1. and BLEEDING DISORDERS
RBC
and BLEEDING DISORDERS
RBC 7.4 microns in diameter

2. RBC and Bleeding Disorders
NORMAL
Anatomy, histology
Development
Physiology
ANEMIAS
Blood loss: acute, chronic
Hemolytic
Diminished erythropoesis
POLYCYTHEMIA
BLEEDING DISORDERS
Topics

3. Classical RBC’s and platelets, as in in the lab or your office with WRIGHT’s stain.

4. TABLE 13-2 -- Adult Reference Ranges for Red Blood Cells *
Measurement (units)
Men
Women
Hemoglobin (gm/dL)
13.6–17.2
12.0–15.0
Hematocrit (%)
39–49
33–43
Red cell count (106 /µL)
4.3–5.9
3.5–5.0
Reticulocyte count (%)
0.5–1.5
Mean cell volume (µm3 ) MCV
82–96
Mean corpuscular hemoglobin (pg) MCH
27–33
Mean corpuscular hemoglobin concentration (gm/dL) MCHC
33–37
RBC distribution width
11.5–14.5
HGB X 3 = HCT, a rough rule of thumb

5. Bone marrow biopsy stained with H&E (left), and smear stained with Giemsa (right). BOTH have special advantages!

6. WHERE is MARROW? Yolk Sac: very early embryo Liver, Spleen: NEWBORN
BONE
CHILDHOOD: AXIAL SKELETON & APPENDICULAR SKELETON BOTH HAVE RED (active) MARROW
ADULT: AXIAL SKELETON RED MARROW, APPENDICULAR SKELETON YELLOW MARROW

7. MARROW FEATURES CELLULARITY 50% MEGAKARYOCYTES at least 1-2/hpf
M:E RATIO  3:1
MYELOID MATURATION  1/3 bands or more
ERYTHROID MATURATION  nucleus/cytoplasm
LYMPHS, PLASMA CELLS  small percentage
STORAGE IRON, i.e., HEMOSIDERIN present
“FOREIGN CELLS”
This is a very intense slide, you may have to write a lot of stuff down and listen well!
This is the basis on which I was trained, and have been reading bone marrows all my life.

8. This is also a very INTENSE slide!

9. ANEMIAS* BLOOD LOSS IN-creased destruction (HEMOLYTIC)
ACUTE
CHRONIC
IN-creased destruction (HEMOLYTIC)
DE-creased production
Platelet analogy also
Losses occur when the rate of destruction is greater then the rate of production, i.e., the rate of production can’t keep up with the rate of destruction!
* A good definition would be a decrease in OXYGEN CARRYING CAPACITY, rather than just a decrease in red blood cells, because you need to have enough blood cells THAT FUNCTION, and not just enough blood cells.

10. Features of ALL anemias
Pallor, where?
Tiredness
Weakness
Dyspnea
Palpitations
Heart Failure (high output)

11. Chronic: lesions of gastrointestinal tract, gynecologic disturbances.
Blood Loss
Acute: trauma
Chronic: lesions of gastrointestinal tract, gynecologic disturbances.
The features of chronic blood loss anemia are the same as iron deficiency anemia, and is defined as a situation in which the production cannot keep up with the loss.

12. HEMOLYTIC HEREDITARY ACQUIRED MEMBRANE disorders: e.g., spherocytosis
ENZYME disorders: e.g., G6PD deficciency
HGB disorders (hemoglobinopathies)
ACQUIRED
MEMBRANE disorders (PNH)
ANTIBODY MEDIATED, transfusion or autoantibodies
MECHANICAL TRAUMA
INFECTIONS
DRUGS, TOXINS
HYPERSPLENISM

13. IMPAIRED PRODUCTION
Disturbance of proliferation and differentiation of stem cells: aplastic anemias, pure RBC aplasia, renal failure
Disturbance of proliferation and maturation of erythroblasts
Defective DNA synthesis: (Megaloblastic)
Defective heme synthesis:
Deficient globin synthesis: (Thalassemias)

14. MODIFIERS MCV, microcytosis, macrocytosis MCHC, hypochromic MCH
RDW, anisocytosis

15. HEMOLYTIC ANEMIAS Life span LESS than 120 days
Marrow hyperplasia (M:E), (erythropoitin (EPO) +
Increased catabolic products, e.g., bilirubin, hemosiderin, haptoglobin-HGB
To understand why there is an erythroid HYPER-plasia in marrows, with patients having HEMOLYTIC anemias, is CRITICAL!
Would you say all the above levels mean that these are good tests for hemolysis? YES
How about hemoglobinuria too? YES

16. HEMOLYSIS INTRA-vascular (vessels) EXTRA-vascular (spleen)
Which one would be more likely to produce hemoglobinuria? ANS: INTRA-

17. M:E Ratio normally 3:1
The most common reason for a DECREASED M:E ratio with a NORMAL marrow cellularity might be a hemolytic anemia, although a DECREASE in the M cells (myeloid) would also cause this, especially if the cellularity was DE-creased. Please understand this!

18. HEREDITARY SPHEROCYTOSIS
Genetic defects affecting ankyrin, spectrin, usually autosomal dominant
Children, adults
Anemia, hemolysis, jaundice, splenomegaly, gallstones (what kind?)
Note lack of a central pallor and a microcytosis, i.e., low MCV
If most of the RBCs are chewed up in the spleen, do you think splenectomy is often helpful in the management of this disease? YES

19. Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
A- and Mediterranean are most significant types
G6PD converts glucose-6-phosphate into 6-phosphoglucono-δ-lactone and is the rate-limiting enzyme of the pentose phosphate pathway.
What are Heinz bodies? (denatured Hgb) Does G6PD deficiency put RBCs at more risk to oxidative DAMAGE? Ans: YES Is that why it is a hemolytic anemia? YES

20. FEATURES of G6PD Defic. Genetic: Recessive, X-linked
Can be triggered by foods (fava beans), oxidant substances drugs (primaquine, chloroquine), or infections
HGB can precipitate as HEINZ bodies
Acute intravascular hemolysis can occur:
Hemoglobinuria
Hemoglobinemia
Anemia
Heinz bodies, precipitated hemoglobin are seen quite well on a methylene blue stain.
Heinz bodies are seen with alpha-thalasemia, NADPH deficiency, and liver disease too.

21. Sickle Cell Disease Classic hemoglobinopathy
Normal HGB is α2 β2: β-chain defects (Val->Glu)
Reduced hemoglobin “sickles” in homozygous
8% of American blacks are heterozygous
Is sickling more likely in oxygenated blood or NON-oxygenated blood? NON (i.e., REDUCED HGB)
Is sickle cell anemia the mother of all hemoglobinopathies? YES

22. Clinical features of HGB-S disease
Severe anemia
Jaundice
PAIN (pain CRISIS)
Vaso-occlusive disease: EVEREWHERE, but clinically significant bone, spleen (autosplenectomy)
Infections: Pneumococcus, Hem. Influ., Salmonella osteomyelitis
What is the normal weight of a spleen? gms

23. At first the spleen may be enlarged (left) because of HYPERPLENISM due to hemolysis, later it may infarct itself due to small vessel occlussive disease and be quite small (right), perhaps only 1/10 its normal size. What is a NORMAL spleen weight? 150 gm, same as kidney, 1/10th liver.