Helicobacter Pylori and it's Hematological Impact

r pylori (H. pylori)is the most common infection in humans, with a marked disparity between developed and developing countries.It presents in over 50% of all stomachs in the world population, making it the most frequent infection in humanS. It displays a marked disparity in occurrence between developed countries, where its prevalence oscillates between 30% and 50%, and developing countries, where its prevalence ranges between 80% and 90%.

Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers.

Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease.

This review focuses on hematologic diseases included in international consensus and management guides for H. pylori infection; specifically iron deficiency Anemia, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and extranodal marginal zone mucosa-associated lymphoid tissue lymphoma (MALT Lymphoma). In addition of other hematologic diseases not included in guides and consensus as auto-immune neutropenia, antiphospholipid syndrome, and plasma cell dyscrasias.

Iron deficiency Iron deficiency (ID) is a serious public health issue, regardless of whether it is associated with anemia . It is especially important to remember that ID is a chronic process with a slow onset, in which the iron imbalance may take several years to establish and manifest clinically. One of the consequences can be observed through blood characteristics such as morphological alterations of erythrocytes or the presence of anemia, according to the criteria of the WHO.ID occurs in three stages: pre-latent (stage 1), in which ferritin is between 12 and 30 μg/L, latent (stage 2) when the ferritin falls below 12 μg/L, and ID anemia (stage 3) when anemia is present in addition to diminished or depleted reservoir iron levels (determined by serum ferritin).

Vitamin B12 deficiency Vitamin B12 is required as a coenzyme for the metabolism of the amino acids methionine, threonine and valine and for the transformation of methyl-tetrahydrofolate to tetrahydrofolate, which is necessary for DNA synthesis. Vitamin B12 deficiency, also known as cobalamin deficiency, is defined by low serum values of vitamin B12 and both homocysteine and methylmalonic acid (two components of the vitamin B12 metabolic pathway). Vitamin B12 deficiency occurs as a result of antibodies directed against gastric parietal cells and intrinsic factor, in addition to achlorhydria and a decrease in pepsinogen I and gastrin.

The laboratory diagnosis of vitamin B12 deficiency is established in accordance with the following criteria:

1. serum vitamin B12 levels < 150 pmol/L (< 200 pg/mL) with clinical features and/or hematological anomalies related to vitamin B12 deficiency
2. serum vitamin B12 levels < 150 pmol/L on two separate occasions .
3. serum vitamin B12 levels < 150 pmol/L and total serum homocysteine levels > 13 μmol/L or methylmalonic acid levels > 0.4 μmol/L (in the absence of renal failure and folate and vitamin B6 deficiencies).
4. serum holotranscobalamin levels < 35 pmol/L. Immune thrombocytopenia Primary immune thrombocytopenia (ITP), previously called idiopathic thrombocytopenic purpura and autoimmune thrombocytopenic purpura.ITP has been redefined as "an autoimmune disorder characterized by isolated thrombocytopenia (peripheral blood platelet count 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia.

Primary ITP is associated with congenital or acquired immune disorders, leading to an autoimmune response against platelets or megakaryocytes and characterized because it is not associated with other alterations.

Gastric MALT lymphoma Gastric MALT lymphoma is a rare form of non-Hodgkin lymphoma that affects B lymphocytes and typically develops in lymphoid tissue associated with mucous membranes and rarely in lymph nodes. It represents approximately 5% of all diagnosed non-Hodgkin lymphomas.

The mechanisms by which H. pylori produces the appearance of a lymphoma similar to gastric carcinogenesis has not been fully clarified, but it is likely that environmental, host, and bacterial-related factors must be involved.H. pylori infection leads to development of MALT lymphoma and can take the following course. First, the infection gives rise to a lymphocyte response that conditions a polyclonal B lymphocyte response and MALT formation through antibody production. Then, different lymphocyte populations would maintain the response provoked by the bacteria. In the polyclonal MALT proliferation, a monoclonal population of B-cells could appear and accumulate cytogenetic changes such as translocations, mutations, microsatellite instabilities, eventually evolving into a low-grade MALT lymphoma that is dependent on H. pylori-related antigen stimuli. Finally, new cytogenetic changes such as translocations, suppressor gene deactivation (p53 and p16, among others), and c-myc activation would make this neoplastic population of monoclonal B-cells escape from its dependence on T lymphocytes and H. pylori antigens and favor its transformation into a high-grade lymphoma. As a result of this sequence of events, a low- or high-grade lymphoma would ultimately develop.

UNRECOGNIZED HEMATOLOGIC MANIFESTATIONS This group includes autoimmune neutropenia, antiphospholipid syndrome, plasma cell dyscrasia including monoclonal gammopathy of undetermined significance and multiple myeloma.