Paroxysmal nocturnal hemoglobinuria (PNH) or Marchiafava-Micheli syndrome is an acquired clonal (emergence of immunocompetent cell clones) disorder of hematopoietic stem cells. The disorder appears due to a somatic mutation that causes a violation of the synthesis of the glycosylphosphaimdylnostol base. As a result, a decrease in the content of the main membrane proteins develops.
The main pathogenetic link of PNH is the increased sensitivity of erythrocytes to the hemolytic action of complement.
Hemolysis is provoked by a variety of factors: infection, surgery, medication, etc., including physiological ones (menstruation, sleep). Iron deficiency often develops, bleeding occurs, which are associated with thrombocytopenia , thrombosis (venous, arterial ). Patients with PNH often develop Budd-Chiari syndrome (obliteration of the suprahepatic veins or a short segment of the inferior vena cava), characterized by the presence of vomiting, abdominal pain, ascites of varying degrees, liver failure, bleeding from varicose veins. Moderate spleno- and hepatomegaly is observed in all patients. When examining a patient, a dark bronze skin tone is noteworthy due to a combination of pallor and yellowness. Patients complain of weakness, headache, abdominal pain, difficulty swallowing .
Anemia in most patients is severe with a hemoglobin level of less than 60 g/l, reticulocytosis. Blood smears show schistocytosis, normoblastosis, polychromatophilia, microcytosis, and hypochromia of erythrocytes due to iron deficiency. Osmotic resistance is normal. In the bone marrow, erythroid hyperplasia is detected, and bone marrow hypoplasia is often observed.
PNH is characterized by: hyperbilirubinemia, hemoglobinemia , methemoglobinemia (methemoglobin is a derivative of hemoglobin, devoid of the ability to carry oxygen). Urine is dark in color in the morning and becomes somewhat lighter during the day. Hematuria, proteinuria, hemoglobinuria, hemosiderinuria are detected .
To confirm the diagnosis , a Hema test is used: pronounced hemolysis of erythrocytes in serum with an acidic environment (pH 6.4–6.5) at a temperature of 37 ° C. Coombs reaction is negative.
In the treatment of PNH, transfusions of washed or thawed erythrocytes , iron preparations are used . If transfusion is not possible, prednisolone 15–40 mg orally every other day is prescribed. High doses of prednisolone are prescribed for the treatment of hemolytic crisis. In the presence of venous thrombosis, indirect anticoagulants are used, because. they do not activate complement. Heparin (capable of activating complement) is used only for severe liver thrombosis.
The average survival rate for patients with PNH is 10 years. Acute leukemia or myelodysplastic syndrome (a common name for bone marrow abnormalities) often develops.
Spur cell hemolytic anemia has been described in patients with severe liver cirrhosis.
The etiology is unknown. The pathogenesis of the disease is associated with excess cholesterol and deficiency of phospholipids in the erythrocyte membrane.
Clinical picture, treatment and prognosis , as in microspherocytic hemolytic anemia. The diagnosis is based on the detection in the blood of erythrocytes with numerous small processes.
Hemolytic anemia due to mechanical damage to red blood cells.
Marching paroxysmal hemoglobinuria (MPG) is characterized by the development of erythrocyte hemolysis in physically strong young people due to an increased load on the muscles of the lower extremities during long walking, marching, running, skiing, as well as on the muscles of the hands during karate techniques. Mechanical hemolysis develops in the vessels of parts of the body that are exposed to a hard surface for a long time. It is more common when wearing hard-soled shoes. What matters is the unusual arrangement of blood vessels, the proximity of the capillary network to the surface of the foot and hand .
The main symptom is the discharge of dark urine , sometimes there is nausea, vague pain in the abdomen, back, legs, there may be moderate transient jaundice . The hemoglobin concentration and hematocrit value are usually below the lower limit of normal, there is a tendency to macrocytosis, erythrocyte polychromatophilia, schistocytosis, spherocytosis . In the clinical picture, severe hemoglobinuric crises are possible. More often, the disease is characterized by a mild course with the presence of moderate hemoglobinemia, hemoglobinuria, a decrease in haptoglobin (a blood serum glycoprotein that interacts with hemoglobin to form a complex compound of blood serum iron and ferritin).
Differentiation is carried out with marching myoglobinuria (myoglobin is muscle hemoglobin that stores oxygen in the muscles), which is characterized by the presence of muscle pain and the detection of myoglobin in the urine. Chills precede hemoglobinuria (dark urine) in paroxysmal cold and nocturnal hemoglobinuria , while chills occur after hemoglobinuria in MPH.
There is no specific treatment for MPG. The prognosis is favorable. Episodes of hemoglobinuria can be prevented by using softer shoes and changing running technique.
Mechanical damage to erythrocytes (erythrocyte fragmentation syndrome) can be observed in the pathology of the heart and large vessels (artificial heart valve, unoperated heart defects, coarctation of the aorta, plastic heart valves), small vessels (hemolytic-uremic syndrome, which includes a combination of intravascular hemolysis and renal microangiopathy in newborns and young children; thrombotic thrombocytopenic purpura); disseminated carcinomas of the stomach, breast, lungs, pancreas; during pregnancy and in the postpartum period (preeclampsia and eclampsia, thrombotic thrombocytopenic purpura, placental abruption); with malignant hypertension, DIC; infections; generalized vasculitis associated with immune disorders (systemic lupus erythematosus, acute glomerulonephritis, scleroderma, Wegener’s granulomatosis, systemic amyloidosis); hemangiomas; in organ transplants.
Clinical manifestations depend on the localization of the primary process and organ damage by intravascular deposits of fibrin and platelets.
Toxic hemolytic anemia. The cause of hemolysis of erythrocytes can be numerous substances of a chemical and bacterial nature (arsenic hydrogen, lead, copper salts, potassium and sodium chlorates, oxygen); insect poisons (bees, spiders, etc.); medicinal substances (sulfonamides, phenacetin, salicylates, phenol, cresol, naphthalene, resorcinol, phenylhydrazine, methylene blue, hematin); infections (bacterial, viral, including HIV infection, mycoplasma, infection with toxoplasma, trypanosomes, malaria, etc.
The pathogenesis of hemolysis can be different. In particular, the denaturation of hemoglobin by oxygen-dependent mechanisms leads to the formation of methemoglobin, sulfohemoglobin and Heinz bodies (when exposed to drugs). The development of hemolysis can occur as a result of lipid peroxidation of membranes and a shortening of the life span of erythrocytes (oxygen), inactivation of enzymes of the pentose-phosphate and glycolytic pathways, damage to the cell membrane (copper); inhibition of heme synthesis and shortening of the life of erythrocytes (lead); damage to the erythrocyte membrane by activated oxygen derivatives (chlorates); direct toxic effect of the poison on the erythrocyte membrane (venom of insects, snakes); direct temperature effects on red blood cells (burns); a decrease in the level of phosphorus in the blood serum of less than 0.6 mg / l, which leads to a deep inhibition of glycolysis and a decrease in the resistance of erythrocytes (alcohol, starvation, long-term therapy with antacids); absorption of immune complexes (viruses); formation of cold agglutinins (mycoplasma); autoimmune mechanisms (toxoplasmosis); intraerythrocyte infection and their destruction in the spleen. In malaria, uninfected erythrocytes are hemolyzed by activation of lipid peroxidation.
Along the way , toxic GA can be acute and chronic. In acute toxic HA, intravascular hemolysis occurs, manifested by hemoglobinemia, hemoglobinuria . In severe cases, it is accompanied by the phenomena of collapse and anuria . Intracellular hemolysis predominates in chronic toxic GA accompanied by hepatosplenomegaly .
Treatment consists in stopping contact with the toxic agent and using appropriate antidotes, and in infectious diseases, therapy for the underlying disease. In severe anemia, replacement transfusion is indicated, with anuria – the introduction of a liquid ( alkaline solutions ).
The prognosis for the acute course of toxic GA can be unfavorable for life. With timely identification and elimination of the cause of hemolysis, a complete recovery is observed.
Clinical examination. All patients with congenital and acquired HA are subject to dispensary observation. In each specific case, an individual plan of management and preventive treatment is developed with regular laboratory blood tests and periodic correction of therapy, if necessary, surgical intervention (splenectomy) is planned. For this category of patients, it is important to organize a protective regime to prevent hemolytic crises – prevention of infections, malaria, allergic reactions, intoxication, cooling, burns, transfusion of blood and its components, taking medications (sulfonamides, antibiotics, analgesics, iron preparations, etc.).