Thrombotic microangiopathy: treatment

Treatment of thrombotic microangiopathy involves the use of freshly frozen plasma, the purpose of which is to prevent or limit intravascular thrombus formation and tissue damage, and maintenance therapy aimed at eliminating or limiting the severity of major clinical manifestations. However, the ratio of these treatments for hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura is different.

Treatment of a typical hemolytic-uremic syndrome

The basis of treatment of post-diarrheal hemolytic-uremic syndrome is maintenance therapy: correction of water-electrolyte disorders, anemia, renal failure. When expressed manifestations of hemorrhagic colitis in children need parenteral nutrition.

Control of water balance

With hypovolemia, replacement of bcc by intravenous administration of colloidal and crystalloid solutions is necessary. In the conditions of anuria, the introduction of large volumes of fluid requires caution because of the high risk of hyperhydration, which requires timely treatment for glomerulonephritis. In the presence of oliguria intravenous administration of crystalloids with high doses of furosemide in some cases helps to avoid glomerulonephritis.

[1], [2], [3], [4], [5]

Correction of anemia

For the treatment of anemia, transfusions of erythrocyte mass are shown. At the same time it is necessary to maintain hematocrit at the level of 33-35%, especially when CNS is affected.

[6], [7], [8], [9], [10], [11]

Treatment of acute renal failure

To treat acute renal failure, hemodialysis or peritoneal dialysis is used.

Dialysis in combination with the correction of anemia and water-electrolyte disorders plays a fundamental role in reducing mortality in the acute period of the disease.

To prevent or limit the microangiopathic process in diarrhea with hemolytic uremic syndrome, specific therapy with freshly frozen plasma is not indicated due to the high incidence of spontaneous recovery and unproven efficacy.

In the treatment of a typical hemolytic-uremic syndrome, antibiotics are contraindicated, since they can cause massive influx of toxins into the bloodstream due to the death of microorganisms, which aggravates microangiopathic damage, and antidiarrheal drugs that depress the motor function of the intestine. Care is needed to administer thrombocyte concentrate in connection with the possibility of enhancing intravascular thrombus formation due to the appearance of fresh platelets in the bloodstream.

To bind verotoxin in the intestine, oral use of sorbents based on synthetic resins has been proposed, but these methods are only being studied.

Treatment of atypical hemolytic-uremic syndrome / thrombotic thrombocytopenic purpura

The basis for the treatment of thrombotic thrombocytopenic purpura and atypical hemolytic-uremic syndrome, including secondary forms of thrombotic microangiopathy, is fresh frozen plasma. There are two modes of therapy for freshly frozen plasma - infusion and plasmapheresis. The goal of the therapy is to stop intravascular thrombus formation by introducing natural components present in the plasma that have proteolytic activity against super-large vWF syndrome multimers, anticoagulants and components of the fibrinolysis system. With plasmapheresis, in addition to replenishing the deficiency of these factors, mechanical removal of mediators supporting the microangiopathic process and multimers of von Willebrand factor are also achieved. The high efficiency of plasmapheresis in comparison with infusions of fresh frozen plasma is believed to be associated with the possibility of introducing large volumes of plasma during its procedure without the risk of hyperhydration. In this regard, anuria, severe lesions of the central nervous system and the heart with the development of circulatory failure are absolute indications for plasmapheresis.

In the treatment of infusions of FFP on the first day, plasma is administered at a dose of 30-40 mg / kg of body weight, in subsequent days - at a dose of 10-20 mg / kg. Thus, the infusion regimen allows one to inject about 1 liter of plasma per day. When carrying out plasmapheresis in patients with TMA, one volume of plasma per session (40 ml / kg of body weight) should be removed, replacing it with an adequate volume of fresh frozen plasma. Replacing the removed plasma with albumin and crystalloids is ineffective. The frequency of plasmapheresis procedures and the total duration of treatment are not exactly defined, however, daily plasma exchange is recommended during the first week followed by sessions every other day. Intensify the treatment with freshly frozen plasma by increasing the volume of plasma exchange. In patients with refractory to the treatment of freshly frozen plasma of thrombotic microangiopathy, the choice method is to conduct plasmapheresis, replacing 1 volume of plasma twice per day, to reduce the time of recirculation of the plasma introduced. Treatment with freshly frozen plasma should be continued until the onset of remission, as evidenced by the disappearance of thrombocytopenia and the cessation of hemolysis. Therefore, fresh-frozen plasma therapy should be monitored daily by determining the number of platelets and the level of LDH in the blood. Their persistent normalization, which lasts for several days, allows to stop plasma treatment. Therapy with freshly frozen plasma is effective in 70-90% of patients with thrombotic microangiopathy, depending on its shape.

The expediency of using anticoagulants (heparin) in thrombotic microangiopathy has not been proven. In addition, there is a high risk of hemorrhagic complications when used in patients with HUS / TTP.

Monotherapy with antiplatelet agents is ineffective in the acute period of the disease and is also associated with the danger of bleeding. The appointment of antiplatelet agents can be recommended during the convalescence phase, when there is a tendency to thrombocytosis, which may be accompanied by increased platelet aggregation and, consequently, the risk of exacerbation. The effectiveness of treatment with prostacyclin drugs, whose goal is to reduce endothelial dysfunction, is currently not proven.

In secondary forms of thrombotic microangiopathy caused by drugs, it is necessary to cancel the appropriate drugs. The development of thrombotic microangiopathy in autoimmune diseases requires active treatment of the main process, primarily the appointment or strengthening of immunosuppressive therapy, against which background fresh-frozen plasma therapy is administered. Treatment with glucocorticoids of classical forms of hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura is ineffective when these drugs are used in the form of monotherapy, and the use in combination with fresh-frozen plasma makes it difficult to assess their effectiveness, and in these forms of thrombotic microangiopathy, the use of prednisolone is impractical. Treatment with cytostatic drugs in the classical forms of thrombotic microangiopathy is not used. There are only single descriptions of the efficacy of vincristine in thrombotic thrombocytopenic purpura. In recent years, attempts have been made to treat thrombotic thrombocytopenic purpura by intravenous administration of IgG, but to date, the effectiveness of such therapy has not been proven.

In chronic recurrent forms of thrombotic microangiopathy, it is recommended to perform splenectomy, which is believed to avoid relapse of the disease in the future.

To treat arterial hypertension in patients with HUS / TTP, ACE inhibitors are a means of choice. However, in case of malignant, hypertensive or hypertensive encephalopathy, bilateral nephrectomy is indicated.

Kidney Transplantation

Successful kidney transplantation is possible for patients with HUS / TTP. However, these patients have a high risk of recurrence of thrombotic microangiopathy in the transplant, which is further increased with cyclosporine A. Therefore, it is advisable to avoid the appointment of sandimmune to patients with HUS / TTP.