Thrombotic microangiopathy - Treatment

Treatment of thrombotic microangiopathy includes the use of fresh frozen plasma, the purpose of which is to prevent or limit intravascular thrombus formation and tissue damage, and supportive therapy aimed at eliminating or limiting the severity of the main clinical manifestations. However, the ratio of these types of treatment in hemolytic uremic syndrome and thrombotic thrombocytopenic purpura is different.

Treatment of typical hemolytic uremic syndrome

The basis of treatment of post-diarrheal hemolytic uremic syndrome is supportive therapy: correction of water-electrolyte disturbances, anemia, renal failure. In case of severe manifestations of hemorrhagic colitis in children, parenteral nutrition is necessary.

Water balance control

In case of hypovolemia, it is necessary to replenish the BCC by intravenous administration of colloid and crystalloid solutions. In conditions of anuria, the administration of large volumes of fluid requires caution due to the high risk of developing hyperhydration, which is why timely treatment of glomerulonephritis is necessary. In the presence of oliguria, intravenous administration of crystalloids with large doses of furosemide in some cases helps to avoid glomerulonephritis.

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Correction of anemia

Transfusions of red blood cells are indicated for the treatment of anemia. It is necessary to maintain hematocrit at a level of 33-35%, especially in cases of CNS damage.

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Treatment of acute renal failure

Hemodialysis or peritoneal dialysis is used to treat acute renal failure.

Dialysis in combination with 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 fresh frozen plasma is not indicated due to the high rate of spontaneous recovery and unproven efficacy.

In the treatment of typical hemolytic uremic syndrome, antibiotics are contraindicated, as they can cause a massive influx of toxins into the bloodstream due to the death of microorganisms, which aggravates microangiopathic damage, and antidiarrheal drugs that inhibit intestinal motility. Caution is required when administering platelet concentrate due to the possibility of increased 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 still being studied.

Treatment of atypical hemolytic uremic syndrome/thrombotic thrombocytopenic purpura

The basis of 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 with fresh frozen plasma - infusions and plasmapheresis. The goal of therapy is to stop intravascular thrombus formation by introducing natural components in plasma that have proteolytic activity with respect to super-large multimers of von Willebrand factor, anticoagulants and components of the fibrinolysis system. During plasmapheresis, in addition to replenishing the deficiency of these factors, mechanical removal of mediators supporting the microangiopathic process and von Willebrand factor multimers is also achieved. The high efficiency of plasmapheresis compared to infusions of fresh frozen plasma is believed to be associated with the possibility of introducing large volumes of plasma during the procedure without the risk of hyperhydration. In this regard, anuria, severe damage to the central nervous system and heart with the development of circulatory failure are absolute indications for plasmapheresis.

When treating with FFP infusions, plasma is administered at a dose of 30-40 mg/kg of body weight on the first day, and at a dose of 10-20 mg/kg on subsequent days. Thus, the infusion regimen allows for the administration of about 1 liter of plasma per day. When performing plasmapheresis in patients with TMA, 1 volume of plasma should be removed per session (40 ml/kg of body weight), 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 precisely defined, but daily plasma exchange is recommended during the first week, followed by sessions every other day. Treatment with fresh frozen plasma can be intensified by increasing the volume of plasma exchange. In patients with thrombotic microangiopathy refractory to treatment with fresh frozen plasma, the method of choice is plasmapheresis with replacement of 1 volume of plasma twice a day to reduce the recirculation time of the administered plasma. Treatment with fresh frozen plasma should be continued until remission occurs, as evidenced by the disappearance of thrombocytopenia and cessation of hemolysis. Therefore, therapy with fresh frozen plasma should be monitored by daily determination of the platelet count and LDH level in the blood. Their stable normalization, which lasts for several days, allows plasma treatment to be discontinued. Fresh frozen plasma therapy is effective in 70-90% of patients with thrombotic microangiopathy, depending on its form.

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

Monotherapy with antiplatelet agents is ineffective in the acute phase of the disease and is also associated with the risk of bleeding. Antiplatelet agents may be recommended during the recovery phase, when there is a tendency towards thrombocytosis, which may be accompanied by increased platelet aggregation and, therefore, the risk of exacerbation. The effectiveness of treatment with prostacyclin drugs, the purpose of which is to reduce endothelial dysfunction, has not yet been proven.

In secondary forms of thrombotic microangiopathy caused by drugs, it is necessary to discontinue the corresponding drugs. The development of thrombotic microangiopathy in autoimmune diseases requires active treatment of the underlying process, primarily the prescription or intensification of immunosuppressive therapy, against the background of which therapy with fresh frozen plasma is carried out. Glucocorticoid treatment of classical forms of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura is ineffective when these drugs are used as monotherapy, and their use in combination with fresh frozen plasma makes it difficult to assess their effectiveness, and therefore, in these forms of thrombotic microangiopathy, prednisolone is inappropriate. Treatment with cytostatic drugs is not used for classical forms of thrombotic microangiopathy. There are only isolated descriptions of the effectiveness of vincristine in thrombotic thrombocytopenic purpura. In recent years, attempts have been made to treat thrombotic thrombocytopenic purpura with intravenous IgG, but the effectiveness of such therapy has not been proven to date.

In chronic recurrent forms of thrombotic microangiopathy, splenectomy is recommended, which is believed to prevent future relapses of the disease.

For the treatment of arterial hypertension in patients with HUS/TTP, the drug of choice is ACE inhibitors. However, in malignant, therapy-resistant arterial hypertension or in the presence of hypertensive encephalopathy, bilateral nephrectomy is indicated.

Kidney transplant

Successful kidney transplantation is possible in patients with HUS/TTP. However, these patients have a high risk of recurrent thrombotic microangiopathy in the graft, which is further increased by the use of cyclosporine A. In this regard, it is advisable to avoid prescribing Sandimmune to patients with HUS/TTP.