Jenny Wright, MD

• • Present a series of patients typically of those seen in medicine clinic, highlighting common patient presentations, diagnoses and management Discussion of anemia in both the outpatient and inpatient setting

• • • • • 51 year old female here today for a preventive health visit. PMHx: Depression/Anxiety, Paroxysmal SVT Medications: Atenolol PRN, Estring, Ambien PRN All: NKDA Habits: Exercises 30 minutes 5 days a week, diet healthy; EtOH: 2-3 glasses of wine a night, no tob, no IVDU

• • • • What cancer screening should we be considering?

Cervical Cancer Breast Cancer Colon Cancer www.ahrq.gov

• • • • • She is in a mutually monogamous relationship and has a history of normal Pap smears, most recently last year. When will she be due for repeat cervical cancer screening?

A. She doesn’t need additional screening unless she has new partners B. A today’s visit C. In four years D. In two years at which time consider also consider HPV screening

•

Recommendations of the USPSTF:

• •

Don’t screening younger than age 21.

Screen women ages 21 to 65 years with cytology (Pap smear) every 3 years or, for women ages 30 to 65 years screen with a combination of cytology and human papillomavirus (HPV) testing every 5 years.

•

Stop screening in women older than age 65 years who have had adequate prior screening and are not otherwise at high risk.

•

Don’t screen women who have had a hysterectomy who do not have a history of a high-grade precancerous lesion or cervical cancer.

• Do you need to screen a sexually active 19 year old?

• Do you need to screen a women who’s s/p hysterectomy for menorrhagia d/t fibroids?

• How often do you need to screen a 28 year old female with HIV disease?

• •

The USPSTF:

•

Biennial screening mammography for women aged 50 to 74 years.

•

“The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take patient context into account, including the patient's values regarding specific benefits and harms.”

• •

+/- clinical breast examination (CBE) Insufficient evidence to assess the additional benefits and harms of screening mammography in women 75 years or older.

•

Recommend against teaching breast self-examination (BSE).

The American Cancer Society, AMA, ACOG: Annual screening beginning at age 40.

• Q: What is the best test to screen for colon cancer?

• •

The USPSTF recommends:

•

screening using fecal occult blood testing, sigmoidoscopy, or colonoscopy beginning at age 50 years and continuing until age 75 years.

• •

recommend against routine screening in adults age 76 to 85 years. There may be considerations that support colorectal cancer screening in an individual patient.

recommends against screening for colorectal cancer in adults older than age 85 years.

The American College of Gastroenterology: Generally agrees though states ‘preferred’ strategy is colonoscopy

• • • • A. Current smokers with a 25 pack-year history, beginning at age 50 B. No one C. Those with a 30 pack year history (current smokers, or those who quit within the past 15 years), aged 55-80 D. Current smokers with a family h/o lung cancer, beginning at age 60

Cervical Breast Colon Lung Cancer, pts with h/o heavy tobacco use only

Age to initiate screening

21 40/50 (USPSTF) 50 55

Age to stop screening

65 75 (?) 75-85 (?) 80

Frequency of screening

3-5 (test specific) 1-2 Modality dependent Annual low dose chest CT

• Are you concerned about her level of alcohol use – 2-3 glasses of wine a night?

• • • Spectrum of unhealthy alcohol use: Risky use → Alcohol abuse CAGE questionnaire screening of abuse: • • • • Cut down Annoyed/angry. Guilty.

Eye opener.

Risky alcohol use: M > 14 drinks a wk or 4 on one occasion F > 7 drinks a wk or more than 3 on one occasion

• 74 year old year old English speaking female with dementia presents with several concerns including a rash. The rash is located under both breasts, time course unclear, has been using clotrimazole, neosproin and hydrocortisone. It doesn't itch or hurt. http://www.aafp.org/afp/2005/0901/ afp20050901p833-f1.jpg

• • Tinea • • • • Tinea pedis: moccasin or btwn the toes Tinea corporis: annular, scaly plaque, “ringworm” Tinea cruris: Men > women, typically spares the scrotum (vs candida) Tinea versicolor: Malassezia furfur yeast, hyper- or hypo- pigmented patches • Can confirm dx with KOH prep of skin scraping Candidiasis • Vivid erythematous rash in intertriginous regions

• A 54 yo male presents with a one week history of a painful, mildly itchy rash under and on the posterior aspect of his L arm. He has a history of eczema and has been using Clobetasol and triamcinolone creams on the rash without improvement.

• • • Herpes Simplex Virus • • Primary infection can be severe with systemic symptoms Confirm dx with DFA/PCR, serologies rarely helpful Herpes Zoster • • • • • Prodrome of pain and burning common If first division of trigeminal nerve involved need ophthalmologic evaluation Treatment with antiviral, ideally within 24-72 hrs decreases duration and severity Post-herpetic neuralgia: 10-15% of patients, more common in older patients Vaccinate! reduces risk of zoster by 50%, or PHN 66% Human Papilloma Virus • Vaccinate!

• 28 yo female with celebral palsy and developmental delay with erythematous, itchy rash in the bilateral antecubital fossae. These developed after pt repeatedly applied shower gel to her arms, thinking it was a moisturizing lotion. http://o.quizlet.com/i/VI H52FPtYT59Acm6A_h6Pw _m.jpg

• • • • • • • Itchy red rashes Contact dermatitis: • • The pattern often gives it away Common offenders: poison ivy, nickel, topical antibiotics, hair dye, fragrances Atopic dermatitis: • • • Typically begins in childhood Wrists, anticubital and popliteal fossae In chronic cases see lichenification Dyshidrotic eczema: intensely pruritic vesicles on hands Xerotic eczema: dry skin, often seen in winter, lower extremities Nummular eczema: Itchy coin-shaped patches, favor extremities Stasis dermatitis: Occurs in the setting of lower extremity edema, confused with cellulitis

32 year old healthy male presents with a rash. He has noted red spots on his back and abd for the past few weeks, they are not itchy or painful. http://www.primehealthchannel.com/wp content/uploads/2011/02.jpg

• • • • Pityriasis rosea: • • • • typically 10-35 yr pts occasionally will be pruritic Herald patch -> multiple small patches on truck resolves within a few months Seborrheic dermatitis: • • • Scalp, eyebrows, ears, nasal folds more common at HIV and Parkinson’s treat with topical azoles or dandruff shampoos, if severe can use topical steroids Psoriasis Lichen planus

• 57 yo male with h/o liver transplant 10 years ago presents with a bump on his L cheek, it’s been present for several months. It isn’t itchy. It comes and goes, he thinks that it’s an ingrown hair because it’ll bleed a little then seem to heal.

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• • • Basal Cell Carcinoma: • Nodular variant – pearly papules with telangectasia Squamous Cell Carcinoma: • • • Precancerous lesion is an actinic keratosis (1-5% -> SCC) Scaly, crusted papule 2-5% risk of metastasis Melanoma: • ABCDE: asymmetry, irregular border, multiple colors, diameter > 6 mm, evolution over time

• • General Population: • USPSTF: “counsel persons with fair skin who are 10 to 24 years of age about sun-protective behaviors” • • Behavior change was found with counseling in this age group Regular sunscreen use can prevent squamous cell carcinoma, but evidence is less strong that it can prevent basal cell carcinoma or melanoma Transplant population: • Much higher risk of skin cancer (ex. Liver transplant pts have 100X the risk of SCC! Skin cancers often more aggressive too) Ann Intern Med. 1 February 2011;154(3):190-201

• A 30 year old male with h/o CVID presents with sinusitis, he is started on Bactrim. Several days later he returns to clinic with a erythematous area near his lip. http://www.your-doctor.net/dermatology_atlas/rwx/rwx.jpg

• • • Wide variety of dermatologic manifestations can occur: Most common: Morbilliform drug rash; antibiotics are common culprits Previous case: Fixed drug eruption: intense dark red round patch; common culprits include beta lactams, macrolides and trimethoprim-sulfa) • Classic “drug rash” http://www.uptodate.com

Series of pigmented lesions and rashes with great pictures

• 66 year old year old male presents for follow up on DM, HTN, HLD. Labs prior to today’s visit: TC 238/TG 173/HDL 37/ LDL 134.

• What are you going to do now?

• • •

General Considerations

Lipids lowering with statin medications reduces CV disease risk in all populations Absolute risk reduction is dependent on patient’s baseline risk, therefore this is the first issue to consider Therapeutic lifestyle changes should be recommended to all patients with hyperlipidemia

ACC/AHA recommendations Risk Group

Clinical ASCVD LDL >190 DM 10 yr ASCVD risk >7.5%

Tx recommendation

Hi intensity statin Hi intensity statin Mod. intensity statin Mod-hi intensity statin

Framingham Pooled Cohort Equation

Risk Group

Clinical ASCVD LDL >190 DM 10 yr ASCVD risk >7.5%

Tx recommendation

Hi intensity statin Hi intensity statin Mod. intensity statin Mod-hi intensity statin

Examples

atorvastatin 80 mg rosuvastatin 20 mg Per above atorvastatin 10 mg simvastatin 20-40 mg lovastatin 40 mg pravastatin 40 mg Per above

• 66 year old year old English speaking male who presents today for follow up on DM, HTN, HLD. Labs prior to todays visit: TC 238/TG 173/HDL 37/ LDL 134 • What are you going to do now?

• “diet and exercise”…

Mediterranean Diet Shown to Ward Off Heart Attack and Stroke!

• • CDC recommendation: • 150 minutes of moderate activity or 75 minutes of vigorous activity a week + muscle-strengthening activities on 2+ days Pedometer use (JAMA 2007;298(19):2296-2304): • Use is associated with increases in physical activity (+2500 steps a day!) and mild weight loss (BMI -0.38) and improvement in blood pressure (SBP -3.8)

• • • • Week one: First wear the pedometer for a week and assess baseline daily average number of steps. Week two: Work to increase daily number of steps by 500. Every two weeks increase daily goal by 500 steps. Keep doing this up to10,000 steps a day (target level).

• • • • Pearls: Baseline LFTs +/- CK recommended • American College of Cardiology, AHA, and NIH Don’t need to follow LFTs • 2012, the US Food and Drug Administration Side effects: • • • Statin myopathy – myalgias are common (up to 10%!), rhabdomyolysis extremely rare FDA recently added memory loss of drug labeling though evidence is sparse Increased risk of diabetes – effect much smaller than known CV benefit

• JAMA Intern Med 2013;on-line publishing June 3 • Cohort of 46,000+ active and retired military patients; from this group propensity score matched about 7000 statin users and non-users • OR for various severity of musculoskeletal complaints (including dx of joint sprain, strain, muscle pain) ranged from 1.09-1.19

• NNH ranged from 37-58

• 39 yo female with a h/o migraines presents to discuss depression. She has a h/o depression and in the past has had trials of sertraline, citalopram and venlafaxine, all with significant side effects -- nausea, worsening of her n/v with her migraines -- and no benefit of her depression symptoms. For the past 3-4 wks she’s had depressed mood, difficulty with concentration, desire to sleep all the time/lethargy, anxiety and inability to manage difficult situations. She is here for suggestions regarding possible treatment.

• • • • • • Which of the following in the most effective treatment of mild moderate depression?

A. Psychotherapy B. SSRIs C. TCAs D. SNRIs E. These are all roughly equally efficacious

PHQ- 9 is helpful for diagnosis and assessment of severity

• • • • Side effects: Minimize by starting at a very low dose and slowly up-titrating Follow up: 1-2 wks (in clinic or by phone) Expect to stat seeing improvement in 2-6 wks If no improvement by 8 wks consider modifications to therapy

• • • • If treatment with one SSRI doesn’t work what should be the next medication you try?

A. Another SSRI B. Anything but an SSRI C. Add another medication to the SSRI

• Lessons: • If pt intolerant or unresponsive to one SSRI may still have benefit to a second • Augmentation with bupropion (better tolerated than augmentation c buspirone) is also effective Initial treatment: Citalopram Switched to sertraline, bupropion, venlafaxine or CBT Augmented with bupropion, buspirone or CBT

 26 year old female with a h/o hypothyroidism presents to clinic for evaluation after attempting to donate blood and being was told that she was anemic. What labs would you order at this visit?

 A) Hematocrit  B) CBC, iron, TIBC, and ferritin  C) TSH, CBC, reticulocyte count  D) TSH, CBC, reticulocyte count, peripheral blood smear, iron, TIBC and ferritin

 Acute blood loss  Decreased production of RBCs:  decreased erythropoetin (epo)  Normal production of epo but decreased ability to respond to epo  Destruction of RBCs:  intravascular  extravascular

ideal  Reticulocyte count: this may be reported as the absolute count (determined by flow cytometry) or the reticulocyte count as a percentage of the total erythrocytes – in this case you want to calculate the reticulocyte index (RI=reticulocyte% x pt’s Hct/45 x 0.5).

 If low-normal (absolute count <75,000, RI<2), bone marrow hypoproliferation: production problems  If high (absolute count >100,000/microL, RI>2), bone marrow hyperproliferation: hemolytic anemia, acute blood loss

http://www.uptodate.com.offcampus.lib.washington.edu/online/content/images/H EME/9131/Polychromatophilia.jpg

ideal  Peripheral blood smear:  Offers important additional information regarding the morphology of the cells that cannot be obtained from other laboratory data.

 Examples include differentiation between types of hemolytic anemia, different types of macrocytic anemias.

 Microcytic (MCV<81): iron deficiency, thalassemia, sideroblastic anemia, anemia of chronic disease  Normocytic (MCV 81-98): anemia of chronic disease, aplastic anemia, bone marrow infiltration, kidney disease, acute blood loss  Macrocytic (MCV >98): alcohol, B12 deficiency, folate deficiency, myelodysplasia, drug toxicity, reticulocytosis, liver disease

26 year old female presenting for evaluation after attempting to donate blood and being was told that she was anemic.

 Her labs reveal: TSH 6.3 microIU/mL (high), low reticulocyte count, Hct 33%, MCV 74, iron 35 (low), TIBC 540 (high), ferritin 14 (low). What do you do next?

 A) treat with oral iron  B) order a colonoscopy  C) increase her levothyroxine dose  D) start oral contraceptive pills

 Ferritin can be the most useful single test, though due to the fact that it is an acute phase reactant, only in patients without infection/inflammation  All pt’s with ferritin <15 are iron deficient (highly specific but not sensitive), values >100 essentially rule out iron deficiency.

 Other characteristic iron study results are: elevated TIBC, low transferrin saturation and low serum iron level

Progression of change: hypochromia (decreased MCHC) → (decreased MCV), → microcytosis anisocytosis (increased RDW)

• • • Iron deficiency (even without anemia) is associated with restless leg syndrome, hair loss, and delayed cognitive development in children Anemia may manifest as fatigue, weakness, headache, irritability Pica is the setting of severe deficiency

 In severe cases may have additional physical exam findings:

 Evaluate for cause:  In post-menopausal females and males you have to evaluate for GI blood loss.  In menstruating females, menses is a common cause.

 Treat: Iron replacement can typically be given orally, ferrous sulfate or gluconate 325 mg, 1-3 times a day.

 Ideally pts are treated with TID medication though this is rarely tolerated  Sulfate salt is cheaper and has more elemental iron but generally less well tolerated

 Three months later pt returns, still being told she can’t give blood! Her Hct is 34% and ferritin 15. TSH nl. What do you do now?

 A) review how she’s taking her medications  B) transfusion  C) give it more time  D) start vitamin C

 Side effects of oral iron replacement lead to low compliance.

 Constipation, stomach upset  May have less symptoms if they take it with food (though this decreases absorption)  Consider other causes of poor absorption: celiac disease, IBD, h/o gastrectomy or gastric bypass, taking with an antacid, PPI, calcium.  Vitamin C enhances absorption  Expect Hct to improve within several weeks of therapy though pts should continue treatment for 6 mo -1 yr, would like to see ferritin level normalized

 A 68 year-old woman with hypothyroidism and HTN, presents for evaluation of unintentional weight loss and night sweats. CBC notable for WBC 11.2, Hct of 32%, MCV 79; TSH nl; CMP with Na 133, Alb 3.0.  What is your differential for her anemia and what labs would you order?

 Lab findings: Hypoproliferative anemia (low reticulocyte count) Typically a normocytic anemia, though 25% of cases are microcytic Classically labs will reveal an normal - elevated ferritin, and low serum iron and TIBC.

 Etiology: multiple contributing factors including decreased transfer of iron to red blood cells, decreased response to Epo, decreased Epo release  Treatment: Treat underlying cause

ACD Fe def.

ACD + Fe def Serum iron TIBC Transferrin saturation Ferritin Low Low - normal Low Normal – high Low - Very low (<15 mcg/dL) High nl - high Low -Very low (<10%) Low - Very low (<15 ng/mL) Low Normal Low Low - normal

Serum ferritin is the single best test for iron deficiency – a ferritin <10 is 99% specific!

Ferritin >100 effectively rules out iron deficiency.

• • • • What is the most common cause of anemia in women?

Iron deficiency What is the most common cause of anemia in men?

Anemia of chronic disease

• • 61 yo female with bipolar disorder, stress incontinence, obesity and COPD presents with back pain. HPI: 6 week h/o low back pain, typically dull, in a band across the low back though with activity occasionally sharp and more central in location. Radiates into the R posterior lower extremity. Worse with activity. Better with naproxen.

• Are you worried or not worried?

Low Back Pain Dangerous Not dangerous

Red Flags

• What are the “red flag” symptoms for back pain?

Why would this make you worry about?

Trauma (even minor in the elderly) Major and progressive motor or sensory deficit New-onset bladder or bowel incontinence or urinary retention Saddle anesthesia, loss of bowel tone H/o cancer, unexplained weight loss, age > 50 H/o IVDU, immunosuppression Known osteoporosis, h/o steroid use Unstable spine Central cord compromise Cauda equina syndrome Cauda equina syndrome Bone metastasis Vertebral diskitits/osteomyelitis/epidural abscess Compression fracture

• What is the differential diagnosis of low back pain without red flag symptoms?

Low Back Pain

Mechanical non-specific LBP Spondylosis (degenerative disk disease, facet joint arthropathy) Spinal stenosis Herniated nucleus pulposus Spondylolisthesis Inflammatory spondyloarthropathy

• • • •

Exam

VS: BP 136/84 | Pulse 80 | Wt 272 lb (123.378 kg) Musculoskeletal: ROM and muscle strength: No scoliosis or splinting. No spinous process tenderness. Has pain to palpation in the paraspinal region bilateral low back. Normal flexion and extension of the back. Muscle strength is grossly normal for the lower extremities. Sensory exam and Reflexes: Patellar DTRs are normal bilaterally. Sensation intact to light touch in the L4 and S1 distributions. Straight leg raising: Reproduces radiating pain when R leg raised, no pain when L leg elevated.

Rational

Spinous process tenderness: Bony etiology Muscle strength, sensation, reflexes: neurologic compromise, pattern • • • Radicular patterns: L4 – quadriceps weakness, patellar reflex diminished, medial foot sensation L5 – great toe and ankle dorsiflexion weakness, no reflex changes S1 – great toe and ankle plantar flexion weakness, Achilles reflex diminished, lateral foot sensation Straight leg raise: testing for nerve impingement in the setting of radicular symptoms When do you need to test rectal tone?

The straight leg raise

Positive ipsilateral straight leg raise: Sensitivity>Specificity Contralateral straight leg raise: High specificity • •

Sensitivity and Specificity

Spin: Highly specific tests are useful for ruling thing in Snout: Highly sensitive tests are useful in ruling things out

Disease No disease

+ test - test A C B D Sensitivity = A/(A+C) Specificity = D/(B+D) Positive Predictive Value = A/(A+B) Negative Predictive Value = D/(C+D)

• • • What if she was 10 years older (71) and presented with back pain radiating to the bilateral posterior thigh regions, worse with ambulation, better if she sits down. Physical exam notable for nl pedal pulses. Diagnosis?

Spinal stenosis: • • Typically presents are bilateral leg pain in elderly patients. Psuedoclaudication: pain worse with standing, walking downhill, better with leaning forward, sitting or lying down

• • • • • Back to our patient, 61 yo female with subacute radicular low back pain. In the setting of acute back pain, what evaluation/mgmt are you going to propose?

A. Non-steroidal anti-inflammatory medications and physical therapy B. MRI C. Inflammatory markers and plain films D. Low dose narcotics and muscle relaxants

• • • • • Back to our patient, 61 yo female with subacute low back pain. In the setting of acute back pain, what evaluation are you going to do?

A. A trial of conservative therapy with non-steroidal anti inflammatory medications and physical therapy B. MRI -- emergent if risk for acute cord compression - suspect unstable spine, infection, pt with cauda equina syndrome C. Inflammatory markers and plain films -- may be helpful if suspect malignancy, compression fracture D. A trial of conservative therapy with low dose narcotics and muscle relaxants

Imaging, when and what

Immediate imaging - Xray and ESR - MRI Defer imaging after trial of therapy - Xray +/- ESR - MRI

Clinical scenario

Major risk factors for cancer Concern for spinal infection Signs of cauda equina Severe neurologic deficits (multiple levels, progressive) Weak risk factors for cancer Concern for ankylosing spondylitis Concern for vertebral comp fx s/s of radiculopathy if considering ESI or surgery s/s of spinal stenosis if candidate for surgery Ann Intern Med 2011;154:181-189

• • • • • • How to do you treat it?

Patient education: “It’s common and the majority of pt’s get better” • though 31% continue to have pain at 6 mo and recurrence is common, 25 62% within 1-2 yrs Avoid bedrest Medications: NSAIDs, muscle relaxants, acetaminophen Physical therapy Heat or ice

• • • She returns to clinic 8 weeks later without significant improvement. At this time she describes radicular pain as most bothersome. What do you do now? Interventions: • • Medications: Trial of Gabapentin, TCA Epidural steroid injection? Consider for radicular pain not responding to conservative therapy • Note, most herniated disk get better on their own Surgery – clearly indicated for acute cord compression, results are mixed for spinal stenosis and persistent nerve root compression

• • • You note that she has chronic back pain, she also has a h/o knee osteoarthritis, HTN and sleep apnea. Her weight is 272 lbs. She has tried to lose weight and been unsuccessful. When do you consider bariatric surgery?

Step 1: Calculate and interpret pts BMI • • 25-29.9 kg/m2 = overweight ≥ 30 kg/m2, varying degrees of obese General Criteria: • BMI ≥ 40 or ≥ 35 with co-morbidities related to obesity (DM, severe OA, HTN, sleep apnea) • • Able to tolerate surgery Failed to lose weight with conservative interventions

Weight loss counseling and lipid management

 48 year old homeless female with alcohol dependence presents to clinic for evaluation of several concerns including fatigue. Labs are remarkable for: Hct 34%, MCV 110, RI <2 . Her PMHx is remarkable for rheumatoid arthritis.

 The most likely diagnosis is:  A. chronic GI blood loss due to gastritis  B. dietary B12 deficiency  C. folate deficiency  D. anemia of chronic disease

 In addition to B12 and folate deficiency, causes include:  Alcohol  Drug toxicity: zidovudine (AZT), hydroxyurea  Hypothyroidism  Liver disease  Hyposplenism  Myelodysplasia  Hemolysis  Be sure to assess reticulocyte count to eval for stress erythropoiesis

 The smear in a patient with macrocytic anemia is helpful in identification of megaloblastic changes – macro-ovalocytes and hypersegmented neutrophils (>5 lobes)  Etiologies include: B12 deficiency, folate deficiency, drugs that cause abnl DNA synthesis or folate metabolism, and myelodysplastic syndromes

Image from Joyce Wipf, MD

 Non-megaloblastic macrocytosis is typical of liver disease and hyposplenism, on smear patients may have large target cells, acanthocytes, and Howell-Jolly bodies.

http://www.uptodate.com.offcampus.lib.washin

gton.edu/online/content/image.do?imageKey= HEME%2F9127

 Found in: Fruits (e.g. citrus, melon, bananas), leafy green vegetables, and fortified grain products  Causes include:  Alcohol: decreases ability to absorb folate and, frequently associated c decreased intake of folate rich food  Malabsorption (celiac disease, IBD)  Diseases/conditions associated with rapid cell turnover such as sickle cell disease*, psoriasis, pregnancy  Medications: phenytoin, methotrexate * Chronic hemolytic anemia = daily folate supplementation

 The body stores large amounts of B12 therefore decreased dietary intake rarely lead to deficiency, typically due to decreased absorption due to pernicious anemia and intrinsic factor deficiency, atrophic gastritis or IBD.  Medications to decrease stomach acid can also contribute to B12 deficiency (PPIs, antacids)  In addition to causing anemia, B12 deficiency can lead to a metabolic peripheral neuropathy and neuropsychiatric disease (not the case for folate deficiency)

• Long term metformin treatment is associated with increased rates of B12 deficiency, <150 pmol/L, (NNH 13.8 per 4.3 yrs) and low B12 150-220 pmol/L (NNH 8.9 per 4.3 yrs) • • Clinical outcomes not measured If and when to screen remains unclear de Jager J, Kooy A, Lehert P, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomized placebo controlled trial. BMJ 2010;340:c2181.

 Labs reveal a low folate level and a normal B12 level (450). You initiate folic acid supplementation with 1 mg po q day.

 As was done here, you always want to assure that pts don’t also have B12 deficiency prior to treating for folate deficiency, you may be able to improve a patients anemia but the neurologic symptoms will progress

 If levels are at the lower limits of normal (200-300), then consider checking methylmalonic acid and homocysteine levels, these will be elevated in the case of B12 deficiency  Should be given orally, IM in rare situations  Oral dosing is 1000 – 2000 mcg po q day  IM dosing is 1000 mcg IM q day x 7 days, then q wk x 4 wks then q month

A 28 year African American old female presents to clinic with fatigue. She has a history of cellulitis and just finished a 14 day course of therapy with Bactrim. TSH is normal, Hct is 25%, MCV 98. What do you think is the most likely cause of her anemia?

 A. hemolysis  B. iron deficiency  C. folate deficiency  D. anemia of chronic disease

 Labs to order: reticulocyte count, peripheral smear, haptoglobin, indirect bilirubin and LDH

 Etiologies of extravascular hemolysis include:  Congenital hemoglobin abnormalities: hemoglobinopathies  Erythrocyte membrane abnormalities: hereditary spherocytosis  Erythrocyte metabolic abnormalities: G6PD deficiency  Auto-immune process: idiopathic, underlying malignancy, CVD, lymphoproliferative disorders, medications (PCN, cephalosporins, NSAIDs)

http://www.uptodate.com/online/content/image.do;jsessionid=49B7B6DD5EECE1FD7800F AECB4D78805.1102?imageKey=HEME%2F8853

 X-linked enzyme deficiency that results in decreased glutathione levels  Most common form results in severe hemolysis with medications (sulfa, dapsone) and infection  Less common Mediterranean form associated with favism  Dx: enzyme activity testing, may have false negative test in the setting of acute hemolysis, re-test at 2-3 months

 Etiologies include:  Microangiopathic hemolytic anemia – TTP/HUS, DIC, HELLP  Shearing due to malfunctioning mechanical heart valves  ABO incompatibility

 She has labs consistent with hemolytic anemia, and the following smear. What do you think is going on and what test can you send to confirm this?

From UpToDate, http://www.uptodate.com/online/c ontent/image.do;jsessionid=B8A AB868DBB1B8B6463E3749C69 5F04E.1004?imageKey=HEME% 2F9278

 You send a direct antiglobulin test (Coombs test) and it is positive for IgG. You suspect a diagnosis of warm auto-immune hemolytic anemia. She is treated with steroids and does well.

 When to transfuse?

 General practice: Hct <21% (based on evidence in critically ill pts), consider at <25% in pt’s with multiple medical problems  Other times to consider: on-going rapid blood loss, highly symptomatic patients, patient with low Hct and severe cardiovascular disease*  You expect the Hct to increase 3% for each unit of blood transfused * controversial, area of active research

63 year old female with DM and stage 5 CKD presents for evaluation of fatigue. Labs reveal Hct 31%, MCV 87, iron 43 (40-155), TIBC 241 (270-535), ferritin 95 (10-180), transferrin sat. 18% (10-45%). How can you treat her anemia?

 A. Transfusion  B. Epo  C. Epo and iron  D. Iron replacement

Burr cells

• • • Hypoproliferative (low reticulocyte count), normocytic anemia For erythropoietin therapy to be effective need adequate iron stores – ferritin >100/200 and transferrin saturation >20% Treatment goal is hemoglobin of 10-11 (Hct 30-33%), higher levels are associated with increased morbidity and mortality – carries a Black Box warning

A 27 yr old man of SE Asian descent comes in for a routine exam required for employment. He is in good health, without weight loss, fatigue or bleeding sx. FH negative for anemia. Exam is unremarkable and pt has no HSM. Neg stool guaiac.

Labs: WBC 5.3, HCT 35%, MCV 65, plts 330K, Retic index 0.8.

What is the best test to confirm the most likely cause of this patient’s anemia?

 A. Obtain CBC on siblings  B. Perform ultrasound for spleen size  C. Measure serum ferritin and iron studies  D. Perform hemoglobin electrophoresis and ferritin

 Thalassemia trait: mild anemia with pronounced microcytosis (MCV <70), nl RDW  Ethnicity: Mediterranean, Asian, African  Pt are asymptomatic  FamHx is often negative  Alpha-thal trait: dx of exclusion  Beta-thal trait: abnl electrophoresis  Beta-thalassemia intermedia: • Ineffective erythropoiesis, more severe anemia, often require frequent transfusions, at risk to develop of iron overload

Microcytic, hypochromic RBC, target and teardrop cells

• • • • Most common genetic disease in persons of African descent, 10% are carriers, 1/600 newborns Abnl beta-globin -> Hb S malforms when de oxygenated -> vaso occlusion Normocytic anemia c high reticulocyte count Dx with hemoglobin electrophoresis Complications: acute chest syndrome, AVN, CVA, cholelithiasis, infection, pain syndrome

 Evaluation:  Reticulocyte count  Smear – morphologic clues to etiology  CBC – eval. RBC data alongside WBC and Plt counts, RBC indices

High Smear Anemia (not due to acute blood loss) Reticulocyte count Microcytic Low Red blood cell indices, MCV Normocytic Macrocytic

 Most common etiologies:  Females – Iron deficiency  Men – Anemia of chronic disease

• • • Microcytic: iron def., thalassemia Normocytic: anemia of chronic disease (25% microcytic), chronic renal failure, marrow disease, hemolytic anemia*, acute blood loss* Macrocytic anemia: Folate def., B12 def., EtOH * Not hypoproliferative

• • • Multiple possible etiologies – iron deficiency, anemia of chronic disease, renal disease, dilutional Anemia is associated with higher mortality rates Evaluation is indicated and, in the case of iron deficiency, treatment may be of benefit Anker SD, et al. Ferric Carboxymaltose in Patients with Heart Failure and Iron Deficiency. N Engl J Med 2009;361:2436-48.

 Definition: Low oxygen carrying capacity in the blood due to low erythrocyte mass.

 We use the hematocrit or hemoglobin as surrogate markers for the erythrocyte mass because that it too difficult to measure.

 Hemoglobin of < 12 g/dL in women or a Hemoglobin of <13 g/dL in men is considered abnormal (WHO criteria).

 The hematocrit is approximately 3 x the hemoglobin.

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 History: Symptoms vary greatly based on the rapidity of the change in Hct, medical co-morbidities and the cause of the anemia.

 Physical exam findings: conjunctival rim pallor is the physical exam finding with the highest positive likelihood ratio (16.7)