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.

• Spleen Disease

  […] type 3, Hypersplenism, Infectious hepatitis, Liver disease, Spleen disease Genetic Acute cholinergic dysautonomia, Chromosome 8, mosaic trisomy, Ghosal syndrome, Homologous wasting disease, Trisomy 8 mosaicism Hematologic Aplastic anemia, Banti syndrome [wikidoc.org]

• Hodgkin Lymphoma

  During this time, 4 patients (1.8%) received clinically significant hematological diagnoses requiring ongoing care; aplastic anemia, chronic lymphocytic leukemia, non-Hodgkins lymphoma (2 patients). [ashpublications.org]

  HIV/AIDS, leukemia, Hodgkin’s lymphoma, hyperthyroidism, myelofibrosis and parasitic diseases can cause leucopenia too. Sepsis and hypersplenism as well as serious allergies can lead to low white blood cell count. [ic.steadyhealth.com]

  Other causes of low white blood cell count include systemic lupus erythematosus, Hodgkin's lymphoma, some types of cancer, typhoid, malaria, tuberculosis, dengue, rickettsial infections, enlargement of the spleen, folate deficiencies, psittacosis, sepsis [en.wikipedia.org]

• Fishing

  Some sources of quality protein are fish, eggs, poultry, beef, milk, Greek yogurt and beans. If your diet is poor, or you're having trouble eating, you can take a multivitamin or supplement with vitamin B12 and folate. [nebraskamed.com]

  If you have neutropenia, you should avoid raw meat, eggs and fish, moldy or expired food, unwashed or moldy fruit and vegetables, and unpasteurized beverages, including fruit and vegetable juice, beer, milk, as well as unpasteurized honey. [oncologynutrition.org]

  Avoid uncooked eggs, raw or undercooked meats, poultry, fish and seafood. These foods can contain harmful organisms. Live plants can be a source of germs. Remove plants from the living area. Avoid cleaning cat litter boxes or birdcages. [cancer.ca]

• Weight Loss

  Anemia occurred independently of the degree of weight loss. The platelet counts decreased by a clinically insubstantial, although statistically significant, amount (281,000-250,000; P < .0005). [ncbi.nlm.nih.gov]

  In our study, the patients with SVR had significant weight loss compared to those without SVR. The association between body weight, weight loss and SVR is controversial. [medsci.org]

  All patients had suffered recent, marked weight loss. Each had a palpably enlarged spleen that was firm and non-tender. [annals.org]

• Collapse

  Other symptoms related to organ failure may supervene, such as acute renal failure, pulmonary oedema, generalized convulsions, circulatory collapse, followed by coma and death.The initial symptoms, which may be mild, may not be easy to recognize as being [who.int]

  From the clinical point of view the greater evidence of pathology appears when the nasal bones, the nasal spine and even the midline maxillary region become affected; the erosion or complete destruction of the latter leads to tissue collapse, with sinking [scielo.isciii.es]

  Collapse mosquito species and temperature regime (°C) no. of replicate infectious feeds dissection days post feed (and total no. mosquitoes dissected for oocysts, and sporozoites) presence of oocysts (and maximum prevalence on a given day) presence of [royalsocietypublishing.org]

  Eventually, severe gastrointestinal hemorrhaging occurs, leading to vascular collapse, shock, and death. If this initial toxic phase is survived, jaundice, renal failure, and peripheral neuropathology may develop ( Merrill et al., 2001 ). [academic.oup.com]

• Anorexia

  To determine whether patients with anorexia nervosa (AN) and leukopenia have an increased risk of infection, we reviewed the incidence of leukopenia and infection in 68 cases of AN and studied the mechanism of profound neutropenia in one. [jamanetwork.com]

  We have analyzed the blood of 18 patients affected by anorexia nervosa and bulimia nervosa collected over a 15-month period. [hindawi.com]

  […] health conditions that might be causing your leukopenia low white blood cell count are: lupus sepsis allergies leukemia HIV/AIDS sarcoidosis myelofibrosis hypersplenism histoplasmosis aplastic anemia allergic reaction Fanconi anemia hyperthyroidism anorexia [healthblurbs.com]

• Aspiration

  Suggested Additional Lab Testing Most important test: WBC count and differential Peripheral blood smear and bone marrow aspirate, with or without bone marrow biopsy, is informative in the diagnosis of certain leukopenias. [renalandurologynews.com]

• Common Cold

  Supplements Echinacea may help stop recurring infections, such as common colds, coughs and respiratory infections. [draxe.com]

• Loss of Appetite

  If you’re experiencing deficiencies and/or weight loss due to malnutrition, loss of appetite, nausea or vomiting, it’s best to be monitored by a doctor and to consider visiting a dietician. [draxe.com]

  The reasons for weight loss among the study population are unclear. Many patients complained of loss of appetite or ate less related to the fatigue. [medsci.org]

  Anemia is associated with the following symptoms (Abrahamian FM et al 2005): Weakness and fatigue Irritability Shortness of breath Headaches Sore tongue and bleeding gums Pallor Nausea and loss of appetite Faintness and dizziness Confusion and dementia [drvitaminsolutions.com]

• Oral Ulcers

  However, serious cases can lead to oral ulcers, stomatitis, pneumonias and liver abscesses. Click on a state below to find eating disorder treatment options that could be right for you. [eatingdisorders.com]

  Person with leukopenia may develop infections due to impaired immune system such as pneumonia, stomatitis and oral ulcers. Women with leucopenia may suffer from metrorrhaggia and menorrhagia. [ic.steadyhealth.com]

  Infections and Ulcers : The person becomes susceptible to various infections and oral ulcers. Craving : The patient develops strong desire to drink hot drinks. [buzzle.com]

  Liver abscesses: Bacterial infection of the liver Metrorrhagia: Infective bleeding from the uterus Menorrhagia : Prolonged and heavy menstruation Neurasthenia: Characterized by fatigue, fever, headache, irritability and hot flashes Oral ulcer and various [healthooze.com]

  Chills Sweating Fever higher than 100.5 ˚F Anemia (lesser number of healthy rbc in the blood) Liver abscesses (bacterial infection in the liver) Oral ulcers & other infections Craving to consume hot drinks Menorrhagia (prolonged and heavy menstruation [hxbenefit.com]

• Hepatomegaly

  These were severe anemia, 36 (18%), prostration, 41 (24%), hyperpyrexia, 16 (8%), respiratory distress, 10 (5%), hemoglobinuria, 14 (7%), persistent vomiting, 16 (8%), and hyperparasitemia, 33 (16.5%), but none had pathology of hepatomegaly and comma. [ncbi.nlm.nih.gov]

  Other signs or symptoms that may help guide workup and management include: Localizing signs or symptoms of infection Lymphadenopathy Hepatomegaly or splenomegaly, Signs of anemia (pallor, cyanosis), Signs of thrombocytopenia (mucosal bleeding, petechiae [cancertherapyadvisor.com]

• Petechiae

  Read Full » Why am I having a bruise under my foot and petechiae on my arm? Query: Hi doctor,I am in my early twenties. I am concerned that I have leukemia. I have a bruise under my foot that I noticed yesterday. [icliniq.com]

  On physical examination, there were no swollen joints - only tenderness at the right metacarpophalangeal and wrists, and petechiae at lower limbs. [scielo.br]

  Other signs or symptoms that may help guide workup and management include: Localizing signs or symptoms of infection Lymphadenopathy Hepatomegaly or splenomegaly, Signs of anemia (pallor, cyanosis), Signs of thrombocytopenia (mucosal bleeding, petechiae [cancertherapyadvisor.com]

  Sepatomegaly or splenomegaly, or abnormal enlargement of the spleen Symptoms of anemia, such as fatigue, weakness, pallor and poor circulation Signs of thrombocytopenia (a decrease in the number of platelets present in the blood), such as mucosal bleeding, petechiae [draxe.com]

• Skin Rash

  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]

  Diaphoresis (excessive sweating) Weight loss Symptoms of a localized infection, such as skin rashes, swelling, pain, tenderness, heat, redness, etc. [draxe.com]

• Eruptions

  THE DIAGNOSIS We diagnosed the patient with DRESS (drug reaction with eosinophilia and systemic symptoms) based on persistent fever, onset of cutaneous manifestations (facial edema and morbilliform eruption), lymphadenopathy, increased liver function [mdedge.com]

  Within 5–15 days after admission, five people (4.8%) developed red papular eruptions, scattered on the back, buttocks, abdomen, chest and arms, and two people (1.9%) exhibited fine bran-like desquamation of the skin mainly on the trunk. hyperpigmentation [academic.oup.com]

• Suggestibility

  If there is no such infection, it is suggested that the mechanism leading to leukopenia be clarified. [ncbi.nlm.nih.gov]

  In order to determine if the above suggested features FULL TEXT [annals.org]

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.

• Cytopenia

  […] stomatitis, gingivitis, dental defects, congenital anomalies • Spleen size Hypersplenism • History of drug exposure Drug-associated neutropenia • Complete blood count with differential and reticulocyte counts Neutropenia, aplastic anemia, autoimmune cytopenias [clinicalgate.com]

  The hazard ratio of death was 0.69 (95% CI, 0.64-0.75) for patients with higher-grade neutropenia or leukopenia compared to patients with lower-grade or lack of cytopenia. [ncbi.nlm.nih.gov]

  With chronic administration, development of megaloblastosis may precede worsening cytopenias. [consultqd.clevelandclinic.org]

  Physicians should be aware of leucopenia as a potential adverse effect to quetiapine, especially in patients with symptoms of infections or cytopenia. [research.regionh.dk]

  As TNF-alpha regulation is related to cellular differentiation of various cellular types involved in immune response through expression of several other cytokines, it is possible that the use of its inhibitors may cause cytopenia. [scielo.br]

• Enlargement of the Liver

  Lymph node enlargement. A swollen liver or spleen. Mucosal bleeding and minor skin bruises. Intensely painful urination. A wound that is draining pus. [icliniq.com]

  Symptoms associated with leukopenia can include: infections, fatigue, fever, enlarged spleen or liver, pneumonia, anemia, headaches and others. [draxe.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.