Precise control of blood clotting and rapid reversal of anticoagulation are essential in many clinical situations. We were successful in modifying a thrombin‐binding aptamer with a red‐light photocleavable linker derived from Cy7 by Cu‐catalyzed Click chemistry. We were able to show that we can successfully deactivate the modified aptamer with red light (660 nm) even in human blood—restoring the blood's natural coagulation capability.

Direct oral anticoagulants (DOACs) apixaban and rivaroxaban are broadly used in the management of venous thromboembolism (VTE). Although not routinely required, measurement of their plasma concentration is advised for an increasing number of indications. Due to the lack of therapeutic ranges, current guidelines recommend reporting DOAC plasma levels together with expected levels from previous pivotal studies. The aim of this study was to assess DOAC level variation in a large VTE patient population. Drug concentrations determined by measurement of the anti-Xa-activity using drug-specific calibrators in citrated plasma samples from patients on rivaroxaban (n = 1471) or apixaban (n = 725) were analyzed. Observed 5th–95th percentile ranges of apixaban peak/trough levels (63–299/13–114 ng/mL for 5 mg, 37–161/7–68 ng/mL for 2.5 mg twice daily) were similar to previously reported mass-spectrometry-based reference data, and 10th–90th percentile ranges of rivaroxaban peak/trough levels (98–367/8–55 ng/mL for 20 mg, 51–211/5–27 ng/mL for 10 mg once daily) were even narrower. Age and drug levels correlated weakly (r ≤ 0.330). Drug levels measured repeatedly in subgroups of patients showed a strong correlation (r ≥ 0.773). In conclusion, anti-Xa-activity-based measurement of apixaban and rivaroxaban yields reliable results. However, the paucity of levels off-range underlines the need for evidence-based thresholds to better assist clinical decision making.

Inactivation of thrombin by the endogenous inhibitor antithrombin (AT) is a central mechanism in the regulation of hemostasis. This makes hereditary AT deficiency, which is caused by SERPINC1 gene mutations, a major thrombophilic risk factor. Aim of this study was to assess to what extent AT mutations impair thrombin inhibition kinetics. The study population included 36 thrombophilic patients with 19 different mutations and mean AT levels of 65% in a thrombin-based functional assay, and 26 healthy controls. To assess thrombin inhibition kinetics, thrombin (3.94 mU/mL final concentration) was added to citrated plasma. Subsequently, endogenous thrombin inhibition was stopped by addition of the reversible thrombin inhibitor argatroban and the amount of argatroban-complexed thrombin quantified using an oligonucleotide-based enzyme capture assay. The plasma half-life of human thrombin was significantly longer in patients with AT mutations than in the controls (119.9 versus 55.9 s). Moreover, it was disproportionately prolonged when compared with preparations of wild type AT in plasma, in whom a comparable thrombin half-life of 120.8 s was reached at a distinctly lower AT level of 20%. These findings may help to better understand the increased thrombotic risk of SERPINC1 mutations with near normal AT plasma levels in functional assays.

To summarize the evidence on non-hemorrhagic adrenal infarction (NHAI) and identify questions arising in diagnosis and management, cases in the PubMed database were merged with our case series. A total of 92 publications were retrieved, 15 of which reported on NHAI during pregnancy. Including the four in our case series, 24 cases have been described so far. Severe, unremitting pain requiring opioid analgesia was the leading symptom, often combined with nausea and vomiting. Laboratory results were non-contributory in most cases. Diagnosis was established via MRI in nine cases (37.5%) and via CT in six (25%); nine patients (37.5%) underwent both investigations. Location was predominantly on the right side (n = 16, 66.7%). In addition to analgesia, anticoagulation with heparin was commenced in 18 cases (75%). When thrombophilia screening was performed, major thrombogenic polymorphisms were detected in six cases (33.3%). One woman developed signs of adrenal insufficiency. The reported perinatal outcome was unremarkable. Unilateral NHAI has emerged as a rare but important cause of severe abdominal pain in pregnancy. The threshold to perform an MRI in pregnant women with characteristic clinical findings should be low. To prevent fetal radiation exposure, diagnostic imaging via CT should be avoided. In addition to symptomatic treatment with opioid analgesia, initiation of anticoagulant treatment should be strongly considered.

Background: To report on prophylactic therapy for hyperfibrinolysis with tranexamic acid (TXA) during expectant management (EM) in the placenta accreta spectrum (PAS). Methods: This is a monocentric retrospective study of women with PAS presenting at our hospital between 2005 and 2021. All data were retrospectively collected through the departmental database. Results: 35 patients with PAS were included. EM was planned in 25 patients prior to delivery. Complete absorption of the retained placenta was seen in two patients (8%). Curettage was performed in 14 patients (56%). A hysterectomy (HE) was needed in seven (28%) patients; 18 patients (72%) underwent uterus-preserving treatment without severe complications. The mean duration of EM was 107 days. The mean day of onset of hyperfibrinolysis and beginning of TXA treatment was day 45. The mean nadir of fibrinogen level before TXA was 242.4 mg/dL, with a mean drop of 29.7% in fibrinogen level. Conclusions: Our data support EM as a safe treatment option in PAS. Hyperfibrinolysis can be a cause of hemorrhage during EM and can be treated with TXA. To our knowledge, this is the first cohort of patients with EM of PAS in whom coagulation monitoring and use of TXA have been shown to successfully treat hyperfibrinolysis.

Objectives: Analysis of platelet glycoprotein (GP) expression by flow cytometry is applied for diagnostic confirmation of GP-associated thrombocytopathies. While platelet-rich plasma may be used for distinct identification of target events, this strategy is not feasible for small sample volumes or for patients showing low platelet counts and/or giant platelets. However, also the use of whole blood (WB) is hampered by the difficulty to discriminate platelets from red blood cells (RBC) in such patients. To circumvent these limitations, we evaluated the feasibility of a RBC gating-out strategy. Methods: In addition to platelet GPIb, GPIIa/IIIa, as well as P-selectin (CD62P), citrated whole blood (CWB) samples were stained for RBC-specific glycophorin A (CD235a). CD235a-negative platelet events were further discriminated by forward-/side-scatter characteristics and platelet GP expressions analyzed relative to that of a healthy control sample processed in parallel. Results: Established reference intervals allowed for clear identification of decreased GPIIb/IIIa- or GPIb expression pattern in samples of patients with confirmed Glanzmann thrombasthenia or Bernard-Soulier syndrome, respectively. It could be shown that the analysis of 2,500 platelet events is sufficient for reliable GP expression analysis, rendering the proposed method applicable to samples with low platelet counts. Conclusions: This study demonstrates the feasibility of CD235a-based exclusion of RBC for platelet GP expression analysis in CWB. In contrast to direct staining of platelet-specific antigens for target identification, this indirect gating out approach is generally applicable independent of any underlying platelet GP expression deficiency.