Therapeutic Plasma Exchange Research Articles

Therapeutic plasma exchange in critically ill children: A single center experience.

Therapeutic plasma exchange (TPE) is used in a wide spectrum of diseases in critically ill pediatric patients. We aim to review the indications, complications, safety, and outcomes of critically ill children who received TPE. All of the TPE procedures performed in a pediatric intensive care unit providing tertiary care during 19 years (January 2013-January 2023) were evaluated retrospectively. A total of 154 patients underwent 486 TPE sessions. Median age was 6 years (2-12.5) and 35 children had a body weight of <10 kg (22.7%). Number of organ failure was 4 (2-6). Liver diseases were the most common indication for TPE (31.2%) followed by sepsis with multiorgan dysfunction syndrome (27.3%). Overall survival rate was 72.7%. The highest mortality was observed in hemophagocytic lymphohistiocytosis group. Non-survivors had significantly higher number of organ failure (p < 0.001), higher PRISM score (p < 0.001), and higher PELOD score on admission (p < 0.001). Adverse events were observed in 68 (13.9%) sessions. Hypotension (7.8%) and hypocalcemia (5.1%) were the most frequent adverse events. TPE is safe for critically ill pediatric patients with experienced staff. Survival rate may vary depending on the underlying disease. Survival decreases with the increase in the number of failed organs.

Efficiency of therapeutic plasma exchange in critically ill systemic rheumatologic diseases: A single-center 9-year experience.

Therapeutic plasma exchange (TPE), an effective method to eliminate harmful soluble mediators associated with tissue injury, serves as a crucial intervention for systemic rheumatologic diseases (SRDs). However, its value in critically ill SRDs remains uncertain. This retrospective study aims to evaluate the efficacy of TPE in SRDs. Critically ill SRD patients admitted to the department of intensive care unit of a large tertiary hospital receiving TPE from January 2011 to December 2019 were included. A total of 91 critically ill SRD patients received TPE were enrolled. Their mean age was 47.67 ± 16.35 years with a female predominance (n = 68). Significant decrease in SOFA score post-TPE treatment was observed (p < 0.05). There were no TPE-related fatalities. Improvement was observed in 64 (70.32%) patients. This study shows favorable clinical outcomes. TPE may be an acceptable treatment option for critically ill SRD patients.

Retrospective evaluation of indications for therapeutic plasmapheresis procedures applied in our center

Aims: Therapeutic plasma exchange (TPE) is a process in which pathological substances (autoantibodies, alloantibodies, immune complexes, lipoproteins, cryoglobulins, etc.) in the patient's plasma are removed from the body along with the patient's plasma and replaced with replacement fluid (allogeneic donor plasma, colloid, crystalloid). It is applied as a complementary treatment method in many diseases that can cause high morbidity and mortality, either in the primary treatment of the disease (main treatment) or as an adjunctive treatment in the main treatment of the disease. Today, TPE is increasingly used in various clinics (toxicology, endocrinology, etc.) for different diseases/causes, especially in hematological, neurological, and nephrological diseases. Methods: Adult patients who underwent therapeutic plasma exchange in our therapeutic apheresis center between May 2017 and May 2019 were included in the study, and the data were obtained by retrospectively reviewing patient records in the therapeutic apheresis center and our hospital's automation system. Results: In the two-year period, a total of 1957 TPE procedures were performed on 441 patients. It was determined that 255 of the patients undergoing TPE procedures (57.8%) had indications related to liver diseases (acute liver failure, acute exacerbation of chronic liver failure, and rejection after liver transplantation), while 186 (42.2%) had indications related to non-liver diseases. Among the 186 patients undergoing TPE for non-liver diseases, it was found that 69 (37.1%) were for hematological, 38 (20.4%) for neurological, 32 (17.2%) for renal, and 47 (25.3%) for other diseases. Conclusion: Due to the large number of liver transplants performed in our Liver Transplant Institute, the majority of TPE indications at our hospital are related to liver diseases. However, the evaluation of TPE indications excluding liver diseases revealed that the indications and frequencies of patients undergoing TPE were consistent with the overall results reported in studies from both our country and abroad.

Management of pediatric liver failure with therapeutic plasma exchange and continuous renal replacement therapy: A retrospective observational study.

Liver failure represents a critical medical condition, marked by the rapid decline of hepatic functions. Emerging therapies, notably therapeutic plasma exchange (TPE) and continuous venovenous hemodiafiltration (CVVHDF), have demonstrated potential in mitigating these conditions through their roles in detoxification and hepatic support. The utility of these treatments, whether applied individually or in tandem, constitutes a significant area of research concerning the management of liver failure in pediatric patients. This study aims to evaluate the role and efficacy of TPE or TPE combined with CVVHDF in the treatment of liver failure among children. This retrospective study was conducted in a LTICU by reviewing the medical history of pediatric patients aged 1 month to 18 years. Patients were admitted between January 1, 2021 and December 1, 2023 due to acute liver failure or acute-chronic liver failure. The study evaluated those who received TPE or continuous renal replacement therapy combined with TPE. In statistical analyses, a P-value of <.05 was considered statistically significant. The study involved 24 patients with liver failure, comprising 13 males and 11 females. Sixteen patients (66.6%) received only TPE, while 8 patients (33.4%) were treated with TPE and CVVHDF. For patients treated only with TPE, the median INR reduced from 3.1 to 1.26, alanine aminotransferase from 1255 to 148, and aspartate aminotransferase from 2189 to 62. Similar significant reductions were observed in the TPE and CVVHDF group: INR from 3.9 to 1.26, alanine aminotransferase from 1749 to 1148, and aspartate aminotransferase from 1489 to 62. These changes were statistically significant with P-values of .01 for each parameter in both groups. Overall, 14 patients survived without requiring a liver transplant, while 4 patients underwent liver transplantation. Our study on pediatric liver failure treatment shows that both standalone TPE and its combination with CVVHDF are effective, especially as a bridge to transplantation. With 58% transplant-free survival, these therapies demonstrate significant clinical improvements. Future multicentric studies are needed for broader validation of these findings in liver failure management.

A lower fibrinogen threshold does not lead to increased bleeding risk in patients receiving therapeutic plasma exchange: A prospective single-center analysis.

Plasma exchange (PLEX) therapy is indicated for several disorders. The 5% albumin is often used as a sole replacement fluid during most PLEX. However, each 1.0 plasma volume exchange depletes coagulation factors by ~65%. Although most coagulation factors recover to hemostatic levels within 24 h post-PLEX, fibrinogen requires 48-72 h to recover. Fibrinogen is the key coagulation protein for hemostasis. Therefore, fibrinogen is often monitored during the acute course of PLEX, and plasma is supplemented to prevent bleeding if fibrinogen is <100 mg/dL. We conducted a prospective, single-center, observational study to evaluate bleeding risk in adults who received an acute course of PLEX with a fibrinogen level of 80-100 mg/dL without plasma supplementation during the procedure or before central venous catheter removal. The study group was compared to patients with plasma fibrinogen >100 mg/dL. Among the 275 patients who received 1406 PLEXes, 62 patients (23%) who underwent 323 PLEXes met the inclusion criteria, and only 2 (3%) patients had bleeding while on oral anticoagulants. In contrast, out of 275 patients, 143 (52%) with fibrinogen levels >100 mg/dL received 751 PLEX treatments, and bleeding occurred in 2 (1%) while on low-molecular-weight heparin. Our findings suggest that a pre-procedure fibrinogen threshold of 80-100 mg/dL without plasma supplementation does not increase bleeding risk unless patients were on anticoagulation.

Continuous renal replacement therapy and therapeutic plasma exchange in pediatric liver failure.

Patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) have significant morbidity and mortality. They require extracorporeal blood purification modalities like continuous renal replacement therapy (CRRT) and therapeutic plasma exchange (TPE) as a bridge to recovery or liver transplantation. Limited data are available on the outcomes of patients treated with these therapies. This is a retrospective single-center study of 23 patients from 2015 to 2022 with ALF/ACLF who underwent CRRT and TPE. We aimed to describe the clinical characteristics and outcomes of these patients.Median (IQR) age was 0.93 years (0.57, 9.88), range 16 days to 20 years. Ten (43%) had ALF and 13 (57%) ACLF. Most (n = 19, 82%) started CRRT for hyperammonemia and/or hepatic encephalopathy and all received TPE for refractory coagulopathy. CRRT was started at a median of 2 days from ICU admission, and TPE started on the same day in most. The liver transplant was done in 17 (74%), and 2 recovered native liver function. Four patients, all with ACLF, died prior to ICU discharge without a liver transplant. The median peak ammonia pre-CRRT was 131 µmol/L for the whole cohort. The mean (SD) drop in ammonia after 48h of CRRT was 95.45 (43.72) µmol/L in those who survived and 69.50 (21.70) µmol/L in those who did not (p 0.26). Those who survived had 0 median co-morbidities compared to 2.5 in non-survivors (aOR (95% CI) for mortality risk of 2.5 (1.1-5.7), p 0.028). Conclusion: In this cohort of 23 pediatric patients with ALF or ACLF who received CRRT and TPE, 83% survived with a liver transplant or recovered with their native liver. Survival was worse in those who had ACLF and those with co-morbid conditions. What is Known: • Pediatric acute liver failure is associated with high mortality. • Patients may require extracorporeal liver assist therapies (like CRRT, TPE, MARS, SPAD) to bridge them over to a transplant or recovery of native liver function. What is New: • Standard volume plasma exhange has not been evaluated against high volume plasma exchange for ALF. • The role, dose, and duration of therapeutic plasma exchange in patients with acute on chronic liver failure is not well described.

Wall-Eyed Bilateral Internuclear Ophthalmoplegia as Part of the Clinical Presentation of Pediatric Multiple Sclerosis, Successfully Treated With Therapeutic Plasma Exchange

Wall-Eyed Bilateral Internuclear Ophthalmoplegia as Part of the Clinical Presentation of Pediatric Multiple Sclerosis, Successfully Treated With Therapeutic Plasma Exchange

Patterns of Multiple Organ Dysfunction and Renal Recovery in Critically Ill Children and Young Adults Receiving Continuous Renal Replacement Therapy.

Acute kidney injury requiring dialysis (AKI-D) commonly occurs in the setting of multiple organ dysfunction syndrome (MODS). Continuous renal replacement therapy (CRRT) is the modality of choice for AKI-D. Mid-term outcomes of pediatric AKI-D supported with CRRT are unknown. We aimed to describe the pattern and impact of organ dysfunction on renal outcomes in critically ill children and young adults with AKI-D. Retrospective cohort. Two large quarternary care pediatric hospitals. Patients 26 y old or younger who received CRRT from 2014 to 2020, excluding patients with chronic kidney disease. None. Organ dysfunction was assessed using the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score. MODS was defined as greater than or equal to two organ dysfunctions. The primary outcome was major adverse kidney events at 30 days (MAKE30) (decrease in estimated glomerular filtration rate greater than or equal to 25% from baseline, need for renal replacement therapy, and death). Three hundred seventy-three patients, 50% female, with a median age of 84 mo (interquartile range [IQR] 16-172) were analyzed. PELOD-2 increased from 6 (IQR 3-9) to 9 (IQR 7-12) between ICU admission and CRRT initiation. Ninety-seven percent of patients developed MODS at CRRT start and 266 patients (71%) had MAKE30. Acute kidney injury (adjusted odds ratio [aOR] 3.55 [IQR 2.13-5.90]), neurologic (aOR 2.07 [IQR 1.15-3.74]), hematologic/oncologic dysfunction (aOR 2.27 [IQR 1.32-3.91]) at CRRT start, and progressive MODS (aOR 1.11 [IQR 1.03-1.19]) were independently associated with MAKE30. Ninety percent of critically ill children and young adults with AKI-D develop MODS by the start of CRRT. Lack of renal recovery is associated with specific extrarenal organ dysfunction and progressive multiple organ dysfunction. Currently available extrarenal organ support strategies, such as therapeutic plasma exchange lung-protective ventilation, and other modifiable risk factors, should be incorporated into clinical trial design when investigating renal recovery.

Extracorporeal Support Strategies in Liver Failure - Focus on Albumin Dialysis and Therapeutic Plasma Exchange

Combining albumin dialysis for the removal of hydrophobic substances with classical haemodialysis in the treatment of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) has a strong theoretical rational and clinical data showed a positive effect on laboratory and partly clinical characteristics of ALF and ACLF. However, neither the MARS nor the Prometheus System has so far been able to demonstrate a mortality benefit in ALF or ACLF patients. To date, only the use of therapeutic plasma exchange (TPE) has demonstrated significant removal of pathogen-associated (PAMPs), damage-associated molecular patterns (DAMPs) and pro-inflammatory cytokines. In addition, TPE also acts simultaneously by replacing protective but depleted mediators, thus improving multiple key pathophysiological principles of both ALF and ACLF. In ALF, both high-volume and standard-volume TPE showed a significant improvement in survival. The data on the use of TPE in ACLF is still sparse, with only two Chinese monocentric studies in patients with exclusively hepatitis B-associated ACLF suggesting potentially improved survival with TPE. The currently recruiting APACHE study will include patients with the modern EASL-CLIF definition of ACLF.

Severe, Refractory Primary Warm Autoimmune Hemolytic Anemia Requiring 90 Erythrocyte Transfusions.

A previously healthy 60-year-old man presented to the hospital with a hemoglobin of 3.5 g/dL. He was diagnosed with severe warm autoimmune hemolytic anemia (wAIHA) with reticulocytopenia on hospital day 1 that was not responsive to steroids, immune globulin, and rituximab. Over a 42-day hospital stay, the patient remained continuously transfusion-dependent with a ninety red cell unit requirement for his refractory disease. He was trialed on therapeutic plasma exchange before ultimately undergoing inpatient splenectomy that led to a response within hours. He remains in complete remission at six months of follow-up.

Plasma exchange improves survival in acute liver failure- An updated systematic review and meta-analysis focussed on comparing within single etiology.

Therapeutic plasma exchange (PLEX) is increasingly used in patients with acute liver failure (ALF) as either stand-alone therapy or bridge to liver transplantation. Etiology plays a major role in prognosis of these patients and benefit of PLEX may consequently differ across etiologies. This systematic review and meta-analysis aims to evaluate the efficacy of PLEX in treating ALF, focussing on studies with single etiology. We conducted a systematic literature search and identified studies comparing PLEX vs. standard medical therapy (SMT) for patients with ALF across all age groups. The protocol was registered in theInternational Prospective Register of Systematic Reviews (PROSPERO) (CRD42023442383). Pooled risk-ratios were determined by Mantel-Haenszel method within a random effect model. Primary outcome was mortality at ≤ 60-days and 90days. Secondary outcome was adverse events attributable to PLEX. Eight studies (pooled sample size in PLEX arm:284; randomized trials:2; Comparative cohorts:6) with retrievable data on ALF were included in this systematic review. Analysis showed that PLEX was associated with significant reduction in mortality at ≤ 60-days (RR 0.64; CI, 0.51-0.80; P < 0.001) and at 90-days (RR 0.67; CI, 0.50-0.90; P = 0.008) as compared to SMT. On sub-group analysis, the survival benefit was noted irrespective of the volume of plasma exchanged during PLEX. Three studies (pooled sample size in PLEX arm: 110; all comparative cohorts) were identified, which included patients with a single etiology for ALF. These studies included patients with Wilson's disease, rodenticidal hepatotoxicity and acute fatty liver of pregnancy. Pooled analysis of studies with single etiology ALF showed better reduction in ≤ 90-day mortality with PLEX (RR 0.53; CI, 0.37-0.74; P < 0.001). Studies reported no major side-effects attributable to PLEX. PLEX is safe and improves survival, independent of the volumes utilized, in patients with ALF as compared to standard medical treatment. The survival benefit is especially pronounced in studies restricted to single etiology.

Carfilzomib-associated thrombotic microangiopathy: clinical features and outcomes.

Carfilzomib, a new proteasome inhibitor indicated for patients with relapsed/refractory myeloma, has been associated with cases of thrombotic microangiopathy (CFZ-TMA). The role of variants in the complement alternative pathway and therapeutic potential of complement blockade with eculizumab remain to be determined. We report 37 cases of CFZ-TMA recorded in the French reference center for TMA with their clinical characteristics, genetic analysis and outcome according to treatments. A trigger was identified in more than half of cases, including 8 influenza and 5 SARS-CoV-2 cases. All patients presented with acute kidney injury (AKI) (KDIGO stage 3 in 31 (84%) patients) while neurological (n=13, 36%) and cardiac damage (n=7, 19%) were less frequent. ADAMTS13 and complement activity were normal (n= 28 and 18 patients tested) and no pathogenic variant in the alternative complement pathway was found in 7 patients tested.TMA resolved in most (n=34, 94%) patients but 12 (44%) still displayed stage 3 AKI at discharge. Nineteen (51%) patients were treated with therapeutic plasma exchange, 14 (38%) patients received corticosteroids and 18 (50%) were treated with eculizumab. However none of these treatments demonstrated a significant impact on outcomes. This study is the largest case series of CFZ-TMA since its approval in 2012. Patients present with severe AKI and experience frequent sequelae. Complement variants and blockade therapy do not seem to play a role in the pathophysiology and prognosis of the disease.

Single-center Experience of Therapeutic Plasma Exchange in Children with Neuroimmunological Disorders: Indications, Efficacy, and Safety

Single-center Experience of Therapeutic Plasma Exchange in Children with Neuroimmunological Disorders: Indications, Efficacy, and Safety

Clinical Profile, Treatment and Outcome of Thrombotic Thrombocytopenia Purpura (TTP) in Rituximab Era- an Experience from Tertiary Care Centre from North India.

Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia (MAHA) resulting from severe deficiency of ADAMTS13. TTP is an acute medical emergency which requires early treatment with therapeutic plasma exchange. With the early use of Rituximab along with PLEX, early response is achieved and relapse rate has gone down. There is lack of published data from India regarding treatment and outcome of TTP. We retrospectively analyzed our data of 21 patients of TTP including 4 patients who had TA-TMA. TTP patients were treated with TPE, pulse methylprednisolone and rituximab. After a median follow up of 57.5months overall survival in TTP patients was 82.3% in our study and one patient relapsed twice but again responded to same treatment. Relapse free survival was 92.8%. The mortality rate in our study in TTP patients was (3/17) 17.6%. The total response rate was 82.3% (14/17). Out of 4 patients of TA-TMA, Only 33.3% patients responded to plasma exchange in TA-TMA while two patients died (2/4) 50%. Immediate TPE and early rituximab are associated with improved survival in TTP patients, however TA-TMA still remains a significant challenge for transplant physicians and more research is needed in guiding the therapy.

A Case Report of Therapeutic Plasma Exchange in Hypertriglyceridemia-Induced Pancreatitis.

To support the evidence of plasma exchange's ability to rapidly lower serum TG levels and provide upcoming research opportunities for evaluating the long-term effects of this treatment,we present the case of a 35-year-old female who was admitted for Hypertriglyceridemia-induced Pancreatitis (HTGP). She underwent Therapeutic Plasma Exchange (TPE) using Spectra Optia Apheresis System on an emergency basis.The patient had a remarkable reduction of serum Triglycerides (TG) from 3953 to 291 mg/dl, which was life saving. On subsequent follow-up the serum TG levels remained constant post-TPE with conservative treatment only.Therapeutic plasma exchange deserves an upgrade in ASFA categorization for the indication in Hypertriglyceridemia induced Pancreatitis.

Assessing the clinical efficacy of low-volume therapeutic plasma exchange in achieving recovery from acute liver failure induced by yellow phosphorous poisoning.

Acute liver failure (ALF) following yellow phosphorous (YP) ingestion is similar to acetaminophen-induced ALF and it has become a public concern in our region. This study assessed low volume therapeutic plasma exchange (LV-TPE) efficacy in improving the transplant free survival in YP poisoning. Adult patients with toxicology reports of YP and ALF requiring critical care were included in the study. LV-TPE was planned for three consecutive days and three more if required. Performed 1.3 to 1.5 plasma volume replacing with 0.9% normal saline, 5% human albumin solution, and fresh frozen plasma based on ASFA 2019 criteria. MELD score, laboratory parameters, LV-TPE details were captured. The study end point was clinical outcome of the patients. Among 36 patients, 19 underwent LV-TPE and 17 opted out of LV-TPE and they were included as a control arm. The MELD score was 32.64 ± 8.05 and 37.83 ± 9.37 in both groups. There were 13 survivors in LV-TPE group leading to a 68.42% reduction in mortality. The coagulation and biochemical parameters showed a significant percentage change after LV-TPE. Refractory shock, delay in initiating procedure and acidosis were independent predictors of mortality. A well-timed LV-TPE improves the survival of patients with ALF due to YP poisoning.

A rare case of a pharyngeal-cervical- brachial variant of Guillain–Barré syndrome

Abstract: Guillain–Barre syndrome (GBS) is an acute, usually symmetrical, and typically de myelinating polyneuropathy, characterized by progressive, ascending paralysis and areflexia, with or without abnormal sensory function. Therapeutic plasma exchange(TPE) was the first therapeutic modality to impact the disease favorably, and several major randomized controlled trials (RCTs) have confirmed its efficacy. Our case is unique, as this critically ill patient admitted in the intensive care unit (ICU), developed a rare form of GBS, the PCB variant of the disease, and was successfully treated with TPE. The diagnosis of PCB can be challenging due to atypical clinical features but its unique presentation does provide sufficient clues to narrow the differential diagnosis, which is helpful in starting empirical therapy at the earliest. Immunomodulation with plasma exchange and IVIG have been found to improve treatment outcomes; 70%–80% of patients usually have a complete recovery. Early diagnosis is very important in the case of the PCB variant of GBS to enable timely intervention. Diagnosis can be made on history and neurological findings alone.

Role of therapeutic plasma exchange in treatment of the hypertriglyceridemia-induced acute pancreatitis: Case report and literature review

Abstract: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is associated with a more severe clinical course than acute pancreatitis due to other etiologies. Presently, these patients are managed with dietary restrictions, analgesia, lipid-lowering agents, insulin/heparin dual therapy, and supportive care to prevent organ failure. Apart from these conventional therapies, therapeutic plasma exchange (TPE) is another potential treatment that is being performed as it results in rapid reduction in serum triglycerides and inflammatory cytokines, thus, leading to drastic improvements in clinical and laboratory findings and patient outcomes. Here, we report our experience of using TPE for HTG-AP in our patients.

Investigation of the Effect of Therapeutic Plasma Exchange for TAFRO Syndrome: A Pilot Study.

TAFRO syndrome is a rare systemic inflammatory disorder with a fatal course. Nevertheless, a definitive treatment strategy has not yet been established. Anti-inflammatory therapies, including glucocorticoid treatment and immunosuppressants, have not been satisfactory. Therefore, new treatment options are needed for patients with TAFRO syndrome. The effectiveness of therapeutic plasma exchange (TPE) has mainly been reported in several case reports. In this case series study, we investigated the effect of TPE on TAFRO syndrome. We reviewed six consecutive cases with TAFRO syndrome treated at Shinshu University Hospital. All of them underwent TPE. A significant improvement in mean blood pressure, albumin, total bilirubin, and C-reactive protein was observed after TPE. Furthermore, early TPE treatment was suggested to have an impact on the prognosis. More intensive studies are needed to emphasize the overall conclusion obtained that TPE can be an effective/acceptable treatment option for TAFRO syndrome.

A rare manifestation presenting as acute pancreatitis of thrombotic thrombocytopenic purpura

AbstractThrombotic thrombocytopenic purpura (TTP) is an unusual disease with a 90% mortality rate without prompt management. The typical clinical manifestations include thrombocytopenia, hemolytic anemia, neurological symptoms, fever, and renal impairment. However, recognizing TTP in its early stages is not always easy due to limited clinical experience and sometimes atypical presentation. We report a 44‐year‐old male who initially suffered from jaundice and skin purpura, followed by epigastric pain. Acute pancreatitis was first suspected after a computerized tomography (CT) scan in the local medical department, without a definite etiology. He was then transferred to our hospital for further investigation of hemolysis. Transient neurological symptoms occurred 1 week after transferring. TTP was later confirmed based on schistocytes noted in peripheral blood smear and ADAMTS‐13 activity = 0%. The patient was discharged successfully after prompt therapeutic plasma exchange and steroid treatment. We present the first case of TTP inducing acute pancreatitis in Asia and remind that acute pancreatitis is a possible cause of abdominal pain, although it's a rare manifestation of TTP.