The major clinical feature of leukopenia is infection, often serious and more likely as neutrophil counts fall. The manifestations mainly depend upon the degree of leukopenia or rather neutropenia. The clinical features seen are due to the bacterial infections. It is necessary to consider [7] neutrophil count as this is the most abundant type of white blood cells and an important marker of infection.

The main symptoms of leukopenia are:

• Anemia: A low level of hemoglobin occurs with decrease in white blood cells. The reason is not yet clearly known but can be due to blood dyscrasias and an increased number of red blood cells that are required for oxygen to be circulated.

• Fatigue: Due to anemia, patient will also show malaise on slightest exertion.

• Fever: Due to decrease in level of immunity and white blood cells, patient is at a higher risk of opportunistic infections. Fever is a strong indication of some infection.

• Pneumonia: Once infection enters the body, it is most likely to infect lungs. It could be viral or bacterial.

Other symptoms include headache, menstrual irregularities, thrombocytopenia , stomatitis and a variety of other infections in literally any part of the body. A patient may show no symptom other than mouth ulcers suggesting of some infection.

• Malnutrition

  Such as chemotherapy, malnutrition and a number of diseases, such as leukemia. A lack of platelets can also be caused by chemotherapy and certain diseases such as leukemia. [awarehiv.com]

  […] low white blood cell count include: Aplastic anemia Chemotherapy HIV/AIDS Hypersplenism (an abnormality of the spleen causing blood cell destruction) Kostmann's syndrome (a congenital disorder involving low production of neutrophils) Leukemia Lupus Malnutrition [mayoclinic.org]

  Malnutrition is another major cause of reduced production of lymphocytes. Causes of Leukopenia Bone marrow affected by cancer – Lymphomas and other forms of cancer affect the bone marrow. [hxbenefit.com]

  […] nervosa multiple myeloma rheumatoid arthritis anaphylactic shock parasite infection ~ malaria radiation therapy, exposure myelodysplastic syndromes chemical exposure, poisoning ~ benzene, arsenic salmonella, tuberculosis, typhus bacterial infections malnutrition [healthblurbs.com]

  Con… • Malnutrition • Leukopenia can be caused by vitamin or mineral deficiencies, such as deficiencies in: • vitamin B-12 • folate • copper • zinc 12. [slideshare.net]

• High Fever

  fever (over 100. 5˚F) Sweating While there is not a way to prevent leukopenia, there are several things patients can do to protect themselves during the time that their white blood cell count is low. [arizonabloodandcancerspecialists.com]

  A person may also experience fatigue, high fever, headache and hot flashes A person with leukopenia is highly irritable Thrombocytopenia in which there is reduction in the level of platelets due to impaired functioning of the bone marrow. [emedicalhub.com]

  Other leukopenia symptoms include: High fever Fatigue Hot flashes Mood changes (easily irritated) Thrombocytopenia (decreased platelet count) Liver disorders or liver abscesses Tongue ulcers Diagnosis The doctor would first ask about your medical history [findatopdoc.com]

• Constipation

  His additional medications included doxazosin 4 mg every morning for benign prostatic hyperplasia, citalopram 60 mg every morning for depressive symptoms, psyllium 1500 g every morning for constipation, clonazepam 1 mg daily at bedtime for anxiety and [academic.oup.com]

• Heart Disease

  Vitamin D: Vitamin D can help stimulate red blood cell synthesis and a deficient blood level is significantly correlated with anemia in heart disease patients. [lifeextension.com]

  Chlamydia pneumonia-specific circulating immune complexes in patients with chronic coronary heart diseases. Circulation, 87 (1993), pp. 1130-1134 [4] P. Vergara Moscoso. Patogenia de las citopenias autoinmunes primarias. [archbronconeumol.org]

  Staphylococcus epidermidis, Propionibacterium acnes, and diphtheroids grown from previously healthy immunocompetent infants (with no history of heart disease, ventriculoperitoneal shunt, indwelling catheter or other prosthetic devices) were categorized [journals.lww.com]

  The only case with electrocardiographic abnormality had a history of heart disease. The levels of urinary arsenic and laboratory tests were normal for 3 of the 104 people, but they none-the-less complained of symptoms related to arsenic poisoning. [academic.oup.com]

• Pruritus

  Decreases in haemoglobin and haematocrit, thrombocytopenia, leucopenia /neutropenia, and cases of agranulocytosis or pancytopenia, have been reported very rarely Side-effects (skin rash, pruritus, supraventricular extrasystoles, tachycardia, water and [glosbe.com]

• Confusion

  This should not be confused with agranulocytosis. This video is targeted to blind users. Attribution: Article text available under CC-BY-SA Creative Commons image source in video [youtube.com]

  This should not be confused with agranulocytosis. Causes[edit] Medical conditions[edit] Low white cell count may be due to acute viral infections, such as a cold or influenza. [en.wikipedia.org]

• Insomnia

  Most often the emotional disturbances include depression, disinterest in normal activities, insomnia, grief, mood changes, anxiety, inability to concentrate, extreme concern about managing a gluten-free lifestyle and other emotional and behavioral challenges [celiac.com]

  Pale skin, leg cramps and insomnia are also common indicators that the patient is suffering from anemia. Menorrhagia Women suffering from leukopenia may suffer from menorrhagia, or an abnormally heavy menstrual period. [md-health.com]

  A low RBC count can cause fatigue, dizziness, pale skin, leg cramps, breathlessness, poor concentration, and a lack of sleep leading to insomnia. 3) Abnormal periods Women who have a low white blood cell count tend to experience heavier bleeding during [findatopdoc.com]

  His additional medications included doxazosin 4 mg every morning for benign prostatic hyperplasia, citalopram 60 mg every morning for depressive symptoms, psyllium 1500 g every morning for constipation, clonazepam 1 mg daily at bedtime for anxiety and insomnia [academic.oup.com]

• Excitement

  Enter a word (“newspaper”), a word combination (“exciting trip”) or a phrase (“with all good wishes”) into the search box. [es.pons.com]

  On the 13th of June 2020, Lepra will be back in Edinburgh to hold this exciting 68 mile ride for anyone ready to commit to that New Years Resolution to get fit! Check out below how YOU can get a ticket and get back in the saddle! Read more [lepra.org.uk]

• Tremor

  Mild restlessness was observed; however, abnormal movements and tremor were absent. He made good eye contact, was casually dressed, and was acceptably groomed. [academic.oup.com]

Severe cases of leukopenia should be investigated and treated urgently. Mild drop in counts without any symptomatic evidence may not need any laboratory investigation and will spontaneously resolve on its own without any treatment [8].

A thorough history of fever, anemia, mouth ulcers and hepatosplenomeagly should be noted. History of intake of drugs should be checked, especially cytotoxic drugs. Any exposure to radiation or chemotherapy should be sought out. Laboratory investigations such as a complete blood profile, urine analysis, ANA, serum protein electrophoresis and vitamin and folate level and anti-neutrophil antibodies tests should be done. Other specific tests include bone marrow examination, bone scan for any metastasis, CT scan to detect any liver or spleen lesion, lymph node biopsy in case of Hodgkin disease.

• Leukopenia

  [leuko(cyte) + G. penia, poverty] leukopenia /leu·ko·pe·nia/ ( -pe´ne-ah ) reduction of the number of leukocytes in the blood below about 5000 per cubic mm.leukope´nic malignant leukopenia, pernicious leukopenia agranulocytosis. leukopenia also leucopenia [medical-dictionary.thefreedictionary.com]

  Lancet, BMJ Media Powerpoint slides on Leukopenia Images of Leukopenia Photos of Leukopenia Podcasts & MP3s on Leukopenia Videos on Leukopenia Evidence Based Medicine Cochrane Collaboration on Leukopenia Bandolier on Leukopenia TRIP on Leukopenia Clinical [wikidoc.org]

  Neutropenia, a subtype of leukopenia, refers to a decrease in the number of circulating neutrophil granulocytes, the most... (39 of 876 words, 1 image) en.wikipedia.org/wiki/Leukopenia Collins Dictionary: leucopenia [pathology] | leukopenia [United States [memidex.com]

  The case described here suggests an immune-related mechanism for the development of leukopenia. Use of the Naranjo probability scale determined the association between cephalosporin use and leukopenia to be probable. [ncbi.nlm.nih.gov]

• Hypoglycemia

  Other manifestations of P falciparum infection include hypoglycemia, lactic acidosis, severe anemia, and multiorgan dysfunction due to hypoxia. [medscape.com]

Leukopenic patients are more susceptible to endogenous and hospital acquired infections. Simple measures which are of paramount importance in treatment of severe cases are good hand washing practices and skin cleaning, especially around orifices. Aseptic techniques, good venous access, minimizing invasive procedures and intramuscular injections are important measures.

Attempts to locate the site of infection and identify the organisms involved should be made in all cases. Cultures of throat, urine, sputum and blood and X-ray chest are mandatory. A combination of broad spectrum antibiotics [9] should be given. Vitamins and steroids are also given to help increase the level of WBCs. Cytokines therapies are advised when cancer is the cause. Most patients with mild to moderate leukopenia do not require any treatment. Antibiotics suffice in case of infection. Autoimmune disorders require steroids to improve counts.

The prognosis of leukopenia depends upon the cause, duration of leukopenia, as well as age of the patient. Due to easy availability of broad spectrum antibiotics along with good supportive care, recovery even for severe cases is good. Morbidity is high in cases of long and severe infections which can be anything from skin infections to systemic infections and septicaemia.
Complications and fatality is high in cases of malignancy and AIDS. Fever due to decreased neutrophils in cancer can affect about 4-30% of individuals. Death occurs if septicaemia is not brought under control. Drug induced leukopenia also carries a high mortality rate , but with timely and vigorous antibiotic treatment outlook is better.

The five types of leukocytes found in peripheral blood are neutrophils, eosinophils and basophils which are the granulocytes, the lymphocytes and the monocytes. The normal white blood count 4000-11,000 per cubic millimeter of blood. A count less than 3,500 cubic millimeter is regarded as leukopenia [3]. There are a number of causes which can lead to leukopenia such as:

• Certain infections like malaria, typhoid, kala azar, influenza, brucellosis and viral hepatitis
• Overwhelming bacterial infections especially in patients with poor resistance like miliary tuberculosis or sepsis [4]
• Drugs, chemicals and physical agents which induce aplasia of the bone marrow e.g. anti metabolites, ionising radiation.
• Certain hematological and other diseases such as pernicious anemia, aplastic anemia, liver cirrhosis, systemic lupus erythematosus, Gaucher disease
• Cachexia and debility
• Anaphylactoid shock
• Certain rare hereditary or familial disorders like cyclic neutropenia, primary splenic neutropenia, idiopathic benign neutropenia
• Vitamin and folate deficiencies
• Deficiency of zinc and copper
• Autoimmune disorders

The incidence of leukopenia is quite common in patients with advanced stage HIV infection, occurring in 85-90% cases of clinical AIDS. The levels of neutrophils and lymphocytes are chiefly affected, neutrophils being less than 1000 per cubic millimeter of blood [5]. Age seems to influence the neutrophil count and elderly people have higher risk of leukopenia than younger individuals. Congenital forms of leukopenia more common in childhood.

Leukopenia tends to have a predilection for women more than men; this can be because of frequent usage of drugs by women. Leukopenia and neutropenia is also common in individuals treated with valproate and quetiapine. Leukopenia occurs frequently on patients receiving chemotherapy and anti tuberculosis treatment, though spontaneous recovery happens. Sometimes the therapy will have to be stopped if the counts fall too low.

A reduction in the counts of any of the 5 leukocytes implies leukopenia [6]. Monocytes, basophils and eosinophils already exist in scant numbers such that a reduction in these does not significantly cause a decrease in total white blood cell count or affect the body significantly. It is mainly a decrease in neutrophils and lymphocytes which are the major white blood cells which can cause leukopenia.

All leukocytes are produced from the precursors present in the bone marrow known as pluripotent hematopoetic stem cells. Due to a short lifespan of these cells, the bone marrow is constantly producing new white blood cells. In the bone marrow they are present in two stages- the proliferative stage and the mature stage. Sites of leukopenia can be limited to any of these stages-
The pathophysiology can be divided into two categories-

• Disorders of production or release of leukocytes from marrow- any damage or injury to bone marrow, bone marrow malignancies. Disorders in the pluripotent haemopoetic cells itself.
• Disorders of disposal or utilisation (spleen, tissues)

As a result of this, leukopenia can lead to severe infection which mainly affects skin, mucus membranes and genital areas.

The most important way to prevent leukopenia is to boost the immune system and keep it strong. It is vital to immediately check and investigate any signs of illness and prevent the infection from progressing [10]. Certain lifestyle modifications can also help such as regular exercising especially if overweight as it can affect the functioning of the immune system.

Leukopenia is a clinical condition characterized by reduction in bone marrow production of white blood cells, especially the granulocytes, leaving the body inadequately protected against bacteria and other agents that might invade the body tissues. This condition predisposes the individual to many serious infections. Leukocytes help to fight off and protect the body from infectious or foreign agents. These cells are produced by the hematopoetic system and found all over the body including blood and lymphatic system. Technically, it implies a fall in neutrophils, monocytes and even lymphocytes. Yet, in clinical practice, it is synonymous with neutropenia [1].

Normally, the human body lives in symbiosis with many bacteria because many mucus membranes of the body are constantly exposed to the environment. Any decrease in the leukocytes is immediately followed by an attack of bacteria that are already present in/on the body. Within two days after the bone marrow stops producing white blood cells, ulcers appear in the mouth and colon or the individual develops some kind of respiratory infection. Without treatment death often ensues in less than a week after acute total leukopenia occurs. Any irradiation by gamma rays, or exposure to drugs and chemicals like benzene is likely to cause aplasia of the bone marrow which produces white blood cells. Many drugs, even certain antibiotics, can cause aplasia of the bone marrow causing leukopenia.

After moderate irradiation injury to the bone marrow, some stem cells may remain undestroyed and are capable of regenerating themselves provided sufficient time is available. A patient properly [2] treated with transfusion plus antibiotics and other drugs to ward off infections usually develops enough new bone marrow within several weeks for white blood cell concentrations to return to normal.

Leukopenia is a medical condition where the White blood cell levels reduce. The White blood cells are basically the soldiers of the body responsible for fighting away all infections and foreign agents. There are 5 types of white blood cells out of which neutrophils are the most abundant one and hence the terms leukopenia and neutropenia are often used interchangeably. They are responsible for protecting the body against all microorganisms. The level of leukocytes can fall due to many reasons ranging from malignancies, any disease of the bone marrow, HIV, any severe infections and autoimmune disorders. There can be many other causes of leukopenia.

Symptoms may vary, some patients may show no symptom other than mouth ulcers and fever indicating of an infection in the body. Other symptoms include tiredness, recurring infections, stomach pains. sore and swollen gums and other symptoms. It is important to consult your doctor who will need to do various tests such as blood tests and other specific tests to come to a diagnosis. Mild infections demand no treatment and are self resolving. In severe cases, antibiotics along with other therapies to build up white blood count in the body will be required. Steroids and cytokine therapies may be required in case of malignancies.

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2. Beutler E, Lichtman MA, Coller BS, Kipps TJ, eds. Williams Hematology. 5th ed. New York, NY: McGraw-Hill; 1995:815-24, 844-58.
3. Lee GR, Foerster J, Lukens J, et al, eds. Wintrobe's Clinical Hematology. Vol 2. 10th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 1999:1862-82.
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5. Hsieh MM, Everhart JE, Byrd-Holt DD, Tisdale JF, Rodgers GP. Prevalence of neutropenia in the U.S. population: age, sex, smoking status, and ethnic differences. Ann Intern Med. Apr 3 2007;146(7):486-92.
6. Welte K, Dale D. Pathophysiology and treatment of severe chronic neutropenia. Ann Hematol. Apr 1996;72(4):158-65.
7. Curnutte J, Coates T. Disorder of phagocyte function and number. In: Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds. Hematology: Basic Principles and Practice. 3rd ed. New York, NY: Churchill Livingstone; 2000:720-62.
8. Levene MI, Lewis SM, Bain BJ, Imelda Bates. Dacie & Lewis Practical Haematology. London: W B Saunders.2001; p. 586.
9. Goulenok T, Fantin B. Antimicrobial Treatment of Febrile Neutropenia: Pharmacokinetic-Pharmacodynamic Considerations. Clin Pharmacokinet. Jun 27 2013;
10. Krell D, Jones AL. Impact of effective prevention and management of febrile neutropenia. Br J Cancer. Sep 2009;101 Suppl 1:S23-6.