EVALUATION OF IMMUNE AND HEMATOPOIETIC DISORDERS - PART I

Functional Assessment of Hematopoiesis: Diagnosis of Myeloproliferative Disorders
All myeloid and lymphoid cells in the blood, bone marrow, lymph nodes, and other organs are ultimately derived from the "pluripotent hematopoietic stem cell." This stem cell is capable of self renewal but is also capable of further differentiation toward an erythroid, myeloid, megakaryocytic, or lymphoid lineage. Progenitor cells at various stages of this differentiation can be identified by characteristic patterns of growth in soft agar where, when given the appropriate growth factors, these cells form small colonies. Hence, various types of hematopoietic progenitors are designated "colony forming units" or "CFU". The particular type of progenitor is further differentiated by subscripts to the CFU designation. Thus, a CFUgemm is a cell which retains the ability to differentiate into granulocyte, erythroid, monocyte, and megakaryocyte lineages, while a CFUgm is a cell which can only differentiate into either granulocytes or monocytes. Cells committed solely to the erythroid lineage are designated CFUe. In the case of erythroid progenitor cells an additional subtype is commonly identified and is known as the BFUe or "burst forming unit of the erythroid lineage".

Each of the above designated progenitors can be measured in the laboratory through cell culture techniques on samples derived from peripheral blood, bone marrow, or umbilical cord blood. The growth and identification of the cells requires approximately three weeks of culture. Under normal circumstances, these cells will not grow unless they are provided with an exogenous source of their crucial growth factors, for example, erythropoietin is necessary for the growth of both CFUe and BFUe.

One of the major uses of these assays is to assess the functional adequacy of peripheral blood, bone marrow, and umbilical cord blood stem cell collections for the purpose of autologous or allogeneic transplantation in the treatment of malignant and genetic disorders. However, another important use of these assays is in the diagnosis of the myeloproliferative disorder Polycythemia Vera, particularly in patients in whom the clinical findings of the disease may be relatively subtle. Polycythemia Vera represents a disorder in which the erythroid progenitor cells are capable of growth and differentiation relatively independent of growth factors, particularly erythropoietin. This independence results in the clinical characteristics of the disease: unrestrained erythrocytosis often accompanied by thrombocytosis, functional platelet abnormalities resulting in both a bleeding and a thrombotic tendency, splenomegaly, bone marrow fibrosis, and, less commonly, leukocytosis. While it is easy to identify patients that have the full blown clinical picture of Polycythemia Vera, patients with more subtle disorders may be impossible to diagnose without hematopoietic progenitor culture assays. In particular, young patients presenting with isolated hepatic vein thrombosis (Budd-Chiari syndrome) may be hematologically grossly normal but nonetheless have a myeloproliferative disorder. Indeed, some authorities believe that up to 30% of young patients presenting with primary Budd-Chiari syndrome fall into this category. Often, in these cases, the diagnosis can only be definitively confirmed by assessing hematopoietic progenitor growth from either blood or bone marrow in the presence and absence of the erythropoietin growth factor. Normal individuals will not grow CFUe and BFUe in the absence of erythropoietin while individuals with myeloproliferative syndromes will show growth since their progenitor cells are relatively independent of this requirement. Although traditionally performed predominantly with bone marrow specimens, it is also possible to carry the test out on blood specimens.

Because of the highly specialized nature of these hematopoietic progenitor assays, they must first be scheduled with the Immunology Laboratory and it is recommended that the ordering physician talks first with the Director of the Laboratory (5-2440) or one of the Laboratory Medicine residents.

Brian R. Smith, M.D.

LABELING BLOOD BANK SAMPLES

With the advent of the CCSS order-entry system, we have changed the way that samples for Blood Bank must be labeled. When a sample is drawn, the patient must be identified from the wristband. The person who draws the sample accepts responsibility and MUST SIGN the sample label. DO NOT bring an unlabeled clot to the computer or addressograph machine and then generate a label. It is less likely you will mix up labeling if you bring the label to the bedside, especially if you are drawing blood from multiple patients. If the order to draw blood was generated via CCSS, use a CCSS label. The Blood Bank WILL NOT accept improperly labeled clots (see Table). For questions, contact the Blood Bank Director, Dr. Edward Snyder (5-2441).

To send a CCSS or Addressograph-labeled clot to Blood Bank:
1. Obtain the label FIRST
2. Go to the bedside and identify the patient by checking the label with the wristband
3. Draw the blood
4. Affix the label (parallel with the tube's long axis).
5. Sign the label

Table 1

TABLE OF LABELING REQUIREMENTS FOR BLOOD BANK SPECIMENS

Acceptable Label	Requirements	Caution
1. Original label affixed on red top tube - either generic white label or special "FOR BLOOD TRANSFUSION SERVICE" label (only if completely filled out as required)	1. Patient first and last name; unit number or date of birth; date drawn; signature of person drawing blood.	1. Only labels completely filled out and signed are acceptable.
2. CCSS computer-generated label only if signed by the person who drew the blood (full signature required)	2. Label affixed to red top tube must have full signature of person drawing blood. NO INITIALS.	2. Must be signed. Unsigned clots will NOT be used. NO EXCEPTIONS.
3. Addressograph label imprinted from the patient blue card, only if signed by the person who drew the blood (full signature required)	3. Label affixed to red top tube must have full signature of person drawing blood. NO INITIALS.	3. Must be signed. Unsigned clots will NOT be used. NO EXCEPTIONS.

NOTE: 1. The Emergency Room has an acceptable emergency patient identification numbering system.
2. Do not use addressograph labels on pediatric size blood tubes.