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Leukopenia

Leucopenia


Presentation

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.

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.

Overeating
  • Although lamotrigine was stopped, her condition deteriorated over the next 48 hours and she was admitted to hospital.[bmj.com]
  • A previously healthy 42-year-old woman presented to the emergency department (ED) for arthralgias and painful lesions on her ears, feet, and knee (Figures 1 and 2) that had developed over the last month.[ncbi.nlm.nih.gov]
  • Over a 3-year period, 3 of 54 LT patients with unexplained anemia tested positive for circulating PVB by a nested polymerase chain reaction (PCR) assay. All of these patients presented with anemia and leukopenia, with a favorable long-term prognosis.[ncbi.nlm.nih.gov]
  • Over a ten-week period of clozapine treatment at 700 mg per day, the patient developed agranulocytosis. Her white blood cell count sharply dropped to 1.6 109 L, and her neutrophils decreased to 0.1 109 L.[ncbi.nlm.nih.gov]
  • Reversible leukoencephaolopathy syndrome symptoms remitted within 72 h but leukopenia persisted over 10 months. The patient received a kidney transplant 15 months after RLS onset and has received cyclosporine since the second post-transplant day.[ncbi.nlm.nih.gov]
Alopecia
  • NUDT15 p.R139C was strongly associated with early leukopenia and severe alopecia (OR for early leukopenia: 107.624, 95% CI 18.857-614.250, p 1.403 10 -7 , OR for severe alopecia: 77.152, 95% CI 17.378-342.526, p 1.101 10 -8 ).[ncbi.nlm.nih.gov]
  • Dose tailoring was associated with acceptable acute non-haematological toxicity with more total alopecia, nausea, vomiting and fatigue. CONCLUSION: Dose tailoring according to leukopenia was feasible.[ncbi.nlm.nih.gov]
Hemorrhagic Bullae
  • The rash was purpuric with violaceous borders and hemorrhagic bullae. While she had mild pain with movement, her joint examination was otherwise normal and without signs of infection.[ncbi.nlm.nih.gov]
Generalized Seizure
  • We report an episode of RLS in a 22-year-old male patient on chronic hemodialysis with well-controlled moderate hypertension who presented with de novo headache and generalized seizures.[ncbi.nlm.nih.gov]

Workup

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.

Mediastinal Mass
  • A 61-year-old man was admitted to our hospital for further examinations of a mediastinal mass. He had underwent an extended thymothymectomy, and had a tumor that was diagnosed as a type B1 thymoma, according to the World Health Organization.[ncbi.nlm.nih.gov]
Mycobacterium Avium Complex
  • We report the first established case of idiosyncratic rifabutin-induced leukopenia in an immunocompetent man treated for pulmonary Mycobacterium avium complex infection.[ncbi.nlm.nih.gov]

Treatment

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.

Prognosis

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.

Etiology

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:

Epidemiology

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.

Sex distribution
Age distribution

Pathophysiology

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.

Prevention

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.

Summary

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.

Patient Information

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.

References

Article

  1. Watts RG. Neutropenia. In: Lee GR, Foerster J, Lukens J, et al, eds. Wintrobe's Clinical Hematology. 10th ed. Baltimore, Md: Lippincott, Williams & Wilkins; 1999:1862-1888.
  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.
  4. Sifton DW, Murray L, Kelly GL, Reilly S, eds. Physicians' Desk Reference. 55th ed. Montvale, NJ: Medical Economics Company, Inc.; 2001:551-6, 847-60, 1275-80, 1396-9, 1793-5, 1998-2002, 3068-71.
  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.

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Last updated: 2019-07-11 22:37