Bleeding and Blood Replacement

Traumatic Bleeding

Surgical bleeding typically occurs after traumatic injuries or in connection with surgery and can be classified as minimal, small, moderate, large, very large, or massive bleeding. Blood volume in ml is usually calculated as 70 times the body weight in kg. A person weighing 50 kg has an estimated blood volume of 3500 ml, a 70 kg person has about 4900 ml, and a 100 kg person has about 7000 ml. Bleeding less than small bleeding is called minimal bleeding and usually does not require volume substitution. Minimal bleeding is primarily treated with local measures such as bandages, compression bandages, tamponade, suturing, or diathermy. Small, moderate, or larger bleeding should be treated surgically and with intravenous fluid therapy to maintain good tissue perfusion and microcirculation.

The optimal Hgb level is controversial, but in Sweden, an Hgb of 9-10 g/dL (90-110 g/l) after trauma or surgery with an EVF of 30-35 is considered optimal for the best rheology and oxygen delivery in the microcirculation. In some American studies, a lower Hgb of 7-9 g/dL has been considered optimal. EVF refers to the ratio between erythrocyte volume and blood volume (EVF = erythrocyte volume fraction). A hematocrit value of 25% is generally a safe lower limit in patients without risk for heart or lung problems. Note that when colloids with dextran are administered, platelet adhesion decreases, and bleeding tendencies can increase, especially with the administration of more than one liter of Macrodex. A rule of thumb recommends administering blood and plasma in a 1:1 ratio after a bleeding volume greater than 20% of blood volume, with the addition of platelets after a bleeding equivalent to the patient’s total blood volume.

Factor concentrates are used when the contents of regular plasma are insufficient without overloading the volume. Administration is guided by clinical and laboratory values (INR, aPTT, fibrinogen, PLT, TEG). Blood products are given in the volume of blood loss to maintain necessary blood volume, adequate rheology, and functional hemostasis. High intraoperative blood pressure and venous filling increase the risk of bleeding, particularly from parenchymal organs such as the liver and spleen during abdominal surgery. Optimal blood pressure is considered to be as low as still provides good tissue perfusion to vital organs, particularly the heart and brain, with some safety margin against critical hypovolemia.

Recommended Transfusion Thresholds for Adult Patients:

• Hgb <7 g/dL:

Hemodynamically stable patient, acute anemia, traumatic brain injury, stable angina, respiratory therapy. Use an Hgb threshold of 7 g/dL and target of 7–9 g/dL

• Hgb ≤7 – ≤8 g/dL:

Oncology/hematology patients under treatment. Initially, use an Hgb threshold of 7 or 8 g/dL and adjust individually.

• Hgb ≤8 g/dL:

Patient with cardiovascular disease, orthopedic surgery, heart surgery, subarachnoid hemorrhage. Use an Hgb threshold of 8 g/dL and target of 8-10 g/dL

• Hgb ≤9 g/dL:

Hemodynamically unstable patient, acute ischemic brain/heart disease. Use an Hgb threshold of 9 g/dL and target of 9-10 g/dL.

Switching to Another ABO Group

The basic rule in transfusion is to give blood of the same ABO group as the recipient (group-compatible). In certain cases, deviations from this rule may be made according to the guidelines below.

Red Blood Cells

O-blood can be given to everyone
A-blood can be given to A and AB
B-blood can be given to B and AB
AB-blood can only be given to AB

Plasma

AB-plasma can be given to everyone
A-plasma can be given to A and O
B-plasma can be given to B and O
O-plasma can only be given to O

Protocol for Massive Transfusion in Bleeding

• Red Blood Cell Concentrate – Plasma – Platelets in a ratio of 4:4:1
• Fibrinogen Concentrate 2–4 g (30–40 mg/kg)
• Tranexamic Acid (Cyklokapron/Statraxen/Tranexa) 2 g within 3 hours
• Calcium 90 mg if free calcium <1.0 mmol/l (often needs to be repeated)

Moderate or large bleeding should normally be addressed through surgical or radiological intervention and fluid replacement. Radiological intervention with coiling has become increasingly prominent in treating internal bleeding in recent years. A traditional rule of thumb is not to delay surgical intervention for bleeding that requires replacement with more than 6 units of blood. A good alternative to surgical intervention for large bleeding is interventional radiology (IR), where bleeding blood vessels can be treated endovascularly with “coiling” (mechanical vessel obstruction with various coils) or different types of tissue adhesives via catheters under fluoroscopy. Endovascular treatment of major bleeding is increasingly becoming the first-line approach at medical centers where interventional radiology is available. The advantage, of course, is that the method is less invasive than open surgery, with less surgical trauma and milder postoperative recovery. The choice between open surgery or catheter-based radiology for bleeding can be tricky and is made in consultation with the anesthesiologist, surgeon, and radiologist involved.

Massive Transfusion Protocol – Pocket Guide

Fluid replacement during bleeding is guided by the size of the bleed and physiological vital signs, primarily pulse, blood pressure, and blood volume estimates. Peripheral circulation is primarily assessed clinically and through repeated blood gas analyses (Hgb, pH, lactate). Coagulation is assessed with laboratory tests and bleeding parameters (Hgb, platelet count, PT/INR, a-PTT, fibrinogen, antithrombin, etc.) and graphical illustration of coagulation, such as with a thromboelastogram. In cases of severe coagulopathy, coagulation experts can be consulted. Intravenous fluid administration during bleeding is generally estimated relatively coarsely in adult patients, but must always relate to the size of the bleed and the coagulation status to achieve good hemostasis and avoid over- or under-resuscitation. Blood replacement in small children needs to be more precise for obvious reasons. Over-transfusion, especially plasma, can lead to difficult-to-manage pulmonary edema and development of “TRALI” (transfusion-related acute lung injury). The technique of thromboelastography has been refined in recent years (NATEM, HEPTEM, etc.), providing the ability to quickly assess the current coagulation status in vitro and decide on appropriate interventions for fluid therapy and blood replacement. During major bleeding, maintaining normal body temperature is crucial, as hypothermia significantly impairs coagulation ability.

Platelet Transfusion Threshold and Indication

Bleeding and Blood Replacement

Blood Volume Calculated As

70-90 ml/kg

Bleeding Replaced According to Blood Volume Loss

• 5-10% Ringer’s Acetate
• More than 10% + Albumin 5%
• More than 20% + Blood
• More than 50% + Plasma

Massive Bleeding

• Guided by thromboelastogram!
• Without thromboelastogram:
• Give Blood/Plasma/Platelets in the ratio: 1:1:0.5

In Case of Coagulation Disorder

• + Platelets 5-10 ml/kg
• + Fibrinogen 30-70 mg/kg
• + Tranexamic Acid 15 mg/kg

Note

• Temperature > 36.5°C
• pH > 7.2
• Monitor s-Ca
• Hgb > 9 g/dL

Fluid Replacement During Bleeding

Significant bleeding should primarily be replaced with blood components, with the addition of crystalloid solutions and colloid solutions as needed. Synthetic colloid solutions should be entirely avoided in cases of major bleeding. Blood should be administered in amounts equivalent to the ongoing blood loss to achieve optimal Hgb and effective hemostasis (Hgb 7-9, EVF 30-35%). Fluid replacement during bleeding is shown in the tables below. In recent years, a more restrictive approach to fluid replacement during traumatic bleeding has replaced the previously liberal administration of fluids, with blood components given as the first line and crystalloids and colloids used more sparingly. HES should be given in the smallest possible amount and entirely avoided in pediatric patients. Mild hypotension is acceptable during ongoing bleeding, with Hgb levels of 7-9 g/dL depending on the patient’s condition and age. In cases of spinal cord injury, higher blood pressure is aimed for, and in cases of head injuries, a slightly higher Hgb is typically preferred.

Small Bleeding

Small bleeding involves 5-15% blood volume loss. A small bleed can usually be replaced with only crystalloid solutions, such as Ringer’s acetate or Plasmalyte. Other solutions are typically not needed. Crystalloid solutions can be administered in volumes one to two times the size of the bleed. Small bleeding involves the following approximate blood losses for a small, normal, or large person:

• 200-500 ml bleeding for a small person weighing 50 kg
• 250-750 ml bleeding for a normal-sized person weighing 70 kg
• 350-1000 ml bleeding for a large person weighing 100 kg

This means that small bleeding can be compensated as follows for a 5-15% loss of blood volume. The fluid can be roughly estimated in adult patients.

• A small person should receive about 1000 ml of crystalloid solution, such as Ringer’s acetate (350-1500 ml)
• A normal-sized person should receive about 1500 ml of crystalloid solution, such as Ringer’s acetate (500-1500 ml)
• A large person should receive about 2000 ml of crystalloid solution, such as Ringer’s acetate (700-2000 ml)

Moderate Bleeding

Moderate bleeding involves 15-50% blood volume loss. This involves the following blood losses for a small, normal, or large person:

• 500-1750 ml bleeding for a small person weighing 50 kg
• 750-2500 ml bleeding for a normal-sized person weighing 70 kg
• 1000-3500 ml bleeding for a large person weighing 100 kg

This means that moderate bleeding can be compensated as follows for 15-50% blood volume loss. The fluid can be roughly estimated in adult patients.

• A small person should receive 1500-2000 ml of crystalloid solution
• A large person should receive 2000-3000 ml of crystalloid solution and blood products.

Moderate bleeding should be replaced with crystalloid solutions plus blood products for bleeding in the higher range of moderate bleeding. Blood is typically administered as transfusion units (SAG) to achieve optimal Hgb and the best reology and microcirculation. Blood is usually given to a small person in cases of acute bleeding over 500 ml, to a normal-sized person in cases of bleeding over 800 ml, and to a large person in cases of bleeding over 1 liter. However, this can be adjusted individually based on the patient’s general condition and current Hgb. Moderate bleeding typically does not require plasma, platelets, or specific medications to achieve good hemostasis. HES should be given in the smallest possible amount and entirely avoided in pediatric patients.

Large Bleeding

Large bleeding involves 50-100% blood volume loss. This involves the following blood losses for a small, normal, or large person:

• 1750-3500 ml bleeding for a small person weighing 50 kg
• 2500-5000 ml bleeding for a normal-sized person weighing 70 kg
• 3500-5000 ml bleeding for a large person weighing 100 kg

This means that a large bleed can initially be treated as follows for 50-100% blood volume loss. The fluid can be roughly estimated in adult patients. Large bleeding usually requires blood transfusions.

• A small person should receive 1500-2000 ml crystalloid solution and a colloid solution, such as albumin.
• A normal to large person can be given 2000-3000 ml crystalloid solution and blood products.

Large bleeding should be replaced with crystalloid solutions plus colloid solutions and blood components. Blood is initially given as with moderate bleeding, where losses are replaced on an ongoing basis, usually with the same amount as the blood loss, to achieve optimal Hgb and good hemostasis. Significant blood dilution (hemodilution) typically leads to impaired hemostasis when Hgb drops below 8 g/dL.

After replacement with 4 units of blood concentrate, equal parts plasma should be added. After administering 8 units of blood (and 4 units of plasma), 2 units of platelets should be given. Platelets should then be administered after every fourth unit of blood. Ionized calcium should be kept normal as this easily decreases during blood transfusions, and calcium often needs to be supplemented generously in tandem with blood transfusions. HES should be given in the smallest possible amount and entirely avoided in pediatric patients.

During large bleeding, fibrinogen should also be given:

• Fibrinogen 1.5 g
• Tranexamic acid (Cyklokapron/Statraxen/Tranexa) 1 g x 2
• Calcium (Calcium-Sandoz) 9 mg/ml 10 ml intravenously, repeated as necessary (based on ionized calcium in blood gas tests)

Check plasma fibrinogen levels.

Very Large Bleeding

Very large bleeding involves a 100-200% blood volume loss. Treating this blood loss requires good venous access through several large-bore peripheral needles, typically three, at least two of which must have a diameter larger than 1.7 mm. Very large bleeding involves:

• 3500-7000 ml bleeding for a small person weighing 50 kg
• 5000-10000 ml bleeding for a normal-sized person weighing 70 kg
• 7000-14000 ml bleeding for a large person weighing 100 kg

This means that very large bleeding can initially be compensated as follows for 100-200% blood volume loss. The fluid can be roughly estimated in adult patients.

• A small person should receive 1500-2000 ml crystalloid solution and a colloid solution, such as albumin.
• A normal to large person should receive 2000-3000 ml crystalloid solution and a colloid solution, such as albumin.

Blood is administered in an amount equivalent to the ongoing blood loss to achieve optimal Hgb and good hemostasis (Hgb 7-9 g/dL). After replacing 4 units of blood concentrate, equal parts plasma should be added. After administering 8 units of blood (and 4 units of plasma), 2 units of platelets should be given. Platelets should then be administered after every fourth unit of blood. Ionized calcium should be kept normal as it easily decreases during blood transfusions, and calcium often needs to be supplemented generously in tandem with blood transfusions. HES should be given in the smallest possible amount and entirely avoided in pediatric patients. Crystalloids are administered with the goal of achieving euvolemia, considering diuresis and volume status in a balanced fluid therapy.

A simple protocol is to repeatedly administer 4 units of blood, 4 units of plasma, and 2 units of platelets.

During very large bleeding, you should always give:

• Fibrinogen 1.5-2 g, may be repeated
• Tranexamic acid (Cyklokapron) 1 g x 2
• Calcium (Calcium-Sandoz) 9 mg/ml 10 ml intravenously, repeated as needed (based on ionized calcium in blood gas results)

Monitor plasma fibrinogen levels at repeated intervals.

Massive Bleeding

Extremely large blood loss, also known as massive bleeding, involves more than 200% blood volume loss. Replacement of large blood losses typically occurs in parallel with ongoing surgery and involves rapid transfusion, usually through a high-transfusion set. High-transfusion is given at 100-300 ml/min. Massive bleeding always involves a coagulopathy that must be treated alongside blood replacement, and body temperature must be maintained. Treating this blood loss requires adequate venous access through several large peripheral needles and large central catheters, such as a central dialysis catheter or a Rapid Infusion Catheter (RIC Line – 8.5F).

Massive bleeding involves:

• More than 7000 ml for a small person weighing 50 kg
• More than 10,000 ml for a normal-sized person weighing 70 kg
• More than 14,000 ml bleeding for a large person weighing 100 kg

This means that massive bleeding can initially be compensated as follows for more than 200% blood volume loss. The fluid can be roughly estimated in adult patients.

• A normal to large person should receive 2000-3000 ml crystalloid solution and a colloid solution, such as albumin.

Blood is administered in the same amount as the ongoing blood loss to achieve optimal Hgb and good hemostasis. After replacing 4 units of blood concentrate, equal parts plasma should be added. After administering 8 units of blood (and 4 units of plasma), 2 units of platelets should be given. Platelets should then be administered after every fourth unit of blood. Ionized calcium should be kept normal, as it easily decreases during blood transfusions, and calcium often needs to be supplemented generously in tandem with blood transfusions. HES should be given in the smallest possible amount and entirely avoided in pediatric patients. Crystalloids are administered with the goal of achieving euvolemia, considering diuresis and volume status in a balanced fluid therapy.

A simple protocol is to repeatedly administer 4 units of blood, 4 units of plasma, and 2 units of platelets.

During massive bleeding, you should always give:

• Fibrinogen 1.5-2 g, may be repeated
• Tranexamic acid (Cyklokapron/Statraxen/Tranexa) 2 g
• Calcium (Calcium-Sandoz) 9 mg/ml 10 ml intravenously, repeated as necessary (based on ionized calcium in blood gas results)

Monitor plasma fibrinogen levels. Coagulation should be repeatedly monitored with thromboelastography and relevant laboratory tests. Aim for normothermia, euvolemia, and good urine output. Mild hypotension is acceptable during ongoing bleeding, with Hgb levels of 7-9 g/dL depending on the patient’s condition and age. In cases of spinal cord injury, higher blood pressure is aimed for, and in cases of head injuries, a slightly higher Hgb is typically preferred.

Erythrocytes

ERYTHROCYTES, LEUKOCYTE-REDUCED (STANDARD COMPONENT)

• Produced by filtering erythrocytes through a leukocyte filter within 36 hours of collection. Considered functionally CMV-negative erythrocytes. Stored in a nutrient solution (containing approximately 10-20 mL of plasma).
• Content: Hgb/unit approximately 53 g (about 19 g/dL), Hct approximately 60%, volume about 280 mL.
• Shelf life: 42 days, stored at +2°C to +6°C.
• Indications: Bleeding or anemia.

ERYTHROCYTES, LEUKOCYTE-REDUCED WASHED

• Produced by washing erythrocytes with saline.
• Contact the blood bank in advance!
• Volume: approximately 300 mL.
• Shelf life: 14 days.
• Indication: Transfusion to patients with antibodies against IgA or patients with allergies to other plasma proteins.

ERYTHROCYTES FOR EXCHANGE TRANSFUSION IN NEWBORNS

• Produced from leukocyte-reduced erythrocytes – no older than 5 days.
• Content: erythrocytes in fresh frozen plasma, Hct approximately 50%.
• Shelf life: 24 hours.
• Compatibility testing with a sample from the mother or child is required.

Contents of blood bags (Erythrocytes)

Plasma (Human Plasma)

Contains centrifuged and separated human blood plasma from the blood bank with the addition of 63 mL citrate solution. Plasma contains reduced levels of labile clotting factors, FVIII and Factor V, and essentially stable levels of other clotting factors.

Fresh frozen plasma (FFP) is frozen within 8 hours after collection and contains at least 70% of FVIII and other labile clotting factors. Each plasma unit comes from a single donor, and the concentration of clotting factors is not controlled and may vary. It takes 30-45 minutes to thaw and cannot be provided immediately. Can be stored frozen for up to 3 years. In leukocyte-depleted/double-centrifuged units, there are <1 x 10⁶ leukocytes/unit.

Dosage: To provide adequate levels of factors in plasma, about 30% of the patient’s estimated plasma volume must be replaced (20-30 mL/kg body weight). To ensure sufficient levels of FV and FVIII, at least 50% of the replacement should be FFP. The minimum effective transfusion volume is 10-15 mL/kg. To increase fibrinogen concentration from 0.5 g/L to 1.5 g/L, at least 4 units of plasma are needed (an increase of 0.25 g/L per unit of plasma). Since the desired fibrinogen level in cases of severe bleeding is >2.5 g/L, plasma treatment often needs to be supplemented with fibrinogen concentrate.

Indication: Perioperative or postoperative bleeding. Complex deficiency of clotting factors, such as coagulopathy due to severe liver failure or massive transfusion. As replacement in cases of clotting factor deficiency in acute situations where a specific clotting factor concentrate, such as Factor V or XI, is not available or when an exact laboratory diagnosis is not possible. To quickly reverse the effects of oral anticoagulants (coumarins or indanedions). In cases of potentially dangerous bleeding associated with fibrinolysis therapy, such as with tissue plasminogen activators, in patients who do not respond to conventional treatment. During plasma exchange, such as in thrombotic thrombocytopenic purpura (TTP).

Side Effects: Risk of hypervolemia and heart failure, risk of transfusion-related acute lung injury (TRALI), potentially increased risk of certain malignancies, risk of edema.

Volume: 210-280 mL/unit.

Warning: Patients with latent heart failure can develop manifest heart failure and pulmonary edema.

Contraindications: Unstable angina pectoris, decompensated heart failure.

Plasma Unit Content

TRALI (Transfusion-Related Acute Lung Injury)

Acute respiratory distress with dyspnea, desaturation, chest X-ray findings, and pulmonary edema within 6 hours after transfusion. TRALI results in non-cardiogenic pulmonary edema, hypotension within 6 hours after transfusion or during transfusion, and low pO₂. Chest X-ray shows bilateral infiltrates.

More common in hematological or surgical patients, often after plasma or platelet transfusions.

HLA or granulocyte-specific antibodies may be present in the blood component given. The chest X-ray shows bilateral perihilar and nodular opacities or “white-out,” with a normal heart size. Initially, neutrophils and monocytes may be low, later rising.

Treatment of TRALI

Adequate respiratory support with CPAP or PEEP in a ventilator, possibly corticosteroids. Diuretics are not helpful. Report findings from the chest X-ray to the blood bank. The blood bank conducts an investigation of HLA/granulocyte antibodies in the donor.

Platelet Concentrate (Platelets)

A platelet unit is prepared from whole blood by pooling platelets from 4-6 donors. Platelet concentrate is always leukocyte-depleted and contains less than 1 x 10⁶ leukocytes per unit. The concentrate is produced from buffy coat, obtained by centrifuging whole blood. It also contains 100 mL of plasma.

Dosage: One to two units per 4 erythrocyte concentrates during massive bleeding. The expected platelet increase in an adult patient is 15-30 x 10⁹/L per transfused unit.

Indication: Massive bleeding or symptomatic thrombocytopenia. The target for good hemostasis is a platelet count > 100 x 10⁹/L. Platelet counts above 60 x 10⁹/L usually provide stable hemostasis. The platelet count should always be maintained above 20 x 10⁹/L if there is no bleeding and above 40 x 10⁹/L if bleeding is present.

Side Effects: Can cause thrombosis in micro or macro vessels. May cause allergic reactions. Thrombocytopenia in TTP may worsen.

Concentration: Content: > 240 x 10⁹ platelets per unit suspended in approximately 350 mL of nutrient solution and plasma.

Platelet Unit Content

Warning: The most common transfusion complication is mild allergic reactions, usually caused by plasma or plasma proteins in the platelet concentrate. Anaphylactic reactions are rare (<1/100,000 transfusions), but when they occur, they are usually caused by plasma. Use special infusion sets with small drip chambers when transfusing platelets.

Platelet Transfusion Threshold and Indication

Albumin

Human albumin is normally available in three concentrations – 40, 50, and 200 g/L. A typical bottle of 100 ml 20% albumin contains 20 g of albumin.

Albumin is administered as a volume expander or to increase low albumin levels. Normal serum albumin levels vary by age and are approximately 40 g/L. Critically ill and/or chronically ill patients often have significantly lower albumin concentrations, leading to hypoalbuminemic alkalosis. Administering albumin induces acidification. Albumin 200 g/L is hyperoncotic and can mobilize fluid from the interstitium. Different manufacturers dissolve albumin in either saline or balanced crystalloid solutions.

Fibrinogen (Riastap, Fibryga)

Human fibrinogen concentrate.

Dosage: To calculate the individual dose, the functional fibrinogen level should be determined. If the patient’s fibrinogen level is unknown, an initial intravenous dose of 70 mg per kg body weight is recommended. The target level (> 2 g/L) for significant bleeding (e.g., head injuries or brain bleeds) should be maintained for seven days. The fibrinogen dose (mg/kg body weight) to be administered = [target level (g/L) – measured level (g/L)] / 0.017 (g/L per mg/kg body weight). Usually, 1-2-4 g is administered intravenously per dose, repeated as necessary after checking bleeding parameters. One gram of fibrinogen increases plasma fibrinogen concentration by approximately 0.5 g/L.

Indication: Massive bleeding, traumatic bleeding. Treatment of bleeding in patients with congenital hypo- or afibrinogenemia with a bleeding tendency. The normal fibrinogen level in plasma is 1.5-4.5 g/L. The critical fibrinogen level in plasma, below which bleeding may occur, is 0.5-1.0 g/L. For major surgical interventions, it is crucial to monitor replacement therapy through coagulation tests accurately.

Concentration: Powder for solution 1 g.

Side Effects: Thromboembolic events, including myocardial infarction and pulmonary embolism. Lack of efficacy.

Warning: Increased risk of thrombosis exists in patients with congenital deficiency when treated with human fibrinogen concentrate, especially at high doses or repeated dosing. Patients receiving human fibrinogen concentrate should be closely monitored for signs and symptoms of thrombosis.

Contraindications: Hypersensitivity to the active ingredient or any of the excipients.

Tranexamic Acid (Cyklokapron/Statraxen)

Fibrinolysis inhibitor. Tranexamic acid inhibits fibrinolysis by preventing the activation of plasminogen to plasmin. Tranexamic acid does not cause thrombosis, but it inhibits the dissolution of existing thrombi.

Dosage: Initially, a slow intravenous injection (over 10 minutes) of 1-2 g IV can be given, repeated after 4-6 hours. Infusion can be administered at a rate of 70-700 mg/hour. Cyklokapron can also be administered orally, or locally applied to mucous membranes, the mouth, and the nose.

Indication: During surgery and for bleeding in patients with increased bleeding tendencies. Used in surgeries associated with increased fibrinolysis, such as mucosal surgeries, mammoplasty, thoracic and liver surgery, and prostate surgery. For operations on patients with an increased risk of bleeding, such as known platelet defects, von Willebrand disease, and hemophilia. Can also be used for massive bleeding due to major trauma.

Concentration: Injectable solution 100 mg/mL.

Side Effects: In cases of disseminated intravascular coagulation (DIC) or microthrombotic syndromes, tranexamic acid can reduce fibrin dissolution in the microcirculation, potentially increasing the risk of organ failure.

Contraindications: Cyklokapron should be avoided for the first six months after acute thrombosis. In cases of severe bleeding, single doses of tranexamic acid can be administered, but several days of treatment should be avoided. Bleeding in the urinary tract is a contraindication due to the risk of obstructive clot formation.

Octostim (Desmopressin)

Hemostatic agent. Octostim is a structural analog of the natural posterior pituitary hormone arginine vasopressin (ADH).

Dosage: 0.3 μg/kg diluted in saline to 10 ml, administered as an intravenous injection over 10 minutes or 0.3 μg/kg as a subcutaneous injection.

Indication: Bleeding. Used to shorten or normalize prolonged bleeding time in cases of uremia, liver cirrhosis, congenital or drug-induced platelet dysfunction, and in patients with prolonged bleeding times of unknown etiology. If a positive effect is achieved, the initial dose of Octostim can be repeated 1-2 times at 6-12 hour intervals.

Concentration: Solution 15 μg/mL.

Side Effects: Risk of reduced urine output, water retention, and hyponatremia with associated symptoms such as headache, nausea, vomiting, weight gain, decreased serum sodium, and in severe cases, seizures.

Warning: Use caution in small children, elderly patients, in conditions requiring diuretics, in cases of fluid and/or electrolyte imbalance, and in situations with increased intracranial pressure risk.

Contraindications: Unstable angina pectoris, decompensated heart failure, von Willebrand disease type 2B.

Confidex (Coagulation Factor Concentrate)

Hemostatic agent, coagulation factor concentrate. Coagulation factors II, VII, IX, and X, which are synthesized in the liver with the help of vitamin K, are known as the prothrombin complex. In addition to the coagulation factors, Confidex contains the vitamin K-dependent coagulation inhibitors, Protein C, and Protein S.

Dosage: The dose is based on the INR before treatment and the target INR. The INR before treatment should be measured as close to the time of dosing as possible to calculate the appropriate dose of Confidex.

Indication: Massive bleeding, bleeding due to liver failure. Treatment of bleeding and perioperative bleeding prophylaxis in acquired deficiency of the coagulation factors in the prothrombin complex, such as deficiency due to treatment with vitamin K antagonists, or in cases of overdose of vitamin K antagonists when rapid correction of the deficiency is required.

Concentration: Powder for solution 250/500/1000 IU. Reconstituted as 250 IU/10 ml.

Side Effects: Thromboembolic events, including myocardial infarction and pulmonary embolism. Lack of efficacy. Headache. Elevated body temperature.

Warning: Patients on vitamin K antagonists may have an underlying hypercoagulable condition, and infusion of prothrombin complex concentrate may exacerbate this. There is a risk of thrombosis or disseminated intravascular coagulation when treating patients with either congenital or acquired deficiency with human prothrombin complex concentrate, particularly with repeated dosing.

Contraindications: Known allergy to heparin or history of heparin-induced thrombocytopenia. In cases of disseminated intravascular coagulation, treatment with prothrombin complex products should only be initiated after the consumptive phase has been passed.

Ocplex (Prothrombin Complex Concentrate)

Hemostatic agent. Coagulation factors II, VII, IX, and X, synthesized in the liver with the help of vitamin K.

Dosage: The dose is determined by the INR before treatment and the target INR. Typically, 2,000-3,000 IU of Ocplex is administered. A single dose should not exceed 3,000 IU (120 ml of Ocplex).

Indication: Massive bleeding, bleeding due to liver failure. Treatment of bleeding and perioperative bleeding prophylaxis in acquired deficiency of prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists (e.g., Warfarin) or overdose of Warfarin, when rapid correction of the deficiency is required. Correction of elevated PT/INR.

Concentration: Powder for solution 500 IU.

Side Effects: Thromboembolic events, including myocardial infarction and pulmonary embolism. Lack of efficacy.

Warning: Patients on vitamin K antagonists may have an underlying hypercoagulable condition, and infusion of prothrombin complex concentrate may exacerbate this. In rare cases (>0.01% and <0.1%), administration of prothrombin complex products can lead to the formation of circulating antibodies that inhibit one or more of the human prothrombin complex factors.

Contraindications: Known allergy to heparin or history of heparin-induced thrombocytopenia.