Association of Hematocrit and Platelet Values Post RBC Exchange (RCE) with Vaso-Occlusive Complications in Sickle Cell Disease (SCD)

Background

Sickle cell disease (SCD) is a genetic red blood cell disorder characterized by vaso-occlusive episodes, chronic hemolytic anemia and multi-organ failure leading to decreased life quality and longevity. Automated red cell exchange (RCE) is a cornerstone treatment to reduce severity of SCD with goal of ameliorating and preventing vaso-occlusion while preserving organ function. RCE is used for treatment of acute stroke, acute chest syndrome, sickle hepatopathy, and primary and secondary stroke prevention. RCE requires 4-8 units of PRBC, based on baseline hematocrit (hct), hemoglobin S (HbS) percent goal and patient characteristics. RBC units have additive solution and a hct of ∼60%, but this can vary. The impact of fluid compartment equilibration may lead to a higher hct a day or two after RCE compared to immediately post-RCE. We hypothesized that increased hct might lead to increased viscosity and an associated increased risk of vaso-occlusive complications (VOC). Previous studies have shown that the platelet count dropped by 41% post RCE (PMID: 36883373). We conducted a retrospective review of pre and post-RCE hcts and platelets to determine if there is a relationship with VOC within 30 days of RCE.

Methods

This is a single center retrospective study of SCD patients who received RCE transfusions from 6/1/2015 to 6/30/2024. Inclusion criteria included >18 years with genotypes HbSS, HbSβ°,HbSβ⁺, or HbSC. Data collected included: RCE indication, age, sex, weight, height, medical history, genotype, disease modifying therapy, date of service, pre and post-RCE Hb electrophoresis, platelets (pre-RCE and immediate post-RCE), Hb, hct (pre-RCE, immediate post-RCE, and up to 7 days post-RCE) and SCD-related complications up to 30 days post-RCE, including vaso-occlusive episode, acute chest syndrome, venous thromboembolism, and priapism leading to hospitalization, emergency or acute care visits. Hcts post-RCE were analyzed via linear mixed effects model to test for VOC by time interaction effect. Platelet counts were analyzed using logistical mixed effects model, where VOC was regressed on inverse-normal transformed platelet counts (Pre, Post-RCE) or platelet count decline (Pre-Post RCE). In a previous study, we analyzed 533 post-RCE hcts for 131 RCEs of 131 patients and found an association of SCD-related complications within 30 days of RCE with greater increase per day in post-RCE hcts. A decreasing hct in RCEs with no VOC [β (95%CI) -0.14 (-0.24 - -0.027) per day, P=0.0149] versus an increasing hct in RCEs with complications [β (95% CI) 0.32 (0.11-0.53) per day, P= 0.0042]. The time by VOC interaction effect of post-RCE hct was significant [β (95%CI) 0.43 (0.18-0.68) per day VOC vs non-VOC, P=0.0007].

Results

Multiple consecutive RCEs were reviewed for 141 patients in the present study. We analyzed 525 pre-RCE hcts and 1370 hcts immediately post-RCE and up to 7 days post-RCE, 521 pre-RCE and 521 post-RCE platelet counts and SCD-related complications within 30 days. There were 156 episodes (30%) of vaso-occlusive complications of 67 patients within 30 days of the 525 RCEs. The median age was 34 years (IQ range 28-46), 79 (57%) females, 117 (85%) with HbSS/HbSβ0, and 51 (37%) on hydroxyurea. Analysis of newly collected data, validated our previous observation of association of SCD-related complications within 30 days of RCE with greater increase per day in post-RCE hcts (VOC interaction effect of post-RCE hct per day VOC vs non-VOC) [β (95%CI) 0.17 (0.026-0.31), P=0.021]. Additionally, we analyzed pre-RCE platelets and immediately post-RCE in the 521 RCEs. Higher pre-RCE platelets [OR (95%CI) 1.7 (1.1-2.4), P=0.0068] or pre-RCE platelets >300 (x1000/uL) [OR (95%CI) 2.5 (1.3-4.7), P=0.0059] are associated with VOC within 30 days of RCE. Greater decline in platelets post RCE [OR (95% CI) 1.5 (1.1-2.1), P=0.017] is associated with an increased risk of VOC post-RCE. A platelet decline >100 (x1000/uL) [OR (95%CI) 1.6 (0.8-3.1), P=0.19] also showed a trend of association with VOC.

Conclusion

We validated our previous finding of increased SCD-related complications within 30 days of RCE according to hct increment post-RCE. In addition, we observed an increased SCD-related complications within 30 days of RCE if pre-RCE platelet count is >300 or decrease in platelet count is >100. Further studies of the relationship of changes in hct and platelet counts during RCE with VOE and other complications are in order.

Gordeuk:Emmaus: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Incyte: Research Funding; Novartis: Research Funding; Modus Therapeutics: Consultancy. Campbell Lee:Association for the Advancement of Blood and Biotherapies: Consultancy, Membership on an entity's Board of Directors or advisory committees. Farooqui:Pfizer: Consultancy, Other: advisory board.