Low Incidence of hepatic sinusoidal obstruction syndrome/veno-occlusive disease in adults undergoing allogenic stem cell transplantation with prophylactic ursodiol and low-dose heparin

Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease (VOD) is a complication after allogenic hematopoietic stem-cell transplantation (allo-HSCT) with high mortality. The purpose of this study was to assess the incidence and outcome of SOS in patients after allo-HSCT with the impact of ursodeoxycholic acid (UDCA) and low-dose heparin as SOS prophylaxis. Out of 1016 patients, 23 developed SOS, with a cumulative incidence of 2.3% (95% CI 1.3–3.3) 6 months after HSCT. Approximately one quarter of these patients (26.1%) had late-onset SOS. A high proportion were very severe SOS cases (74%), and 83% of the patients were treated with defibrotide (DF). In multivariate analysis, advanced disease (p = 0.003), previous HSCT (p = 0.025) and graft versus host disease (GvHD) prophylaxis by post-transplant cyclophosphamide (PTCy) (p = 0.055) were associated with the development of SOS. The 1-year overall survival (OS) was significantly lower in the SOS group compared to patients without SOS (13% versus 70%, p = 0.0001). In conclusion, we found a low incidence of SOS in patients receiving low-dose heparin and UDCA prophylactically, but among SOS patients, a high mortality. Low-dose heparin and UDCA might be a prophylactic approach for SOS.

Optimal antithrombotic regimen in patients with cardiogenic shock on ImpellaTM mechanical support: less might be more

Background Bleeding and ischemic complications are the main cause of morbidity and mortality in critically ill cardiogenic shock patients, supported by short-term percutaneous mechanical circulatory support (pMCS) devices. Hence, finding the optimal antithrombotic regimen is challenging. Bleeding not only occurs because of heparin and antiplatelet therapy (both required in the prevention of pump and acute stent thrombosis) but also because of device- and disease related coagulopathy. To prevent clotting-related device failure, most centers target full therapeutic heparin anticoagulation levels in left ventricular (LV) Impella™ supported patients in analogy with Veno-Arterial Extracorporeal Membrane Oxygenation. We aimed to investigate the safety (related to bleeding and thrombotic complications) of targeting low-dose versus therapeutic heparin levels in left Impella™-supported cardiogenic shock patients on dual antiplatelet therapy (DAPT). Methods In this hypothesis generating pilot study, we investigated 114 patients supported for at least two days by LV Impella™ mechanical support due to cardiogenic shock at three tertiary ICUs, highly specialized in mechanical support. Low-dose heparin (aPTT 40–60s or anti-Xa 0.2–0.3) was compared to standard of care (aPTT 60–80s or anti-Xa 0.3–0.5). Major adverse cardio- and cerebrovascular events (MACCE; composite of death, myocardial infarction, stroke/transient ischemic attack) and BARC bleeding (bleeding academic research consortium classification) during 30 day follow-up were assessed. Inverse probability of treatment weighting (IPTW) analysis was calculated with age, gender, arterial hypertension, diabetes mellitus, smoking, chronic kidney disease, previous stroke, previous myocardial infarction, previous coronary arterial bypass grafting, hypercholesterolemia and DAPT as matching variables. COX regression analysis was conducted to test for robustness. Results IPTW revealed 52 patients in the low-dose heparin group and 62 patients in the therapeutic group. Mean age of patients after IPTW was 62±16 years in the intermediate and 62±13 years in the therapeutic group (p=0.99). 25% and 42.2% were male (p=0.92). Overall bleeding events and major (BARC3b) bleeding events were higher in the therapeutic heparin group (overall bleeding: Hazard ratio [HR]=2.58, 95% confidence interval [CI] 1.2–5.5; p=0.015; BARC 3b: HR=4.4, 95% CI 1.4–13.6, p=0.009). Minor bleeding (BARC3a) as well as MACCE and its single components (ischemic events) did not differ between both groups. These findings were robust in the COX regression analysis. Conclusion In this pilot analysis, low-dose heparin in 114 LV Impella™ cardiogenic shock patients was associated with less bleeding without increased ischemic events, adjusted for DAPT. Reducing the target heparin levels in critically ill patients supported by LV Impella™ might improve the outcome of this precarious group. These findings need to be validated in randomized clinical trials. Funding Acknowledgement Type of funding source: None

P1119ASSOCIATION OF VARIOUS RISK FACTORS WITH HEMODIALYZER SET CLOT INCIDENCES WHEN USING LOW DOSE UF- HEPARIN OF 400 IU BOLUS AND 400 IU INFUSION IN MAINTENANCE DIALYSIS SESSION : A CASE CONTROL STUDY

Background and Aims Efforts were made in the past to reduce the use of heparin as anticoagulation to escape from the its Sid effects like Bleeding and HIT among others. We use Low dose UF -heparin use with bolus of 400 IU and 400 IU/hour infusion as an anticoagulation in hemodialysis patients. Set clot incidences were comparable to other studies. The objectives of this study is to see aassociations of different risk factors with hemodialyzer set clot incidences using Low dose heparin Infusion protocol in maintenance haemodialysis session. Method Data were obtained from the outpatient haemodialysis unit at tertiary care Hospital in Karachi, Pakistan. UF-low dose heparin 400 I.U bolus and 400 I.U maintenance infusion protocol were given to all patient. Case to control ratio was approximately 1:4. 300 cases of set clot were taken and 1200 control sessions without set clot outcome were matched for heparin use taken from the dialysis unit. The crude odds ratios (OR’s) and adjusted ORs (aORs) for various risk factors were obtained using conditional logistic regression. Results In a prelimary part of the study the incidence of set clot was 7% (309/4000 sessions) Age, dialysis vintage, hemoglobin level, Blood flow rate and type of anti-platelet therapy were significantly associated to the incidence of set clot. Among patients having age > 40 yrs. the odds of set clot were 2.8 (95% CI= 1.8-4.3) as compare to the patients with age ≤ 40 yrs. The odds of set clot were 0.268(95% CI=0.081-.88) among patients with hemodialysis vintage less than 1 year as compare to those who have more than 1 year. Blood flow rate <350 ml/min have an odds of 1.03(95%CI=0.76-1.40) of set clot incident as compare to BFR>350 ml/min. Those patients with Hemoglobin < 9 gm/dl have odds of set clot of 0.67(95%CI =0.48-0.92) as compare to hemoglobin > 9 gm/dl. Off all patients ,60.36% patients were either on aspirin or clopidogrel while around 9.58% were on combine antiplatelets therapy. The odds of set clot were 4.6 (95% CI =1.9-10.8) among patients on Combine antiplatelet therapy as compare to no antiplatelet therapy. Conclusion Age, low Blood flow rate and combine antiplatelet therapy (aspirin and clopidogrel) are positively associated with set clot accidents in dialysis sessions. Dual anti platelet therapy patients are given in ischemic heart disease patients hence Blood flow pumps are kept at lower speed which can increase the risk of set clot. Lesser duration on Hemodialysis (i.e. less than 1 year) and low hemoglobin levels are protective for incidence of set clot in our study population.

Activated Clotting Time (ACT) for Monitoring of Low-Dose Heparin: Performance Characteristics in Healthy Adults and Critically Ill Patients

Dose adjustment of unfractionated heparin (UFH) anticoagulation is an important factor to reduce hemorrhagic events. High doses of heparin can be monitored by Activated Clotting Time (ACT). Because of limited information about the monitoring of low-dose heparin we assessed monitoring by ACT, aPTT and anti-Xa. Blood samples from healthy volunteers (n = 54) were treated ex vivo with increasing UFH doses (0-0.4 IU/ml). Samples from ICU-patients (n = 60), were drawn during continuous UFH infusion. Simultaneous ACT measurements were performed using iSTAT and Hemochron. In UFH treated blood, iSTAT and Hemochron showed a significant change of ACT at ≥0.075 IU/ml and ≥0.1 IU/ml UFH, respectively. In ICU-patients no relationship between ACT and either UFH dose, aPTT and anti-Xa was observed. Hemochron was affected by antithrombin and platelet count. iSTAT was sensitive to CRP and hematocrit. A moderate correlation was identified between UFH dose and aPTT (R2 = 0.196) or anti-Xa (R2 = 0.162). In heparin-spiked blood, ACT is sensitive to heparin at levels of ≥0.1 IU/ml heparin. In ICU-patients, ACT did not correlate with UFH dose or other established methods. Both systems were differently influenced by certain parameters.