Acquired Pure Red Cell Aplasia
Authoritative source
Summary from authoritative source:
Overview
Pure red cell aplasia (PRCA) is an extremely rare profound anemia characterized by a very low reticulocyte count and the virtual absence of erythroid precursors in the bone marrow. All other cell lineages (e.g., WBC and platelets) are present in normal numbers and appear morphologically normal. The most common form of primary PRCA is an idiopathic autoimmune disorder. It maybe part of a myelodysplastic syndrome (MDS) isolated to one cell line. Secondary PRCA maybe due to drugs, viral infections.
Presentation
PRCA generally presents insidiously, with most individuals lacking signs and symptoms of anemia until the reduction in hemoglobin and hematocrit becomes quite severe, often to a hematocrit of <10 percent. Extreme pallor or decreased exercise tolerance may be the first signs of this disorder in a previously healthy individual.
Anemia is often severe with hemoglobin <4 g/dL and hematocrit <10 percent.
- Normocytic, normochromic anemia.
- Absolute reticulocyte count <10,000/microL (or reticulocyte percentage <0.5 percent; typically <0.2 percent).
- Normal WBC and platelet counts, in the absence of a concurrent disorder such as CLL.
- Normocellular bone marrow, with erythroblasts totaling <1 percent or proerythroblasts plus basophilic erythroblasts totaling <5 percent of nucleated cells.
- No significant abnormalities in the myeloid, lymphocytic, or megakaryocyte lineages, unless the patient has a concurrent diagnosis of CLL or chronic myeloid leukemia (CML). There may be a slight increase in polyclonal lymphocytes or plasma cells.
Timing: Slow onset. The anemia in PRCA occurs gradually because circulating RBCs die and are not replaced. The loss of RBCs occurs at an approximate rate of 0.8 percent per day. This daily percentage reflects the typical RBC lifespan of 120 days (0.8 percent is 1/120 of the circulating RBCs). This pace is slow enough to allow the body to compensate for a reduced oxygen-carrying capacity, which explains why patients with PRCA may not present until a significant degree of anemia is present.
Assessments
The anemia is normochromic and normocytic. The diagnosis of PRCA is suspected in an individual with isolated anemia with severe reticulocytopenia ( absolute reticulocyte count <10,000/microL).
Plan
Observe for spontaneous remission. If an underlying condition is thought to explain - manage it. Transfusions if severe and symptomatic.
Prognosis
Spontaneous remissions are seen in most cases, but duration of disease is variable. Provide supportive therapy, find, and treat cause. PRCA generally does not shorten survival if appropriate therapy is given and the individual does not succumb to their underlying disorder.
- Can it re occur? Yes, but this is an extremely rare disease. so re-occurrence would be very very rare.
- How long is the condition expected to last once diagnosed – not clear
- If it can re-occur how long do you think is the gap between the end of prior episode and start of next episode. not clear
Strengtheners
- Bone marrow biopsy
Disqualifiers
- Congenital forms of anemia: Diamond-Blackfan anemia, Transient erythroblastopenia of childhood, Sideroblastic anemia all time
Phenotype development:
- We decided to model this cohort as only one event per person. This is because it is a very rare disease, its prognosis is not clear (may have spontaneous remission or lead to death, may last for short or long-term). We may be able to model the end of the disease by looking for indicators of normocytic anemia, but we did not do this.
- Because the condition may be insidious in onset, we expected the persons with the condition to have index date misclassification ie. mismatch between date of diagnosis and date of true disease onset. So, we built the cohort definition to be indexed on either anemia or diagnosis, as long as the anemia is followed by the diagnosis.
- Remove persons with congential or genetic anemia: we decided to remove persons with hereditary red blood cell disorders including hemoglobinopathy, congential anemia, sickling disorder, thalassemia, sickle cell trait. This is based on our opinion that presence of this condition would offer an alternate diagnosis.
- Remove persons with consititutional red cell aplasia: we evaluated a cohort of persons with constitutional red cell aplasia and found these persons to have a congenital forms of this condition. Since we were interested in acquired form - we decided to exclude persons with congential form.
- No bone marrow transplant: we removed from consideration persons who had bone marrow translant in the past. Bone marrow transplant is not a treatment for pure red cell aplasia, as the other cell lines are expected to be normal. So the presence of bone marrow transplant might suggest another reason for anemia.
- Normal hemoglobin or hematocria: if a person with the diagnosis of pure red cell aplasia, has at the same time, normal hemoglobin or hematocrit (or a diagnosis of polycythemia) - we removed such persons because these are mutually exclusive to pure red cell aplasia.
Potential problems with this phenotype:
- Miss rate/False negative rate/Sensitivity - we believe it is hard to get an accurate diagnosis of this condition as there is no specific test. Clinicians should suspect patients to have this condition when they present with isolated normocytic anemia. The differential diagnosis is a long list of anemias. We expect it would be hard to get an accurate diagnosis. We do not know how many people with the condition may have a related diagnosis and never get the diagnosis of pure red cell aplasia.
- Index date misclassification - because of insidious onset, it is possible that this condition may go undiagnosed for a long time.
- Specificity - we cannot rule out the possibility of other types of normocytic anemia being called pure red cell aplasia.
Cohort Submission:
C207 [P] Acquired Pure Red Cell Aplasia available on data.ohdsi.org/PhenotypeLibrary
Phenotype evaluation:
Insights from Cohort Diagnostics
- inclusion rule: we loose approximately 10% the number of persons in the cohort each for the two rules - 1. no congential or genetic anemia, 2. no constitutional pure red cell aplasia. We think these are justified as we determined that the diagnosis code of constitutional red cell aplasia represents persons who do not have acquired pure red cell aplasia
- incidence rate: as expected the condition was rare at around 0.02 per 1,000 persons per year.
- Characterization:
day 0/index date
condition domain: iron deficiency anemia, acute post hemorrhagic anemia, gastrointestinal hemorrhage is observed. This suggested specificity errors. thymoma was observed in about 10% of persons,
procedure domain: blood draw, blood typing, emergency blood transfusion
Overall impression:
- while some of the persons may truly have acquired pure red cell aplasia as evidenced by treatments such as blood transfusion, the presence of diagnosis of hemorrhagic anemia and gastrointestinal hemorrhage suggests the present of specificity errors.
- There are several errors in this cohort definition and its use should be done cautiously. We cannot rule out sensitivity errors because of the rule removing persons with constitutional red cell aplasia and congenital anemias. Because of the nature of the insidious onset in this phenotypes - we expect index date misclassification. We have also observed evidence of specificity error because the persons are reported to have concomitant hemorrhage and iron deficiency.
- Before using this cohort definition or its derivatives, it is recommended to consider the impact of these errors on a study.
Performance characteristics
PheValuator is not feasible for this cohort definition.
see https://data.ohdsi.org/PhenotypeLibrary/ cohort id
C207 [P] Acquired Pure Red Cell Aplasia