B型血友病如何进行诊断？

首次的生物活性测试

试验

APTT(1) 
(活化脑磷脂时间)

混合试验
(2)    

PT
(凝血酶原时间) 

TT
(凝血时间)    

BT
(出血时间)

结果

增加

修正

正常

正常

正常

(1) APPT活化部分凝血酶原时间在孤立的试验中呈增加趋势；时间延长的程度取决于凝血因子IX的缺失程度和试剂对血凝因子IX缺失的敏感性。

(2)（活化部分凝血酶原时间）的延长可以通过向病人血浆中混入等量正常血浆成分进行修正。

特异性试验

  • 凝血因子IX的凝血活性可以被用来作为进行疾病诊断和鉴别血友病的严重程度的依据。试验通过对一系列稀释浓度的病人血浆样品进行分析以排除血液中循环的红斑狼疮抗凝血抗体的干扰。
  • 确保其它凝血因子（凝血因子VII,XI和XII）处于水平正常，这些凝血因子均可以造成APTT的延长。
  • Von Willebrand因子（利托菌素辅助因子/抗原活性）处于正常水平。 

鉴别诊断

Differential diagnosis involves ruling out other causes for lengthening of APTT associated with decreased activity of factor IX.

Anti-factor IX antibodies

Acquired haemophilia B is associated with the presence in non-haemophiliac subjects of antibodies directed against factor IX. This is a rare disease that can occur in particular in women during or at the end of pregnancy, in patients with autoimmune disease, and in elderly subjects.
The most common clinical sign is the presence of marked haematomas. Since the disease may be life-threatening, appropriate therapy must be given quickly.
Diagnosis involves screening for a specific inhibitor directed against factor IX using the Bethesda method or the Nijmegen method. These inhibitors are also seen more frequently (10 to 15% of patients) in haemophiliac subjects receiving replacement therapy containing factor IX, against which they are immunised due to the development of antibodies directed against factor IX.

Vitamin K deficiency

Since the synthesis of factor IX is dependent upon vitamin K, levels of factor IX are low in the event of vitamin K deficiency or treatment with vitamin K antagonists.
In this event, the levels of other vitamin K-dependent coagulation factors (II, VII, X) are also low, as are proteins S and C.

 

鉴别诊断主要涉及排除影响凝血因子IX降低而促使APTT时间延长的因素。

抗凝血因子IX抗体

获得性B型血友病与存在非血友病相关的凝血因子IX抗体有关。获得性B型血友病是非常罕见的，仅发生在怀孕后期的孕妇，这些孕妇通常伴有自身免疫性疾病和高龄产妇。
最常见的临床症状是表现出明显的血肿。这类病人因为可能有生命危险，所以必须给予紧急治疗处理。

公司提供的方法，以筛选出血凝因子IX特异性抑因子的方法来进行诊断。这些抑制因子在接受以凝血因子IX代替治疗的血友病病人中的检出率比较高（10%到15%），相对病人通过凝血因子IX抗体的产生而的机体免疫应答。

维生素K缺乏症

因为凝血因子IX的合成依赖于维生素K的存在，所以当存在维生素K缺乏症或者使用维生素K颉抗物进行治疗时，患者的凝血因子IX水平将处于较低水平。

这时其它依赖于维生素K的凝血因子（II,VII,X）也将维持低水平，也包括蛋白S和蛋白C。