הריון בפוליציטמיה

שלום ד"ר!!! תודה רבה על תשובותיך הקודמות שאלה לי נוספת, החלטנו אשתי ואני באישור הרופא שלנו לצאת שוב לדרך - לקראת כניסה להריון - אשתי חולה כאמור בפוליצטמיה וורה. המשמעות היא מעבר מטיפול בכדורי אגרלין לזריקות אינטרפרון (או אינטרון) שזהו הטיפול היחידי האפשרי לבחורה הרוצה להרות עם מחלה זו שאלתי - רציתי לשמוע את דעתך, כמה זמן יש להמתין מרגע הפסקת האגרלין עד לזמן שניתן להתחיל להיכנס להריון כלומר כמה זמן צריך לחכות מרגע הפסקת השימוש באגרלין??? הייתי שמח לשמוע את דעתך גם בנושא - האם ידועה לך דרך טיפול אחרת בתקופת הריון בפוליצטמיה??? תודה רבה לילי

בלינק הבא תמצאו מידע על אגרילין והריון. http://www.agrylin.net/page5.shtml ההשפעה של אגרילין על הטרומבוציטים פגה לאחר 4-8 ימים מהפסקת התרופה. המאמר לעיל מאזכר נשים שהפסיקו את התרופה רק כאשר נודע להן שהן הרות ילדו ילדים נורמליים. יש מאמרים הפוכים כך שבודאי אין להסתכן. אני משער - ויש להתייעץ עם הגינקולוג - שאין כל חשש מכניסה להריון לאחר שבועיים הפסקה של התרופה. לגבי הריון ופוליציטמיה - ברור שמדובר בהריון בסיכון גבוה ויש צורך בליווי צמוד של גינקולוג והמטולוג. אני חושב שאם יש טרומבוציטוזיס צריך יהיה לקבל גם אספירין, אבל צריל להתייעץ עם המטפלים בנושא זה. מצרף כמה תקצירים שיכולים לסייע. http://www.nlm.nih.gov/medlineplus/druginfo/anagrelidesystemic203493.html http://www.emedicine.com/med/topic1864.htm *********************************************************** על הריון וטרומבוציטוזיס: Eur J Haematol 2001 Mar;66(3):152-9 A single institutional experience with 43 pregnancies in essential thrombocythemia. Wright CA, Tefferi A Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA. OBJECTIVES: We describe the periconception circumstances and outcome of 43 consecutive pregnancies in an unselected group of young women with essential thrombocythemia (ET). PATIENTS AND METHODS: We retrospectively studied 74 consecutive cases of young women with ET seen at our institution, among whom 43 pregnancies occurred in 20 patients. Results: Of the 43 pregnancies, 22 (51%) were successful (21 term and 1 preterm live births) and 21 (49%) ended in miscarriages (1 ectopic pregnancy, 2 elective abortions, 16 first-trimester spontaneous abortions, 1 stillbirth at 22 wk, and 1 abruptio placentae at 33 wk). Management of ET at the time of conception included either no specific therapy (16 cases) or the use of aspirin alone (24 cases), a cytoreductive agent (2 cases), or heparin (1 case). There were no significant differences with respect to platelet count or the effect of treatment with aspirin, either at the time of conception or during the first trimester, among cases of successful pregnancies (22), all miscarriages (21), or first-trimester spontaneous abortions (16). The findings were similar when the analysis was restricted to only first-time pregnancies. In patients with multiple pregnancies, the outcome of a subsequent pregnancy was not predicted by the outcome of the first. In general, in successful cases the last two trimesters were mostly uneventful, with healthy offspring being reported in all cases. Conclusions: Pregnant patients with ET have an increased risk of first-trimester abortion which is not predictable by preconception platelet count or aspirin therapy. In addition, our experience does not support the use of prophylactic platelet apheresis during delivery. **************************************************************************************** Clin Appl Thromb Hemost 2000 Jan;6(1):31-5 Essential thrombocythemia in young adults: major thrombotic complications and complications during pregnancy--a follow-up study in 68 patients. Randi ML, Rossi C, Fabris F, Girolami A Department of Medical and Surgical Science, University Medical School of Padua, Italy. OBJECTIVES: Although essential thrombocythemia (ET) is usually primarily considered a disorder of middle age, it has been observed in children and young adults. However, the real risk for thrombosis in these patients has not been clearly established. DESIGN: Prospective analysis of consecutive patients younger than 40 at the time of the diagnosis of ET and followed in our department between 1980 and 1998. SUBJECTS: Sixty-eight patients (28 males and 40 females, median follow-up 99.14 months) affected by ET diagnosed in agreement with the Polycythemia Vera Study Group criteria. INTERVENTIONS: Asymptomatic ET patients were not treated. In contrast, patients with associated atherosclerotic risk factors, microvascular disturbances, or a previous major arterial thrombosis were given acetyl salicylic acid (ASA 100 mg/day). Only patients with major thrombotic complications and a platelet count > 1,000 x 10(9)/L received cytoreductive therapy. OUTCOME MEASURES: (1) to evaluate thrombotic complications in young patients with ET, (2) to relate thrombotic risk to the presence of general atherosclerotic risk factors, and (3) to adopt treatment, and (4) to report the outcome of the pregnancies monitored in our population. RESULTS: Fifteen patients had major thrombosis, 11 of which were the presenting features of ET. No rethrombosis has been observed. Only one patient with thrombotic complications was under efficient treatment. Atherosclerotic risk factors are more common in patients with major arterial thrombosis than in asymptomatic subjects. Thirteen normal babies were delivered out of 16 pregnancies, 6 of the pregnant women were on ASA therapy. CONCLUSIONS: Most thrombosis in young ET patients occurred at the time of the diagnosis, and venous thrombotic events represent one-third of total thrombosis. Cardiovascular risk factors seem to be concurrent stimuli for arterial thrombosis in ET. The thrombotic complication rate was 2.6/100 patients/year ASA reduces microvascular disturbances, thrombosis, and rethrombosis and possibly reduces obstetric complications in women with ET. **************************************************************************************** אגרילין: Expert Opin Pharmacother 2000 Mar;1(3):537-46 Anagrelide: a novel agent for the treatment of myeloproliferative disorders. Pescatore SL, Lindley C Division of Pharmacotherapy, University of North Carolina at Chapel Hill, Beard Hall CB 7360, Chapel Hill, NC 27514, USA. [email protected] Anagrelide hydrochloride (Agrylin, Roberts Pharmaceutical Corp.) is an oral imidazoquinazoline agent that has been shown to reduce elevated platelet counts and the risk of thrombosis in patients with thrombocythaemia in various myeloproliferative disorders (MPD). It is currently approved by the FDA as oral treatment for essential thrombocythaemia (ET) and thrombocythaemia associated with polycythaemia vera (PV). Anagrelide selectively suppresses bone marrow megakaryocytes by interfering with the maturation process and decreasing platelet production without affecting the erythroid and myeloid progenitor cells. Other medications indicated for the treatment of thrombocythaemia, including interferon alpha (IFN-alpha), alkylating agents and hydroxyurea, suppress all cell lines. Anagrelide is known to inhibit platelet cyclic adenosine monophosphate (cAMP) phosphodiesterase at concentrations that exceed those achieved at doses used to treat ET. Anagrelide is extensively metabolised in the liver and its metabolites are primarily excreted in the urine. Adverse effects associated with the use of anagrelide are primarily caused by the drugs' direct vasodilating and positive inotropic effects. These include headache, hypotension and diarrhoea. It has also been known to cause fluid retention, tachycardia, nausea, abdominal pain and arrhythmias. The starting dose of anagrelide ranges from 0.5 mg q.i.d. to 1 mg b.i.d. with a maximum dose of 2.5 mg q.i.d. Adequate responses have been maintained with a median dose of 2-2.5 mg/day. Platelet counts begin to decrease in 7-10 days, however, they return to pre-treatment levels within 4-8 days if therapy is stopped. Anagrelide 2 mg/day for one year costs approximately US$6439, and treatment must continue indefinitely [1]. ******************************************************************************************** Pathol Biol (Paris) 2001 Mar;49(2):178-83 Management of patients with essential thrombocythemia: current concepts and perspectives. Briere J, Guilmin F Service d'hematologie clinique, hopital Beaujon, 92110 Clichy, France. Essential thrombocythemia must now be regarded as a heterogeneous disease. Recent availability of clonality studies have repeatedly shown that a significant number of female patients diagnosed as E.T. according the most stringent criteria had a definitely polyclonal myelopoiesis. Although the incidence of patients newly diagnosed every year is low, there is in fact a conspicuous population of E.T., followed as outpatients in every department of hematology or internal medicine, including a large number of young females. These eventualities should be integrated in further discussions of the benefit/risk ratio of cytoreduction with the presently available drugs. The combination of several evidence-based data is the basis of a widely accepted stratification of high-risk patients defined by any of the following features. Age > 60 to 65. History of thrombosis or embolic or major ischemic events. Platelet counts in excess of 1000 or 1500 x 10(9)/L. In the question of chemotherapy in E.T., growing concern comes from the potential leukemogenic risk associated with the presently available drugs and extends beyond Melphalan, Busulfan and other alkylating agents and includes non-alkylating agents like Hydroxyurea. At the same time, much attention has been paid to the introduction of very precise initial diagnostic criteria directed to elimination of other myeloproliferative or myelodysplastic disorders with an increased risk of transformation. Present treatment of E.T. is a compromise between prevention of E.T. related thrombotic and bleeding complications on one hand and long term side effects and toxicity of the presently available drugs on the other hand. The recent availability of non mutagenic drugs like Interferon and most of all Anagrelide; the recognition of the role of antiaggregating agents in the treatment of platelet related microvascular ischemic events gives the opportunity for further comparative prospective trials. The use of aspirin in the management of pregnant E.T. patients is now widely accepted but there is still controversies concerning the use of Interferon in this situation. ***************************************************************************** את המאמר הבא כדאי אולי לקרוא בשלמותו - בספריה של אחד מבתי החולים או באוניברסיטה. Am J Med 2000 Aug 1;109(2):141-9 A clinical update in polycythemia vera and essential thrombocythemia. Tefferi A, Solberg LA, Silverstein MN Division of Hematology and Internal Medicine (AT, MNS), Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA. Polycythemia vera and essential thrombocythemia pose specific management issues that distinguish them from other chronic myeloproliferative disorders. They are associated with a better prognosis, as well as a variable risk of thrombohemorrhagic complications. In addition, essential thrombocythemia occurs comparatively more often in young people and women. Treatment strategies for patients with polycythemia vera and essential thrombocythemia must consider the possibility of long-term survival, morbidity from thrombotic complications, transformation into myelofibrosis with myeloid metaplasia or acute myeloid leukemia, and the effect of specific therapies on the incidence of leukemic transformation and on pregnancy. There is increasing concern about the possible leukemogenic effect of hydroxyurea. Newer therapeutic agents, including interferon alpha and anagrelide, are being used more often. Ongoing studies are reexamining the effects of low-dose aspirin in preventing thrombotic complications