van Veen Joost J, Hampton Kingsley K, Maclean Rhona, Fairlie Fiona, Makris Michael
Sheffield Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital,Sheffield, United Kingdom.
Blood Transfus. 2007 Nov;5(4):204-9. doi: 10.2450/2007.0023-07.
Severe FX deficiency is a rare disorder with a variable bleeding tendency but spontaneous life threatening haemorrhage can occur. Treatment for invasive procedures and spontaneous bleeding is with prothrombin complex concentrates (PCC). When used in large or repetitive doses these are associated with a thrombotic tendency. FX:C levels of 0.15 - 0.30 IU/ mL are thought to be haemostatic during surgery . There is only limited information on the outcome and management of pregnancy in severe FX deficiency. Caesarean section is suggested as delivery mode to reduce the risk of intracranial/abdominal neonatal haemorrhage, but successful vaginal deliveries are also described. The calibrated automated thrombin generation assay (CAT) is a global coagulation test that measures the time course of thrombin generation. It has been reported to correlate with prothrombotic states and the severity of bleeding in rare coagulation disorders. The variability in phenotype, the uncertainty of the minimal haemostatic FX:C concentration and the association of PCC's with thrombosis make thrombin generation of interest in the management of FX deficient patients.
We describe the use of CAT as a possible means to monitor treatment with PCC (Beriplex) in a patient with severe FX deficiency (FX:C < 0.01 IU/mL) during successful vaginal delivery and epidural anaesthesia.
Thrombin generation was normal at FX:C 0.80 IU/mL but only borderline normal at FX:C 0.25 IU/mL. Repetitive doses over 3 days increased thrombin generation to the upper limit of normal at FX:C 0.25 IU/mL consistent with a prothrombotic tendency after multiple doses. The increase in thrombin generation was not related to prothrombin levels.
The data suggest that CAT may be used to monitor treatment with PCC in FX deficiency. Higher levels than previously thought may be needed to normalize thrombin generation. Further studies into the correlation with bleeding or thrombosis are needed before the approach can be accepted in clinical practice.
严重因子X（FX）缺乏症是一种罕见疾病，出血倾向各异，但可能发生危及生命的自发性出血。侵入性操作和自发性出血的治疗方法是使用凝血酶原复合物浓缩剂（PCC）。大剂量或重复使用这些药物会有血栓形成倾向。FX：C水平在0.15 - 0.30 IU/mL被认为在手术期间具有止血作用。关于严重FX缺乏症患者妊娠结局和管理的信息有限。建议剖宫产作为分娩方式以降低颅内/腹腔内新生儿出血风险，但也有成功阴道分娩的报道。校准自动凝血酶生成试验（CAT）是一种全面的凝血试验，可测量凝血酶生成的时间进程。据报道，它与血栓形成状态以及罕见凝血障碍中的出血严重程度相关。表型的变异性、最小止血FX：C浓度的不确定性以及PCC与血栓形成的关联使得凝血酶生成在FX缺乏症患者的管理中受到关注。
我们描述了在一名严重FX缺乏症（FX：C < 0.01 IU/mL）患者成功阴道分娩和硬膜外麻醉期间，使用CAT作为监测PCC（贝赋）治疗的一种可能方法。
FX：C为0.80 IU/mL时凝血酶生成正常，但FX：C为0.25 IU/mL时仅临界正常。3天内重复给药使FX：C为0.25 IU/mL时凝血酶生成增加至正常上限，这与多次给药后的血栓形成倾向一致。凝血酶生成的增加与凝血酶原水平无关。
数据表明CAT可用于监测FX缺乏症患者的PCC治疗。可能需要比先前认为的更高水平才能使凝血酶生成正常化。在该方法被临床实践接受之前，需要进一步研究其与出血或血栓形成的相关性。
