Clinical Characteristics and Outcomes of Patients with Paroxysmal Nocturnal Hemoglobinuria: A Retrospective Study from a Tertiary Care Centre in South India

Introduction Paroxysmal Nocturnal Hemoglobinuria (PNH) is a chronic acquired disorder that can cause hemolysis, thrombosis and aplastic marrow , with an incidence of 1-10 cases per million people. Studies focusing on PNH in the Indian population are relatively sparse. Although C5 inhibitors are approved for the treatment of PNH by the FDA, their availability in low and middle-income countries like India is limited. We aimed to study the clinical characteristics and outcomes of patients diagnosed with PNH attending a tertiary care center in South India without access to C5 inhibitors. Methods Details of patients who have performed a PNH test by flow cytometry (FCM) were collected retrospectively from the electronic medical records and patients who were positive for PNH were selected. Specific gating markers used for flow cytometry analysis were CD15 for granulocytes and CD64 for monocytes along with GPI-AP markers, CD24 for granulocytes and CD14 for monocytes. The patients with either granulocyte clones or monocyte clones > 5% were included for analysis. Relevant clinical information including the onset of the first symptom, date of diagnosis, last follow-up date, blood investigation at the time of symptom onset and at the time of diagnosis, bone marrow cellularity as well as treatment received were recorded. Continuous variables were summarized using mean and standard deviation. Symptoms were catagorised and analysed using a contingency table. The p-value was calculated using Fisher's exact test. Laboratory measurements were summarized using median, interquartile range (IQR), and frequency percentages. The p-values were determined using the Wilcoxon rank-sum test and Pearson's chi-square test to evaluate the associations between laboratory measurements, and disease development. The average time to diagnosis was also calculated. The Kaplan-Meier curve was used to determine the overall survival(OS) of the patients. All statistical analyses were conducted in R version 4.3.0. Results PNH (FCM) tests were done in 468 patients between January 1st, 2018 and July 1st, 2024 of which 63 (%) tested positive . From this, those having either granulocyte clones or monocyte clones > 5% were further selected (n=45). The male: female ratio was 7:8. The median age at the onset of symptoms was 35 years (7-69). Most patients n=42(93%) were referred for symptomatic cytopenias while 6(13.3%) presented with thrombosis and another 5(11.1%) presented with hemoglobinuria. Mean duration between symptom onset and diagnosis was 1.88 years(0-17.8). The median follow-up period was 2.49 years(IQR 1.10 - 4.07). Out of the 39 evaluable reports, 29(74 %) had hypocellular marrow and 20(51.2%) had erythroid hyperplasia. The mean Hemoglobin was 7.3±2.3gm/dL, total count was 3770±1790 cells/mm3,and platelet count was 50300±70600 cells/mm3. Thirty (66.67%) patients had hemolytic picture (elevated LDH, raised retic count and indirect hyperbilirubinemia); the Mean LDH was 1046.8±1371.9 IU/mL, reticulocyte count 3.3±3.7% and the total bilirubin 1.3±1.2 mg/dL. The mean granulocyte and monocyte clones were 47±36.9% and 49.5±35.8 % respectively . The average number of admissions required per patient was 2.4 (0-16). Treatment received includes steroids 12(29 %), calcineurin inhibitors 18(42.5 %), danazol 27(64%), thrombopoetin receptor agonists (14,33%) and anti-thymocyte globulin 4 (9.5%). Thirty (66.67%) required transfusion after diagnosis. On followup,hemolytic manifestations were seen to be more common than thrombotic manifestations. 6/45(13.3%) developed venous thrombosis (5 mesenteric vein, 1 cerebral venous thrombosis) and 1/45(2%) developed arterial thrombosis. Out of 45 patients, 13 patients expired, and 3 patients were lost to follow up. 6/13 (46%) died due to bleeding (intracranial bleed and Upper GI bleed) while 6/13 (46%) died due to sepsis and 1 patient died due to unrelated cause.10-year OS was 33.4%, 95% CI(0.147,0.761). 2 patients underwent an allogenic stem cell transplant but both of them succumbed. Conclusion This study was limited by it's retrospective nature . However it underscores the significant morbidity and mortality associated with PNH in a resource-limited setting, highlighting the urgent need for access to advanced therapies such as C5 inhibitors to improve patient outcomes.