Högt Hb hos vuxna och barn utredning och klinik Jan Samuelsson Vetenskaplig sekreterare
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
Polyglobulier hos barn/ungdomar Medfödda EPO receptormutation VHL, Chuvash HIF-2α mutation Högaffinitetshemoglobin Gravt hjärtfel Förvärvade Polycytemia vera
Normal Pseudo- (Relativ) Absolut
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.
Figure 1. JAK/STAT signal transduction pathway in responses to hematopoietic growth factors Schafer, A. I. Blood 2006;107:4214-4222 Copyright 2006 American Society of Hematology. Copyright restrictions may apply.
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
Polycytemia vera naturalförloppet Chiewitz & Thiede Acta Med Scand 1962 250 pat Obehandlad PCV 18 mån medianöverlevnad 70 % av dödsfallen i trombos, fr a stroke
38 % mortalitet inom 20 år hos patienter diagnosticerade innan 50åå Passamonti et al. Haematologica 2003; 88: 13-18
15 % risk för AML, 10 % risk för MF efter 20 år
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)
Age distribution of 36 pediatric patients. with polycythemia vera Cario et al Ann Hematol 2009; 88:713
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
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 155-267) Hematocrit 61 (41-80) Leukocytes 13,2 (3,3-22,2) Platelets 600 (83-2020)
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
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;110:3384-6. 8 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
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!?
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;110:3384-6. 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
Eero MÄNTYRANTA Naturally Rich Blood
Time for questions!
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)