What Is a Stem Cell Transfusion?

Blood transfusion refers to a method of transfusion of blood to a patient through a vein, and is widely used clinically.

Shi Hongxia	(Deputy Chief Physician)	Institute of Hematology, Peking University People's Hospital
Liu Kaiyan	(Chief physician)	Institute of Hematology, Peking University People's Hospital
Huang Xiaojun	(Chief physician)	Institute of Hematology, Peking University People's Hospital

Blood transfusion refers to a method of transfusion of blood to a patient through a vein, and is widely used clinically.

Introduction to blood transfusion

History of blood transfusion: The earliest blood transfusion was in 1667. A French nobleman transfused 280ml of calf blood to a deranged tramp in an attempt to treat his mental problems. After suffering a severe immune response and wandering several times at the ghost gate, the unlucky patient miraculously survived and maintained a period of calm, so the blood transfusion therapy was accepted by some innovative doctors.

For the next 300 years, blood transfusion therapy is still in the exploratory stage. Without the relevant knowledge (such as blood type), blood transfusions have caused many deaths, but doctors have also found that blood transfusions can really save lives. It was not until 1912 that the Frenchman, Dr. Alexis Carrel, received the Nobel Prize for blood transfusion for blood vessel anastomosis.

The person who really made transfusion a scientific and effective treatment was Karl Landsteiner, a pathologist in Vienna. He discovered the ABO blood group and agglutination law of humans from 1901, providing a solid pathophysiology for modern blood transfusion. Basically, in the following 20 years, other doctors gradually established blood anticoagulation and cross-matching technology, and blood transfusion became a routine treatment method that can be performed in all hospitals. Lansteiner also won the Nobel Prize in Physiology / Medicine in 1930.

Transfusion in the narrow sense refers to transfusion of whole blood. Transfusion in the broad sense is the transfusion of various tangible or non-formed components made from blood, including whole blood. Strictly speaking, hematopoietic stem cells (bone marrow or peripheral blood) are also considered as A special blood transfusion ^[2] .

Transfusion classification

Transfusion whole blood

Whole blood is blood that is collected from a vein and mixed with a certain amount of anticoagulant preservation solution. It is stored in the original container at 2 ° C to 6 ° C. It is mainly red blood cells (about 40% to 50%) and plasma (about 50%). ~ 60%), can improve the oxygen carrying capacity and maintain osmotic pressure, but there are few platelets and granulocytes, and the concentration of coagulation factors is also low. The anticoagulant preservation solution is composed of the following components: sodium citrate (C), which combines with calcium ions in the blood to prevent blood coagulation; phosphate (P), which supports red blood cell metabolism during storage, and ensures that red blood cells release oxygen more easily in the tissue Glucose (D), which maintains the red blood cell membrane to prolong storage time; Adenine (A), which provides energy ^[3] .

Freshly collected blood can retain all its properties for a certain period of time. When the whole blood is stored for more than 24 hours, the factor IX, leukocytes, and platelets in it quickly apoptosis. With the increase of storage time, various components of whole blood in storage will change to varying degrees, such as decreased red blood cell oxygen affinity and gradual loss of vitality; pH, ATP, 2, 3-DPG decreased; potassium ions in plasma It rises and the sodium ion decreases slightly; the formation of micropolymers and so on. The time limit for the storage of whole blood in vitro is determined by keeping at least 70% of the recovery rate of red blood cells stored in the whole blood after being transfused into the recipient for 24 hours. The shelf life of ACD and CPD anticoagulant preservation solution is 21 days, and CPDA is 35 days.

The definition of fresh blood is not clearly defined. In terms of red blood cells, fresh blood was used within 5 days of anticoagulation with ACD and 10 days with CPD. Because red blood cells enter the body can immediately play the role of oxygen transport. For platelets, 50% of platelets are lost after 6 hours at 2 ° C to 6 ° C, and white blood cells can only be stored for more than ten hours. Within 48 hours after blood collection, coagulation factor decreased to 10% to 20% of normal, and other factors and were relatively stable.

450mL of whole blood contains 63mL of anticoagulant, hemoglobin 120g / 100mL, hematocrit of 35% (45%), does not contain functional platelets, and does not contain unstable coagulation factors ( and ).

Since the whole blood is not disinfected, if there is an infectious disease pathogen in the blood cells or plasma, it may be transmitted if it is not detected by routine testing of transfusion-transmitted infectious diseases ^[4] .

Blood products

Blood components include: blood components separated from whole blood, such as concentrated red blood cells, red blood cell suspensions, plasma, and platelets; plasma or platelets collected by apheresis; low-temperature precipitates prepared from fresh frozen plasma, rich in blood coagulation Factor and fibrinogen.

(1) Various types of red blood cell products

1.Concentrated red blood cells

Condensed red blood cells (condensed red blood cells, concentrated red blood cells or less plasma blood) are the simplest products of red blood cell components. About 80% of blood is transfused into red blood cells in the clinic, and more concentrated red blood cells are now provided. The whole blood is naturally precipitated in a refrigerator at 2-6 ° C overnight, or prepared by centrifugation with a low-temperature centrifuge of a specific specification. The plasma layer is removed, and the additive is stored at 2 ° C-6 ° C. The hematocrit is between 50% and 90%, and 70 % Is better, the plasma content is not much and the viscosity is not high. Concentrated red blood cells also contain leukocytes from collected whole blood ^[5] .

150 200mL of red blood cells, most of the plasma has been separated; hemoglobin is about 20g / 100mL (not less than 45g / unit); specific volume of red blood cells is 55% 75%.

2.Red blood cell suspension

The red blood cell suspension is prepared by separating the plasma and adding an "addition" dilution.

Contains 150 200mL of red blood cells and a small amount of plasma, and add 110mL of SAGM (additives, including physiological saline, adenine, glucose and mannitol) or the same amount of red blood cell nutrient solution; hemoglobin about 15g / 100mL (not less than 45g / unit) Hematocrit is 50% to 70%.

3. In addition to "white membrane" red blood cells

The whole blood is centrifuged to precipitate red blood cells at the bottom of the blood bag, and the white blood cells (and most platelets) form a layer of white blood cells between the red blood cells and the plasma, called a "white membrane". In addition to "white membrane" red blood cells still retain red blood cells, concentrated red blood cells contain about 10% of white blood cells. Reduces the risk of transmitting intracellular infectious diseases (pathogens) during red blood cell transfusions caused by leukocyte and leukocyte antibody responses. The "white membrane layer" can be used to prepare concentrated platelets.

4. Remove leukocytes (filter) red blood cells or whole blood

In addition to leukocyte (filtration) red blood cells or whole blood transfusion can reduce the occurrence of immune (response) caused by white blood cells; reduce the acute transfusion reaction; if the (residual) white blood cells per bag of blood after filtration is less than 1 × 10, reduce the transmission of giant cells The danger of the virus.

In general, after 1 unit of red blood cell suspension or concentrated red blood cells have been removed (filtered), the number of white blood cells is less than 5 × 10; the hemoglobin content and hematocrit depend on the type of blood product; the risk of cytomegalovirus transmission is reduced ^{[6 ]} .

5.Wash red blood cells

Washing red blood cells three times with 0.9% physiological saline can remove a large number of white blood cells (up to 80%) and almost all plasma proteins, but red blood cells also have a certain loss (about 20%) and damage, and become washed red blood cells. The original closed system was destroyed during the process, so it should be stored at 4 6 , and must be infused within 24 hours. It is mainly used for those with a history of severe blood transfusion allergy, paroxysmal nocturnal hemoglobinuria, those with anti-IgA plasma protein antibodies, and neonatal hemolytic disease transfusion.

Evaluation of efficacy after red blood cell transfusion:

Generally, infusion of 2U concentrated red blood cells, it is estimated that the concentration of hemoglobin can be increased by 10-20g / L.

Clinical evaluation after blood transfusion, including hemoglobin concentration, hematocrit, tissue hypoxic clinical symptoms and signs of improvement.

l Effective: The clinical symptoms and signs of tissue hypoxia are improved; the hemoglobin concentration is increased by 10-20g / L and the hematocrit is increased correspondingly, and it can continue to be stable.

Ineffective: The clinical symptoms and signs of tissue hypoxia have not improved, and the hemoglobin concentration and hematocrit have not changed or decreased on the original basis.

Analysis of the reasons for the ineffectiveness of red blood cell transfusion: It varies according to clinical conditions, and the main reasons include the presence of active bleeding, the presence of hemolysis, and complications that are not effectively corrected.

(Two) platelets

Platelet transfusion is used to treat and prevent bleeding caused by decreased platelet counts or platelet function defects, but not all thrombocytopenia and platelet function defects can be transfused. In some cases, platelet transfusion is forbidden or used with caution. Note. Platelet transfusion can reduce the incidence of bleeding and mortality, but it can also cause allergic reactions, allergic reactions, transfusion-related lung injury, and transfusion-transmitted diseases. Therefore, clinicians must weigh the pros and cons to make a decision ^[7] .

1. Whole blood combined preparation of concentrated platelets: Platelets prepared from 4 to 6 units of whole blood separation are combined into a platelet preparation sufficient for a single adult therapeutic dose. National blood transfusion guidelines generally require that this product contain at least 240 × 10 / L platelets. 1 unit of product contains 50-60mL, containing at least 55 × 10 / L platelets; red blood cells 1.2 × 10 / L; white blood cells 0.12 × 10 / L.

2. Apheresis platelet concentration: The platelet apheresis method collects a sufficient infusion dose from one blood donor, avoids the transfusion of blood from multiple blood donors, and reduces the risk of transmitting infectious diseases due to the combined preparation of platelets. The volume is 150-300mL; the platelet content is 150-550 × 10, which is equivalent to 3-10 units (whole blood separation and concentrated platelets); the platelet content, plasma volume, and leukocyte contamination depend on the collection method.

Evaluation of the effects of platelet transfusion:

The clinical evaluation of platelet transfusion effects mainly observes whether bleeding is controlled. The index for evaluating the efficacy of platelet transfusion is mainly the platelet adjusted increase value (CCI value). The CCI value is calculated as follows:

CCI = (count after platelet transfusion-count before platelet transfusion) / input platelet number (10) × body surface area (m)

Platelet transfusion is not effective if CCI <10 × 10 / L 1 hour after platelet transfusion and CMI <7.5 × 10 / L 24 hours after transfusion. The platelet count 1 hour after transfusion can be used to know whether the number of platelets input is sufficient, to help understand and detect the effect, like a kind of immunity, and the count after 24 hours can understand the survival time of platelets, allowing doctors to determine the frequency of platelet transfusion.

There are two main types of factors that affect the effect of platelet transfusion: one is non-immune factors, such as patients with fever, infection, hypersplenism and DIC can affect the effect of transfusion; the other is ineffective immune transfusion, Caused by HLA- antibodies and HPA antibodies. In addition to the above two factors, the quality of platelet preparations is an important factor, such as the process of platelet collection, storage conditions, the number of platelets, the number of mixed white blood cells, and the number of mixed red blood cells can affect the transfusion effect. When platelet transfusion is ineffective, the cause should be analyzed. If it is due to ineffective immune platelet transfusion, a platelet cross-fit test should be performed to find platelet-matching donors for platelet transfusion.

(Three) plasma products

Many of the currently used indications for plasma products such as fresh frozen plasma (FFP) and cryoprecipitate are not supported by sufficient clinical evidence-based medicine. In fact, the indications for plasma products are very limited, and adverse reactions caused by infusion and transmission of blood transfusion The risk of sexually transmitted diseases is similar to other components of blood products and may be unpredictable.

Fresh frozen plasma (FFP)

Plasma disease isolated from 1 unit of whole blood within 6 hours after collection is rapidly frozen to -25 ° C or below; it contains stable blood clotting factors, albumin and immunoglobulin in normal plasma; at least 70 in fresh plasma % Clotting factor .

Risk of infectious diseases: The risk is the same as that of whole blood without further treatment, and the risk is reduced if it is treated with melanin / ultraviolet radiation.

Indications: deficiency of various coagulation factors such as liver disease, dicoumarin anticoagulation overdose, and loss of coagulation factors in patients receiving large-dose transfusions; diffuse intravascular coagulation; thrombotic thrombocytopenic purpura; Anticoagulant factor deficiency, such as protein C deficiency, can easily lead to thrombosis, and protein F is supplemented with FFP when surgery is needed.

Infusion: Normally, ABO isotype should be used to avoid hemolysis in patients; Cross-matching is not required; It should be thawed in 30 37 water before infusion. Excessive temperature will destroy coagulation factors and proteins; Infusion as soon as possible; unstable coagulation factors will be quickly destroyed, and infused within 4 hours after melting; if it needs to be stored after melting, it should be placed in a refrigerator at 2 ~ 6 , not more than 24 hours.

Virus inactivated plasma

Plasma is treated with melanin / ultraviolet radiation to reduce the risk of AIDS, hepatitis B and C. This method is less effective at inactivating other viruses, such as hepatitis A virus and parvovirus B19. The cost of this preparation is much higher than conventional fresh frozen plasma.

3. cryoprecipitate

By processing fresh frozen plasma, a component with a capacity of 10 ml to 20 ml containing a cryoglobulin component is obtained. Cryoprecipitate can be stored at below -20 ° C for one year, and contains half of whole blood of factor and fibrinogen. Each bag is prepared from 200ml of fresh frozen plasma and contains approximately: factor VIII 80IU to 100IU; vWF factor 20% to 30%; factor VIII 20% to 30%, fibrinogen 150mg to 250mg, and fibronectin 500mg.

Risk of infectious diseases: same as plasma.

Indications: as a substitute for concentrated coagulation factor products to treat hereditary coagulation factor deficiency, such as factor vW (vascular hemophilia), factor (hemophilia A), factor XIII; in the treatment of acquired coagulopathy It is used to supplement fibrinogen, such as DIC.

Infusion: If possible, apply ABO homologous products; Do not need cross-matching; Infusion as soon as possible through a standard blood transfusion device; Must be infused within 4 hours after thawing; After thawing, save if needed , Should be placed in the refrigerator at 2 ~ 6 , can not exceed 24 hours.

(IV) Plasma protein products

Human plasma protein products prepared under the conditions of drug production, such as albumin, concentrated coagulation factor products, and immunoglobulins. Heat treatment or chemical treatment of plasma protein products to reduce the risk of virus transmission, these methods currently applied are very effective for inactivating lipid enveloped viruses. Non-lipid-enveloped viruses, such as hepatitis A virus and parvovirus B19, are less effective at inactivating.

Human albumin solution

It is prepared by separating human plasma components in large volumes.

Infectious disease risk: if production is normal, there is no risk of transmitting viral infectious diseases

Indications: therapeutic plasma exchange; anti-diuretic edema in patients with hypoproteinemia; there is no evidence that albumin is superior to crystal fluid in acute volume replacement therapy.

Contraindications: Cannot be used as an intravenous nutritional supplement and cannot be used to supplement major amino acids.

Infusion: No cross-fit test is required; No filter is required.

Note: Infusion of 20% albumin has the potential to increase the volume of blood vessels and cause pulmonary edema.

2. Concentrated factor products

A partially purified factor VIII preparation made from a large volume of mixed plasma.

Risk of infectious diseases: HIV, HTLV and hepatitis C virus have not been transmitted by current virus-inactivated products. These viruses are lipid-enveloped viruses; for non-lipid-enveloped viruses, such as hepatitis A virus and parvovirus B19, the inactivation effect is poor.

Indications: hemophilia A; medium purity products contain vW factor, which can be used to treat vW disease.

Substitute products: cryogenic precipitation, fresh frozen plasma; factor products prepared by recombinant DNA technology.

3. Concentrated factor products / prothrombin complex concentrate (PCC)

Contains , , X; PCC is made by removing F from plasma and also contains factor . To reduce the induced thrombosis, the current PCC has added heparin or / and antithrombin (AT) to prevent PCC. Activation of coagulation factors and excess thrombin formation.

Risk of infectious diseases: the same factor products.

Indications: hemophilia B; prolonged prothrombin time requires surgery, use PCC; active bleeding caused by vitamin K deficiency, requires emergency surgery.

Contraindications: PCC is not suitable for patients with a tendency to thrombosis; Vitamin K deficiency should be supplemented with vitamin K first; DIC lacks a variety of coagulation factors, and PCC does not contain all coagulation factors, and some factors have been activated, which may worsen DIC, PCC is not recommended for DIC treatment; Severe liver disease deficiency is not only a vitamin K-dependent coagulation factor, but also due to liver disease and hepatorenal syndrome may lack AT, and some factors in PCC have been activated, and thromboembolism will occur after PCC infusion PCC is not recommended.

Infusion: Same factor products.

Alternative: Plasma.

4. Fibrinogen

Fibrinogen is prepared from cryoprecipitate or plasma with a purity> 70%. Generally, 1g fibrinogen can increase the plasma fibrinogen concentration by 0.25-0.5g / L, usually the first dose is 0.01kg / L, and the hemofibrosis can be achieved by increasing the plasma fibrinogen concentration to above 1.25g / L.

Indications: congenital afibrinogenemia or fibrinogen abnormality; reduced fibrinogen synthesis (such as severe liver disease) or excessive consumption (such as DIC, pathological obstetrics, etc.); bleeding caused by primary hyperfibrinolysis , Such as acute promyelocytic leukemia.

5. Intravenous immunoglobulin

Concentrated human plasma IgG antibody solution, processed to make the product safe and suitable for intravenous injection.

Indications: idiopathic thrombocytopenic purpura and some other immune diseases; immune deficiency status; hypogammaglobulinemia; HIV-related diseases.

Contraindications: Selective IgA deficiency patients with IgA antibodies can cause shock and death due to allergies.