Age: 0.33
Sex: M
Vaccine: DTAPHEPBIP, HIBV, RV5, UNK
Symptoms: White blood cell count increased
Clinical narrative: Transverse myelitis; Fever; Progressive weakness; edema in the gray matter of the upper spinal cord (C1-T5); Lethargic; weak cry; difficulty feeding; Muscle weakness; Decreased balance; decreased coordination; Abnormal tone; impaired mobility; This case was reported in a literature article and described the occurrence of myelitis transverse in a 4-month-old male patient who received DTPa-HBV-IPV (Pediarix) for prophylaxis.  Co-suspect products included HAEMOPHILUS INFLUENZA B VACCINE (PEDVAX HIB) for prophylaxis, ROTAVIRUS VACCINE (ROTATEQ) for prophylaxis and PCV-13 PNEUMOCOCCAL VACCINE for prophylaxis.   The patient's past medical history included ventricular septal defect.   On an unknown date, the patient received Pediarix at an unknown dose, PEDVAX HIB at an unknown dose, ROTATEQ at an unknown dose and PCV-13 PNEUMOCOCCAL VACCINE at an unknown dose. On an unknown date, less than a month after receiving Pediarix, the patient experienced myelitis transverse (serious criteria hospitalization and GSK medically significant), fever (serious criteria hospitalization), weakness (serious criteria hospitalization), spinal cord edema (serious criteria GSK medically significant), lethargy, crying, feeding disorder of infancy or early childhood, muscle weakness, balance difficulty, decrease in coordination, muscle tone disorder and mobility decreased. The patient was treated with methylprednisolone and immunoglobulins nos (Ivig). On an unknown date, the outcome of the myelitis transverse, fever, weakness, spinal cord edema, lethargy, crying, feeding disorder of infancy or early childhood, muscle weakness, balance difficulty, decrease in coordination, muscle tone disorder and mobility decreased were unknown.   It was unknown if the reporter considered the myelitis transverse, fever, weakness, spinal cord edema, lethargy, crying, feeding disorder of infancy or early childhood, muscle weakness, balance difficulty, decrease in coordination, muscle tone disorder and mobility decreased to be related to Pediarix.  Additional details were provided as follows: This case was reported in a literature article and described the occurrence of transverse myelitis in a 4-month-old male patient who was vaccinated with Pediarix (GlaxoSmithKline), PRP-OMP (PedVax HIB), RotaTeq (Merck for both) and unspecified pneumococcal conjugate 13-valent (PCV-13) vaccine (manufacturer unknown) for prophylaxis. The patient weighed 8.9 kg and had a past medical history of ventricular septal defect. No information on patient's family history or concurrent condition or concomitant medication were provided. On an unspecified date, the patient had received his 4 months vaccination of Pediarix, PRP-OMP (PedVax HIB) (90647), RotaTeq and unspecified pneumococcal conjugate 13-valent (PCV-13) (90670) vaccine (administration route and site unspecified; dosages unknown, batch number not provided). On an unspecified date, the patient presented with 2 days of fever and progressive weakness. He was admitted to the hospital, where he appeared lethargic, had a weak cry, and had difficulty feeding. There were no reported recent illnesses, no known sick contacts at home, and no changes to his medications. Neurological examination demonstrated low tone and weakness, with the greatest symptoms in his lower extremities. His complete blood count, as reported prior to the first therapeutic plasma exchange (TPE), showed a white blood cell (WBC) count of 18.5 × 10E9/L (reference interval 6.0-14.0 × 10E9/L), a hemoglobin level of 114 g/L (reference interval 90-180 g/L), a hematocrit (HCT) of 34 percent (reference interval 28 percent- 55 percent), and a platelet count of 542 × 10E9/L (reference interval 160-370 × 10E9/L). Magnetic resonance imaging revealed marked edema in the gray matter of the upper spinal cord (C1-T5), with expansile T2 hyperintensity most consistent with myelitis of infectious or post-vaccinal etiology. The remainder of the spine appeared normal. Lumbar puncture with spinal fluid analysis showed nucleated cells at 58 × 10E6/L (reference interval 0-10 × 10E6/L), red blood cells (RBCs) at 11 × 10E6/L (reference interval 0-0 × 10E6/L), and a WBC differential count of 50 percent neutrophils, 48 percent macrophages, and 2 percent lymphocytes. The glucose level was 6.216 mmol/L (reference interval 2.22-4.44 mmol/L), and the protein level was 1060 mg/L (reference interval 150-400 mg/L). Initial therapy based on a diagnosis of transverse myelitis consisted of 261 mg (30 mg/kg) intravenous (IV) glucocorticosteroid (methylprednisolone) daily for 5 days and 8.7 g (1 g/kg) IV immunoglobulin (IVIg) daily for 2 days. Despite this treatment, there was no improvement in the patient's neurologic exam. TPE has been shown to be effective in acute central nervous system demyelinating diseases that fail to respond to first-line therapy. Accordingly, five single-plasma volume TPEs were planned and performed every other day. Dual-needle procedure TPEs were performed using Optia version 11 with 5 percent albumin as replacement fluid. Normal saline (0.9 percent sodium chloride) was used to prime the machine and then it was displaced with the custom priming (CP). Anticoagulant citrate dextrose solution A, which was, acid citrate dextrose solution A, was used as a regional anticoagulant at an anticoagulant-to-whole blood ratio of 1:10-15. All procedures were performed using a central venous dialysis catheter placed in the right internal jugular vein. For each procedure, a blood prime unit (BPU) of O-positive, leukoreduced RBCs with additive solution (AS-1 for the first, third, fifth, and sixth TPEs and AS-3 for the second and fourth TPEs) was used for CP. The BPU volume was 300 mL. After entering the patient's age and weight, Optia software prompted the TBV to be calculated manually. The TBV was calculated by multiplying the expected blood volume for the infant's age group (73-82 mL/kg) by the patient's weight (8.7 kg). The patient's calculated total blood volume (TBVs) were 635.1 and 713.4 mL, respectively, with an average of 674.25 mL, which was rounded down to 670 mL. Priming with blood was required to prevent or minimize intraprocedural (IP) changes to the patient's HCT. Without blood priming, the patient's IP HCT would have been reduced from 34 percent to 25 percent, as calculated by subtracting the Optia red cell volume (RCV) of 62.2 mL (Optia extracorporeal volume (ECV) of 183 mL × 0.34) from the patient's RCV of 227.8 mL (670 mL × 0.34), dividing by 670 mL, and multiplying by 100. A BPU HCT value of 57 percent was entered into the apheresis system software according to apheresis unit policy. This practice was based on an HCT range of 55 percent-65 percent (the mean of which was 57 percent), as provided by blood supplier, which was consistent with acceptable ranges reported in the circular of information. As part of the priming procedure, the circuit, warmer, and extension tubing were first primed with normal saline. Then, the centrifuge chamber was primed with 230 mL of packed RBCs, as calculated by Optia, and the normal saline was diverted into a waste bag. The circuit volume was 275 mL in total, with 40 mL for the warmer and 5 mL for the extension tubing. The IP fluid balance was set at 100 percent according to policy. After processing 75 mL of inlet volume (InV), the interface control started. During the first 96 mL of InV, the system returned CP fluid to the patient and did not remove any patient plasma. The priming process was completed after processing the second 96 mL of InV. Then, the exchange portion of the procedure was started. No rinse-back was performed according to protocol for patients with low TBV and the use of a BPU. The first treatment completed 25 percent of TPE but was then aborted because of the clot formation in the extracorporeal circuit, which was initially attributed to the patient's high platelet count. Accordingly, the AC ratio was adjusted from 1:15 to 1:10 for subsequent treatments without further circuit clotting issues. Repeat TPE was performed 2 days later, with no technical complications. Prior to the start of the third procedure, it was noted that the patient's HCT had increased after each of the prior TPEs. The patient's HCT increased from 34 percent to 38 percent after the first aborted procedure and from 38 percent to 42 percent after the repeated TPE. During that time, there was no RBC transfusion, diuresis, dialysis, or fluid restriction that could explain the increase in the patient's HCT. Terumo BCT was consulted by phone about the unexpected increases in the patient's HCT after two TPEs. It was informed that a value of 57 percent used for the BPU HCT during apheresis machine programming for both TPEs according to policy and that it was suspected the patient's unexpected HCT increases could be attributed to the BPUs since it was ruled out the previously mentioned reasons. The response from Terumo BCT was that "Optia will adjust the HCT of the patient to keep it stable; however, it relies on accurate data entry, including the HCT of the BPU." A decision was made to measure the actual HCT of the BPU (a sample was obtained from the bag) for subsequent treatments. Unexpectedly, the measured HCTs of the RBC units used for CP were 68 percent, 67 percent, and 69 percent, respectively, which were higher than the mean HCT provided by blood supplier. For the final three TPE procedures, the measured HCTs of the BPUs were used to set up the apheresis machine software. Subsequently, the patient's HCT did not increase and remained in the 40 percent to 42 percent range for the remainder of his hospital stay. After completion of the final session of TPE, the patient received two extra doses of IVIg to replace any immunoglobulins that were removed secondary to the TPE. Despite completion of therapy, he continued to demonstrate muscle weakness, decreased balance and coordination, abnormal tone, and impaired mobility. He was scheduled for physical therapy visits after discharge with the hope of improving and/or restoring strength and balance, as determined by the inpatient physical therapy team. This case has been considered as serious due to hospitalization. The outcome of the event was not provided. The authors did not comment on the relationship between the event of transverse myelitis and unspecified Pediarix. The authors stated, "Based on the experience reported in the current case report, the practices of respondents to our informal survey, and the previously published literature, we suggest measuring the HCT of BPUs for children who are 10 kg or less who require priming of the apheresis circuit with RBC units to ensure that accurate values are entered into the software. Performing this additional measurement for our patient resulted in successful subsequent procedures with stable patient HCT values. This new practice of measuring the HCT of BPUs for TPE in children who are 10 kg or less has been implemented at our institution. Furthermore, the impact and applicability of performing BPU HCT measurements for patients undergoing similar procedures, such as extracorporeal membrane oxygenation and CRRT, must be evaluated." This article corresponding to this case is not available for regulatory submission due to copyright restriction.      Lab Comments: Lab test done on an unknown date. Neurological examination demonstrated low tone and weakness, with the greatest symptoms in his lower extremities. Magnetic resonance imaging revealed marked edema in the gray matter of the upper spinal cord (C1-T5), with expansile T2 hyperintensity most consistent with myelitis of infectious or post-vaccinal etiology. The remainder of the spine appeared normal. Lumbar puncture with spinal fluid analysis showed nucleated cells at 58 × 10E6/L (reference interval 0-10 × 10E6/L), red blood cells (RBCs) at 11 × 10E6/L (reference interval 0-0 × 10E6/L), and a WBC differential count of 50 percent neutrophils, 48 percent macrophages, and 2 percent lymphocytes. Despite this treatment, there was no improvement in the patient's neurologic exam.