1/7

RELATIONSHIPS BETWEEN RBC INDICES

RBC count

a. Used to calculate the Hct (Hct = MCV x RBC count)
b. Used by some to predict iron deficiency vs. thalassemia (e.g., Meltzer index)
b. Largely ignored because it says nothing about the size/Hbization of RBCs 2/7

... you could have LOTS of SMALL RBCs or FEWER LARGE RBCs amounting to the same Hct (viscosity) and Hb (oxygen carrying capacity)!

1/4

APPROACH TO NORMOCYTIC ANEMIA

This is the most common type of anemia, and its differential diagnosis can sometimes feel overwhelming, and 'all over the place'.

The following is organizational scheme with simple diagnostic buckets that covers virtually all causes: 2/4

BUCKET LIST 1:

Appropriate vs. inappropriate retic response (appropriate defined by absolute retic count > 120 x 10^9/L or 0.12 x 10^12/L)?

BUCKET LIST 2:

If appropriate retic response, is there bleeding or hemolysis?

1/5

COAGULATION IN VITRO/IN VIVO

In vitro (test tube):

1. The clotting cascade in plasma is activated by the addition of a negative charge, which activates the intrinsic pathway (aPTT) or tissue factor, which activates the extrinsic pathway (PT) in presence of Ca2+ and PL. 2/5

2. Once the ingredients are added together, the "stop watch" is started and time to clot formation at 37C is measured (the assays do not discriminate between crosslinked and uncrosslinked fibrin).

1/6

NORMOCYTIC, NORMOCHROMIC IRON DEFICIENCY ANEMIA (IDA)

We tend to think of IDA as being microcytic (more consistently than hypochromic). However, there are certain situations in which the MCV is normal in IDA. 2/6

Examples include:

1. A patient with high-normal baseline MCV whose MCV falls within the normal range in IDA (see first graphic for an example).

2. A patient with baseline macrocytosis, for example from concomitant liver disease, B12 deficiency, MDS or hydroxyurea use.

1/7

ANISOCHROMIA

We are used to considering variation in RBC size (increased variation = anisocytosis) by examining a blood smear or evaluating the RDW.

What about variation in RBC Hb concentration ([Hb]) (anisochromia)? 2/7

We can often identify cell-to-cell differences in central pallor on a blood smear.

While we may make mental note of such differences, we rarely incorporate the finding in a summary of the smear. And there is no lab equivalent to the RDW for Hb concentration or "chromia".

1/6

TRANSFUSION AS IRON THERAPY

Yesterday I posted a poll showing CBC data from a patient with severe iron deficiency anemia and asked: assuming she receives 4 units pRBCs (which of course would be excessive here), does she need iron therapy on top of that?

70% answered YES. 2/6

Each unit of RBC contains about 250 mg Fe. So she will have received about 1000 mg of Fe, not far off from her total needs. However, such is iron is bound up in Hb inside the donor RBCs and is not readily accessible for erythropoiesis.

1/4

CORTICOSTEROIDS IN ITP

I tweeted a poll asking whether you would treat a patient with newly diagnosed ITP with high-dose dexamethasone (HD-DXM) or prednisone (PRED).

57% chose HD-DXM. 2/4

I have done a deep dive into this question, and found that compared with PDN, HD-DXM:

1. Achieves higher and faster initial response
2. Is associated with less bleeding
3. Has fewer adverse effects
4. Has comparable response at 6 months

1/4

IGNORE THE MCH!

I don't know about you, but our institution provides the mean corpuscular hemoglobin (MCH) with the CBC.

Not only is it a virtually useless (and redundant) parameter, but it often gets confused with the much more meaningful MCHC. 2/4

The MCH is the ave weight of the RBC in Hb (reported in pg). In contrast to the MCHC, it has no place in diagnostic algorithms for anemia.

MCH tracks with the MCV and MCHC (MCH = MCV x MCHC; MCV has the largest effect because % deviation is far greater than with the MCHC).

1/4

DEFINITION OF ANEMIA

Yesterday, I posted a poll showing Hb 10.4 and Hct 41 and asked whether or not the patient had anemia.

About 62% of respondents answered YES.

That is the CORRECT answer. 2/4

Anemia is best defined by the Hb because patients with anemia have a deficit in oxygen carrying capacity. Hb binds and carries oxygen. The Hct, by contrast, is a function of cell size (MCV) and RBC count. It is impervious to the contents of the RBC.

1/12

PERNCIOUS ANEMIA AND ENDOSCOPY

I posted a poll yesterday asking whether you would refer a patient with pernicous anemia (PA) to a gastroenterologist for consideration of upper endoscopy.

Most of you answered YES. 2/12

There is no evidence that initial or surveillance endoscopy affects the outcome of patients with PA.

That being said, most GI practice guidelines recommend endoscopy, whereas the sole hematology guideline (BSH) does not.

1/7

CASE

Yesterday, I posted a time series of CBCs and reticulocyte counts and asked a series of questions.

Let's address each question in turn. 2/7

Q1. Describe the CBC on 2/11.
A1. Leukocytosis (WBC > 11 x 10^9/L) with normocytic, normochromic anemia (Hb < 12-13 g/dL, MCV 80-100 fL, MCHC 32-36 g/dL), anisocytosis (RDW-SD > 46 fL) and thrombocytosis (PLT > 400 x 10^9/L).

1/5

SVT - TO ANTICOAGULATE OR NOT TO ANTICOAGULATE

I posted a poll asking whether and how you would anticoagulate a patient with superficial vein thrombosis (SVT) of the leg. There was a pretty even split in votes between the 4 options. 2/5

Most respondents chose to anticoagulate, though there was no clear consensus on the type/duration of anticoagulation.

In fact, clinical practice guidelines would recommend anticoagulating this patient with either fondaparinux or rivaroxaban for 45 days.

1/5

DVT IN BEHCET SYNDROME - TO ANTICOAGULATE OR NOT TO ANTICOAGULATE

I posted a poll yesterday asking whether you'd choose to anticoagulate a 41 yo F with a history of Behcet syndrome (BS) presenting with a DVT. 2/5

Most responded YES, which actually reflects current practices (in a 2012 survey 87% of physicians from USA preferred anticoagulation in this setting) but runs counter to some expert opinion and clinical guidelines.

1/4

DIC or CIRRHOSIS?

I posted a poll last week showing two lab results:

1. Low FV
2. Elevated FVIII

I asked whether this patient was likely to have congenital/acquired FV deficiency, DIC or cirrhosis.

Most responded CIRRHOSIS. 2/4

In fact, one could make a case for any of the 4 possibilities:

1. Congenital or acquired FV deficiency but only in setting of acute phase response (e.g., infection, inflammation) causing the elevated FVIII.

2. Cirrhosis - low V/high VIII is classic.

1/8

DEVELOPMENTAL PLASTICITY AND IRON DEFICIENCY

Developmental plasticity refers to the property (typically adaptive) by which the same genotype produces distinct phenotypes depending on the environmental conditions under which development takes place. 2/8

Developmental plasticity acts by definition over long time-scales, linking conditions present during early stages (development) to phenotypes that may not arise for many years (e.g., late childhood-adulthood).

1/5

I posted a poll asking whether you would treat a patient with acquired TTP using rituximab (anti-CD20 therapy) and/or caplacizumab (anti–von Willebrand factor nanobody) .

Interestingly, the leading response was neither!

Let's look at what the guidelines recommend. 2/5

International Society on Thrombosis and Haemostasis (ISTH):

The ISTH recommends using both rituximab and caplacizumab for acquired TTP, first acute event (conditional recommendation).

1/8

HEREDITARY HYPERFERRITEMIA CATARACT SYNDROME (HHCS)

Yesterday I tweeted a series of labs and asked for a story. Let's look at the data a little more closely. Follow along with the numbers on the graphic. 2/8

Let's begin with the CBC:

1. Acquired microcytosis, thus not thalassemia (unless acquired HbH). Iron deficiency (ID) most likely, though cannot r/u anemia of inflammation based on just the MCV.

2. Hypochromia (low MCHC) concomitant with the microcytosis, most c/w ID.

1/8

FOLATE SUPPLEMENTATION IN HEMOLYTIC ANEMIA

The votes are in as to how much (in any) supplemental folic acid to give a patient with hemolytic anemia!

The most popular answer was 5 mg/day. 2/8

This is a really tough one to nail down because with the exception of a single trial in children with SSD published in 1983 (PMID: 6347243), there have been no randomized studies exploring the risks-benefits or dose effects of folic acid supplements in hemolytic anemia.

1/8

SERUM FERRITIN

Ferritin serves to store/sequester iron inside cells. Small amounts of ferritin are found in the serum and their levels are used clinically in the ddx of anemia and as an indicator of iron overload or inflammation. 2/8

A single ferritin nanocage (24 subunits of L and H chains) is capable of accumulating up to 4,500 atoms of iron. Compared with intracellular ferritin, serum ferritin has few H chains and is iron poor.

1/12

TREATMENT OF SEVERE IDA

I tweeted a poll yesterday asking how you would treat a 31 yo F with chronic iron deficiency anemia and a Hb 5.9 g/dL. The options included transfusion alone, iron alone or transfusion followed by iron. 2/12

With over 6,500 votes cast, the most popular choice was transfusion followed by IV iron replacement therapy, but there was a spread across all answers. There were lots of interesting comments (examples shown in graphic), and some healthy back-and-forth.

1/10

ORAL IRON IN IRON DEFICIENCY ANEMIA (IDA)

I tweeted a poll asking how you would treat a case of uncomplicated IDA with oral iron. The options and responses are shown below: 2/10

There is no one right answer, though existing data (notwithstanding clinical practice guideline recommendations) support the use of a single dose of oral iron on alternative days. Most of you concurred.