Sie sind auf Seite 1von 35


A 70-year-old woman presented with progressive weakness and fatigue.
The symptoms had begun about a month earlier, and she no longer felt
well enough to do her housework or take her daily walk. Although her
breathing was normal at rest, she was too short of breath to walk more
than two or three blocks.

The results of the complete blood cell count (CBC) performed in her
physician's office were:
hemoglobin, 5.4 gm/dL;
mean corpuscular volume (MCV), 103 m3;
red cell distribution width (RDW), 19.8% (normal, 12%-15%),
white blood cell count, 3,900/mm3 (48% neutrophils, 43% lymphocytes,
8% monocytes, 1% eosinophils);
and platelets, 62,000/mm3.
Based on these results, the patient was hospitalized.
She had no history of recent bleeding, jaundice, fever, anemia, or heart
disease. She had not been exposed to medications (other than occasional
vitamins and aspirin) or toxins. She had not abused alcohol and had no
previous hospitalizations. Findings on the physical examination were
unremarkable except for mild tachycardia at rest (96 bpm), a blood
pressure of 146/84 mm Hg recumbent and 142/78 mm Hg standing, pallor,
external hemorrhoids, and trace pitting edema of the feet. Neither the
liver nor spleen were palpable. The stool was negative for occult blood.

A chest x-ray was normal, and an electrocardiogram showed only sinus
tachycardia. The blood urea nitrogen (BUN) level was 15 mg/dL; glucose,
108 mg/dL; and total bilirubin, 1.2 mg/dL (normal, <1.2). Electrolyte levels
were normal. A sickle cell preparation was negative.


A 57-year-old woman presents to the clinic for evaluation of
ataxia, weakness. The patient has been taking a multivitamin

Hematocrit is 38%

white blood cell count 4,000; platelet count 100,000

What tests would you order next ?

What are th?

A 39-year-old woman was referred to our institution for evaluation of anemia.
She was known to have multiple comorbidities and had a baseline hemoglobin
concentration of approximately 10.5 g/dL. About 6 months before her referral,
the patient began having recurrent episodes of severe anemia, with
hemoglobin values as low as 3.5 g/dL. She had become transfusion-dependent
and had received about 30 units of packed red blood cells (RBCs) in the
preceding 3 months. The patient denied any history of easy bruisability,
menorrhagia, or overt evidence of bleeding from any site. Additionally, she
denied any change in the appearance or color of her urine and had no history
of jaundice. There was no family history of anemia or any other hematologic
disorder. As an outpatient, she had undergone an extensive evaluation at
another institution, but results failed to provide an explanation for her

The patient's medical history was remarkable for severe asthma, thought to be
due to Churg-Strauss syndrome. She had a tunneled central venous catheter
for self-administration of intravenous corticosteroids at the earliest sign of an
asthmatic exacerbation. Her other medications included bronchodilators,
weekly erythropoietin injections, intravenous iron therapy, an antidepressant,
and an anxiolytic.
At presentation, the patient's vital signs were normal. Physical
examination was unremarkable except for mild generalized pallor. A
complete blood count on the day of admission revealed the following
(reference ranges shown parenthetically): hemoglobin, 4.9 g/dL (12.0-15.5
g/dL); mean corpuscular volume (MCV), 94.4 fL (81.6-98.3 fL); hematocrit,
13.4% (34.9%-44.5%); leukocyte count, 6.0 10
/L (3.5-10.5 10
/L); and
platelet count, 203 10
/L (150-450 10
/L). The patient's partial
thromboplastin time and prothrombin time (PT)/international normalized
ratio were normal. These results were obtained within 24 hours of her last
Which one of the following is the least likely in the differential diagnosis of
this patient's anemia?
Chronic blood loss
Acute hemolysis
Chronic disease
Myelodysplastic syndrome
Acquired pure red cell aplasia

With the observation that the patient's anemia was normocytic with an
MCV of 94.4 fL, the next task was to narrow the list of differential
diagnoses and establish whether this was due to premature destruction or
acute loss of RBCs vs decreased bone marrow production.

Which one of the following would be the next best test to narrow the list of
differential diagnoses?
Peripheral blood smear
Absolute reticulocyte count
Serum ferritin
Bone marrow biopsy and aspiration

The reticulocyte count is a good indicator of this and is the only test listed
that could have directly provided this necessary piece of information.
Our patient had a reticulocytosis of 13.3% (0.60%-1.83%), with an
absolute reticulocyte count of 238.8 10
/L (29.5-87.3 10

At this time, which one of the following series of tests would be most
helpful in further narrowing the differential diagnosis?
Total and indirect bilirubin levels, haptoglobin, lactate dehydrogenase
Peripheral blood smear
Direct Coombs test
Indirect Coombs test
Activated partial thromboplastin time (aPTT), PT, fibrinogen, soluble fibrin
monomer complex, and D-dimers

In this patient with an absolute reticulocytosis, ie, an adequate bone marrow response,
the next step would be in differentiating between hemolysis and acute blood loss.

Hemolysis is usually characterized by elevated indirect bilirubin concentrations,
decreased serum haptoglobin concentrations (with intravascular hemolysis in
particular), and increased serum LDH levels, and this series of tests would be most
useful in narrowing the differential diagnoses at this point.

The peripheral blood smear is less specific, but in the presence of hemolysis, it may
reveal abnormally shaped RBCs, including fragmented RBCs (schistocytes, helmet cells),
spherocytes, elliptocytes, or RBC inclusions, which may be seen in certain hemolysis-
producing infections, such as malaria, babesiosis, and Bartonella.

Hemolytic anemias may be acquired and immune, in which case there is immunologic
destruction of RBCs mediated by autoantibodies directed against antigens on the
patient's RBCs.

The direct and indirect Coombs tests detect antibodies on the surface of the patient's
RBCs and in the patient's serum, respectively. However, the presence of hemolysis must
first be established, especially since a patient may have a mildly positive Coombs test
that is clinically insignificant if not associated with ongoing hemolysis.
The patient had a mildly reduced haptoglobin level at 14 mg/dL (30-200
mg/dL), likely secondary to her multiple transfusions. However, her LDH
level was normal at 205 U/L (122-222 U/L), as were her total and direct
bilirubin levels at 0.4 mg/dL (0.1-1.0 mg/dL) and 0.1 mg/dL (0.0-0.3
mg/dL), respectively.

A peripheral blood smear showed no abnormally shaped RBCs. The overall
picture was not in keeping with hemolysis. On the first day of her
evaluation, the patient's hemoglobin concentration was 11.1 g/dL.

By day 2 of her outpatient work-up, it had decreased to 5.6 g/dL, and she
received 4 units of packed RBCs.

Despite the transfusions, her hemoglobin concentration decreased further
within 24 hours to 4.9 g/dL. At this point, the patient was admitted and
received 3 more units of packed RBCs. During this time, she was
asymptomatic, and her vital signs remained stable.
At this point, which one of the following would be the best step in the
management of this patient?
Computed tomography (CT) of the abdomen and pelvis
Transfer to the intensive care unit
Angiography of the gastrointestinal (GI) tract
The patient had no overt signs or symptoms of bleeding, and it would be unlikely for
her to have occult GI bleeding that resulted in such dramatic decreases in her
hemoglobin concentration.

Also, results of fecal occult blood testing were negative. Therefore, neither upper nor
lower GI endoscopy would be expected to reveal any useful information.

However, the patient could have occult intra-abdominal bleeding, and noncontrast CT
of her abdomen and pelvis would be crucial in ruling this out.

The patient's mental status remained normal, and she was exhibiting no overt evidence
of decreased perfusion or hemodynamic instability other than mild tachycardia.

Therefore, she could be deemed clinically stable, and transferring her to the intensive
care unit would be unnecessary at this time.

She was well compensated despite the severity and acuteness of the anemia, no doubt
in part due to her age and lack of other cardiac comorbidities. In this patient who is
exhibiting no overt evidence of GI bleeding, angiography would not be the next best
Noncontrast CT of her abdomen and pelvis revealed normal findings.
During the night of hospital day 2, an astute nurse noticed what appeared
to be bloodstains on the patient's gown.

The patient reported that she had spilled cranberry juice on the gown.
Closer inspection of her room revealed several blood-soaked tissues and
Styrofoam cups filled with fresh blood in her wastebasket.

The patient was also found to have dried, crusted blood all over her
fingernails, and a blood-stained 10-mL syringe, most of its labeling worn
away by overuse, was found in her gown pocket

Which one of the following is the most likely cause of this patient's anemia?
Factitious disorder
Munchausen by proxy
Somatization disorder
With the discovery made in the patient's room, in particular the syringe, the patient's
self-phlebotomy became evident, leading to a diagnosis of factitious anemia.

The most chronic and extreme form of factitious illness, Munchausen syndrome,
typically includes travel from hospital to hospital combined with the willingness to
submit to multiple procedures for self-fabricated signs of illness, as occurred with our
patient before her presentation at our institution.

In Munchausen by proxy, caregivers (usually mothers) induce illness in their children to
obtain care and support for themselves.

Somatization refers to the tendency to experience psychological distress in the form of
somatic symptoms not intentionally produced, thus differentiating this disorder from
factitious illness or malingering.

Hypochondriasis refers to a preoccupation with believing one is ill as a result of
misconstruing physical symptoms that are not self-generated.

The patient was seen by the psychiatry service, and although she was obviously at risk
of purposeful self-harm, she denied suicidal or homicidal ideation.

It became evident that she had a history of severe depression, borderline personality
disorder, chemical dependency, and a history of repeated episodes of parasuicide by
means of wrist cutting.
a 33-year-old, well-conditioned male athlete who presented to a referring
hospital with a 4-day history of fatigue, lethargy, fever, chills, jaundice,
dark urine, and abdominal pain.

His medical history included ocular toxoplasmosis in childhood. Several
years before admission, he had become acutely anemic and was
successfully treated with red blood cell (RBC) transfusions and

He was then lost to follow-up until the onset of this illness. He took
vitamins and nutritional supplements, used smokeless tobacco, and
denied alcohol or drug abuse.

He had recently started a job working with refrigerated and frozen food.
Sodium: 134 mEq/L (136-142)
Potassium: 4 mEq/L (3.8-5.0)
Chlorine: 104 mEq/L (95-103)
Carbon dioxide: 22 mmol/L (24-30)
Glucose: 172 mg/dL (70-110)
Creatinine: 1.4 mg/dL (0.6-1.2)
Blood urea nitrogen: 39 mg/dL (8-23)
Calcium: 8.4 mg/dL (9.2-11.0)
Magnesium: 1.9 mg/dL (1.8-3.0)
Serum iron: 267 g/dL (60-150)
Total iron-binding capacity: 291 g/dL (250-
Transferrin: 208 mg/dL (215-380)
Sedimentation rate: 119 mm/h (10-12)
Acute hepatitis panel: negative

White blood cell count: 16,200 cells/L
Hemoglobin: 3.6 g/dL
Hematocrit: 10.6%
Mean corpuscular volume: 104.7 fL
Platelet count: 340,000 cells/L
Reticulocyte count: 8.4% (0.5%-2.3%)
Haptoglobin: 6 mg/dL (36-195)
Lactate dehydrogenase (LDH): 943 U/L
Aspartate aminotransferase: 100 U/L
Alanine aminotransferase: 35 U/L (4-36)
Total bilirubin: 7.0 mg/dL (0.1-1.0)
Direct bilirubin: 0.9 mg/dL (< 0.3)
Albumin: 3.4 g/dL (3.2-4.5)
Total protein: 7.0 g/dL (6.0-7.8)

Upon admission to our hospital, the patient's hemoglobin level was 4.6
g/dL, and all other laboratory results were consistent with those from the
referring hospital.

Blood and urine cultures were negative.

Peripheral smears demonstrated RBC agglutinates, microspherocytes,
polychromasia, and nucleated RBCs.

The patient had mixed-type warm IgG/IgM-mediated AIHA.

The combination of massive intravascular hemolysis, vasoconstriction, and
vaso-occlusion caused prolonged inadequate tissue oxygenation leading
inexorably to multiple organ failure and death.

A 61-year-old woman was admitted to this hospital because of epigastric pain,
vomiting, diarrhea, anemia, and acute kidney injury.

The patient had been well until approximately 3 weeks before admission, when
vomiting, diarrhea, fevers, arthralgias, and episodes of epigastric pain of increasing
frequency and severity developed, which she attributed to a viral gastroenteritis.

Two weeks before admission, epigastric and midabdominal pain worsened, with
diarrhea and one episode of vomiting.

The next day, she came to the emergency department at this hospital. She rated the
pain at 4 on a scale of 0 to 10 (with 10 indicating the most severe pain) and reported
that it was worse when she was lying flat.

The blood pressure was 150/82 mm Hg, and the pulse 101 beats per minute; other vital
signs were normal.

The abdomen was soft, and there was mild epigastric tenderness without rebound; the
remainder of the examination was normal.

A stool specimen revealed occult blood.
Laboratory Data.
Bazari H et al. N Engl J Med 2014;370:362-373.
Pertinent Clinical Details
This 61-year-old woman presented with a 4-week history of epigastric pain, diarrhea,
and vomiting.

Arthralgias, fever, anemia, and acute kidney injury developed.

The stool was guaiac-positive and positive for H. pylori antigen, and an
esophagogastroduodenoscopy was normal.

In the past, she had had hyperlipidemia and gastroesophageal reflux disease.

On examination, she had mild abdominal tenderness.

Pertinent laboratory values include progressive anemia, an absence of leukocytosis,
progressive renal failure, elevated blood levels of aminotransferase and alkaline
phosphatase, serum immune electrophoresis with no monoclonal protein detected, and
a high serum free light-chain ratio (kappa:lambda ratio, 3.1; normal range, 0.3 to 1.7).

Urinalysis was pathognomonic for an acute glomerulonephritis, with proteinuria and
red-cell casts. The rheumatoid factor was weakly positive. Testing for ANA was negative,
and blood levels of complement were low (C4, very low; and C3, slightly decreased).
Evaluation for anemia was consistent with anemia of chronic disease. A bone marrow
biopsy specimen showed 3% monoclonal B cells, which were CD5 CD10 kappa+.
Serum free light-chain assays are the most sensitive tests for the detection of
abnormal immunoglobulin-secreting B-cell clones.

Furthermore, flow-cytometric analysis of the bone marrow specimen confirms
the presence of a small, clonal B-cell population, without an excess of plasma

The patient does not meet the criteria for a diagnosis of overt myeloma or
lymphoma. It is possible that she has monoclonal gammopathy of
undetermined significance and a monoclonal B lymphocytosis both of
which are relatively frequent findings in older adults which may be
unrelated to her current illness.

Other considerations are cryoglobulinemia, immunotactoid
glomerulonephritis, and deposition disease with light chains, light and heavy
chains, or heavy chains
A 22 month old boy presents to your office with a chief complaint of pallor.

A visiting relative who has not seen the child for 5 months told his mother that
the boy appears pale.

The mother brings him in for a checkup even though she notices no change in
his coloring (he has always been fair skinned).

On review of symptoms you find that he is an active toddler, with no recent
fatigue, exercise intolerance, or increase in sleeping.
He has had no blood in his diapers and no black or tarry stools.

He is a picky eater, taking small amounts of chicken, pork and some
vegetables, but loves milk and drinks six to eight bottles of whole milk per day.

Family history reveals a distant aunt who had anemia when she was pregnant
but which subsequently resolved. There is no history of splenectomy, gall
stones at an early age, or other anemia in the family.
Exam: VS: T 37.5, BP 90/52, P 145, RR 16, Height 85.5 cm (50th %ile), Weight
13.2 kg (75th %ile). General appearance: He is a pale appearing, active toddler,
holding a bottle, tearing and eating paper from your exam table. Eyes: No
scleral icterus. Pale conjunctiva. Mouth: Dental caries. Chest: Clear. Heart:
Mild tachycardia as above, grade II/VI systolic ejection murmur heard best
over the upper left sternal border. Abdomen: No hepatosplenomegaly. Rectal:
Dark brown, soft stool, negative for occult blood.

CBC: WBC 6,100, Hgb 6.2 g/dl, Hct 19.8%, Plt 589,000, MCV 54 fL, RDW 17%.
Reticulocyte count is 1.8%. The lab reports microcytosis, hypochromia, mild
anisocytosis and polychromasia. There is no basophilic stippling.

You correctly diagnose iron deficiency anemia, start oral iron and limit his milk
intake. You see him in 3 days to assure compliance and his RDW is 27% and his
reticulocyte count 17%. When you see him back in two weeks his mother is
amazed at his new interest in table foods. His Hgb is now 8.5 g/dl, and his MCV
64 fL. Two months later his hemoglobin has completely normalized, and you
continue iron therapy for three more months.
ML is a 64-year old male who has not had any primary care for several
years. When he tried to give blood last week, he was told that he was
anemic. He presents to your clinic for evaluation.

What would you do??
HPI: Ive been a little more tired than usual, but Ive been busy at work.
Im getting close to retirement. Nothing else is unusual. I avoid doctors if I
PMH: Inguinal hernia repair 20 yrs ago
FH: F & MGF-heart attack(age 80), brother-alcoholism
SH: Married x44yr, smokes 1ppd, a couple beers/night
MEDS: daily multivitamin
ROS:+fatigue, +urine seems a little darker lately

Only a CBC w/ diff was obtained:
WBC: 8.2, HCT 32.2, MCV 79, Platelets 221, differential - normal

Initial Thoughts?
Blood loss?
Age places him at risk for colon CA
Decreased Production?
Alcohol use, Iron deficiency
Increased Destruction?
Darker urine lately

Peripheral Blood Smear
Reticulocyte count
Iron Studies
% Saturation
Colonoscopy referal

More Results
Smear reveals microcytic, microchromic RBCs
Retic count is interpreted as low
Urinalysis negative for hemoglobin
Iron Studies
Ferritin: 10
TIBC: 350
% Sat: 15

Colonoscopy revealed small
suspicious lesion in sigmoid
colon, pathology revealing
adenocarcinoma. Excised
surgically, no mets.

Routine labs, one year later,
reveal an HCT of 40%. He feels
better than ever!

42 yo admitted with anemia
Hemoglobin 8.8 g/dl
MCV 80 fL Retic 5.8%
WBC 12.0/uL
86% PMN
10% lymphs
4% monocytes
Platelets 676/uL

80 yo CM admitted for diarrhea, anorexia, fall
PMH EtOH, hemicolectomy for CA
Hgb 9.4 g/dL LDH 600 U/L
MCV 124 fL
WBC 3.4
Plt 144
Retic 1.4%

26 yo CM.
Hct 36 Meds: none
WBC 5.6 PMH: none
Plt 214
LDH nl
Hapto <6
36 yo AAM with fever, rash, arthralgias, pain
PMH: SS dz
Hgb 5.2 LDH 612
MCV 88 Bili 4.5
WBC 5.0
plt 130
51 YO female presents with fatigue, occasional tingling of her hand and
feet. She reports decrease in concentration and memory
PSHx: cholecystectomy, gastric bypass
Social Hx: negative for drug, tobacco and alcohol
WBC 1.7
HGB 8.9 G/DL
MCV 109
SEGS 52%
EOS 2%

47 YO African American Female presents with fatigue, heavy menstrual
bleeding, body aches.
FHx: anemia of unknown etiology
Social Hx, PMHx is unremarkable
WBC 5K, HGB 9.8 g, PLT 166,000, MCV 56
How do you approach this case?

Serum Ferritin 15
Iron saturation 9%
TIBC 470
B12 and folate are normal
Retic 2.6%
Bone marrow biopsy ?