Genetics of thrombosis in pseudotumor cerebri of nephropathic cystinosis

使用血栓易感性小组，我们筛查发生PTC的肾病性胱氨酸病患者，以及对照无PTC的肾病性胱氨酸病患者。包括凝血酶原时间(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(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)。在重度同型半胱氨酸血症(大于或等于100mmoL/L)患者中，我们筛查了Fv Leiden突变、Fv G1628A多态、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名既往有肾病囊虫病的PTC患者。血栓筛查小组显示两名患者凝血酶时间(TT)缩短，一名患者出现高效价抗心磷脂(ACA)IgM抗体，一名患者出现活化蛋白C抵抗(APCR)。凝血酶时间衡量纤维蛋白单体聚合的速度，是纤维蛋白原减少或异常最敏感的筛查试验(凝血酶时间缩短表明纤维蛋白单体聚合加速，从而导致血栓形成)。活化蛋白C抵抗是一种导致高凝状态的疾病，增加了静脉血栓形成的风险；ACA的IgM同型已被证明与静脉血栓形成有关。因此，在所研究的患者中，似乎不存在发生PTC的单一危险因素。

Using a thrombosis susceptibility panel, we screen nephropathic cystinosis patients who develop PTC as well as control nephropathic cystinosis patients without PTC. The panel includes 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). In patients with severe homocysteinemia (greater than or equal to 100 micro mol/l), we screen for the FV Leiden mutation, FV G1628A polymorphism, FV R2 allele, prothrombin 20210 mutation, and 5,10-methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphisms. To date, we have recruited five patients with PTC 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 (a shortened TT demonstrates an acceleration of fibrin monomer polymerization, which contributes to thrombotic tendency). Activated protein C resistance is a condition that leads to a hypercoagulable state with an increased risk for venous thrombosis; the IgM isotype of ACA has been shown to be associated with venous thrombosis. Thus, there appears to be no single risk factor for the development of PTC in the patients studied.