LOW NEUTROPHIL GRANULOCYTES or NEUTROPENIA: symptoms and causes

The feedback from low neutrophilic granulocytes (more properly: low granulocytes or neutropenia) is not uncommon, and is often accompanied by the presence of low leukocytes (leukopenia), with neutrophils being the main components of white blood cells together with lymphocytes. The causes of low neutrophils they are mainly disorders of bone marrow production, neoplasms, but also drugs, acute and chronic inflammatory states, infections, bacterial or viral. THE symptoms of neutropenia they are generally asthenia (tiredness), malaise, fever, ease of getting infections. Very often, however, there is no specific symptom associated with the finding of reduced neutrophilic granulocytes.

Low neutrophils or neutropenia

Granulocytes are the main circulating white blood cells. Among the granulocytes, neutrophils are undoubtedly the most important and the most represented, being responsible for more than 90% for total granulocytes and 60% for total leukocytes.

What does it mean to have reduced neutrophils? The feedback from low neutrophilic granulocytes (more properly: low granulocytes or neutropenia) is not uncommon, and is often accompanied by the presence of low leukocytes (leukopenia), with neutrophils being the main components of white blood cells together with lymphocytes. The causes of low neutrophils they are mainly disorders of bone marrow production, neoplasms, but also drugs, acute and chronic inflammatory states, infections, bacterial or viral. THE symptoms of neutropenia they are generally asthenia (tiredness), malaise, fever, ease of getting infections. Very often, however, there is no specific symptom associated with the finding of reduced neutrophilic granulocytes.

What are neutrophils?

What are granulocytes? Called more correctly polymorphonuclear granulocytes, the granulocytes they represent the majority of total leukocytes, and are so called due to the presence of typical granulations in the cytoplasm (which is the liquid contained in the cells) and a polylobed nucleus (ie formed by many lobes). Granulocytes are represented by neutrophil granulocytes (60% of total white blood cells), i basophilic granulocytes (basophils, they are about 1% of total leukocytes) and i eosinophilic granulocytes (called eosinophils, they represent approximately 5% of total white blood cells).

Together with T lymphocytes, B lymphocytesmonocytes is macrophages form total leukocytes. They are commonly measured by the so-called formula leukocyte, as part ofblood count, which also measures other very important parameters such as red blood cells, hemoglobin, MCV, platelets.

THE granulocytes neutrophils are therefore the main circulating white blood cells, and allow the body to defend itself from attacks by harmful external agents. They are particularly important in bacterial infections, and are activated in synergy with lymphocytes and monocyte-macrophages. The neutrophilic leukocytes, activated by the presence of inflammatory substances and cytokines, reach the place where the insult is taking place through the chemotaxis, and make contact with foreign antigens via the phagocytosis, a technique that allows the agent to be incorporated into the granulocyte cell.

Once inside, the microorganism or "enemy" antigen is destroyed by enzymes details with lithic capacity such as peroxidasephosphatase is hydrolase.

Neutrophilic granulocytes have a average life  a few hours (8-10 hours on average as circulating neutrophils and 2-3 days in body tissues).

The main cells that make up blood, together with plasma. The deficiency of neutrophilic granulocytes is called neutropenia.

 Low neutrophil values - Neutropenia values

What is the number of neutrophils below which can we speak of neutropenia?

THE low values of neutrophilic granulocytes (neutropenia) are values less than 2.0 * 10 ^ 9 / l, i.e. less than 2 billion neutrophils per liter of blood.

In some laboratories this number is expressed as 2,000 neutrophil granulocytes / mm3 or ml, i.e. values of neutropenia less than two thousand neutrophil granulocytes per cubic millimeter or milliliter of blood.

In the children and in newborns the diagnosis of low neutrophils occurs when values lower than:

  • 1.0 * 10 ^ 9 / l (1000 neutrophil granulocytes per cubic millimeter of blood) in children under 12 months
  • 1.5 * 10 ^ 9 / l (1500 neutrophil granulocytes per cubic millimeter of blood) in children aged 12 months to 14 years

THE normal values of neutrophils in fact they oscillate between 2000 and 6000 neutrophil granulocytes per cubic millimeter of blood.

There diagnosis of neutropenia takes place thanks to a simple venous sampling on which one of the simplest blood tests is performed, the blood count with leukocyte count.

Low Neutrophil Granulocytes Causes - Neutropenia Causes

What are the main causes of neutropenia (i.e. the causes of low neutrophilic granulocytes in the blood)? As we will see in the following list, the main causes are of an oncohematological or infectious type. The causes of low neutrophils are roughly the same as the causes of low white blood cells (low leukocytes).

The main ones causes of low granulocytes I'm:

  • Blood tumors, which damage the bone marrow and impair the production of blood cells:
    • Leukemia: they are distinguished according to the rapidity of expression (acute leukemias and chronic leukemias), as well as according to the type of cells affected (myeloid leukemias and lymphatic or lymphoid leukemias.
    • Lymphomas: they are a kind of solid leukemia, with the disease mainly affecting the organs of the immune system such as lymph nodes, spleen and intestinal immunological stations.
    • Myelodysplasia: myelodysplasia, more correctly defined myelodysplastic syndromeit is a blood disease caused by damage to one or more stamina cells present inside the bone marrow. Damaged stem cells therefore fail to produce adequate amounts of functioning blood cells, resulting in a shortage of red blood cells, white blood cells and / or platelets. There are various types of myelodysplastic syndromes. In a certain percentage of cases, myelodysplastic syndromes develop into a more aggressive form of haematological disease, the acute myeloid leukemia.
    • Myeloproliferative syndromes: Blood diseases derived from a diseased stem cell, with uncontrolled proliferation of the pathological clone, include various types of blood pathology, including chronic myeloid leukemia (CML, often classified as leukemias instead of myeloproliferative), polycythemia vera ( PV), essential thrombocythemia (TE), and idiopathic myelofibrosis (MFI).
  • Neoplasms: the presence of tumors that damage the bone marrow directly (by proximity) or at a distance (with tumor metastases) can lead to bone marrow hypoplasia or aplasia, with leukopenia, neutropenia, possible anemia (low red blood cells) and thrombocytopenia (low platelets).
  • Myelofibrosis: progressive replacement of the bone marrow with fibrotic material. In addition to idiopathic myelofibrosis, which we have seen before, a picture of myelofibrosis sometimes represents the terminal phase of leukemia, lymphomas and other cancers. It is characterized by bone marrow hypoproduction, with leukopenia, lymphopenia and neutropenia, associated with anemia and thrombocytopenia (low platelets).
  • Congenital or acquired disorders which alter the hematopoietic function of the bone marrow, decreasing its productivity, and leading to the finding of reduced leukocytes, often also with low erythrocytes and reduction of platelets. For example
    • Aplastic anemia: decreased production of all types of circulating cells by the marrow, causing a condition of pancytopenia. It can be genetic or acquired.
    • Paroxysmal nocturnal hemoglobinuria: is an acquired hematopoietic cell disease characterized by haemolytic anemia, bone marrow failure and frequent thrombotic episodes of the great vessels.
    • Cyclic neutropenia: this neutropeniais characterized by a regular fluctuation (cycle from 21 to 28 days) of neutrophils associated with less important, but nevertheless present, fluctuations in other blood lines such as red blood cells and platelets. Mild neutropenia is often observed in this pathology
  • Medicinesthat damage circulating leukocytes:
    • Antibiotics, such as minocycline (Minocin), trimethoprim-sulfamethoxazole (Bactrim) sulfasalazine (Salazopyrin)
    • Antipsychotics, such as clozapine (Leponex)
    • Antidepressantssuch as bupropion (Wellbutrin)
    • Antiepilepticssuch as valproic acid (Depakin)
    • Antithyroid drugslike tapazole
    • Monoclonal antibodiessuch as Rituximab (Mabther
  • Medicines or therapieswhich interfere with the hematopoietic function of the bone marrow
    • chemotherapyall chemotherapy drugs they can cause neutropenia and lymphopenia, as well as low eosinophils and low basophils.
    • chronic therapy with corticosteroids (Please note: the use of cortisone can also cause an increase in white blood cells and neutrophils, which is reflected in the blood tests ofhigh neutrophilic granulocytes or neutrophilia).
    • immunosuppressants: azathioprine, methotrexate, cyclosporine, everolimus, tacrolimus: these are all drugs that depress the immune system and can cause leukopenia.
    • Radiation or radiation therapy: irradiation with ionizing rays at the medullary or neighboring level can result in a reduced functionality of the latter. Even in cases of nuclear disasters, such as Chernobyl or Fukushima, the very high concentration of radiation present in the surrounding area has increased the incidence of blood diseases, with bone marrow hypoproduction and even fatal.
  • Autoimmune Diseaseswhich reduce bone marrow production of blood cells
    • Rheumatoid arthritis
    • Autoimmune hyperthyroidism(e.g. Graves' disease)
    • Systemic lupus erythematosus
    • Myasthenia gravis
    • Sarcoidosis
  • Infectionswhich determine a broad cell consumption and destruction blood, including leukocytes;
    • Malaria
    • HIV: Human Immunodeficiency Virus, is the virus that causes the justly feared Acquired Immunodeficiency Syndrome, or AIDS.
    • Dengue: hemorrhagic fever, characterized by fever and hemorrhagic manifestations
  • Infections(especially acute viral infections) that alter the bone marrow function:
    • HIV: the HIV virus damages both the circulating cells and the bone marrow directly. If not treated, it leads to the onset of AIDS, the acquired immunodeficiency syndrome, with a reduction of circulating neutrophil granulocytes up to a few tens per ml.
    • Hepatitis B: HBV infection can inhibit proper bone marrow hematopoiesis, resulting in a drop in white blood cells.
    • CMV infection: cytomegalovirus (CMV) can impair bone marrow production
    • EBV infection: Epstein Barr Virus also behaves like CMV.
    • Tuberculosis: especially if with vertebral or medullary localization.
    • Sepsis: Although infections normally cause an increase in white blood cells (leukocytosis with neutrophilia), a severe infection can also be characterized by low neutrophils (see older sepsis criteria).
    • Parasitic or protozoal diseases
  • GVHD: Graft Versus Host Disease, graft versus host disease, is a form of rejection after bone marrow transplant
  • Hypersplenism: Entrapment and / or premature destruction of circulating blood cells within the spleen, which appears enlarged and hypertrophic. The enlarged spleen is frequent in blood disorders such as leukemia, lymphomas, myelodysplasias and lymphoproliferative syndromes, but also in diseases such as liver cirrhosis.
  • Vitamin deficiencies, such as that of folate and vitamin B12 (cyanocobalamin): the lack of these substances essential for the growth of circulating blood cells often causes a reduction in white blood cells and neutrophils, with simultaneous megaloblastic anemia.
  • Deficiencies of trace elements: the lack of substances such as zinc and copper can lead to a reduction in leukocytes.
  • Kostmann syndrome, a congenital disorder characterized by a reduced synthesis of neutrophils.
  • Myelocatessi: myelocathexis is a congenital disorder (present from birth) characterized by the failure of neutrophils to enter the bloodstream, resulting in neutropenia.

Bacterial infections are a non-negligible cause of decreased neutrophil granulocyte counts. Low neutrophils are a more severe sign of infection and sepsis than high leukocytosis and high neutrophils.

Low neutrophils in children

The feedback from reduced neutrophils in children it has roughly the same causes as in adults. The difference is that in the genesis of neutropenia, genetic syndromes such as the aforementioned myelocathexis and Kostmann's syndrome have a greater weight, but also:

  • Neutropeniaby congenital activation of the WASP gene
  • Neutropeniaethnic (involves some ethnic groups such as Bedouins or Sephardi)
  • Neonatal alloimmune neutropenia
  • Autoimmune neutropenia primitive of childhood

 Low Neutrophils Symptoms - Neutropenia Symptoms

What are the symptoms of low neutrophils? The main symptoms of neutropenia I'm:

  • asthenia: tiredness, weakness in common daily activities
  • weight loss, weight loss
  • frequent infections
  • bone pains
  • fever or low temperature
  • frequent bleeding, even spontaneous
  • pale skin, lips and nails (nail pallor)
  • Jaundice (yellow skin) and high bilirubin: in case of liver disease or paroxysmal nocturnal hemoglobinuria, hyperbilirubinemia manifests itself with the accumulation of bilirubin on the skin tissues, with the appearance of yellow / green color of the skin
  • Abdominal pain
  • Hepatomegaly: enlarged liver
  • Splenomegaly: enlarged spleen
  • Ascites: presence of fluid in the abdomen (ascitic effusion in the peritoneal cavity)
  • Headache or migraine (headache).
  • Frequent bleeding, especially gum bleeding or epistaxis (nosebleeds).
  • Renal failure: finding of high creatinine following overload of the lysis products of red blood cells and defective white blood cells in the kidneys.

Low neutrophils and high lymphocytes

In some cases there may be a finding of low neutrophilic granulocytes with high lymphocytes. What does it mean and what are the causes of this alteration?

The causes main factors of the simultaneous presence of neutropenia and lymphocytosis can be many. Among the most important causes of high lymphocytes and low neutrophils in children as in adults remember:

  • Viral infections: viruses activate the production and release of lymphocytes, which will then increase in concentration, to the detriment of other cells of the immune system such as neutrophil granulocytes
  • Acute lymphatic leukemia (ALL): in this case a clone of "crazy" lymphocyte begins to replicate out of control: the neutrophils in the blood tests will be reduced, with a large amount of lymphocytes and blasts (immature lymphocytes) and reduction of the others blood cells.
  • Chronic lymphocytic leukemia (CLL): it is the evolution over time of the acute lymphoblastic leukemia just described.

 Low neutrophils and high eosinophils

The finding of neutropenia with eosinophilia is not that rare, and occurs mainly in the following conditions:

  • Allergies
  • Parasitic infections (parasites)
  • Vasculitis
  • Autoimmune Diseases
  • Leukemias with eosinophilic predominance
  • Food intolerance
  • Mycosis
  • Interstitial nephropathy
  • Lymphoma, both Hodgkin and non-Hodgkin
  • Pernicious anemia
  • Rheumatoid arthritis and other rheumatological diseases
  • Urcerative colitis
  • Addinson's disease
  • Tumors and neoplasms
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