scholarly journals Plasma exchange in thrombotic microangiopathies (TMAs) other than thrombotic thrombocytopenic purpura (TTP)

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 632-638 ◽  
Author(s):  
Jeffrey L. Winters

Abstract Thrombotic microangiopathies (TMAs) are a diverse group of disorders that are characterized by common clinical and laboratory features. The most commonly thought-of TMA is thrombotic thrombocytopenic purpura (TTP). Because of the marked improvement in patient mortality associated with the use of therapeutic plasma exchange (TPE) in TTP, this therapy has been applied to all of the TMAs. The issue, however, is that the pathophysiology varies and in many instances may represent a disorder of the endothelium and not the blood; in some cases, the pathophysiology is unknown. The use of TPE is further obscured by a lack of strong supporting literature on its use, with most consisting of case series and case reports; controlled or randomized controlled trials are lacking. Evidence supporting the use of TPE in the treatment of TMAs (other than TTP and TMA–complement mediated) is lacking, and therefore its role is uncertain. With the greater availability of genetic testing for mutations involving complement regulatory genes and complement pathway components, there seems to be a percentage of TMA cases, other than TMA–complement mediated, in which complement pathway mutations are involved in some patients. The ability of TPE to remove abnormal complement pathway components and replace them with normal components may support its use in some patients with TMAs other than TTP and TMA–complement mediated.

2004 ◽  
Vol 47 (1) ◽  
pp. 59-60
Author(s):  
Leo McCarthy ◽  
Atillio Orazi ◽  
Charles Miraglia ◽  
Daniel Waxman ◽  
Elaine Skipworth ◽  
...  

Although much has been learned about the pathophysiologic process of thrombotic thrombocytopenic purpura (TTP), both diagnostically and therapeutically, since its initial description by Moschowitz in 1924, its etiology and treatments remain, in many instances, problematic. Thrombotic thrombocytopenic purpura remains a rare entity whose etiology is usually unknown, but several drugs and infections have now been implicated in its development. Although treatment by plasma exchange has gained worldwide acceptance, the optimal exchange media is not known, nor the volume and duration of exchange therapy, not appropriate salvage therapies. Without the benefit of randomized controlled trials, its treatment, to a large extent, remains not evidence-based but “eminence-based“, making the same mistakes with increasing confidence over decades.


2011 ◽  
Vol 07 (02) ◽  
pp. 143
Author(s):  
Jens M Chemnitz ◽  
Michael Hallek ◽  
Christof Scheid ◽  
◽  
◽  
...  

The use of therapeutic plasma exchange has reduced mortality rates in thrombotic thrombocytopenic purpura (TTP) from 90 to 10–20%. However, TTP is a potentially lethal disorder, and management of patients with TTP refractory to plasma exchange or frequently recurrent disease is difficult. In those cases, rituximab might be a therapeutic option, although current data are based primarily on case reports and smaller case series. While initial response rates to rituximab are reported to be high, long-term follow-up data of patients treated with rituximab are rare; however, it is important to estimate the safety and benefit of this treatment. In this article we focus on current experience with rituximab in the treatment of TTP, including recent results with long-term follow-up.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Jing Zhou ◽  
Yunyang Yu ◽  
Biwei Cao ◽  
Xiaoya Li ◽  
Miao Wu ◽  
...  

To date, a growing number of clinical studies have demonstrated the safety and health benefits from Baduanjin intervention. Based on this, our objective is to systematically retrieve and summarize the clinical studies on Baduanjin, with a view to providing more evidence-based evidence in support of the application of Baduanjin for healthcare, and to identify the shortcomings of existing research and provide feasibility suggest for further clinical research. Both four English language and four Chinese language electronic databases were used to search articles related to Baduanjin during 2000–2019. SPSS 22.0 software was used to analyze the data, and the risk of bias tool in the RevMan 5.3.5 software was used to evaluate the methodological quality of randomized controlled trials. A total of 810 publications were identified, including 43 (5.3%) systematic reviews, 614 (75.8%) randomized controlled trials, 66 (8.1%) nonrandomized controlled clinical studies, 84 (10.4%) case series, and 3 (0.4%) case reports. The top 10 diseases/conditions included diabetes, chronic obstructive pulmonary disease, hypertension, low back pain, neck pain, stroke, coronary heart disease, cognitive impairment, insomnia, and osteoporosis or osteopenia. The style of State General Administration of Sport of China in 2003 was the most commonly used version of Baduanjin, and Baduanjin was practiced with an average of 35 minutes, 1 or 2 times a day, 3–5 days per week, and a 18-week average duration. It is also worth noting that there were no serious adverse events related to Baduanjin intervention. Most studies were small sample size research, and the methodological quality of randomized controlled trials is generally low. The clinical studies of Baduanjin have a substantial quantity and evidence base. However, there are significant differences among different studies in the specific intervention measures such as style, intensity, duration, learning, and practice methods, which need to be further standardized and unified. Further high-quality designed and reporting studies are recommended to further validate the clinical benefits of Baduanjin.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3993-3993 ◽  
Author(s):  
Sameer A. Tulpule ◽  
Yvonne A. Francis ◽  
Deepti Radia ◽  
Claire N. Harrison ◽  
Beverely J. Hunt

Abstract Introduction: Thrombotic thrombocytopenic purpura (TTP) is a life threatening condition requiring rapid diagnosis and treatment. Plasma exchange (PEX) is the mainstay of treatment. Various forms of immunosuppression (IS) have been used which include steroids, cyclosporine, cyclophosphamide, vincristine and rituximab. The percentage of patients relapsing is unclear. There is a suggestion that up to half of the patients with severe acquired deficiency of von Willebrand factor -cleaving protease (vWF-CP) activity relapse within a year. There are no reports of the use of mycophenolate mofetil (MMF) in acquired TTP. We describe three patients with acquired TTP, treated with MMF at relapse, with the intention to prevent further relapse. Methods: The 3 patients presented with acute acquired TTP. They all had at least 3 of the clinical pentad of fever, microangiopathic haemolytic anaemia, thrombocytopenia, neurological and renal impairment plus a vWF-CP level of < 2% at initial presentation. All of them underwent PEX until remission (platelet count of >150 x 109/L for at least 2 consecutive days with resolution of neurological and renal signs). MMF was introduced at remission after relapse at a dose of 500mg BD, post PEX, increasing upto a maximum dose of 750 mg BD. MMF was introduced at 4th relapse for patient A, 2nd relapse for patient B and 1st relapse for patient C. Results: All 3 patients were females. The ages at presentation were 63, 72 and 46 years. At presentation, the haemoglobin was 6.0, 8.7 and 6.7 g/dL and platelet count was 19, 36 and 21 x 109 /L respectively. Patient A relapsed eight times at day (d) 9, d20, d53, d89, d198, d209, d221 and d231. She was treated with PEX in conjunction with steroids and vincristine, cyclosporine, cyclophosphamide and rituximab for the first 3 relapses respectively. During the third relapse the patient’s condition deteriorated and she became unconcious requiring ventilation. MRI brain showed multiple small foci consistent with vascular disease. She recovered, but relapsed again despite cyclophosphamide and rituximab. After the 4th relapse on d102, MMF was started reaching a maximum dose of 750mg BD. She had regular full blood counts checked. At d187 she was found to be neutropenic and the MMF was stopped. She relapsed in 11 days and was recommenced on MMF at 500mg bd after PEX. MMF was continued at the dose of 750mg BD after the 7th and 8th relapse. Despite full dose MMF, she relapsed and was treated with PEX and a further course of rituximab was given at the 8th relapse. Patient B had received 500mg of methyl prednisolone on ITU with PEX at initial presentation. MMF (500mg BD) was commenced at remission after second relapse (d23) after undergoing plasma exchange. Patient C was commenced on MMF (500mg BD) after first relapse (d36). All 3 are in remission and continue on MMF at a follow up of 12, 2 and 4 months respectively since last relapse. MMF was tolerated very well except for transient neutropenia (patient A) and transient diarrhoea (patient C). Conclusion: MMF appears to be safe in patients with relapsed TTP who received multiple lines of treatment. Due to the small size of this case series it is unclear whether MMF is efficacious in reducing the risk of relapse in TTP; a formal longer study may be warranted.


2017 ◽  
Vol 18 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Wesley J. Rose ◽  
Jan M. Sargeant ◽  
W. J. Brad Hanna ◽  
David Kelton ◽  
Dianna M. Wolfe ◽  
...  

AbstractAcupuncture has become increasingly popular in veterinary medicine. Within the scientific literature there is debate regarding its efficacy. Due to the complex nature of acupuncture, a scoping review was undertaken to identify and categorize the evidence related to acupuncture in companion animals (dogs, cats, and horses). Our search identified 843 relevant citations. Narrative reviews represented the largest proportion of studies (43%). We identified 179 experimental studies and 175 case reports/case series that examined the efficacy of acupuncture. Dogs were the most common subjects in the experimental trials. The most common indication for use was musculoskeletal conditions, and the most commonly evaluated outcome categories among experimental trials were pain and cardiovascular parameters. The limited number of controlled trials and the breadth of indications for use, outcome categories, and types of acupuncture evaluated present challenges for future systematic reviews or meta-analyses. There is a need for high-quality randomized controlled trials addressing the most common clinical uses of acupuncture, and using consistent and clinically relevant outcomes, to inform conclusions regarding the efficacy of acupuncture in companion animals.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4799-4799
Author(s):  
Mohamed Abu Haleeqa ◽  
Hanan Al Raeesi ◽  
Fatima Alkaabi

Background and Purpose Thrombotic thrombocytopenic purpura (TTP) is a heterogeneous disease primarily characterized by thrombocytopenia and microangiopathic hemolytic anemia. Therapeutic plasma exchange has dramatically improved mortality, allowing for emergence of refractory, relapsing, and atypical presentations. in this case series we aim to present our institutional data for Apheresis in Sheikh khalifa medical City in AbuDhabi. We will also present patient demographic and clinical presentation and treatment protocol we use Methodology -Case series with Retrospective review. -Routine laboratory tests such as peripheral blood cell counts, reticulocyte count, coagulation profile, serum lactate dehydrogenase (LDH), bilirubin, serum creatinine, cardiac enzymes, and urinalysis, were performed. -ADAMTS13 levels and inhibitor titer were determined for all patient in outside lab -Baseline demographic characteristics were calculated in frequencies and percentages. (include age ,Gender , clinical manifestations and treatment strategy) Results and Discussions thrombotic thrombocytopenic purpura (TTP) pentad consisting of fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological abnormalities, and renal failure. less than 5 % of patient reported in literature have all associated clinical features. -Total of 10 patients M:F 4:2 , Median Age 44yr 50% presented with Neurological manifestations and renal disease , 30% presented with Fever only 20% had cardiac manifestation on admission . None of the patient presented with all 5 pentad. -All patients received TPE , steroid . -90 % of the patients received Rituximab except for 1 because of Allergy. -All patients has low ADAMTS 13 , except one has normal ADAMTS13 but came with relapse and on first admission had low ADAMTS13 -All patient presented with MAHA and TCP except 2 patient whom had normal Hb but significant schistocytes on peripheral blood with TCP both patient where relapsed cases. -3 patient were relapsed 7 de novo , the 3 relapsed cases all did not receive Rituximab in first remission . One of them relapsed twice but did not received Rituximab due to allergy -Although some publication include large number of TTP patients, but only few case reports have evaluated the clinical feature, laboratory parameters and therapeutic outcome of TTP. Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange (TPE) mortality decreases to about 10%-20%. A disintegrin and metalloprotease with thrombospondin Type 1 motif, Member 13 (ADAMTS13) levels less than 5% are a hallmark of TTP. We do ADAMTS 13 Activity and inhibitor titre levels in outside facility TAWAM hospital with turn-around time of 7 days which is helpful in planning Rituximab treatment. with availability of Rituximab our relapse rates are low but not zero Conclusions -Thrombotic thrombocytopenic purpura (TTP) pentad consisting of fever, thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurological abnormalities, and renal failure. -5 % of patient reported in literature have all associated clinical features. -We found that majority of patient presented with evidence of thrombocytopenia and MAHA only. -Without treatment, TTP is almost uniformly fatal with a mortality rate approaching 90%. With the timely institution of therapeutic plasma exchange (TPE) mortality decreases to about 10%-20%. -TPE ,steroid and rituximab was very effective in achieving sustain remission in 100% of ours patients with median follow up 8 month -More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities. Figure Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 12 ◽  
Author(s):  
Max J. Dullaart ◽  
Marijn Kip ◽  
Adriana L. Smit ◽  
Inge Stegeman

Objectives: To systematically review studies on the effect of treatment of subjective tinnitus in children.Data Sources: We searched for studies in MEDLINE and EMBASE databases, after which additional studies were hand searched using Scopus databases. The methods are described in the study protocol, which has been registered in the PROSPERO register. PRISMA guidelines were followed in the reporting of this study.Eligibility Criteria: We considered for inclusion randomized controlled trials (RCTs), observational studies, case reports, and case series, with tinnitus as primary outcome in children (0–18 years old) with acute or chronic subjective tinnitus. We excluded studies in which both children and adults participated but outcomes were not specifically reported for children, as well as animal studies, studies with a non-original study design and studies about children with pulsatile or objective tinnitus.Data Selection: Two reviewers independently assessed studies for eligibility and quality, collected and extracted data. Statistical analyses were performed in case of homogeneous outcomes.Results: The search yielded a total of 4,447 studies. Of these, 147 eligible studies were selected. One case report and five observational studies met the eligibility criteria. Three studies applied counseling and (simplified-)TRT and reported improvement in tinnitus outcome in 68 out of 82 children after 3–6 months of treatment. Two studies used pharmacological treatments and reported improvement in 74 out of 86 patients after 10 days to 3 months of treatment. One study reported the outcome of biofeedback therapy, describing an improvement in tinnitus loudness and annoyance after 2 months of treatment.Conclusion: Due to the high risk of bias of the included studies, we cannot determine the effectiveness of the treatment of subjective tinnitus in children. Also, owing to brief follow-up periods, it is not possible to draw conclusions regarding long-term effects. Randomized controlled trials with longer follow-up periods are necessary to provide substantial evidence of the effects of therapies for children affected by tinnitus. https://www.crd.york.ac.uk/prospero/Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier [CRD42020178134].


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2794-2794
Author(s):  
Harjot Kaur ◽  
Appalanaidu Sasapu ◽  
Michele H Fox ◽  
Pooja Motwani

Abstract Introduction We present a case of TTP refractory to usual therapies treated successfully with eculizumab. Case presentation A 64 year-old African American female with history of diabetes and hypertension presented with left sided weakness and seizure-like activity preceded by 2 days of headaches and 2 weeks of easy bruising. On admission her vital signs and physical exam were unremarkable. Her basic metabolic panel, ANA panel, hepatitis panel, HIV, and anti-phospholipid panel was negative. Her hemoglobin was 9.0 g/dL, platelets were 13K/uL, LDH was 954IU/L, haptoglobin <30 mg/dL, eGFR was 50, and blood smear showed 4-5 schistocytes/high power field. ADAMTS13 activity was <5% and there was an inhibitor level of 1.1BU. C3 level was 75.3 (normal range 90-180mg/dL), C4 was <10 mg/dL (normal range 15-45 mg/dL). On day 1, she was started on oral prednisone (1mg/kg/day) and daily plasma exchange (TPE). changes. After 6 days of TPE without signs of improvement, the first dose of rituximab 375 mg/msq/dose was given on day 7. During the second week of hospitalization, patient also developed delirium and mental status changes. Vincristine 2 mg was given on day 13 for refractory TTP. Due to clinical worsening of microangiopathy and mental status, a decision was made to administer eculizumab 900 mg on day 17. Within a few hours of eculizumab administration, her platelets improved from 8k/uL to 21k/uL and to 47k/uL 12 hours later. After the second dose of eculizumab on day 24, platelets improved to 117k/uL and continued to rise. Eculizumab 900 mg was given weekly for 4 weeks, at which time ADAMTS13 activity was 75% and ADAMTS13 inhibitor was undetectable. Eculizumab 1200 mg was then given every two weeks, for a total of 3 more doses, during which the CBC, LDH, and haptoglobin remained in the normal range. Eculizumab was stopped, and after four months of close follow up, platelets, LDH, renal function and mental status were still normal range. C3 level was 203 (normal range 90-180 mg/dl), C4 was 35 mg/dl (normal range 15-45 mg/dl), ADAMTS 13 activity assay is >100% and there is no inhibitor. Discussion TTP and aHUS are both thrombotic microangiopathies (TMA). TTP is caused by acquired or inherited deficiency of the ADAMTS 13 protein or due the formation of an inhibitor to the ADAMTS13 protein. aHUS results, in most cases, from a genetic mutation in complement factor H in the alternative pathway of the complement cascade. Recent studies have described the importance of the complement system in all forms of TMA (Update on the role of the complement system in the pathogenesis of thrombotic microangiopathies. Prilozi. 2014;35(1):115-22). While plasma exchange is the cornerstone of TTP treatment, complement inhibition with drugs such as eculizumab is the treatment of choice for aHUS. The use of complement inhibiting drugs has not yet been studied in TTP. We report an unusual case of TTP, with confirmed ADAMTS 13 inhibitor and low activity, which did not respond to conventional treatment for TTP. Theorizing that this patient either had concurrent aHUS or had TTP with a dysregulated alternate complement pathway, we used eculizumab, to which the patient had a remarkable and persistent response. There are other reports in literature of patients with aHUS having reduced levels of ADAMTS13 protein; however, these patients did not have an inhibitor as was seen in our patient (Partial ADAMTS13 deficiency in atypical hemolytic uremic syndrome. Blood. 2013 Aug 22;122(8):1487-93). There is one other case in the literature where TTP was treated successfully with eculizumab. In that case, discontinuation of eculizumab was associated with a relapse of TTP and so had to be continued (Eculizumab in the treatment of refractory idiopathic thrombocytopenic purpura. Br J Haematology. 2012 June;157 (6):772-4). To our knowledge, we report the first case of a confirmed diagnosis of TTP treated successfully with eculizumab with remission continuing 3 months after discontinuation of the drug. The use of eculizumab and the role of the complement pathway in TTP deserves further study. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.


Sign in / Sign up

Export Citation Format

Share Document