Successful Use of Plasma Exchange Preceding RBC Exchange in Sickle Cell Disease Hyperhemolytic Crisis with Hepatic Sequestration: A Case Report

Introduction

Hyperhemolytic crisis is an uncommon complication of SCD that may cause multiorgan failure and lead to significant mortality. There are no current national or international guidelines for management of hyperhemolytic crisis and associated complications. There have been limited number of case reports and series that demonstrated utility of plasma exchange in the patients with multiorgan failure resulting from hemolysis complications (Zaidi GZ et al.,2020). We are presenting the case where hyperhemolytic crisis was complicated by hepatic sequestration and acute liver failure, that was dramatically reversed by 2 plasma exchange treatments followed by RBC exchange.

Case report

We present a case of a 35-year-old African American male with SCD and beta thalassemia trait with frequent hospitalizations for sickle cell pain crisis. He presented with pain typical for his acute pain crises and was admitted for intravenous hydration and pain control. The next morning, lab work showed bicytopenia with a drop in hemoglobin from 10.5 to 5.8 g/dL and platelets (PLT) from 100 to 22 X10E3/uL. Lactate dehydrogenase (LDH) increased from 434 to 2848 U/L, haptoglobin was 36 mg/dL, but disseminated intravascular coagulation (DIC) and Heparin-induced Thrombocytopenia (HIT) antibody panel were negative. The blood urea nitrogen (BUN) creatinine (Cr) ratio was also elevated (30.6) suggesting renal damage as well. He was transferred to the intensive care unit and started on Intravenous Immunoglobulin (IVIG) 0.4 grams/kilogram daily for 5 days and methylprednisolone 500 mg daily for 2 days followed by a prednisone taper. Liver enzymes continued to trend upward with AST of 19,866 U/L and ALT of 3,675 U/L on day 3 of hospitalization. Ultrasound of abdomen demonstrated mild splenomegaly with a spleen measuring 13.3 cm. The clinical presentation and hepatocellular pattern of injury was consistent with hepatic sequestration crisis. Despite receiving 1 unit of platelet 3 units of pRBC, there was little improvement and apheresis service was consulted. Plasma exchange was initiated for 2 procedures on consecutive days followed by RBC exchange with rapid improvement in clinical status and laboratory findings with a reduction of LDH (1304), AST (129), ALT (204), Hgb (8.0), PLT (41), BUN/Cr (20.0). He was discharged on day 7 at baseline status.

Discussion

Although the mechanism of development of hyperhemolysis in SCD is not fully understood, the hemolysis leads to release of free hemoglobin (Hb) and free heme that activate neutrophils, and vascular endothelial cells via TLR-4. This ultimately leads to inflammatory, coagulative, and cytotoxic damages and decreased nitric oxide (NO) bioavailability which further contributes to SCD complications such as pulmonary and systemic vasculopathy, pain crisis and acute chest syndrome and multi organ failure (Louie JE et al., 2018). This provides a rationale for plasma exchange - removal of free heme from the patient plasma and replenishing exhausted haptoglobin and hemopexin reserves from donor plasma.

Hemolytic crisis causing visceral organ damage is relatively rare. There are no current guidelines for management of such patients. In 1996 Betrosian et al. discussed the first case of liver failure in a SCD with vasa-occlusive crisis treated with RBC and plasma transfusions (Betrosian A et al., 1996). Since then, there have been case reports/series of plasma exchange/plasma transfusions in SCD with multi organ failure (Geigel EJ et al., 1997, Louie JE et al., 2018) but reports about use of plasma exchange in SCD patients with hepatic sequestration have not been identified by our literature review.

Our case demonstrates that plasma exchange in hyperhemolysis and hepatic sequestration is:

• Safe

• Leads to quick and significant improvement in hemolysis laboratory values.

• Results in quick and durable reversal of hepatic sequestration and associated liver failure.

• Adds plasma exchange as therapeutic apheresis modality in addition to previously accepted RBC exchange.

• Provides data about priority of plasma exchange over RBC exchange in this clinical situation.