SAA patients don't generally share demographic features, but a medical history of seronegative hepatitis no longer than a year before presentation may be indicative of post-hepatitis SAA. Moreover, any reference to previous episodes of hematological disorders should be taken into account even though they may not have been related to clinical symptoms.

Symptoms associated with SAA correspond to those of severe anemia, thrombocytopenia and - usually during later stages of the disease - neutropenia.

• Anemia typically manifests in form of poor performance, fatigue, headaches and dizziness. Patients may report tachycardia, palpitations and dyspnea, particularly when under exercise. They may appear cyanotic.
• Thrombocytopenia is consistent with an increased bleeding propensity. SAA patients may thus report to be prone to hematoma, and they may show petechiae.
• Since neutrophils play an essential role in host defense against bacterial pathogens, neutropenia renders the affected individual very susceptible to bacterial infection. SAA patients may thus present with any type of infection, most commonly with stomatitis and gingivitis, upper respiratory infection, pneumonia, and urinary tract infection.

Pancytopenia as well as any combination of anemia, thrombocytopenia and neutropenia may also be diagnosed incidentally during routine analyses of blood samples. Single hematological disorders don't usually prompt a suspicion of SAA, those patients are often treated with standard therapies, e.g., dietary supplementation of iron, folate or vitamin B12, administration of corticosteroids.

• Easy Bruising

  Platelets are responsible for normal blood clotting and low numbers can result in easy bruising and bleeding which can be deadly. [clinicaltrials.gov]

  These include fatigue, shortness of breath, fever, recurrent infections, easy bruising or unusual bleeding. [leukemiabmtprogram.org]

  Some symptoms include tiredness, paleness, frequent infections, and easy bruising and bleeding. Aplastic anemia is diagnosed with blood and bone marrow tests. Treatment depends on the cause. [urmc.rochester.edu]

  Signs and symptoms of aplastic anemia include fatigue, infections that last a long time, and easy bruising or bleeding. [nhlbi.nih.gov]

• Anemia

  […] issues related to transplantation for severe aplastic anemia. [aspho.org]

  Red blood cells are responsible for carrying oxygen to all of the organ systems in the body, and low numbers (anemia) can cause difficulty breathing and fatigue. [clinicaltrials.gov]

  It has been associated with hematologic disorders, such as aplastic anemia. The clinical features and long-term outcomes of patients with eosinophilic fasciitis and associated aplastic anemia have been poorly described. [ncbi.nlm.nih.gov]

  Here, moderate aplastic anemia (MAA), severe aplastic anemia (SAA) and very severe aplastic anemia (VSAA) are distinguished. [symptoma.com]

• Fatigue

  Patients typically have fatigue, infections, and increased or unusual bleeding. A bone marrow biopsy establishes the diagnosis. Treatment includes hematopoietic stem cell transplant or immunosuppressive therapy. [ncbi.nlm.nih.gov]

  Red blood cells are responsible for carrying oxygen to all of the organ systems in the body, and low numbers (anemia) can cause difficulty breathing and fatigue. [clinicaltrials.gov]

  Symptoms include chronic anemia, fatigue, yellow skin and eyes (jaundice), pale skin, and missing fingers and toes at birth. Some people never need treatment. [webmd.com]

  These include fatigue, shortness of breath, fever, recurrent infections, easy bruising or unusual bleeding. [leukemiabmtprogram.org]

  It stops production of blood cells and causes fatigue, and can lead to infections and excessive bleeding. This condition can happen at any age, and often occurs suddenly. [mazecordblood.com]

• Fever

  Dengue fever has rarely been reported as an etiology for aplastic anemia. An 8-year-old girl was admitted with fever, myalgia and petechiae. Dengue virus IgM antibodies were positive. She recovered completely, but her thrombocytopenia persisted. [ncbi.nlm.nih.gov]

  A rare association between dengue fever and AA has been reported. Dengue fever is a disease endemic to the western region of Saudi Arabia. [omicsonline.org]

• Weakness

  You end up feeling weak, tired, and short of breath. Anemia comes in many forms. Iron-deficiency anemia is most common. Other types of the disease affect only small numbers of people. [webmd.com]

  The most common symptom of all anemias is weakness. [everydayhealth.com]

  When you are anemic, your body does not transport oxygen efficiently and this can make you tired and weak. RBCs carry oxygen using a protein called hemoglobin. Hemoglobin is necessary for efficient oxygen transport. [healthline.com]

  Symptoms of chronic aplastic anemia include weakness and fatigue in the early stages, followed by shortness of breath, headache, fever, and pounding heart. [britannica.com]

• Pain

  She also complained of pain in the palatal area and the mandibular anterior region. [ncbi.nlm.nih.gov]

  Sickle cells are stiff and sticky and tend to block blood flow in the vessels of the limbs and organs, causing pain and raising the risk for infection. [everydayhealth.com]

  Symptoms for both types include: Chest pain Fast heartbeat, or tachycardia Headaches Trouble breathing Weakness and fatigue Treatment for sideroblastic anemia depends on the cause. [webmd.com]

  Radiation therapy- radiation may help a small number of people who have bone pain. It can also help reduce the size of the spleen, when surgical removal isn't an option. [ohsu.edu]

• Pneumonia

  Although the patient had pneumonia on day 11, it was resolved promptly after engraftment on day 16. [ncbi.nlm.nih.gov]

  SAA patients may thus present with any type of infection, most commonly with stomatitis and gingivitis, upper respiratory infection, pneumonia, and urinary tract infection. [symptoma.com]

  Fungal pneumonias decreased from 30% to 3% ( P P = .05). Aspergillus species were the most common fungal pathogens recovered in this patient population. Table 4. [cid.oxfordjournals.org]

  के लिए नियमित टीकाकरण से लाभ आज influenzae, S. influenzae, एस pneumoniae, and Neisseria meningitidis. pneumoniae, और Neisseria meningitidis. [helpebookhindi.wikifoundry.com]

• Dyspnea

  A 16-yr-old male patient with hemochromatosis due to multiple packed red blood cell transfusions was referred to our emergency center for the treatment of severe aplastic anemia and dyspnea. He was diagnosed with aplastic anemia at 11-yr of age. [ncbi.nlm.nih.gov]

  Patients may report tachycardia, palpitations and dyspnea, particularly when under exercise. They may appear cyanotic. Thrombocytopenia is consistent with an increased bleeding propensity. [symptoma.com]

  CASE A 60-year-old woman who complained of cough and dyspnea visited the Pulmonary Department in April 2000. Chest radiography and computed tomography (CT) showed a large mass in the anterior mediastinum, compatible with a thymoma ( Figure 1 ). [kjim.org]

  Aplastic anemia may present with the following signs and symptoms: Fatigue Dyspnea on exertion Easy bruising and bleeding (for example, epistaxis, gum bleeding, heavy menses, subconjunctival hemorrhages, melena, etcetera.) [cancertherapyadvisor.com]

  Specific manifestations include the following: Anemia: May manifest as pallor, headache, palpitations, dyspnea, fatigue, or foot swelling Thrombocytopenia: May result in mucosal and gingival bleeding or petechial rashes Neutropenia: May manifest as overt [emedicine.medscape.com]

• Loss of Appetite

  Have a loss of appetite or lose weight. Have paler-than-normal skin. Have trouble breathing. Have rapid heartbeat. Have reduced ability to exercise or climb stairs. Low White Blood Cell Count A low white blood cell count is called neutropenia. [aamds.org]

• Palpitations

  Patients may report tachycardia, palpitations and dyspnea, particularly when under exercise. They may appear cyanotic. Thrombocytopenia is consistent with an increased bleeding propensity. [symptoma.com]

  Anaemia due to lack of red blood cells – weakness, tiredness, shortness of breath, light-headedness, palpitations. [leukaemiacare.org.uk]

  Clinical manifestations are proportional to the peripheral-blood cytopenias and include: Patients with aplastic anaemia most commonly present with symptoms of anaemia (pallor, headache, palpitations, dyspneoa, fatigue, or ankle oedema) and thrombocytopenia [patient.info]

  Specific manifestations include the following: Anemia: May manifest as pallor, headache, palpitations, dyspnea, fatigue, or foot swelling Thrombocytopenia: May result in mucosal and gingival bleeding or petechial rashes Neutropenia: May manifest as overt [emedicine.medscape.com]

• Tachycardia

  Symptoms for both types include: Chest pain Fast heartbeat, or tachycardia Headaches Trouble breathing Weakness and fatigue Treatment for sideroblastic anemia depends on the cause. [webmd.com]

  Patients may report tachycardia, palpitations and dyspnea, particularly when under exercise. They may appear cyanotic. Thrombocytopenia is consistent with an increased bleeding propensity. [symptoma.com]

  Physical Examination Physical examination may show signs of anemia (eg, pallor, tachycardia) and of thrombocytopenia (eg, petechiae, purpura, ecchymoses). Overt signs of infection are usually not apparent at diagnosis. [emedicine.medscape.com]

  अविकासी संकट रोगी के आधारभूत रक्ताल्पता की भारी worsenings हैं, पीलापन, tachycardia उत्पादक, और थकान. This crisis is triggered by parvovirus B19, which directly affects erythropoiesis (production of red blood cells). [helpebookhindi.wikifoundry.com]

• Bleeding Gums

  The intraoral examination identified bleeding gums; petechiae of the palate, tongue and cheek mucosa; and an atrophic, smooth and shining dorsal surface of the tongue. [ncbi.nlm.nih.gov]

  When present, signs and symptoms can include: Fatigue Shortness of breath Rapid or irregular heart rate Pale skin Frequent or prolonged infections Unexplained or easy bruising Nosebleeds and bleeding gums Prolonged bleeding from cuts Skin rash Dizziness [mayoclinic.org]

  Physical findings : • Anemia with fatigue and pallor; • Bruising; • Petechiae (non-raised hemorrhage in the skin or in a membrane); • Bleeding gums; • Bleeding of internal organs; • Frequent or severe infections; • Nosebleeds; • Rapid heart rate; • Rash [secure.ssa.gov]

  Symptoms include: Bleeding gums Easy bruising Nose bleeds Rash, small pinpoint red marks on the skin (petechiae) Frequent or severe infections (less common) Mild cases of aplastic anemia that do not have symptoms may not require treatment. [nlm.nih.gov]

• Jaundice

  Symptoms include chronic anemia, fatigue, yellow skin and eyes (jaundice), pale skin, and missing fingers and toes at birth. Some people never need treatment. [webmd.com]

  He was noted to have diffuse jaundice, hepatomegaly, and mild epigastric tenderness on examination. [hindawi.com]

  If you have PNH, you have a higher risk of developing blood. which can cause symptoms such as severe leg, abdominal or chest pain, shortness of breath, jaundice or headache. [ohsu.edu]

  A preceding history of jaundice, usually 2-3 months before, may indicate a post-hepatitic aplastic anaemia. The history should include drug exposure and occupation (exposure to chemicals or pesticides). [patient.info]

• Arthralgia

  Serum sickness, characterized by fever, skin rash, arthralgia, and serpentinous lesions on palms and soles, was observed in two patients (8%) and resolved with administration of prednisone. [scielo.br]

• Osteoporosis

  Other conditions that will put you under the prescription of winstrol include decubitus ulcers, aplastic anemia, osteoporosis, decreased fibrinolytic activity, or growth failure. [tr-ex.me]

• Petechiae

  An 8-year-old girl was admitted with fever, myalgia and petechiae. Dengue virus IgM antibodies were positive. She recovered completely, but her thrombocytopenia persisted. Six weeks later she became pancytopenic. [ncbi.nlm.nih.gov]

  Symptoms result from anemia, thrombocytopenia (petechiae, bleeding), or leukopenia (infections). Diagnosis requires demonstration of peripheral pancytopenia and a bone marrow biopsy revealing a hypocellular marrow. [msdmanuals.com]

  Physical findings : • Anemia with fatigue and pallor; • Bruising; • Petechiae (non-raised hemorrhage in the skin or in a membrane); • Bleeding gums; • Bleeding of internal organs; • Frequent or severe infections; • Nosebleeds; • Rapid heart rate; • Rash [secure.ssa.gov]

• Purpura

  This initial indication was for adult patients with chronic immune thrombocytopenic purpura (ITP) following an insufficient response to corticosteroids, immunoglobulins, or splenectomy. [onclive.com]

  Mild anemia and macrocytosis may indicate SAA in patients otherwise possibly diagnosed with immune thrombocytopenic purpura. [symptoma.com]

  Aplastic anemia and idiopathic thrombocytopenic purpura with antibody to platelet glycoprotein IIb/IIIa following resection of malignant thymoma. Acta Haematol 90:42–451993. 5. Dinol G, Saka B, Aktan M, Nalaci M, Keskin H. [kjim.org]

  This means a persistent hematocrit of 26% or less and reticulocyte (recently produced red blood cell) count of 4% or greater, or purpura (bleeding under the skin) and thrombocytopenia (reduced platelet count) of 40,000 platelets/cu.mm. or less despite [disabilitysecrets.com]

• Tinnitus

  Other symptoms may include a waxy pallor to the skin and mucous membranes, bleeding gums, a lack of energy during exercise, and tinnitus (ringing in the ears). Premenopausal women may have an increased menstrual flow and duration. [chealth.canoe.com]

• Headache

  Share on Pinterest Headaches, dizziness, and fatigue are common symptoms of aplastic anemia. When a person has aplastic anemia, their bone marrow does not create the blood cells it needs. [medicalnewstoday.com]

  Anemia typically manifests in form of poor performance, fatigue, headaches and dizziness. Patients may report tachycardia, palpitations and dyspnea, particularly when under exercise. They may appear cyanotic. [symptoma.com]

  When receiving the treatment, some common side effects are: Chills Fever Hives Nausea Vomiting Diarrhea Dizziness Headache These side effects usually go away after treatment. Horse vs. [aamds.org]

  Symptoms of chronic aplastic anemia include weakness and fatigue in the early stages, followed by shortness of breath, headache, fever, and pounding heart. [britannica.com]

  The most common adverse reactions were nausea (33%), fatigue (28%), cough (23%), diarrhea (21%), and headache (21%). [onclive.com]

• Difficulty Concentrating

  Symptoms of systemic mastocytosis include allergic skin reactions, difficulty concentrating and diarrhea. Doctors diagnose systemic mastocytosis by taking a small tissue sample called a biopsy. [ohsu.edu]

As per definition, SAA may be diagnosed if a patient presents with bone marrow cellularity <25% (up to 50% in case less than a third of visible cells correspond to hematopoietic stem cells) and at least two of the following: neutropenia with <0.5×10^9/l, thrombocytopenia with <20×10^9/l and reticulocyte counts <20×10^9/l [1]. Accordingly, diagnosis of SAA requires the analysis of bone marrow specimens and blood samples.

In SAA patients, complete blood count and reticulocyte count usually reveal pancytopenia and decreased levels of reticulocytes; lymphopenia is rare. The mean corpuscular volume is often augmented. Mild anemia and macrocytosis may indicate SAA in patients otherwise possibly diagnosed with immune thrombocytopenic purpura. It may be recommendable to repeat laboratory analyses of blood samples to rule out temporary anomalies due to medication or environmental factors.

In order to evaluate the condition of the bone marrow, both aspirates and biopsy specimens should be analyzed [1]. Hypocellularity and prominent fat spaces are the hallmarks of SAA, and besides overall reduced hematopoiesis and lack of myeloid progenitor cells, dyserythropoiesis may also be observed. In contrast, excess blasts, striking dysplasia or hemophagocytosis are not characteristic of SAA. Upon cytogenetic analysis, bone marrow cells of most SAA patients do not show any chromosomal aberrations. In only 10% of samples, monosomy or trisomy may be detected [16]. These are not necessarily incompatible with a good response to immunosuppressive treatment.

• Neutropenia

  The authors present a case with severe aplastic anemia that did not respond to classic and immunosuppressive treatment for disease and developing invasive cardiac mucormycosis despite empiric treatment for febrile neutropenia. [ncbi.nlm.nih.gov]

  Pancytopenia as well as any combination of anemia, thrombocytopenia and neutropenia may also be diagnosed incidentally during routine analyses of blood samples. [symptoma.com]

• Cytopenia

  His cytopenia and organ dysfunctions began to be gradually recovered since about 2002, following a 4-yr deferoxamine treatment. He showed completely normal ranges of peripheral blood cell counts, heart size, and liver function two years ago. [ncbi.nlm.nih.gov]

  These cytopenias include agranulocytosis, PRCA and aplastic anemia. In fact, the overall long-term survival of patients with thymoma is poor once cytopenias occur. [kjim.org]

  The term aplastic anemia commonly implies a panhypoplasia of the marrow with cytopenias in at least two hematopoietic lineages. In contrast, pure RBC aplasia is restricted to the erythroid cell line. [msdmanuals.com]

  Treatment should be based on the degree of cytopenia, not the marrow cellularity. Patients with asymptomatic cytopenias probably need no treatment. [patient.info]

• Leukopenia

  Symptoms result from anemia, thrombocytopenia (petechiae, bleeding), or leukopenia (infections). Diagnosis requires demonstration of peripheral pancytopenia and a bone marrow biopsy revealing a hypocellular marrow. [msdmanuals.com]

  Low red cell count (anemia) can cause: Fatigue Pallor (paleness) Rapid heart rate Shortness of breath with exercise Weakness Lightheadedness upon standing Low white cell count (leukopenia) causes an increased risk for infection. [mountsinai.org]

  TESTING, PHYSICAL FINDINGS, AND ICD-9-CM CODING Diagnostic testing : Bone marrow aspirate and biopsy is required for diagnosis and to rule out other causes of pancytopenia such as cancer or infection; blood counts documenting anemia, thrombocytopenia, leukopenia [secure.ssa.gov]

• Macrocytic Anemia

  Anemias can also be described based on the RBC size and concentration of hemoglobin in them. If cell size is much smaller than normal, it is known as microcytic anemia. If it is much bigger than normal, then it is macrocytic anemia. [labtestsonline.org]

  Diamond-Blackfan anemia Diamond-Blackfan anemia (DBA) is characterized by a normochromic macrocytic anemia that can be isolated, or it can be associated with growth retardation or congenital malformation in the upper limbs, heart, and genitourinary systems [emedicine.medscape.com]

• Macrocytosis

  Mild anemia and macrocytosis may indicate SAA in patients otherwise possibly diagnosed with immune thrombocytopenic purpura. [symptoma.com]

  Although the anemia is often normocytic, mild macrocytosis can also be observed in association with stress erythropoiesis and elevated fetal hemoglobin levels. [emedicine.medscape.com]

SAA patients require supportive care and causative treatment. Contrary to MAA, watchful waiting is not an option in SAA [17].

Immediate medical attention should be provided to compensate for the effects of pancytopenia. Patients suffering from anemia, thrombocytopenia and a bleeding diathesis should receive transfusions of the respective blood products. Additional measures should be taken to avoid trauma and further hemorrhages. Antimicrobials may be administered both prophylactically and therapeutically to prevent or manage bacterial infections. Broad spectrum antibiotics are indicated to this end; underdosing and early termination of drug therapy should strictly be avoided. SAA patients are also at high risks of fungal infections, but prophylactic use of antimycotics has so far only been recommended for VSAA patients [18]. As a general measure to prevent infection, patients should be advised to avoid contact with garbage and compost, and possibly with animals and plants.

With regards to causative therapy, immunosuppression by means of the combined administration of antithymocyte globulin and cyclosporin A is the approach of choice. In most patients, hematopoiesis can be restored this way [13]. Some patients only show partial responses to immunosuppressive therapy and may later be considered for HSCT. Indeed, experts recommend to refer every SAA patient for HSCT if a matched sibling donor is available [19] [20]. In case of partial or non-responders to immunosuppressive treatment and in the absence of a matched sibling donor, HSCT by an unrelated matched donor should be offered. Of note, the prophylactic measures described above should be maintained during the first months after initiation of immunosuppressive therapy or HSCT.

Survival rates of AA patients have constantly been increasing. To date, 68% of AA patients who receive immunosuppressive treatment are alive ten years after the initial diagnosis and this also applies to 73% of individuals who were treated with HSCT [15]. In the 1990s, the 3-months-survival was 73% [11]. Old age continues to be an unfavorable prognostic factor. Furthermore, disease severity negatively correlates with survival and patients diagnosed with MAA generally have a better prognosis than those suffering from SAA.

If left untreated or if the patient does not respond to therapy, they are at risk of life-threatening hemorrhages or develop severe immunodeficiency, recurrent infections and eventually lethal sepsis open link. Clonal disease due to aggressive immunosuppression and complications of HSCT are the main risks associated with available treatment options.

Congenital AA is a very rare condition, with the most common underlying disease being Fanconi anemia. Fanconi anemia is inherited with an autosomal recessive trait and results from mutations of genes encoding for the so-called Fanconi anemia complementation group proteins. Accordingly, these genes have been designated FANC genes. The respective gene products are involved in recognition and repair of DNA damage [4]. Furthermore, congenital AA has occasionally been related to Shwachman-Diamond syndrome or Diamond-Blackfan syndrome [5].

More commonly, SAA is acquired. In recent years, acquired SAA has increasingly been recognized as an autoimmune disease characterized by T cell-mediated destruction of hematopoietic stem cells. According to current knowledge, autoreactive, cytotoxic CD8+ T cells play a key role in AA pathogenesis [6]. These cells trigger a type 1 autoimmune response dominated by cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), which may induce expression of Fas receptor and subsequent apoptosis of CD34+ stem cells and which impair proliferation of progenitor cells [7]. Still, little is known about the trigger of this autoimmune reaction. Historically, AA has been related to numerous infectious, non-infectious diseases, exposure to physical and chemical noxious agents. AA may follow an episode of seronegative hepatitis, or may be associated with eosinophilic fasciitis or pregnancy [8].

The overall incidence of AA is two cases per million per year in the western world [8]., with this number comprising MAA, SAA as well as VSAA. Interestingly, incidence rates in Asia are more than twice as high. This observation implies higher exposure to etiologic agents in the respective geographic regions, which led to the suspicion of infectious pathogens to act as triggers of the autoimmune response underlying the disease [9]. Despite its low incidence, SAA is still the most common condition prompting HSCT besides myeloid and lymphoid malignancies.

AA may affect patients of both genders and all age groups, but about half of all cases are diagnosed in individuals aged less than 30 years [8]. Adults aged 30 to 60 years are least frequently affected and incidence rises again among the elderly. With regards to the severe form of the disease, a trend towards an increase of incidence with age has been reported recently [10]. In that same study, a male predominance has been observed. Similar results have been obtained in other retrospective studies [11].

The autoimmune response underlying acquired SAA is triggered by an as-of-yet unknown stimulus, possibly by bacterial or viral pathogens or non-infectious agents. This stimulus is directly followed by clonal expansion of cytotoxic T cells that mediate the destruction of hematopoietic stem cells by means of distinct downstream events:

• Proliferation of cytotoxic T cells is induced by interleukin-2 (IL-2), and while this process is usually subjected to control and suppression by regulatory T cells (T_reg), the vast majority of AA patients presents with depleted T_reg populations [12]. Proliferation of autoreactive T cells thus becomes self-containing since new clones continue to release IL-2. Of note, recovery of T_reg cell counts and function is considered an indicator of response to therapy. On the other hand, further impairment of immunoregulatory mechanisms by immunosuppressive therapy may favor the development of myeloproliferative disorders like myelodysplasia and acute myelocytic leukemia or paroxysmal nocturnal hemoglobinuria [13].
• Cytotoxic T cells also release IFN-γ and TNF-α, and those cytokines induce the expression of cell death surface receptor Fas on CD34+ hematopoietic stem cells. In fact, the autoimmune reaction displayed by SAA patients is mainly directed against CD34+ stem cells [14]. Binding of Fas ligand to Fas receptor induces apoptosis. Accordingly, a good response to therapy is associated with a reduction of Fas expression by those cells.

Families affected by congenital SAA may benefit from genetic counselling. With respect to acquired SAA, specific measures cannot be recommended due to remaining knowledge gaps regarding the disease etiology.

Aplastic anemia (AA) is a rare, potentially life-threatening hematological disorder provoked by bone marrow failure and extensive disturbances of hematopoiesis. Patients may suffer from congenital or acquired AA, and this distinction implies a heterogenous etiology for this condition: Congenital AA results from genetic defects, acquired AA is nowadays considered an autoimmune disease.

Furthermore, AA cases may be classified according to the severity of the disease. Here, moderate aplastic anemia (MAA), severe aplastic anemia (SAA) and very severe aplastic anemia (VSAA) are distinguished. As has been indicated above, the clinical hallmark of AA is pancytopenia and accordingly, peripheral blood cell counts reflect the severity of hematopoietic defects [1].:

For SAA to be diagnosed, at least two of the aforementioned cell count criteria should be fulfilled. Furthermore, bone marrow hypocellularity with cell counts reduced to <25% of physiological values are required.

Hematopoietic stem cell transplantation (HSCT) is curative in both congenital and acquired SAA, but the limited availability of matched donors as well as the high risk of complications restrict its application. Considerable shares of patients suffering from acquired SAA respond to immunosuppressive therapy [2]. - a fact that prompted research efforts as to the autoimmune nature of AA -, but myeloproliferative disorders like myelodysplasia and acute myelocytic leukemia may be induced by such treatment. The risk of clonal disease after immunosuppressive therapy has been estimated to be about 3% [3].

Human blood consists of many different types of cells, mainly of erythrocytes (also called red blood cells, they carry oxygen), leukocytes (also known as white blood cells, they constitute essential parts of the immune system) and platelets (required for coagulation). All these cells originate from hematopoietic stem cells in the bone marrow which differentiate from progenitor cells and other developmental stages until finally turning into mature blood cells. Thus, disturbances of blood cell formation at a very early stage, namely at the level of hematopoietic stem cells, results in reduced cell counts of all blood cells. This condition is termed pancytopenia. It is the hallmark of aplastic anemia, whereby "aplastic" refers to the disease affecting the formation of blood cells in the bone marrow and "anemia" describes the shortage of red blood cells, which commonly manifests first. If cell counts of erythrocytes, leukocytes and platelets are severely reduced, the patient may be diagnosed with severe aplastic anemia (SAA).

Symptoms associated with SAA are those of anemia, leukocytopenia and thrombocytopenia, i.e., lack of the respective populations of blood cells. Anemia most frequently causes fatigue, headaches and dizziness; thrombocytopenia provokes a tendency to bleed. Patients may note themselves prone to hematomas and observe small bleedings in the skin. Leukocytopenia renders the patient susceptible to infections, but typically manifests at later stages. Patients may tend to contract stomatitis, gingivitis, upper respiratory infection or pneumonia, among others.

If a patient is diagnosed with SAA, they will receive supportive care to compensate for pancytopenia. This may comprise transfusion of blood products and prophylactic and therapeutic use of antimicrobials. Eventually, causative treatment is required. Immunosuppressive therapy is effective in the majority of patients and is preferred if siblings who may donate stem cells are not available. Otherwise, the patient is referred to for stem cell transplantation. Ideally, these cells are donated by a suitable sibling, but they may also be donated by a non-related person.

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