קרישי דם בשיליה

שלום רב, לפני כחצי שנה נאלצתי לעשות הפסקת הריון בשבוע 21 , זאת משום מימצא של שליה גדולה עם המיטומות, גם הבדיקה הפתולוגית דיווחה על 95 אחוז מהשיליה היה עם קרישי דם רבים. עשיתי בדיקות לקרישיות יתר, הכל היה תקין למעט MTHFR שהיה הומוזיגוט. הרופא שלי החליט שבהריון הנוכחי החדש (אני בשבוע 14) אני אטול כדורי מיקרופרין וכן אקבל זריקות קלקסן. וכן חומצה פולית 5 מ"ג כל יום למשל כל החיים. אבל מכיוון שההרוין הנוכחי התחיל עם דימומים שממשיכים ממש עד לעצם רגע זה, נאלצתי לא לקחת את הזריקות עד לאחר שיפסק הדימום. השאלות שלי: 1. האם המימצא הנ"ל אכן מספק כדי להבין מה קרה שלי בשיליה? 2. האם כשאקח את הזריקות ואחרי תקופה יחזור הדימום יש בכך סיכון? 3.יש בדיקות נוספות שאולי כדאי לי לעשותבהריון הנוכחי? 4. האם יש סיכוי שהתופעה הנ"ל הייתהחד פעמית ולא תחזור על עצמה גם ללא טיפול מיוחד? תודה מראש על הקדשת הזמן והתשובות איילת

שלום איילת ממה שכתבת אני מבין שלא נמצאה עדות לאנטיקרדיוליפין או אנטיפוספוליפיד או צירקולייטינג אנטיקואגולנט. כתבת שנמצאת הומוזיגוטית ל- MTHFR ואת זה מתקנים עם מתן חומצה פולית. האם היו לך מאורעות טרומבוטיים אחרים ? הבנתי גם שהיתה לך הפלה בודדת. האם היו לך הריונות תקינים ? ההגדרה של "הפלות נרגלות" (habitual abortions) מתייחסת ל- 3 הריונות (ומעלה) לא מוצלחים רצופים (ראי לינק מצורף המתייחס למחקר בנשים הרות שנמצאה אצלן התסמונת שרשמתי את שמה להלן). http://www.cmecourses.com/Gateway/CMECourseimages/Includes/digestsmain.cfm?MDDigestID=0519 ממה שכתבת עד כה - לא הבנתי מה היתה האינדיקציה למתן האספירין והקלקסן ? מה הסביר לך רופאך ? האם את מתכוונת לגינקולוג המטפל ? ומה לדעתו האבחנה המבדלת של הסיבות להפלה שהיתה לך - במקרה שלא מדובר בקרישיות יתר ? כאמור, הטיפול מיועד לנשים שאצלן קיימת התסמונת "אנטי פוספוליפיד סינדרום" וממה שכתבת הבנתי שלא נמצא אצלך כדבר הזה. לעניין הדימומים - מה סיבתם ? בודאי שהצירוף של מיקרופירין והפרין מגדיל את הסיכון לדימום. בשלב זה קשה לי להתייחס בצורה יותר מעשית לשאלותייך. אשמח לקרוא את התייחסותך למה שכתבתי ואנסה לסייע. בברכה

ד"ר צ. שלום, תודה על התיחסותך. לגבי שאלותך: א. לא היו לי מאורעות אחרים של טרומבופיליות. ב. חוץ מMTHFR הומוזיגוט לא נמצא ממצא חריג אחר (יכול להיות שגם לא הופנתי לעשות את כל הבדיקות האפשריות) ג. הגניקולוג שלי אמר לי שאנשים עם HTFR הומוזיגוט יש נטייה לקרישי דם , יש כאלה שזה לא בא לידי ביטוי בכלל, יש כאלה שעלולים ללקות בהתקף לב וכד'. מכיוון שלא היה שום מימצא אחר שהיסביר את התופעה שהייתה לי הוא אמר כי ייתכן ואני באופן מיוחד רגישה וכי הצטברות קרישי הדם בשיליה עלולה הייתה לנבוע מנטייה גנטית זאת. ומכוון שלא רציתי לקחת שום סיכון להפלה נוספת אז הטיפול הוא ליתר ביטחון...(שוב, זאת למרות שקיימת אפשרות שגם ללא טיפול ההריון הנ"ל יהיה מוצלח). ד. היו לי 2 הפלות בעבר. אין לי ילדים. אני בת 30 . ה. האם אתה מכיר תופעה כזאת של השליה כפי שתארתי לך? תודה שוב, איילת

הנה לינק נוסף, גינקולוגי, המתייחס להפלות: 30% מההפלות הן בגלל מלפורמציות שלייתיות. http://www.vnh.org/OBGYN/abpreg.html#Miscarriage והנה ציטוט מהמאמר Miscarriage Another term for spontaneous abortion. Since the term "spontaneous abortion" may be misunderstood by laymen, the word "miscarriage" is sometimes substituted. A miscarriage occurs once in every 5 or 6 pregnancies. 60% are due to chromosome abnormalities, 30% are due to malformations of the placenta, and the remaining 10% are due to a variety of miscellaneous reasons, which are essentially unpreventable

מצורפי עוד מאמרים בנושא: 1. הנה מאמר המתייחס לקרישים בשליה בנשים עם קרישיות יתר וללא קרישיות יתר. לדברי המחברים אין קשר בין הממצא של קרישים בשליה ובין קרישיות יתר. Hum Reprod 2000 Aug;15(8):1830-3 Do placental lesions reflect thrombophilia state in women with adverse pregnancy outcome? Mousa HA, Alfirevic1 Z University Department of Obstetrics and Gynaecology, Liverpool Women's Hospital, UK. We examined the relationship between placental histology and thrombophilia status in women who were admitted with severe pre-eclampsia/eclampsia, placental abruption, intrauterine growth restriction or unexplained stillbirth. All women had thrombophilia screen at least 10 weeks after delivery (antithrombin III, protein C, protein S, activated protein C resistance, anticardiolipin antibodies, lupus anticoagulant, fasting plasma homocysteine and specific mutations to methylenetetrahydrofolate reductase C677T, G20210A prothrombin gene and factor V Leiden. Placental histology reports were examined to identify the frequency of thrombotic lesions in the placenta including fetal stem vessel thrombosis, fetal thrombotic vasculopathy, placental infarction, perivillous fibrin deposition, intervillous thrombosis and placental floor infarction. During a 17 month period, a cohort of 79 women met the study criteria. Thirty (70%) out of 43 women with abnormal thrombophilia screen had abnormal placental histology. Twenty-eight (78%) out of 36 women with negative thrombophilia screen had abnormal placentae. No specific histological pattern could be identified when thrombophilia positive and thrombophilia negative groups were compared. We propose that there is a poor correlation between thrombophilia status and pathological changes of the placenta in women with severe pregnancy complications. 2. מאמר לגבי היפרהומוציסטאינמיה וסיבוכי הריון. ההמלצה היא לבחון את השפעת מתן חומצה פולית על ההריונות. Br J Obstet Gynaecol 1999 Mar;106(3):273-8 The placenta in maternal hyperhomocysteinaemia. Khong TY, Hague WM Department of Histopathology, Adelaide Women's and Children's Hospital, Australia. It is becoming increasingly apparent that mild or moderate hyperhomocysteinaemia may be associated with adverse perinatal complications and outcomes. The placental pathology in 14 pregnancies from 11 women diagnosed retrospectively to have hyperhomocysteinaemia, following a recent history of intrauterine fetal growth restriction, abruption or of thromboembolic disease, were reviewed. Most of the placental findings indicated abnormal placentation but these were not specific to maternal hyperhomocysteinaemia nor found in every placenta. Features observed included absence of trophoblast-induced physiological vascular changes, acute atherosis, intraluminal endovascular trophoblast in the third trimester, infarction, retroplacental haematoma formation and accelerated villous maturity. Uteroplacental vascular thrombosis was also seen. Three of the women had a subsequent pregnancy where they were treated empirically with folic acid, and these resulted in improved perinatal outcomes. The finding of placental pathology warrants investigation of the woman for hyperhomocysteinaemia. Further randomised controlled trials of folic acid supplementation in preventing pregnancy complications associated with hyperhomocysteinaemia should be conducted. 3. עוד מאמר בנושא: Fertil Steril 2000 Dec;74(6):1196-9 Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Nelen WL, Blom HJ, Steegers EA, den Heijer M, Eskes TK Department of Obstetrics and Gynecology, Nijmegen, The Netherlands. Objective: To quantify the risk of recurrent early pregnancy loss in the presence of elevated fasting or afterload homocysteine concentrations or homozygosity for the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (T/T genotype). Design: Case-control studies published between January 1992 and November 1999 were identified with a MEDLINE-search. These studies were combined with a recent case-control study performed by our own research group.Setting: Academic research environment.Patient(s): Studies published in the English language, concerning two or more pregnancy losses before 16 weeks' menstrual age were included. Intervention(s): Meta-analysis of all of the studies included.Main Outcome Measure(s): The number of subjects with and without hyperhomocysteinemia or with the T/T genotype were derived, if necessary the study was supplemented by personal communication with the original authors.Result(s): Pooled risk estimates of 2.7 (1.4 to 5.2) and 4.2 (2.0 to 8.8) were calculated for fasting and afterload plasma homocysteine concentrations, respectively. For the MTHFR T/T genotype a pooled risk estimate of 1.4 (1.0 to 2.0) was found. Conclusion(s): These data support hyperhomocysteinemia as a risk factor for recurrent early pregnancy loss. Further research should be focused on the pathophysiology of this relationship and on the clinical efficacy of B vitamin supplementation. 4. במאמר הבא יש התייחסות לנושא טיפול אנטיקואגלונטי במקרים של היפרהומוציסטאינמיה, אך ללא הוכחה וללא עדות מחקרית שאכן הדבר נחוץ או מועיל. Eur J Obstet Gynecol Reprod Biol 2000 Dec;93(2):157-65 Hyperhomocysteinemia and pregnancy - review of our present understanding and therapeutic implications. Aubard Y, Darodes N, Cantaloube M Division of Obstetrics and Gynecology, CHU Dupuytren 2 av. Martin-Luther-King 87042, Cedex, Limoges, France. Homocysteine results from the transmethylation of methionine. Its metabolism depends primarily on three enzymes and several vitamin cofactors. Genetic abnormality in these enzymes or deficiency of these vitamins lead to hyperhomocysteinemia (HHCh). HHCh is usually biologically defined by a fasting value >15 &mgr;mol/l. HHCh belongs among the congenital hypercoagulable states and is a long-known vascular disease risk factor. The discovery that HHCh may also be responsible for several pregnancy complications has only recently been made. Studies in this area are still scarce and report on limited numbers of patients. It nevertheless appears clear that HHCh is associated with the syndromes of repeated miscarriage, pre-eclampsia, placenta abruptio, thromboembolic events, neural tube defects, and perhaps with fetal death-in-utero and intra-uterine growth retardation. Supplementation with vitamin B9 can reduce plasma HC levels, and is thus recommended in patients with HHCh. The prevention of thromboembolic events during pregnancy by anticoagulant treatment is also desirable in these patients. 5. תוצאות טיפול בחומצה פולית + ויטמין B6 + אספירין: Am J Obstet Gynecol 1998 Jul;179(1):135-9 Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. Leeda M, Riyazi N, de Vries JI, Jakobs C, van Geijn HP, Dekker GA Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Free University Hospital, Amsterdam, The Netherlands. OBJECTIVE: Our purpose was to assess the incidence of hyperhomocysteinemia in patients with a history of preeclampsia or fetal growth restriction, to evaluate the effects of vitamin supplementation on the methionine loading test, and to study the course of subsequent pregnancies in women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. STUDY DESIGN: A total of 207 consecutive patients with a history of preeclampsia or fetal growth restriction was tested for hyperhomocysteinemia. Thirty-seven were found to be positive and were treated with folic acid and vitamin B6, and 27 had a second methionine loading test after vitamin supplementation. Fourteen patients became pregnant again while receiving vitamins and aspirin. RESULTS: All patients who underwent a methionine loading test after vitamin supplementation had a completely normalized methionine loading test. Of the 14 pregnancies in women receiving vitamins and aspirin, 7 were complicated by preeclampsia. Birth weights were 2867 +/- 648 g compared with 1088 +/- 570 g in the previous pregnancies. CONCLUSIONS: Vitamin B6 and folic acid correct the methionine loading test in patients with hyperhomocysteinemia. Perinatal outcome in patients with a history of preeclampsia or fetal growth restriction and hyperhomocysteinemia appears to be favorable. 6. מתן חומצה פולית + B6 --> הריון מוצלח לאחר 5 הפלות: Fertil Steril 1998 Jan;69(1):152-4 A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages. Quere I, Bellet H, Hoffet M, Janbon C, Mares P, Gris JC Service de Medecine B--Medecine vasculaire, Hopital Saint Eloi, Montpellier, France. OBJECTIVE: To evaluate the medical relevance of hyperhomocysteinemia in women with primary recurrent miscarriages. DESIGN: Case report and retrospective cross-sectional study. SETTING: Hematology outpatient department of a university hospital. PATIENT(S): Case report concerning a woman with five consecutive fetal losses. One hundred consecutive women with primary recurrent unexplained miscarriages (study group) and matched healthy controls (control group) with no antecedent fetal loss. INTERVENTION(S): Venous blood sample collection in resting individuals. MAIN OUTCOME MEASURE(S): Plasma total homocysteine concentrations, plasma folate concentrations, and DNA analysis for the C677T mutation of the 5,10 methylene tetrahydrofolate reductase gene. Normal threshold homocysteine concentration was obtained from values found in the control group (95th percentile). RESULT(S): The case patient was hyperhomocysteinemic, was homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene, and had plasma folate deficiency. Folic acid and pyridoxine administration normalized the homocysteine concentration and favored a successful pregnancy. In the retrospective study, 12 of 100 patients were hyperhomocysteinemic. Twenty percent had the C677T methylene tetrahydrofolate reductase genotype and 15% had low plasma folate concentrations. The highest values of homocysteine concentration were found in patients with both the C677T genotype and folate deficiency. CONCLUSION(S): Hyperhomocysteinemia should be identified in women with recurrent miscarriages because therapeutic normalization might permit a normal birth. 7. טיפול בהיפרהומוציסטאינמיה Curr Atheroscler Rep 2001 Jan;3(1):54-63 Diagnosis and Treatment of Hyperhomocysteinemia. Keebler ME, De Souza C, Fonseca V Section of Endocrinology, Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue (SL 53), New Orleans, LA 70112, USA. [email protected] Hyperhomocysteinemia has emerged as an important risk factor for cardiovascular disease. However, its place in clinical practice is somewhat unclear, due to the lack of clinical trials documenting the benefit of treatment on reducing cardiovascular events. Vitamin therapy, particularly with folic acid, reduces plasma homocysteine significantly and improves other surrogate markers of cardiovascular risk such as endothelial function. Although a consensus is lacking on the right approach to diagnosis and treatment of this risk factor, we have suggested an algorithm based on data from clinical studies. We are optimistic that such an approach will be helpful for the clinician until clinical trials, with cardiovascular events as endpoints, are completed. 8. חומצה פולית בלבד מספיקה לתקן את רמת ההומוציסטאין: J Intern Med 2000 Sep;248(3):223-9 The effect of different treatment regimens in reducing fasting and postmethionine-load homocysteine concentrations. van der Griend R, Biesma DH, Haas FJ, Faber JA, Duran M, Meuwissen OJ, Banga JD Departments of Internal Medicine and Clinical Chemistry, Sint Antonius Hospital, Nieuwegei, The Netherlands. OBJECTIVES: To determine the homocysteine-lowering effect of different treatment regimens on both fasting and postmethionine-load plasma total homocysteine (tHcy) concentrations. DESIGN: Descriptive study of consecutive hyperhomocysteinaemic subjects per treatment regimen. Homocysteine was measured in the fasting state and 6 h after methionine loading, both before and after 8 weeks of vitamin therapy. Hyperhomocysteinaemia was defined as a fasting tHcy and/or increase in tHcy (postmethionine-load minus fasting tHcy concentration) exceeding the 95th percentile of local controls. SETTING: Outpatient clinic of internal medicine of a large non-academic teaching hospital. SUBJECTS: One hundred and seventeen hyperhomocysteinaemic subjects (vascular patients and first-degree relatives). INTERVENTIONS: There were four regimens: pyridoxine, 200 mg; folic acid, 5 mg; combination of folic acid 0.5 mg and pyridoxine 100 mg; and folic acid, 0.5 mg daily. RESULTS: All regimens, except pyridoxine 200 mg, significantly reduced fasting tHcy without differences in the percentage reduction (32-38%). All regimens produced a significant reduction in the increase in tHcy and postmethionine-load tHcy. The reduction in postmethionine-load tHcy was smaller for pyridoxine 200 mg than for combination therapy. No differences were found in the percentage reduction (for both increase in tHcy and postmethionine-load tHcy) between folic acid 5 mg and folic acid 0.5 mg. CONCLUSIONS: Monotherapy folic acid (0.5 mg daily) is the lowest effective therapy for reducing both fasting and postmethionine-load tHcy concentrations, with the same results as high-dose folic acid (5 mg daily). Pyridoxine has no additional value.