Dabigatran in Cerebral Sinus Vein Thrombosis and Thrombophilia.

BACKGROUND AND PURPOSE: Thrombophilic gene alterations are a major risk factor for cerebral sinus vein thrombosis (CSVT). Up to 30% of all patients with cerebral sinus vein thrombosis (CSVT) are found to have thrombophilic defects such as prothrombin mutation (PTM) or factor V Leiden (FVL). Their repercussions on the plasma levels of dabigatran etexilate are unclear. In this prospective case-control study, we aimed to investigate whether thrombophilia in CSVT has an influence on dabigatran peak-plasma levels. METHODS: We monitored 10 patients over 12 months with acute CSVT, genetic thrombophilia with off-label use of dabigatran etexilate 150 mg twice a day and measured dabigatran peak-plasma levels and radiological outcome. We also monitored patients without genetic thrombophilia with dabigatran etexilate 150 mg twice a day and compared the efficiency and dabigatran peak-plasma levels. RESULTS: Patients with homozygote PTM had significantly lower dabigatran peak concentration compared to patients with FVL or the control group (23 ± 4.2 vs. 152.3 ± 27.5 and 159.6 ± 63.08; p-value ≤ 0.05) There was no significant difference in dabigatran etexilate plasma levels between the heterozygote PTM group compared to patients with FVL or the control group (p = 0.29). There was no correlation between dabigatran peak concentration and delayed thrombus dissolution. CONCLUSIONS: Dabigatran peak concentration was stable in patients with heterozygote FVL and heterozygote PTM, but not in homozygote PTM, compared to controls. Genetic screening for thrombophilia in patients after CSVT may be useful to make patient tailored therapeutic decisions regarding oral anticoagulation and may decrease thrombotic events.

A sudden creatinine increase: A case report.

Creatinine and estimated glomerular filtration rate (eGFR) are first-line laboratory parameters in the diagnosis of various renal diseases. In recent decades, cystatin C (cysC) has furthered the laboratory repertoire regarding renal status assessment and has been implemented in many clinical guidelines. Accordingly, with the establishment of cysC as a renal routine biomarker, further opportunities for assessing eGFR have been attained. Nevertheless, various limitations are still associated with cysC and creatinine analysis. Preanalytical errors could cause false results in both biomarkers. In our case, we were confronted with implausibly elevated creatinine levels due to preanalytical errors.

A Balanced Robertsonian Translocation in a Patient with a Janus Kinase 2-Positive Polycythemia Vera.

A male patient with a persistent, combined erythrocytosis, leukocytosis, and thrombocytosis without representative evidence of reactive increase emerged as having a myeloproliferative disorder. Molecular-biological assessment yielded Janus kinase 2-positive results, and the patient was diagnosed with polycythemia vera. In addition to these findings, further karyotyping accounted for a Robertsonian translocation. Because this rearrangement was a balanced variant, we concluded that this cytogenetic result might not significantly alter the diagnosis of polycythemia vera.

Troponin interference with special regard to macrocomplex formation.

Biomarkers, such as troponin-T and troponin-I, are regarded as the gold standard laboratory parameter for diagnosing many cardiological diseases. These parameters have been approved for clinical use. Many cardiological guidelines recommend the analysis of troponins in the majority of cardiological disease diagnoses and to also gain prognostic information. Nonetheless, many medical circumstances could cause false troponin elevations. In this article, we focus on troponin artifacts, particularly macro-immune complex formation, as important interference factors. Therefore, we performed a literature search from 2006 to 06/2021.

Virus-induced senescence is a driver and therapeutic target in COVID-19.

Derailed cytokine and immune cell networks account for the organ damage and the clinical severity of COVID-19 (refs. 1-4). Here we show that SARS-CoV-2, like other viruses, evokes cellular senescence as a primary stress response in infected cells. Virus-induced senescence (VIS) is indistinguishable from other forms of cellular senescence and is accompanied by a senescence-associated secretory phenotype (SASP), which comprises pro-inflammatory cytokines, extracellular-matrix-active factors and pro-coagulatory mediators5-7. Patients with COVID-19 displayed markers of senescence in their airway mucosa in situ and increased serum levels of SASP factors. In vitro assays demonstrated macrophage activation with SASP-reminiscent secretion, complement lysis and SASP-amplifying secondary senescence of endothelial cells, which mirrored hallmark features of COVID-19 such as macrophage and neutrophil infiltration, endothelial damage and widespread thrombosis in affected lung tissue1,8,9. Moreover, supernatant from VIS cells, including SARS-CoV-2-induced senescence, induced neutrophil extracellular trap formation and activation of platelets and the clotting cascade. Senolytics such as navitoclax and a combination of dasatinib plus quercetin selectively eliminated VIS cells, mitigated COVID-19-reminiscent lung disease and reduced inflammation in SARS-CoV-2-infected hamsters and mice. Our findings mark VIS as a pathogenic trigger of COVID-19-related cytokine escalation and organ damage, and suggest that senolytic targeting of virus-infected cells is a treatment option against SARS-CoV-2 and perhaps other viral infections.

Spontaneous Intracerebral Hemorrhage Due to Delta Storage Pool Disease in a Patient on a Serotonin-Norepinephrine Reuptake Inhibitor.

We report a case of spontaneous intracerebral hemorrhage (sICH) due to delta storage pool disease in a 60-year-old female on a serotonin-norepinephrine reuptake inhibitor (SNRI). Increased susceptibility to SNRI-effects on hemostasis was due to a genetic disposition mediated by a polymorphism of the SLC6A4 gene coding for the human serotonin transporter (SERT). Pathophysiological and clinical implications of these findings are discussed.

Characterization of Von Willebrand Factor Multimer Structure in Patients With Severe Aortic Stenosis.

Acquired von Willebrand syndrome (AVWS) associated with severe aortic stenosis (AS) has been frequently subclassified into a subtype 2A based on the deficiency of high-molecular-weight (HMW) multimers as it is seen in inherited von Willebrand disease (VWD) type 2A. However, the multimeric phenotype of VWD type 2A does not only include an HMW deficiency but also a decrease in intermediate-molecular-weight (IMW) multimers and an abnormal inner triplet band pattern. These additional characteristics have not been evaluated in AVWS associated with severe AS. Therefore, we recruited N = 31 consecutive patients with severe AS and performed a high-resolution Western blot with densitometrical band quantification to characterize the von Willebrand factor (VWF) multimeric structure and reevaluate the AVWS subtype classification. Study patients showed an isolated HMW VWF multimer deficiency without additional abnormalities of the IMW portions and the inner triplet structure in 65%. In conclusion, the multimeric pattern of AVWS associated with severe AS does neither resemble that seen in AVWS type 2A nor that seen in inherited VWD type 2A. Therefore, a subclassification into a type 2A should not be used.

Haemophagocytic lymphohistiocytosis associated with fulminant hepatitis and multiorgan failure following primary Epstein-Barr virus and herpes simplex virus type 1 infection.

We present a case of severe fatal hepatitis in a young patient presumably triggered by two ubiquitous viral diseases which occurred in close succession. This case is unusual because of the exceptional chronological sequence of primary Epstein-Barr virus and herpes simplex virus type 1 infection causing systemic immune dysregulation associated with rapidly developing liver failure and consecutive multiorgan failure. Clinical, laboratory and histopathological findings indicated the development of secondary haemophagocytic lymphohistiocytosis triggered by these closely succeeding viral primary infections.

Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests.

BACKGROUND: Dabigatran etexilate is a new oral anticoagulant for the therapy and prophylaxis of venous thromboembolism and stroke prevention in patients with atrial fibrillation. To investigate the extent of interactions of this new anticoagulant with frequently used coagulation assays, we completed a multicenter in vitro trial with Conformité Européenne(CE)-labeled dabigatran-spiked plasma samples. METHODS: Lyophilized plasma samples with dabigatran concentrations ranging from 0.00 to 0.48 µg/mL were sent to the coagulation laboratories of six major Austrian hospitals for evaluation. Coagulation assays were performed under routine conditions using standard reagents and analyzer. RESULTS: Dabigatran led to a dose-dependent prolongation of the clotting times in coagulometric tests and influenced the majority of the parameters measured. Statistically significant interference could be observed with the prothrombin time (PT), activated partial thromboplastin time (aPTT) and PT/aPTT-based assays (extrinsic/intrinsic factors, APC-resistance test) as well as lupus anticoagulant testing. Even non-clotting tests, such as the colorimetric factor XIII activity assay and to a minor extent the amidolytic antithrombin activity assay (via factor IIa) were affected. CONCLUSIONS: This multicenter trial confirms and also adds to existing data, demonstrating that laboratories should expect to observe strong interferences of coagulation tests with increasing concentrations of dabigatran. This finding might become particularly important in the elderly and in patients with renal impairment as well as patients whose blood is drawn at peak levels of dabigatran.