Click to Enlarge: Kaplan–Meier survival curve on mortality by TTP plus treatment status using adjusted inverse propensity score weights. Abbreviations used: TTP = thrombotic thrombocytopenic purpura, Dx = diagnosis. Source: Diseases Journal
AUGUSTA, GA — Patients with end-stage renal disease (ESRD) with thrombotic thrombocytopenic purpura (TTP) who are treated by therapeutic plasma exchange (TPE) are at lower risk of mortality than ESRD patients without this diagnosis. That indicated that TPE is warranted when there is clinical suspicion of TTP, according to a recent study.
The retrospective cohort study published in the journal Diseases aimed to determine whether TTP is an independent risk factor for mortality. The research team investigated the association of TPE-treated TTP in ESRD patients with mortality, demographics and clinical comorbidities.1
The study authors are affiliated with Medical College of Georgia at Augusta University in Augusta, GA, and the VA Augusta (GA) Health Care System.
TTP, a rare blood disorder in which blood clots form in small blood vessels throughout the body, exhibits 90% mortality without prompt treatment. The serious condition, with 1.5-6 cases per million adults annually, occurs due to a decrease in the activity or absence of the enzyme ADAMTS13. TTP results from either congenital or immune-mediated factors, and the most common risk factors for immune-mediated TTP are antiplatelet drugs, immunosuppressive agents, human immunodeficiency virus (HIV), combination oral contraceptives and pregnancy.
TTP incidence also is associated with certain demographics, including female sex (incidence 2 to 3 times that of men) and African-American race (eight-fold higher incidence than Caucasian race). Pregnancy can also sometimes lead to TTP, the investigators explained.
Prompt diagnosis and treatment of TTP is crucial: Without proper treatment, death has been reported in only 4 days. For both types of TTP, the primary treatment is plasma infusion or plasma exchange. The authors wanted to conduct this study, because kidney damage is a potential consequence of TTP.
“We wondered what the effects of this disease would be on those whose kidneys had already failed,” Wendy Bollag, PhD, a Regents’ Professor of Physiology at Medical College of Georgia at Augusta University, told U.S. Medicine. “We found that the demographics were similar to those for the general population.”
Using the United States Renal Data System, the researchers identified ESRD patients starting dialysis between Jan. 1, 2005, and Dec. 31, 2018, using International Classification of Diseases (ICD)-9 and ICD-10 codes for thrombotic microangiopathy, with a TPE procedure code entered within 7 days. Since the ICD-9 and ICD-10 codes for TTP encompass other thrombotic microangiopathies, this study defined a patient with TTP as having at least one diagnosis of thrombotic microangiopathy with a TPE treatment procedure code within 7 days of that diagnosis (TPE-treated TTP).
Patients included in the study were between 18 and 100 years old and had an average age of 63.8. Also, 44% of patients were female, 27% were of black race, 7% were of other race, and 16% were Hispanic. Nearly all were on hemodialysis, and the majority used a catheter for their access type (81%). In addition, 12% had hypothyroidism, 1.3% had illicit drug use, 13% used tobacco, and 4% were alcohol dependent.
The investigators used statistical analyses to assess mortality, adjusting for demographic and clinical factors. The primary outcome of interest was time to death in years.
“The study reaffirms the current practice of providing therapeutic plasma exchange (TPE) in cases of thrombotic thrombocytopenic purpura (TTP), in that patients with end-stage renal disease (ESRD) with TTP or thrombotic microangiopathy provided TPE were at lower risk of mortality than ESRD patients without the diagnosis,” said Bollag, also a research career scientist at the VA Augusta Health Care System. “The take-home message is that in patients for whom there is any clinical suspicion of TTP, TPE is warranted.”
“The study validates the current practice of TPE as the first-line treatment for TTP,” she explained. “It also suggests that, if physicians suspect cases of patients with ESRD exhibiting potential signs of TTP, TPE should be ordered.”
With TPE-treated TTP, treatment is given daily until remission, which is defined as a sustained clinical response (normalized platelet count) with either no TPE and no anti-VWF therapy after 30 days or the normalization of ADAMTS13 levels. Second-line treatments are available to avoid relapse, the authors pointed out.
The study found that 66% of the 1,155,136 patients with ESRD included in the study died during the study period. The average time to death was 3.5 months.
The analysis also determined that increased age, black race and Hispanic ethnicity were associated with a lower risk of TPE-treated TTP diagnosis, while female sex and tobacco use had a higher risk. A claim for TPE-treated TTP carried a lower risk of death (adjusted hazard ratio = 0.024, CI: 0.021-0.028). Female sex, black race, Hispanic ethnicity and hypothyroidism were also associated with decreased all-cause mortality, according to the study.
“The fact that patients are automatically enrolled in Medicare once dialysis is initiated shows the benefits of access to medical care in that our study showed that Black and other race (compared to White race) and Hispanic ethnicity were associated with a reduced risk of mortality,” Bollag said. “In addition, our results suggest that when in doubt about whether or not a patient may be exhibiting signs of TTP, physicians should order TPE.”
This protection from mortality may be attributed to the well-established treatment regimen for this condition, as compared to other disease processes with more complex and nuanced treatments, the researchers suggested.
Study authors noted that a large percentage of ESRD patients identified with TPE-treated TTP were also diagnosed with hypothyroidism, but they couldn’t provide exact numbers or percentages due to reporting regulations that protect patient confidentiality. The low frequency of treated TTP patients without hypothyroidism also precluded a determination of the odds ratio, according to the study.
“Our study detected an unexpected potential association of TTP with hypothyroidism which we think warrants further investigation,” Bollag added.
The investigators recommended that future studies to assess potential endocrine associations with TTP may be warranted, in addition to research to determine the effects of new drugs, like caplacizumab, on all-cause mortality associated with TTP.
- Kincaid BS, Kim K, Waller JL, Baer SL, Bollag WB, Bollag RJ. Association of Therapeutic Plasma Exchange-Treated Thrombotic Thrombocytopenic Purpura with Improved Mortality Outcome in End-Stage Renal Disease. Diseases. 2025 Aug 5;13(8):247. doi: 10.3390/diseases13080247. PMID: 40863221; PMCID: PMC12385575.
