scholarly journals Impact of Residual Effects and Complications of Thrombotic Thrombocytopenic Purpura (TTP) on Daily Living: A Qualitative Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 931-931
Author(s):  
Deirdra Terrell ◽  
Spero Cataland ◽  
Laura Beebe ◽  
San Keller ◽  
Julie Panepinto ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Focus Group ◽  
Focus Groups ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Daily Living ◽  
Research Funding ◽  
Full Range ◽  
High Impact ◽  
Thrombocytopenic Purpura

Introduction: Adverse health outcomes following recovery from thrombotic thrombocytopenic purpura (TTP) are under-recognized. The Oklahoma (OK) TTP Registry has documented that patients have residual complications following recovery. TTP survivors have an increased prevalence of major depression, decreased quality of life, minor cognitive impairment, and a decreased life expectancy compared to the general population. Additionally, Chaturvedi et. al (2017), reported that 32% of TTP survivors met the provisional diagnosis of post-traumatic stress disorder related to their TTP. Yet studies have failed to assess the significance of residual complications from the survivor's perspective. The goal of this study was to determine from the survivor's perspective, long-term outcomes that impact daily activities during remission. Patients: TTP survivors were recruited from the OK Registry and the Ohio State University (OSU) TTP Research Program. Eligibility included: 1) age >18 years, 2) documented ADAMTS13 deficiency, 3) in clinical remission from TTP, and 4) able to read and understand English. A non-probabilistic purposive sampling approach was utilized to select survivors from whom the most could be learned. To understand the full range of health challenges during remission, we intentionally included > 1 person who had experienced a TTP relapse in each focus group. Methods: Qualitative focus groups were conducted using a semi-structured discussion guide to facilitate and standardize the discussion. Prior to use, the discussion guide was pilot-tested and revised accordingly. All the focus groups were conducted in-person and moderated by the first author. During the focus group, TTP survivors described symptoms following recovery. All of the mentioned symptoms were transferred to index cards and given to each person. Patients individually sorted the cards into 'high', 'medium', and 'low' impact on daily living. Next, patients discussed views on what makes a symptom high, medium, or low impact. Additionally, patients were asked to list their top 3 symptoms on an index card (regardless of if it had been previously mentioned). Patients were also asked about discussions with their physicians regarding these symptoms. Frequencies were calculated for quantitative responses. Qualitative data were analyzed for themes. Results: Focus groups (4 in OK; 3 in OSU) were conducted from May-Oct. 2018, were 54-94 minutes, and digitally recorded. Overall, there were 25 patients (76% female, 52% black, median age 46 years) (Table 1). Eighty percent of patients were >5 years from their last episode, 52% had experienced a TTP relapse. The top 2 symptoms listed on the cards were: cognitive impairment 19/25 (76%) and fatigue 17/25 (68%). These symptoms were ranked as high in patients who were both < and >5 years from their last episode. High-impact symptoms occurred daily and negatively affected self-esteem, relationships, and careers. In 6/7 focus groups, survivors described high-impact symptoms caused feelings of being a burden, embarrassment, depression, and anxiety. Fatigue kept survivors from activities with loved ones and the hobbies they enjoyed prior to TTP. Cognitive impairment was described as difficulty 'getting the right words out', forming complete thoughts, and problems with memory and concentration. Cognitive impairment often resulted in arguing and frustration with loved ones. In 4/7 focus groups, memory and concentration problems were detrimental to marriages/long-term relationships. In 5/7 focus groups, cognitive impairment significantly impacted a person's ability to do their job. In 1 focus group, patients who worked in healthcare stated they changed careers because they feared their memory problems would negatively impact the health of others. Yet, many patients were hesitant to discuss these symptoms with a physician because they: 1) did not want to complain, 2) did not want to be prescribed additional medication, and 3) did not think these symptoms were relevant to their 'blood doctor'. Conclusion: Cognitive impairment and fatigue have serious impacts on daily living even >5 years after TTP. Yet, patients were often hesitant to discuss the issues with their doctor and failed to connect these symptoms with the TTP recovery process. Phase II of this study is currently underway, the goal is to identify from the TTP survivor's perspective, preferred ways to assess and manage these symptoms. Disclosures Terrell: National Institutes of Health: Research Funding. Cataland:Alexion: Consultancy, Research Funding; Ablynx/Sanofi: Consultancy, Research Funding. Panepinto:NIH: Research Funding.

Relapsing Thrombotic Thrombocytopenic Purpura: A Single Center Experience

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3732-3732
Author(s):  
Arielle L Heeke ◽  
Craig M. Kessler ◽  
Catherine Broome
Keyword(s):  
Disease Control ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Research Funding ◽  
Activity Level ◽  
High Dose ◽  
Adamts13 Activity ◽  
Thrombocytopenic Purpura ◽  
The Mean ◽  
Term Management

Abstract Thrombotic thrombocytopenic purpura (TTP) is due to a severe deficiency of the von Willebrand factor (vWF) cleaving serine metalloprotease ADAMTS13 and is most commonly diagnosed in adults due to autoantibodies against ADAMTS13. Standard therapy includes plasma exchange (PEX) until platelet counts normalize plus concurrent high dose corticosteroids. In refractory cases, weekly pulse Rituximab for 4 doses is often added. Successful long-term management of relapsing patients beyond these treatments is unclear, in part because the mechanisms for relapsing TTP are unknown. Dysfunctional immunoregulatory systems likely play a role in relapsing disease. Several case series have described disease control following bortezomib therapy (Patriquin 2016). Other immunomodulators including complement pathway and tyrosine kinase inhibitors may prove to offer benefit. Further, supplementing PEX with N-acetylcysteine (Rottenstreich 2016) & Caplacizumab (anti-vWF humanized immunoglobulin) (Peyvandi 2016) has shown promising preliminary clinical results when used to treat an acute episode. Effects on relapse rates with these treatments have not been fully evaluated. Eight cases of relapsing TTP were identified at MedStar Georgetown University Hospital May 2004 to July 2016. Relapsing TTP was defined as recurrent episode(s) of thrombocytopenia, microangiopathic hemolysis, and confirmed ADAMTS13 activity levels <10% following remission from the initial TTP episode. Retrospective chart review was completed to evaluate demographic and clinicopathologic features, laboratories and treatment at relapse(s), and clinical outcomes. In our 8 patient cohort, 75% are female (6/8), 62.5% are African American (AA) (5/8), and the mean age at initial TTP diagnosis is 35.38 (range 16-67). The mean number of relapses is 3.38 (range 2-9) with a mean platelet nadir of 45,000/mcL. All patients remain alive. Two are ANA positive, 1 with known systemic lupus erythematosus (SLE) and 1 with suspected SLE. None are HIV positive, and none endorse a family history of TTP. Four identified infections as triggers for their TTP, 1 patient developed TTP during pregnancy and hormonal fertility treatments, and 3 had no identifiable triggers. All had an increased titer of ADAMTS13 inhibitor (Bethesda titer range 0.7 - >8) at the time of relapse(s). Normalization of ADAMTS13 activity was confirmed in most following treatment (n=6), with a mean ADAMTS13 activity level between relapses of 50.5% (range 32-88%). At the time of each relapse, all patients underwent daily PEX with fresh frozen plasma plus high dose corticosteroids for at least 5 days (range 5-21 days), with some requiring gradual PEX weaning over 1-4 weeks and steroid tapering over months based on lab parameters. Two relapsed quickly after PEX discontinuation, both in the setting of systemic illness (lupus flare, cholecystitis). Sequelae of TTP (neurologic, renal, hematologic anomalies) resolved with treatment. All patients received Rituximab therapy during the 1st or 2nd relapse. For the majority (87.5%, 7/8), this intervention did not lead to long-term remission, although 100% (2/2) who transitioned to prophylactic bolus Rituximab every 6 months post splenectomy achieved long-term disease control. It is difficult to distinguish whether remission resulted from maintenance Rituximab, the splenectomy, or a combination of the two. Patients who underwent splenectomy were vaccinated and have not had difficulty with infections or thrombosis. In conclusion, our cohort of patients with relapsing TTP all had documented ADAMTS13 inhibitors and acutely responded to daily PEX (most requiring PEX wean based on lab parameters) plus high dose corticosteroids. Although Rituximab therapy during initial relapse did not offer a high percentage of long-term remissions, the addition of prophylactic Rituximab every 6 months post splenectomy has achieved long-term control in 2 patients. In our cohort the majority are AA, suggesting genetic susceptibility. HLA/immune transcript levels and ribosomal gene signatures may correlate with TTP disease activity and risk for relapse (Edgar 2015), and could be used to identify high-risk patients in need of more intensive therapy. Given the complexity and severity of this disease, there is an ongoing need for evaluation of relapsing TTP and best strategies for long-term management. Disclosures Kessler: Octapharma: Consultancy, Research Funding; Novo Nordisk: Consultancy, Research Funding; Grifols: Consultancy; Genentech: Consultancy, Research Funding; Biogen: Consultancy; Pfizer: Consultancy; Bayer: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; LFB: Other: Member of DSMB. Broome:True North Therapeutics: Honoraria; Alexion Pharmaceuricals: Honoraria.

scholarly journals Long-term Kidney Outcomes in Patients With Acquired Thrombotic Thrombocytopenic Purpura

2017 ◽  
Vol 2 (6) ◽  
pp. 1088-1095 ◽  
Author(s):  
Dustin J. Little ◽  
Lauren M. Mathias ◽  
Evaren E. Page ◽  
Johanna A. Kremer Hovinga ◽  
Sara K. Vesely ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura

Physician Scientists In Hematology: Hematologists' Experiences of Research and Recruitment to Academia - A Mixed Methods, Qualitative Approach

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2570-2570
Author(s):  
Tom Butler ◽  
John G. Gribben ◽  
Ann Hodgson
Keyword(s):  
Focus Groups ◽  
Academic Medicine ◽  
Research Funding ◽  
Clinical Skills ◽  
Local Network ◽  
Full Time ◽  
Research Experience ◽  
Medical Specialties ◽  
Physician Scientists

Abstract Abstract 2570 Physician-scientists spend a significant proportion of their time doing research, alongside clinical practice and teaching. Recruitment to academic medicine appears insufficient for workforce needs, with a perception of a 'crisis' in academic medicine (Andrew I. Schafer The Vanishing Physician Scientist 2009). Policy initiatives are in place to counter this recruitment problem and make an academic medicine career more attractive to trainees. Hematologists have a unique translational role in medicine and research, straddling the divide between laboratory and patient care. Since hematology may be inherently more academic compared to other medical specialties, this recruitment crisis may be more relevant to our specialty. Hematologists' experiences of research have been poorly reported. We employed mixed qualitative methods to explore hematologists' views on these issues, using focus groups (14 participants) to explore the experiences of research and higher degrees. Following themes from these, we used an online survey to gain quantitative data and obtained results from 39 hematologists in the local network in North East London serving approximately 4 million people, including two teaching hospitals. Among attendings, 72% had completed a research degree and 52% were in academic positions. Of trainees, 36% were enrolled in a higher degree program. The focus groups felt that hematology has a strong role in research because of the inherently lab-based aspects of the work, access to tissue for research and the history of translational research. The survey supported this, with most feeling that the lab experience facilitated the transition of hematologists to research, and 77% agreeing that 'compared to other medical specialities, hematology is more academic'. The focus groups explored the benefits of doing a research degree, such as a PhD. These included gains in critical thinking, data interpretation skills, a chance to study a topic in depth and CV development. Drawbacks included dislike of the work involved, financial loss and the stress of research. Some expressed concern about losing clinical skills during years of full-time research, whilst others felt that skills gained during research translated to better clinical acumen in the long term. The survey explored this further. 74% felt that whilst clinical acumen decreased during full-time research, this returned almost immediately on return to practice. 21% felt that clinical skills were better in the long term as a result of doing a PhD. Competition for non-academic hematology posts in the UK is low, and most doctors who do research will not become academics. However, there are expectations that hematologists need a research experience to further their careers, and most participants felt that there was greater pressure for hematologists to do research compared to other disciplines, with this pressure greater in London. We considered this perception of pressure in the context of UK research funding. The Royal College of Pathologists estimate that of ≤450 million spent on UK cancer research, ≤50-100 million are spent on hematological malignancies. Research funding is therefore out of proportion to the disease burden of blood cancers (8% of cancer deaths). London has 31% of UK academic doctors, 5 medical schools and receives 33% of UK research funding. These data help explain the greater pressure (or opportunity) for hematologists to undertake research, particularly in London. We explored views on recruitment to academic medicine. Whilst ‘becoming an academic doctor’ was rated as the strongest motivation for hematologists to do a PhD, doctors who subsequently did not proceed to an academic career benefitted from the research experience. Whilst academic doctors felt that more hematologists need to do research and become academic doctors, this view was not held by non-academic hematologists (p<0.05). In conclusion, hematologists consider their specialty to be more academic, with the nature of the work facilitating research. Particular motivations drive hematologists to undertake research. The pressure to do research may be higher in hematology compared to other areas of medicine, despite low competition for jobs overall. Concerns about loss of clinical skills do not appear to be justified. The perception of a recruitment problem within academic hematology varies depending on whether academic or non-academic hematologists are surveyed. Disclosures: Gribben: Roche: Consultancy; Celgene: Consultancy; GSK: Honoraria; Napp: Honoraria.

Long-term remission in a patient with refractory thrombotic thrombocytopenic purpura treated with rituximab and plasma exchange

2007 ◽  
Vol 87 (4) ◽  
pp. 321-323 ◽  
Author(s):  
A. L. Basquiera ◽  
J. C. Damonte ◽  
P. Abichaín ◽  
A. G. Sturich ◽  
J. J. García
Keyword(s):  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura

Rituximab Provided Long-term Remission in a Patient with Refractory Relapsing Thrombotic Thrombocytopenic Purpura

2005 ◽  
Vol 81 (5) ◽  
pp. 433-436 ◽  
Author(s):  
Satoru Kosugi ◽  
Masanori Matsumoto ◽  
Yasushi Ohtani ◽  
Hironori Take ◽  
Hiromichi Ishizashi ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura

scholarly journals Describing the Point Prevalence and Characteristics of Venous Thromboembolism in Patients with Thrombotic Thrombocytopenic Purpura

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2381-2381
Author(s):  
Brandon Tse ◽  
Gloria Lim ◽  
Michelle Sholzberg ◽  
Katerina Pavenski
Keyword(s):  
Venous Thromboembolism ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Symptom Onset ◽  
Research Funding ◽  
Point Prevalence ◽  
Thrombocytopenic Purpura ◽  
Platelet Recovery ◽  
Vein Thrombosis ◽  
Superficial Vein Thrombosis ◽  
History Of

Background: Thrombotic thrombocytopenic purpura (TTP) presents with microangiopathic hemolytic anemia, thrombocytopenia and microvascular thrombosis. Arterial thromboembolic events are relatively common and well-described in these patients. However, the literature describing venous thromboembolism (VTE) in this patient population is scarce and outdated. We hypothesize that patients with TTP are at greater risk for VTE due to the use of central venous catheters and use of solvent-detergent plasma (SDP) for plasma exchange (PLEX). Methods: Eligible patients from a single tertiary care centre were identified through apheresis records, and a retrospective chart review was conducted. The criteria for TTP diagnosis included the presence of accepted clinical/laboratory criteria and ADAMTS13 activity <10%. We considered the diagnosis of VTE if any of the following were present: pulmonary embolism (PE), deep vein thrombosis (DVT) or superficial vein thrombosis (SVT). Data were analyzed using simple descriptive statistics. Institutional research ethics board approval was obtained. Results: We identified 77 consecutive patients with 123 episodes of TTP between January 1, 2008 and December 31, 2018. 51 patients (66%) were female, and 74 (96%) had immune TTP. Standard of care was daily PLEX and high-dose steroids, while rituximab was used for relapsed/refractory disease. In addition, 6 patients received caplacizumab. 13 of the 77 patients (17%) experienced a VTE (14 events: 6 PE, 5 DVT, 3 SVT), all of which were acute and associated with admission for either first presentation or relapse of TTP. None of the VTEs were catheter related. 8/13 patients were female, and all had immune TTP. Median age at diagnosis of VTE was 45 years (IQR: 36.0-56.5 years). 10/14 events were symptomatic; diagnosis was confirmed a median of 1.5 days after VTE symptom onset (IQR: 1-3 days). All patients were treated with PLEX, receiving a median of 17 exchanges (IQR: 10-23 exchanges). In addition, 13/14 TTP episodes were treated with corticosteroids, 9 with rituximab, and no patients received caplacizumab. 8 patients experienced a VTE while receiving daily PLEX; the majority (6/8) were being exchanged with SDP. VTE was diagnosed a median of 13.5 days after initiation of PLEX (IQR: 9.2-23.5 days). At TTP presentation, median platelet count was 11 x 109/L (IQR: 7-16 x 109/L), and median LDH was 894 U/L (IQR: 508-1272 U/L). At VTE diagnosis, the median platelet and LDH levels were 170 x 109/L (IQR: 126-248 x 109/L), and 232 U/L (IQR: 176-254 U/L) respectively. No patients had D-dimer testing at VTE symptom onset or diagnosis. Of the 6 patients with PE, 3 had elevated troponin levels (>0.040 ug/L) at VTE diagnosis. In terms of VTE risk factors, median BMI was 30.0 (IQR: 28.7-32.1); the majority of patients (7/13) were obese (BMI>30). 4/13 patients were active cigarette smokers. No patients had a history of lupus or antiphospholipid antibody syndrome. 2 patients had a past history of VTE, one was associated with a prior TTP episode. Most VTEs (8/14) occurred while patients were not on any pharmacologic thromboprophylaxis. For the remaining patients, dalteparin (3), ASA (2) and rivaroxaban (1) were used. VTE events were treated with direct oral anticoagulants (DOACs) including rivaroxaban and apixaban, in 10 cases. 7 of these patients were started on a DOAC after a brief initial period of low molecular weight or unfractionated heparin, 3 patients were given DOAC as upfront therapy. 4 cases were treated with warfarin (3 bridged with heparin and 1 following rivaroxaban). One distal DVT was not treated. None of the VTEs were fatal. Discussion: The point prevalence of VTE was 17% over one decade amongst patients with TTP; this is higher than previously reported in the literature. Our data also suggests that TTP patients may be at greater risk for VTE compared to general hospitalized medical patients. The majority of affected patients on PLEX were receiving SDP at VTE diagnosis. SDP contains reduced levels of proteins C and S and may have a pro-thrombotic effect. Almost all VTEs occurred after platelet recovery and normalization of hemolytic markers, suggesting a different pathophysiology than arterial thrombosis in this setting. VTE thromboprophylaxis was uncommon since it was often held due to thrombocytopenia and not resumed upon platelet recovery. Our findings suggest the need to implement VTE thromboprophylaxis earlier in patients admitted with TTP. Disclosures Sholzberg: Novartis: Honoraria; Amgen: Honoraria, Research Funding. Pavenski:Ablynx: Honoraria, Research Funding; Alexion: Honoraria, Research Funding; Shire: Honoraria; Octapharma: Research Funding; Bioverativ: Research Funding.

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