For Oncohematologists

Plasmapheresis in incompatibility of the recipient with the donor for ABO system antigens before allogeneic bone marrow transplantation.

The presence of incompatibility between the donor and the recipient for ABO system antigens is not a contraindication to allogeneic bone marrow transplantation. According to the international classification, 2 types of incompatibility for ABO system antigens are distinguished. Major incompatibility means the presence in the recipient of natural antibodies to the erythrocyte antigens of the donor; in this situation a risk of hemolytic complications arises. To prevent such a complication, the donor erythrocytes are removed from the graft to the greatest possible extent and an exchange plasmapheresis is performed in the recipient in order to remove the antibodies. Minor incompatibility for ABO system antigens is the presence in the donor of isohemagglutinins to the erythrocyte antigens of the recipient; in such cases it is sufficient to remove the plasma from the graft.

Indications:

The presence of incompatibility between the donor and the recipient for ABO system antigens.

Method:

Depending on the level of isohemagglutinins in the blood of the recipient, on average from 1 to 3 plasma exchange procedures are performed, the last one on the day of the bone marrow transplantation. One volume of circulating plasma is removed. Replacement of the removed plasma is carried out in an isovolemic mode with FFP of blood group AB(IV) – 75%, albumin 5% – 25%, at a normal level of the protein fractions. If necessary, premedication with antihistamines, glucocorticoids and calcium preparations is carried out. During the plasma exchange, calcium preparations are administered prophylactically after every 500.0 ml of FFP introduced.

Criteria of effectiveness

A decrease of the level of isohemagglutinins in the blood of the recipient below a dilution of 1:16 (a decrease to 1: 4 - 1: 2 is more favourable).

Plasmapheresis and leukocytapheresis in the treatment of hyperleukocytosis

Hyperleukocytosis is an emergency condition in hematological practice associated with severe life-threatening complications and therefore requiring urgent, special therapeutic measures. Hyperleukocytosis is considered to be an increase of the level of leukocytes in the peripheral blood above 30 x 10⁹/l. An increase of the number of leukocytes to 100 x 10⁹/l (in acute leukemias) is defined as extreme.

In hyperleukocytosis: accumulations of leukoaggregates and thrombi of leukemic cells are formed in the vessels of the brain, the kidneys and the heart. Clinically this is manifested by encephalopathy, respiratory distress syndrome, intracranial and pulmonary hemorrhages, hyperuricemic syndrome leading to renal failure. As a consequence of the high level of proliferation of the tumor cells, of metabolism and of cellular breakdown, severe metabolic disorders may develop, including hyperkalemia, hypocalcemia and hyperphosphatemia.

Indications for leukocytapheresis in patients with acute myeloblastic leukemia:

Patients with a number of leukocytes in the blood above 100 x 10⁹/l, even without signs of leukostasis.

Against the background of hydroxyurea therapy, with a leukocyte content in the blood above 100 x 10⁹/l.

In the presence of clinical signs of leukostasis.

Very rapid progression of the disease: doubling of the number of leukocytes per day from 50 x 10⁹/l.

Ineffectiveness of hydroxyurea therapy within 24 hours, i.e. a decrease of the level of leukocytes by less than 30% of the initial level.

Impossibility of taking hydroxyurea.

Method of performing therapeutic leukocytapheresis and plasmapheresis:

Against the background of hydroxyurea therapy LCAP is performed daily until the leukocyte content decreases to about 50 x 10⁹/l. Two or more CBV are processed per procedure. If it is not possible to reduce the level of leukocytes to these figures, chemotherapy is started after the second LCAP. 6-8 hours after the beginning of the specific treatment PP is added with the removal of 50% of the CPV, with replacement by FFP and 5-10% albumin solution depending on the initial level of total protein.

The indication for emergency plasmapheresis is pronounced cytolysis (destruction of more than 50% of the leukocytes). After the LCAP and PP procedure it is recommended to carry out a transfusion of erythrocyte and platelet mass (according to indications).

A contraindication to LCAP is an agonal state of the patient, massive hemorrhage into the brain, profuse bleeding.

Indications for LCAP in patients with chronic myeloid leukemia:

• Pronounced intoxication against the background of hyperleukocytosis above 50-100 x 10⁹/l and hyperthrombocytosis above 350 x 10⁹/l, leading to stasis in the vessels of the brain.
• Developed resistance to polychemotherapy (in the progressive stage and blast crisis) for the purpose of removing a large tumor mass, which leads to an increase of the proliferative activity of the bone marrow and to an increase of the effectiveness of subsequent courses of PCT.

A course of LCAP consists of 2-3 procedures performed daily, until the level of leukocytes decreases 2-fold, with a subsequent transition to PCT. In the presence of hypercoagulation and hyperthrombocytosis heparin is administered intravenously. Replacement is carried out with 5-10% albumin or FFP taking into account the volumes of the leukocyte mass removed.

Indications for LCAP in patients with CLL:

• Hyperleukocytosis above 150-200 x 10⁹/l combined with anemia, thrombocytopenia, splenomegaly and the ineffectiveness of various programs of cytostatic treatment.
• LCAP is performed on blood separators according to the LCAP program in a course of up to 2-3 procedures with an interval of 7-10 days. Administration of heparin and of protein blood substitutes according to indications.

Criteria of effectiveness:

• A decrease of the level of leukocytes.
• A reduction of the signs of intoxication (weakness, sweating, etc.).
• A reduction of the size of the spleen.
• An improvement of the hemoglobin and erythrocyte values with a preceding increase of the number of reticulocytes.
• An increase of the number of platelets.

Therapeutic plasmapheresis in paraproteinemic hemoblastoses

Paraproteinemic hemoblastoses are a group of diseases characterized by monoclonal proliferation of cells of the B-lymphoid line that secrete immunoglobulins; first of all they include multiple myeloma and Waldenström's macroglobulinemia. Multiple myeloma is characterized by hyperparaproteinemia; hyperviscosity syndrome (at a level of the monoclonal protein Ig G or Ig A above 50 g/l), bleeding, retinopathy, neurological symptoms (paresthesia, drowsiness, headache, dizziness), paraproteinemic coma, osteoporosis and osteolysis, hypercalcemic nephropathy (accumulation of myeloma proteins and amyloid in the renal tubules, Bence-Jones proteinuria, hypercalcemia). In Waldenström's macroglobulinemia a pronounced hyperviscosity syndrome occurs owing to the high content of immunoglobulin M and cryoglobulinemia.

Indications:

• Hyperparaproteinemia (total protein above 90-100 g/l), bleeding, hyperviscosity syndrome, renal failure that cannot be relieved.
• Emergency indications:
• Paraproteinemic precoma and coma (total protein above 130 -140 g/l).

Method.

The course of plasmapheresis is daily until the controlled parameters stabilize (total protein, blood rheology), subsequently - repeated procedures in case of a tendency to hyperparaproteinemia, with manifestations of hyperviscosity syndrome (2 times a week). Replacement is carried out with isotonic sodium chloride solution and 5% albumin solution at an initial hypoalbuminemia below 3

Criteria of effectiveness:

• A decrease of the level of total serum protein to 85 g/l.
• A decrease of the level of paraproteins (m-gradient below 30 g).
• Normalization (improvement) of the rheological parameters of the blood; plasma viscosity, erythrocyte aggregation).
• Relief (or reduction) of the bleeding.

Plasmapheresis in porphyria

Plasmapheresis is used in the combined treatment of porphyria during the period of exacerbation, mainly in such forms as acute intermittent porphyria and cutaneous porphyria.

Indications:

• Peripheral polyneuropathy.
• An increased level of porphyrins.

Method:

a course of PP of 8-10 procedures with an interval of 3 to 5 days.

Volumes of plasma removed per session:

in the acute intermittent form of porphyria - 1 volume of circulating plasma (CPV).

in the cutaneous form of porphyria – 0.25-0.5 CPV (depending on the degree of increase of the level of porphyrins).

Plasmapheresis is performed in an isovolemic mode. The following are used as plasma-substituting solutions: sodium chloride solution (when removing 0.25 CPV); isotonic sodium chloride solution + 6% rheopolyglucin solution in a ratio of 2 : 1 (when removing 0.5 CPV); isotonic sodium chloride solution + protein solutions (FFP, 5% albumin solution with replacement of 50-60% of the removed protein) when (removing 1 CPV). In the presence of signs of hypercoagulation – heparin at a dose of 5-10 thousand IU.

Criteria of effectiveness:

Improvement of the clinical indicators: disappearance of peripheral polyneuropathy, of disorders of the function of the central nervous system, of increased photosensitivity.

Normalization of the laboratory indicators of porphyrin metabolism.

Plasmapheresis in patients with aplastic anemia (in sensitization and

refractoriness to transfusions)

Aplastic anemia (AA) is a disease characterized by profound pancytopenia and insufficiency of bone marrow hematopoiesis, caused by the development of aplasia of the bone marrow. This nosology presupposes frequent and numerous blood transfusions, which leads to sensitization. Alloimmunization in its turn causes refractoriness to the blood components transfused.

Indications:

Ineffectiveness of transfusions of platelet concentrate in hemorrhagic syndrome.

Method:

Plasmapheresis is performed 2 times a week in a volume of 0.5 CPV, 5-10 procedures per course. Replacement with FFP at the rate of 20-25 ml/kg (the use of a leukocyte filter is recommended). At a low content of albumin – replacement with 5% albumin solution (40% of the volume of the removed protein). After each plasmapheresis procedure a transfusion of platelet concentrate from an individually selected donor is recommended.

Criteria of effectiveness:

• A decrease of the level of antileukocyte and antiplatelet antibodies.
• An increase of the rise of platelets and erythrocytes after transfusion of blood components at 1, 6, 15, 24 hours.
• A reduction or absence of hemorrhagic syndrome.

Plasmapheresis in hematogenous thrombophilias

Hematogenous thrombophilias manifest themselves as a hypercoagulation syndrome in certain defects of the cellular and plasma elements of the blood, which leads to thromboses. This variant is observed in: AT III deficiency, anomalies of the protein C and protein S system, mutant factor V Leiden, mutation of the methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia, mutant prothrombin G202210A, anticoagulant autoantibodies to phospholipids, the syndrome of sharply increased platelet aggregation - the "sticky platelet" syndrome, a significant increase of the level or of the multimerity of von Willebrand factor and the activity of factor VIII, a high level of coagulation factor XIII of the blood.

Indications:

• Thromboses.
• Changes of the coagulogram parameters: AT III deficiency, anomalies of the protein C and protein S system, mutant factor V Leiden, mutation of the methylenetetrahydrofolate reductase (MTHFR) gene, a significant increase of the level or multimerity of von Willebrand factor and of the activity of factor VII of the blood, a high level of XIII.
• Hyperhomocysteinemia, mutation of integrins.
• The syndrome of sharply increased platelet aggregation – the "sticky platelet" syndrome.

Method:

A course of membrane plasmapheresis (MP) consists of up to 8-10 procedures with an interval of 1-2 days. The volumes of plasma removed per PP session amount to 300-400 ml of plasma. Replenishment is carried out with isotonic sodium chloride solution. In some cases the plasma removed is replaced by protein preparations (albumin, FFP, etc.) MP is performed in an isovolemic mode. A course of MP can be carried out against the background of the use of various combinations of therapeutic agents and approaches: intravenous continuous administration (by infusion pump) of unfractionated heparin (on average 1000 IU/h); the use of low-molecular-weight heparins; indirect anticoagulants (warfarin, sincumar, pelentan, etc.); sulodexide; antiplatelet agents (aspirin, ticlid, plavix); vasaprostan; vitamins B12, B6, folic acid; corinfar; nicotinic acid.

Criteria of effectiveness:

• Improvement of the clinical indicators of the underlying disease.
• Normalization of the changed coagulogram parameters.