Unal Selma, Varan Ali, Yalçin Bilgehan, Büyükpamukçu Münevver, Gürgey Aytemiz
Section of Pediatric Hematology, Department of Pediatrics, Faculty of Medicine, Hacettepe University, 06100, Ankara, Turkey.
Ann Hematol. 2005 Jun;84(6):395-9. doi: 10.1007/s00277-005-1004-x. Epub 2005 Feb 26.
The purpose of this study was to evaluate inherited and acquired prothrombotic risk factors among children with malignancies who have thrombosis and emphasize the importance of inherited prothrombotic risk factors. Thirty-seven consecutive children with thrombosis and malignancy were included in this study. The patients were evaluated separately for time of development of thrombosis, insertion of a central venous line (CVL), history of L: -asparaginase usage, and recent infections. Prothrombotic risk factors such as factor V G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin III deficiencies, factor VIII and lipoprotein(a) elevation, and antiphospholipid antibodies were analyzed for all patients. Of 387 children with thrombosis, 37 (9.5%) had a malignancy. Thrombosis was detected in 9 patients at the time of diagnosis, during maintenance therapy in 25 patients, and after the discontinuation of treatment in 3 patients. One or two additional prothrombotic risk factors other than L: -asparaginase therapy and insertion of central venous lines were present in 20 of these patients (54%). It was found that eight patients had the factor V G1691A mutation in the heterozygote state. One of them had the factor V G1691A mutation associated with a history of infection and one patient had the factor V G1691A mutation associated with factor VIII elevation. One had the the prothrombin G20210A mutation in the heterozygote state, four had lipoprotein(a) elevation, two had factor VIII elevation, one had a decreased protein S level, one had a decreased protein C level, one had antiphospholipid positivity, and two had histories of infection. Malignancy is an important risk factor for the development of childhood thrombosis. However, the risk of thrombosis increases when accompanied by additional prothrombotic risk factors. For this reason, especially children with malignancy and at high risk for the development of thrombosis, such as those who have received L: -asparaginase or a replaced CVL during their therapy, might be screened for additional prothrombotic risk factors and appropriate measures might be taken to prevent the development of thrombosis.
本研究的目的是评估患有血栓形成的恶性肿瘤儿童的遗传性和获得性血栓前危险因素，并强调遗传性血栓前危险因素的重要性。本研究纳入了37例连续的患有血栓形成和恶性肿瘤的儿童。对患者分别评估血栓形成的时间、中心静脉导管（CVL）的置入情况、左旋门冬酰胺酶的使用史以及近期感染情况。对所有患者分析血栓前危险因素，如因子V G1691A和凝血酶原G20210A突变、蛋白C、蛋白S、抗凝血酶III缺乏、因子VIII和脂蛋白(a)升高以及抗磷脂抗体。在387例患有血栓形成的儿童中，37例（9.5%）患有恶性肿瘤。9例患者在诊断时检测到血栓形成，25例在维持治疗期间，3例在治疗中断后。除左旋门冬酰胺酶治疗和中心静脉导管置入外，这些患者中有20例（54%）存在一种或两种额外的血栓前危险因素。发现8例患者处于杂合状态的因子V G1691A突变。其中1例因子V G1691A突变与感染史相关，1例患者因子V G1691A突变与因子VIII升高相关。1例处于杂合状态的凝血酶原G20210A突变，4例脂蛋白(a)升高，2例因子VIII升高，1例蛋白S水平降低，1例蛋白C水平降低，1例抗磷脂阳性，2例有感染史。恶性肿瘤是儿童血栓形成的重要危险因素。然而，当伴有额外的血栓前危险因素时，血栓形成的风险会增加。因此，尤其是患有恶性肿瘤且血栓形成风险高的儿童，如在治疗期间接受过左旋门冬酰胺酶或更换过CVL的儿童，可能需要筛查额外的血栓前危险因素，并采取适当措施预防血栓形成。
