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Investigation: since this was a journal publication presenting data of a prospective study to assess the efficacy and safety of tpe using spectra optia in patients with alcohol associated acute on chronic liver failure (aclf) from (b)(6) 2019 to (b)(6) 2020, the disposable set was not requested for return.This was a single center prospective, nonrandomized, open-labeled, interventional pilot study conducted in the department of transfusion medicine and department of hepatology of a tertiary care center of north india over a period of one and half year ((b)(6) 2019 to (b)(6) 2020).The study had the approval of the institutional ethics committee, and all patients (or their caregiver) gave an informed written consent to participate in the study.Patients with alcohol-associated aclf of grade ii or moderate severity as per apasl aclf research consortium score (aarc score of 8-10) (aarc aclf scoring system detailed in table 1) were screened for the study and were managed with smt.Those not improving on smt after 1 week (failure to improve aarc score by =2 points) and without any microbiological/radiological evidence of infection were advised liver transplantation and were offered standard volume tpe if they did not have prospects for liver transplantation.Patients who agreed to undergo tpe were defined as cases and those not willing for tpe were taken as controls.Aclf patients with nonalcoholic etiologies, coexisting hepatocellular carcinoma or extra-hepatic malignancy, bleeding, pregnancy, multiorgan failure (=3 organ failures), severe pre-existing cardiopulmonary disease, apasl-aarc score >10 or <8, known allergic to plasma, protamine, or heparin, mechanically ventilated and requiring inotropic support at the time of enrolment were excluded from the study.Also, post liver transplant patients and those with severe systemic illness like hiv were excluded.In cases, standard volume tpe was performed on alternate days, using cell separator (optia spectra terumo bct).One to 1.5 plasma volume of the patient was removed in a single session at a rate of 40 ml/min with an equal volume of replacement fluid (group specific fresh frozen plasma [80%] and normal saline 20%).A total of five procedures were planned per patient (case).However, only nine cases completed all five tpes (refer to section 3).Venous access was obtained via a peripheral vascular access (preferably) or via central venous catheters (jugular/femoral, preferably jugular) in patients with poor peripheral veins.Control group had aarc scores similar to that of cases (grade ii apasl aclf) and was administered smt only.It involved empirical antibiotics as per protocol.Hepatic encephalopathy (he) was treated with lactulose and rifaximin.Ascites with diuretics if not contraindicated because of renal insufficiency or he.All patients received salt restricted, high protein diet (1.5 g/kg of proteins) either enterally/parenterally in addition to thiamine and multivitamins.Enrolled patients undergoing tpe or smt were monitored for any adverse event (ae) throughout the course of admission and were documented, classified into mild/moderate/severe, and managed.Aes were further analyzed for their imputability to tpe in cases.Follow-up of each patient was done telephonically on day 30 and then on day 90 of enrolment for mortality assessment.We enrolled 28 patients, 14 cases and 14 controls with a male:female ratio of 27:1.The baseline parameters of two groups were compared as shown in table 2.The mean duration of hospital stay was 19.57 ± 8.62 days for cases without any ventilatory support and 12.14 ± 8.34 days for the controls which was significantly less (p =.03) than that of cases.Also, the icu stay in the cases (6.5 days, iqr 9) was more than that of controls (2.5 days, iqr 6) but was not significantly different (p =.26).We observed 30-day mortality as 21% in both cases and controls (p =.50).The 90-day mortality was higher in the controls (50%) than in cases (36%), however, the difference was not statistically significant (p =.22).For the subset of cases who received all five tpes (n = 9), the 30-day mortality was nil vis-à-vis 21% for the control group (p =.07) and the 90-day mortality was 11% vis-à-vis 50% for the controls (p =.03).Among the 14 cases, only 9 patients underwent all 5 tpes as per the original treatment plan.Among the rest, one patient received three tpes post which the patient left against medical advice and in rest of the four patients, we could perform only a single procedure owing to aes.Of these, one patient refused to give consent for subsequent sessions and in the rest of the four, on account of serious aes, we decided to abort further sessions in discussion with the treating physician.Aes were noted in both cases (36%) and controls (29%) but this difference was not statistically significant (p =.67).Tpe procedure-related ae was seen in 1 out of total 51 procedures done (2%) in the form of a mild allergic reaction (itching on face and back) to replacement fluid (ffp) which was managed, and procedure was completed.Of the remaining four cases who witnessed aes, we noted asymptomatic hyponatremia (serum sodium <135 mmol/l) 24 h after the first pe in one patient which was corrected before further sessions.The other three cases experienced serious aes which were spontaneous bacterial peritonitis (n = 1), coagulopathy related ic bleed (n = 1) and atrial tachycardia (n = 1).We also observed aes in four controls, all of which were serious and necessitated medical intervention to preclude further deterioration.Two patients (14%) had coagulopathy related bleeding from the central line site insertion which was managed by compression with adrenaline-soaked gauze packs following which coagulopathy was corrected with guidance of sonoclot.One patient (7%) developed fever on day 5 which was attributed to fungal pneumonia (organism isolated: aspergillus fumigatus), was started on antifungal treatment, however patient expired 2 weeks later.Another control (7%) developed spontaneous bacterial peritonitis and was started on intravenous antibiotics however patient succumbed to death eventually.In this study, we assessed the efficacy and tolerability of tpe as against smt in alcohol-related apasl aclf patients and found that tpe was effective in reduction of serum bilirubin, ammonia, aptt, pt, inr and severity scores (aarc, mdf, and meld).Also, the procedure was well-tolerated with procedure-related aes in 2% of procedures only.Since this was a journal publication presenting data of a prospective study to assess the efficacy and safety of tpe using spectra optia in patients with alcohol associated acute on chronic liver failure (aclf) from january 2019 to may 2020, the lot numbers were not requested; therefore, a dhr search could not be conducted for this specific incident.All lots must meet acceptance criteria for release.According to the aabb circular of information for the use of human blood components (revised 2017), allergic reactions frequently occur (ie, 1-3% of plasma-containing components) as mild or self-limiting urticaria or wheezing that usually respond to antihistamines.More severe manifestations, including respiratory and cardiovascular symptoms, are more consistent with anaphylactoid/anaphylactic reactions and may require more aggressive therapy (see below).No laboratory procedures are available to predict these reactions.Anaphylactic reactions, characterized by hypotension, tachycardia, nausea, vomiting and/or diarrhea, abdominal pain, severe dyspnea, pulmonary and/or laryngeal edema, and bronchospasm and/or laryngospasm, are rare (<10/100,000 transfused units) but dangerous complications requiring immediate treatment with epinephrine.While these reactions have been reported in iga-deficient patients with anti-iga antibodies and patients with haptoglobin deficiency, most reactions are idiosyncratic and not associated with a specific serum protein deficiency, polymorphism, or identifiable cause.According to the scientific journal by nayak, ¿tpe induces marked changes in electrolytes but these changes are transient and do not warrant any intervention¿.According to the scientific journal by zhang, ¿spontaneous bacterial peritonitis is an infection of abdominal fluid, called ascites, that does not come from an obvious place within the abdomen, such as a hole in the intestines or a collection of pus.The condition typically affects people with liver disease, who often develop ascites as their disease worsens.According to therapeutic apheresis: a physician's handbook, when plasma is exchanged with a non plasma replacement solution, coagulopathy caused by dilution of coagulation factors is a potential problem.The prothrombin time and activated partial thromboplastin time rise and fibrinogen falls to an extent related to the intensity of the exchange.Despite these hemostatic alterations, hemorrhagic complications of dilutional coagulopathy are seldom encountered unless a patient is hemostatically compromised before treatment.Routine supplementation of replacement fluids with plasma or other sources of clotting factors is not recommended for nonbleeding patients whose baseline coagulation is normal.Redistribution and ongoing synthesis raise levels of most coagulation factors rapidly in the hours following an exchange.Fibrinogen is usually replaced more slowly and might be considered the rate-limiting factor determining the frequency of procedures performed without replacement of coagulation factors.However, the production of this acute-phase protein varies greatly among patients.Fibrinogen levels may decrease somewhat below 100 mg/dl if several procedures are performed on consecutive days.A level near 100 mg/ml is generally sufficient for hemostasis unless the individual has another hemostatic challenge.If fibrinogen decreases a great deal below 100 mg/dl, some physicians will then increase the interval between procedures or will use plasma replacement during the last part of the procedure to avoid a potential bleeding diathesis.18 fresh frozen plasma (ffp) is the preferred source of fibrinogen, and it supplies other coagulation factors as well.Ffp is seldom required, though, if tpe is performed at intervals of 72 hours or greater.Hemorrhage is rarely reported in patients undergoing a tpe series without plasma replacement if there is no underlying predisposition to bleeding.According to therapeutic apheresis: a physician's handbook, adverse events occur during therapeutic procedures with a frequency of 4.8%.Some of the most common reactions include fever, urticaria, hypocalcemic symptoms, pruritus, dyspnea, tachycardia, and mild hypotension.Root cause: a root cause assessment was performed for the allergic reaction.The authors attributed the replacement fluid, fresh frozen plasma as the root cause.A root cause assessment was performed for the asymptomatic hyponatremia which was corrected before further sessions.Based on the available information a definitive root cause could not be determined but it is likely due to one or a combination of the possible causes listed below: patient underlying disease large volume exchange conducted over a relatively short period treatment.A root cause assessment was performed for the bacterial peritonitis.The most likely root cause is the progression of the patient¿s liver failure.A root cause assessment was performed for the coagulopathy related ic bleed.Based on the available information a definitive root cause could not be determined but it is likely due to one or a combination of the possible causes listed below: exchanged with a non-plasma replacement solution resulting in coagulopathy caused by dilution of coagulation factors.Large volume exchange conducted over a relatively short period treatment.Patient was hemostatically compromised before treatment.A root cause assessment was performed for the atrial tachycardia.Based on the available information a definitive root cause could not be determined.Tachycardia are common side effects of therapeutic apheresis procedures.They are typically caused by the patient's disease state, the rate of ac infusion, the length of the procedure, the patient's sensitivity to the procedure and/or the hemodynamic stress of the procedure.Article citation: ramakrishnan, s.,hans, r.,duseja, a.,sharma, r.R.Therapeutic plasma exchange is a safe and effective bridge therapy in patients with alcohol-associated aclf not having immediate prospects for liver transplantation¿a case-control, pilot study.Journal of clinical apheresis.2022;1¿10.
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