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William Aird

@WilliamAird4

Dec 5

1/4

HYPERSPLENISM

History: First described by Wiseman and Doan in 1942

Definition: A syndrome characterized by:

1. Splenomegaly
2. Blood cytopenia(s)
3. Compensatory hyperplasia of the bone marrow (BM)
4. Correction of cytopenia(s) with splenectomy (rarely done today)

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Causes:

1. Cirrhosis & portal hypertension (PH)
2. Congestive splenomegaly
3. Gaucher disease
4. Leukemia/lymphoma
5. Sarcoidosis
6. Malaria
7. Schistosomiasis

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Mechanisms:

1. Sequestration of blood cells in spleen (primary mechanism)

2. Increased splenic destruction of blood cells (minor role)

(In the 1940s there was an opposing argument that the spleen releases humours which suppress blood cell production in/release from BM)

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William Aird

@WilliamAird4

Nov 29

1/

The ABCs of acute phase proteins (APPs):

1. APPs are a component of the acute phase response, an evolutionarily conserved response to injury or infection.

... other components include fever, leukocytosis, anemia of inflammation, thrombocytosis, negative nitrogen balance...

2/

2. APPs are synthesized primarily but not exclusively by liver hepatocytes (endothelial cells synthesize VIII and vWF, which are considered APPs)

3. APPs are not only useful diagnostically, they also play a protective and at times pathophysiological role in the host response

3/

4. From clinical standpoint consider: 2 NEGATIVE APPs (albumin and transferrin) and 4 POSITIVE APPs (ferritin, fibrinogen, haptoglobin, CRP)

5. APRs tend to go up and down in tandem, but different patterns appear between different diseases and between different patients

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William Aird

@WilliamAird4

Nov 10

57 yo F underwent a hysterectomy that was complicated by excessive bleeding (day 1).

You are called 8 days later (day 8), because she has anemia associated with positive hemolytic indices (DAT/Coombs negative).

What is the source of her hemolysis?

A review of the patient's chart reveals that:

1. Two days after hysterectomy (day 3) she was taken to the operating room for evacuation of hemoperitoneum.

2. The following day (day 4), a CT pelvis showed active extravasation from internal iliac artery and large pelvic hematoma.

The source of the hemolytic markers is the patient's resorbing hematoma. The body clears extravasated blood just as it destroys RBCs in cases of extravascular hemolysis (e.g., in warm AIHA), leading to some combination of increased LDH/bili and decreased hapto.

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William Aird

@WilliamAird4

Nov 5

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Trauma patients bleed whole blood, so we would not expect their Hb/Hct to change until fluid shifts from the interstitial space to the vascular space and/or until they receive IV fluids.

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Classic teaching is that the shift of fluid from interstitium to vasculature occurs slowly over hours, hence early assays for Hb/Hct are not reliable (i.e. they remain normal).

What's your understanding?

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Turns out that controlled studies in animals and humans have shown an almost immediate drop in Hb/Hct after hemorrhage - within minutes - indicating near instantaneous transvascular fluid exchange to compensate for the loss in blood volume (see graphic for examples).

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William Aird

@WilliamAird4

Nov 3

1/6

48 yo F with chronic elevation in serum ferritin x years presents with pagophagia (ice craving).

She has new microcytic anemia with elevated RDW, and her TIBC - which was always normal - is now off the charts (736 mcg/dL).

What's going on?

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You suspect iron deficiency, but how does one explain the persistently elevated ferritin.

... and is there a test to confirm the diagnosis of iron deficiency in this setting?

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Inflammation increases serum ferritin, but virtually never > 100 ng/ml when there is concomitant iron deficiency (CKD/ESRD patients are an exception).

So inflammation cannot explain this patient's elevated ferritin in the setting of presumed iron deficiency anemia.

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William Aird

@WilliamAird4

Oct 31

1/11

The incidental finding of a low white cell count in asymptomatic individuals of African ancestry is not uncommon.

The condition used to be called BENIGN ETHNIC NEUTROPENIA (BEN).

2/11

It has been suggested that the term BEN be changed to a name that avoids the suggestion that ethnicity alone is causal or that this common variant is abnormal.

One of the proposed terms is Duffy-null associated neutrophil count (DANC).

3/11

DANC results from a polymorphism in a gene called ACKR1 that encodes for Duffy antigen receptor for chemokines (DARC, also called Duffy antigen), a membrane glycoprotein that acts as a chemokine receptor for proinflammatory cytokines.

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