Hematology Course Overview Flashcards
What is the difference between serum and plasma, and what is the buffy coat layer of centrifuged blood?
Plasma - Contains albumin, immunoglobulins, coagulation factors, and complement system
Serum - plasma minus clotting factors
Buffy coat - layer of WBCs - mainly neutrophils and lymphocytes
What zone of a slide do we read in a blood smear?
The very thin zone called zone of morphology - on the edge of the smear, where the cells are less densely packed
What test is normally ordered as a first step of working up a blood disorder? How do you know the relative split of cell types?
Complete Blood Count (CBC)
to see what specific cells are present, order a differential
What is the lifespan of an average neutrophil, platelet, or RBC?
Neutrophil - 6-8 hours
Platelet - 7-10 days
RBC - 120 days
Where does hematopoesis first begin and where does it ultimately move to / when?
Starts in yolk sac, then liver / spleen, before finally moving to bone marrow
Moves to primarily bone marrow / some lymph nodes by birth
How is bone marrow directly accessed in clinic? What is the myeloid:erythroid ratio?
Bone marrow biopsy / aspiration via a needle in the iliac crest
-> very painful procedure
Me = 2:1
Two myeloid for 1 erythroid cells
What three things do we expect to see in a bone marrow core biopsy?
- Fat cells
- Hematopoeitic cells
- Bone Trabeculae
What measure are we trying to estimate in bone marrow core biopsy and how is this done?
Cellularity of bone marrow -> what percent of the non-bone areas are hematopoeitic stem cells (and not fat)
Subtract Fat % from cellularity
I.e. Aplastic anemia is all fat = 0% cellularity
Why does pallor tend to occur in anemia?
Blood is shunted away from skin to vital organs
What changes in the eye occur due to anemia?
Retinal hemorrhage can occur due to hypertension caused from high output cardiac state to maintain oxygenation in a state of anemia
When is the only time in which we care about whether an anemia is hypochromic / normochromic and how is this measured?
When the anemia is microcytic or normocytic. We don’t care for macrocytic.
Measured via mean corpuscular hemoglobin (MCH)
MCH < 27 pg = hypochromic
MCH > 27 pg = normochrombic
What are the three size classifications of anemia and the cutoffs?
Microcytic: MCV < 80 fL
Normocytic: MCV 80-99 fL
Macrocytic: MCV > 99 fL
What is the normal reticulocyte percentage and what does it suggest if it is not raised in an anemic patient?
0.5-2.5%
Suggests impaired marrow function or lack of erythropoietin stimulus
What is it important to look at a blood film always if a patient is anemic, even if MCV is normal?
In some cases as in mixed iron deficiency and folate/cobalamin deficiency, the MCV can be normal but there may be a “dimorphic” appearance with some microcytic cells and some macrocytic due to the two deficiencies
Also, WBC / platelet abnormalities will be obvious
What are anisocytosis and poikilocytosis?
Anisocytosis - variations in size
Poikilocytosis - variations in shape
Cell variations seen in anemia
What are Heinz bodies?
Oxidized, denatured hemoglobin precipitating in aggregates
-> common in G6PDH deficiency
How are reticulocytes and Heinz bodies shown as blue? Why are reticulocytes blue?
Methylene blue stain (supravital staining)
Reticulocytes are blue because they are new RBCs and still have some residual RNA which stain blue
What are Pappenheimer bodies?
Accumulations of iron within the RBC, often seen in sideroblastic anemia
What is a Howell-Jolly body and when is it seen?
A DNA remnant in an RBC normally removed by the spleen
It is seen in patients with Sickle cell disease or Hereditary spherocytosis post-splenectomy.
What causes basophilic stippling in RBCs?
Denatured RNA, seen in sideroblastic anemia, lead poisoning, etc
From what cell line do NK cells develop and where are they produced?
Arise from the lymphoid line, same precursor as T cells
Develop in the thymus
What is lymphadenopathy?
Enlargement of a lymph node, usually indicates infection (Reactive lymphadenopathy) or sometimes cancer (lymphoma)
What are the three dividing and non-dividing precursors of neutrophils?
Dividing: Myeloblast -> promyelocyte -> myelocyte
Non-dividing: Metamyelocyte -> band cell -> neutrophil
What are myeloid precursors called, where should they be found, and what CD markers are they positive for?
Myeloblasts, present in small amounts in bone marrow (should NOT be in blood)
Positive for CD34 and CD117
When is G-CSF used?
To produce a rise in circulating neutrophils:
- Post-chemotherapy, radiotherapy, or stem-cell transplant to shorten neutropenia
- Severe neutropenia (congenital or acquired)
Where are neutrophils typically stored when waiting to fight infection, and which are actually measured in the CBC?
CBC = circulating neutrophils (may even be decreased in infection if they enter the tissues)
Marginating pool - not included in CBC, include the large numbers of band / segmented neutrophils held in the marrow
What makes up the reticuloendothelial system?
All the sites in the body which have cells which do antigen processing / phagocytosis, USUALLY derived from monocytes
(except in kidney, where intraglomerular mesangial cells are derived from smooth muscle)
How is diagnosis of neutropenia evaluated?
Determine if isolated or part of pancytopenia (CBC w/differential), then examine bone marrow to see whats causing the issue
How is neutropenia managed?
Stop suspected causes (i.e. drugs)
Give antibacterial prophylaxis and treat infections aggressively as neutropenia often leads to infection / sepsis)
G-CSF often helps
What is a Leukemoid reaction and how can it be told apart from leukemia? What causes it?
Marked reactive leukocytosis with many bands / immature neutrophils, but few dividing pre-neutrophils,
i.e. myeloblasts ->
myelocytes (differentiates from leukemia)
Common in children / young adults in the presence of severe bacterial infection / hemolysis
What is Leukoerythroblastic reaction and what causes it?
Presence of nucleated RBCs and left shift in blood
- > Leukemoid reaction + nucleated RBCs
- > usually caused by myelofibrosis
What are the three broad ways in which neutrophil function can be defective?
- Defects in chemotaxis
- Defects in phagocytosis
- Defects in killing
What are some causes of neutrophil defects in chemotaxis?
Congenital - LAD1
Acquired - corticosteroid therapy (downregulates P-selectin), myelodysplastic syndromes
What are some causes of neutrophil defects in phagocytosis?
Congenital or acquired, usually due to a lack of opsonization (lack of immunoglobulins or complement)
What are some causes of neutrophil defects in killing?
Chronic granulomatous disease
Myeloperoxidase deficiency
Chediak-Higashi syndrome - deficiency in lysosomal trafficking
What leukemia is especially associated with monocytopenia?
Hairy cell leukemia
What are the four most common causes of eosinophilia?
Allergic diseases, parasitic diseases, skin diseases (i.e. psoriasis, atopic dermatitis), drug sensitivity reactions
What is it called when eosinophil count is elevated for over 6 months?
Hypereosinophilic syndrome
What is the usual cause of basophilia?
Chronic myeloid leukemia
Very rarely reactive basophilia, i.e. ulcerative colitis, myxedema
What markers are Langerhans cells positive for?
CD1a, S-100
What is Hand-Schuller-Christian disease and what is it associated with?
Langerhan’s cell histocytosis seen in age >2 (greater than 2 names)
-> scalp rash, skull defects, exophthalmos, and diabetes insipidus (due to posterior pituitary involvement)
How does eosinohpilic granuloma typically present?
Pathologic bone fracture in an adolescent, skin is not involved
(Type of Langerhans cell histiocytosis)
What is hemophagocytic syndrome? Symptoms?
Usually an acquired disease where histiocytes in bone marrow ingest RBCs, white cells, and/or platelets
Due to infection or cancer
Symptoms: pancytopenia, hepatosplenomegaly, fever, multi-organ dysfucnction
What is Rosai-Dorfman disease?
Sinus Histiocytosis with Massive Lymphadenopathy
- > Marked expansion of lymph node sinuses causng a lymphadenopathy
- > chronic, cervical lymphadenopathy of unknown cause
What disorder does Gaucher’s disease put you at increased risk of?
Multiple myeloma
What are the three forms of Gaucher’s disease?
- Chronic, adult-type with no CNS involvement (most common)
- Acute, infantile type - CNS involvement but not bone involvement
- Subacute with CNS and bone, adolescent onset, better prognosis
What are the features of all Gaucher’s types?
All three diseases affect glucocerebrosidases and hence will have hepatosplenomegaly + cytopenias (secondary to hypersplenism)
How long does it take to synthesize one RBC from myeloid precursor cell to reticulocyte?
About 7 days
In what states will you see target cells and why?
Target cells caused by too much cytoskeleton which is normally removed by spleen and liver to not be removed.
Can be seen in asplenia or liver disease
Also seen in iron deficiency -> overproduction of hypochromic, microcytic RBCs which do not have time to be properly filtered by spleen
