BEUDAMED
    FDA Adverse Event Injury Summary report: N

    LEUKOGUARD RS LEUKOCYTE REDUCTION FILTER FOR INTRAOPERATIVELY SALVAGED WASHED BL

    MDR report key: 3530636 · Received December 20, 2013

    Report

    Report Number
    9617787-2013-00004
    Event Type
    Injury
    Date Received
    December 20, 2013
    Date of Event
    November 15, 2013
    Report Date
    January 28, 2014
    Manufacturer
    PALL MEXICO MANUFACTURING
    Product Code
    CAK
    PMA / PMN Number
    K873666
    Adverse Event
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    SW
    Reporter Occupation
    OTHER HEALTH CARE PROFESSIONAL

    Narratives

    Additional Manufacturer Narrative · 1

    REGARDING THE MANUFACTURING REGISTRATION NUMBER LISTED FOR THIS MDR INITIAL SUBMISSION, (B)(4), FOR THE INVOLVED DEVICE, PART NUMBER RS1VAE, REPRESENTS WHERE THE PRODUCT WAS IN FACT MANUFACTURED IN 2012, PALL (B)(4) MANUFACTURING FACILITY. SINCE THEN, IT IS IMPORTANT TO NOTE THAT HAEMONETIC'S CORPORATION HAS RECENTLY ACQUIRED CERTAIN ASSETS OF THE PALL CORPORATION BLOOD COLLECTION, FILTRATION AND PROCESS PRODUCT LINES. AS SUCH, THE ACTIVE REGISTRATION NUMBER, (B)(4), AS OF 2013 HAS BEEN TRANSFERRED TO HAEMONETICS (B)(4) MANUFACTURING.

    Additional Manufacturer Narrative · 1

    SUMMARY OF THE EVENT: 5 MALE CANCER PATIENTS AT (B)(6) EXPERIENCED A HYPOTENSIVE TRANSFUSION REACTION DURING REINFUSION OF CELLSAVER SALVAGED BLOOD THAT HAD BEEN FILTERED USING A LEUKOGUARD RS LEUCOCYTE REMOVAL FILTER WITH ATTACHED SET FOR SALVAGED BLOOD (PRODUCT CODE RS1VAE). WE UNDERSTAND THAT THE PATIENTS WERE UNDERGOING A UROLOGY SURGICAL PROCEDURE THAT INVOLVED PROSTATECTOMY AND THAT THE PATIENTS WERE TAKING ACE INHIBITOR MEDICATION. NONE OF THE IMPLICATED FILTERS WERE RETAINED FOR INVESTIGATION. WE HAVE PREVIOUSLY RECEIVED A SMALL NUMBER OF OTHER REPORTS OF THIS NATURE AND SUBMITTED MDR REPORTS FOR THEM. ALL BUT A SINGLE REPORTING HEALTH CARE FACILITY HAVE BEEN IN EUROPE. HYPOTENSIVE TRANSFUSION REACTIONS WHEN USING LEUKOCYTE REDUCTION FILTERS IN GENERAL HAVE BEEN THE SUBJECT OF A FDA CLINICAL ALERT DATA MAY 4, 1999. TRANSFUSION INDUCED HYPOTENSION IS A RECOGNIZED PHENOMENON AND HAS BEEN REPORTED BOTH WITH AND WITHOUT THE USE OF BEDSIDE LEUCOCYTE REMOVAL FILTERS. ALTHOUGH SOME PUBLICATIONS HAVE SUGGESTED THAT THIS IS AN EVENT SECONDARY TO THE USE OF LEUCOCYTE REMOVAL FILTERS1, A NINE YEAR STUDY BY DOMEN AND HOELTGE OF ADVERSE TRANSFUSION REACTIONS FOUND AN OVERALL INCIDENCE OF ANAPHYLACTIC OR ANAPHYLACTOID REACTION RATE OF 1.3% (21 OF 1613) AND OF THESE, NINE (42.9%) HAD ASSOCIATED HYPOTENSION2. NONE OF THESE REACTIONS INVOLVED THE USE OF BEDSIDE LEUCOCYTE REMOVAL FILTERS. WHERE HYPOTENSIVE TRANSFUSION REACTIONS HAVE BEEN OBSERVED WHEN A BEDSIDE LEUCOCYTE REMOVAL FILTER HAS BEEN EMPLOYED, THIS PHENOMENON HAS BEEN REPORTED WITH BOTH NEGATIVELY1 AND POSITIVELY3 CHARGED FILTERS FROM VARIOUS MANUFACTURERS. WE CAN ADVISE THAT THE LEUKOGUARD RS FILTER HAS A NET NEGATIVE CHARGE (ZETA POTENTIAL). MOST REPORTED CASES OF TRANSFUSION ASSOCIATED HYPOTENSION OCCUR DURING TRANSFUSION OF PLATELET CONCENTRATES4. VASOACTIVE KININS, SUCH AS BRADYKININ (BK) AND DES-ARG9-BK ARE OFTEN THOUGHT TO PLAY A ROLE IN THE DEVELOPMENT OF THESE REACTIONS. HOWEVER, IN YOUR CUSTOMER'S FACILITY WE UNDERSTAND THAT THE REPORTED HYPOTENSIVE EPISODES OCCURRED DURING REINFUSION OF WASHED SALVAGED (IE AUTOLOGOUS) BLOOD. WASHING SALVAGED BLOOD IS WELL RECOGNISED AS EFFECTIVE IN SIGNIFICANTLY REDUCING PLASMA CONSTITUENTS5. FURTHERMORE INFUSION OF AUTOLOGOUS BLOOD IS LIKELY TO REDUCE THE LIKELIHOOD OF THE PATIENT DEVELOPING AN ALLERGIC REACTION TO AN ENDOGENOUS PLASMA CONSTITUENT. THEREFORE, WHETHER THE AMOUNT OF VASOACTIVE KININS PRESENT IN WASHED SALVAGED BLOOD WOULD, IN ITSELF, BE SUFFICIENT TO ELICIT A SIGNIFICANT HYPOTENSIVE EVENT IS DEBATABLE. IF VASOACTIVE KININS DID PLAY A PART IN THE HYPOTENSIVE REACTIONS OBSERVED, FACILITY IT IS WORTHY OF NOTE THAT, ALTHOUGH THE TRIGGER FOR CONTACT SYSTEM ACTIVATION REMAINS UNCLEAR, IT HAS BEEN SPECULATED THAT THE RAPID INFUSION OF BLOOD BY THE BLOOD INFUSER OR THE WARMING OF BLOOD FOR REINFUSION BY A BLOOD WARMER MAY BE CONTRIBUTING FACTORS6. SOME AUTHORS HAVE ALSO SUGGESTED THAT BEDSIDE LEUCOCYTE REMOVAL FILTERS MAY THEMSELVES ACTIVATE THE CONTACT SYSTEM4. HOWEVER, OTHER GROUPS, USING TECHNIQUES SUCH AS THE PARTICLE CONCENTRATION FLUORESCENCE IMMUNOASSAY (PCFIA), HAVE DEMONSTRATED THAT BEDSIDE LEUCOCYTE REMOVAL FILTERS DO NOT ACTIVATE THE CONTACT SYSTEM NOR DO THEY CAUSE A CHANGE IN THE CONCENTRATION OF CLEAVED KININOGEN BI-PRODUCTS7. IT HAS PREVIOUSLY BEEN REPORTED THAT A SMALL NUMBER OF UROLOGY PATIENTS, WHERE PROSTATECTOMY HAS BEEN PERFORMED, HAVE EXPERIENCED A HYPOTENSIVE REACTION DURING REINFUSION OF WASHED SALVAGED BLOOD VIA AN RS1VAE FILTER SET. HOWEVER, IT HAS BEEN DEMONSTRATED THAT PATIENTS UNDERGOING PROSTATECTOMY, PARTICULARLY IF TAKING ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITORS MAY HAVE AN INCREASED RISK OF EXPERIENCING A HYPOTENSIVE TRANSFUSION REACTION6. HUMAN PROSTATIC TISSUE IS A RICH SOURCE OF PROSTATE-SPECIFIC HUMAN GLANDULAR KALLIKREIN 2 (HK2) AND PROSTATE-SPECIFIC ANTIGEN (HK3). RELEASE OF HK2 DURING SURGICAL MANIPULATION OF PROSTATIC TISSUE MAY FACILITATE BK AND DES-ARG9-BK GENERATION. WE NOTE THAT THE PATIENTS WHO EXPERIENCED A HYPOTENSIVE REACTION IN THESE EVENTS WERE UNDERGOING UROLOGY SURGICAL PROCEDURE THAT INVOLVED PROSTATECTOMY. THE SURGICAL PROCEDURE MAY THEREFORE HAVE BEEN A CAUSAL OR CONTRIBUTORY FACTOR TO THE HYPOTENSIVE REACTIONS OBSERVED WITH THESE PATIENTS. IT HAS ALSO BEEN DOCUMENTED THAT THE ACCUMULATION OF KININS IS FACILITATED BY THE PRESENCE OF ACE INHIBITORS AND THAT PATIENTS TAKING THIS TYPE OF MEDICATION MAY HAVE AN INCREASED RISK OF DEVELOPING A HYPOTENSIVE TRANSFUSION REACTION PARTICULARLY IF THEY ALSO HAVE AN INHERENT DEFECT IN THEIR ABILITY TO DEGRADE KININS8. IT HAS BEEN SPECULATED THAT THE MORE FREQUENT REPORTS OF HYPOTENSIVE TRANSFUSION REACTIONS NOW BEING REPORTED MAY, AT LEAST IN PART, BE DUE TO THE INCREASED USE OF ACE INHIBITORS IN RECENT YEARS 6. WE NOTE THAT THE PATIENTS WHO EXPERIENCED A HYPOTENSIVE REACTION IN YOUR CUSTOMER'S FACILITY WERE TAKING ACE INHIBITOR MEDICATION. THIS MEDICATION MAY THEREFORE HAVE ALSO BEEN A CAUSAL OR CONTRIBUTORY FACTOR TO THE HYPOTENSIVE REACTIONS OBSERVED WITH THESE PATIENTS. IN SUMMARY SEVERAL FACTORS COULD HAVE CAUSED OR CONTRIBUTED TO THE HYPOTENSIVE REACTIONS REPORTED HERE. ALTHOUGH, FROM THE INFORMATION AVAILABLE TO US, WE CANNOT CATEGORICALLY RULE OUT THE LEUKOGUARD RS FILTER AS POTENTIALLY BEING ONE OF THESE FACTORS WE CAN CONFIRM THAT A REVIEW OF THE MANUFACTURING RECORDS, SHOWS THAT THE IMPLICATED RS1VAE LOT NUMBER AND THE FILTER LOT NUMBER INCORPORATED INTO THIS RS1VAE LOT NUMBER WERE BOTH MANUFACTURED AND QUALITY CONTROL TESTED IN ACCORDANCE WITH DOCUMENTED PROCEDURES AND MET ALL CRITERIA REQUIRED FOR RELEASE. WE CAN ALSO ADVISE THAT NO OTHER REPORTS OF THIS NATURE HAVE BEEN RECEIVED FOR PRODUCT CODE RS1VAE LOT NUMBER 1250317. REFERENCES 1. CYR M, EASTLUND T, BLAIS C JR, ROULEAU JL, ADAM A. BRADYKININ METABOLISM AND HYPOTENSIVE TRANSFUSION REACTIONS. TRANSFUSION 2001; 41: 136-150. 2. DOMEN RE, HOELTGE GA. ALLERGIC TRANSFUSION REACTIONS: AN EVALUATION OF 273 CONSECUTIVE REACTIONS. ARCH PATHOL LAB MED 2003; 127: 316-320. 3. CLEMENTS DH, SCULCO TP, BURKE SW, MAYER K, LEVINE DB. SALVAGE AND REINFUSION OF POST-OPERATIVE SANGUINEOUS WOUND DRAINAGE. J BONE JOINT SURG 1992; 74A: 645-651. 4. SHIBA M, TADOKORO K, SAWANOBORI M, NAKAJIMA K, SUZUKI K, JUJI T. ACTIVATION OF THE CONTACT SYSTEM BY FILTRATION OF PLATELET CONCENTRATES WITH A NEGATIVELY CHARGED WHITE CELL-REMOVAL FILTER AND MEASUREMENT OF VENOUS BLOOD BRADYKININ LEVEL IN PATIENTS WHO RECEIVED FILTERED PLATELETS. TRANSFUSION 1997; 87; 457-462. 5. NITESCU N, BENGTSSON A, BENGTSON JP. BLOOD SALVAGE WITH A CONTINUOUS AUTOTRANSFUSION SYSTEM COMPARED WITH A HAEMOFILTRATION SYSTEM. PERFUSION 2002; 17: 357-362 6. ARNOLD DM, MOLINARO G, WARKENTIN E, DITOMASSO J, WEBERT KE, DAVIS I, LESIUK L, DUNN G, HEDDLE NM, ADAM A, BLAJCHMAN MA. HYPOTENSIVE TRANSFUSION REACTIONS CAN OCCUR WITH BLOOD PRODUCTS THAT ARE LEUKOREDUCED BEFORE STORAGE. TRANSFUSION 2004; 44: 1361-1366 7. SCOTT CF, BRANDWEIN H, WHITBREAD J, COLMAN RW. LACK OF CLINICALLY SIGNIFICANT CONTACT SYSTEM ACTIVATION DURING PLATELET CONCENTRATE FILTRATION BY LEUKOCYTE REMOVAL FILTERS. BLOOD 1998; 92: 616-622. 8. MOLINARO G, CUGNO M, PEREZ M, LEPAGE Y, GERVAIS N, AGOSTONI A, ADAM A. ANGIOTENSIN-CONVERTING ENZYME INHIBITOR-ASSOCIATED ANGIOEDEMA IS CHARACTERIZED BY A SLOWER DEGRADATION OF DES-ARGININE(9)-BRADYKININ. J PHARMACOL EXP THER 2002; 303: 232-237. UNLESS SUBSTANTIALLY SIGNIFICANT INFORMATION BECOMES AVAILABLE, THIS CONSTITUTES A FINAL REPORT.

    Description of Event or Problem · 1

    IT WAS REPORTED THAT THE HOSPITAL REINFUSED CELLSAVER SALVAGED BLOOD FROM CANCER (PROSTATECTOMY) PATIENTS THROUGH AN RS1VAE FILTER SET. ON SEVERAL OCCASIONS, IT HAS BEEN OBSERVED THAT THE PATIENTS BECAME SEVERELY HYPOTENSIVE AFTER THE REINFUSION. THE HOSPITAL REPORT THAT THEY HAVE SEEN FREE BRADYKININ WHEN THE CELLS ARE BINDING TO THE FILTER. THE PATIENTS WERE RECEIVING ACE INHIBITOR MEDICATION. THE IMPLICATED PRODUCTS WERE DISCARDED BY THE HOSPITAL. NO PERMANENT ADVERSE EFFECTS ON ANY OF THE PATIENTS WERE REPORTED.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    668806 LEUKOGUARD RS LEUKOCYTE REDUCTION FILTER FOR INTRAOPERATIVELY SALVAGED WASHED BL MICROFILTER, BLOOD TRANSFUSION CAK PALL MEXICO MANUFACTURING RS1VAE 1250317

    Patients

    Seq Age Sex Outcome Treatment
    1 Required Intervention