128 Erythrocyte and Thrombocyte Abnormalities

Clinically Relevant Classification Principle for Anemias: Mean Erythrocyte Hemoglobin Content (MCH)

In current diagnostic practice, erythrocyte count and hemoglobin content (grams per 100 ml) in whole blood are determined synchronously. This allows calculation of the hemoglobin content per individual erythrocyte (mean corpuscular hemoglobin, MCH) using the following simple formula (p. 10):

Hb (g/dl) · 10

Ery (106/µl)

The mean cell volume, hematocrit, MCH, and erythrocyte size can be used for various calculations (Table 22; methods p. 10, normal values Table 2, p. 12). Despite this multiplicity of possible measures, however, in routine diagnostic practice the differential diagnosis in cases of low Hb concentration or low erythrocyte counts relies above all on the MCH, and most forms of anemia can safely be classified by reference to the normal data range of 26–32 pg Hb/cell (1.61–1.99 fmol/cell) as normochromic (within the normal range), hypochromic (below the), or hyperchromic (above the norm). The reticulocyte count (p. 11) provides important additional pathophysiological information. Anemias with increased erythrocyte production (hyper-regenerative anemias) suggest a high reticulocyte count, while anemias with diminished erythrocyte production (hyporegenerative anemias) have low reticulocyte counts (Table 22).

It should be noted that hyporegenerative anemias due to iron or vitamin deficiency can rapidly display hyper-regeneration activity after only a short course of treatment with iron or vitamin supplements (up to the desirable “reticulocyte crisis”).

The practical classification of anemia starts with the MCH:

—26–32 pg = normochromic

—Less than 26 pg = hypochromic

—More than 32 pg = hyperchromic

Hypochromic Anemias

Iron Deficiency Anemia

Most anemias are hypochromic. Their usual cause is iron deficiency from various causes (Fig. 44). To distinguish quickly between real iron deficiency and an iron distribution disorder, iron and ferritin levels should be determined.

					Hypochromic Anemias	129
	Insufficient iron absorption:			Chronic bleeding and pathological
	●	Lower than normal acidity, no		loss of iron in the following diseases:
		acidity, stomach resection,		●	Disorders of the stomach and
		accelerated passage from			intestines (positive benzidine
		stomach to intestines			test)
	●	Substances that inhibit ab-		●	Diseases of the urethra
		sorption of iron, such as citric			(hematuria!)
		acids and lactic acids, mucus and		●	Diseases of the female repro-
		similar materials			ductive cycle (menorrhagia,
	●	Substances that facilitate iron			metrorrhagia)
		absorption are missing
		(e.g. vitamin C)

Insufficient iron supplementation:

●Iron-deficient diet

●In newborns: insufficient iron transfer from the mother during gravidity

Increased iron requirement:

●Growth/maturation

●Increased production of the new blood cells

Endogenous redistribution:

●Tumors, infections, lung hemosiderosis

Physiological iron loss in females:

●Menses

●Lactation

●Pregnancy

Iron deficiency:

●Fatigue, koilonychia, infectious angle (angulus infectiosus oris), PlummerVinson syndrome, possibly “iron deficiency fever”

●Anemia

●Hypochromy, ring-shaped erythrocytes

●Light serum, deficient in color components

●Serum iron very reduced

Fig. 44 The most important reasons for iron deficiency (according to Begemann)

130 Erythrocyte and Thrombocyte Abnormalities

Table 22 Diagnostic findings and work-up for the most important disorders of the red cell series

Clinical	Hb	MCH	Erythro-	Reti-	Leuko-	Seg-	Lym-	Other cells	Throm-
findings			cyte mor-	culo-	cytes	mented	pho-		bocytes
			phology	cytes		nuclei	cytes
						(%)	(%)
Fatigue,	!	!	Ring-shaped	!	n	n	n	-	n/"
pallor			erythrocytes,
(dysphagia)			anisocytosis
Possibly	!	!	Anisocytosis,	!	n/"	n	n	Possibly	n
fever, weight			poikilocytosis					eosinophils
loss								"
								monocytes "
								left shift
Diffuse	!	!/n/" All sizes,		!	n/!	n	n	-	n/!
symptoms			dimorphic
Acute	!	n	n	n	n	(")	(!)	-	n/!/"
hemorrhage
Subjaundice	!	n	n or pathol.,	""	n/!	n	n	Possibly nor-	n/!
			possibly					moblasts
			spherocytes
Spleen "	!	!	Target cells	"	n	n	n	Possibly nor-	n
								moblasts
Paller	!	n	n	!!	!	!	"	Possibly	!!
possibly								monocytes"
infections
and bleeding
tendency
Pallor	!	"	Macrocytes,	!	!	!	"	Possibly	!/n
possibly			megalocytes					hyperseg-
alcohol his-								mented
tory								granulocytes,
								possibly nor-
								moblasts
Plethora,	"	n	n	n	n/"	n	n	-	n/"
possibly
spleen
Acute bleed-	!	n	n	(")	n	n	n	-	!!
ing tendency

Diagnostic steps proceed from left to right. The next step is usually unnecessary; :. the next step is optional; #the next step is obligatory. n = normal value, != lower than normal, "= elevated, ( ) = test not relevant, BSG = erythrocyte sedimentation rate.

Hypochromic Anemias

131

BSG

Elec-

Iron

Ferritin

Trans-

Tentative

Evidence/

Bone marrow

Ref.

tro-

and

ferrin

diagnosis

further diag-

page

pho-

others

nostics

resis

n

n

!

Ferritin

"

Iron deficiency

Determine

Erythropoiesis " p. 132

!

anemia

source of bleed-

sideroblasts !,

ing; check iron

iron in macro-

absorption

phages !

.

"

? α2" !

Ferritin

!

Acquired/sec-

Search for

Erythropoiesis !,

p. 134

γ"

n/"

ondary anemia

trigger

sideroblasts !

(infectious/

iron in macro-

toxic, paraneo-

phages"

plastic)

.

n

n

"

n/"

!

Sideroachrestic

#

Erythropoiesis ",

p. 106

anemia,

ring sideroblasts

myelodysplasia

present

n

n

n/! –

n/"

Anemia due to

Search for

(Erythropoiesis

p. 140

hemorrhaging

source and

")

reason for

hemorrhages

n

n

n

Hapto-

(n/!)

Hemolytic

Osmotic

(Erythropoiesis

p. 140

globu-

anemia

resistance,

", right shift)

lin !!

Coombs test,

increased storage

n

n

n

Hapto-

Especially:

Hb electro-

of iron

p. 138

globu-

thalassemia

phoresis and

lin !!

further tests

.

"

n

"/(n)

n/"

(!/n)

Aplastic ane-

Search for trig-

Hypoplasia of all

p. 146,

mia or bone

ger or tumor

cell series, or car-

148, 150

marrow carci-

cinoma cells

nosia

n

n

n/" Vitamin

(!)

Megaloblastic

Gastroscopy,

Erythropoietic

p. 152

B12

anemia

determination

megaloblasts

folic acid

of antibodies,

!

possibly

Schilling test

n/! n

!

"

"

Polyeythemia,

ALP, progress- .

Erythropoiesis " p. 162

DD: hypergam-

ion

maglobuline-

mia

n

n

!

duration

–

Thrombocyto-

Search for trig-

Elevated mega-

p. 166

of

penic purpura

gers, possibly

karyocyte count

hemor-

(ITP)

also for anti-

rhaging

bodies

""

PTT n

132 Erythrocyte and Thrombocyte Abnormalities

Table 23 Normal ranges for physiological iron and its transport proteins

	Old units	SI units
Serum iron	150–200 µg/dl	27–36 µmol/l
Newborns
Adults
Female	60–140 µg/dl	11–25 µmol/l
Male	80–150 µg/dl	14–27 µmol/l
TIBC	300–350 µg/dl	54–63 µmol/l
Transferrin	250–450 µg/dl	2.5–4.5g/l
Serum ferritin		30–300 µg/l
	(15–160 µg/l premenopausal)

TIBC = Total iron binding capacity.

This usually renders determination of transferrin and total iron binding capacity (TIBC) unnecessary. If samples are being sent away to a laboratory, it is preferable to send serum produced by low-speed centrifugation, since the erythrocytes in whole blood can become mechanically damaged during shipment and may then release iron. Table 23 shows the variation of serum iron values according to gender and age.

It is important to note that acute blood loss causes normochromic anemia. Only chronic bleeding or earlier serious acute blood loss leads to iron deficiency manifested as hypochromic anemia.

Iron Deficiency and Blood Cell Analysis Focusing on the erythrocyte morphology is the quickest and most efficient way to investigate hypochromic anemia when the serum iron has dropped below normal values. In hypochromic anemia with iron and hemoglobin deficiency (whether due to insufficient iron intake or an increased physiological iron requirement), erythrocyte size and shape does not usually vary much (see Fig. 45). Only in advanced anemias (from approx. 11 g/dl, equivalent to 6.27 mmol/l Hb) are relatively small erythrocytes (microcytes) with reduced MCV and MCH and grayish stained basophilic erythrocytes (polychromatic erythrocytes) seen, indicating inadequate hemoglobin content. Cells with the appearance of relatively large polychromatic erythrocytes are reticulocytes. The details of their morphology can be seen after supravital staining (p. 141). A few target cells (p. 139) will be seen in conditions of severe iron deficiency.

In severe hemoglobin deficiency (! 8 g/dl, equivalent to 4.96 mmol/l) the residual hemoglobin is found mostly at the peripheral edge of the erythrocyte, giving the appearance of a ring-shaped erythrocyte.

Small, hemoglobin-poor erythrocytes indicate iron deficiency

a b

c d

Fig. 45 Iron deficiency anemia. a and b Erythrocyte morphology in iron deficiency anemia: ring-shaped erythrocytes (1), microcytes (2) faintly visible target cells (3), and a lymphocyte (4) for size comparison. Normal-sized erythrocytes (5) after transfusion. c Bone marrow cytology in iron deficiency anemia shows only increased hematopoiesis and left shift to basophilic erythroblasts (1). d Absence of iron deposits after iron staining (Prussian blue reaction). Megakaryocyte (1).

133