What kinds of operations are likely to cause massive bleeding?

Surgeries of the lung, heart, pancreas, prostate gland, uterus, spleen, kidney, breast cancer, etc., which often enhance fibrinolysis, are likely to cause massive bleeding.

Why does patient bleed easily during operation?

Because the fibrinolysis is accentuated by stress associated with invasive surgical procedure. There are a lot of stimuli such as anxiety, anesthesia, blood loss, irradiation, administration of anticancer drugs, etc. Those stimuli and various conditions such as weakness of the patient may combine to abnormal bleeding

What is the mechanism of the fibrinolytic system?

The fibrinolytic system is a physiological reaction that is invoked at the final stage of the hemostatic mechanism. It decomposes fibrin, the end product of the coagulation system, which is therefore called “fibrinolytic system”. There is plasminogen in the plasma, and it is converted to the active enzyme plasmin as often as required. Plasmin is a strong protease which effectively decomposes fibrin in blood. Plasminogen is activated by serine protease called plasminogen activator (PA). There are two types of plasminogen activator in the living body : urokinase PA (u-PA or UK) and tissue PA (t-PA). On the other hand, alpha 2 plasmin inhibitor (α 2-PI) and PA inhibitor (PAI) inhibit activation of plasmin and PA, respectively thus controlling activation of the fibrinolytic system.

What kinds of blood coagulation factors are there?

More than 10 kinds of blood coagulation factors are involved in coagulating blood. If any one of the coagulation factors dose not work well, it takes long before blood coagulates, or if it coagulates, the coagulation is not firm enough. Hemophilia, known as a typical disease with bleeding problems, is caused by factor VIII or factor IX deficiency.

What is the mechanism of blood coagulation?

When endothelial cells in a vessel are injured, platelets gather around the site (coagulation), adhere to each other changing their forms (adhesion), and block the broken vessel temporarily. This triggers blood coagulation. Injured endothelial cells and platelets act on blood coagulation factors in blood plasma, and fibrinogen transforms into filiform fibrins, causing blood coagulation. The process of blood coagulation is attributable to two types of actions : autogenous action mainly by constituents of blood and exogenous action associated with components in the injured tissue.

What is the mechanism of blood coagulation?

When endothelial cells in a vessel are injured, platelets gather around the site (coagulation), adhere to each other changing their forms (adhesion), and block the broken vessel temporarily. This triggers blood coagulation. Injured endothelial cells and platelets act on blood coagulation factors in blood plasma, and fibrinogen transforms into filiform fibrins, causing blood coagulation. The process of blood coagulation is attributable to two types of action: autogenous action mainly by constituents of blood and exogenous action associated with components in the injured tissue

What is the minimum amount of bleeding which may require blood transfusion?

A person may not have significant symptoms as long as the amount of bleeding is up to 15% of the circulating blood owing to the compensatory effect of the living body. When the amount of bleeding is 20% to 30%, it’s impact is significant and blood transfusion is required. It is said that hemorrhagic shock occurs in no time, when more than 30% of circulating blood is lost.

What is the blood volume of a human?

The blood volume of a human is one 13th of the body weight, that is, the blood volume (amount of circulating blood) of an adult is approximately 5 liters. 1 liter is in capillary vessels of the lung, 2 liters in vessels of the venous system, and 1 liter each in the heart, vessels of the arterial system, and capillary vessels.

What are precautions for administration of Transamin to patients with chronic renal failure?

Because Transamin is excreted via the kidney, care must be taken not to administer it at high doses for long periods. The drug has a wide range of doses, it should be administered to such patients at lower doses while observing patient’s conditions.

What are precautions for intravenous injection of Transamin?

It needs to be injected slowly in the same manner for injection of calcium preparations. Although Transamin is an easy-to-use drug which rarely entails adverse reactions, it may cause nausea, vomiting, or transient decrease in blood pressure when injected rapidly. If any of these adverse reactions occured, the injection should be discontinued to give the patient a rest. These adverse reactions are just transient ones and patients will recover from them soon. When the relationship between the incidence of nausea/vomitting and injection of Transamin was investigated using dog models, the injection speed had a larger influence on the incidence of nausea than the concentration of the drug. When 30 mg/kg of Transamin was intravenously injected into normal healthy dogs, there was no effect. When it was injected in a dose of 40 to 300 mg/kg, however, a vomitory effect was observed depending on the dose. It was found that induction of vomiting could be relieved by reducing the injection speed.

What is the initial dose of Transamin injection for bleeding?

The adequate dose of the drug is 10 to 30 mg per kilogram of body weight. Normally, 20 mg/kg is used. For example, the average dose of the drug for a patient who weighs 50 kg is 1,000 mg, but it can be increased according to the amount of bleeding.

Why is it necessary to administer Transamin before surgery?

Abnormal bleeding may occur suddenly during or after operation. Although Transamin is a quick-acting medicine for abnormal bleeding, it is administered before operation to prevent the risk of bleeding beforehand. Doctors used to administer hemostatic drugs after abnormal bleeding occured, but it is an old custom whose time has passed. As preoperative therapy, Transamin is often orally administered. When oral administration is not possible, the drug is injected.

What kinds of diseases are the main targets of Transamin?

Transamin is effective for systemic diseases and diseases possibly associated with the accentuation of local fibrinolysis.

Typical diseases or conditions which possibly enhance fibrinolysis

Transient accentuation of fibrinolysis

Injection of adrenalin, pyrogenic substances, stress, transfusion-associated shock, and surgery of the uterus, lung, pancreas, or prostate gland

Persistent accentuation of fibrinolysis

Liver cirrhosis, leukemia, aplastic anemia, thrombocytopenia, idiopathic renal hemorrhage, prostate cancer, prostatic hypertroph, systemic metastasis of cancer, pancreatic diseases, thyroid diseases, pneumonia, pulmonary suppuration, lung tumor, burn injury, and allergic reaction

Secondary accentuation of fibrinolysis

Early separation of the placenta, dead fetus in uterus, amniotic fluid embolism, acute promyelocytic leukemia, systemic metastasis of stomach cancer, purpura fulminans, thrombolytic purpura, and disseminated intravascular coagulation syndrome (DIC)

What kinds of diseases are the main targets of Transamin?

Transamin is effective for systemic diseases and diseases possibly associated with the accentuation of local fibrinolysis.

Typical diseases or conditions which possibly enhance fibrinolysis

Transient accentuation of fibrinolysis

Injection of adrenalin, pyrogenic substances, stress, transfusion-associated shock, and surgery of the uterus, lung, pancreas, or prostate gland

Persistent accentuation of fibrinolysis

Liver cirrhosis, leukemia, aplastic anemia, thrombocytopenia, idiopathic renal hemorrhage, prostate cancer, prostatic hypertroph, systemic metastasis of cancer, pancreatic diseases, thyroid diseases, pneumonia, pulmonary suppuration, lung tumor, burn injury, and allergic reaction

Secondary accentuation of fibrinolysis

Early separation of the placenta, dead fetus in uterus, amniotic fluid embolism, acute promyelocytic leukemia, systemic metastasis of stomach cancer, purpura fulminans, thrombolytic purpura, and disseminated intravascular coagulation syndrome (DIC)

What is the pharmacokinetic of Transamin after administration?

Pharmacokinetic parameters of Transamin after oral administration or injection are follows :

Tranexamic acid is rapidly absorbed when orally administered to healthy adult volunteers in a single dose of 250 or 500 mg, intramuscularly administered in a dose of 500 mg, or intravenously administered in a dose of 1,000 mg. Approximately 40 to 70% (when orally administered in a dose of 250 or 500 mg) or 80% and 76% (when intramuscularly administered in a dose of 500 mg and intravenously administered in a dose of 1,000 mg) respectively) of the drug are excreted into urine as unchanged compounds within 24 hours after administration.

How Transamin has the hemostatic effect?

Tranexamic acid firmly binds to the lysine binding site (LBS), which is the fibrin affinity site of plasmin or plasminogen, and prevents access of plasmin or plasminogen to the fibrin molecule. Therefore, degradation of fibrin by plasmin is strongly inhibited. Tranexamic acid is considered to stop bleeding by blocking the degradation of fibrin.

What is FDP?

FDP is an abbreviation of fibrinogen/fibrin degradation products. In the broad sense, it is a product of fibrinogen or fibrin decomposed by plasmin, which is a typical marker of accentuation of fibrinolysis. FDP is a generic name which covers primary fibrinolysis, i.e., fibrinogen degradation products (FgDP), and secondary fibrinolysis, i.e., degradation products derived from fibrin (FDP in a narrow sense). If the FDP value is high, the patient is suspected of having primary or secondary enhancement of fibrinolysis, disseminated intravascular coagulation syndrome (DIC), thrombosis, hemorrhage, malignant tumor, or megadoses of urokinase

What is oozing?

Oozing is exudative bleeding caused by accentuated fibrinolysis. It is said that oozing easily occurs when adhesions are lysed, cancerous lesions are removed, or organs such as the lung, kidney, liver, prostate gland, and uterus are removed. To treat oozing, firm pressure may be applied using gauze moistened with warm physiological saline. If fibrinolysis has progressed, however, bleeding does not stop and there will be the need for hemostatic agents. Although bleeding from thick vessels can be stopped using hemostatic forceps of ligation, administration of hemostatic agents may be required to stop bleeding from thin vessels, because it not only makes operative manipulations difficult prolonging the operation time, but also worsens patient’s general conditions increasing the outflow of blood.

What are symptoms of abnormal bleeding associated with hemorhagic diseases such as purpura, aplastic anemia, cancer, and leukemia?

Patients with hemorrhagic disease commonly develop purpura, epistaxis, and/or bleeding from the dental root. Other symptoms are coma, vomiting, shock, etc. caused by intracranial hemorrhage. There are also pain and swelling caused by hemorrhage of joint.

What should we do if a patient exhibits shock symptomps after administering Transamin?

Because all the reports on adverse reactions associated with Transamin have been made voluntarily or in foreign countries, its incidence is unknown. However, it is true that administration of Transamin may cause shock. If such an adverse reaction should occur, it is necessary to discontinue administration and take appropriate measures against shock symptoms.