1. Clinical typing of hemophilia B
Bleeding in patients with hemophilia B is often related to the amount of coagulation factor IX activity (FⅨ:C) in the blood. If the FⅨ:C level is <1%, there will often be repeated spontaneous bleeding, while FIX:C levels >25-45% will not have spontaneous bleeding, but often abnormal bleeding after trauma and surgery. Therefore, patients are clinically classified into 4 types according to their blood FⅨ:C levels and tendency to bleed.
Typing FⅨ:C level (%) Clinical characteristics
Heavy type <1 Spontaneous recurrent bleeding, seen in skin, joints, muscles, mucous membranes, internal organs, etc.
Moderate type 1-5 with spontaneous bleeding, mostly in trauma, severe bleeding after surgery
Mild type >5-25 No spontaneous bleeding, bleeding is obvious after trauma and surgery, and bleeding does not stop after tooth loss or extraction.
Subclinical type >25-45 often have abnormal bleeding after trauma and surgery.
2.Grading of hemophilia B
Patients with hemophilia B are classified into the following three categories according to their bleeding sites. If bleeding from important parts of the torso, which may cause serious danger, is severe bleeding, while skin petechiae and hematomas are mild bleeding.
Severe bleeding: This includes bleeding from special sites, such as bleeding from the central nervous system (intracranial) and soft airways (throat, neck); bleeding from the gastrointestinal tract, urinary tract, respiratory tract, and peritoneum.
tract, respiratory tract bleeding, intraperitoneal M retroperitoneal bleeding and fundus bleeding.
Moderate hemorrhage: including joint hemorrhage, muscle hemorrhage, oral hemorrhage, soft tissue hemorrhage, etc.
Mild bleeding: including skin petechiae, subcutaneous hematoma, nasal bleeding, etc.
3.Hemophilia B replacement therapy dose
The dose of hemophilia B replacement therapy depends on its bleeding site. For example, the more common central nervous system (intracranial) bleeding in infants and children is severe bleeding, and the blood needs to reach a level of FⅨ:C (%) of at least 40 to 50%. The following classification of the degree of bleeding is based on the classification of hemophilia B described above.
Degree of bleeding Target FIX:C level (%) Dose (UMkg) x number of times M days Course of treatment (days)
Severe bleeding 40～50 (30～40)×2 7～10
Moderate bleeding 30～40 (20～30)×2 5～7
Mild bleeding 20～30 (15～20)×2 3～4
In general, it is necessary to maintain the patient’s plasma FⅨ:C level above the hemostatic level (20%-30%) and the APTT below 50-60 seconds (reference range 31-43 seconds).
Special site bleeding may increase FⅨ:C levels to >50%.
APTT and FⅨ:C measurements are used as a reference for dose adjustment.
Since the metabolic half-reduction period of FⅨ is 18-24 hours, patients with hemophilia B need to start with one infusion in 12 hours, and then extend the gap time as appropriate until the bleeding stops.
4.Hemophilia B replacement therapy drugs
Prothrombin complex (PCC) (containing coagulation factors II, VII, IX and X).
Befu (genetically recombinant coagulation factor IX)
Fresh frozen plasma (FFP).
Fresh blood (within 3 days).
5.Dose calculation for hemophilia B replacement therapy
For example, if PCC is administered, 1 unit (U) of Mkg is administered to raise FIX (FIX:C) by 1%.
Patient’s FⅨ(U) per dose (kg) × (% of target FIX:C level – % of measured patient’s FIX:C level) × 1.0
Example: Patient 50kg, target FIX:C 50%, measured FIX:C 1%, FIX(U)50 x (501) x 1.02 450UM times per session