ANEMIA CASES

1.•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 µm3; •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 preparation.

• Hematocrit is 38%

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

• What tests would you order next ?

• What are th?

2.

3.• 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 anemia.

• 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 × 109/L (3.5-10.5 × 109/L); and platelet count, 203 × 109/L (150-450 × 109/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 transfusion.

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• Erythropoietin• 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 × 109/L (29.5-87.3 × 109/L).

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 (LDH)

• 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?•Esophagogastroduodenoscopy•Colonoscopy•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 step.

• 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• Hypochondriasis

• 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.

4.• 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 immunosuppression.

• 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 µg/dL (60-150)• Total iron-binding capacity: 291 µg/dL (250-400)• Transferrin: 208 mg/dL (215-380)• Sedimentation rate: 119 mm/h (10-12)• Acute hepatitis panel: negative

• White blood cell count: 16,200 cells/µL• • Hemoglobin: 3.6 g/dL• • Hematocrit: 10.6%• • Mean corpuscular volume: 104.7 fL• • Platelet count: 340,000 cells/µL• • Reticulocyte count: 8.4% (0.5%-2.3%)• • Haptoglobin: 6 mg/dL (36-195)• • Lactate dehydrogenase (LDH): 943 U/L

(91-180)• • Aspartate aminotransferase: 100 U/L

(8-33)• • 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.

5.• 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 cells.

• 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

6.• 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.

7.

• 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: “I’ve been a little more tired than usual, but I’ve been busy at work. I’m getting close to retirement. Nothing else is unusual. I avoid doctors if I can”

• 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• ALLERGIES: none• 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

– Ferritin– TIBC– % Saturation

• Urinalysis• 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

Diagnosis

• 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”!

8.• 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

• ?

9.

• 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%

• ?

10.

• 26 yo CM.• Hct 36 Meds: none• WBC 5.6 PMH: none• Plt 214• LDH nl• Hapto <6

11.

• 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

12.

• 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• LABS:

WBC 1.7 HGB 8.9 G/DLPLATELETS 109,000MCV 109SEGS 52%LYMPHS 40%MONO 5%EOS 2%METAMYELOCYTES 1%

13.

• 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 ?