Question 11
Thrombocytopenia is traditionally taught with distinguishing between a bone marrow disorder, ruling out splenic sequestration, or peripheral destruction.
Discussion points: Discuss the differential diagnosis of thrombocytopenia.
Decreased production:
- Congenital bone marrow disorders (TAR, Fanconi’s)
- Aplasia (chemotherapy, radiation, alcohol, medications)
- Infiltration
- Hereditary disorders (May Hegglin, Bernard Soulier)
- Nutritional deficiencies (n.b. – it can take 2 weeks for platelets to return to normal levels following replacement)
Distribution:
- Splenomegaly (30% of plts are stored in the spleen)
- Hypothermia
- Dilution post massive transfusion
Destruction:
- Immune mediated destruction (drug induced and chronic/acute immune thrombocytopenia)
- Consumption (TTP, DIC, TTP, HUS, HELLP)
Question 12
The CBC is the most commonly ordered test in medicine. What are the components of the CBC?
Components of the CBC:
- RBC = # of RBCs per liter
- MCV = mean cell volume
- MCH = avg. amount of Hb in an individual cell
- Decreased in hypochromic anemias
- Total mass of Hb / # RBCs in volume of blood
- MCHC = avg. concentration of Hb in a cell
- Increased in HS and Hb SS
- RDW = reflection of anisocytosis
- Ddx: IDA, reticulocytosis, blood transfusion etc
- HCT = measures the volume of red blood cells compared to the total blood volume (red blood cells and plasma)
Question 13
What factors cause a factitiously elevated hemoglobin?
Measuring hemoglobin values:
- Automated cell counter from a tube of well-mixed EDTA-anticoagulated blood filled to a predetermined level.
- RBCs are lysed, all forms of hemoglobins are converted to the colored protein cyanomethemoglobin and measured by a colorimeter.
- An inadequate sample, whether due to insufficient volume or inadequate anticoagulation, may give false readings.
- Hemoglobin is quantified based on its absorption characteristics. Conditions such as hyperlipidemias, hyperbilirubinemia, a very high white blood cell count, and high serum protein can interfere with this measurement and result in falsely elevated hemoglobin values.
Question 14
List the indications for a bone marrow biopsy. What investigations can be collected from a bone marrow aspirate and biopsy?
Indications for a bone marrow biopsy:
- Evaluation of anemia or a cytopenia NYD
- Staging for lymphoproliferative disorders
- Diagnosis of hematologic malignancies including AML, myeloma, MDS, and MPNs
- Gold standard for evaluation of iron stores
- Evaluation of other diseases (i.e. macrophage activation syndrome, storage disease) or infections
Distinguish the differences of an aspirate compared to a biopsy.
| Investigation | Bone Marrow Aspirate | Bone Marrow Biopsy |
| Cytology | Ensure spicules in collection
Allows assessment of bone marrow cellularity and cytology of cells |
Preferred 2cm length of biopsy
Assesses bony architecture |
| Flow cytometry | Allows for evaluation of diagnosis and clonality re identification of CD markers (i.e. in leukemias and lymphomas) | Not routinely done on a biopsy specimen
Can try to obtain if separate biopsy specimen is placed in a sterile medium More common: Perform immunohistochemistry stains on biopsy material |
| Cytogenetics | Evaluate chromosomal aberrations (i.e. deletions, translocations)
Imperative to be collected for AML, ALL, CML, CLL, MM, MDS, and certain lymphoproliferative disorders |
Can try to obtain if a separate biopsy specimen is placed in a sterile medium |
| Molecular studies | PCR based testing
Must be collected in suspected cases of acute leukemia, CML, and myeloproliferative neoplasms |
Can try to obtain if a separate biopsy specimen is placed in a sterile medium |
Question 15
Paroxysmal Nocturnal Hemoglobinuria has an incidence of 0.13/100,000. What is the primary defect in this disorder and how does it lead to its primary hematologic abnormalities?
- What are the main signs/ symptoms of PNH?
Symptoms emerge with the increased platelet aggregation and hemolysis with resultant reductions in nitrous oxide:- Thrombosis (consider in cases with unusual VTE such as the mesenteric arterial / venous system)
- Deficiencies in nitric oxide: abdominal pain with smooth muscle bowel wall spasm, erective dysfunction, symptoms of pulmonary hypertension
- “Red urine” (due to hemoglobinuria)
- Anemia/ pancytopenia including elevations of markers of hemolysis
- What is the leading cause of mortality?
One-third of patients will die in 5 years, with 40% dying of clot-related disease. - What therapies are efficacious?
Treatment: Most problems in PNH are due to the unopposed complement against PNH cells. Eculizumab is an approved antibody directed therapy blocking the cleavage of C5 and thereby preventing formation of the membrane attack complex and resultant destruction of blood cells. It is essential patients are vaccinated against N. Meningitides prior to receiving this medication.
Points to consider: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia caused by the expansion of a hematopoietic progenitor cell that has acquired a mutation in the X-linked PIGA gene. PIGA is essential for the synthesis of glycosyl phosphatidylinositol (GPI) anchor molecules CD55 and CD59 which protect stem cells aginst complement mediated hemolysis.
It may be acquired with disorders such as aplastic anemia or MDS wherein immune dysregulation and stem cell mutations allow a PNH clone in the bone marrow to proliferate.
