Bone marrow attenuation

Marrow attenuation is a condition in which hematopoietic stem cells are damaged and stop to function sufficiently; thus (pan)cytopenia develops. It can be a primary marrow attenuation, the so-called aplastic anemia, when the stem cells die idiopathically (probably on the basis of immune mechanisms). The bone marrow can also be damaged secondarily by another process, pancytopenia is usually milder, only temporary and restore without treatment.

Clinical picture
Due to leukopenia, patients tend to have septic infections. Based on thrombocytopenia, platelet-type bleeding is present - petechiae to purpura, ecchymoses, epistaxis, gynecological bleeding, hematuria. However, major bleeding may occur, and bleeding into the CNS may be fatal.

Anemia can result in anemic syndrome - paleness, fatigue, shortness of breath, tachycardia - but it is less common.

Primary marrow attenuation
The primary marrow attenuation is aplastic anemia. There are mild, heavy and very heavy. Severe degrees are defined as meeting at least two cytopenia criteria:


 * reticulocytes <0.1% (or 40 × 109 / l)
 * neutrophil segments <0.5 × 109 / l
 * platelets 20 × 109 / l

Aplastic anemia is thought to be due to immune mechanisms in which noxa (eg. viruses of hepatitis, EBV, parvovirus B19, HIV, radiation, drugs) act as antigen-activating T-lymphocytes that cause hematopoietic stem cell apoptosis. At 70%, the starter cannot be detected.

Diagnostics
The diagnosis is made on the basis of the peripheral blood count, in which cytopenia is present, and on the basis of bone marrow puncture and trepanobiopsy, where there is bone marrow attenuation (fat eyes), and the diagnosis is made per exclusionem: it is excluded myelodysplasia, myelofibrosis, chromosomal aberration, hematological or solid tumor.

Differencial diagnostics
The clinical picture may be similar to the following diseases: myelodysplastic syndrome, paroxysmal nocturnal hemoglobinuria, primary myelofibrosis, lymphoproliferative disorders, rarely infections (TB, legionellosis) or severe hypothyroidism.

Treatment
Treatment with curative intent

At the beginning of treatment at a milder stage immunosuppression by antithymocyte globulin with corticosteroids is used and subsequent long-term administration of cyclosporine A.

Allogeneic bone marrow transplantation is indicated in more severe forms and in younger patients who can handle such drastic treatment.


 * Supportive treatment

Substitution of blood derivatives in the form of erythrocytes and platelets is applied. Prophylactic treatment with antifungals and broad-spectrum antibiotics is also in place. Stimulation of hematopoiesis by growth factors is used.

Secondary marrow attenuation
In secondary marrow attenuation, the hematopoietic stem cell is not damaged by its own immune mechanisms, but by another etiological agent, such as infection or as a side effect of drugs. The attenuation is not so deep, usually lasts several days and adjusts on its own after removing the cause.

The most common infections are: CMV, EBV, parvovirus B19 in patients with hemolysis (hematopoietic cells become depleted by hemolysis) or very severe (anergic, hypothermic) sepsis.

Of the drugs, marrow attenuations are typically caused by cytostatics. Occasionally, unexpected attenuation occurs after methotrexate even at low rheumatological doses. Attenuation is classically described as a side effect of chloramphenicol. Attenuations after thyrostatics (thiamazole, carbimazole, but also propylthiouracil) are relatively common. They may also occur after the administration of older antidepressants.

Related articles

 * Aplastic anemia
 * Myelodysplastic syndrom