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Summary: Pregnancy is a potential trigger of acute thrombotic thrombocytopenic purpura (TTP). The management of pregnancy‐associated immune‐mediated TTP (iTTP) can be challenging, especially when it is refractory to standard treatment. Caplacizumab, a nanobody to von Willebrand factor (VWF) blocking its A1 domain, is a valuable new therapeutic option. Its use is, however, not approved during pregnancy and breastfeeding. We describe the successful off‐label administration of caplacizumab during pregnancy and delivery in a patient with refractory iTTP. The favourable outcome without significant thrombotic or haemorrhagic complications indicates that caplacizumab may be an effective and safe treatment option in refractory iTTP during pregnancy. [ABSTRACT FROM AUTHOR]

While implanted port catheters ("PORTs") have historically been the standard device for intravenous systemic anticancer therapy, the use of peripherally inserted central catheters (PICCs) has increased continuously and reliable catheter selection guidelines are lacking. We compare complication rates of PORTs and PICCs in cancer treatment in a retrospective study of 3365 patients with both solid organ (n = 2612) and hematologic (n = 753) malignancies, between 2001 and 2021. 26.4% (n = 890) of all patients were treated via PICCs and 73.6% (2475) via PORTs. 20.7% (578) experienced a major catheter‐related complication with a higher rate in PICCs than in PORTs (23.5% vs 14.9%, P <.001). Among major complications, infections and mechanical complications were more common in PICCs than in PORTs (11.9% vs 6.4%, P =.001, 7.3% vs 4.2%, P =.002), whereas the rate of thrombosis was similar (3.4% vs 3.0%, P =.9). While PORTs had a higher rate of periprocedural complications (2.7% vs 1.1%, P <.05), PICCs overall complication rate exceeded PORTs within 3 days from implantation. Median follow‐up was 49 (PICC) and 60 weeks (PORT). PORTs are safer and therefore should be preferred in this setting regardless of catheter dwell time. [ABSTRACT FROM AUTHOR]

Background: This study investigates the impact of preoperative calculated rivaroxaban (RXA) plasma concentration on perioperative red blood cell (RBC) loss.Study Design and Methods: In this retrospective single-center study, we identified patients with RXA intake according to a preoperative determination of RXA levels within 96 hours before surgery. RXA plasma concentration at the beginning of surgery was then calculated from the last RXA intake using a single-compartment pharmacokinetic model with four categories of RXA concentration (≤20, 21-50, 51-100, and >100 μg/L). Patients were classified into surgery with high (≥500 mL) or low (<500 mL) expected blood loss. Perioperative bleeding was determined by calculating RBC loss.Results: We analyzed 308 surgical interventions in 298 patients during the period from January 2012 to July 2018. Among patients undergoing surgery with low expected blood loss, RBC loss varied from 164 mL (standard deviation [SD], 189) to 302 mL (SD, 397) (p = 0.66), and no association of calculated RXA concentration with RBC loss was observed. In patients undergoing surgery with high expected blood loss, we found a significant correlation of calculated RXA concentration with RBC loss (Pearson's correlation coefficient, 0.29; p = 0.002). RBC loss increased with rising RXA concentration from 575 mL (SD, 365) at RXA concentration of 20 μg/L or less up to 1400 mL (SD, 1300) at RXA concentration greater than 100 μg/L. RXA concentration greater than 100 μg/L was associated with a significant increase of in RBC loss of 840 mL (95% confidence interval, 360-1300; p < 0.001). Transfusion of RBC and fresh frozen plasma units tended to increase in patients with RXA concentrations greater than 100 μg/L. The proportion of patients treated with prothrombin complex concentrate and coagulation factor XIII concentrate increased significantly with higher RXA concentrations.Conclusion: Only in surgery with high expected blood loss, a calculated RXA concentration of greater than 100 μg/L was associated with a significant increase of perioperative RBC loss. [ABSTRACT FROM AUTHOR]

Robust viability assessment of grafts during normothermic liver perfusion is a prerequisite for organ use. Coagulation parameters are used commonly for liver assessment in patients. However, they are not yet included in viability assessment during ex situ perfusion. In this study, we analysed coagulation parameters during one week ex situ perfusion at 34℃. Eight discarded human livers were perfused with blood‐based, heparinised perfusate for one week; perfusions in a further four livers were terminated on day 4 due to massive ongoing cell death. Coagulation parameters were well below the physiologic range at perfusion start. Physiologic levels were achieved within the first two perfusion days for factor V (68.5 ± 35.5%), factor VII (83.5 ± 26.2%), fibrinogen (2.1 ± 0.4 g/L) and antithrombin (107 ± 26.5%) in the livers perfused for one week. Despite the increased production of coagulation factors, INR was detectable only at 24h of perfusion (2.1 ± 0.3) and prolonged thereafter (INR > 9). The prolongation of INR was related to the high heparin level in the perfusate (anti‐FXa > 3 U/mL). Intriguingly, livers with ongoing massive cell death also disclosed synthesis of factor V and improved INR. In summary, perfused livers were able to produce coagulation factors at a physiological level ex situ. We propose that single coagulation factor analysis is more reliable for assessing the synthetic function of perfused livers as compared to INR when using a heparinised perfusate. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Data on the perioperative bleeding risk associated with elevated plasma levels of direct factor Xa inhibitors (FXa inhibitors) are limited. This study examines perioperative red blood cell (RBC) loss in patients undergoing urgent surgery with a residual FXa inhibitor level exceeding 100 mcg/L and without preoperative FXa inhibitor reversal.This retrospective analysis includes data from 32 patients who underwent urgent noncardiac surgery between 2018 and 2022. This study aims to analyze perioperative RBC loss in patients undergoing urgent surgery with a residual FXa inhibitor level exceeding 100 mcg/L and without preoperative FXa inhibitor antidote‐based reversal or unspecific treatment with 4‐factor prothrombin complex concentrate (PCC). All patients were managed using a watch‐and‐wait strategy.The last determination of FXa inhibitor plasma concentration prior to surgery showed a median of 245 mcg/L (IQR 144–345), with a median time interval of 3.8 h (IQR 2.4–7.2) before incision. Median RBC loss during surgery was 49 mL (IQR 0–253), 189 mL (IQR 104–217) until POD1 and 254 mL (IQR 58–265) until POD3. Only one patient required intraoperative treatment with 4‐factor‐PCC and none required reversal with andexanet alfa. Linear regression models found no significant influence of FXa inhibitor plasma levels on intraoperative RBC loss. Rivaroxaban was associated with higher RBC loss until postoperative Day 1 compared with apixaban. No thromboembolic events were observed.Despite markedly elevated plasma concentrations of residual direct FXa inhibitors, perioperative RBC loss was limited in patients undergoing urgent noncardiac surgery. The intraoperative watch‐and‐wait strategy with selective intraoperative FXa inhibitor reversal or treatment only when required appears to be an appropriate approach. [ABSTRACT FROM AUTHOR]

Summary: A universal anti‐Xa assay for the determination of rivaroxaban, apixaban and edoxaban drug concentrations would simplify laboratory procedures and facilitate widespread implementation. Following two pilot studies analysing spiked samples and material from 698 patients, we conducted a prospective multicentre cross‐sectional study, including 867 patients treated with rivaroxaban, apixaban or edoxaban in clinical practice to comprehensively evaluate a simple, readily available anti‐Xa assay that would accurately measure drug concentrations and correctly predict relevant levels in clinical practice. Anti‐Xa activity was measured by an assay calibrated with low‐molecular‐weight heparin (LMWH) in addition to ultra‐high performance liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). As an external validation, LMWH‐calibrated anti‐Xa activity was also determined in nine external laboratories. The LMWH‐calibrated anti‐Xa activity correlated strongly with rivaroxaban, apixaban or edoxaban drug levels [rs = 0·98, 95% confidence interval (CI) 0·98–0·98]. The sensitivity for the clinically relevant cut‐off levels of 30, 50 and 100 µg/l was 96·2% (95% CI 94·4–97·4), 96·4% (95% CI 94·4–97·7) and 96·7% (95% CI 94·3–98·1) respectively. Concordant results were obtained in the external validation study. In conclusion, a universal, LMWH‐calibrated anti‐Xa assay accurately measured rivaroxaban, apixaban and edoxaban concentrations and correctly predicted relevant drug concentrations in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Different types of fresh-frozen plasma (FFP) exist, and the concentrations of plasma proteins vary between individuals and blood groups. Furthermore, processing may also influence the content. Quarantine-stored plasma (qFFP) and plasma that was pathogen-reduced using blood-safety (Intercept) technology (piFFP) were analyzed regarding procoagulant and anticoagulant hemostasis proteins, including endogenous thrombin (thrombin-generation) potential (ETP).Materials and Methods: Thirty-five samples of each type of FFP were analyzed using only male Blood Group O donors. FFP units were stored frozen for comparable periods of time before plasma protein content was assessed. Once the units were thawed, all tests were completed within 4 hours. The results are presented as means ± standard deviations or as median (minimum; maximum) and were compared using independent-sample t tests (significance, p < 0.01).Results: Significantly higher concentrations of adintegrin-like and metalloprotease with thrombospondin type-13 motifs (ADAMTS13), fibrinogen, Factor (F)V, FVIII, FXIII, protein S, protein S activity, antithrombin, microvesicle (<900 nm), and α2 antiplasmin were observed in qFFP. The variability of factors was significantly lower in piFFP. Tissue factor (TF) at 1 picomolar (pM) exhibited significantly longer lag time, a lower peak, lower ETP, and a lower velocity index in qFFP compared with piFFP. In TF at 5 pM, significant differences in lag time (longer in qFFP), velocity index (lower in qFFP), and peak (lower in qFFP) were observed. Rotational thromboelastometry revealed a significantly longer (p = 0.002) clot-formation time with intrinsic thromboelastometry for piFFP and a significantly shorter clotting time (p = 0.004) with thromboelastometry fibrinogen testing for piFFP.Conclusion: Pathogen reduction reduces procoagulant and anticoagulant coagulation factors as well as variability. A thrombin-generation assay showed no reduced ETP and no supraphysiological thrombin generation. None of the FFP preparations is likely to be effective for treating fibrinogen deficiency. [ABSTRACT FROM AUTHOR]

Background Trials of transfusions of platelets ( PLTs) treated with amotosalen-based pathogen reduction ( PR) showed lower corrected count increments ( CCIs) compared to conventional PLT components ( PCs). However, PR-PLTs and conventional PCs often differed in various factors besides PR. We compared transfusion efficacy of single-donor apheresis PCs treated with PR or gamma irradiation. Study Design and Methods Hematologic patients were assigned to receive PR-PLTs or gamma-irradiated conventional PCs, both prepared in PLT additive solution ( PAS). One-hour CCI (primary endpoint), 24-hour CCI, time to next PLT transfusion, and transfusion requirement of red blood cells and plasma were analyzed. Results Forty-four patients assigned to PR-PLTs received 220 PR-PLTs and 136 conventional PCs; 72 controls received 517 conventional PCs. No differences between patient groups were observed for mean (±standard deviation [SD]) 1-hour CCI (11.4 [±4.9] for PR-PLT vs. 11.0 [±4.9] for controls), mean (±SD) 24-hour CCI (6.1 [±4.4] for PR-PLTs vs. 6.2 [±4.8] for controls), and for the other evaluated outcomes. No differences between PC types were observed for mean (±SD) 1-hour CCI (10.6 [±6.7] for PR-PLTs vs. 9.9 [±6.2] for conventional PCs) and mean 24 hour- CCI (3.3 [±3.9] for PR-PLTs vs. 4.2 [±5] for conventional PCs). Thirty-five percent of PR-PLTs and 38% of conventional PCs (p = 0.63) were associated with 1-hour CCIs of less than 7.5. Inadequate 24-hour CCIs were observed for 72% of PR-PLTs and 64% of conventional PCs (p = 0.002). Conclusions Transfusion efficacy of single-donor apheresis PCs in PAS treated with amotosalen PR versus gamma irradiation is comparable. [ABSTRACT FROM AUTHOR]

Summary. Genetic analysis of the ADAMTS13 locus identified six mutations in the ADAMTS13 genes of two brothers suffering from constitutional thrombotic thrombocytopenic purpura (TTP): a stop codon leading to a truncated protein on the paternal ADAMTS13 allele and five amino acid exchanges on the maternal allele, three of which were single nucleotide polymorphisms. The other two mutations, not detected in 230 sequenced alleles of healthy control subjects, are, therefore, probably responsible, alone or as part of a combination, for the severe ADAMTS13 deficiency. We also investigated the feasibility of using recombinant ADAMTS13 (rADAMTS13) for normalization of von Willebrand factor-cleaving protease (VWF-cp) activity in plasma of the two congenitally deficient patients. Addition of rADAMTS13 to their plasma restored the VWF-processing pattern to normal, suggesting the potential usefulness of rADAMTS13 for therapy and prophylaxis of familial TTP. [ABSTRACT FROM AUTHOR]