Overcoming technical challenges when treating atypical hemolytic uremic syndrome with therapeutic plasma exchange
A 21-year-old female with a known history of aHUS presented to our emergency department in September 2012. She complained of general aches and pains consistent with her previous episodes of aHUS. She had three relapses before when she was aged 8, 10, and 20. They all occurred in September. She presented with 3 days of fever and sore throat followed by dark urine. On examination, she was found to be afebrile, alert, oriented, and she was talking in full sentences. Her sitting blood pressure was 140/90 mmHg and her heart rate was 70 beats per minute with an oxygen saturation of 99% on room air.\nHematological investigations revealed a hemoglobin (Hb) count of 96 g/L, platelet count 16 × 109/L, red cell count 3.01 × 1012/L, and a hematocrit of 0.27 L/L. These results were consistent with normochromic normocytic anemia with mild polychromasia. There was also marked thrombocytopenia and microangiopathic anemia on the film, features suggestive of relapse of known HUS. Biochemistry results showed a lactate dehydrogenase (LDH) level of 1,201 U/L, haptoglobin <0.06 g/L, potassium 3.7 mmol/L, urea 20.7 mmol/L, creatinine 202 umol/L, estimated glomerular filtration rate 27 mL/minute, and C-reactive protein (CRP) of 27 mg/L. High levels of LDH and low haptoglobin levels pointed to severe hemolysis while the renal markers, such as creatinine, urea, and estimated glomerular filtration rate showed a deteriorating renal function. Earlier attempts to perform the biochemical tests had been futile due to severe hemolysis.\nAfter a multidisciplinary team collaboration that involved the Intensive Care Unit, Hematology, Nephrology, and the Emergency Department, a left femoral vascath was inserted with the view of commencing TPE using 3 L of fresh frozen plasma (FFP). The procedure was scheduled to be done in the emergency department using a membrane based TPE machine (mTPE). Plasma FLUX PSu 2S plasma exchange filters manufactured by Fresenius SE & Co (Bad Homberg, Germany) were used. These filters have a surface area of 0.6 m2, blood priming volume of 70 mL, and a plasma sulphone membrane. Filtration is primarily based on pressure gradients allowing filtration of molecules of up to 1,000 kDa including immunoglobulins, complement factors, and albumin. Soon after commencing TPE, the machine showed a blood leak alarm and it was evident that the membrane had ruptured gauging by the color of the effluent (). The filter was replaced with another one which also did not last long before the machine showed a blood leak alarm. The procedure was aborted after exchanging only three bags of FFP. An attempt was made to resume treatment with a centrifuge based TPE machine (cTPE). The centrifugal device we used was a Spectra Optia Apheresis System, a product of Terumo BCT (Lakewood, CO, USA). This machine operates by separating blood products according to their specific gravity using centrifugal force. The spill over alarm persisted on cTPE and “red blood cell detected” was shown on the machine. At this point, it was agreed to stop TPE due to the nature of the technical problems which were attributed to severe hemolysis.\nOn day 2, it was agreed that the patient could be treated with eculizumab (complement C5 blocker), but the drug was not available for compassionate access. We then revisited cTPE and the consultant overseeing our cTPE machine was contacted. We were advised to “disable” the red blood cell detector and cTPE was initiated successfully using a very low inlet flow rate ranging from 20–70 mL/minute with an anticoagulant infusion rate of 1.0 mL/minute. Heavily hemolyzed effluent was noted (). The patient continued to receive daily cTPE until day 16 when a decision was made that she had reached clinical remission, and she was discharged home. Her hematological () and biochemical () results continued to improve. A follow up of this patient after 6 weeks revealed that she was clinically well and had resumed her normal daily routines. However, plans had been made for her to have a permanent vascular access in the form of an arterio-venous fistula (AVF) in the setting of these recurrent aHUS episodes which seem to resolve after aggressive TPE treatment.