Thrombocytopenia in Pregnancy
Yıl 2016,
Cilt: 25 Sayı: 3, 420 - 432, 30.09.2016
Mehmet Özsürmeli
,
Mete Sucu
Cihan Çetin
Ghanim Khatib
Cansun Demir
Öz
Thrombocytopenia, which is encountered in 7-10% of pregnancies is characterized with decreased number of thrombocytes. The most frequent cause of thrombocytopenia during pregnancy is gestational thrombocytopenia. These patients usually do not have symptoms due to mild thrombocytopenia. The diagnosis is usually established by excluding connective tissue disorders, drug effects and obstetric causes. The etiology of thrombocytopenia during early pregnancy is most frequently due to autoimmune causes. Thrombocytopenia secondary to obstetric causes like preeclampsia, HELLP syndrome should always be kept in mind. Under these circumstances the thrombocytopenia will not resolve unless pregnancy is terminated. The clinician should be able to distinguish between thrombocytopenia that does not require treatment and the causes that require emergent and serious medical interventions.
Kaynakça
- Myers B. Diagnosis and management of maternal thrombocytopenia in pregnancy.Br J Haematol. 2012;158:3-15.
- Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med. 1993;329:1463-6.
- Adams TM,Allaf MB, Vintzileos AM. Maternal thrombocytopenia in pregnancy: diagnosis and management. Clin Lab Med. 2013;33:327-41.
- Burrows RF, Kelton JG. Thrombocytopenia at delivery: a prospective survey of 6715 deliveries. Am J Obstet Gynecol. 1990;162:731–4.
- George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996; 88:3-40.
- Silver RM, Branch DW, Scott JR. Maternal thrombocytopenia in pregnancy: time for a reassessment. Am J Obstet Gynecol. 1995;173:479–82.
- Allford SL, Hunt BJ, Rose P, Machin SJ. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol. 2003;120:556-73.
- Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190-207.
- Segal JP, Powe NR. Prevalence of immune thrombocytopenia: analysis of administrative data. J Thromb Haemost. 2006;4:237–83.
- Webert KE, Mittal R, Sigouin C, Heddle NM, Kelton JG. A retrospective 11 year analysis of obstetric patients with idiopathic thrombocytopenia purpura. Blood. 2003;102:4306–11.
- Payne SR, Resnik R, Moore TR, Hedriana HL, Kelly TF. Maternal characteristics and risk of severe neonatal thrombocytopenia and intracranial hemorrhage in pregnancies complicated by autoimmune thrombocytopenia. Am J Obstet Gynecol.1997;177:149–55.
- Ünüvar A. Çocukluk çağında primer immün trombositopeni. Turkiye Klinikleri J Hematol-Special Topics. 2014;7:46-59
- Samuels P, Bussel JB, Braitman LE, Tomaski A, Druzin ML, Mennuti MT, et al. Estimation of the risk of thrombocytopenia in the offspring of pregnant women with presumed immune thrombocytopenic purpura. N Engl J Med. 1990; 26:229-35.
- Şahin Ş, Bingöl U, Özsoy ZA,Taşlıyurt T. Gebelikte trombositopeni. Abant Med J. 2014;3:99-104.
- ACOG practice bulletin: Thrombocytopenia in pregnancy. Number 6, September 1999. Clinical management guidelines for obstetrician-gynecologists. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1999;67:117-28.
- Samama CM, Bastien O, Forestier F, Denninger MH, Isetta C, Juliard JM et al.Antiplatelet agents in the perioperative period: expert recommendations of the French Society of Anesthesiology and Intensive Care. Can J Anaesth. 2002;49:26–35.
- Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168–86.
- Asano T, Sawa R, Araki T, Yamamoto M. Incidence of thrombocytopenia in infants born to mothers with idiopathic thrombocytopenic purpura. Acta Paediatr Jpn.1998;40:112-5.
- Iyori H, Fujisawa K, Akatsuka J. Thrombocytopenia in neonates born to women with autoimmune thrombocytopenic purpura. Pediatr Hematol Oncol.1997;14:367-73.
- McCrae KR, Samuels P, Schreiber AD. Pregnancy-associated thrombocytopenia: pathogenesis and management. Blood. 1992;80:2697–714.
- McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin Apher. 2001;16:202–9.
- Dashe JS, Ramin SM, Cunningham FG. The long-term consequences of thrombotic microangiopathy (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) in pregnancy. Obstet Gynecol. 1998;91:662-8.
- Furlan M, Robles R, Solenthaler M, Lämmle B. Acquired deficiency of von Willebrand factor- cleaving protease in a patient with thrombotic thrombocytopenic purpura. Blood. 1998;91:2839– 46.
- Scully M, Thomas M, Underwood M, Watson H, Langley K, Camilleri RS,et al. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood. 2014;124:211-9.
- Peyvandi F, Ferrari S, Lavoretano S, Canciani MT, Mannucci PM. Von Willebrand cleaving protease (ADAMTS13) and ADAMTS13 neutralizing autoantibodies in 100 patients with thrombotic thrombocytopenic purpura. Br J Haematol. 2004;127:433–9.
- Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158:323–35.
- Ambrose A, Welham RT, Cefalo RC. Thrombotic thrombocytopenic purpura in early pregnancy. Obstet Gynecol.1985;66:267–72.
- Wurzei JM. TTP lesions in placenta but not fetus. N Engl J Med.1979;301:503-4.
- Fujimura Y, Matsumoto M, Kokame K, Isonishi A, Soejima K, Akiyama N et al. Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients. Br J Haematol. 2009;144:742-54.
- Weiner CP. Thrombotic microangiopathy in pregnancy and the postpartum period. Semin Hematol. 1987;24:119-29.
- Weiner CP, Kwaan HC, Xu C, Paul M, Burmeister L, Hauck W. Antithrombin III activity in women with hypertension during pregnancy. Obstet Gynecol. 1985;65:301-6.
- Fakhouri F, Roumenina L, Provot F, Sallée M, Caillard S, Couzi L et al. Pregnancy associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol. 2010;21:859–67.
- Visentin GP, Ford SE, Scott JP, Aster RH. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest. 1994;93:81-8.
- Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106:2710-5.
- Aster RH, Curtis BR, McFarland JG, Bougie DW. Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management. J Thromb Haemost. 2009;7:911-8.
- Greinacher A, Fuerll B, Zinke H, Müllejans B, Krüger W, Michetti N et al. Megakaryocyte impairment by eptifibatide-induced antibodies causes prolonged thrombocytopenia. Blood. 2009;114:1250-3.
- Newman PJ. Switched at birth: a new family for PECAM-1. J Clin Invest. 1999;103:5-9.
- Curtis BR, McFarland JG, Wu GG, Visentin GP, Aster RH. Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium-dependent epitopes on the glycoprotein IIb/IIIa complex. Blood. 1994;84:176-83.
- Reese JA, Li X, Hauben M, Aster RH, Bougie DW, Curtis BR et al. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods. Blood. 2010;116:2127-33.
- Keti DB, Muhtaroğlu S, Kalay N. Antikoagülanların tam kan sayımına etkisi: EDTA’ya bağlı psödotrombositopeni. Türkiye Klinikleri Biyokimya Dergisi. 2015;13:79-82.
- Rattray DD, O'Connell CM, Baskett TF. Acute disseminated intravascular coagulation in obstetrics: a tertiary centre population review.J Obstet Gynaecol Can. 2012;34:341-7.
- Sullivan AK, Raben D, Reekie J, Rayment M, Mocroft A, Esser S et al. Feasibility and effectiveness of indicator condition-guided testing for HIV: results from HIDES I (HIV indicator diseases across Europe study). PLoS One. 2013;8:e52845.
- Sİgaard OS, Lohse N, Østergaard L, Kronborg G, Rİge B, Gerstoft J et al. Morbidity and risk of subsequent diagnosis of HIV: a population based case control study identifying indicator diseases for HIV infection. PLoS One. 2012;7:e32538.
- Keskin EY, Kabasakal H, İnce H, Keskin M, İğde M, Öksüz BG. B12 vitamini eksikliğine ikincil hemoliz bulguları olan yaşamı tehdit eden anemi, trombositopeni ve beyin atrofisi. Cukurova Medical Journal. 2014;39:900-4.
- Aster RH. Pooling of platelets in the spleen: role in the pathogenesis of"hypersplenic" thrombocytopenia. J Clin Invest. 1966;45:645-57.
- Correspondence Address / Yazışma Adresi Mehmet Özsürmeli
- Çukurova Üniversitesi Tıp Fakültesi
- Kadın Hastalıkları ve Doğum Anabilim Dalı,
- Perinatoloji Bilim Dalı, Adana, Turkey
- e-mail: ozsurmeli@gmail.com
- Geliş tarihi/ Received: 18.02.2016
- Kabul tarihi/Accepted: 04.03.2016
Yıl 2016,
Cilt: 25 Sayı: 3, 420 - 432, 30.09.2016
Mehmet Özsürmeli
,
Mete Sucu
Cihan Çetin
Ghanim Khatib
Cansun Demir
Öz
Trombositopeni gebeliklerin %7-10’unda saptanan, trombosit sayısının düşüklüğüyle karakterize bir
durumdur. Gebelikte görülen trombositopenin en sık sebebi gestasyonel trombositopenidir. Bu
hastalarda trombositopeni genelde hafif olduğundan semptom görülmez. Tanı çoğunlukla bağ dokusu
hastalıklarının,ilaç etkilerinin, obstetriyle ilişkili sebeplerin dışlanmasıyla konulur. Erken gebelik
haftalarında görülen trombositopenin etyolojisinde en fazla otoimmun sebepler rol alır.
Preeklampsi,HELLP sendromu gibi obstetriyle ilişkili nedenlere ikincil gelişen trombositopeniler ise her
zaman akılda tutulmalıdır. Bu durumların varlığında çoğu zaman doğum gerçekleşmeden
trombositopeni düzelmeyecektir. Klinisyen; tedavi gerektirmeyen trombositopenilerle, annenin
fetusun hayatını tehdit eden ve bu nedenle acil ve ciddi bakım gerektiren trombositopeni sebepleri
arasında ayırımı iyi yapabilmelidir.
Kaynakça
- Myers B. Diagnosis and management of maternal thrombocytopenia in pregnancy.Br J Haematol. 2012;158:3-15.
- Burrows RF, Kelton JG. Fetal thrombocytopenia and its relation to maternal thrombocytopenia. N Engl J Med. 1993;329:1463-6.
- Adams TM,Allaf MB, Vintzileos AM. Maternal thrombocytopenia in pregnancy: diagnosis and management. Clin Lab Med. 2013;33:327-41.
- Burrows RF, Kelton JG. Thrombocytopenia at delivery: a prospective survey of 6715 deliveries. Am J Obstet Gynecol. 1990;162:731–4.
- George JN, Woolf SH, Raskob GE, Wasser JS, Aledort LM, Ballem PJ et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood. 1996; 88:3-40.
- Silver RM, Branch DW, Scott JR. Maternal thrombocytopenia in pregnancy: time for a reassessment. Am J Obstet Gynecol. 1995;173:479–82.
- Allford SL, Hunt BJ, Rose P, Machin SJ. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol. 2003;120:556-73.
- Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190-207.
- Segal JP, Powe NR. Prevalence of immune thrombocytopenia: analysis of administrative data. J Thromb Haemost. 2006;4:237–83.
- Webert KE, Mittal R, Sigouin C, Heddle NM, Kelton JG. A retrospective 11 year analysis of obstetric patients with idiopathic thrombocytopenia purpura. Blood. 2003;102:4306–11.
- Payne SR, Resnik R, Moore TR, Hedriana HL, Kelly TF. Maternal characteristics and risk of severe neonatal thrombocytopenia and intracranial hemorrhage in pregnancies complicated by autoimmune thrombocytopenia. Am J Obstet Gynecol.1997;177:149–55.
- Ünüvar A. Çocukluk çağında primer immün trombositopeni. Turkiye Klinikleri J Hematol-Special Topics. 2014;7:46-59
- Samuels P, Bussel JB, Braitman LE, Tomaski A, Druzin ML, Mennuti MT, et al. Estimation of the risk of thrombocytopenia in the offspring of pregnant women with presumed immune thrombocytopenic purpura. N Engl J Med. 1990; 26:229-35.
- Şahin Ş, Bingöl U, Özsoy ZA,Taşlıyurt T. Gebelikte trombositopeni. Abant Med J. 2014;3:99-104.
- ACOG practice bulletin: Thrombocytopenia in pregnancy. Number 6, September 1999. Clinical management guidelines for obstetrician-gynecologists. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1999;67:117-28.
- Samama CM, Bastien O, Forestier F, Denninger MH, Isetta C, Juliard JM et al.Antiplatelet agents in the perioperative period: expert recommendations of the French Society of Anesthesiology and Intensive Care. Can J Anaesth. 2002;49:26–35.
- Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB et al. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010;115:168–86.
- Asano T, Sawa R, Araki T, Yamamoto M. Incidence of thrombocytopenia in infants born to mothers with idiopathic thrombocytopenic purpura. Acta Paediatr Jpn.1998;40:112-5.
- Iyori H, Fujisawa K, Akatsuka J. Thrombocytopenia in neonates born to women with autoimmune thrombocytopenic purpura. Pediatr Hematol Oncol.1997;14:367-73.
- McCrae KR, Samuels P, Schreiber AD. Pregnancy-associated thrombocytopenia: pathogenesis and management. Blood. 1992;80:2697–714.
- McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin Apher. 2001;16:202–9.
- Dashe JS, Ramin SM, Cunningham FG. The long-term consequences of thrombotic microangiopathy (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome) in pregnancy. Obstet Gynecol. 1998;91:662-8.
- Furlan M, Robles R, Solenthaler M, Lämmle B. Acquired deficiency of von Willebrand factor- cleaving protease in a patient with thrombotic thrombocytopenic purpura. Blood. 1998;91:2839– 46.
- Scully M, Thomas M, Underwood M, Watson H, Langley K, Camilleri RS,et al. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood. 2014;124:211-9.
- Peyvandi F, Ferrari S, Lavoretano S, Canciani MT, Mannucci PM. Von Willebrand cleaving protease (ADAMTS13) and ADAMTS13 neutralizing autoantibodies in 100 patients with thrombotic thrombocytopenic purpura. Br J Haematol. 2004;127:433–9.
- Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012;158:323–35.
- Ambrose A, Welham RT, Cefalo RC. Thrombotic thrombocytopenic purpura in early pregnancy. Obstet Gynecol.1985;66:267–72.
- Wurzei JM. TTP lesions in placenta but not fetus. N Engl J Med.1979;301:503-4.
- Fujimura Y, Matsumoto M, Kokame K, Isonishi A, Soejima K, Akiyama N et al. Pregnancy-induced thrombocytopenia and TTP, and the risk of fetal death, in Upshaw-Schulman syndrome: a series of 15 pregnancies in 9 genotyped patients. Br J Haematol. 2009;144:742-54.
- Weiner CP. Thrombotic microangiopathy in pregnancy and the postpartum period. Semin Hematol. 1987;24:119-29.
- Weiner CP, Kwaan HC, Xu C, Paul M, Burmeister L, Hauck W. Antithrombin III activity in women with hypertension during pregnancy. Obstet Gynecol. 1985;65:301-6.
- Fakhouri F, Roumenina L, Provot F, Sallée M, Caillard S, Couzi L et al. Pregnancy associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol. 2010;21:859–67.
- Visentin GP, Ford SE, Scott JP, Aster RH. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest. 1994;93:81-8.
- Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood. 2005;106:2710-5.
- Aster RH, Curtis BR, McFarland JG, Bougie DW. Drug-induced immune thrombocytopenia: pathogenesis, diagnosis, and management. J Thromb Haemost. 2009;7:911-8.
- Greinacher A, Fuerll B, Zinke H, Müllejans B, Krüger W, Michetti N et al. Megakaryocyte impairment by eptifibatide-induced antibodies causes prolonged thrombocytopenia. Blood. 2009;114:1250-3.
- Newman PJ. Switched at birth: a new family for PECAM-1. J Clin Invest. 1999;103:5-9.
- Curtis BR, McFarland JG, Wu GG, Visentin GP, Aster RH. Antibodies in sulfonamide-induced immune thrombocytopenia recognize calcium-dependent epitopes on the glycoprotein IIb/IIIa complex. Blood. 1994;84:176-83.
- Reese JA, Li X, Hauben M, Aster RH, Bougie DW, Curtis BR et al. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods. Blood. 2010;116:2127-33.
- Keti DB, Muhtaroğlu S, Kalay N. Antikoagülanların tam kan sayımına etkisi: EDTA’ya bağlı psödotrombositopeni. Türkiye Klinikleri Biyokimya Dergisi. 2015;13:79-82.
- Rattray DD, O'Connell CM, Baskett TF. Acute disseminated intravascular coagulation in obstetrics: a tertiary centre population review.J Obstet Gynaecol Can. 2012;34:341-7.
- Sullivan AK, Raben D, Reekie J, Rayment M, Mocroft A, Esser S et al. Feasibility and effectiveness of indicator condition-guided testing for HIV: results from HIDES I (HIV indicator diseases across Europe study). PLoS One. 2013;8:e52845.
- Sİgaard OS, Lohse N, Østergaard L, Kronborg G, Rİge B, Gerstoft J et al. Morbidity and risk of subsequent diagnosis of HIV: a population based case control study identifying indicator diseases for HIV infection. PLoS One. 2012;7:e32538.
- Keskin EY, Kabasakal H, İnce H, Keskin M, İğde M, Öksüz BG. B12 vitamini eksikliğine ikincil hemoliz bulguları olan yaşamı tehdit eden anemi, trombositopeni ve beyin atrofisi. Cukurova Medical Journal. 2014;39:900-4.
- Aster RH. Pooling of platelets in the spleen: role in the pathogenesis of"hypersplenic" thrombocytopenia. J Clin Invest. 1966;45:645-57.
- Correspondence Address / Yazışma Adresi Mehmet Özsürmeli
- Çukurova Üniversitesi Tıp Fakültesi
- Kadın Hastalıkları ve Doğum Anabilim Dalı,
- Perinatoloji Bilim Dalı, Adana, Turkey
- e-mail: ozsurmeli@gmail.com
- Geliş tarihi/ Received: 18.02.2016
- Kabul tarihi/Accepted: 04.03.2016