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Patient 1
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 ANTICOAGU...