A number of clinical syndromes, usually revealed through a careful history and physical examination, are associated with AA (see box on Diagnostic Algorithm in Aplastic Anemia and Tables 1 and 2).

Table1. A Classification of Aplastic Anemia

Table2. Classification of Drugs and Chemicals Associated With Aplastic Anemia

Posttransfusion and Post Solid Organ Transplant Associated Graft-Versus-Host Disease

Almost uniformly fatal AA is a constant feature of transfusion-associated GVHD, produced by the transfusion of competent lymphocytes into immunodeficient hosts, including children with congenital syndromes, solid organ transplant patients, cancer patients receiving high-dose chemotherapy, and patients with adoptive cellular immunotherapy for leukemia. In rare circumstances, competent donor lymphocytes can be also transferred with the transplanted organ. Rarely, posttransfusion GVHD occurs in an apparently immunocompetent recipient in the special circumstance in which the donor is homozygous for an HLA haplotype also shared by the recipient, as can occur among first-degree family members. Small numbers of lymphocytes are sufficient to produce the syndrome, which is resistant to immunosuppressive therapy.

Pregnancy

 Pregnancy is common in the age groups most susceptible to BM failure, and in many cases, its association is probably only coincidental. The true frequency of AA in pregnancy is unknown, but from the number of cases reported, it appears rare, although BM hypoplasia may be relatively common during pregnancy. A causal relationship is suggested by the temporal relationship between the onset of pan cytopenia and that of pregnancy and by resolution after delivery and spontaneous or induced abortion; some patients who have developed AA are remitted after each delivery. Survival rates for AA in pregnancy have been relatively high for the mother and baby, with most pregnancies successful. Hemorrhage is the most common cause of death from AA during pregnancy. The published data are insufficient to guide management of a pregnant woman with AA, especially because it is clear that AA, in some cases, is serendipitously diagnosed and can persist beyond parturition. A woman who desires a child can be maintained with transfusions, with the understanding that any clinical deterioration is a criterion for interruption or termination of the pregnancy. The hazard of pregnancy to the woman who has recovered from immune AA is unknown, but most hematologists, recognizing the risk of relapse, advise patients not to become pregnant, especially if thrombocytopenia and a PNH clone are present. The risk associated with PNH has been now greatly reduced with the use of complement inhibitors.

Hepatitis

Hepatitis-associated AA has several distinctive features.9 Typically, an uneventful episode of apparent viral hepatitis in a young man is followed in 1 to 2 months, during convalescence from the liver inflammation, by very severe pancytopenia. Depression of blood cell counts during the course of hepatitis is common; leukopenia, atypical lymphocytosis, macrocytosis, and thrombocytopenia mimic in milder forms the hematologic changes of AA. However, posthepatitis AA has a very poor prognosis, with early estimates of mortality of 90% at one year, and a history of AA with hepatitis has been considered an indication for early stem cell transplantation. Patients with posthepatitis AA can successfully undergo stem cell transplantation without an increased risk of venoocclusive disease. Patients with hepatitis-associated aplasia have markers of immune system activation and respond to intensive immunosuppressive therapy. Almost all cases have been non-A, non-B, non-C hepatitis. Posthepatitis AA is linked to fulminant hepatitis of childhood and acute seronegative hepatitis. Acute viral hepatitis that is seronegative differs clinically from hepatitis C disease; parenteral exposure is not a risk factor, liver functions abnormalities are more severe during the acute phase, and late complications are more common. Even next generation sequencing has failed to find evidence of infection in acute seronegative hepatitis, making the likely mechanism immune.

Postmononucleosis Aplastic Anemia

Acute infection with Epstein-Barr virus (EBV) causes infectious mononucleosis that is commonly associated with neutropenia and other hematologic abnormalities, but, like acute hepatitis, is only rarely complicated by AA. Pancytopenia can be first observed during the acute mononucleosis syndrome or shortly thereafter. Some patients have recovered spontaneously, and others after therapy with corticosteroids or antithymocyte globulin (ATG). EBV can occasionally be demonstrated in the BM cells of patients with AA, in association with serologic evidence of a primary or reactivated viral infection.

Hemophagocytic Syndrome

 The BM is hypocellular in approximately one-third of the cases with hemophagocytic syndrome. In this disorder, there can be progression from BM hypercellularity to aplasia; myelofibrosis is also common. Pancytopenia occurs in most cases; anemia is a universal finding; thrombocytopenia and neutropenia are also common. In contrast to typical AA, these patients are systemically ill and have a fulminant course, with fever and constitutional symptoms, and peripheral blood count depression is often associated with abnormalities of other organ systems: hepatosplenomegaly, elevation of transaminases lymphadenopathy, cutaneous eruptions, and pulmonary infiltrates. The syn drome is associated with a wide variety of diseases. In the infectious category, viral infections are most common and include EBV, cytomegalovirus (CMV), herpes simplex, herpes zoster, B19 parvovirus, and HIV-1; bacterial and parasitic infections have also been associated with hemophagocytosis. Hemophagocytosis can be observed on supravital or Wright-Giemsa staining of the BM of patients with immune AA, and it is also a morphologic feature of graft rejection after BM transplantation. In virus-associated hemophagocytosis, there is evidence of immune system activation. The sera of patients contain high levels of IFN-γ, TNF-α, interleukin (IL)-6, soluble CD8, and soluble IL-2 receptor, and T cells overproduce IFN-γ in vitro. The clinical response to cyclosporine or anti-IFN-γ is consistent with a T cell–mediated hematopoietic failure state. In younger patients, hereditary forms of the syndrome (familial hemophagocytic lymphohistiocytosis [HLH])) are most common and should be investigated by appropriate testing for germline alterations, chiefly PRF1 or UNC13D genes. Secondary hemophagocytic syndrome in adults can be a presentation of lymphomas.

Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia

 There is a strong association between AA and PNH. These diseases are frequently diagnosed concurrently or sequentially in the same individual, and they share similar clinical and pathologic features. The presence of an expanded PNH clone is associated with HLA-DR15, and has been reported as a good prognostic marker for responsiveness to immunosuppressive therapy. Clinical BM failure can be present at the onset of PNH or can develop after diagnosis. By flow cytometry of granulocytes for glycosylphosphoinositol-anchored proteins, there is expansion of a PNH clone in 50% or more of AA cases at presentation. Longitudinal studies of patients with de novo PNH or PNH developing from AA indicate a low probability of spontaneous remission; in most patients, the contribution of the PNH clones remains stable for years, buthemolytic PNH with frank hemolysis can develop in up to 15% of patients.

Rheumatologic Diseases

AA is a component of the collagen vascular syndrome called eosinophilic fasciitis. This severe, scleroderma-like disease is characterized by fibrosis of subcutaneous and fascial tissue, localized skin induration, eosinophilia, hypergammaglobulinemia, and an elevated erythrocyte sedimentation rate. The rheumatologic symptoms of fasciitis respond to corticosteroids, but the associated AA has a very poor prognosis. A few patients have survived after BM transplantation or immunosuppressive therapy. More rarely, AA has complicated systemic lupus erythematosus and rheumatoid arthritis, but in many cases, the role of concomitant drug therapy is confounding. Rarely, AA can accompany Sjögren syndrome, multiple sclerosis, and immune thyroid disease. AA occasionally occurs in individuals with hypogammaglobulinemia or congenital immunodeficiency syndrome, thymoma, or thymic hyperplasia.

اخر الاخبار

اخبار العتبة العباسية المقدسة

المجمع العلمي يقيم مهرجانًا بذكرى الولادات الشعبانية في بغداد

معهد القرآن الكريم النسوي يباشر استعداداته لإقامة مهرجان السقاء القرآني السنوي الخامس

بالتعاون مع جامعة ستانفورد.. جامعة الكفيل تعتمد منهجًا متطورًا لطب الطوارئ

سماحة السيد الصافي يستقبل وفد شركة (سيتي فارما) الباكستانية المختصة في الأدوية

المزيد

الآخبار الصحية

اللحظات الأخيرة قبل الموت.. هذا هو تسلسل "فقدان الحواس"

وخز الأطراف وضعف الذاكرة.. علامات على نقص فيتامين هام

عادة صباحية بسيطة.. تأثيرها قد يحسن ضغط الدم

عادات يومية تدمر قلبك بصمت.. خبراء يطلقون التحذير

المزيد

الآخبار التكنلوجية

الذكاء الاصطناعي يفك لغز آثار أقدام الديناصورات

القمر أولا.."سبيس إكس" تؤجل خططها الخاصة بالرحلات إلى المريخ

الذكور أم الإناث؟ دراسة "تنسف الشائع" بشأن التوحد

خبير يكشف عن اقتراب العلماء من فك شفرات "لغات الحيوانات" !

المزيد

مواضيع ذات صلة

Hyperthyroidism: Etiology and Treatment

Clinical Features of Hyper- and Hypothyroidism

Typical and Atypical Presentations of Aplastic Anemia

Pathophysiologic Pathways Leading to Aplastic anemia

Epidemiology of Aplastic anemia

Pneumonia

Bronchitis

Pathogenesis of the respiratory tract: Microorganism Factors

Pathogenesis of the respiratory tract: Host Factors

Clinical Manifestations of Bloodstream Infections

Definition of Sepsis

Types of Bloodstream Infections