Högt Hb hos vuxna och barn utredning och klinik. Jan Samuelsson Vetenskaplig sekreterare

Transkript

1 Högt Hb hos vuxna och barn utredning och klinik Jan Samuelsson Vetenskaplig sekreterare

2 Conflict of interest statement I have a bagful of interesting conflicts, and I would prefer to keep them to myself (R Horton, chief editor Lancet 2003) Konsultuppdrag åt Swedish Orphan och Roche Advisory board Shire Pharmaceuticals

3 Polyglobulier hos barn/ungdomar Medfödda EPO receptormutation VHL, Chuvash HIF-2α mutation Högaffinitetshemoglobin Gravt hjärtfel Förvärvade Polycytemia vera

4 Normal Pseudo- (Relativ) Absolut

5 Diagnostic algorithm for polycythemia vera Hb > 18,5 (men) and >16,5 (women) or Hct > 52 (male) and >48 (female) or PV related feature Medical history and relevant physical investigation Full blood count Low EPO Serum EPO Increased EPO Mutation screening for JAK2 V617F and bone marrow examination Normal EPO Clinical / laboratory clues for PV PV unlikely. Evaluate secondary erythrocytosis. No Diagnosis confirmed in the presence of JAK2 V617F and a consistent histology. Yes Mutation screening for JAK2 V617F and bone marrow examination PV unlikely. Follow up may be indicated.

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7 Figure 1. JAK/STAT signal transduction pathway in responses to hematopoietic growth factors Schafer, A. I. Blood 2006;107: Copyright 2006 American Society of Hematology. Copyright restrictions may apply.

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9 Hur vanligt är PCV? Incidens ~ 200 pat/år i Sverige Uppskattad prevalens ~ 2500 pat 5 % < 40 år vid diagnos 1 % < 25 år 0,1 % < 20 år

10 Polycytemia vera naturalförloppet Chiewitz & Thiede Acta Med Scand pat Obehandlad PCV 18 mån medianöverlevnad 70 % av dödsfallen i trombos, fr a stroke

11 38 % mortalitet inom 20 år hos patienter diagnosticerade innan 50åå Passamonti et al. Haematologica 2003; 88: 13-18

12 15 % risk för AML, 10 % risk för MF efter 20 år

13 Föreslagna rekommendationer för behandling PV Flebotomi för att hålla EVF < 0.45 (grad B rekommendation). Inget stöd för olika nivåer kvinna/man Acetylsalicylsyra 75 mg/dag om ej kontraindicerat (grad A rekommendation) Stöd rökstopp (grad C)

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16 Age distribution of 36 pediatric patients. with polycythemia vera Cario et al Ann Hematol 2009; 88:713

17 Clinical presentation and complications in 36 children Cario et al Ann Hematol 2009; 88:713 Before/at diagnosis Follow-up Budd-Chiari 5 2 Gangrene 1 Thrombotic stroke 1 Hemorrhagic stroke 1 Pulmonary embolism 1 Gastointestinal hemorrhage 1 Other types of bleeding 3

18 Clinical presentation in 36 children Cario et al Ann Hematol 2009; 88:713 Other presenting symptoms include headache, nausea, syncope, dizziness, pruritus, impaired vision Hemoglobin 189 (median, range ) Hematocrit 61 (41-80) Leukocytes 13,2 (3,3-22,2) Platelets 600 ( )

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20 Clinical presentation in 36 children Cario et al Ann Hematol 2009; 88:713 17/19 patients subnormal S-EPO JAK2 V617F mutation 9/16, exon 12 mutation 2/16 10/16 (62 %) mutationsfrekvens

21 The revised WHO diagnostic criteria for Ph-negative myeloproliferative diseases are not appropriate for the diagnostic screening of childhood polycythemia vera and essential thrombocythemia. Teofili et al Blood. 2007;110: children with PV (morphology and increased red cell mass) JAK2V617F mutation, 3/8 pat Exon 12 JAK2 mutations 0/8 Low serum Epo 2/8 EEC growth 3/8

22 Conclusions childhood PV PV in children and adolescents very rare Serious disorder; 3 pts died (8 %, Budd- Chiari and stroke) It is currently not possible to treat an individual patient with an evidencebased regimen. Treatment ranged from phlebotomy +aspirin to marrow transplant IFN logical therapy!?

23 The revised WHO diagnostic criteria for Ph-negative myeloproliferative diseases are not appropriate for the diagnostic screening of childhood polycythemia vera and essential thrombocythemia. Teofili et al Blood. 2007;110: Diagnostic screening of pediatric patients should first investigate whether other family members show similar hematologic abnormalities. In such patients, a careful screening for specific hereditary mutations should be performed

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26 Eero MÄNTYRANTA Naturally Rich Blood

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30 Time for questions!

31 Benmärgshämmande behandling Problem att tolerera flebotomibehandling Symptomatisk eller progressiv splenomegali Andra tecken till sjukdomsprogress t ex viktnedgång, nattliga svettningar TPK > 1500 x 10 9 /l för att förhindra blödning och trombos (grad B) Alla nivåer av TPK stegring hos patient med tidigare trombos eller hos patienter > 60 år för att förhindra trombos (grad C) Behandlingsförsök med IFN till pat < 60 år med TPK > 600 x 10 9 /l hos patienter < 60 år för att uppnå molekylär remission (grad C)