Report of the Meeting of the Hematology Working Group of the Belgian Commission for Clinical Biology - 15 th February 2017

Transcription

1 Report of the Meeting of the Hematology Working Group of the Belgian Commission for Clinical Biology - 15 th February 2017 Present : Anne Demulder, Marc Jacquemin, François Mullier, Annemie Van Ruymbeke, Tom Van Maerken, Nathalie Vandevelde Excused : Xavier Bossuyt, Geneviève Bulliard, Francis Corazza, Hanane El Kenz, André Gothot, Beatrice Gulbis, Ronald Malfait, Jean-Marc Minon, Pascale Saussoy Content : A. Action 1 Belgian Plan for rare diseases ANALYSES of Clinical biology THAT SHOULD BE ADDED to the NOMENCLATURE : 1 Analysis of HEMATOLOGY p of COAGULATION and HEMOSTASIS pages 3-13 B. Other analyses that should be discussed during the next meetings Proposition of Pr. D. Kieffer (UZ Leuven ; 29 th June 2016) : concerning some specific analyses used in the context of hemoglobinopathies p.14 Proposition of Pr. F. Mullier (CHU UCL Namur ; 10 th February 2017) : Other analyses that should be discussed during the meeting p.15 Proposition of Pr. T. Van Maerken (UZ Gent ; 15 th February 2017) : change of appellation (Ristocetin Cofactor activity => von Willebrand factor activity) p.15 Next Meeting of the Hematology Working Group : late April Dr. A. Demulder will send a doodle to the members of the Working group. 1

2 of hematology that should be added to the nomenclature (1/1) 387 b, d, e, f, q c Proposed diagnostic rule (meeting 28 th June 2016) : Maximum 1 analysis/day ; Only reimbursed in the case of positive results of the cryohemolysis test. However, the cryohemolysis test should be clearly defined. Comment and proposition of Pr. J. Philippé ( 1 st August 2016): The cryohemolysis test is obsolete and cannot be proposed as a prior test for the EMA test. A condition could be at least the finding of spherocytes in the peripheral blood smear, or a familial history of spherocytosis, and maybe (to be discussed) there should also be an indication for hemolysis being present in the patient, based upon clinical findings or laboratory findings (increased reticulocytes, LDH or bilirubin, or decreased haptoglobin). Eosin 5-maleimide binding (EMA) test Proposition of Pr. K. Devreese (16 th January 2017) : Aanwezigheid van sferocyten, tekens van hemolyse of familiale anamnese van sferocytose Comment of Pr. F. Mullier (10 th February 2017) : Pr. Mullier agrees with the proposition of Pr. Philippé and refers to the publication of King et al, 2015, Int. J. Lab. Hemato. Jun, 37(3): Of Note the CHU UCL Namur also performs this analysis (annual volume not communicated). Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed in the case of presence signs of hemolysis (increased reticulocytes, LDH or bilirubin, or decreased haptoglobin) or family history of spherocytosis. Max 1/day 2

3 of coagulation and hemostasis that should be added to the nomenclature (1/11) = 194 a, b, c, d, q / no specific diagnostic rule ; max 1 analysis per day Proposition of Pr. K. Devreese (16 th January 2017) : Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van een ernstige bloedingsdiathese Dosage of α2- antiplasmin Proposition of Pr. F. Mullier (10th February 2017) : Diagnostic rule : in the case of bleeding diathesis, max 1 per day Of Note the CHU UCL Namur also performs this analysis (annual volume not communicated). Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed in the case of bleeding diathesis. Max 1/day 3

4 of coagulation and hemostasis that should be added to the nomenclature (2/11) 970 a, b, c, d, e, f, q h Only reimbursed in the case of suspicion (diagnosis) or follow-up of thrombotic microangiopathies ; max 1 analysis per day Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van vermoeden trombotische trombocytopenische purpura (TTP) of atypisch hemolytisch uremisch syndroom (HUS). von Willebrand protease (ADAMTS13) - functionnal assay Proposition of Dr. J. Smet (16th January 2017) : A difference has to be done between an inhibitor of the von Willebrand protease (ADAMTS13) and an anti-adamts13 auto-antibody. We should propose this latest (autoab) in the nomenclature as it is used in the literature (cf Goodship et al, 2017, Kidney International 91, or Canpolat, 2015, Turk Pediatri Ars ; 50 : 73-82) => We propose then: Functionele test van de von Willebrand protease (ADAMTS13) : B3000 Only reimbursed in the case of suspicion (diagnosis) or follow-up of thrombotic microangiopathies ; frequency has to be discuss with haematologists but max 1 analysis per day sounds too much: once a month?) Detection of an auto-ab anti von Willebrand protease (ADAMTS13) : B3000 Only reimbursed in case of decreased (how much? To be discussed) ADAMTS13 activity or for the following if positive at the diagnosis;( frequency has to be discuss with haematologists but max 1 analysis per day sounds too much: once a month?) Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed in the case of suspicion (diagnosis or follow-up) of thrombotic microangiopathies. Max 1/week 4

5 of coagulation and hemostasis that should be added to the nomenclature (3/11) 324 a, b, c, d, e, f, q h Only reimbursed in the case of suspicion (diagnosis) or follow-up of thrombotic microangiopathies and only if the functional assay (see above) gives positive results; max 1 analysis per day Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van gedaalde (<0.4 IU/mL, 40 IU/dl= 40%) ADAMTS13 activiteit Identification of an Proposition of Dr. J. Smet (16th January 2017) : cf comment and proposition on the previous analysis inhibitor of the von Willebrand protease Proposition of Pr. F. Mullier (10th February 2017) : (ADAMTS13) only reimbursed if ADAMTS13 <20% (or 10%) Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed if the functional assay gives results (<0.3 IU/mL = <30%). No specification of the frequency 5

6 of coagulation and hemostasis that should be added to the nomenclature (4/11) Diagnosis of von Willebrand disease (VWD) Type 2N (Normandy) = von Willebrand factor- Factor VIII binding capacity 44 a, c, e, f b, d Only reimbursed if the ratio VWF:RCo / VWF:Ag is normal ( 0.6) but that the Factor VIII is decreased (ratio FVIII:C / VWF:Ag lower than 0.5, according to the scientific literature) ; max 1 analysis per day (References : Ng et al, Blood Mar 26; 125(13): ; Castaman et al, Haemophilia May; 20(0 4): 65 70). Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van gedaalde FVIII dosage (<40%) Comment and proposition of Dr. J-M Minon (19 th January 2017) : VWF/CB has the ability to reduce misdiagnosis of the 2 VWD. So, I think that a VWF:RCO/VWF:Ag < 0.6 is more restrictive. References : Although VWF:RCo and VWF:CB assess different aspects of VWF function, both are sensitive to the loss of HMW multimers and both the VWF:RCo to VWF:Ag ratio and the VWF:CB to VWF:Ag ratio will be reduced in type 2A disease, though the latter ratio is better at differentiating type 2A from type 1 disease (Favaloro et al, 2000, Am J Clin Pathol;114: ). Recommendations (Laffan et al, Guidelines BCSH, BJH 2014) : - In the initial investigation for VWD, FVIII, VWF:Ag and VWF activity should be measured(1a). - VWF activity should be assessed by its ability to bind both GPIb and collagen (2B). - We recommend against using assays based on monoclonal antibodies directed against the VWF GPIb-binding site (1B). Fressinaud, 2014, Hematologie ; 20 : : «Ce test est complémentaire, le VWF:RCo restant le test de première intention pour évaluer l activité du VWF [21]. Il faut cependant noter que les très rares anomalies isolées du VWF de liaison au collagène ne peuvent être mises en évidence que par le VWF:CB, le VWF:RCo étant dans les limites de la normale. Un rapport VWF:CB/VWF:Ag < 0,6 est en faveur soit d un type 2A (IIA, IIC, IID) soit d un type 2B de VWD. Un rapport VWF:CB/VWF:Ag > 0,6 est en faveur soit d un type 1, soit d un type 2M ou d un type 2A(IIE) de VWD. Les tests développés actuellement utilisent des collagènes I et III». Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed if the ratio FVIII:C/VWF:Ag is <0.6. No specification of the frequency 6

7 of coagulation and hemostasis that should be added to the nomenclature (5/11) 189 a, e, f, h, q b, h Only reimbursed if the ratio VWF:RCo / VWF:Ag is lower than 0.6 ; max 1 analysis per day von Willebrand factor collagen-binding activity Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van gedaalde von Willebrand factor activiteit (<40%) Proposition of Dr. J-M Minon (19th January 2017) : cf comment and proposition on the previous analysis Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed in the case of bleeding diathesis. 7

8 of coagulation and hemostasis that should be added to the nomenclature (6/11) 426 a, c, e, f / Only reimbursed if the ratio VWF:RCo / VWF:Ag is lower than 0.6 (ref: Ng et al, Blood Mar 26; 125(13): ); max 1 analysis per day von Willebrand factor multimers analysis Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van gedaalde von Willebrand factor activiteit (<40%) Proposition of Dr. J-M Minon (19th January 2017) : cf comment and proposition on the previous analyses Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed if the ratio VWF:RCo /VWF:Ag is <0.6 or in the case of a VWF activity lower than 40%. 8

9 of coagulation and hemostasis that should be added to the nomenclature (7/11) von Willebrand factor propeptide analysis 40 e, f b, q max 1 analysis per day ; Suggestion of Pr. K. Devreese and A. Gadisseur : only reimbursed in the case of von Willebrand factor antigen and/or activity lower than 50% Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van gedaalde von Willebrand factor activiteit en/of antigen (<50%) Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed in the case of von Willebrand factor antigen or activity < 40%.. 9

10 of coagulation and hemostasis that should be added to the nomenclature (8/11) Heparin-Platelet Factor 4 antibody (HIT detection) 2739 a, b, c, d, e, f, g, h, j, k, l, m, n, q / Only reimbursed if the 4Ts score (thrombocytopenia, timing of platelet count fall, thrombosis or other sequelae, other causes of thrombocytopenia) is 4 (ref: Cuker et al, 2012 Nov 15;120(20):4160-7) ; max 1 analysis per day Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van vermoeden van heparine geïnduceerde trombopenie (gedaald aantal trombocyten en gebruik van heparine) Maximum 1 Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed in the case of clinical suspicion of HIT on the basis of the 4T s score Reimbursed in the case of clinical suspicion of HIT (as judged by platelet count fall, timing of platelet count fall, thrombosis or other sequelae, absence of other causes of thrombocytopenia). Max 1/day *The members of the Hematology working group suggested to refer to the 4T s score without specifying a threshold value for it and without taking the presence of thrombocytopenia (one of the 4T s score indicator) into account (other possible causes than rare diseases). 10

11 of coagulation and hemostasis that should be added to the nomenclature (9/11) B- values 230 a, b, o, q / Only reimbursed if the HIT detection assay (see above) gives positive results ; max 1 analysis per day Heparin-induced thrombopenia (HIT) antibodies: functional analysis Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van aanwezigheid van heparine-geïnduceerde antistoffen bepaald met immunologische techniek (nomenclatuurnummer van Detectie van anti-plaatjesfactor 4 antilichamen ). Maximum 1 Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed in the case of presence of heparine-induced antibodies determined using an immunological technique OR if the 4T s score is >6 (cf. Cuker et al, 2012 Nov 15;120(20):4160-7) Max 1/day 11

12 of coagulation and hemostasis that should be added to the nomenclature (10/11) 1450 a, b, c, d, e, h, q / no diagnostic rule ; max 1 analysis per day Maximum 1 Platelet secretion assay Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Reimbursed in the case of bleeding diathesis. Max 1/day 12

13 of coagulation and hemostasis that should be added to the nomenclature (11/11) 31 c / Only reimbursed in the case of prolonged activated partial thromboplastin time (aptt) with normal Prothrombin Time (PT) and normal levels of Factor VIII, IX, XI and XII ; max 1 analysis per day ; (ref: Patel et al, Anesthesiol Open J. 2016; 1(1): 19-23). Human plasma prekallikrein (Fletcher factor) clotting activity and antigen levels and high molecular weight kininogen dosage Diagnoseregel: mag alleen worden aangerekend aan de ZIV in geval van verlengde aptt ( ) Proposal of diagnostic rule selected by the Hematology working group (WG) during the meeting that took place on Wednesday 15 th February 2017 (on the basis of the proposals made by the Belgian experts [cf. above] and the opinions of the members of Hematology WG). Only reimbursed in the case of prolonged activated partial thromboplastin time (aptt) with normal levels of Factor II, V, VIII, IX, X, XI, XII and fibrinogen Max 1 /day 13

14 B. OTHER ANALYSES THAT HAVE BEEN/SHOULD BE DISCUSSED DURING THE (NEXT) MEETINGS OF THE HEMATOLOGY WORKING GROUP : Proposition of Pr. D. Kieffer (UZ Leuven ; 29 th June 2016) concerning some specific analyses used in the context of hemoglobinopathies : Pr. Kieffer suggests to submit a proposal to the Commission for Clinical Biology in order to adapt the existing nomenclature for analyses used in order to detect hemoglobinopathies (Biochemistry Blood - codes , and ) and, in that context and for that purpose, to change the current appellations of these nomenclature codes (and perhaps also the number of different codes : to combine them) in order to remove the specifications of techniques (for the screening, as well as for the confirmation) with, eventually, the addition of a sentence that indicates that the confirmation can be made using a complementary method. Please see his below : lk vergat nog te vragen of de wijziging van de bestaande nomenclatuur voor hemoglobinopathie ook nog zou besproken worden? In een van mijn voorgaande mails suggereerde ik om de methodiek (chromatografie,elektroforese zure ph, elektroforese alkalische ph,...) NIET meer te vermelden noch voor screening noch voor confirmatie. Eventueel kan er wei gesteld worden dat de confirmatie dient te gebeuren met een complementaire methode. Op de vergadering op het WIV die ik bijwoonde waren de aanwezige experten hiermee akkoord. Comment Beatrice Gulbis - Tue 2/14/2017 5:23 PM Bonjour et merci pour cet , Concernant la réunion de demain et l'adaptation de la nomenclature pour les hémoglobinopathies, si on ne spécifie plus les techniques je propose néanmoins de spécifier que: - la technique est dédiée aux hémoglobinopathies - si plusieurs techniques sont utilisées pour détecter un variant de l'hémoglobine, elles doivent être basées sur des principes de séparation différents. Ce qui n'est pas souhaitable, est d'utiliser une technique chromatographique dédiée au dosage d'hba1c et non validée pour les fractions d'hb autres ou pour la détection de variants, ou d'utiliser deux techniques chromatographiques de principe identique mais de fabricants différents. La très bonne idée de Davy KIEFFER est de ne pas pénaliser de nouvelles techniques validées car la nomenclature ne suit pas l'innovation. Bien à vous, Béatrice GULBIS => The members of the Hematology Working group approved the proposal of Professors D. Kieffer and Beatrice Gulbis. This suggestion will be submitted to the Commission for clinical biology. 14

15 Proposition of Pr. F. Mullier (CHU UCL Namur ; 10 th February 2017) : Pourrait-on revoir les conditions de remboursement des analyses ci-dessous spécifiées lors des prochaines réunions du Groupe de travail «Hématologie»? - phénotypage des LCR en cytométrie en flux - quantification des glycoprotéines plaquettaires - recherche de cristaux dans les liquides - activateur tissulaire du plasminogène - quantification des schizocytes - quantification des cellules souches - analyse de la morphologie plaquettaire - PAI: Inhibiteur de l'activateur du plasminogène (PAI-1) - cytologie des empreintes ganglionnaires - phénotypage des ganglions en cytométrie en flux => These analyses will be discussed during the next meetings of the «Hematology» working group of the Commission (the next meeting will probably take place in late April 2017). In order to make a cost estimation for new reimbursement conditions for these analyses, the WIV-ISP will provide the addresses of all Belgian laboratories of clinical biology registered with the WIV-ISP for external quality assessment programs to Dr. Demulder. Suggestion of Pr. Tom Van Maerken (UZ Gent ; 15 th February 2017) : Based on the current recommendations and terms used in the scientific literature, Pr. Tom Van Maerken suggested to replace the following appellation von Willebrand Ristocetin Cofactor activity [FR: activité du co-facteur de la ristocétine de von Willebrand ; NL : von Willebrand ristocetine co-factor activiteit], already used in the nomenclature (please see. Art. 24. Nomenclature code ) by the following terms : von Willebrand factor activity. This change should be made for existing (cf. above), as well as, for new nomenclature codes. => Globally, the members of the Hematology Working Group who attended the meeting on Wednesday 15 February 2017 agree with this proposal. However, they suggested to put this specific point on the agenda of the next meeting of the Working Group in order to have more time to define how this proposal would eventually be submitted to the Commission for Clinical Biology in the coming weeks. Next Meeting of the Hematology Working Group : late April Dr. A. Demulder will send a doodle to the members of the Working group. 15