Overview.
Hepatitis-associated aplastic anemia, also known as posthepatitis aplastic anemia, is often a lethal complication of hepatitis in children and young adults, and is now generally regarded as an independent disease. Clinical manifestations include pallor, dizziness, palpitations, fatigue and other obvious manifestations of ischemia and hypoxia and cardiac insufficiency. The anemia is progressively aggravated, the frequency of blood transfusion is high, and there is often a severe anemia that is difficult to be corrected even with large amounts of blood transfusion. This syndrome can be treated with bone marrow transplantation and anti-thymocyte globulin combined with androgens.
Etiology
The etiology has not been clearly defined; a few cases of viral hepatitis A, B, C, and E have been reported in the literature to be secondary to recrudescence, but hepatitis-associated recrudescence is more often caused by serologically negative hepatitis. Usually patients start with acute hepatitis, jaundice, transaminases are obviously elevated, 1 to 2 months later with the improvement of hepatitis gradually recovered, the patient began to appear progressive hematopoiesis, bone marrow hematopoietic failure, and most of them progressed to severe or very severe retroviruses.
Symptoms
The disease is more common in young adults, and is more common in males than females. Clinical manifestations are similar to those of general cataracts, but the disease is severe and develops rapidly. Jaundice and liver function impairment are often present during the course of the disease. Severe infection and massive bleeding are lethal complications, and the onset of the disease is not related to the severity of hepatitis or changes in hepatitis.
1.General condition
Mental depression, tiredness and fatigue. Those with more than moderate anemia may have low-grade fever, and there may be different degrees of fever if infection exists.
2. Skin and mucous membrane
The skin and mucous membranes are anemic to varying degrees (pale face, lips, conjunctiva, nail beds, etc.). Cyanosis can be seen in the skin and mucous membranes, and large petechiae or subcutaneous hematomas can be seen in severe hemorrhagic tendency, as well as oozing of blood from the gums and nasal mucous membranes. Anemia coexists with hemorrhage.
3. Infection
Fever often occurs during the course of the disease and is almost always caused by infection, which often occurs in the oropharynx and perianal necrotic ulcers, leading to sepsis. The patient’s body temperature is often above 38.5 ℃, and individual patients are in uncontrollable high temperature from the onset of the disease to death. When the peripheral blood granulocytes are obviously low, the infection is difficult to trigger a local inflammatory response such as oral cavity, pharyngeal infection can be no local congestion; soft tissue infections without abscess formation, the boundaries are not clear. Therefore, the possibility of sepsis should be considered for those who have high fever without obvious foci of infection.
4.Other
Anemia may lead to increased heart rate, systolic murmur in the precordial region, and signs of cardiac insufficiency in severe cases. Prolonged anemia may lead to cardiac enlargement. If there is internal bleeding, such as intracranial hemorrhage, there may be corresponding cranial hypertension and neurological signs.
Examination
1. Laboratory examination
(1) Blood picture: The counts of white blood cells, red blood cells and platelets in peripheral blood are obviously reduced.
(2) Bone marrow image: At least one part of bone marrow is hypoproliferative or severely hypoproliferative (if hyperplasia is active, there must be a significant decrease in megakaryocytes), and there is an increase in small granular non-hematopoietic cells of the bone marrow. Bone marrow biopsy and other tests, if possible, will show that there is a decrease in hematopoietic tissue and an increase in adipose tissue.
(3) Virology Most of the hepatitis-associated retroviruses are serologically negative.
(4) Liver tissue biopsy Most of them show normal liver tissue or liver changes after hepatitis is cured.
2. Other auxiliary examinations
Chest radiograph, ultrasound, CT and other examinations are selected according to clinical needs.
Diagnosis
Diagnosis can be made according to clinical manifestations and laboratory tests.
Differential diagnosis
Except for other diseases that cause pancytopenia, such as paroxysmal sleep hemoglobinuria, myelodysplastic syndrome, acute hematopoietic arrest, myelofibrosis, acute leukemia, malignant histiocytosis, and so on.
Complications
Severe disease and rapid progress of the disease often complicate ischemia and hypoxia and cardiac insufficiency; complications of serious infection and internal bleeding, especially intracranial hemorrhage often endanger the patient’s life; can be complicated by cardiac insufficiency, often with jaundice, liver function damage; serious infection and massive bleeding are lethal complications.
Treatment
The standard treatment for hepatitis-associated severe aplastic anemia is intensive immunotherapy (IST) with anti-thymocyte globulin (ATG)/anti-lymphocyte globulin (ALG) and cyclosporine (CsA) plus pro-hemopoietic therapy for patients ≥40 years of age, or <40 years of age without a HLA-compatible sibling donor, and pro-hemopoietic therapy for patients <40 years of age without an HLA-compatible sibling donor. HLA-matched sibling donor bone marrow transplantation is preferred for patients with severe aplastic anemia <40 years of age who have an HLA-matched sibling donor in the absence of active infection and bleeding; HLA-matched unrelated donor bone marrow transplantation is used only in young patients with severe aplastic anemia who have failed ATG/ALG and CsA therapy. Bleeding and infection must be controlled prior to bone marrow transplantation. G-CSF mobilized peripheral blood stem cell transplantation is not recommended. Transfusion-dependent non-severe aplastic anemia may be treated with CsA + pro-hematopoietic (androgens, hematopoietic growth factors), or as severe aplastic anemia if treatment is ineffective for 6 months. Non-severe aplastic anemia that does not depend on blood transfusion can be treated with CsA and/or pro-hematopoietic therapy. Allogeneic hematopoietic stem cell transplantation is the only effective means of eradicating the disease.
Prognosis
The prognosis is aggressive, with a 3-month mortality rate of more than 90% if untreated.