Longitudinal characterization of symptoms, healthcare resource utilization, and costs among people with thrombotic thrombocytopenic purpura compared with non-thrombotic thrombocytopenic purpura controls.

AIMS: Thrombotic thrombocytopenic purpura (TTP) is an ultra-rare blood disorder, characterized by severe ADAMTS13 deficiency. Affected individuals present with potentially life-threatening acute events and may experience sub-acute and chronic TTP manifestations often resulting in long-term organ damage. Incremental symptom prevalence before, during, and after an acute event as well as healthcare resource utilization (HCRU) and costs during and after an acute event were compared between people with TTP and matched non-TTP controls. METHODS: This retrospective, matched study used data from Merative MarketScan Commercial Database and Medicare Supplemental Database (from January 1, 2008, through September 30, 2021) to identify people with TTP (inpatient diagnosis for "thrombotic microangiopathy (TMA)" or "congenital TTP," and ≥1 claim for plasma exchange or infusion). People with TTP were matched (1:2) with non-TTP controls on age, sex, geographic region, index year, and select Elixhauser comorbidities. RESULTS: 255 people with TTP were matched with 510 non-TTP controls. Both cohorts had a mean age of 43.9 years; 71% were female. Overall, more people with TTP reported symptoms compared with non-TTP controls prior to (51% vs 43%), during (99% vs 52%), and after an acute event (85% vs 50%; p < 0.05 for all periods). Symptom prevalence decreased following an acute event compared with during an acute event, but remained high-85% of people with TTP experienced symptoms compared with 50% of non-TTP controls. HCRU and mean costs per patient per month were significantly higher in all care settings among people with TTP compared with non-TTP controls (p < 0.05). LIMITATIONS: Identification of patient populations may have been limited due to coding errors, as the data were obtained from an administrative claims database. CONCLUSIONS: TTP is associated with a substantial symptom burden and increased costs and HCRU during and up to almost a year after acute events, demonstrating the longitudinal burden of this disease.

Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab ± other immunomodulatory agents. The addition of caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery and reduce TPE treatments and hospital length of stay in TTP patients treated in 2 major randomized clinical trials. The addition of caplacizumab to SOC also led to increased bleeding from transient reductions in von Willebrand factor and increased relapse rates. Using data from the 2 clinical trials of caplacizumab, we performed the first-ever cost-effectiveness analysis in TTP. Over a 5-year period, the projected incremental cost-effectiveness ratio (ICER) in our Markov model was $1 482 260, significantly above the accepted 2019 US willingness-to-pay threshold of $195 300. One-way sensitivity analyses showed the utility of the well state and the cost of caplacizumab to have the largest effects on ICER, with a reduction in caplacizumab cost demonstrating the single greatest impact on lowering the ICER. In a probabilistic sensitivity analysis, SOC was favored over caplacizumab in 100% of 10 000 iterations. Our data indicate that the addition of caplacizumab to SOC in treatment of acquired TTP is not cost effective because of the high cost of the medication and its failure to improve relapse rates. The potential impact of caplacizumab on health system cost using longer term follow-up data merits further study.

Utilizing a PLASMIC score-based approach in the management of suspected immune thrombotic thrombocytopenic purpura: a cost minimization analysis within the Harvard TMA Research Collaborative.

The PLASMIC score is a recently described clinical scoring algorithm that rapidly assesses the probability of severe ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) deficiency among patients presenting with microangiopathic haemolytic anaemia. Using a large multi-institutional cohort, we explored whether an approach utilizing the PLASMIC score to risk-stratify patients with suspected immune thrombotic thrombocytopenic purpura (iTTP) could lead to significant cost savings. Our consortium consists of institutions with an unrestricted approach to ADAMTS13 testing (Group A) and those that require pre-approval by the transfusion medicine service (Group B). Institutions in Group A tested more patients than those in Group B (P < 0·001) but did not identify more cases of iTTP (P = 0·29) or have lower iTTP-related mortality (P = 0·84). Decision tree cost analysis showed that applying a PLASMIC score-based strategy to screen patients for ADAMTS13 testing in Group A would have reduced costs by approximately 27% over the 12-year period of our study compared to the current approach. Savings were primarily driven by a reduction in unnecessary therapeutic plasma exchanges, but lower utilization of ADAMTS13 testing and subspecialty consultations also contributed. Our data indicate that using the PLASMIC score to guide ADAMTS13 testing and the management of patients with suspected iTTP could be associated with significant cost savings.

ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysis.

BACKGROUND: The ADAMTS13 test distinguishes thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies (TMAs). The PLASMIC score helps determine the pretest probability of ADAMTS13 deficiency. Due to inherent limitations of both tests, and potential adverse effects and cost of unnecessary treatments, we performed a cost-effectiveness analysis (CEA) investigating the benefits of incorporating an in-hospital ADAMTS13 test and/or PLASMIC score into our clinical practice. STUDY DESIGN AND METHODS: A CEA model was created to compare four scenarios for patients with TMAs, utilizing either an in-house or a send-out ADAMTS13 assay with or without prior risk stratification using PLASMIC scoring. Model variables, including probabilities and costs, were gathered from the medical literature, except for the ADAMTS13 send-out and in-house tests, which were obtained from our institutional data. RESULTS: If only the cost is considered, in-house ADAMTS13 test for patients with intermediate- to high-risk PLASMIC score is the least expensive option ($4,732/patient). If effectiveness is assessed as measured by the number of averted deaths, send-out ADAMTS13 test is the most effective. Considering the cost/effectiveness ratio, the in-house ADAMTS13 test in patients with intermediate- to high-risk PLASMIC score is the best option, followed by the in-house ADAMTS13 test without the PLASMIC score. CONCLUSIONS: In patients with clinical presentations of TMAs, having an in-hospital ADAMTS13 test to promptly establish the diagnosis of TTP appears to be cost-effective. Utilizing the PLASMIC score further increases the cost-effectiveness of the in-house ADAMTS13 test. Our findings indicate the benefit of having a rapid and reliable in-house ADAMTS13 test, especially in the tertiary medical center.

Health care utilization of patients diagnosed with idiopathic thrombotic thrombocytopenic purpura in a commercially insured population in the United States.

BACKGROUND: Incident idiopathic thrombotic thrombocytopenic purpura (TTP) is an uncommon, potentially fatal blood disorder for which there are little or no data on health care costs. STUDY DESIGN AND METHODS: Patients satisfying a validated claims-based algorithm including an inpatient diagnosis of TTP and plasma exchange (PE) procedure during the period January 1, 2001 to May 31, 2008 were identified in the HealthCore Integrated Research Database. To characterize patterns of treatment and payments, a quantitative evaluation of comorbidities and treatments, health care utilization, and payments among this population of patients was conducted. All patients were followed until death, end of health plan enrollment, or 365 days after the TTP hospitalization, whichever occurred first. RESULTS: One hundred fifty-one patients met the claims coding algorithm. Mean total health care payments for the TTP hospitalization were $56,347 (standard deviation [SD] $80,230). Ten patients (6.6%) died during the hospitalization for TTP. Mean payments for PE services in the month following discharge were $9127 (SD $20,840). Several patients required prolonged PE during the acute TTP phase (up to 116 separate exchanges over a period of 365 days), prolonging required treatment and skewing payments and resource utilization during the 365-day period following discharge from the index TTP hospitalization. CONCLUSION: These data document the health care resource utilization by patients with idiopathic TTP, demonstrating that management of these patients is not only expensive but also skewed, with some patients requiring prolonged treatment. These data can contribute to cost-effectiveness models when new treatments for TTP become available.

[Comparison of laparoscopic splenectomy in supine position with hanging-spleen technique in idiopathic thrombocytopenic purpura]. / Vergleich der laparoskopischen Splenektomie in Steinschnittlage mit der Hanging-Spleen-Technik bei idiopathischer thrombozytopenischer Purpura.

BACKGROUND: Laparoscopic splenectomy has become the gold standard intervention for elective splenectomy. Several techniques have been described, which differ in trocar localisations and patient positions. The hanging-spleen technique was examined in comparison to the conventional laparoscopic splenectomy in the supine position among the patient population in our institution over a period of 8 years. PATIENTS AND METHODS: On the basis of a retrospective analysis, data were collected on all patients who underwent elective laparoscopic splenectomy for idiopathic thrombocytopenic purpura between May 1994 and April 2002 and were examined for operation time, blood loss and peri-operative complications. Two types of operation were compared, the conventional laparoscopic splenectomy in the supine position (group A) and the hanging-spleen technique (group B). Finally, the costs of materials of the two operation techniques were compared. RESULTS: For 51 patients (43.1 % men, 56.9 % women) (mean age: 45.5 ± 17.5 years) the mean operation times were 134.2 ± 47.3 min (group A) and 9.8 ± 39.9 min (group B). The mean blood losses were 691.3 ± 544.4 mL in group A and 638.3 ± 1050.6 mL in group B. The perioperative complications were 38.8 % in group A and 21.2 % in group B. There was no significant difference found for operation time, blood loss and perioperative complications in a multivariate analysis. The cost of materials was reduced in group B (use of Endo-GIA 42.4 % in group B, 100 % in group A). In group A 4 incisions, in group B 3 incisions were necessary. CONCLUSIONS: Regarding operation time, blood loss and perioperative complications the 2 laparoscopic techniques for splenectomy do not differ significantly. Merely reduced material costs and a reduction of incisions were found in patients -operated with the hanging-spleen technique. Whether the hanging-spleen technique is the method of choice will have to be shown by further prospective studies.

Laparoscopic splenectomy for idiopathic thrombocytopenic purpura: comparison of laparoscopic surgery and conventional open surgery.

In chronic idiopathic thrombocytopenic purpura (ITP), the two main therapeutic choices are steroid treatment or splenectomy. The adult form of ITP is described as a disease found primarily in young adults, with a female predominance. Treatment with steroids effects a complete response in less than 30% of patients, whereas splenectomy is successful in more than 60% of patients who undergo it. The minimal access afforded by laparoscopic splenectomy is considered highly desirable for these patients. The purpose of this study was to compare the clinical benefits of a laparoscopic splenectomy with those of conventional open surgery for patients with ITP. From 1968 to 1993, splenectomy was performed on 51 patients: 10 operations done laparoscopically and 41 performed conventionally. Complications, postoperative pain, recovery, and hospital charges were then compared. Laparoscopic splenectomy involved minimal incisions, and a significantly lower frequency of analgesia was required for postoperative abdominal pain (1.3 vs. 3.3); hospital stay was shorter (8.2 vs. 20.1 days) (p < 0.005). Operative time was significantly longer for the laparoscopic surgery (249.2 vs. 99.8 min) (p < 0.0001), but blood loss was less (176.0 vs. 511.7 g) (p < 0.01). No intraoperative or postoperative major complications occurred with the laparoscopic procedures, compared with 46.3% with conventional surgery. Finally, the total hospital costs were lower with laparoscopic splenectomy, especially for postoperative care (p < 0.05). A laparoscopic splenectomy may well be considered the surgical treatment of choice for patients requiring a splenectomy in view of both quality of life and economy.

Should intravenous immunoglobulin G be first-line treatment for acute thrombotic thrombocytopenic purpura? Case report and review of the literature.

Acute thrombotic thrombocytopenic purpura (TTP) is a rare and serious disease. Treatment with prednisone, anticoagulation, antiplatelet drugs, splenectomy, exchange transfusions, vincristine, and plasmapheresis may be effective in some patients, but the response to these therapies is inconsistent and all carry the potential for serious side effects. We, and others, have recently seen dramatic responses to intravenous (IV) immunoglobulin G (IgG) when other treatments have failed. Although IV IgG is expensive, its costs are low compared with those extended plasmapheresis regimens. Since the response to treatment can usually be evaluated within a few days and the side effects appear less than with other treatments, we believe a strong case can be made for the use of IV IgG as first-line therapy for acute TTP. Continued multicenter studies are necessary to finally solve the problem of competing and confusing treatment attempts and synergism of treatment in acute TTP.