MAUDE data represents reports of adverse events involving medical devices. This maude entry was filed from a health professional,user faci report with the FDA on 2017-02-06 for DADE B4219 SMN 10445714 manufactured by Siemens Healthcare Diagnostics Products Gmbh.
[66664085]
Siemens has investigated the potential cause of the discordance between the siemens bcs xp system actin fsl aptt results and the non-siemens stago system heparin anti-xa results. Siemens has determined that the patient had multiple conditions and was being treated with multiple medications/multiple therapy regimens that may have contributed to the discordance between the two relevant monitoring methods, the siemens actin fsl aptt results and the non-siemens stago system heparin anti-xa results. Due to the complex, multiple conditions that the patient was experiencing and the multiple medications that the patient was on, decisions on opposing/conflicting therapy regimens are always difficult and critical. In regard to the patient's multiple conditions/disorders and in context with multiple medications/therapy regimens, it is, in turn, a very complex medical constellation and, in turn, unpredictable how an aptt will respond. Major determinants for the pathogenesis of the coagulopathy of acute leukemia are the following: factors associated with leukemic cells, including procoagulant, fibrinolytic and proteolytic properties; cytotoxic; and concomitant infectious complications. Life-threatening bleeding occurs more frequently when patients with acute leukemia have concomitant infections. Other factors, besides inhibition of plasmatic coagulation, could strongly contribute to severe bleedings, like low platelet counts (reported in the relevant patient), von willebrand factor (vwf) activity (not known), increased fibrinolysis (d-dimer not known) and factor xiii deficiency (not known) and generally therapy regimens applied on acute myeloid leukemia (aml) patients. Therapy regimens bleeding contribution: in adult patients with aml, 1% of lethal bleedings on day of admission have been observed. Recent data in patients with aml show a rate of haemorrhagic death of 9. 9%, whereas in studies reporting hemorrhage as a contributory cause of death, the rate increases up to 33%. {1} literature: [1] barbui t, falanga a: hemorrhage and thrombosis in acute leukemia. Hematological reports, 2005, 1(9), 48-51. The dade actin fsl activated ptt reagent instructions for use state the following: "aptt testing encompasses the entire clotting process from contact activation to fibrin formation and is therefore more susceptible to variations than specific individual tests. The control and use of aptt is therefore subject to inherent limitations. Studies have shown variability in original estimates of the quality of unfractionated heparin from different sources and different manufacturers. In-vivo reactivity varies with the type of heparin administered, the metabolism of the individual and other coadministrated medications. Blood clotting factor deficiencies which should produce prolonged clotting times may be compensated for or made to appear normal by elevated levels of one or more different clotting factors. Similarly, the presence of active intermediates which would tend to reduce the clotting time may also mask conditions that would normally lead to prolongation of the aptt. Action of heparin as an anticoagulant is related to its ability in conjunction with a plasma cofactor to interfere with several aspects of the coagulation mechanism, thus retarding the rate of fibrin formation. Low levels of antithrombin iii can decrease the responsiveness of patients to heparin therapy. Antithrombin iii slowly forms an inactive complex with the coagulant serine proteases, thrombin and factors ixa, xa, xia and xiia. Heparin greatly accelerates this inactivation and this forms the basis for the therapeutic effect of these naturally occurring polysaccharide compounds. The test will not detect qualitative or quantitative platelet disorders, isolated factor vii and factor xiii deficiencies or vascular disorders. Aptt values for patient samples containing non-specific lupus-like anticoagulants are prolonged using actin fsl. Results of this test should always be interpreted in conjunction with the patient's medical history, clinical presentation and other findings. " in general it could be deducted that the patient faced a hypercoagulable status with strongly impaired physiological systems (e. G. Coagulation, fibrinolysis, complement- / immune system, liver - /renal- / cardiac functions etc. ). Aml is particularly critical towards thromboembolism, severe bleedings as well as disseminated intravascular coagulation (dic). Further, the guidelines in anticoagulation therapy (e. G. ) are stating, if a discordance between aptt and heparin anti-xa levels is observed, always a heparin therapy resistance should be taken into account. That means, the patient's condition may be related to low antithrombin iii (at iii) levels and/or excess of heparin binding proteins (e. G. Pf4 , hbp and other acute phase reactants etc. ). [2], [3], [4], [5]. Smythe ma, priziola j, dubesh pp, wirth d, cuker a, wittkowsky ak. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J. Thromb. Thrombolysis 2016,41, 165-186. Kaiser p, harenberg j, walenga jm, huhle g, giese c, prechel m, hoppensteadt d, and fareed j: effects of a heparin-binding protein on blood coagulation and platelet function. Seminars in thrombosis and hemostasis, volume 27, no. 5, 2001. Elevated plasma heparin-binding protein is associated with early death after resuscitation from cardiac arrest ristagno g et al critical care 2016 20:251"elevated plasma levels of hbp at icu admission were independently associated with early death in icu " heparin-binding protein is important for vascular leak in sepsis. Bentzer p et al. Intensive care med exp 2016 dec; 4:33. It is unknown what other tests were performed on this patient and what medications she was given that may have impacted the aptt results. The customer has confirmed that the siemens bcs xp system and the siemens dade actin fsl aptt reagent performed as expected. The customer also stated that the physician used a heparin nomogram that was not developed specifically for the coagulation system/aptt reagent in use at their facility, which may have had an impact on the heparin treatment given to the patient. After review of the provided reaction curves of the aptt (actin fsl) it only could be confirmed that the instrument evaluated these curves as expected, via the evaluation of the results, as well as the "flagging" performed in the way the settings are programmed. Based on the information shared by the customer, and our investigation, we believe that the siemens bcs xp system and the siemens dade actin fsl aptt reagent performed as expected and within specifications; accordingly, this mdr is being filed for fda's information and in an excess of caution.
Patient Sequence No: 1, Text Type: N, H10
[66664086]
As part of a mortality review that is being conducted by the customer, the customer requested an explanation for the discordance observed between the activated partial thromboplastin time (aptt) result obtained on the siemens bcs xp system and the heparin anti-xa result obtained on the stago system (non-siemens system) for one patient. Testing was performed by the customer over a two day period on both systems. The customer reported that all controls for the siemens' aptt and stago system's heparin anti-xa (non-siemens assay) were within range at the time of testing and has stated that they do not suspect an issue with the siemens aptt assay nor with the siemens bcs xp system. They stated that the sample collection technique was verified and that samples were not clotted and were found acceptable for coagulation testing. The customer also stated that the physician used a heparin nomogram that was not developed specifically for the coagulation system/aptt reagent in use at their facility. The customer stated that the patient was over heparinized due to the inappropriate monitoring of the patient with the aptt assay, which may have contributed to the death of the patient due to an intracranial hemorrhage. The customer is inquiring what clinically could influence the results to create the pattern observed between the aptt and the heparin anti-xa results.
Patient Sequence No: 1, Text Type: D, B5
| Report Number | 9610806-2017-00013 |
| MDR Report Key | 6304257 |
| Report Source | HEALTH PROFESSIONAL,USER FACI |
| Date Received | 2017-02-06 |
| Date of Report | 2017-02-06 |
| Date of Event | 2016-12-18 |
| Date Mfgr Received | 2017-01-10 |
| Device Manufacturer Date | 2015-03-17 |
| Date Added to Maude | 2017-02-06 |
| Event Key | 0 |
| Report Source Code | Manufacturer report |
| Manufacturer Link | Y |
| Number of Patients in Event | 0 |
| Adverse Event Flag | 3 |
| Product Problem Flag | 3 |
| Reprocessed and Reused Flag | 3 |
| Health Professional | 3 |
| Initial Report to FDA | 3 |
| Report to FDA | 3 |
| Event Location | 3 |
| Manufacturer Contact | JAMES MORGERA |
| Manufacturer Street | GLASGOW BUSINESS COMMUNITY 500 GBC DRIVE PO BOX 6101 |
| Manufacturer City | NEWARK DE 197146101 |
| Manufacturer Country | US |
| Manufacturer Postal | 197146101 |
| Manufacturer Phone | 3026318356 |
| Manufacturer G1 | SIEMENS HEALTHCARE DIAGNOSTICS PRODUCTS GMBH |
| Manufacturer Street | EMIL VON BEHRING STRASSE 76 |
| Manufacturer City | MARBURG, D-35041 |
| Manufacturer Country | GM |
| Manufacturer Postal Code | D-35041 |
| Single Use | 3 |
| Previous Use Code | 3 |
| Event Type | 3 |
| Type of Report | 3 |
| Brand Name | DADE |
| Generic Name | DADE ACTIN FSL ACTIVATED PTT REAGENT |
| Product Code | GGW |
| Date Received | 2017-02-06 |
| Catalog Number | B4219 SMN 10445714 |
| Lot Number | 547459A |
| Device Expiration Date | 2017-02-19 |
| Operator | HEALTH PROFESSIONAL |
| Device Availability | N |
| Device Eval'ed by Mfgr | N |
| Device Sequence No | 1 |
| Device Event Key | 0 |
| Manufacturer | SIEMENS HEALTHCARE DIAGNOSTICS PRODUCTS GMBH |
| Manufacturer Address | EMIL VON BEHRING STRASSE 76 MARBURG, D-35041 GM D-35041 |
| Patient Number | Treatment | Outcome | Date |
|---|---|---|---|
| 1 | 0 | 2017-02-06 |