Partsialynaya krasnokletochnaya aplasia – Autoimmune hemolytic anemia with antibody to bone marrow erythrokaryocytes

Partsialynaya krasnokletochnaya aplasia (PKKA) - Autoimmune disease, associated with exposure to the antibodies, in most cases directed against the antigen erythrokaryocytes marrow. Manifested severe anemia with reticulocytopenia, reduction of red sprout bone marrow with normal number of neutrophils and platelets.

The first description was made in PKKA 1922 g. Currently, there are about 300 cases. Proved, that the partial red cell aplasia - this is not one, and several different diseases. In some cases, even with long-term monitoring of patients to communicate PKKA with any other diseases can not be (idiopathic form PKKA), in other PKKA associated with tumor of the thymus gland - thymoma.

Often PKKA is the first stage of any hemoblastosis. There was a kind of clinical picture PKKA congenital form, Diamond Blekfena. Obtained special juvenile form PKKA with favorable course.

Pathogenesis partial red cell aplasia

At present, the fact of the autoimmune nature of the majority of cases there is no doubt PKKA. Established, that in the plasma of patients have antibodies PKKA, belonging to the class IgG, which have effects on the cytology of bone marrow red cells, as well as inhibit the growth of erythroid colonies. Long-term treatment of mice with the sick PKKA leads to severe anemia and an increase in the amount of erythropoietin: serum of the same patient in remission has no effect on erythropoiesis.

Detected, in the serum of patients with significant portion PKKA detected antibodies, directed against a common antigen interspecific, located on the surface of erythrokaryocytes mice with Rauscher erythroblastosis. This antigen is found on the surface of human erythrokaryocytes, as well as other mammals. Antibodies to said antigen detected in the sera of most adult patients regardless PKKA, whether there are in these patients in the future or not signs hemoblastosis. The antibodies can not be detected in the serum of children with the syndrome Diamond Blekfena and in patients with adolescent form of the disease. A huge number of these antibodies detected in the serum of patients with thymoma.

On the surface of red blood cells of the peripheral blood of patients have antibodies PKKA, often related to the class IgA, less IgG class. These antibodies can not be detected by Coombs, they are detected only with the use of the sample agregatgemagglyutinatsionnoy. Unlike antibodies, characteristic of autoimmune hemolytic anemia with partial heat agglutinins, antibodies, Taken from the surface of red blood cells of patients with PKKA, fixed on all donor erythrocytes, except treated with papain: These antibodies are directed against an antigen Pr. Antibodies, eluted from the red blood cells of patients with autoimmune hemolytic anemia, fixed as unchanged donor erythrocytes, and in papain-treated. The significance of these antibodies in the pathogenesis is not yet ascertained PKKA, but they are identified as in adults, suffering PKKA, and adolescents, as well as those with congenital form PKKA.

Some patients PKKA detected in serum M-gradient, t. it is. there are monoclonal antibodies. Proved, that some patients PKKA M-gradient - is anti-idiotypic antibodies, antibodies directed against the antigen erythroblastic. The presence of these antibodies possibly due to a softer for PKKA M-gradient.

Probably, not in all cases PKKA antibody directed against an antigen erythroblastic. Besides, currently known cases PKKA, in which killer T detected, directly destroy erythrokaryocytes.

The pathogenesis of juvenile form PKKA and congenital forms Diamond Blekfena is not yet known. Sometimes there are family cases. Serum antibodies to the antigen erythroblastic thus can not be identified. On the surface of red blood cells of peripheral blood revealed antibodies, directed against an antigen Pr. Expected, that the syndrome Diamond Blekfena are immune lymphocytes, violate erythroid hematopoiesis, However, clear evidence of this fact is not obtained. No firm belief in the fact, that Diamond syndrome is an autoimmune disease Blekfena.

Clinical manifestations of partial red cell aplasia

The disease begins slowly. Patients complain of severe weakness, fatigue, precordial pain. A marked pallor of the skin and mucous membranes with no signs of jaundice. Body temperature is not increased. Sometimes there is enlargement of the liver due to hemosiderosis. The spleen is occasionally also increases.

Laboratory findings partial red cell aplasia

The majority of patients detected PKKA expressed normochromic anemia with low reticulocyte; the number of leukocytes often normal or even increased, however, some patients revealed moderate leukopenia, sometimes found netrofilny shift to the left. Platelet counts in most cases normal, much less - a little low. Found a significant increase in ESR.

The bone marrow is most often observed in the inhibition of erythroid normal amount of megakaryocytes and granulocytes. Sometimes revealed phagocytosis by macrophages erythrokaryocytes. In trepanate relationship between fat and part of the hematopoietic bone marrow normal or marked hyperplasia.

In some cases, the first stage of disease at a low level in the bone marrow reticulocytes, instead of the reduction it is marked red sprout hyperplasia (ineffective erythropoiesis). Later, however, this step is replaced by a reduction of red sprout.

The disease runs a chronic. Participating patients can obtain remission, however, most individuals, suffering PKKA, despite the massive therapy, there is no remission. Some patients PKKA gradually beginning to show signs of hemoblastosis. Revealed stab shift, reminiscent of an anomaly in the absence of leukocytes Pelgera it in the family of the patient. Marked basophilia, eozinofilija, sometimes monocytosis. When cytogenetic studies in the early stages of the disease changes are noted. Sometimes gradually revealed no distinctive myeloproliferative disease Rh-chromosome. In some cases, developing erythromyelosis, sometimes - acute leukemia, undifferentiated immunologically, on the surface of antigen blasts revealed erythroblastic.

Teenager form PKKA

At the beginning of the adolescent form PKKA gradual, but more rapid, than in adults. Body temperature is normal. Some patients unable to palpate a spleen. Morphologically, this form is not different from adults PKKA. Revealed severe anemia in the absence of reticulocytes, normal number of neutrophils and platelets, absence or a sharp decrease in the number of bone marrow erythrokaryocytes. M-gradient in the form of missing teen. To identify serum antibodies can not antieritroblastnye. On the surface of red blood cell antibodies detected by agregatgemagglyutinatsii, often they belong to the class IgA, реже — IgG, directed against an antigen Pr. Further development is not observed. Sick teenage form PKKA much easier to care, than adults, remission of their persistent.

Diamond Syndrome Blekfena

The syndrome Diamond Blekfena first manifestations of the disease occur in children under the age of 4 months. Most often draws the attention of the child's sudden pallor. Sometimes a random study of blood in these children revealed severe anemia.

With the increase in the degree of anemia child becomes restless, loses appetite. It appears systolic murmur over the apex of the heart, which is sometimes mistaken for a sign of congenital heart disease. As with Fanconi anemia, Sometimes there are changes to the thumbs. Some patients have a short neck, reminiscent of the neck in patients with Turner's syndrome. Increased liver and spleen is not typical, except in cases of multiple blood transfusions. In these cases, hepatomegaly and splenomegaly associated with hemosiderosis. Often there is stunting.

When a blood test revealed severe anemia, reticulocytopenia, red sprout inhibition of bone marrow with normal number of neutrophils and platelets. Characteristically increase in fetal hemoglobin.

Detect in the serum of children antibodies to erythroblasts can not. On the surface of red blood cells by the method agregatgemagglyuti- nation often detect antibodies of IgA, less IgG against the antigen Pr.

Diagnosis PKKA

About PKKA in adults should think in those cases, if severe anemia in the patient no reticulocytes or drastically reduced their number in the normal or near-normal levels of platelets and neutrophils. In the bone marrow with the often absent or almost absent erythrokaryocytes under normal number of granulocytes and megakaryocytes, No increase in the number of blasts.

Reduction krasnogo rostka can be observed not only when PKKA, but also in the form of a conventional thermal AIHA with incomplete agglutinins during severe exacerbation, when antibodies become much, that they kill not only the peripheral erythrocytes, antigen against which they are directed, but erythrokaryocytes, on the surface of which also has the antigen, but in much smaller numbers. In such forms AIHA unlike PKKA marked fever. Correct diagnosis helps to study the specificity of the antibody (their focus against the antigen Pr, the presence of antibodies in serum antneritroblastnyh). They often come to light when PKKA and absent in AIHA.

It should be taken into account, what in chronic T-lymphocytic leukemia sometimes there comes a reduction of red germ hematopoiesis, what, perhaps, due to the destruction of T-lymphocytes erythrokaryocytes.

After identifying a need PKKA exclude tumor of the thymus gland, Why radiographically scrutinize the anterior mediastinum, and in suspected thymoma produce pnevmomediastinograficheskoe study.

Children with the syndrome Daymonda- Blekfena characterized by the same changes in blood, as with other forms of PKKA. Due to the fact that these children are easily glikokortikoidnoy therapy, during the initial investigation of the content of reticulocytes and holding the sternal puncture after the appointment of prednisolone may be diagnostic errors. In these cases, the irritation is detected red growth marrow, not his oppression and increase of reticulocytes, instead of lowering. Therefore, research is needed bone marrow and content of reticulocytes until the appointment of prednisolone or some time after its cancellation, When blood counts decrease.