SPECTRA OPTIA
Report
- Report Number
- 1722028-2025-00091
- Event Type
- Death
- Date Received
- April 17, 2025
- Date of Event
- January 29, 2025
- Report Date
- April 17, 2025
- Manufacturer
- TERUMO BCT
- Product Code
- GKT
- UDI-DI
- 05020583122208
- PMA / PMN Number
- K183081
- Adverse Event
- Yes
- Report Source
- Manufacturer report
- Reporter Location
- BR
- Reporter Occupation
- OTHER HEALTH CARE PROFESSIONAL
- Health Professional
- Yes
Narratives
THIS REPORT IS BEING FILED TO PROVIDE ADDITIONAL INFORMATION IN B.5, H.1, H.6 AND H.11 INVESTIGATION: THIS IS AN OBSERVATIONAL CASE-SERIES UNICENTRIC STUDY EVALUATING TWO DIFFERENT TPE STRATEGIES FOR PATIENTS WITH A SEVERE FORM OF YELLOW FEVER DURING THE SAO PAULO, BRAZIL 2018¿2019 YELLOW FEVER OUTBREAK. IT WAS CONDUCTED AT HOSPITAL DAS CLINICAS (HCFMUSP), A 2200-BED TERTIARY CARE TEACHING HOSPITAL AFFILIATED TO THE UNIVERSITY OF SAO PAULO WITH 110 INTENSIVE CARE BEDS AND A 7-BED INFECTIOUS DISEASE INTENSIVE CARE UNIT (ID-ICU). ON 9 JANUARY 2018, THE ID-ICU HAD BECOME THE CENTER OF EXPERTISE FOR SEVERE FORMS OF YF IN SP. SEVERITY CRITERIA FOR ID-ICU ADMISSION WERE: ASPARTATE AMINOTRANSFERASE (AST) OR ALANINE AMINOTRANSFERASE (ALT) > 3000 U/L; INR > 1.5; PLATELET COUNT < 90 × 109/L; KIDNEY DYSFUNCTION; HEMORRHAGIC MANIFESTATIONS; ENCEPHALOPATHY; OR HEMODYNAMIC INSTABILITY. HOWEVER, IN 2019, A YELLOW FEVER OUTBREAK OCCURRED IN A REGION OF THE STATE OF SAO PAULO WHERE TRANSPORTATION TO HCFMUSP TAKES AT LEAST 6 H. FOR THIS REASON, ALL PATIENTS WHO HAD ALT/AST > 500 WERE REFERRED TO HCFMUSP. FROM 9 JAN TO 15 FEB 2018, TREATMENT CONSISTED OF STANDARD INTENSIVE CARE SUPPORT (ICS). IN THE SECOND HALF OF FEBRUARY 2018, HIGH-VOLUME TPE (HV-TPE) WAS USED IN SOME PATIENTS WITH SEVERE YF IN OUR SERVICE. TRANSIENT IMPROVEMENT OF LABORATORY RESULTS WAS OBSERVED, HOWEVER HEMORRHAGIC PHENOMENA OCCURRED BETWEEN SESSIONS OF HV-TPE WITHOUT CHANGING THE OUTCOME. SINCE APRIL 2018, THIS STRATEGY WAS MODIFIED TO MORE INTENSIVE TPE TWICE A DAY AND SUPPORTIVE TRANSFUSION, IF NECESSARY. THIS INTENSIVE PROTOCOL WAS USED ON ONE PATIENT IN 2018 SUCCESSFULLY, AND SINCE THEN IT HAS BEEN USED IN THE STATE OF SAO PAULO¿S 2019 YF OUTBREAK. TPE WAS ADMINISTERED TO PATIENTS WITH LEVELS OF AMMONIA > 70 MCMOL/L AND/OR FACTOR V (FV) < 50%. THE DEFINITION OF THE CUT-OFF OF AMMONIA WAS BASED ON THE 2018 EXPERIENCE WHEN PATIENTS WITH AMMONIA > 70 MCMOL/L HAD A HIGHER RELATIVE RISK OF DEATH (RR 2.0) (DATA NOT PUBLISHED). THE CUT-OFF OF FV < 50% WAS DEFINED BASED ON CLICHY¿S CRITERIA, CONSIDERING A REDUCTION OF 30% FROM THE REFERENCE VALUE OF 70¿150% FOR ALL PATIENTS. IN ORDER TO COMPARE TO PREVIOUS CASES, ALL PATIENTS WITH AMMONIA > 70 MCMOL/L AND/OR FV < 50% WERE SELECTED. FOR THIS ANALYSIS, PATIENTS WERE CLASSIFIED INTO THREE GROUPS ACCORDING TO TYPE OF TREATMENT GIVEN: GROUP ONE (G1)¿ICS; GROUP TWO (G2)¿ICS AND HV-TPE; AND GROUP THREE (G3)¿ICS AND INTENSIVE TPE. CLINICAL AND LABORATORY DATA WERE EXTRACTED RETROSPECTIVELY AND STORED IN THE REDCAP WEB PLATFORM. HV-TPE STRATEGY (G2): PROPOSED TREATMENT CONSISTED OF THREE CONSECUTIVE DAYS OF PLASMA EXCHANGE. THE VOLUME CHANGED WAS 10% OF BODY WEIGHT (BW) WITH FRESH FROZEN PLASMA (FFP). ONE TO THREE ADDITIONAL SESSIONS OF ONE PLASMA VOLUME EACH WERE IMPLEMENTED ACCORDING TO AMMONIA LEVELS. SUPPORTIVE TRANSFUSION WAS GUIDED MAINLY BY HEMORRHAGIC EPISODES. INTENSIVE-TPE STRATEGY (G3): VOLUME OF EXCHANGE WITH FFP WAS CALCULATED ACCORDING TO BW, HEMATOCRIT (HT), AND PLASMA VOLUME (BW × 0.7 × [1 - HT]), CONSIDERING ONE PLASMA VOLUME PER SESSION. PROCEDURE WAS PERFORMED TWICE A DAY, WITH ADDITIONAL FFP INFUSION (10 ML/KG) AT NIGHT. PLATELET CONCENTRATE WAS TRANSFUSED TO KEEP PLATELET COUNT > 30 × 109/L OR, IN THE PRESENCE OF BLEEDING, >50 × 109/L. IN SEVERE OR LIFE-THREATENING BLEEDS, TARGET WAS >80¿100 × 109/L. CRYOPRECIPITATE TRANSFUSION WAS INDICATED IF FIBRINOGEN LEVEL WAS <100 MG/DL. BASED ON BLEEDING AS WELL AS FV AND/OR AMMONIA LEVELS, THE FREQUENCY OF TPE WAS TAPERED TO ONCE A DAY, EVERY OTHER DAY AND DISCONTINUATION. DURING THE DE-ESCALATION PERIOD, FFP WAS INFUSED (5 ML/KG) 1¿2 TIMES/DAY, FOLLOWING THE SAME CRITERIA ABOVE. TRANEXAMIC ACID (10 MG/KG/DOSE, IV, EVERY 6¿8 H) WAS PRESCRIBED UNTIL DISCONTINUATION OF TPE AND TOPICAL USE WAS IMPLEMENTED IN CASES OF MUCOCUTANEOUS BLEEDING. TPE WAS PERFORMED USING FFP REPLACEMENT, WITHOUT ANTICOAGULANT (CITRATE), ONCE ALL PATIENTS HAD ALF. CALCIUM CHLORIDE WAS ADMINISTERED AT THE FOLLOWING RATES: FOR HV-TPE GROUP, 5 MMOL PER EACH LITER OF PLASMA EXCHANGE; FOR INTENSIVE-TPE GROUP, FIXED 6.8 MMOL OF CALCIUM PER SESSION. AFTER EACH SESSION, SERUM CALCIUM LEVEL WAS ASSESSED, AND ADDITIONAL SUPPLEMENTATION WAS CONSIDERED. COBE SPECTRA AND OPTIA (TERUMOBCT, TOKYO, JAPAN) AND COM.TECR (FRESENIUS KABI, BAD HOMBURG, GERMANY) TPE DEVICES WERE EMPLOYED, USING A WITHDRAWAL FLOW OF 70 ML/MINUTE ON AVERAGE. IN CASES WHERE CONTINUOUS VENOVENOUS HEMODIALYSIS WAS INDICATED, THE PLASMA EXCHANGE SYSTEM WAS CONNECTED TO THE RETURN CIRCUIT OF THE DIALYSIS SYSTEM. YFV-RNA WAS ISOLATED FROM 250 ¿L OF SERUM SAMPLES AND 20 ¿G OF RNASE-FREE GLYCOGEN WERE ADDED TO THE AQUEOUS PHASE AS AN RNA CARRIER. REAL-TIME QUANTITATIVE YFV REVERSE TRANSCRIPTION (RT-QPCR) WAS CARRIED OUT USING SUPERSCRIPTR III ONE-STEP RT-QPCR SYSTEM WITH PLATINUMR TAQ DNA POLYMERASE (INVITROGEN, THERMO FISHER SCIENTIFIC BRAND, CARLSBAD, CA, USA). THE YFV 5'NON-CODING REGION WAS TARGETED USING SPECIFIC PRIMERS AND PROBE, AS PREVIOUSLY DESCRIBED. ALL SAMPLES WERE TESTED IN TRIPLICATE. THE PRIMARY END POINT WAS MORTALITY. BASELINE CLINICAL AND LABORATORY ASPECTS WERE COMPARED AMONG GROUPS. SURVIVAL CURVES WERE CONSTRUCTED USING THE KAPLAN¿MEIER METHOD, AND THE LOG-RANK TEST WAS USED TO ASSESS DIFFERENCES BETWEEN CURVES. PROPORTIONAL HAZARD ASSUMPTION WAS CHECKED GRAPHICALLY BY LOG-MINUS-LOG VS. LOG (TIME) PLOT. COMPARISONS BETWEEN TWO GROUPS WERE ASSESSED USING THE STUDENT T-TEST, OR THE MANN¿WHITNEY TEST IF APPROPRIATE FOR QUANTITATIVE VARIABLES, AND THE FISHER EXACT TEST FOR CATEGORICAL VARIABLES. ASSUMPTIONS OF NORMALITY AND HOMOGENEITY OF VARIANCE FOR T-TEST WERE EVALUATED. DIFFERENCES BETWEEN THE 3 GROUPS IN QUANTITATIVE VARIABLES WERE EVALUATED BY THE KRUSKAL¿WALLIS TEST. COMPARISON OF PROPORTIONS BETWEEN THE 3 GROUPS WAS PERFORMED BY USING THE FISHER-EXACT TEST. QUANTITATIVE VARIABLES WERE PRESENTED AS MEDIAN (INTERQUARTILE RANGE [IQR]). CATEGORICAL VARIABLES WERE EXPRESSED AS COUNTS AND PERCENTAGES. NORMALITY WAS ASSESSED BY THE SHAPIRO¿WILK NORMALITY TEST, THE D¿AGOSTINO¿PEARSON OMNIBUS NORMALITY TEST, AND VISUAL INSPECTION OF HISTOGRAMS. ALL P-VALUES WERE TWO-SIDED. RESULTS WERE CONSIDERED SIGNIFICANT IF P < 0.05. STATISTICAL ANALYSES WERE PERFORMED USING SAS VERSION 9.4 (SAS INSTITUTE INC., CARY, NC, USA). DURING THE 2018/2019 YELLOW FEVER OUTBREAK IN SÃO PAULO, 114 CONFIRMED CASES OF YELLOW FEVER WERE REFERRED TO THE ID-ICU OF HCFMUSP. SIXTY-SIX PATIENTS HAD LEVELS OF AMMONIA > 70 MCMOL/L AND/OR AN FV OF <50% AND WERE INCLUDED FOR ANALYSIS: 41 (62%) WERE TREATED WITH ICS (G1), 11 (17%) RECEIVED ICS PLUS HV-TPE (G2) AND 14 (21%) RECEIVED ICS PLUS INTENSIVE TPE (G3). THERE WERE NO DIFFERENCES AMONG THE THREE GROUPS RELATED TO SEX AND CLINICAL PRESENTATION AT ADMISSION. ALL GROUPS HAD VALUES OF AST/ALT > 3000 U/L, HOWEVER PATIENTS OF G3 HAD LOWER LEVELS OF AST/ALT COMPARED TO THE OTHER GROUPS, PROBABLY AS A CONSEQUENCE OF THE CHANGE IN THE TRANSFER CRITERIA, WHICH ALLOWED EARLIER ASSISTANCE, PREVENTING THE PROGRESSION OF THE DISEASE. NO DIFFERENCES WERE OBSERVED AMONG THE GROUPS WITH RESPECT TO THE OTHER LABORATORY TESTS. CONCERNING G3, THE PATIENTS WERE ADMITTED WITH A MEDIAN OF SIX DAYS OF SYMPTOMS AND FEVER WAS NOTED IN 86% OF THEM. SURPRISINGLY, JAUNDICE WAS PRESENT IN ONLY 43% OF THE PATIENTS AT ADMISSION. HEMORRHAGIC PHENOMENA OCCURRED IN 11 PATIENTS (79%), THE VAST MAJORITY BEING GASTROINTESTINAL BLEEDING. TWELVE PATIENTS (86%) HAD SEIZURES AND/OR HEADACHES AS NEUROLOGIC MANIFESTATIONS. ONE OF THE FEMALE PATIENTS (LO) WAS PREGNANT AND WAS DIAGNOSED WITH REACTIVE HEMOPHAGOCYTIC SYNDROME, WHICH WAS SUCCESSFULLY TREATED WITH HUMAN INTRAVENOUS IMMUNOGLOBULIN. THE MEDIAN VOLUME TREATED AND TIME PER PROCEDURE WERE HIGHER IN G2 (P = 0.005 AND P < 0.001, RESPECTIVELY) ALTHOUGH G3 HAD A HIGHER MEDIAN NUMBER OF PROCEDURES PER PATIENT (P < 0.001) (TABLE 1). HOWEVER, 45% OF THE G2 PATIENTS DIED BEFORE CONCLUDING THE PROPOSED TREATMENT (THREE CONSECUTIVE DAYS). TRANSFUSION REACTIONS SUCH AS TRANSFUSION-RELATED ACUTE LUNG INJURY, TRANSFUSION ASSOCIATED CIRCULATORY OVERLOAD OR ABO INCOMPATIBILITY WERE NOT OBSERVED. ONLY MILD ALLERGIC SYMPTOMS OCCURRED DURING OR SOON AFTER THE PROCEDURE. HYPOCALCEMIA (IONIC CALCIUM < 4.0 MG/DL) WAS MORE FREQUENT IN G2 (P < 0.001). THE MORTALITY RATES IN G1 AND G2 WERE SIMILAR, AT 85% AND 82%, RESPECTIVELY. THE MORTALITY RATE FOR PATIENTS IN G3 WAS SIGNIFICANTLY INFERIOR, AS DEMONSTRATED IN THE KAPLAN¿MEIER SURVIVAL CURVE. ONLY TWO PATIENTS DIED IN G3. ONE WAS A 48-YO MALE PATIENT (VPP) WHO REPORTED LONG-TERM USE OF ALCOHOL, WITH FOUR DAYS OF SYMPTOMS. AST AND ALT LEVELS WERE MARKEDLY ELEVATED (403 AND 148 TIMES GREATER THAN THE UPPER LIMIT OF NORMAL [ULN], RESPECTIVELY), WITH HIGH AMMONIA LEVELS (3.7 TIMES THE ULN) AND LOW LEVELS OF FV (REDUCTION OF 90% FROM NORMAL). FOUR DIFFERENT BACTERIA WERE IDENTIFIED 48 HS LATER IN ADMISSION BLOOD CULTURE (E. COLI, S. VIRIDIANS, S. PNEUMONIAE AND F. NUCLEATUM). DESPITE ICS, ANTIBIOTICS, AND INTENSIVE TPE, THE PATIENT PRESENTED WITH A MASSIVE ALVEOLAR HEMORRHAGE AND DIED 72 HS AFTER ADMISSION (TABLE 2). THE SECOND WAS ALSO A 48-YO MALE PATIENT (VSS), PREVIOUSLY VACCINATED AGAINST YFV (10 YEARS BEFORE), WITH SIX DAYS OF SYMPTOMS. AST AND ALT LEVELS WERE MARKEDLY ELEVATED (163 AND 103 TIMES THE ULN, RESPECTIVELY), HIGH AMMONIA LEVELS (2.3 TIMES THE ULN), AND NORMAL LEVELS OF FV. AFTER FIVE DAYS OF INTENSIVE TPE, ALL LABORATORY RESULTS WERE NORMALIZED. HOWEVER, ON THE SIXTH DAY OF ADMISSION, S. AUREUS WAS IDENTIFIED IN A BLOOD CULTURE AND THE PATIENT DIED SEVEN DAYS LATER. COMPARING G2 AND G3, THE EVOLUTION OF THE MEDIAN LEVELS OF AMMONIA EXHIBITED OPPOSITE DIRECTIONS: AN INCREASING TENDENCY FOR G2 AND A DECREASING TENDENCY FOR G3 (P = 0.0002). ON THE OTHER HAND, THE LEVELS OF FV SHOWED A SIMILAR INCREASING TENDENCY IN G2 AND G3, HOWEVER, WITH STATISTICAL SIGNIFICANCY (P = 0.014). (FIGURE 2A,B). THREE DAYS AFTER TPE (DAY 4), THE SERUM YF VIRAL LOAD BECAME UNDETECTABLE IN 91.7% OF G3 COMPARED TO 28.6% OF G2. THE HIGH MORTALITY RATES OF SEVERE YF FORMS DURING THE YF OUTBREAK IN SP DESPITE INTENSIVE CARE SUPPORT PROMPTED US TO USE HV-TPE FOR YF-ALF. IN OUR CASUISTIC, USING A SIMILAR LARGE-VOLUME EXCHANGE STRATEGY, WE COULD NOT OBSERVE ANY BENEFIT IN MORTALITY. G1 AND G2 HAD SIMILAR MORTALITY RATES DESPITE THE USE OF TPE. WE IMPUTE THIS FINDING TO THE FULMINANT ONSET AND AGGRESSIVE COURSE OF ALF-YF, FASTER THAN THAT OBSERVED IN OTHER ETIOLOGIES. THIS HYPOTHESIS WAS CORROBORATED BY THE SHORT SURVIVAL OF G1 PATIENTS AND BY THE TRANSIENT IMPROVEMENT OF LABORATORY RESULTS OBSERVED AFTER HV-TPE IN G2. THE CLOSE RELATIONSHIP BETWEEN ELEVATED AMMONIA LEVELS AND THE DEVELOPMENT OF ENCEPHALOPATHY IS WELL ESTABLISHED. DURING THE FIRST MONTH OF THE OUTBREAK, WE OBSERVED THAT A PRESENCE OF AMMONIA > 70 MCMOL/L AND/OR FV < 50% WERE ASSOCIATED WITH HIGHER MORTALITY. AMONG 59 PATIENTS WITH THIS LABORATORY PROFILE, THE FIRST 48 WERE TREATED WITH ICS OR LT, AND THIRTY-NINE (81%) OF THEM DIED. CLEMMESEN ET AL., USING HV-TPE IN 11 PATIENTS WITH ALF AND HEPATIC ENCEPHALOPATHY GRADE III-IV, DEMONSTRATED A REDUCTION OF ARTERIAL AMMONIA. NEVERTHELESS, IN OUR CASUISTIC USING A SIMILAR STRATEGY, WE OBSERVED AN INCREASING TREND OF AMMONIA LEVELS INSTEAD. IN LARSEN¿S STUDY, AN INITIAL SIGNIFICANT DECREASE OF AMMONIA LEVELS WAS OBSERVED ALTHOUGH IT WAS NOT SUSTAINED AFTER DAY THREE. IN ORDER TO OVERCOME THE AGGRESSIVE BEHAVIOR OF ALF-YF AND AIMING TO OBTAIN SAFE LEVELS OF AMMONIA, A LOWER VOLUME OF TPE PER SESSION AND A REDUCTION OF THE INTERVAL BETWEEN THE PROCEDURES WERE IMPLEMENTED (INTENSIVE TPE). THIS APPROACH ALLOWED A SUSTAINED DECREASE OF AMMONIA (FIGURE 2A, G3), RESULTING IN A HIGHER SURVIVAL RATE. THE STUDIES ON HV-TPE IN HEPATOTROPIC VIRAL DISEASES ARE LIMITED. LARSEN ET AL. INCLUDED ONLY 11 PATIENTS WITH ACUTE VIRAL HEPATITIS, AND SIX OF THEM SUBMITTED TO HV-TPE [13]. ONLY TWO AMONG 11 PATIENTS TREATED BY CLEMMESEN ET AL. HAD VIRAL HEPATITIS. LIKEWISE, AKDOGAN ET AL., USING A STANDARD PLASMA EXCHANGE PROTOCOL, HAD ONLY 20% (8/39) CASES OF VIRAL HEPATITIS IN THEIR CASUISTIC. UNLIKE DRUG-INDUCED OR TOXIC HEPATITIS, IN VIRAL ETIOLOGIES THE CAUSAL AGENT IS STILL PRESENT AND THE LIVER INJURY PERSISTS. DESPITE THE FACT THAT COMMON KNOWLEDGE PRESUMES A VIREMIA OF FIVE DAYS IN YF, RECENT STUDIES DEMONSTRATED LONGER PERSISTENCE OF THE VIRUS IN THE SERUM AND OTHER ORGANS. ADDITIONALLY, IN A COHORT OF THE 2018 SP OUTBREAK, A HIGHER VIRAL LOAD WAS DEMONSTRATED TO BE AN INDEPENDENT PREDICTOR FACTOR ASSOCIATED WITH DEATH. AND, AS WE HAVE SHOWN, INTENSIVE TPE WAS ABLE TO REMOVE THE VIRUS, THUS REDUCING LIVER DAMAGE, ANOTHER POSSIBLE REASON TO JUSTIFY THE SUCCESS OF INTENSIVE TPE IN SEVERE YELLOW FEVER. ALTHOUGH TRANSAMINASE LEVELS IN G3 PATIENTS WERE LOWER THAN IN G2, THEY REMAINED MORE THAN 100 TIMES ABOVE THE UPPER LIMIT OF NORMAL, UNDERSCORING THE SEVERITY OF THE DISEASE. ADDITIONALLY, STUDIES HAVE INCREASINGLY DEMONSTRATED THAT THE YELLOW FEVER VIRUS EXHIBITS TROPISM FOR ORGANS BEYOND THE LIVER, WITH RNA OR ANTIGENS DETECTABLE IN THE MYOCARDIUM, LUNGS, KIDNEYS, PANCREAS, AND SPLEEN. FURTHERMORE, COAGULOPATHY HAS BEEN SHOWN TO OCCUR INDEPENDENTLY OF HEPATOCELLULAR TROPISM. THESE FINDINGS HIGHLIGHT THAT THE INVOLVEMENT OF MULTIPLE ORGANS SIGNIFICANTLY CONTRIBUTES TO THE SEVERITY OF THE DISEASE, AND THEREFORE SHOW THE ROLE OF TPE IN RESTORING METABOLIC AND IMMUNOLOGICAL BALANCE AND REPLENISHING COAGULATION FACTORS. INTENSIVE TPE APPARENTLY WAS SAFER WITH A LOWER INCIDENCE OF HYPOCALCEMIA COMPARED TO HV-TPE. IT WAS ALSO ASSOCIATED WITH A REDUCED MEDIAN VOLUME TREATED AND SHORTER TIME PER SESSION, ALLOWING SEQUENTIAL TREATMENT FOR A MAJOR NUMBER OF PATIENTS. THE POSSIBILITY OF SIMULTANEOUS TREATMENT FOR A LARGE NUMBER OF PATIENTS IS PARTICULARLY IMPORTANT CONSIDERING THE DRAMATIC INCREASE OF YF IN REGIONS WITH HEALTH RESOURCE CONSTRAINTS, AND THE SEASONAL PATTERN OF THE DISEASE IN OUTBREAKS. LT IS A RECOGNIZED APPROACH FOR THE MANAGEMENT OF ALF, HOWEVER THERE IS VERY RESTRICTED EXPERIENCE IN ITS USE AS A TREATMENT FOR ALF-YF. MOREOVER, THE HIGH COST OF LT AND THE SHORTAGE OF LIVER DONORS CURTAIL THE FEASIBILITY OF THE PROCEDURE. SOME LIMITATIONS OF OUR STUDY INCLUDE THE SMALL SAMPLE SIZE AND THE NEED FOR RANDOMIZED TRIALS TO CONFIRM THE EFFICACY OF THIS STRATEGY. HOWEVER, GIVEN THE FULMINANT PROGRESSION AND HIGH LETHALITY OF THE DISEASE, AN ADAPTIVE PRAGMATIC TRIAL COULD REPRESENT A FEASIBLE APPROACH TO DEMONSTRATE THIS TREATMENT¿S EFFECTIVENESS. WE DEMONSTRATED THAT IN PATIENTS WITH ALF SECONDARY TO YF, INTENSIVE TPE ASSOCIATED WITH GUIDED TRANSFUSION IS A FEASIBLE AND EFFECTIVE ARTIFICIAL SUPPORT TO KEEP PATIENTS ALIVE UNTIL HEPATIC REGENERATION AND RECOVERY OCCURS. THIS WAS DEMONSTRATED BY A REDUCTION OF 84% IN MORTALITY. THEREFORE, IT IS IMPORTANT TO SHARE OUR SUCCESSFUL EXPERIENCE, ALTHOUGH LIMITED TO A SMALL NUMBER OF CASES. UNDOUBTEDLY THERE ARE MANY KNOWLEDGE GAPS RELATED TO THE EFFECTS OF THERAPEUTIC PLASMA EXCHANGE IN THE COURSE OF YF AND OUR LIMITATIONS OF A SMALL SAMPLE SIZE, AND THE OBSERVATIONAL AND SINGLE-CENTER NATURE OF THIS STUDY. FURTHER STUDIES ARE REQUIRED TO BETTER UNDERSTAND THE ROLE OF TPE IN SEVERE YF. SINCE THIS WAS A JOURNAL PUBLICATION AN OBSERVATIONAL STUDY EVALUATING TWO DIFFERENT TPE STRATEGIES FOR PATIENTS WITH A SEVERE FORM OF YELLOW FEVER DURING THE SAO PAULO, BRAZIL 2018¿2019 YELLOW FEVER OUTBREAK, THE LOT NUMBERS WERE NOT REQUESTED; THEREFORE, A DISPOSABLE LOT HISTORY SEARCH COULD NOT BE CONDUCTED. ACCORDING TO THERAPEUTIC APHERESIS: A PHYSICIAN'S HANDBOOK, ADVERSE EVENTS OCCUR DURING THERAPEUTIC PROCEDURES WITH A FREQUENCY OF 4.8%. SYMPTOMS OF THESE ALLERGIC REACTIONS MAY INCLUDE HIVES, DYSPNEA, WHEEZING, BURNING EYES, TACHYCARDIA, HYPOTENSION, AND OR FACIAL SWELLING AND FLUSHING. MILD REACTIONS CAN BE TREATED WITH DIPHENHYDRAMINE ADMINISTERED THROUGH AN IV. ACCORDING TO THERAPEUTIC APHERESIS: A PHYSICIAN'S HANDBOOK, ADVERSE EVENTS OCCUR DURING THERAPEUTIC PROCEDURES WITH A FREQUENCY OF 4.8%. SOME OF THE MOST COMMON REACTIONS INCLUDE FEVER, URTICARIA, HYPOCALCEMIC SYMPTOMS, PRURITUS, DYSPNEA, TACHYCARDIA, AND MILD HYPOTENSION. TRANSIENT HYPOCALCEMIA ASSOCIATED WITH APHERESIS IS USUALLY WELL TOLERATED. SYMPTOMS OFTEN SHOW AS PARESTHESIA (TINGLING) BUT PATIENTS MAY ALSO EXPERIENCE UNUSUAL TASTE, NAUSEA, LIGHTHEADEDNESS, SHIVERING, AND TREMORS. SEVERE HYPOCALCEMIA MAY ALSO CAUSE MUSCLE CONTRACTIONS AND CAN PROGRESS TO TETANY AND SEIZURES IF HYPOCALCEMIA ESCALATES AND IS NOT CORRECTED. SINCE THIS WAS A JOURNAL PUBLICATION AN OBSERVATIONAL STUDY EVALUATING TWO DIFFERENT TPE STRATEGIES FOR PATIENTS WITH A SEVERE FORM OF YELLOW FEVER DURING THE SAO PAULO, BRAZIL 2018¿2019 YELLOW FEVER OUTBREAK, THE LOT NUMBERS WERE NOT REQUESTED; THEREFORE, A DHR SEARCH COULD NOT BE CONDUCTED FOR THIS SPECIFIC INCIDENT. ALL LOTS MUST MEET ACCEPTANCE CRITERIA FOR RELEASE. BASED ON THE CLINICAL INFORMATION PROVIDED, THE SPECTRA OPTIA PERFORMED AS INTENDED, THERE WERE NO SUGGESTED DEVICE FAILURES, MALFUNCTIONS, MISLABELING, IMPROPER OR INADEQUATE DESIGN OR MANUFACTURING ERRORS, NOR WAS THERE ANY REPORTED USER ERRORS THAT CONTRIBUTED TO OR CAUSED ADVERSE EVENTS. ROOT CAUSE: A ROOT CAUSE ASSESSMENT WAS PERFORMED FOR THE FIRST PATIENT DEATH. ACCORDING TO THE AUTHORS, ¿ONE WAS A 48-YO MALE PATIENT (VPP) WHO REPORTED LONG-TERM USE OF ALCOHOL, WITH FOUR DAYS OF SYMPTOMS. AST AND ALT LEVELS WERE MARKEDLY ELEVATED (403 AND 148 TIMES GREATER THAN THE UPPER LIMIT OF NORMAL [ULN], RESPECTIVELY), WITH HIGH AMMONIA LEVELS (3.7 TIMES THE ULN) AND LOW LEVELS OF FV (REDUCTION OF 90% FROM NORMAL). FOUR DIFFERENT BACTERIA WERE IDENTIFIED 48 HRS LATER IN ADMISSION BLOOD CULTURE (E. COLI, S. VIRIDIANS, S. PNEUMONIAE AND F. NUCLEATUM). DESPITE ICS, ANTIBIOTICS, AND INTENSIVE TPE, THE PATIENT PRESENTED WITH A MASSIVE ALVEOLAR HEMORRHAGE AND DIED 72 HS AFTER ADMISSION.¿ THE PATIENT IN QUESTION HAD UNDERLYING LIVER DISEASE DUE TO HIS LONG-TERM ALCOHOL USE WHICH PREDISPOSED HIM TO RISKS OF ADDITIONAL COMPLICATIONS. THIS COMBINED WITH YELLOW FEVER WOULD HAVE WORSENED HIS ALREADY COMPROMISED LIVER FUNCTION. A ROOT CAUSE ASSESSMENT WAS PERFORMED FOR THE SECOND PATIENT DEATH. ACCORDING TO THE AUTHORS, ¿THE SECOND WAS ALSO A 48-YO MALE PATIENT (VSS), PREVIOUSLY VACCINATED AGAINST YFV (10 YEARS BEFORE), WITH SIX DAYS OF SYMPTOMS. AST AND ALT LEVELS WERE MARKEDLY ELEVATED (163 AND 103 TIMES THE ULN, RESPECTIVELY), HIGH AMMONIA LEVELS (2.3 TIMES THE ULN), AND NORMAL LEVELS OF FV. AFTER FIVE DAYS OF INTENSIVE TPE, ALL LABORATORY RESULTS WERE NORMALIZED. HOWEVER, ON THE SIXTH DAY OF ADMISSION, S. AUREUS WAS IDENTIFIED IN A BLOOD CULTURE AND THE PATIENT DIED SEVEN DAYS LATER. BASED ON THE AVAILABLE INFORMATION A DEFINITIVE ROOT CAUSE COULD NOT BE DETERMINED BUT IT IS LIKELY DUE TO PROGRESSION OF THE PATIENT¿S DISEASE AND/OR COMPLICATIONS ASSOCIATED WITH YELLOW FEVER. A ROOT CAUSE ASSESSMENT WAS PERFORMED FOR THE REPORTED MILD ALLERGIC SYMPTOMS OCCURRED DURING OR SOON AFTER THE PROCEDURE. BASED ON THE AVAILABLE INFORMATION A DEFINITIVE ROOT CAUSE COULD NOT BE DETERMINED BUT IT IS LIKELY DUE TO ONE OR A COMBINATION OF THE POSSIBLE CAUSES LISTED BELOW: HYPERSENSITIVITY TO THE ETHYLENE OXIDE USED TO STERILIZE THE DISPOSABLE SET. HYPERSENSITIVITY TO THE COMPONENTS INSIDE THE DISPOSABLE SET. ALLERGIC REACTIONS TO THE REPLACEMENT FRESH FROZEN PLASMA. ANAPHYLACTIC REACTIONS HAVE BEEN REPORTED IN IGA-DEFICIENT PATIENTS WITH ANTI-IGA ANTIBODIES AND PATIENTS WITH HAPTOGLOBIN DEFICIENCY, MOST REACTIONS ARE IDIOSYNCRATIC AND NOT ASSOCIATED WITH A SPECIFIC SERUM PROTEIN DEFICIENCY, POLYMORPHISM, OR IDENTIFIABLE CAUSE. IMMEDIATE HYPERSENSITIVITY REACTION (PRODUCTION OF IGE ANTIBODIES IN RESPONSE TO ALLERGENS (PLASMA PROTEINS IN FRESH FROZEN PLASMA). PASSIVE SENSITIZATION (PASSIVE TRANSFER OF DONOR ALLERGENS OR DONOR ANTIBODIES (E.G. ALLERGEN-SPECIFIC IGE); TRANSIENT ALLERGIC SENSITIVITY TO ALLERGENS. A ROOT CAUSE ASSESSMENT WAS PERFORMED FOR THE REPORTED HYPOCALCEMIA. THESE REACTIONS OCCUR DUE TO DECREASED IONIZED CALCIUM IN CIRCULATION AS A RESULT OF EXOGENOUS CITRATE ADMINISTERED DURING THE APHERESIS PROCEDURE AND ARE INFLUENCED BY PATIENT PHYSIOLOGY, THE PATIENT'S DISEASE STATE, THE RATE OF AC INFUSION, THE CITRATE CONTENTS IN THE REPLACEMENT FLUID, AND/OR THE LENGTH OF THE PROCEDURE. THESE SYMPTOMS MAY BE TREATED WITH ORAL OR INTRAVENOUS CALCIUM SUPPLEMENTS OR BY ADJUSTING THE AC INFUSION RATE. HO, Y., NUKUI, Y., VILLAÇA, P. R., OKAZAKI, E., TATSUI, N. H., NETTO, L. C., JOELSONS, D., DA ROCHA, T. R. F., DE MELLO MALTA, F., PINHO, J. R. R., SEGURADO, A. A. C., & ROCHA, V. (2025). INTENSIVE THERAPEUTIC PLASMA EXCHANGE¿NEW APPROACH TO TREAT AND RESCUE PATIENTS WITH SEVERE FORM OF YELLOW FEVER. TROPICAL MEDICINE AND INFECTIOUS DISEASE, 10(2), 39. HTTPS://DOI.ORG/10.3390/TROPICALMED10020039.
INVESTIGATION: THIS IS AN OBSERVATIONAL CASE-SERIES UNICENTRIC STUDY EVALUATING TWO DIFFERENT TPE STRATEGIES FOR PATIENTS WITH A SEVERE FORM OF YELLOW FEVER DURING THE SAO PAULO, BRAZIL 2018¿2019 YELLOW FEVER OUTBREAK. IT WAS CONDUCTED AT HOSPITAL DAS CLINICAS (HCFMUSP), A 2200-BED TERTIARY CARE TEACHING HOSPITAL AFFILIATED TO THE UNIVERSITY OF SAO PAULO WITH 110 INTENSIVE CARE BEDS AND A 7-BED INFECTIOUS DISEASE INTENSIVE CARE UNIT (ID-ICU). ON 9 JANUARY 2018, THE ID-ICU HAD BECOME THE CENTER OF EXPERTISE FOR SEVERE FORMS OF YF IN SP. SEVERITY CRITERIA FOR ID-ICU ADMISSION WERE: ASPARTATE AMINOTRANSFERASE (AST) OR ALANINE AMINOTRANSFERASE (ALT) > 3000 U/L; INR > 1.5; PLATELET COUNT < 90 × 109/L; KIDNEY DYSFUNCTION; HEMORRHAGIC MANIFESTATIONS; ENCEPHALOPATHY; OR HEMODYNAMIC INSTABILITY. HOWEVER, IN 2019, A YELLOW FEVER OUTBREAK OCCURRED IN A REGION OF THE STATE OF SAO PAULO WHERE TRANSPORTATION TO HCFMUSP TAKES AT LEAST 6 H. FOR THIS REASON, ALL PATIENTS WHO HAD ALT/AST > 500 WERE REFERRED TO HCFMUSP. FROM 9 JAN TO 15 FEB 2018, TREATMENT CONSISTED OF STANDARD INTENSIVE CARE SUPPORT (ICS). IN THE SECOND HALF OF FEBRUARY 2018, HIGH-VOLUME TPE (HV-TPE) WAS USED IN SOME PATIENTS WITH SEVERE YF IN OUR SERVICE. TRANSIENT IMPROVEMENT OF LABORATORY RESULTS WAS OBSERVED, HOWEVER HEMORRHAGIC PHENOMENA OCCURRED BETWEEN SESSIONS OF HV-TPE WITHOUT CHANGING THE OUTCOME. SINCE APRIL 2018, THIS STRATEGY WAS MODIFIED TO MORE INTENSIVE TPE TWICE A DAY AND SUPPORTIVE TRANSFUSION, IF NECESSARY. THIS INTENSIVE PROTOCOL WAS USED ON ONE PATIENT IN 2018 SUCCESSFULLY, AND SINCE THEN IT HAS BEEN USED IN THE STATE OF SAO PAULO¿S 2019 YF OUTBREAK. TPE WAS ADMINISTERED TO PATIENTS WITH LEVELS OF AMMONIA > 70 MCMOL/L AND/OR FACTOR V (FV) < 50%. THE DEFINITION OF THE CUT-OFF OF AMMONIA WAS BASED ON THE 2018 EXPERIENCE WHEN PATIENTS WITH AMMONIA > 70 MCMOL/L HAD A HIGHER RELATIVE RISK OF DEATH (RR 2.0) (DATA NOT PUBLISHED). THE CUT-OFF OF FV < 50% WAS DEFINED BASED ON CLICHY¿S CRITERIA, CONSIDERING A REDUCTION OF 30% FROM THE REFERENCE VALUE OF 70¿150% FOR ALL PATIENTS. IN ORDER TO COMPARE TO PREVIOUS CASES, ALL PATIENTS WITH AMMONIA > 70 MCMOL/L AND/OR FV < 50% WERE SELECTED. FOR THIS ANALYSIS, PATIENTS WERE CLASSIFIED INTO THREE GROUPS ACCORDING TO TYPE OF TREATMENT GIVEN: GROUP ONE (G1)¿ICS; GROUP TWO (G2)¿ICS AND HV-TPE; AND GROUP THREE (G3)¿ICS AND INTENSIVE TPE. CLINICAL AND LABORATORY DATA WERE EXTRACTED RETROSPECTIVELY AND STORED IN THE REDCAP WEB PLATFORM. HV-TPE STRATEGY (G2): PROPOSED TREATMENT CONSISTED OF THREE CONSECUTIVE DAYS OF PLASMA EXCHANGE. THE VOLUME CHANGED WAS 10% OF BODY WEIGHT (BW) WITH FRESH FROZEN PLASMA (FFP). ONE TO THREE ADDITIONAL SESSIONS OF ONE PLASMA VOLUME EACH WERE IMPLEMENTED ACCORDING TO AMMONIA LEVELS. SUPPORTIVE TRANSFUSION WAS GUIDED MAINLY BY HEMORRHAGIC EPISODES. INTENSIVE-TPE STRATEGY (G3): VOLUME OF EXCHANGE WITH FFP WAS CALCULATED ACCORDING TO BW, HEMATOCRIT (HT), AND PLASMA VOLUME (BW × 0.7 × [1 - HT]), CONSIDERING ONE PLASMA VOLUME PER SESSION. PROCEDURE WAS PERFORMED TWICE A DAY, WITH ADDITIONAL FFP INFUSION (10 ML/KG) AT NIGHT. PLATELET CONCENTRATE WAS TRANSFUSED TO KEEP PLATELET COUNT > 30 × 109/L OR, IN THE PRESENCE OF BLEEDING, >50 × 109/L. IN SEVERE OR LIFE-THREATENING BLEEDS, TARGET WAS >80¿100 × 109/L. CRYOPRECIPITATE TRANSFUSION WAS INDICATED IF FIBRINOGEN LEVEL WAS <100 MG/DL. BASED ON BLEEDING AS WELL AS FV AND/OR AMMONIA LEVELS, THE FREQUENCY OF TPE WAS TAPERED TO ONCE A DAY, EVERY OTHER DAY AND DISCONTINUATION. DURING THE DE-ESCALATION PERIOD, FFP WAS INFUSED (5 ML/KG) 1¿2 TIMES/DAY, FOLLOWING THE SAME CRITERIA ABOVE. TRANEXAMIC ACID (10 MG/KG/DOSE, IV, EVERY 6¿8 H) WAS PRESCRIBED UNTIL DISCONTINUATION OF TPE AND TOPICAL USE WAS IMPLEMENTED IN CASES OF MUCOCUTANEOUS BLEEDING. TPE WAS PERFORMED USING FFP REPLACEMENT, WITHOUT ANTICOAGULANT (CITRATE), ONCE ALL PATIENTS HAD ALF. CALCIUM CHLORIDE WAS ADMINISTERED AT THE FOLLOWING RATES: FOR HV-TPE GROUP, 5 MMOL PER EACH LITER OF PLASMA EXCHANGE; FOR INTENSIVE-TPE GROUP, FIXED 6.8 MMOL OF CALCIUM PER SESSION. AFTER EACH SESSION, SERUM CALCIUM LEVEL WAS ASSESSED, AND ADDITIONAL SUPPLEMENTATION WAS CONSIDERED. COBE SPECTRA AND OPTIA (TERUMOBCT, TOKYO, JAPAN) AND COM.TECR (FRESENIUS KABI, BAD HOMBURG, GERMANY) TPE DEVICES WERE EMPLOYED, USING A WITHDRAWAL FLOW OF 70 ML/MINUTE ON AVERAGE. IN CASES WHERE CONTINUOUS VENOVENOUS HEMODIALYSIS WAS INDICATED, THE PLASMA EXCHANGE SYSTEM WAS CONNECTED TO THE RETURN CIRCUIT OF THE DIALYSIS SYSTEM. YFV-RNA WAS ISOLATED FROM 250 ¿L OF SERUM SAMPLES AND 20 ¿G OF RNASE-FREE GLYCOGEN WERE ADDED TO THE AQUEOUS PHASE AS AN RNA CARRIER. REAL-TIME QUANTITATIVE YFV REVERSE TRANSCRIPTION (RT-QPCR) WAS CARRIED OUT USING SUPERSCRIPTR III ONE-STEP RT-QPCR SYSTEM WITH PLATINUMR TAQ DNA POLYMERASE (INVITROGEN, THERMO FISHER SCIENTIFIC BRAND, CARLSBAD, CA, USA). THE YFV 5'NON-CODING REGION WAS TARGETED USING SPECIFIC PRIMERS AND PROBE, AS PREVIOUSLY DESCRIBED. ALL SAMPLES WERE TESTED IN TRIPLICATE. THE PRIMARY END POINT WAS MORTALITY. BASELINE CLINICAL AND LABORATORY ASPECTS WERE COMPARED AMONG GROUPS. SURVIVAL CURVES WERE CONSTRUCTED USING THE KAPLAN¿MEIER METHOD, AND THE LOG-RANK TEST WAS USED TO ASSESS DIFFERENCES BETWEEN CURVES. PROPORTIONAL HAZARD ASSUMPTION WAS CHECKED GRAPHICALLY BY LOG-MINUS-LOG VS. LOG (TIME) PLOT. COMPARISONS BETWEEN TWO GROUPS WERE ASSESSED USING THE STUDENT T-TEST, OR THE MANN¿WHITNEY TEST IF APPROPRIATE FOR QUANTITATIVE VARIABLES, AND THE FISHER EXACT TEST FOR CATEGORICAL VARIABLES. ASSUMPTIONS OF NORMALITY AND HOMOGENEITY OF VARIANCE FOR T-TEST WERE EVALUATED. DIFFERENCES BETWEEN THE 3 GROUPS IN QUANTITATIVE VARIABLES WERE EVALUATED BY THE KRUSKAL¿WALLIS TEST. COMPARISON OF PROPORTIONS BETWEEN THE 3 GROUPS WAS PERFORMED BY USING THE FISHER-EXACT TEST. QUANTITATIVE VARIABLES WERE PRESENTED AS MEDIAN (INTERQUARTILE RANGE [IQR]). CATEGORICAL VARIABLES WERE EXPRESSED AS COUNTS AND PERCENTAGES. NORMALITY WAS ASSESSED BY THE SHAPIRO¿WILK NORMALITY TEST, THE D¿AGOSTINO¿PEARSON OMNIBUS NORMALITY TEST, AND VISUAL INSPECTION OF HISTOGRAMS. ALL P-VALUES WERE TWO-SIDED. RESULTS WERE CONSIDERED SIGNIFICANT IF P < 0.05. STATISTICAL ANALYSES WERE PERFORMED USING SAS VERSION 9.4 (SAS INSTITUTE INC., CARY, NC, USA). DURING THE 2018/2019 YELLOW FEVER OUTBREAK IN SÃO PAULO, 114 CONFIRMED CASES OF YELLOW FEVER WERE REFERRED TO THE ID-ICU OF HCFMUSP. SIXTY-SIX PATIENTS HAD LEVELS OF AMMONIA > 70 MCMOL/L AND/OR AN FV OF <50% AND WERE INCLUDED FOR ANALYSIS: 41 (62%) WERE TREATED WITH ICS (G1), 11 (17%) RECEIVED ICS PLUS HV-TPE (G2) AND 14 (21%) RECEIVED ICS PLUS INTENSIVE TPE (G3). THERE WERE NO DIFFERENCES AMONG THE THREE GROUPS RELATED TO SEX AND CLINICAL PRESENTATION AT ADMISSION. ALL GROUPS HAD VALUES OF AST/ALT > 3000 U/L, HOWEVER PATIENTS OF G3 HAD LOWER LEVELS OF AST/ALT COMPARED TO THE OTHER GROUPS, PROBABLY AS A CONSEQUENCE OF THE CHANGE IN THE TRANSFER CRITERIA, WHICH ALLOWED EARLIER ASSISTANCE, PREVENTING THE PROGRESSION OF THE DISEASE. NO DIFFERENCES WERE OBSERVED AMONG THE GROUPS WITH RESPECT TO THE OTHER LABORATORY TESTS. CONCERNING G3, THE PATIENTS WERE ADMITTED WITH A MEDIAN OF SIX DAYS OF SYMPTOMS AND FEVER WAS NOTED IN 86% OF THEM. SURPRISINGLY, JAUNDICE WAS PRESENT IN ONLY 43% OF THE PATIENTS AT ADMISSION. HEMORRHAGIC PHENOMENA OCCURRED IN 11 PATIENTS (79%), THE VAST MAJORITY BEING GASTROINTESTINAL BLEEDING. TWELVE PATIENTS (86%) HAD SEIZURES AND/OR HEADACHES AS NEUROLOGIC MANIFESTATIONS. ONE OF THE FEMALE PATIENTS (LO) WAS PREGNANT AND WAS DIAGNOSED WITH REACTIVE HEMOPHAGOCYTIC SYNDROME, WHICH WAS SUCCESSFULLY TREATED WITH HUMAN INTRAVENOUS IMMUNOGLOBULIN. THE MEDIAN VOLUME TREATED AND TIME PER PROCEDURE WERE HIGHER IN G2 (P = 0.005 AND P < 0.001, RESPECTIVELY) ALTHOUGH G3 HAD A HIGHER MEDIAN NUMBER OF PROCEDURES PER PATIENT (P < 0.001) (TABLE 1). HOWEVER, 45% OF THE G2 PATIENTS DIED BEFORE CONCLUDING THE PROPOSED TREATMENT (THREE CONSECUTIVE DAYS). TRANSFUSION REACTIONS SUCH AS TRANSFUSION-RELATED ACUTE LUNG INJURY, TRANSFUSION ASSOCIATED CIRCULATORY OVERLOAD OR ABO INCOMPATIBILITY WERE NOT OBSERVED. ONLY MILD ALLERGIC SYMPTOMS OCCURRED DURING OR SOON AFTER THE PROCEDURE. HYPOCALCEMIA (IONIC CALCIUM < 4.0 MG/DL) WAS MORE FREQUENT IN G2 (P < 0.001). THE MORTALITY RATES IN G1 AND G2 WERE SIMILAR, AT 85% AND 82%, RESPECTIVELY. THE MORTALITY RATE FOR PATIENTS IN G3 WAS SIGNIFICANTLY INFERIOR, AS DEMONSTRATED IN THE KAPLAN¿MEIER SURVIVAL CURVE. ONLY TWO PATIENTS DIED IN G3. ONE WAS A 48-YO MALE PATIENT (VPP) WHO REPORTED LONG-TERM USE OF ALCOHOL, WITH FOUR DAYS OF SYMPTOMS. AST AND ALT LEVELS WERE MARKEDLY ELEVATED (403 AND 148 TIMES GREATER THAN THE UPPER LIMIT OF NORMAL [ULN], RESPECTIVELY), WITH HIGH AMMONIA LEVELS (3.7 TIMES THE ULN) AND LOW LEVELS OF FV (REDUCTION OF 90% FROM NORMAL). FOUR DIFFERENT BACTERIA WERE IDENTIFIED 48 HS LATER IN ADMISSION BLOOD CULTURE (E. COLI, S. VIRIDIANS, S. PNEUMONIAE AND F. NUCLEATUM). DESPITE ICS, ANTIBIOTICS, AND INTENSIVE TPE, THE PATIENT PRESENTED WITH A MASSIVE ALVEOLAR HEMORRHAGE AND DIED 72 HS AFTER ADMISSION (TABLE 2). THE SECOND WAS ALSO A 48-YO MALE PATIENT (VSS), PREVIOUSLY VACCINATED AGAINST YFV (10 YEARS BEFORE), WITH SIX DAYS OF SYMPTOMS. AST AND ALT LEVELS WERE MARKEDLY ELEVATED (163 AND 103 TIMES THE ULN, RESPECTIVELY), HIGH AMMONIA LEVELS (2.3 TIMES THE ULN), AND NORMAL LEVELS OF FV. AFTER FIVE DAYS OF INTENSIVE TPE, ALL LABORATORY RESULTS WERE NORMALIZED. HOWEVER, ON THE SIXTH DAY OF ADMISSION, S. AUREUS WAS IDENTIFIED IN A BLOOD CULTURE AND THE PATIENT DIED SEVEN DAYS LATER. COMPARING G2 AND G3, THE EVOLUTION OF THE MEDIAN LEVELS OF AMMONIA EXHIBITED OPPOSITE DIRECTIONS: AN INCREASING TENDENCY FOR G2 AND A DECREASING TENDENCY FOR G3 (P = 0.0002). ON THE OTHER HAND, THE LEVELS OF FV SHOWED A SIMILAR INCREASING TENDENCY IN G2 AND G3, HOWEVER, WITH STATISTICAL SIGNIFICANCY (P = 0.014). (FIGURE 2A,B). THREE DAYS AFTER TPE (DAY 4), THE SERUM YF VIRAL LOAD BECAME UNDETECTABLE IN 91.7% OF G3 COMPARED TO 28.6% OF G2. THE HIGH MORTALITY RATES OF SEVERE YF FORMS DURING THE YF OUTBREAK IN SP DESPITE INTENSIVE CARE SUPPORT PROMPTED US TO USE HV-TPE FOR YF-ALF. IN OUR CASUISTIC, USING A SIMILAR LARGE-VOLUME EXCHANGE STRATEGY, WE COULD NOT OBSERVE ANY BENEFIT IN MORTALITY. G1 AND G2 HAD SIMILAR MORTALITY RATES DESPITE THE USE OF TPE. WE IMPUTE THIS FINDING TO THE FULMINANT ONSET AND AGGRESSIVE COURSE OF ALF-YF, FASTER THAN THAT OBSERVED IN OTHER ETIOLOGIES. THIS HYPOTHESIS WAS CORROBORATED BY THE SHORT SURVIVAL OF G1 PATIENTS AND BY THE TRANSIENT IMPROVEMENT OF LABORATORY RESULTS OBSERVED AFTER HV-TPE IN G2. THE CLOSE RELATIONSHIP BETWEEN ELEVATED AMMONIA LEVELS AND THE DEVELOPMENT OF ENCEPHALOPATHY IS WELL ESTABLISHED. DURING THE FIRST MONTH OF THE OUTBREAK, WE OBSERVED THAT A PRESENCE OF AMMONIA > 70 MCMOL/L AND/OR FV < 50% WERE ASSOCIATED WITH HIGHER MORTALITY. AMONG 59 PATIENTS WITH THIS LABORATORY PROFILE, THE FIRST 48 WERE TREATED WITH ICS OR LT, AND THIRTY-NINE (81%) OF THEM DIED. CLEMMESEN ET AL., USING HV-TPE IN 11 PATIENTS WITH ALF AND HEPATIC ENCEPHALOPATHY GRADE III-IV, DEMONSTRATED A REDUCTION OF ARTERIAL AMMONIA. NEVERTHELESS, IN OUR CASUISTIC USING A SIMILAR STRATEGY, WE OBSERVED AN INCREASING TREND OF AMMONIA LEVELS INSTEAD. IN LARSEN¿S STUDY, AN INITIAL SIGNIFICANT DECREASE OF AMMONIA LEVELS WAS OBSERVED ALTHOUGH IT WAS NOT SUSTAINED AFTER DAY THREE. IN ORDER TO OVERCOME THE AGGRESSIVE BEHAVIOR OF ALF-YF AND AIMING TO OBTAIN SAFE LEVELS OF AMMONIA, A LOWER VOLUME OF TPE PER SESSION AND A REDUCTION OF THE INTERVAL BETWEEN THE PROCEDURES WERE IMPLEMENTED (INTENSIVE TPE). THIS APPROACH ALLOWED A SUSTAINED DECREASE OF AMMONIA (FIGURE 2A, G3), RESULTING IN A HIGHER SURVIVAL RATE. THE STUDIES ON HV-TPE IN HEPATOTROPIC VIRAL DISEASES ARE LIMITED. LARSEN ET AL. INCLUDED ONLY 11 PATIENTS WITH ACUTE VIRAL HEPATITIS, AND SIX OF THEM SUBMITTED TO HV-TPE [13]. ONLY TWO AMONG 11 PATIENTS TREATED BY CLEMMESEN ET AL. HAD VIRAL HEPATITIS. LIKEWISE, AKDOGAN ET AL., USING A STANDARD PLASMA EXCHANGE PROTOCOL, HAD ONLY 20% (8/39) CASES OF VIRAL HEPATITIS IN THEIR CASUISTIC. UNLIKE DRUG-INDUCED OR TOXIC HEPATITIS, IN VIRAL ETIOLOGIES THE CAUSAL AGENT IS STILL PRESENT AND THE LIVER INJURY PERSISTS. DESPITE THE FACT THAT COMMON KNOWLEDGE PRESUMES A VIREMIA OF FIVE DAYS IN YF, RECENT STUDIES DEMONSTRATED LONGER PERSISTENCE OF THE VIRUS IN THE SERUM AND OTHER ORGANS. ADDITIONALLY, IN A COHORT OF THE 2018 SP OUTBREAK, A HIGHER VIRAL LOAD WAS DEMONSTRATED TO BE AN INDEPENDENT PREDICTOR FACTOR ASSOCIATED WITH DEATH. AND, AS WE HAVE SHOWN, INTENSIVE TPE WAS ABLE TO REMOVE THE VIRUS, THUS REDUCING LIVER DAMAGE, ANOTHER POSSIBLE REASON TO JUSTIFY THE SUCCESS OF INTENSIVE TPE IN SEVERE YELLOW FEVER. ALTHOUGH TRANSAMINASE LEVELS IN G3 PATIENTS WERE LOWER THAN IN G2, THEY REMAINED MORE THAN 100 TIMES ABOVE THE UPPER LIMIT OF NORMAL, UNDERSCORING THE SEVERITY OF THE DISEASE. ADDITIONALLY, STUDIES HAVE INCREASINGLY DEMONSTRATED THAT THE YELLOW FEVER VIRUS EXHIBITS TROPISM FOR ORGANS BEYOND THE LIVER, WITH RNA OR ANTIGENS DETECTABLE IN THE MYOCARDIUM, LUNGS, KIDNEYS, PANCREAS, AND SPLEEN. FURTHERMORE, COAGULOPATHY HAS BEEN SHOWN TO OCCUR INDEPENDENTLY OF HEPATOCELLULAR TROPISM. THESE FINDINGS HIGHLIGHT THAT THE INVOLVEMENT OF MULTIPLE ORGANS SIGNIFICANTLY CONTRIBUTES TO THE SEVERITY OF THE DISEASE, AND THEREFORE SHOW THE ROLE OF TPE IN RESTORING METABOLIC AND IMMUNOLOGICAL BALANCE AND REPLENISHING COAGULATION FACTORS. INTENSIVE TPE APPARENTLY WAS SAFER WITH A LOWER INCIDENCE OF HYPOCALCEMIA COMPARED TO HV-TPE. IT WAS ALSO ASSOCIATED WITH A REDUCED MEDIAN VOLUME TREATED AND SHORTER TIME PER SESSION, ALLOWING SEQUENTIAL TREATMENT FOR A MAJOR NUMBER OF PATIENTS. THE POSSIBILITY OF SIMULTANEOUS TREATMENT FOR A LARGE NUMBER OF PATIENTS IS PARTICULARLY IMPORTANT CONSIDERING THE DRAMATIC INCREASE OF YF IN REGIONS WITH HEALTH RESOURCE CONSTRAINTS, AND THE SEASONAL PATTERN OF THE DISEASE IN OUTBREAKS. LT IS A RECOGNIZED APPROACH FOR THE MANAGEMENT OF ALF, HOWEVER THERE IS VERY RESTRICTED EXPERIENCE IN ITS USE AS A TREATMENT FOR ALF-YF. MOREOVER, THE HIGH COST OF LT AND THE SHORTAGE OF LIVER DONORS CURTAIL THE FEASIBILITY OF THE PROCEDURE. SOME LIMITATIONS OF OUR STUDY INCLUDE THE SMALL SAMPLE SIZE AND THE NEED FOR RANDOMIZED TRIALS TO CONFIRM THE EFFICACY OF THIS STRATEGY. HOWEVER, GIVEN THE FULMINANT PROGRESSION AND HIGH LETHALITY OF THE DISEASE, AN ADAPTIVE PRAGMATIC TRIAL COULD REPRESENT A FEASIBLE APPROACH TO DEMONSTRATE THIS TREATMENT¿S EFFECTIVENESS. WE DEMONSTRATED THAT IN PATIENTS WITH ALF SECONDARY TO YF, INTENSIVE TPE ASSOCIATED WITH GUIDED TRANSFUSION IS A FEASIBLE AND EFFECTIVE ARTIFICIAL SUPPORT TO KEEP PATIENTS ALIVE UNTIL HEPATIC REGENERATION AND RECOVERY OCCURS. THIS WAS DEMONSTRATED BY A REDUCTION OF 84% IN MORTALITY. THEREFORE, IT IS IMPORTANT TO SHARE OUR SUCCESSFUL EXPERIENCE, ALTHOUGH LIMITED TO A SMALL NUMBER OF CASES. UNDOUBTEDLY THERE ARE MANY KNOWLEDGE GAPS RELATED TO THE EFFECTS OF THERAPEUTIC PLASMA EXCHANGE IN THE COURSE OF YF AND OUR LIMITATIONS OF A SMALL SAMPLE SIZE, AND THE OBSERVATIONAL AND SINGLE-CENTER NATURE OF THIS STUDY. FURTHER STUDIES ARE REQUIRED TO BETTER UNDERSTAND THE ROLE OF TPE IN SEVERE YF. SINCE THIS WAS A JOURNAL PUBLICATION AN OBSERVATIONAL STUDY EVALUATING TWO DIFFERENT TPE STRATEGIES FOR PATIENTS WITH A SEVERE FORM OF YELLOW FEVER DURING THE SAO PAULO, BRAZIL 2018¿2019 YELLOW FEVER OUTBREAK, THE LOT NUMBERS WERE NOT REQUESTED; THEREFORE, A DISPOSABLE LOT HISTORY SEARCH COULD NOT BE CONDUCTED. ACCORDING TO THERAPEUTIC APHERESIS: A PHYSICIAN'S HANDBOOK, ADVERSE EVENTS OCCUR DURING THERAPEUTIC PROCEDURES WITH A FREQUENCY OF 4.8%. SYMPTOMS OF THESE ALLERGIC REACTIONS MAY INCLUDE HIVES, DYSPNEA, WHEEZING, BURNING EYES, TACHYCARDIA, HYPOTENSION, AND OR FACIAL SWELLING AND FLUSHING. MILD REACTIONS CAN BE TREATED WITH DIPHENHYDRAMINE ADMINISTERED THROUGH AN IV. ACCORDING TO THERAPEUTIC APHERESIS: A PHYSICIAN'S HANDBOOK, ADVERSE EVENTS OCCUR DURING THERAPEUTIC PROCEDURES WITH A FREQUENCY OF 4.8%. SOME OF THE MOST COMMON REACTIONS INCLUDE FEVER, URTICARIA, HYPOCALCEMIC SYMPTOMS, PRURITUS, DYSPNEA, TACHYCARDIA, AND MILD HYPOTENSION. TRANSIENT HYPOCALCEMIA ASSOCIATED WITH APHERESIS IS USUALLY WELL TOLERATED. SYMPTOMS OFTEN SHOW AS PARESTHESIA (TINGLING) BUT PATIENTS MAY ALSO EXPERIENCE UNUSUAL TASTE, NAUSEA, LIGHTHEADEDNESS, SHIVERING, AND TREMORS. SEVERE HYPOCALCEMIA MAY ALSO CAUSE MUSCLE CONTRACTIONS AND CAN PROGRESS TO TETANY AND SEIZURES IF HYPOCALCEMIA ESCALATES AND IS NOT CORRECTED. SINCE THIS WAS A JOURNAL PUBLICATION AN OBSERVATIONAL STUDY EVALUATING TWO DIFFERENT TPE STRATEGIES FOR PATIENTS WITH A SEVERE FORM OF YELLOW FEVER DURING THE SAO PAULO, BRAZIL 2018¿2019 YELLOW FEVER OUTBREAK, THE LOT NUMBERS WERE NOT REQUESTED; THEREFORE, A DHR SEARCH COULD NOT BE CONDUCTED FOR THIS SPECIFIC INCIDENT. ALL LOTS MUST MEET ACCEPTANCE CRITERIA FOR RELEASE. INVESTIGATION IS IN PROCESS, A FOLLOW-UP REPORT WILL BE PROVIDED. HO, Y., NUKUI, Y., VILLAÇA, P. R., OKAZAKI, E., TATSUI, N. H., NETTO, L. C., JOELSONS, D., DA ROCHA, T. R. F., DE MELLO MALTA, F., PINHO, J. R. R., SEGURADO, A. A. C., & ROCHA, V. (2025). INTENSIVE THERAPEUTIC PLASMA EXCHANGE¿NEW APPROACH TO TREAT AND RESCUE PATIENTS WITH SEVERE FORM OF YELLOW FEVER. TROPICAL MEDICINE AND INFECTIOUS DISEASE, 10(2), 39. HTTPS://DOI.ORG/10.3390/TROPICALMED10020039.
PER JOURNAL ARTICLE "INTENSIVE THERAPEUTIC PLASMA EXCHANGE¿NEW APPROACH TO TREAT AND RESCUE PATIENTS WITH SEVERE FORM OF YELLOW FEVER" BY HO, Y., NUKUI, Y., VILLAÇA, P. R., OKAZAKI, E., TATSUI, N. H., NETTO, L. C., JOELSONS, D., DA ROCHA, T. R. F., DE MELLO MALTA, F., PINHO, J. R. R., SEGURADO, A. A. C., & ROCHA, V. THE STUDY DISCUSSES THE USE OF INTENSIVE THERAPEUTIC PLASMA EXCHANGE (TPE) IN PATIENTS WITH SEVERE YELLOW FEVER, UTILIZING TERUMO BCT'S COBE SPECTRA AND OPTIA DEVICES. WHILE THE STUDY REPORTS A SIGNIFICANT REDUCTION IN MORTALITY WITH INTENSIVE TPE, IT ALSO NOTES ADVERSE EVENTS SUCH AS HYPOCALCEMIA AND ALLERGIC REACTIONS DURING THE PROCEDURES. SPECIFICALLY, ONE PATIENT EXPERIENCED AN ALLERGIC REACTION DURING TPE, WHICH IS A CONCERN FOR PATIENT SAFETY. THE USE OF TERUMO PRODUCTS IN THIS CONTEXT RAISES QUESTIONS ABOUT THE MANAGEMENT OF SUCH ADVERSE EVENTS AND THE NEED FOR MONITORING DURING PROCEDURES. THE FINDINGS SUGGEST THAT WHILE THE DEVICES ARE EFFECTIVE IN MANAGING SEVERE YELLOW FEVER, THERE ARE POTENTIAL RISKS ASSOCIATED WITH THEIR USE THAT NEED TO BE ADDRESSED TO ENSURE PATIENT SAFETY. THIS OBSERVATIONAL CASE-SERIES STUDY EVALUATES THE EFFECTIVENESS OF INTENSIVE THERAPEUTIC PLASMA EXCHANGE (TPE) IN TREATING SEVERE YELLOW FEVER, PARTICULARLY IN PATIENTS WITH ACUTE LIVER FAILURE. THE STUDY INVOLVED THREE GROUPS OF PATIENTS RECEIVING DIFFERENT TREATMENT REGIMENS, WITH A FOCUS ON THE OUTCOMES ASSOCIATED WITH INTENSIVE TPE USING TERUMO BCT'S COBE SPECTRA AND OPTIA DEVICES. THE RESULTS INDICATED A SIGNIFICANT REDUCTION IN MORTALITY RATES AMONG PATIENTS RECEIVING INTENSIVE TPE COMPARED TO THOSE RECEIVING STANDARD INTENSIVE CARE SUPPORT OR HIGH-VOLUME TPE. HOWEVER, THE STUDY ALSO HIGHLIGHTED ADVERSE EVENTS, INCLUDING ALLERGIC REACTIONS AND HYPOCALCEMIA, WHICH OCCURRED DURING THE PROCEDURES. THE AUTHORS CONCLUDED THAT INTENSIVE TPE IS A FEASIBLE AND EFFECTIVE INTERVENTION FOR SEVERE YELLOW FEVER, BUT FURTHER STUDIES ARE NEEDED TO CONFIRM THESE FINDINGS AND ADDRESS THE ASSOCIATED RISKS. THE SECOND WAS ALSO A 48-YO MALE PATIENT (VSS), PREVIOUSLY VACCINATED AGAINST YFV (10 YEARS BEFORE), WITH SIX DAYS OF SYMPTOMS. AST AND ALT LEVELS WERE MARKEDLY ELEVATED (163 AND 103 TIMES THE ULN, RESPECTIVELY), HIGH AMMONIA LEVELS (2.3 TIMES THE ULN), AND NORMAL LEVELS OF FV. AFTER FIVE DAYS OF INTENSIVE TPE, ALL LABORATORY RESULTS WERE NORMALIZED. HOWEVER, ON THE SIXTH DAY OF ADMISSION, S. AUREUS WAS IDENTIFIED IN A BLOOD CULTURE AND THE PATIENT DIED SEVEN DAYS LATER. ONLY MILD ALLERGIC SYMPTOMS OCCURRED DURING OR SOON AFTER THE PROCEDURE. HYPOCALCEMIA (IONIC CALCIUM < 4.0 MG/DL) WAS MORE FREQUENT IN G2 (P < 0.001) THE COLLECTION SET IS NOT AVAILABLE FOR RETURN BECAUSE IT WAS DISCARDED BY THE CUSTOMER. SPECIFIC DETAILS, SUCH AS FURTHER PATIENT INFORMATION AND OUTCOME, WERE NOT INCLUDED IN THE ARTICLE FOR THESE EVENTS, THEREFORE THIS REPORT IS BEING PROVIDED AS A SUMMARY OF THE EVENTS. IT IS UNKNOWN AT THIS TIME IF MEDICAL INTERVENTION WAS REQUIRED FOR THESE EVENTS THIS REPORT IS BEING FILED DUE TO PATIENT DEATH, ALTHOUGH PER CURRENT INFORMATION THERE IS NO DETECTABLE MALFUNCTION WITH THE TERUMO BCT DEVICE OR ALLEGATION OF A MALFUNCTION.
PER JOURNAL ARTICLE "INTENSIVE THERAPEUTIC PLASMA EXCHANGE¿NEW APPROACH TO TREAT AND RESCUE PATIENTS WITH SEVERE FORM OF YELLOW FEVER" BY HO, Y., NUKUI, Y., VILLAÇA, P. R., OKAZAKI, E., TATSUI, N. H., NETTO, L. C., JOELSONS, D., DA ROCHA, T. R. F., DE MELLO MALTA, F., PINHO, J. R. R., SEGURADO, A. A. C., & ROCHA, V. THE STUDY DISCUSSES THE USE OF INTENSIVE THERAPEUTIC PLASMA EXCHANGE (TPE) IN PATIENTS WITH SEVERE YELLOW FEVER, UTILIZING TERUMO BCT'S COBE SPECTRA AND OPTIA DEVICES. WHILE THE STUDY REPORTS A SIGNIFICANT REDUCTION IN MORTALITY WITH INTENSIVE TPE, IT ALSO NOTES ADVERSE EVENTS SUCH AS HYPOCALCEMIA AND ALLERGIC REACTIONS DURING THE PROCEDURES. SPECIFICALLY, ONE PATIENT EXPERIENCED AN ALLERGIC REACTION DURING TPE, WHICH IS A CONCERN FOR PATIENT SAFETY. THE USE OF TERUMO PRODUCTS IN THIS CONTEXT RAISES QUESTIONS ABOUT THE MANAGEMENT OF SUCH ADVERSE EVENTS AND THE NEED FOR MONITORING DURING PROCEDURES. THE FINDINGS SUGGEST THAT WHILE THE DEVICES ARE EFFECTIVE IN MANAGING SEVERE YELLOW FEVER, THERE ARE POTENTIAL RISKS ASSOCIATED WITH THEIR USE THAT NEED TO BE ADDRESSED TO ENSURE PATIENT SAFETY. THIS OBSERVATIONAL CASE-SERIES STUDY EVALUATES THE EFFECTIVENESS OF INTENSIVE THERAPEUTIC PLASMA EXCHANGE (TPE) IN TREATING SEVERE YELLOW FEVER, PARTICULARLY IN PATIENTS WITH ACUTE LIVER FAILURE. THE STUDY INVOLVED THREE GROUPS OF PATIENTS RECEIVING DIFFERENT TREATMENT REGIMENS, WITH A FOCUS ON THE OUTCOMES ASSOCIATED WITH INTENSIVE TPE USING TERUMO BCT'S COBE SPECTRA AND OPTIA DEVICES. THE RESULTS INDICATED A SIGNIFICANT REDUCTION IN MORTALITY RATES AMONG PATIENTS RECEIVING INTENSIVE TPE COMPARED TO THOSE RECEIVING STANDARD INTENSIVE CARE SUPPORT OR HIGH-VOLUME TPE. HOWEVER, THE STUDY ALSO HIGHLIGHTED ADVERSE EVENTS, INCLUDING ALLERGIC REACTIONS AND HYPOCALCEMIA, WHICH OCCURRED DURING THE PROCEDURES. THE AUTHORS CONCLUDED THAT INTENSIVE TPE IS A FEASIBLE AND EFFECTIVE INTERVENTION FOR SEVERE YELLOW FEVER, BUT FURTHER STUDIES ARE NEEDED TO CONFIRM THESE FINDINGS AND ADDRESS THE ASSOCIATED RISKS. ONE WAS A 48-YO MALE PATIENT (VPP) WHO REPORTED LONG-TERM USE OF ALCOHOL, WITH FOUR DAYS OF SYMPTOMS. AST AND ALT LEVELS WERE MARKEDLY ELEVATED (403 AND 148 TIMES GREATER THAN THE UPPER LIMIT OF NORMAL [ULN], RESPECTIVELY), WITH HIGH AMMONIA LEVELS (3.7 TIMES THE ULN) AND LOW LEVELS OF FV (REDUCTION OF 90% FROM NORMAL). FOUR DIFFERENT BACTERIA WERE IDENTIFIED 48 HS LATER IN ADMISSION BLOOD CULTURE (E. COLI, S. VIRIDIANS, S. PNEUMONIAE AND F. NUCLEATUM). DESPITE ICS, ANTIBIOTICS, AND INTENSIVE TPE, THE PATIENT PRESENTED WITH A MASSIVE ALVEOLAR HEMORRHAGE AND DIED 72 HS AFTER ADMISSION (TABLE 2). THE SECOND WAS ALSO A 48-YO MALE PATIENT (VSS), PREVIOUSLY VACCINATED AGAINST YFV (10 YEARS BEFORE), WITH SIX DAYS OF SYMPTOMS. AST AND ALT LEVELS WERE MARKEDLY ELEVATED (163 AND 103 TIMES THE ULN, RESPECTIVELY), HIGH AMMONIA LEVELS (2.3 TIMES THE ULN), AND NORMAL LEVELS OF FV. AFTER FIVE DAYS OF INTENSIVE TPE, ALL LABORATORY RESULTS WERE NORMALIZED. HOWEVER, ON THE SIXTH DAY OF ADMISSION, S. AUREUS WAS IDENTIFIED IN A BLOOD CULTURE AND THE PATIENT DIED SEVEN DAYS LATER. ONLY MILD ALLERGIC SYMPTOMS OCCURRED DURING OR SOON AFTER THE PROCEDURE. HYPOCALCEMIA (IONIC CALCIUM < 4.0 MG/DL) WAS MORE FREQUENT IN G2 (P < 0.001) THE COLLECTION SET IS NOT AVAILABLE FOR RETURN BECAUSE IT WAS DISCARDED BY THE CUSTOMER. SPECIFIC DETAILS, SUCH AS PATIENT INFORMATION AND OUTCOME, WERE NOT INCLUDED IN THE ARTICLE FOR THESE EVENTS, THEREFORE THIS REPORT IS BEING PROVIDED AS A SUMMARY OF THE EVENTS. IT IS UNKNOWN AT THIS TIME IF MEDICAL INTERVENTION WAS REQUIRED FOR THESE EVENTS THIS REPORT IS BEING FILED DUE TO PATIENT DEATH, ALTHOUGH PER CURRENT INFORMATION THERE IS NO DETECTABLE MALFUNCTION WITH THE TERUMO BCT DEVICE OR ALLEGATION OF A MALFUNCTION.
Devices
| Seq | Brand | Generic | Product Code | Manufacturer | Model | Lot | UDI-DI |
|---|---|---|---|---|---|---|---|
| 24324 | SPECTRA OPTIA | SPECTRA OPTIA EXCHANGE SET | GKT | TERUMO BCT | 05020583122208 |
Patients
| Seq | Age | Sex | Outcome | Treatment |
|---|---|---|---|---|
| 1 | 48 YR | Male | Other |