Aspirin resistance in patients with ventricular assist devices-A follow-up study.

BACKGROUND: Despite combined anticoagulation therapy consisting of a vitamin K antagonist and an antiplatelet agent, thromboembolic complications often occur in patients with a left ventricular assist device (LVAD). In addition, bleeding events are also common. Resistance to antiplatelet drugs is a well-known phenomenon; however, the utilization of laboratory chemistry testing for the presence of such resistance, and then switching therapy, is controversial. METHODS: We tested 132 patients with LVAD (HeartWare n = 57, HeartMate II n = 22, HeartMate 3 n = 53) on acetylsalicylic acid (ASA) therapy for resistance and followed them for a maximum of 7 years regarding pump thrombosis. Light transmission aggregometry (LTA) and impedance aggregometry (IPA) were performed for testing platelet function. RESULTS: We could show that patients with ASA resistance displayed an increased risk of pump thrombosis, regardless of the test used (LTA: OR = 6.20, CI [1.86-20.64], p = 0.003; IPA: OR = 12.14, CI [3.00-49.07], p < 0.001). In patients with a HeartMate 3, we could not detect any pump thrombosis associated with aspirin resistance. Furthermore, there was no significant difference in bleeding events between patients with ASA resistance and ASA responders. CONCLUSION: Laboratory testing of ASA resistance seems to be a good tool to detect an increased risk of pump thrombosis, at least for patients with a HeartWare or HeartMate II. The extent to which these thromboses can be prevented with a change of medication has to be investigated in further studies. No pump thrombosis was detected in patients with a HeartMate 3, and the question should be asked as to what constellation of underlying and concomitant diseases must be present to justify ASA therapy for these patients.

Clinical Course and Management of Patients with Emergency Surgery Treated with Direct Oral Anticoagulants or Vitamin K Antagonists-Results of the German Prospective RADOA-Registry.

(1) Background: The clinical management of anticoagulated patients treated with direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA) needing emergency surgery is challenging. (2) Methods: The prospective German RADOA registry investigated treatment strategies in DOAC- or VKA-treated patients needing emergency surgery within 24 h after admission. Effectiveness was analysed by clinical endpoints including major bleeding. Primary observation endpoint was in hospital mortality until 30 days after admission. (3) Results: A total of 78 patients were included (DOAC: 44; VKA: 34). Median age was 76 years. Overall, 43% of the DOAC patients and 79% of the VKA patients were treated with prothrombin complex concentrates (PCC) (p = 0.002). Out of the DOAC patients, 30% received no hemostatic treatment compared to 3% (1/34) of the VKA patients (p = 0.002), and 7% of the DOAC patients and 21% of the VKA patients developed major or clinically relevant non-major bleeding at the surgical site (p = 0.093). In-hospital mortality was 13% with no significant difference between the two treatment groups (DOAC: 11%, VKA: 15%; p > 0.20). (4) Conclusions: The 30-day in-hospital mortality rate was comparable between both patient groups. VKA patients required significantly more hemostatic agents than DOAC patients in the peri- and postoperative surgery period.

Changes in the Proteome of Platelets from Patients with Critical Progression of COVID-19.

Platelets, the smallest cells in human blood, known for their role in primary hemostasis, are also able to interact with pathogens and play a crucial role in the immune response. In severe coronavirus disease 2019 (COVID-19) cases, platelets become overactivated, resulting in the release of granules, exacerbating inflammation and contributing to the cytokine storm. This study aims to further elucidate the role of platelets in COVID-19 progression and to identify predictive biomarkers for disease outcomes. A comparative proteome analysis of highly purified platelets from critically diseased COVID-19 patients with different outcomes (survivors and non-survivors) and age- and sex-matched controls was performed. Platelets from critically diseased COVID-19 patients exhibited significant changes in the levels of proteins associated with protein folding. In addition, a number of proteins with isomerase activity were found to be more highly abundant in patient samples, apparently exerting an influence on platelet activity via the non-genomic properties of the glucocorticoid receptor (GR) and the nuclear factor κ-light-chain-enhancer of activated B cells (NFκB). Moreover, carbonic anhydrase 1 (CA-1) was found to be a candidate biomarker in platelets, showing a significant increase in COVID-19 patients.

Immature platelets in COVID-19.

Platelets play a critical role in immune response. Coronavirus disease 2019 (COVID-19) patients with a severe course often show pathological coagulation parameters including thrombocytopenia, and at the same time the proportion of immature platelets increases. In this study, the platelet count and the immature platelet fraction (IPF) of hospitalized patients with different oxygenation requirements was investigated daily over a course of 40 days. In addition, the platelet function of COVID-19 patients was analyzed. It was found that the number of platelets in patients with the most severe course (intubation and extracorporeal membrane oxygenation (ECMO)) was significantly lower (111.5 ∙ 106 /mL) than in the other groups (mild (no intubation, no ECMO): 203.5 ∙ 106 /mL, p < .0001, moderate (intubation, no ECMO): 208.0 ∙ 106 /mL, p < .0001). IPF tended to be elevated (10.9%). Platelet function was reduced. Differentiation by outcome revealed that the deceased patients had a highly significant lower platelet count and higher IPF (97.3 ∙ 106 /mL, p < .0001, 12.2%, p = .0003).

What is the context? Pathological coagulation is a feature of severe cases of COVID-19, with both bleeding complications and thrombosis. Patients with severe COVID-19 are frequently treated with extracorporeal membrane oxygenation (ECMO), which is often associated with bleeding complications. Platelets play an important role in blood clotting. The proportion of immature platelets has been characterized as hyperreactive and associated with high prothrombotic activity. In addition, they are discussed as predictors of COVID-19 disease severity.What is new? In grading the severity of disease in our patient cohort, we consider the required oxygenation measures. Thus, the focus is on severe cases requiring intubation and ECMO compared to moderate (intubation, no ECMO) and mild (no intubation, no ECMO) cases.What is the impact? This study focuses on severely ill patients who require ECMO treatment. Therefore, this study provides further evidence to use immature platelet fraction to predict the outcome of severe COVID-19 courses.

Pharmacokinetics of Phenprocoumon in Emergency Situations-Results of the Prospective Observational RADOA-Registry (Reversal Agent Use in Patients Treated with Direct Oral Anticoagulants or Vitamin K Antagonists Registry).

Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings (n = 82) and with urgent surgery (n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22% vs. 4.2% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days.

The Human Myofibroblast Marker Xylosyltransferase-I: A New Indicator for Macrophage Polarization.

Chronic inflammation and excessive synthesis of extracellular matrix components, such as proteoglycans (PG), by fibroblast- or macrophage-derived myofibroblasts are the hallmarks of fibrotic diseases, including systemic sclerosis (SSc). Human xylosyltransferase-I (XT-I), which is encoded by the gene XYLT1, is the key enzyme that is involved in PG biosynthesis. Increased cellular XYLT1 expression and serum XT-I activity were measured in SSc. Nothing is known so far about the regulation of XT-I in immune cells, and their contribution to the increase in measurable serum XT-I activity. We utilized an in vitro model, with primary human CD14+CD16+ monocyte-derived macrophages (MΦ), in order to investigate the role of macrophage polarization on XT-I regulation. The MΦ generated were polarized towards two macrophage phenotypes that were associated with SSc, which were classified as classical pro-inflammatory (M1-like), and alternative pro-fibrotic (M2-like) MΦ. The fully characterized M1- and M2-like MΦ cultures showed differential XT-I gene and protein expressions. The fibrotic M2-like MΦ cultures exhibited higher XT-I secretion, as well as increased expression of myofibroblast marker α-smooth muscle actin, indicating the onset of macrophage-to-myofibroblast transition (MMT). Thus, we identified XT-I as a novel macrophage polarization marker for in vitro generated M1- and M2-like MΦ subtypes, and broadened the view of XT-I as a myofibroblast marker in the process of MMT.

Treatment Algorithm for Patients With von Willebrand Syndrome Type 2A and Congenital Heart Disease-A Treatment Algorithm May Reduce Perioperative Blood Loss in Children With Congenital Heart Disease.

OBJECTIVES: In children with congenital heart disease (CHD), excessive perioperative bleeding is associated with increased morbidity and mortality, thus making adequate perioperative hemostasis crucial. We investigate the prevalence of acquired von Willebrand syndrome type 2A (aVWS) in CHD and develop a treatment algorithm for patients with aVWS and CHD (TAPAC) to reduce perioperative blood loss. DESIGN: Retrospective cohort study. SETTING: Single-center study. PATIENTS: A total of 627 patients with CHD, undergoing corrective cardiac surgery between January 2008 and May 2017. INTERVENTIONS: The evaluation of perioperative bleeding risk was based on the laboratory parameters von Willebrand factor (VWF) antigen, ristocetin cofactor activity, platelet function analyzer (PFA) closure time adenosine diphosphate, and PFA epinephrine. According to the bleeding risk, treatment was performed with desmopressin or VWF. MEASUREMENTS AND MAIN RESULTS: aVWS was confirmed in 63.3 %, with a prevalence of 45.5% in the moderate and 66.3 % in the high-risk group. In addition, prevalence increased with ascending peak velocity above the stenosis (v max ) from 40.0% at less than or equal to 3 m/s to 83.3% at greater than 5 m/s. TAPAC reduced mean blood loss by 36.3% in comparison with a historical control cohort ( p < 0.001), without increasing the number of thrombotic or thromboembolic events during the hospital stay. With ascending v max , there was an increase in perioperative blood loss in the historical cohort ( p < 0.001), which was not evident in the TAPAC cohort ( p = 0.230). CONCLUSIONS: The prevalence of aVWS in CHD seems to be higher than assumed and leads to significantly higher perioperative blood loss, especially at high v max . Identifying these patients through appropriate laboratory analytics and adequate treatment could reduce blood loss effectively.

Humoral and cellular immune response levels at a 1-year follow-up after mild COVID-19.

The primary objective of this study was to establish a 1-year follow-up of patients after mild COVID-19 with no or only short-term detection of antibodies shortly after disease. At 1 year after disease, cellular memory against SARS-CoV-2, as measured by IFN-γ release by T cells, was detected in 76% (38/50) of participants. The data suggest that even if antibody levels decline after the primary infection has resolved, a cellular immune response may be detectable for longer.

Intracranial bleeding under vitamin K antagonists or direct oral anticoagulants: results of the RADOA registry.

BACKGROUND AND PURPOSE: The use of direct oral anticoagulants (DOAC) has increased sharply and DOAC are the oral anticoagulant therapy (OAT) of choice for the majority of patients with newly-diagnosed atrial fibrillation. Intracranial hemorrhage is the most severe adverse event of OAT. Systematic data on the course of intracranial hemorrhage under DOAC compared to vitamin K antagonists (VKA) are warranted to enable shared decision making in AF patients needing OAT. METHODS: This is a secondary analysis of the patients with intracranial bleedings from the prospective multicenter emergency department-based RADOA registry, which collected data on patients admitted with major bleeding while taking VKA or DOAC. The primary endpoint was in-hospital mortality until day 30. We evaluated hematoma volume and short-term clinical outcomes in relation to the extent of active OAT according to coagulation parameters and OAT plasma levels measured by UPLC-MS/MS. RESULTS: Of 193 patients with major bleeding, 109 (56.5%) had intracranial hemorrhage [52.3% intracerebral (ICH), 33.9% subdural (SDH), 11.0% subarachnoidal (SAH)]. 64 (58.7%) were on VKA and 45 (41.2%) were on DOAC. On admission, we could confirm active anticoagulation in 97.7% of VKA-treated patients based on either INR > 1.3 or phenprocoumon levels and in 75.8% of DOAC-treated patients based on DOAC levels. Patients suffering an intracranial hemorrhage under VKA showed significantly larger hematoma volumes and a higher in-hospital mortality. Especially in intracerebral hemorrhage, we observed a higher initial severity and numerically greater proportion of early changes towards palliative therapy under VKA, which coincided with a numerically higher case fatality. CONCLUSIONS: We show significantly smaller hematoma volumes for ICH and SDH under DOAC in comparison to VKA and a significantly lower 30-day in-hospital mortality rate of DOAC-ICH, even before the introduction of specific antidotes. These data strongly support the use of DOAC whenever possible in patients requiring OAT. TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov ; Unique identifier: NCT01722786.

The impact of acquired coagulation factor XIII deficiency in traumatic bleeding and wound healing.

Factor XIII (FXIII) is a protein involved in blood clot stabilisation which also plays an important role in processes including trauma, wound healing, tissue repair, pregnancy, and even bone metabolism. Following surgery, low FXIII levels have been observed in patients with peri-operative blood loss and FXIII administration in those patients was associated with reduced blood transfusions. Furthermore, in patients with low FXIII levels, FXIII supplementation reduced the incidence of post-operative complications including disturbed wound healing. Increasing awareness of potentially low FXIII levels in specific patient populations could help identify patients with acquired FXIII deficiency; although opinions and protocols vary, a cut-off for FXIII activity of ~ 60-70% may be appropriate to diagnose acquired FXIII deficiency and guide supplementation. This narrative review discusses altered FXIII levels in trauma, surgery and wound healing, diagnostic approaches to detect FXIII deficiency and clinical guidance for the treatment of acquired FXIII deficiency.

Graft-derived Cell-free DNA as a Noninvasive Biomarker of Cardiac Allograft Rejection: A Cohort Study on Clinical Validity and Confounding Factors.

BACKGROUND: Circulating graft-derived cell-free DNA (dd-cfDNA) is a new marker of cardiac allograft damage that is used for noninvasive rejection diagnostics. We performed dd-cfDNA (%) in heart transplant recipients during the first posttransplant year. METHODS: In 87 patients, serial dd-cfDNA determination at predefined time-points was performed in 770 single samples. dd-cfDNA fraction (%) was measured using an established universal droplet digital polymerase chain reaction method, providing same-day turn-around. Rejection was diagnosed according to clinical parameters and biopsies. RESULTS: Median dd-cfDNA (%) was high (5.36%) immediately after reperfusion and decreased to a median (interquartile range) of 0.10% (0.05%-0.24%) in clinically stable patients by postoperative day 10. Compared to dd-cfDNA (%) samples in clinically stable patients, values were higher (P < 0.001) in biopsy-proven rejection ISHLT 1R (0.42% [0.15%-0.53%]) and 2R rejection (0.84% [0.39%-0.97%]). Moreover, dd-cfDNA (%) was already significantly increased 9-30 days before biopsy-proven rejection (0.36% [0.20%-0.61%]). An as yet unknown finding was a slightly, but significantly (P < 0.0001) higher dd-cfDNA (%) value in samples of stable patients with pericardial effusions (PEs) (n = 94; 0.18% [0.07%-0.30%]) compared to samples of non-PE patients (n = 132; 0.07% [0.04%-0.17%]). Using a cutoff of 0.35%, sensitivity and specificity of dd-cfDNA for cardiac rejection were 0.76 and 0.83 (area under the curve [AUC] ROC-curve: 0.81 [95% confidence interval, 0.73-0.89]). Omitting PE samples from the control group yielded an AUC of 0.86 [95% confidence interval, 0.76-0.95]. Samples drawn <12 hours after endomyocardial biopsy showed high (0.40% [0.15%-1.21%]) dd-cfDNA values, also in ISHLT0R (0.36% [0.10%-0.60%]). CONCLUSIONS: dd-cfDNA plasma values were significantly associated with cardiac rejection. However, PE or improper sampling (eg, shortly after biopsy) should be considered as confounders for rejection diagnoses using dd-cfDNA.

Pharmacokinetics of Direct Oral Anticoagulants in Emergency Situations: Results of the Prospective Observational RADOA-Registry.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly used worldwide. Little is known so far about their pharmacokinetics in emergency situations. METHODS: A prospective, observational registry was performed to determine the clinical course in consecutive patients with major bleeding or urgent surgery treated with DOACs. In samples collected as part of routine care DOAC drug concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Anticoagulant intensity at first presentation and drug half-life (t 1/2), tested in repeat samples, were evaluated. RESULTS: A total of 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. Note that 67% (89/132) experienced life-threatening bleeding and 33% (43/132) needed an urgent surgery. For pharmacokinetic analysis a total of 605 blood samples was available. Median concentration on admission was 205 ng/mL for rivaroxaban and 108 ng/mL for apixaban. All treatment groups showed a high variation of drug concentrations at baseline. In rivaroxaban-treated patients t ½ was 17.3 hours (95% confidence interval [CI]: 15.4-19.7) without significant difference in both groups (major bleeding: t ½ 16.7 hours, 95% CI: 14.7-19.3; urgent surgery: t ½ 19.7 hours, 95% CI: 15.2-27.9; p = 0.292). In apixaban-treated patients t ½ was 25.0 hours (95% CI: 22.9-27.6) with a longer t ½ after urgent surgery (t 1/2: 30.8 hours; 95% CI: 26.9-36.4) compared with severe bleeding (t 1/2: 20.8 hours; 95% CI: 18.8-23.2; p < 0.001). CONCLUSION: Emergency patients under DOAC treatment show a high variation of anticoagulant concentrations at baseline. Compared with rivaroxaban, apixaban showed a lower median concentration on admission and a longer t ½.

Evidence of Long-Lasting Humoral and Cellular Immunity against SARS-CoV-2 Even in Elderly COVID-19 Convalescents Showing a Mild to Moderate Disease Progression.

We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 ± 8.4 years). While anti-SARS-CoV-2 antibodies were still detectable in 95% of convalescents up to 8 months post infection, an antibody-decay over time was generally observed in most donors. Using a multiplex assay, our data additionally reveal that most convalescents exhibit a broad humoral immunity against different viral epitopes. We demonstrate by flow cytometry that convalescent donors show a significantly elevated number of natural killer cells when compared to healthy controls, while no differences were found concerning other leucocyte subpopulations. We detected a specific long-lasting cellular immune response in convalescents by stimulating immune cells with SARS-CoV-2-specific peptides, covering domains of the viral spike, membrane and nucleocapsid protein, and measuring interferon-γ (IFN-γ) release thereafter. We modified a commercially available ELISA assay for IFN-γ determination in whole-blood specimens of COVID-19 convalescents. One advantage of this assay is that it does not require special equipment and can, thus, be performed in any standard laboratory. In conclusion, our study adds knowledge regarding the persistence of immunity of convalescents suffering from mild to moderate COVID-19. Moreover, our study provides a set of simple methods to characterize and confirm experienced COVID-19.

Pharmacokinetics and Biologic Activity of Apixaban in Healthy Dogs.

Thrombosis is common in critically ill dogs and causes considerable morbidity and mortality. The direct factor Xa inhibitor apixaban is safe, efficacious, and convenient in humans. This study aimed to determine the pharmacokinetics (PK), bioactivity, protein binding, and bioavailability of apixaban following intravenous (IV) and oral (PO) administration to healthy dogs. Six healthy, adult, mixed-breed dogs were administered apixaban 0.18 mg/kg IV and then following a minimum 2-week washout period administered apixaban 0.2 mg/kg PO. Dogs were monitored using an apixaban-calibrated anti-Xa bioassay, prothrombin time (PT) and activated partial thromboplastin time (aPTT) and tissue-factor thromboelastography (TF-TEG). Plasma apixaban concentrations were measured using liquid chromatography-tandem mass spectrometry. Concentration-time plots were constructed, and PK modeling performed using compartmental methods. Administration of IV and PO apixaban was well-tolerated. Following IV administration, mean half-life was 4.1 h, and volume of distribution was 177 ml/kg. Apixaban was highly protein bound (98.6%). Apixaban concentrations and anti-Xa activity were highly correlated (R2 0.994, P < 0.0001). Intravenous apixaban significantly prolonged PT at time points up to 1 h, and aPTT at time points up to 0.25 h post-administration. Coagulation times were positively correlated with apixaban concentrations (PT R2 0.599, P < 0.0001; aPTT R2 0.430, P < 0.0001) and TF-TEG R-time was significantly prolonged 0.25 h post-administration. Following oral administration, mean bioavailability was 28.4%, lag time was 2 h, time to Cmax was 5 h and the apparent elimination half-life was 3.1 h. Oral apixaban significantly prolonged PT at 4, 6, and 8 h but aPTT and TF-TEG were not consistently affected by oral apixaban. Apixaban concentrations are best monitored using anti-Xa activity. Future studies should determine PK and bioactivity of other doses using commercial tablets and following multidose administration and establish safe, effective dosing ranges in sick dogs.

Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants including edoxaban.

BACKGROUND: Direct oral anticoagulants (DOAC) including edoxaban are increasingly used for stroke prevention in atrial fibrillation. Despite treatment, annual stroke rate in these patients remains 1-2%. Rapid assessment of coagulation would be useful to guide thrombolysis or reversal therapy in this growing population of DOAC/edoxaban-treated stroke patients. Employing the Hemochron™ Signature Elite point-of-care test system (HC-POCT), clinically relevant plasma concentrations of dabigatran and rivaroxaban can be excluded in a blood sample. However, no data exists on the effect of edoxaban on HC-POCT results. We evaluated whether edoxaban plasma concentrations above the current treatment thresholds for thrombolysis or anticoagulation reversal (i.e., 30 and 50 ng/mL) can be ruled out with the HC-POCT. METHODS: We prospectively studied patients receiving a first dose of edoxaban. Six blood samples were collected from each patient: before, 0.5, 1, 2, 8, and 24 h after drug intake. HC-POCT-based INR (HC-INR), activated clotting time (HC-ACT+ and HC-ACT-LR), activated partial thromboplastin time (HC-aPTT), and mass spectrometry for edoxaban plasma concentrations were performed at each time-point. We calculated correlations, receiver operating characteristics (ROC) and test-specific cut-offs for ruling out edoxaban concentrations > 30 and > 50 ng/mL in a blood sample. RESULTS: One hundred twenty blood samples from 20 edoxaban-treated patients were analyzed. Edoxaban plasma concentrations ranged from 0 to 512 ng/mL. HC-INR/HC-ACT+/HC-ACT-LR/HC-aPTT ranged from 0.7-8.3/78-310 s/65-215 s/19-93 s, and Pearson's correlation coefficients showed moderate to very strong correlations with edoxaban concentrations (r = 0.95/0.79/0.70/0.60). With areas under the ROC curve of 0.997 (95% confidence interval: 0.991-0.971) and 0.989 (0.975-1.000), HC-INR most reliably ruled out edoxaban concentrations > 30 and > 50 ng/mL, respectively, and HC-INR results ≤1.5 and ≤ 2.1 provided specificity/sensitivity of 98.6% (91.2-99.9)/98.0% (88.0-99.9) and 96.8% (88.0-99.4)/96.5% (86.8-99.4). CONCLUSIONS: Our study represents the first systematic evaluation of the HC-POCT in edoxaban-treated patients. Applying sufficiently low assay-specific cut-offs, the HC-POCT may not only be used to reliably rule out dabigatran and rivaroxaban, but also very low edoxaban concentrations in a blood sample. Because the assay-specific cut-offs were retrospectively defined, further investigation is warranted. TRIAL REGISTRATION: ClinicalTrials.gov, registration number: NCT02825394 , registered on: 07/07/2016, URL.

Retrospective analysis of 426 donors of a convalescent collective after mild COVID-19.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread across the world. The aim of our study was to characterize mild courses and to determine the antibody status for these patients. METHODS: We initiated an appeal for convalescent plasma donations. 615 people contacted us, and we ultimately included 426 in our analyses, in whom it was possible to assume COVID-19 based on detection of specific SARS-CoV-2 antibodies or virus detection during the disease using RT-PCR. RESULTS: The median duration of the disease was 12 days and the most common symptoms were fatigue, cough and olfactory and gustatory dysfunction. Anti-SARS-CoV-2 IgG was detected in 82.4% of the persons and IgA antibodies were found in 73.9%. In 10.8%, no antibodies were detectable despite a positive RT-PCR result during the disease. Nevertheless, of 24 persons with asymptomatic courses of COVID-19, antibodies against SARS-CoV-2 could be detected in 23 (96%). Furthermore, there was a correlation between the duration of the disease and the detection of IgG antibodies. In addition, a correlation between the determined IgG antibodies and neutralizing antibodies was shown. CONCLUSION: In this study, we were able to describe mild COVID-19 courses and determine antibody statuses for them. It could be shown that, despite SARS-CoV-2 detection during the disease, not all individuals developed antibodies or their level of antibodies had dropped below the detection limit shortly after the end of the disease. The extent to which immunity to re-infection is given in persons with undetectable antibodies (IgG, IgA) needs to be investigated in future studies.

Specific Point-of-Care Testing of Coagulation in Patients Treated with Dabigatran.

BACKGROUND AND PURPOSE: Accurate and rapid assessment of coagulation status is necessary to guide thrombolysis or reversal of anticoagulation in stroke patients, but commercially available point-of-care (POC) assays are not suited for coagulation testing in patients treated with direct oral anticoagulants (DOACs). We aimed to evaluate the direct thrombin monitoring (DTM) test card by Helena Laboratories (Texas, United States) for anti-IIa-specific POC coagulation testing, hypothesizing that its POC-ecarin clotting time (POC-ECT) accurately reflects dabigatran plasma concentrations. METHODS: A prospective single-center diagnostic study (ClinicalTrials.gov-identifier: NCT02825394) was conducted enrolling patients receiving a first dose of dabigatran and patients already on dabigatran treatment. Blood samples were collected before drug intake and 0.5, 1, 2, 8, and 12 hours after intake. POC-ECT was performed using whole blood (WB), citrated blood (CB), and citrated plasma (CP). Dabigatran plasma concentrations were determined by mass spectrometry. RESULTS: In total, 240 blood samples from 40 patients contained 0 to 275 ng/mL of dabigatran. POC-ECT with WB/CB/CP ranged from 20 to 186/184/316 seconds. Pearson's correlation coefficient showed a strong correlation between dabigatran concentrations and POC-ECT with WB/CB/CP (R2 = 0.78/0.90/0.92). Dabigatran concentrations >30 and >50 ng/mL (thresholds for thrombolysis, surgery, and reversal therapy according to clinical guidelines) were detected by POC-ECT with WB/CB/CP (>36/35/45 and >43/45/59 seconds) with 95/97/97 and 96/98/97% sensitivity, and 81/87/94 and 74/60/91% specificity. CONCLUSION: This first study evaluating DOAC-specific POC coagulation testing revealed an excellent correlation of POC-ECT with actual dabigatran concentrations. Detecting clinically relevant dabigatran levels with high sensitivity/specificity, the DTM assay represents a suitable diagnostic tool in acute stroke, hemorrhage, and urgent surgery.

Direct oral anticoagulants and cardiac surgery: A descriptive study of preoperative management and postoperative outcomes.

OBJECTIVE: Recommendations for perioperative management of direct oral anticoagulant (DOAC) treatment in cardiac surgery are lacking. To establish a standardized approach for these patients, we compared hemorrhagic complications and clinical outcomes in patients on DOAC medication, patients on vitamin K antagonists (VKA), and patients without preoperative anticoagulation. METHODS: All 3 groups underwent major cardiac surgery and were retrospectively analyzed: patients on DOAC were advised to take their last DOAC dose 4 days before hospital admission, and DOAC plasma levels were measured the day before surgery. In patients with plasma levels of >30 ng/mL, surgery was postponed until plasma level was below this threshold level. Postoperative chest tube drainage, bleeding complications, use of blood products, and thromboembolic events were collected for all groups. RESULTS: A total of 5439 patients no anticoagulation, 239 patients on VKA, and 487 patients on DOAC medication were included between April 2014 and July 2017. Adjusted postoperative chest tube drainage did not differ between the DOAC and VKA groups for the strategy applied in this study (380 mL/12 hours vs 360 mL/12 hours). Moreover, secondary endpoint measures, such as rethoracotomy (30 [6.16%] vs 15 [6.28%]), 30-day-mortality 12 [2.46%] vs 7 [2.93%]), blood-product use, and stroke, were not significantly different through implementation of our standardized study management (P > .05). CONCLUSIONS: Our standardized management for perioperative discontinuation of DOAC therapy may provide a safe approach to minimize hemorrhagic complications in cardiac surgery in patients on DOACs.

How would we treat our own heparin-induced thrombocytopenia during cardiac surgery?

The aim of this article is to provide a comprehensive review of the current state of knowledge on heparin-induced thrombocytopenia (HIT) in cardiac surgery. The management of HIT patients undergoing cardiac surgery with cardiopulmonary bypass is complex and requires an interdisciplinary and patient-tailored approach because available evidence is limited and current anticoagulation strategies have potential risks. An index case is used to discuss both the established and new perioperative therapeutic options in HIT patients undergoing urgent cardiac surgery with cardiopulmonary bypass.