Leiden mutation (factorVLeiden,FVL) in coagulation factor V (this reads 5), Leiden is the city in the Netherlands where the abnormal gene was first identified. This is a rare bleeding disorder (Rareinheritedcoagulationdisorders, RICD, knowing this is good for searching the literature). But this disease is also prone to thrombosis. The incidence of this disease is very low, so for the benefit of physicians and patients, this is a general overview.
FVL is an autosomal dominant disease (the father or mother is the carrier, usually does not develop the disease, is generally inherited, of course, their own genetic mutation may also have, but the possibility is very small), 99% of FVL is heterozygous. Generally there are abnormalities in the blood clotting, and the diagnosis can be made by checking the clotting factors.
Incidence
A US study of 4047 men and women found a 5.3% incidence of FVL in whites and a 0.45% incidence of FVL in Asian Americans, which appears to be less common in Asians than whites [2], and there have been no studies of FVL incidence in China. The median age at diagnosis was 7 years (birth to 73 years) in 294 patients in the US Rare Bleeding Disorders Registry [3]. the risk of bleeding from FVL is relatively low compared to other rare coagulation factors [4].
How much coagulation factor is enough for FVL?
The risk of bleeding is the same as normal with a clotting factor viability of 20% to 70%. If clotting factor viability is 1% to 10%, bleeding is likely, but many patients with viability <1% have lower than expected bleeding [5].
Association with lupus anticoagulants
Of the 55 children with prolonged APTT preoperatively, 71% tested positive for lupus anticoagulants [1]. Positive anticardiolipin antibodies must exclude lupus according to the 2019 EULAR/ACR and 2012 SLICC criteria, as well as anticardiolipin antibody syndrome. Lupus and anticardiolipin antibody syndrome are also associated with an increased risk of thrombosis, and clotting abnormalities are often not corrected by normal plasma.
Thrombosis
Only 5-10% of FVL heterozygotes have venous thrombosis in their lifetime.
If there is protein S and protein C deficiency, prothrombin G20210A mutation (coagulation factor II) and increased risk of thrombosis, the children are checked and there is no increased risk of thrombosis.
Non-O blood types (e.g. A, B or AB) have 2-4 times more deep vein thrombosis than our O blood type [6].
Patients should not take birth control pills, which increase the risk of thrombosis, and proteinuria, elevated body mass index and smoking also increase thrombosis [7-9].
FVL is associated with arterial thromboembolism, although data are mixed and this effect is small.
FVL may play a role in some cases of recurrent late miscarriage of unknown origin, which may be due to placental vascular thrombosis [10,11]. However, patients with FVL are less likely to have recurrent miscarriages compared to other risk factors.
Site of thrombus
The most common sites of thrombosis in FVL are deep vein thrombosis and pulmonary artery thrombosis, but also thrombosis in the brain, mesenteric or portal veins [81-83].
Pregnancy
Heterozygotes without a history of thrombosis do not require routine thromboprophylaxis. If thrombosis is present at the time of pregnancy, or in patients who are receiving thromboprophylaxis, low-molecular heparin is usually started in the first trimester of pregnancy, provided there is no vaginal bleeding, and warfarin cannot be used. Thromboprophylaxis is available if there is a family history of deep vein thrombosis, mobility problems, cancer or surgery patients. Thromboprophylaxis may be considered for individuals who are pure congeners or otherwise prone to thrombotic defects, but must be individualized. For heterozygotes delivered by cesarean section, two weeks of postpartum prophylactic dose anticoagulation may be considered in addition to standard pneumatic compression during hospitalization.
Thromboprophylaxis during travel or prolonged sedentary periods
Frequent walking (every one to two hours) and/or stretching of the calf and thigh muscles is recommended during air travel or prolonged sedentary periods (more than 4-6 hours). For high risk of deep vein thrombosis, the use of below-knee graduated compression stockings is recommended, especially in patients with leg edema. Some patients take low-dose aspirin without probative medical evidence and do not support or oppose it.
Surgery
Patients with FVL undergoing surgery should be treated as a high-risk group with prophylactic anticoagulation to reduce DVT (e.g., with low molecular heparin, sulforaphane, or plain heparin). Such patients are at increased risk of bleeding during surgery [12,13] and require fresh frozen plasma transfusions (see table below for treatment details).
Treatment
There is no synthetic coagulation factor V for FVL, and only fresh frozen plasma can be transfused, with less thawed plasma coagulation factors [14]. Factor V has a half-life of 16 to 36 hours and generally maintains clotting factor viability of 20% or more during surgery, treatment is shown in the table below [15]. Later, when gene therapy matures, it is possible to eradicate the patient, for which there is no cure. No oral effective drugs are yet available. Some experts also advocate the use of platelet transfusions, as normal platelets contain factor V concentrated at the bleeding site [16]. Be sure to pay attention to the balance of volume and diuresis if necessary. The use of 3-5 days of rice for hemorrhage facilitates edema absorption. Gene therapy is not yet mature and is a future development.
Factor replacement for FVL bleeding or surgery
Coagulation factor V activity
Major bleeding/surgery (treat until complete healing)
Minor bleeding/surgery (treated for 2 to 3 days)
Prevention
Target level >20%
Transfusion of fresh frozen plasma: 15 to 20 mL/kg
Transfusion of fresh frozen plasma: 15 to 20 ml/kg
Transfusion of fresh frozen plasma: 15 to 20 ml/kg
Iron deficiency anemia
If a woman has a heavy menstrual flow, this can lead to iron deficiency anemia that is difficult to cure and requires iron supplementation for several days per month (generally the author recommends the same number of days of iron supplementation as the number of days of menstrual flow, e.g., 5 days; data are being compiled).
Incidence of coagulation factor inhibitors
Two patients in the rare bleeding disorders registry developed inhibitors after treatment (3%) [8], one in a patient with FVL and the other in a patient with coagulation factor XIII (this read 13) deficiency. If coagulation factor inhibitors occur, melphalan, hormones, immunosuppressants, etc. are available, and there is no evidence of inquisitorial medicine to refer to hemophilia A, which has the highest incidence.
Blood transfusion reaction
In some medically underdeveloped areas, inpatient transfusions are required in tertiary care hospitals, which increases health care costs and increases the amount of work for both health care providers and patients, for fear of transfusion reactions. The incidence of side effects after plasma transfusion in the United States Rare Bleeding Disorders Registry is 2-26% [3]. When a side effect occurs, stop the plasma transfusion, rehydrate, and use antihistamines and hormones. (Doctors are humans not gods, and not every patient with anaphylaxis can be saved, so we advise people to transfuse less blood if they can).
Vaccinations
Infections have the potential to cause a decrease in clotting factor activity, and appropriate vaccination is important for patients [17]. Subcutaneous administration reduces the risk of intramuscular hematoma, but the ability to administer subcutaneously depends on the type of vaccine, e.g., pneumonia vaccine, inactivated polio vaccine, hepatitis A vaccine, and hepatitis B vaccine can be administered subcutaneously [18]. All vaccinations should be administered using a fine needle (e.g., 23-gauge or smaller caliber) with only pressure and no rubbing.