms or was diagnosed with VTE. All 151 patients were contacted after 3 months; none of them had clinical signs of VTE. Of the 177 patients excluded, 45 (25%) were diagnosed with VTE. Of the 176/328 (151+177) patients with normal D-dimer levels, only 1 had VTE (<0.01%). CONCLUSION: A normal PTP using the Wells score and a normal D-dimer safely excludes VTE at the emergency department. A follow-up D-dimer test adds no further information.

Pulmonary embolism associated with the use of anabolic steroids.

We present the case of a 56-year-old man with deep vein thrombosis (DVT) and pulmonary embolism (PE). He had been given intramuscular injections of testosterone and the anabolic-androgenic steroid nandrolone, due to a muscle injury, a total of three times prior to manifestation of the symptoms. An ultrasonographic examination of the right leg revealed a DVT and computed tomography of the pulmonary arteries showed PE. The thromboembolic episodes in this previously healthy patient were in all probability associated with intramuscular injections of testosterone and nandrolone, to which there is a clear correlation in time.

Initial symptoms in pulmonary embolism differ from those in pneumonia: a retrospective study during seven years.

OBJECTIVE: To compare initial symptoms in pulmonary embolism with community-acquired pneumonia and relate to C-reactive protein and pulmonary infiltrates in order to improve the clinical assessment at the emergency department. METHODS: A retrospective review of patients with pulmonary embolism diagnosed in the clinic for infectious diseases (CID), (n=25), and a randomized sample of patients with pulmonary embolism diagnosed in the department of medicine (n=64), and a randomized sample of patients with community-acquired pneumonia (n=54) diagnosed in the clinic for infectious diseases. RESULTS: Initial symptoms in pulmonary embolism, dominated by dyspnoea and/or pleuritic chest pain were significantly different from those in community-acquired pneumonia, dominated by fever, chills and/or cough (P<0.001). On admission, C-reactive protein and body temperature were significantly higher and pulmonary infiltrates were more common in pneumonia compared with randomized pulmonary embolism patients. Twenty-five patients with a final diagnosis of pulmonary embolism were erroneously suspected of having lung infection, owing to increased C-reactive protein, presence of pulmonary infiltrates and/or high fever. However, they had classical symptoms of pulmonary embolism. CONCLUSIONS: Pulmonary infiltrates, high fever and a high level of C-reactive protein can deceive the physician to suspect pneumonia instead of pulmonary embolism. Classical initial symptoms ought to direct the physician in diagnosing pulmonary embolism. We emphasize a detailed patient history of initial symptoms.

A comparison of spiral computed tomography and latex agglutination D-dimer assay in acute pulmonary embolism using pulmonary arteriography as gold standard.

OBJECTIVE: To compare the diagnostic accuracy of contrast medium enhanced spiral computed tomography of the pulmonary arteries (s-CTPA) and a latex agglutination D-dimer assay in patients with suspected acute pulmonary embolism (PE) by using pulmonary arteriography (PA) and clinical follow-up as reference method. DESIGN: Ninety hemodynamically stable patients with symptoms of acute pulmonary embolism were prospectively evaluated with s-CTPA and pulmonary arteriography (PA) within 24 h from admission. Plasma D-dimer levels on admittance were analyzed using a rapid latex agglutination D-dimer assay. The outcome of D-dimer concentrations in plasma below 0.25 and 0.5 mg/l was studied. RESULTS: All PA and s-CTPA investigations were regarded as of acceptable diagnostic quality in a consensus reading. Thirty-three patients had a positive PA (37%). Three patients had false negative and two patients had false positive s-CTPA findings. s-CTPA had 91% sensitivity, 96% specificity, 94% positive predictive value (PPV) and 95% negative predictive value (NPV). The sensitivity and specificity for D-dimer below 0.5 mg/l were 79 and 88%, respectively. The PPV and NPV were 81 and 87%. If a cut-off level of 0.25 mg/l was used the corresponding figures were 91, 65, 63 and 92%. CONCLUSION: s-CTPA has a higher sensitivity and specificity than latex agglutination D-dimer. A cut-off level of 0.25 mg/l can be used as screening method, but s-CTPA must be performed to exclude false positive cases.