Specific manifestations include the following:

• Anemia manifests as pale skin, palpitations, dyspnea, etc.
• Leukopenia results as frequent, reccurent infections and fever
• Thrombocytopenia causes easy bruising, nose bleeds, bleeding of gums and unexplained bleeding of the internal organs

Systemic and general symptoms may include weakness, exhaustion and loss of appetite.

• Easy Bruising

  HIV infection should also be ruled out especially if the patient presents with pancytopenia and a combination of fatigue, easy bruising, spontaneous bleeding, fever, rigors. [info.isabelhealthcare.com]

  Leukopenia results as frequent, reccurent infections and fever Thrombocytopenia causes easy bruising, nose bleeds, bleeding of gums and unexplained bleeding of the internal organs Systemic and general symptoms may include weakness, exhaustion and loss [symptoma.com]

  In addition to fatigue and easy bruising, the patient reports a history of unexplained lower extremity swelling and recurrent herpes infections. [hematology.org]

  Affected patients may complain of fatigue, easy and prolonged bleeding, easy bruises, frequent infections, and abdominal discomfort. The vast majority of patients with HCL have splenomegaly (prevalence ranges from 66% to 100%) [8–11]. [hindawi.com]

• Hemophilia A

  However, hematological side effects can be seen with this drug, for example thrombotic/thrombocytopenic purpura, neutropenia, acquired hemophilia, and isolated thrombocytopenia. [archivesofrheumatology.org]

• Anemia

  Figure 1: (a) 6yr/female diagnosed as Aplastic anemia. Bone marrow aspiration, (b) 6yr/female diagnosed as Aplastic anemia. Bone marrow biopsy Click here to view Figure 2: 35yr/male diagnosed as megaloblastic anemia. [mjdrdypu.org]

  neutropenia Consider appropriate consults (e.g. heme/onc, infectious disease) Disposition See Also Anemia Thrombocytopenia Neutropenia, Leukopenia Immunocompromised antibiotics Aplastic anemia External Links References [wikem.org]

  The commonest cause for pancytopenia was megaloblastic anemia (74.04%), followed by aplastic anemia (18.26%). [jlponline.org]

  Key Words: Aplastic Anemia, Bone Marrow Biopsy, Megaloblastic Anemia, Pancytopenia INTRODUCTION Pancytopenia is the simultaneous presence of anemia, leucopenia and thrombocytopenia. [ncbi.nlm.nih.gov]

  Dimorphic anemia (46%) was the predominant blood picture followed by macrocytic anemia. The commonest bone marrow finding was megaloblastic erythroid hyperplasia. [jmscr.igmpublication.org]

• Weakness

  The symptoms are numerous and may include weakness, fatigue, frequent infections, bruising or spontaneous bleeding. Treatment can be various and depends on the etiology. [symptoma.com]

  However, approximately within 3 weeks of continuing the prescribed drugs, the patient was readmitted for complaints of loose watery stools, weakness, and giddiness. [ncbi.nlm.nih.gov]

  The next common complaint was easy fatigability and weakness, seen in 20% each. In a study by Khodke et al., fever (40%) was the most common symptom followed by weakness (30%) and bleeding manifestation (20%). [mjmsr.net]

  Exposures to ionizing radiation, EBV, organic chemicals, woodworking, and farming have been cited as possible causes.4 Symptoms of hairy cell leukemia include fatigue, weakness, and weight loss. [mdedge.com]

• Sepsis

  He was admitted for severe sepsis related to the L1-L2 region osteomyelitis and discitis. [cureus.com]

  While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's syndrome), it is also important to consider the diagnosis of hypopituitarism [ncbi.nlm.nih.gov]

  ‘Despite initial pancytopenia and neutropenic sepsis, she has tolerated three cycles of chemotherapy.’ ‘One month after laparotomy, laboratory studies showed the development of pancytopenia with normocytic red cells.’ [en.oxforddictionaries.com]

• Weight Loss

  She also notes a 1 year history of intermittent fevers, fatigue, chills, night sweats, weight loss, and LUQ abdominal fullness. On exam, she was noted to be febrile to 39.3 with diffuse lymphadenopathy and splenomegaly. [uscmedicine.blog]

  A 27-year-old male patient who presented to the emergency room with complaints of sweating, palpitations, heat intolerance, insomnia and weight loss for the last 3 months. His medical history was significant for hypertension. [ncbi.nlm.nih.gov]

  Unexplained Weight loss 6. Itchy Skin Cancer Sourcebook 36. [slideshare.net]

  Reported is the case of a 58-year-old man who presented with dyspnea on exertion, fatigue, and unintentional weight loss. He was found to have severe anemia (hemoglobin 3.3 g/dL) in association with pancytopenia and hemolysis. [journalmc.org]

  One cannot forget about these possibilities while contemplating the more worrisome symptoms of the past 4 weeks, especially weight loss in a growing adolescent. [journalofhospitalmedicine.com]

• Short Stature

  Besides bone marrow failure, our patient had only modest clinical signs pointing to Fanconi anaemia in the form of slightly short stature and café-au-lait macules. [tidsskriftet.no]

  Other features which may be found on examination are short stature, structual abnormalities of limbs, eyes and ears, hyperpigmentation, café au lait spots, purpura or petechiae. [info.isabelhealthcare.com]

  Short stature is often secondary to hormonal deficiencies. Fertility is almost totally impaired in males, and is highly disturbed in half of females. Pregnancy is often complicated. [orpha.net]

  stature synovitis abnormal thumb 9. [slideshare.net]

  We were left with a diagnosis of IBMFS; however, the lack of the characteristic short stature, craniofacial abnormalities or pancreatic insufficiency associated with Shwachman-Diamond syndrome, the lack of the classic radial bone aplasia associated with [ncbi.nlm.nih.gov]

• Dyspnea

  CC: Dyspnea on exertion ID: 42 yo male with no past medical history presents with dyspnea on exertion and fatigue for 3 weeks. He becomes short of breath with walking ½ block when his baseline was walking miles. [uscmedicine.blog]

  Reported is the case of a 58-year-old man who presented with dyspnea on exertion, fatigue, and unintentional weight loss. He was found to have severe anemia (hemoglobin 3.3 g/dL) in association with pancytopenia and hemolysis. [journalmc.org]

  Background Anemia + Thrombocytopenia + Leukopenia Clinical Features Signs/symptoms of anemia (e.g. fatigue, dyspnea, tachycardia, pallor) Signs/symptoms of thrombocytopenia (e.g. petechiae/purpura, mucosal bleeding, GI bleed, hematuria, intracranial hemorrhage [wikem.org]

  A 36-year-old male with a history of HIV presents to the ED complaining of dyspnea on exertion and fatigue. He is homeless and has been poorly compliant with his anti-retroviral medications. [emdocs.net]

  Case: A 51-year old woman was admitted to the Hospital of Lithuanian University of Health Sciences, Kaunas clinics with 6 months history of tachycardia, bilateral leg oedema and progressive dyspnea. [endocrine-abstracts.org]

• Diarrhea

  Be careful: Travel history plus vomiting, diarrhea, anorexia, and abdominal pain may lead you to diagnosis Travelers Diarrhea. Complications P. falciparum leads to the most complications and deaths. [pedemmorsels.com]

  Symptoms at presentation included: oral mucositis (n = 37); fever (n = 24); diarrhea (n = 12), bleeding gums (n = 5) and purpura (n = 3). [ncbi.nlm.nih.gov]

  This is attributed to immune-mediated destruction of precursors in marrow as a consequence of bovine virus diarrhea vaccination of dams, with calves receiving offending allo-antibodies from colostrum. [eclinpath.com]

  Study done by Iqbal et al also included pediatric population and reported leishmaniasis in 4.8% of cases as compared to none seen in our study. 4 The major cause of megaloblastic anemia in our study is fever as 56.4% and chronic diarrhea (Table 2) as [ayubmed.edu.pk]

• Hematochezia

  Gastrointestinal bleeding due to colon cancer Iron-deficiency anemia, hematochezia, melena, a change in bowel habits, and abdominal pain may be manifestations of colon cancer. [mdedge.com]

  She had not had any melena, hematochezia, hematuria or hemoptysis. She recalled being told when she was pregnant that she was temporarily anemic, but she never required any treatment or blood transfusion. [healio.com]

  Furthermore, the patient denied a recent history of hematemesis, hematochezia or melena. [cureus.com]

• Blood in Stool

  An adult differential checklist for Pancytopenia will also take into account Paroxysmal nocturnal hemoglobinuria which may have symptoms of previous venous thrombosis, fatigue, intermittent abdominal pain, dark urine, blood in stool and pancytopenia. [info.isabelhealthcare.com]

• Hypertension

  His medical history was significant for hypertension. On examination, he was tachycardic, hypertensive, had tremors of the upper extremities and a smooth goitre with a thyroid bruit. [ncbi.nlm.nih.gov]

  Abdominal CT showed liver cirrhosis with splenomegaly related with portal hypertension. In the study of anemia, a severe deficiency of folic acid was discovered. [ejinme.com]

  CASE REPORT: A brain MRI of a 79-year-old female with a medical history of hypertension, Type II diabetes, and CVA revealed a right temporoparietal mass. [hsrc.himmelfarb.gwu.edu]

  Hypersplenism secondary to portal hypertension (cirrhosis) was the second most common diagnosis. Aplastic anemia, septicemia and myelodysplasia were other common causes of pancytopenia (Table 1). [ayubmed.edu.pk]

• Heart Disease

  CONTINUE SCROLLING OR CLICK HERE FOR RELATED SLIDESHOW SLIDESHOW Heart Disease: Causes of a Heart Attack See Slideshow [medicinenet.com]

  Some of the possible causes of pancytopenia include: Chemotherapy-induced bone marrow suppression Drug-induced: drugs other than chemotherapy drugs, from antibiotics to heart-disease medications, have been cited as causes. [verywellhealth.com]

  Some of the possible causes of pancytopenia may include: Chemotherapy-induced bone marrow suppression Drug-induced: Drugs other than chemotherapy drugs, from antibiotics to medications used for heart disease, have been cited as causes. [verywell.com]

• Bleeding Gums

  Symptoms at presentation included: oral mucositis (n = 37); fever (n = 24); diarrhea (n = 12), bleeding gums (n = 5) and purpura (n = 3). [ncbi.nlm.nih.gov]

  The list of symptoms is long, and each can vary in frequency and severity: Weakness Fatigue Skin problems, such as rashes or easy bruising Pale skin Rapid heart rate Shortness of breath Bleeding problems, such as bleeding gums, nosebleeds or internal [stjude.org]

  More severe pancytopenia can cause symptoms including: shortness of breath pale skin fatigue weakness fever dizziness easy bruising bleeding tiny purple spots on your skin, called petechiae larger purple spots on your skin, called purpura bleeding gums [healthline.com]

• Visual Impairment

  He was diagnosed with Johanson–Blizzard syndrome in infancy and had hypoplasia of alae nasi, hearing deficit (requiring aids), visual impairment, hypodontia (later) and exocrine pancreatic insufficiency. [nature.com]

• Hyperpigmentation

  Other features which may be found on examination are short stature, structual abnormalities of limbs, eyes and ears, hyperpigmentation, café au lait spots, purpura or petechiae. [info.isabelhealthcare.com]

  An interesting case of fever, pancytopenia and hyperpigmentation. Ann Trop Med Public Health 2013;6:586-8 How to cite this URL: Mangaraj S, Sethy G, Behera SK, Sahu NC. An interesting case of fever, pancytopenia and hyperpigmentation. [atmph.org]

  Their characterlstic associated abnormalities include peripheral pancytopenia, hyperpigmentation, deformity of the thumbs and genital hypoplasia. 3. [sentencedict.com]

   Abdominal examination : organomegaly lymphadenopathy  skin examination : malar rash purpura hypo or hyperpigmentation  Musculoskelatal system : short stature synovitis abnormal thumb 9. [slideshare.net]

  Figure 1 The patient had hyperpigmentation and freckles in her armpits. One diagnosis we considered was Fanconi anaemia. [tidsskriftet.no]

• Bone Disorder

  BRA Institute Rotary Cancer Hospital (AIIMS), 110029 - New Delhi/IN 3 Pathology, All India Institute of Medical Sciences, 110029 - New Delhi/IN Abstract Case Summary INTRODUCTION Osteopetrosis, is a dysplastic bone disorders due to dysfunctional osteoclast [oncologypro.esmo.org]

• Asthenia

  The main clinical signs were pallor [‏100%]‏, asthenia [‏100%]‏ and fever [‏30.5%]‏. Mean haemoglobin was 6.5 g/dL [‏range 2.9-9.2 g/dL]‏, mean white blood ... [apps.who.int]

  […] opening, flippancy, occupancy, eye-opening, discrepancy, occupancy rate, cytosine, cytology, cytokinesis, cytoskeleton, pinocytosis, phagocytosis, leukocytosis, ability to pay, phytoplankton, xenia, genial, denial, menial, venial, spaniard, eugenia, asthenia [sentencedict.com]

• Renal Insufficiency

  The potential risk factors were: hypoalbuminemia (n = 23), renal insufficiency (n = 14), dosing errors (n = 13) and non-supplementation of folates (n = 7). Thirteen patients died. WBC at admission was found to determine survival (P < 0.05). [ncbi.nlm.nih.gov]

  Conclusions : Women, the elderly, and renal insufficiency can be risk factors of severe pancytopenia induced by MTX even if low dosage. We should carefully treat these patients with MTX. [repo.lib.tokushima-u.ac.jp]

• Kidney Failure

  Change in mental status Seizures Focal neurologic findings Kidney failure Severe hypoglycemia Pulmonary edema Speticemia Shock Kyriacou DN., Spira AM., Talan DA., Mabey DCW. [pedemmorsels.com]

To diagnose pancytopenia, bone marrow aspiration and biopsy are often necessary [8]. Bone marrow in patients with pancytopenia has fatty replacement and may show relatively increased non-hematopoetic elements. Consider dysplasia as well, and exclude the possibility of metastatic tumor.

In peripheral blood smear in pancytopenia is obvious paucity of all types of blood cells. Levels of hemoglobin and hematocrit are low, but level of hemoglobin in particular erythrocytes is around normal. Life duration of red blood cells is shorter than usual. Number of leukocytes is also reduced, especially number of granulocytes (granulocytes more than lymphocytes, that's why "relative lymphocytosis" occurs). The absolute numbers of platelets and reticulocytes are also reduced.

Many peripheral blood tests exist and may be useful, such as hemoglobin electrophoresis and blood-group testing, fluorescence-activated cell sorter (FACS) profiling, fluorescent-labeled inactive toxin aerolysin (FLAER) testing, histocompatibility testing, and many others [9].

• Decreased Platelet Count

  Though iron deficiency is associated with a reactive thrombocytosis, increasing severity of iron deficiency leads to normalisation and occasionally even decrease platelet counts. [njlm.net]

Pancytopenia can be treated differently. In the beginning of disease, but often not for long, blood transfusion may help to improve blood count. After a while, effectiveness of transfusion decreases. In most cases, patients are treated with drugs. If pancytopenia is suspected to be idiopathic and result of autoimmune response, the best solution is to use immunosuppressant drugs, such as corticosteroids, cyclosporine A, cyclophosphamide, thymoglobulin, and others.

In many cases, bone marrow-stimulators can be helpful. This group of drugs includes epoetin alfa, filgrastim and sargramostim. In not many cases, and among younger patients, bone marrow transplantation, or therapy with stem cells may be an option. The advantage of bone marrow transplantation compared to other kinds of treatment has been established in multicentric trials [10].

The outcome of patients with pancytopenia is improving because of better supportive care. The mortality is around 50% in first year after diagnosing aplastic anemia, without any treatment, but for patients that are receiving immunosuppressive treatment, 10-year survival rate is 68%, and for those who get hematopoietic cell transplantation is even higher, and amounts 73% [7].

Pancytopenia can be idiopathic or secondary. In more than fifty percent of cases it is idiopathic, which means that the real cause of disorder is not actually known and detected [2]. It may be a response of body's immune system to its own substances.

In other cases, cause is well known and proven. It can be one of the physical agents, chemical agents or drugs, or the result of allergic reaction or infection. Also, sometimes pancytopenia occurs as result of bone marrow infiltration with fibrin, or lipoid or malignant cells. Sometimes, even a physiological condition as pregnancy may lead to pancytopenia, although it's very rare [3].

Epidemiological studies have shown that the annual incidence of aplastic anemia in Europe is 2 cases per million population [4]. In Asia, the incidence is higher [5]. These studies have also shown that there is no racial or sexual predisposition for aplastic anemia. However, the incidence is slightly higher within younger patients (children and youth under age of 25).

When there is insufficiency of bone marrow, it becomes fatty and empty in pluripotent hematopoetic stem cells. Still it is not defined what causes this insufficiency, and many theories tried to explain it. According to one theory, there is abnormality in structure of hematopoietic stem cells. In others, abnormality of hematopoietic microenvironment is suggested. Most likely, it is a result of immune response to different antigens, whether they are originally from outside or inside the organism [6].

Pancytopenia is sometimes hereditary, and it is not possible to prevent it [11]. But in other cases, when the environmental factor is well known and detected, pancytopenia can be prevented by simple avoiding exposure (that is possible when cause is radiation, or use of drugs such as chloramphenicol, aspirin, mezanthion).

Erythrocytes have main role in oxygenating body's tissues, leukocytes defend the body against microorganisms and other antigens, and platelets are needed in hemostasis and blood coagulation. In pancytopenia, the disorder is expected in particular blood cell function. The symptoms are numerous and may include weakness, fatigue, frequent infections, bruising or spontaneous bleeding. Treatment can be various and depends on the etiology. Blood transfusion, medications such as corticosteroids, immunosuppressant drugs, bone marrow-stimulating drugs, stem-cell therapy, or bone marrow transplantation are common options. Also, sometimes removing some environmental factors may help.

• Definition: Pancytopenia is deficiency of blood cells, including all types of cells (red, white and platelets). With bone marrow hypoplasia, it is main characteristic of some hematological diseases, such as aplastic anemia.
• Cause: It can be caused by environmental factors, such as radiation, microorganisms (especially viruses), some particular drugs, and then it is secondary pancytopenia, because the cause is known. However, in most cases it is idiopathic, which means that cause is not known or detected. It could be the immune response to antigens, but that is just one of many pathophysiological theories.
• Symptoms: The main symptoms are a result of blood cell function failure, and include tachycardia, weakness, pale skin (lack of red blood cells), frequent hyperthermia and infections (lack of white blood cells), unexplained bleeding, easy bruising (lack of platelets), and many others.
• Diagnosis: Blood count and peripheral blood smear are necessary for diagnosing pancytopenia. In vitro analyzing cultures of hematopoietic tissue (myelogram) also can be useful. Bone marrow aspiration and biopsy are almost always required.
• Treatment: There are several possibilities in treatment of pancytopenia - transfusion, immunosuppressive drugs and bone marrow-stimulating drugs, corticosteroids, antibiotics, bone marrow transplantation, and stem cell therapy.

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