Step 3 Hematology II

• Pernicious anemia is associated with a type of gastritis called autoimmune metaplastic atrophic gastritis (AMAG).
• AMAG is caused by autoimmune aggression against gastric mucosa.
• An immune response is mainly directed against oxyntic cells and intrinsic factor.
• The three main components of AMAG are glandular atrophy, intestinal metaplasia and inflammation. Atrophy affects mainly the gastric body and fundus.

• It may be caused by two large groups of disorders: 1) diseases with decreased red blood cell production, and 2) hemolytic disorders.
• To determine the predominant pathophysiologic mechanism of anemia in this patient, a reticulocyte count must be obtained.

• Secondary brain tumors are the more common type of brain tumors.
• The common primary sites of origin of brain metastasis, in the order of frequency, are: lung, breast, unknown primary, melanoma, and colon cancer.
• Small cell lung cancer has a predilection for early metastasis to the brain. The most common route of spread of the cancer is by hematogenous spread.
• The diagnostic imaging of choice to evaluate a patient with suspected metastatic disease is a contrast-enhanced MRI scan.

The clues to the presence of a metastatic brain lesion (as compared to a primary brain tumor) on radiographic imaging are the presence of multiple, well-circumscribed lesions, and a relatively large amount of vasogenic edema as compared to the size of the lesion.

• Anemia of chronic disease is a common complication of rheumatoid arthritis and other inflammatory diseases.
• The precise etiology is not fully understood but is generally thought to be due to suppression of hematopoiesis by inflammatory cytokines.
• Hematologic studies typically show a low serum iron, elevated ferritin levels, and normal transferrin saturation (approximately 25% of ACD patients may have low transferrin saturation).
• Mean corpuscular volume is usually low-normal to mildly decreased. ACD is usually a relatively mild anemia, but approximately 20% of patients may have hemoglobin less than 8 g/dl.

• The foundation of treatment for ACD is addressing the underlying inflammatory disorder.
• In rheumatoid arthritis, anti-TNF-a antibody (eg, infliximab) infusions have been shown to lessen the severity of anemia.
• If patients have low or inappropriately normal erythropoietin levels, they may respond to injections of erythropoietin or darbepoetin.
• Patients with appropriately elevated erythropoietin levels (especially more than 500 mU/mL) do not respond.
• Those who have severe, symptomatic anemia who do not improve with initial measures may need periodic red cell transfusions.

Plasmapheresis is used to reduce levels of circulating autoantibodies in conditions such as Guillain-Barre syndrome, myasthenia gravis, and thrombotic thrombocytopenic purpura.

• It is a nonmalignant lesion that arises in the terminal ducts and lobules of the breast.
• It is an occasional incidental finding on breast biopsy that has no mammographic or clinical correlate.
• While the lesion itself has no malignant potential, it signifies an increased risk of developing invasive lobular or ductal carcinoma in either breast (roughly 7-18 times the risk of the general population).

• It is recommended that cases where LCIS is diagnosed by needle biopsy proceed to excisional biopsy since up to 38% of cases may be upstaged to ductal carcinoma in situ (DCIS) or invasive cancer when the entire lesion is removed.
• After the lesion has been excised, management is more controversial. The most common management course is follow-up surveillance.
• Chemoprevention with selective estrogen receptor modulators (SERMs), such as tamoxifen or raloxifene, is an alternative option. Some patients may request prophylactic bilateral mastectomy which is also a viable alternative.

• Folinic acid is more potent than folic acid in 'rescuing' red blood cells from the deficiency by bypassing the block on DHFR.
• It is therefore the drug of choice for folate deficiency anemia induced by chronic, high dose methotrexate therapy.

• The best initial test for determining the cause of polycythemia is a serum erythropoietin level.
• In polycythemia secondary to chronic hypoxia, a high serum erythropoietin level is expected as a compensatory mechanism to correct for the hypoxia.
• Erythropoietin may be inappropriately elevated in the presence of certain tumors that secrete the hormone, such as renal cell carcinoma.
• A low erythropoietin level would suggest polycythemia vera, a chronic myeloproliferative disorder.

• Chronic hypoxia is the most common cause of secondary polycythemia.
• Carboxyhemoglobin levels should be obtained to exclude carbon monoxide poisoning in certain patients, including those who smoke heavily.
• Sleep apnea should be considered in patients with a relatively normal oxygen saturation on physical examination, as the hypoxia may be only intermittently present at night time.

• Several studies have suggested a strong correlation between alcohol intake and the development of colon cancer, especially in those individuals consuming 45 grams or more of alcohol per day (for sake of comparison, the amount of alcohol in a 12 oz beer is 13 grams).
• It is thought that the mechanism responsible may involve interference of folate absorption or decreased folate intake.

Fibrous diets rich in fruit and vegetables, regular NSAID use, hormone replacement therapy, and regular exercise have been identified as protective factors.

• Anemia in patients with end-stage renal disease (ESRD) is usually due to decreased renal erythropoietin production.
• Other causes include iron deficiency, severe hyperparathyroidism (which causes erythropoietin resistance), folate deficiency, systemic inflammation, and aluminum toxicity.
• These patients can develop iron deficiency due to blood loss from frequent blood testing, gastrointestinal blood loss (common in those with ESRD), or dialysis itself.

• Absolute iron deficiency is defined as transferrin saturation less than 20% or ferritin less than 100 ng/ml.
• However, the underlying inflammation associated with ESRD and dialysis can significantly increase serum ferritin and make it a less accurate measure of iron deficiency.
• Other markers of iron stores (eg, serum iron, transferrin saturation, total iron-binding capacity) can help clarify iron status.

• Patients with ESRD can have functional iron deficiency (normal iron stores with inability to mobilize the stores in response to erythropoietin), defined as transferrin saturation less than 20% with ferritin of 100-800 ng/ml or higher.
• Because erythropoietic-stimulating agents (ESAs) increase iron demand, these patients should have iron studies prior to starting ESAs.
• ESAs such as erythropoietin are recommended for ESRD patients with hemoglobin less than 10 g/dl.
• The goal is to increase hemoglobin by 1.5-2 g/dl over 4-6 weeks to target hemoglobin to 10-11.5 g/dl.

• Iron supplementation is recommended for ESRD patients with transferrin saturation less than 30% and ferritin less than 500 ng/ml.
• As a result, intravenous iron is suggested for patients on hemodialysis or peritoneal dialysis (oral iron is preferred for non-dialysis patients due to cost and convenience).
• Patients with ferritin more than 500 ng/ml (generally reflecting good iron stores) usually respond to increased ESA dose but may require intravenous iron if there is no response.

Accurate histological identification and staging of the tumor, along with preoperative physiologic assessment of lung function, is an important initial step in the optimal management of patients with lung cancer.

• Over-expression of HER-2/neu (an oncogene that encodes a transmembrane receptor belonging to the epidermal growth factor receptor family) is traditionally associated with a worse prognosis in breast carcinoma.
• There is some clinical evidence that HER-2/neu over expression may be associated with relative resistance to alkylating agents and probably endocrine therapy.
• Monoclonal antibodies against HER-2/neu (Trastuzumab, Herceptin) are effective in treating patients with over-expression of this oncogene.
• These also increase the patient's sensitivity to chemotherapeutic drugs.

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• Spinal cord compression develops in up to 25% of patients with Pancoast tumor during the course of the disease and may result in paraplegia.
• Early recognition and appropriate therapy (which may include corticosteroid therapy, surgery, and radiation) is imperative to preserve neurologic function and patient autonomy.

• Asymptomatic patients on tamoxifen do not need additional screening for endometrial cancer other than an annual gynecologic examination with a complete history and routine Pap smears.
• Symptomatic patients with vaginal bleeding or other symptoms warrant further investigation with TVUS or endometrial biopsy.

• Almost all patients with serum ferritin concentrations of less than the traditional cutoff of 15 ng/ml are iron deficient.
• However, the sensitivity using this cutoff is only modest at best and it cannot be used to exclude the diagnosis of iron deficiency since the majority of patients with a level of 15-30 ng/ml are also iron deficient.
• The gastrointestinal tract is the major source of blood loss leading to iron deficiency anemia in males.

• A number of studies have shown that a course of combined chemotherapy and radiotherapy, also known as chemoradiotherapy (CRT), promises superior results over chemotherapy or radiotherapy alone.
• It not only increases the 5-year survival rate, but also renders some inoperable HNC cases operable after treatment.