BEUDAMED
    FDA Adverse Event Malfunction Summary report: N

    FLOSEAL HEMOSTATIC MATRIX

    MDR report key: 1278015 · Received November 18, 2008

    Report

    Report Number
    2954761-2008-00059
    Event Type
    Malfunction
    Date Received
    November 18, 2008
    Date of Event
    April 9, 2009
    Report Date
    October 27, 2008
    Manufacturer
    BAXTER HEALTHCARE - HAYWARD
    Product Code
    LMF
    PMA / PMN Number
    P990009
    Product Problem
    Yes
    Report Source
    Manufacturer report
    Reporter Location
    IL, US
    Reporter Occupation
    OTHER

    Narratives

    Additional Manufacturer Narrative · 1

    BAXTER MEDICAL ASSESSMENT: THIS IS ONE OF SEVEN REPORTS FROM A RECENT PEER-REVIEWED PUBLICATION [HENKEL, A., COOPER, R. A., WARD, K.A. BOVA, D., & YAO, K (2008). MALIGNANT-APPEARING MICROCALCIFICATIONS AT THE LUMPECTOMY SITE WITH THE USE OF FLOSEAL HEMOSTATIC SEALANT. AJR AM J ROENTGENOL, 191(5), 1371-1373]. THE PUBLICATION DESCRIBES BENIGN MAMMOGRAPHIC CALCIFICATIONS THAT OCCUR AT THE LUMPECTOMY SITE AFTER USE OF FLOSEAL. SINCE THESE CALCIFICATIONS MAY HAVE AN APPEARANCE SIMILAR TO THAT OF RECURRENT CARCINOMA, THEY MAY MASK A RECURRENT TUMOR GROWTH AND THUS NEGATIVELY IMPACT THE TIMELY THERAPEUTIC MANAGEMENT OF THESE MALIGNANCIES. ACCORDING TO THE OPERATING SURGEON, (FOLLOW-UP (B)(4) WITH DR. (B)(6)) 5ML FLOSEAL HAVE BEEN APPLIED IN ALL SEVEN CASES AFTER HEMOSTASIS HAS BEEN ACHIEVED. ALL SEVEN REPORTED CASES SHOW A SERIES OF THREE USER ERRORS, WHICH ARE IN CONFLICT WITH THE FLOSEAL INSTRUCTIONS FOR USE: FLOSEAL APPLICATION (5ML) IN THE ABSENCE OF ACTIVE BLEEDING. THE EXCESS PRODUCT (MATERIAL NO INCORPORATED IN THE HEMOSTATIC CLOT), WHICH IN THE ABSENCE OF BLEEDING HAS BEEN ABOUT 5 ML OF NON-REACTED FLOSEAL, HAS NOT BEEN IRRIGATED AND LEFT IN SITU. APPLICATION OF FLOSEAL AGAINST THE IFU WARNING THAT FLOSEAL MATRIX "... IS NOT INTENDED TO BE USED AS A PROPHYLACTIC HEMOSTATIC AGENT." THIS FALSE EXPECTATION IS ALSO ENFORCED IN THE "MATERIAL AND METHODS" SECTION OF THE PUBLICATION IN WHICH FLOSEAL IS WRONGLY PRESENTED AS AN ALTERNATIVE TO FIBRIN SEALANTS (WHICH INDEED HAVE THE ABILITY TO PREVENT POSTOPERATIVE BLEEDING, BASED ON THEIR SEALING PROPERTIES). IN THE AREA OF THE BREAST, TISSUE TENDS TO CALCIFIED. THIS APPLIES TO RECURRENT BREAST TUMORS, BUT ALSO TO FOREIGN BODIES LEFT IN PLACE. WITH A HIGH DEGREE OF CERTAINTY THE DESCRIBED CLINICAL SITUATION OUTLINED IN THE PUBLICATION OF HENKEL ET AL. IS SUGGESTIVE FOR CALCIFICATIONS OF THE RESIDUAL FLOSEAL GELATIN GRANULES, WHICH ARE VISIBLE IN THE RADIOLOGIC FOLLOW-UP. THE SIX CASES (B)(6), WHICH SHOWED MULTIPLE MICROCALCIFICATIONS AFTER SIX MONTHS MIGHT BE SEEN AS NON SERIOUS INJURIES, SINCE THE PATIENTS DID NOT EXPERIENCE ANY RELATIVE SYMPTOMS. NEVERTHELESS, THE PRESENCE OF EVEN ASYMPTOTIC CALCIFICATIONS IS POTENTIALLY NEGATIVELY IMPACTING PATIENT SAFETY, SINCE AT FOLLOW-UP MAMMOGRAPHIC EXAMINATION, THESE CALCIFICATIONS MAY MASK MALIGNANT MICROCALCIFICATIONS THAT OFTEN REPRESENT AN INDICATOR OF CANCER RECURRENCE. THE DELAYED DIAGNOSIS MAY NEGATIVELY IMPACT TIMELY SURGERY, AND THE ENTIRE OUTCOME OF TREATMENT. ALSO, AS A POTENTIALLY ADDED RISK SITUATION IS THE REPORT OF THE ONE PATIENT (B)(6) WHO HAS BEEN RE-OPERATED AFTER ONE MONTH UNDER THE ASSUMPTION THAT THE MICROCALCIFICATIONS MAY BE MALIGNANT (WHICH HAS BEEN INFIRMED BY HISTOLOGY). THIS SITUATION MAY EXPOSE THE PATIENT TO ADDITIONAL RISKS OF A SECOND, NEEDLES SURGERY AND GENERAL ANESTHESIA. WHAT EVER OF THESE TWO SITUATIONS OCCUR, THIS MAY POTENTIALLY HAVE A NEGATIVE IMPACT ON SECONDARY PATIENT SAFETY. MAMMOGRAPHY IS AN ESSENTIAL PART OF THE FOLLOW-UP PROGRAM IN ORDER TO DETECT A RECURRENCE IN THE TREATED BREAST, AS WELL AS A CANCER IN THE CONTROLATERAL BREAST CANCER. THE OPTIMAL INTERVAL FOR FOLLOW-UP MAMMOGRAPHY HAS NOT BEEN DETERMINED, ALTHOUGH PROGRAM EMPLOYING MAMMOGRAPHY ON A YEARLY BASIS AFTER TREATMENT HAVE BEEN ASSOCIATED WITH THE DETECTION OF EARLY RECURRENCES AND EXCELLENT SURVIVAL AFTER SALVAGE MASTECTOMY FOR THESE RECURRENCES. IN CONCLUSION: FLOSEAL APPLIED AT THE LUMPECTOMY SITE MIMICS THE APPEARANCE OF MALIGNANT MICROCALCIFICATIONS, THUS LIMITING EVALUATION FOR RESIDUAL OR RECURRENT DISEASE, OR FALSELY SUGGESTING THE NEED FOR SURGICAL RE-INTERVENTION. ALL THE ASPECTS OF THE ABOVE DESCRIBED USER ERRORS ARE CLEARLY AND REPEATEDLY ADDRESSED IN THE FLOSEAL IFU. THE REPORTING SURGEON HAS BEEN RE/TRAINED AN ALL THE ABOVE ASPECTS OF CORRECT PRODUCT APPLICATION DURING THE FOLLOW UP DISCUSSION WITH (B)(4). IF FLOSEAL IS INDICATED AND APPLIED AS OUTLINED IN THE INSTRUCTIONS FOR USE THIS PRODUCT CAN-AGAINST THE RECOMMENDATION IN THE PUBLICATION - BE SAFELY USED FOR HEMOSTASIS ON BREAST TISSUE. AS THE REPORTING SURGEON HAS BEEN ADVISED OF THE CORRECT PRODUCT APPLICATION AND AS THE ARTICLE WRITTEN IS ADDRESSING THE IMPROPER USE OF THE PRODUCT, NO FURTHER ACTIVITY IS REQUIRED.

    Description of Event or Problem · 1

    (B)(6). FROM LITERATURE: BOVA, D., COOPER, R.A., HENKEL, A., WARD, K., AND YAO, K. (2008). MALIGNANT-APPEARING MICROCALCIFICATIONS AT THE LUMPECTOMY SITE WITH THE USE OF FLOSEAL HEMOSTATIC SEALANT. AMERICAN ROENTGEN RAY SOCIETY, AJR 2008; 191: W1371-W1373. SUMMARY OF PUBLICATION FROM AJR WOMEN'S IMAGING: RECENTLY AT (B)(6), FLO SEAL WAS USED FOR HEMOSTASIS DURING SEVEN LUMPECTOMIES PERFORMED FOR TREATMENT OF BREAST CANCER. FOLLOW-UP MAMMOGRAMS FOR ALL SEVEN PATIENTS IN WHOM FLOSEAL WAS USED, SHOWED INNUMERABLE PUNCTUATE RADIOPAQUE DENSITIES THROUGHOUT THE LUMPECTOMY SITE THAT MIMICKED THE APPEARANCE OF MALIGNANT MICROCALCIFICATIONS. THESE MICROCALCIFICATIONS WERE OBSERVED ON THE 6-MONTH FOLLOW-UP MAMMOGRAM IN SIX PATIENTS. IN ANOTHER CASE, THE CALCIFICATIONS WERE SLIGHTLY FEWER IN NUMBER ON THE MAMMOGRAM, 1 YEAR AFTER LUMPECTOMY, THAN ON THE INITIAL 6 MONTH POSTOPERATIVE STUDY, SUGGESTING THAT THEY MAY EVENTUALLY BE REABSORBED. HOWEVER, THE RISK FOR RECURRENT DISEASE AFTER TREATMENT OF BREAST CANCER IS HIGHEST IN THE FIRST 5 YEARS AFTER SURGERY. FLOSEAL WAS APPLIED TO AN EXCISED BREAST SPECIMEN, BUT SAW NO MICROCALCIFIED DENSITIES WHEN THE SPECIMEN UNDERWENT BOTH ANALOG AND DIGITAL EXAMINATION. THEREFORE, THE DEVELOPMENT OF CALCIFICATIONS IS A RESPONSE TO FLOSEAL THAT REQUIRES A LIVING HOST. THE GELATIN MATRIX AND THROMBIN-BASED HEMOSTATIC AGENT FLOSEAL APPLIED AT A LUMPECTOMY SITE MIMICS THE APPEARANCE OF MALIGNANT MICROCALCIFICATIONS ON MAMMOGRAPHY, THUS LIMITING EVALUATION FOR RESIDUAL OR RECURRENT DISEASE AND IS NOT RECOMMENDED FOR USE ON BREAST TISSUE. DR. (B)(6), THE OPERATING SURGEON IN THE SEVEN FLOSEAL CASES, STATED THAT AFTER COMPLETING THE LUMPECTOMY, SHE OBTAINED HEMOSTASIS USING CAUTERY. SHE THEN COATED THE RESECTION BED WITH FLOSEAL, CLOSED THE INCISION AND APPLIED A COMPRESSION BRA AS PART OF THE ROUTINE WOUND DRESSING. NO IRRIGATION WAS USED. PERFORMING A ONE MONTH POST OPERATIVE MAMMOGRAM WAS NOT THEIR ROUTINE, HOWEVER, THE ONE PATIENT (B)(4) REQUIRED THIS PRIOR TO INITIATING RADIATION THERAPY. IT WAS THIS PATIENT WHO DEMONSTRATED THE MOST MICROCALCIFICATIONS. THE OTHER SIX PATIENT'S WHO RECEIVED FLOSEAL IN THIS MANNER HAD ROUTINE SIX MONTH POST OPERATIVE MAMMOGRAMS, AND SHOWED LESS IMPRESSIVE MICROMODIFICATIONS, BUT ONES THAT WERE CLEARLY QUESTIONED IF THEY WERE RECURRENCES OF THE TUMOR OR FLOSEAL. DR. (B)(6), AND THE RADIOLOGY TEAM LOOKED AT THE CONTENTS OF FLOSEAL AND SAW IT DID CONTAIN CALCIUM CHLORIDE, WHICH THEY THOUGHT CONTRIBUTED TO THE MICROCALCIFICATIONS. GIVEN THE IMPORTANCE OF MAMMOGRAPH IN BREAST CANCER THERAPY, SHE FELT THIS WAS A REMARKABLE FINDING AND WANTED TO INFORM HER COLLEAGUES VIA THE PUBLICATION. THE INDICATION FOR USE OF FLOSEAL AND THE REQUIREMENT TO APPLY THE PRODUCT ONLY ONTO SITES THAT WERE VISIBLY BLEEDING, WAS EXPLAINED TO DR. (B)(6), BY (B)(4). MATRIX THAT IS INCORPORATED IN THE HEMOSTATIC CLOT IS LEFT IN SITU, WHILE ALL EXCESS MATRIX IS REMOVED WITH GENTLE IRRIGATION. THE FLOSEAL CLOT IS BROKEN DOWN AND RESORBED WITHIN 6 - 8 WEEKS, WHEN EXCESS MATERIAL IS REMOVED. WITHOUT THE REMOVAL OF EXCESS MATRIX, THE EXCESS MATERIAL IS NOT BROKEN DOWN DURING THE FIBRINOLYSIS OF THE HEMOSTATIC CLOT. THE BREAKDOWN AND RESORPTION OF LOOSE MATRIX HAS NOT BEEN STUDIED. DR. (B)(6) STATED THAT SHE THOUGHT SHE COULD USE FLOSEAL TO PREVENT HEMATOMA FORMATION IF THE PATIENT WAS TO BLEED POST-OPERATIVELY, BUT NOW CLEARLY UNDERSTANDS THAT IT HAS NO PLACE AS A PROPHYLACTIC AGENT. (B)(4) ALSO INDICATED THAT DR. (B)(6) HAS LEFT THIS USER FACILITY AND CANNOT OBTAIN THE PATIENTS' CHART DATA.

    Devices

    Seq Brand Generic Product Code Manufacturer Model Lot UDI-DI
    1 FLOSEAL HEMOSTATIC MATRIX LMF BAXTER HEALTHCARE - HAYWARD NA UNK

    Patients

    Seq Age Sex Outcome Treatment
    1 UNK