Identification of genetic susceptibility to thrombosis i

鉴于我们关于假性脑瘤(PTC)对血栓形成的遗传易感性的研究结果，我们正在研究血栓在肾病性膀胱氨酸病PTC发生中的作用。采用凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、活化蛋白C抵抗力(APCr)、血清蛋白C和S、抗凝血酶III、纤维蛋白原、总同型半胱氨酸、抗磷脂抗体(ACA组和狼疮AC)等血栓易感性指标，筛查重度同型半胱氨酸血症患者的FV Leiden突变、FV G1628A多态性、FV R2等位基因、凝血酶原20210突变和5，10-亚甲基四氢叶酸还原酶基因C677T多态性。到目前为止，我们已经招募了5名既往存在肾性膀胱炎的假瘤脑病患者。血栓筛查小组显示两名患者凝血酶时间(TT)缩短，一名患者出现高滴度抗心磷脂(ACA)IgM抗体。活化蛋白C抵抗(APCR1例)。凝血酶时间测量纤维蛋白单体聚合率，是纤维蛋白原减少或异常的最敏感的筛查试验。缩短的TT表明纤维蛋白单体聚合加速，导致血栓形成。活化蛋白C抵抗是一种导致高凝状态的疾病，会增加静脉血栓形成的风险，而IgM同型ACA已被证明与静脉血栓形成有关。 为识别血栓嗜血症(MERT)而发展的方法 Dogulu，Chan，Rennert，与Su合作 静脉血栓每年每1000人中就有1人受到影响，是死亡和发病的主要原因之一，仅在美国每年就导致约30万人住院和50000人死亡。然而，如果实行目前可用的预防性治疗，它是一种可以避免的疾病。我们已经设计了一种方法(正在申请专利)，通过对8个不同基因中所有已知的143个静脉血栓相关的反复突变和多态进行快速、同步的筛查，可以预测和准确评估几个种族群体的遗传性血栓形成，以便为风险适应预防制定分层方案。

Given our findings regarding genetic susceptibility to thrombosis in pseudotumor cerebri (PTC), we are studying the role of thrombosis in the development of PTC in nephropathic cystinosis. We are screening nephropathic cystinosis patients who develop PTC and control nephropathic cystinosis patients without PTC by using a thrombosis susceptibility panel including prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), activated protein C resistance (APCR), serum levels of protein C and S, antithrombin III, fibrinogen, total homocysteine, antiphospholipid antibodies (ACA panel and Lupus AC) and screening for FV Leiden mutation, FV G1628A polymorphism, FV R2 allele, Prothrombin 20210 mutation and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism in patients with severe homocysteinemia (>100 micro mol/l). To date, we have recruited five patients with Pseudotumor Cerebri with pre-existing Nephropathic Cystinosis. The thrombosis screening panel revealed shortened thrombin time (TT) in two patients, high titer Anticardiolipin (ACA) IgM antibodies in one patient and. Activated Protein C Resistance (APCR) in one patient. Thrombin time measures the rate of fibrin monomer polymerization and is the most sensitive screening test for decreases or abnormalities in fibrinogen. The shortened TT demonstrates an acceleration of fibrin monomer polymerization leading to thrombotic tendency. Activated protein C resistance is a condition which leads to a hypercoagulable state with an increased risk for venous thrombosis and IgM isotype of ACA has been shown to be associated with venous thrombosis. Method Evolved for Recognition of Thrombophilia (MERT) Dogulu, Chan, Rennert, in collaboration with Su Venous thrombosis affects 1 per 1000 individuals annually and is one of the leading causes of mortality and morbidity resulting in approximately 300,000 hospitalizations and 50,000 fatalities per year in the United States alone. It is, however, an avoidable disease if currently available prophylactic treatment is instituted. We have devised an approach (patent pending) that will allow prediction and accurate assessment of hereditary thrombophilia in several ethnic populations by rapid, concurrent screening of an array of all known 143 venous thrombosis associated recurrent mutations and polymorphisms in 8 different genes in order to develop stratification protocols for risk-adapted prophylaxis.