Thrombotic complications in patients with end-stage kidney disease are frequent. While being a lifesaving treatment for these patients, hemodialysis introduces a thromboinflammatory environment. Additionally, the extracorporeal hemodialysis circuit itself is prone to clotting because of an interaction between different activation mechanisms of the coagulation system, platelets, and the immune system. Anticoagulation of the patient and the machine is frequently complicated by bleeding. We discuss the factors important in this balancing act and touch on potential strategies that are on the horizon to target thromboinflammation.

Objective: Due to the high prevalence and incidence of cardio- and cerebrovascular diseases among dialysis-dependent patients with end-stage renal disease (ERSD) scheduled for kidney transplantation (KT), the use of antiplatelet therapy (APT) and/or anticoagulant drugs in this patient population is common. However, these patients share a high risk of complications, either due to thromboembolic or bleeding events, which makes adequate peri- and post-transplant anticoagulation management challenging. Predictive clinical models, such as the HAS-BLED score developed for predicting major bleeding events in patients under anticoagulation therapy, could be helpful tools for the optimization of antithrombotic management and could reduce peri- and postoperative morbidity and mortality. Methods: Data from 204 patients undergoing kidney transplantation (KT) between 2011 and 2018 at the University Hospital Leipzig were retrospectively analyzed. Patients were stratified and categorized postoperatively into the prophylaxis group (group A)—patients without pretransplant anticoagulation/antiplatelet therapy and receiving postoperative heparin in prophylactic doses—and into the (sub)therapeutic group (group B)—patients with postoperative continued use of pretransplant antithrombotic medication used (sub)therapeutically. The primary outcome was the incidence of postoperative bleeding events, which was evaluated for a possible association with the use of antithrombotic therapy. Secondary analyses were conducted for the associations of other potential risk factors, specifically the HAS-BLED score, with allograft outcome. Univariate and multivariate logistic regression as well as a Cox proportional hazard model were used to identify risk factors for long-term allograft function, outcome and survival. The calibration and prognostic accuracy of the risk models were evaluated using the Hosmer−Lemshow test (HLT) and the area under the receiver operating characteristic curve (AUC) model. Results: In total, 94 of 204 (47%) patients received (sub)therapeutic antithrombotic therapy after transplantation and 108 (53%) patients received prophylactic antithrombotic therapy. A total of 61 (29%) patients showed signs of postoperative bleeding. The incidence (p < 0.01) and timepoint of bleeding (p < 0.01) varied significantly between the different antithrombotic treatment groups. After applying multivariate analyses, pre-existing cardiovascular disease (CVD) (OR 2.89 (95% CI: 1.02−8.21); p = 0.04), procedure-specific complications (blood loss (OR 1.03 (95% CI: 1.0−1.05); p = 0.014), Clavien−Dindo classification > grade II (OR 1.03 (95% CI: 1.0−1.05); p = 0.018)), HAS-BLED score (OR 1.49 (95% CI: 1.08−2.07); p = 0.018), vit K antagonists (VKA) (OR 5.89 (95% CI: 1.10−31.28); p = 0.037), the combination of APT and therapeutic heparin (OR 5.44 (95% CI: 1.33−22.31); p = 0.018) as well as postoperative therapeutic heparin (OR 3.37 (95% CI: 1.37−8.26); p < 0.01) were independently associated with an increased risk for bleeding. The intraoperative use of heparin, prior antiplatelet therapy and APT in combination with prophylactic heparin was not associated with increased bleeding risk. Higher recipient body mass index (BMI) (OR 0.32 per 10 kg/m2 increase in BMI (95% CI: 0.12−0.91); p = 0.023) as well as living donor KT (OR 0.43 (95% CI: 0.18−0.94); p = 0.036) were associated with a decreased risk for bleeding. Regarding bleeding events and graft failure, the HAS-BLED risk model demonstrated good calibration (bleeding and graft failure: HLT: chi-square: 4.572, p = 0.802, versus chi-square: 6.52, p = 0.18, respectively) and moderate predictive performance (bleeding AUC: 0.72 (0.63−0.79); graft failure: AUC: 0.7 (0.6−0.78)). Conclusions: In our current study, we could demonstrate the HAS-BLED risk score as a helpful tool with acceptable predictive accuracy regarding bleeding events and graft failure following KT. The intensified monitoring and precise stratification/assessment of bleeding risk factors may be helpful in identifying patients at higher risks of bleeding, improved individualized anticoagulation decisions and choices of antithrombotic therapy in order to optimize outcome after kidney transplantation.

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

: Low molecular weight heparins are used during haemodialysis for thromboprophylaxis of the dialysis circuit, with plasma antifactor-Xa (anti-Xa) activity used as a surrogate measure for effective anticoagulation. However, this pharmacokinetic parameter does not always correlate with pharmacodynamic effects in patients. The aim of this study was to investigate the relationship between actual plasma levels of the low molecular weight heparins enoxaparin, anti-Xa activity, and global coagulation measurement of thrombin generation during haemodialysis. Blood was analysed from 16 adult patients with end-stage kidney disease at 0, 2, 4 h, and at completion of 31 dialysis sessions where single fixed doses of 20 (n = 3), 40 (n = 16), 60 (n = 6), or 80 (n = 6) mg of enoxaparin (equating to 0.23-1.07 mg/kg) were used as thromboprophylaxis. Plasma enoxaparin oligosaccharides [degree of polymerization (dp)6-dp16] were measured by high-performance size exclusion chromatography, anti-Xa activity by colourimetric assay, and thrombin generation by calibrated automated thrombogram. Plasma enoxaparin fragments were undetectable at the beginning of each dialysis, peaked at 2 h to levels that correlated with dose (r = 0.68, P < 0.001) then remained relatively stable. In contrast, therapeutic anti-Xa levels achieved at 2 h in 18 cases (58%) quickly dropped to only six cases (19%) at the end of dialysis, by which time thrombin generation had also recovered in 81% of patients. Statistical modelling revealed a threshold value of anti-Xa at 0.53 IU/ml that supressed thrombin generation to 15.28% of baseline (P < 0.001). Despite loss of anticoagulant activity in the majority of patients, plasma levels of enoxaparin oligosaccharides remained detectable and relatively unchanged throughout dialysis.

Heparin-induced thrombocytopenia (HIT) is a common antibody-mediated adverse reaction that occurs after heparin exposure. However, few case reports exist regarding nonantibody-mediated HIT.

An 81-year-old female diagnosed with rapidly progressive glomerulonephritis (RPGN) presented with atypical presentation of non antibody-meditated HIT after using heparin during hemodialysis.

Patient was initiated on hemodialysis and presented with thrombocytopenia following administration of heparin during dialysis. After ruling out all other causes of thrombocytopenia, HIT was suspected to be the cause. Patient's 4Ts score was 6 points, and Naranjo adverse drug reaction probability scale was a score of 10. However, enzyme-linked immunoassay for platelet factor 4 (PF4)/heparin antibodies was negative, indicating non-antibody mediated HIT. Patient eventually continued hemodialysis without heparin.

This patient case presented a rare presentation of HIT type I reaction due to heparin and demonstrated the importance of timely recognition of thrombocytopenia, appropriate diagnosis and management, and possible existence of a new atypical or subtype of HIT reaction.

Fibrinolysis is one of the methods extending the use of vascular access in patients with tunneled venous catheters thrombosis. The aim of this study was to assess one-year maintenance of tunneled catheters patency after first effective thrombolysis with urokinase and identify its predictors.

Retrospective analysis included 85 patients (age 69 ± 13 years) with permanent venous catheter thrombosis treated with urokinase at one center in the period 2010-2016. Urokinase was used (depending on weight) at a dose of 10,000 or 20,000 IU in an 8 h infusion to each catheter line. Assessment of one-year efficacy of fibrinolysis included the time between fibrinolysis and following thrombosis of the same catheter in patients that have previously obtained at least partial blood flow. The analysis included medication, comorbidities, catheter patency time and INR value during first thrombosis episode.

There were 62.4% patients with type-2 diabetes and 11.8% with neoplasm. The thrombolysis procedure was effective in 73 patients (85.9%). An analysis of the one-year efficacy of thrombolysis procedure included 73 patients. Among them, 23 experienced next episode of catheter-related thrombosis within a year postprocedure. Diabetes increased the risk for recurrent thrombosis [HR =3.19 (1.09-9.41); p = .03].

Patients with diabetes are at higher risk of recurrent catheter-related thrombosis and therefore may require more aggressive anticoagulation therapy for its prevention.