1. Clinical typing of hemophilia A
Bleeding in patients with hemophilia A is often related to the amount of coagulation factor VIII activity (FⅧ:C) in the blood. If the FⅧ:C level is <1%, there will often be repeated spontaneous bleeding, while FⅧ:C levels >25-45% will not show spontaneous bleeding, but often abnormal bleeding after trauma and surgery. Therefore, patients are clinically classified into four types according to their blood FⅧ:C levels and their tendency to bleed.
Classification FⅧ: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 >5-25 No spontaneous bleeding, bleeding is obvious after trauma and surgery, and bleeding does not stop after tooth loss or extraction.
No stopping.
Subclinical type >25-45 often have abnormal bleeding after trauma or surgery.
2.Grading of hemophilia A
Patients with hemophilia A 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: including bleeding from special sites, such as bleeding from the central nervous system (intracranial) and soft airways (throat, neck); bleeding from the gastrointestinal tract, the
urinary 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, nosebleeds, etc.
3.Hemophilia A replacement therapy dose
When a patient with hemophilia A bleeds and needs hemostatic treatment, first determine whether the bleeding is severe, moderate, or mild according to the site of bleeding, i.e., according to the disease classification mentioned above. The blood FⅧ:C level (%) to be achieved to effectively stop the bleeding is determined according to the disease classification. For example, in the case of severe central nervous system (intracranial) bleeding, which is more common in infants and children, the blood needs to reach a level (%) of FIX:C of at least 40 to 50% in order to achieve therapeutic effect.
The following are the FⅧ:C levels (%) that need to be achieved according to the degree of bleeding and the duration of treatment.
Degree of hemorrhage Target FⅧ:C level (%) Dose (UMkg) × number of times M days Course of treatment (days)
Severe 40～50 (30～40)×3 7～10
Moderate 30～40 (20～30)×2 5～7
Mild 20～30 (15～20)×2 3～4
Another important specific site of bleeding can raise FⅧ:C levels to >50%.
Since the half-reduction period of FⅧ:C metabolism is 8 to 12 hours, patients with hemophilia A need one infusion in 8 to 12 hours at the beginning, and later extend the gap time as appropriate until bleeding stops.
APTT and FⅧ:C measurement are generally used as a reference for dose adjustment.
In general, plasma FⅧ:C levels need to be maintained above the hemostatic level (20%-30%) and APTT below 50-60s (reference range 31-43s) in hemophilia A patients treated for bleeding.
4. Hemophilia A replacement therapy drugs
Recombinant human activated FⅧ (rhFⅧ) products (Bycocci, etc.) are preferred.
Plasma-derived FⅧ concentrate (anti-hemophilic globulin, AHG).
Cold precipitates (containing VIII, XIII, vWF, fibrinogen, etc.; 80-120 U of FⅧ per bag), and
fresh frozen plasma (FFP) (FⅧ: 1U/ml).
Fresh blood (collected within 6h).
5. Dose calculation for hemophilia A replacement therapy
In the absence of FⅧ inhibitors, the dose is increased by 2% of FⅧ (FⅧ:C) by administering 1 unit (U) of FⅧ preparation Mkg?
The FⅧ(U) required for each patient is the patient’s body weight (kg) × (target FⅧ:C hemostasis level % – measured patient FⅧ:C level % ) × 0.5.
Example: If the patient is 50 kg, the target FⅧ:C is 50%, and the measured FⅧ:C is 1%, the FⅧ(U) required for one visit is 50 × (50-1) × 0.5 1,225 UM.