EXAMMASTER Hematology

A 5-year-old girl is brought to her pediatrician by her mother. Her mother notes that the patient has been bruising easily for the last few weeks, but she does not recall any major injury. The patient began feeling tired around this time as well. The mother initially thought she had the flu, but she brought the patient in when it became apparent she was not improving. On examination, the patient is pale and appears fatigued. Her skin has multiple areas of bruising and petechiae. She is febrile. A CBC/Diff is significant for the following: Test Result WBC 72.2 x 103 mm3 Hgb 8.4 gm/dL Hct 22.30% Platelets 30 x 103/µL Neutrophils 5% Lymphocytes 0% Monocytes 0% Basophils 0% Eosinophils 0% Blasts 95% Bone marrow biopsy is obtained and confirms presence of blasts. Stains for myeloperoxidase and Sudan Black are negative. Question What is the most likely diagnosis? 1 Acute myeloid leukemia 2 Acute lymphocytic leukemia 3 Chronic myeloid leukemia 4 Chronic lymphocytic leukemia 5 Hairy cell leukemia

Correct Answer: Acute lymphocytic leukemia Acute lymphocytic leukemia (ALL) is the most common form of leukemia in children. ALL typically presents in ages 3-7. Leukemic blast cells take over the bone marrow, impairing cell production. This can cause symptoms of thrombocytopenia, such as petechiae and easy bruising, as well as symptoms of anemia, such as fatigue and pallor. Patients are at risk for infection despite a high white blood cell count; the white blood cells in these patients are actually immature blasts, and they do not function properly. The patient's CBC is significant for anemia, thrombocytopenia, and leukocytosis with presence of blasts. The presentation is classic for acute leukemia; the patient's young age and negative stains for myeloperoxidase and Sudan Black suggest ALL.

A 5-year-old boy presents with his mother with a history of fever, hemorrhages, and repeated bacterial infections. On exam, lymphadenopathy and hepatosplenomegaly are present. Blood work shows a white blood cell count of 50,000/µL. Question Highlights What is the most likely diagnosis? 1 Acute myelogenous leukemia 2 Chronic myelogenous leukemia 3 Acute lymphocytic leukemia 4 Chronic lymphocytic leukemia 5 Hairy cell leukemia

Correct Answer: Acute lymphocytic leukemia Acute lymphocytic leukemia (ALL) occurs mainly in children and is the most common form of leukemia in children. T-cell markers are found in 15% of cases. The cells of most childhood ALL appear to be precursor B cells. There is an abrupt onset with fever, weakness, hemorrhages, and infections. Most common physical exam findings are enlarged lymph nodes and hepatosplenomegaly. Lymphoblasts predominate in the peripheral blood and lymph nodes, and these cells infiltrate the bone marrow. The peripheral white count is usually greater than 1 x 105/µL. With chemotherapy, more than 90% of affected children achieve complete remission.

A 16-year-old African American girl with hemoglobin S disease has experienced several complications, including multiple acute splenic sequestration crises that resulted in a splenectomy when she was 14. She no longer receives antibiotic prophylaxis. Her last polyvalent pneumococcal vaccine was 2 years ago. She presents to the emergency department with a 2-day history of fever up to 104.3°F without localizing symptoms. She notes malaise, abdominal discomfort, and one episode of vomiting. Examination reveals a temperature of 103.2°F; pulse 110; blood pressure 116/76 mm Hg; and respirations 21. Hydration is normal, and no localizing findings are present. Question Highlights What is the next step in the management of this patient? 1 Admit patient, obtain cultures, and begin IV ceftriaxone and vancomycin. 2 Await input from the infectious disease consultant. 3 Discharge the patient on oral amoxicillin/clavulanate. 4 Examine a peripheral blood smear for Howell-Jolly bodies. 5 Obtain blood cultures and discharge the patient pending results.

Correct Answer: Admit patient, obtain cultures, and begin IV ceftriaxone and vancomycin. A splenectomized patient is at risk for overwhelming post-splenectomy sepsis (OPSS) due to decreased phagocytosis of bacteria-complement/immunoglobulin complexes. OPSS can present with a nondescript picture that mimics a viral illness but progresses rapidly to sepsis, coagulopathy, organ failure, and death. Antibiotic prophylaxis with amoxicillin/clavulanate and immunization against Streptococcus pneumonia, Neisseria meningitides, and Haemophilus influenzae type b should be administered. Any fever should be addressed as a possible prodrome of OPSS. Since the likelihood of this patient having septicemia is high, immediate cultures should be obtained with intravenous broad-spectrum antibiotics begun directly after.

A 41-year-old woman is found to have anemia with Hb of 10 g/dL on a routine physical exam and labs. Patient has a history of hypercholesterolemia, depression, and rheumatoid arthritis. She is on a low cholesterol diet, escitalopram (Lexapro) 10 mg daily, and diclofenac 50 mg twice daily. Physical examination was essentially unremarkable except for mild arthritic changes at the proximal interphalangeal joints of both hands. Further labs reveal normal MCV and MCHC on peripheral smear. Serum iron and TIBC levels are low, percentage saturation with iron is normal, and ferritin level is moderately high. Question Highlights What condition does this patient most likely have? 1 Anemia of chronic disease 2 Pernicious anemia 3 Thalassemia 4 Iron deficiency anemia 5 Aplastic anemia

Correct Answer: Anemia of chronic disease Anemia of chronic disease is characterized by HB of 10-11 g/dL in mild cases, but 20% of patients may have a Hb of <8 g/dL. It is associated with any chronic disease, like collagen vascular diseases, renal failure, diabetes mellitus with nephropathy, heart diseases, other inflammatory conditions, and malignancies. In this case, the anemia is due to rheumatoid arthritis. The anemia is not due to iron deficiency, rather due to diminished iron utilization by the bone marrow or impaired marrow response to erythropoietin. Labs show normocytosis and normochromia. Serum iron level may be normal or slightly low; TIBC is low; ferritin is normal or high. Correction of the underlying disease is the treatment.

A 65-year-old woman presents after being on hemodialysis for the past 1.5 years for diabetic nephropathy. Despite stable subcutaneous erythropoietin and intravenous iron doses, her hemoglobin level has decreased from 12 g/dL to 10 g/dL over the past month. Oral lanthanum doses have been stabilized. Diabetes is treated with glyburide. She developed a foot ulcer 2 weeks ago and was treated with antibiotics. Additional tests include: Ferritin 800 ng/dL Transferrin Saturation 20% Total white blood cell count 7x103/mm3 Platelet count 250,000/mL TSH (thyroid stimulating hormone) 0.5 ng/mL PTH (Parathryoid hormone) 160 pg/mL (150-300 pg/mL normal for dialysis patients, National Kidney Foundation) Aluminum level, serum Normal Question Highlights What is the most likely cause of her anemia? 1 Myelodysplasia 2 Pernicious anemia 3 Iron deficiency 4 Anemia of chronic disease 5 Hyperparathyroidism

Correct Answer: Anemia of chronic disease The most likely cause of the decrease in hemoglobin level for this patient is anemia of chronic disease (also referred to as anemia of inflammation) that accompanied her foot ulcer. In the setting of inflammation, proinflammatory cytokines impair erythrocyte responsiveness to erythropoietin. Prior to the infection, she was on stable doses of erythropoietin to treat anemia, a common problem in dialysis patients. Her anemia is multifactorial; there is an erythropoietin deficiency due to the lack of erythropoietin being synthesized by the renal system, and it is often accompanied by blood loss with dialysis and poor gastrointestinal iron absorption.

A 20-month-old boy presents for a routine visit. He is eating well and drinking at least a bottle of cow's milk daily for the last several months. His history and physical are normal except for mild pallor. Urinalysis is normal, and the rest of his laboratory findings are below: Result Normal Values Hemoglobin 9.5 10.5-14.0 g/dL RDW 52 38.5-49.0% MCV 72 76.0-90.0 fl Platelets 280,000 150,000-450,000/μL WBC 6.7 5,000-14,500/μL Question Highlights What additional finding might you expect in this child? 1 Anisocytosis 2 Drepanocytosis 3 Schistocytosis 4 Elevated bilirubin 5 Increased hemoglobin A2

Correct Answer: Anisocytosis Anisocytosis results in elevated RDW. In this age group, the most common cause is iron deficiency anemia: when a large number of immature RBC (reticulocytes) found in the blood is a result of prematurely release from the bone marrow during blood formation, causing elevated RDW and polychromasia. An increase in the reticulocyte count is a sign of active erythropoiesis. The cause of his anemia most probably is the introduction of cow's milk in the first year of life. Cow's milk is low in iron, and its iron is poorly absorbed; it also decreases the absorption of iron.

A 24-year-old woman notices that she has a bruising tendency. She frequently has numerous small bruises and purple blotches on her skin. She hates having dental work because of the associated bleeding. On physical exam, you note that she has numerous petechiae. Her lab results are shown in the chart. TEST RESULTS REFERENCE RANGE Hematocrit 42 40-50 (male) 36-44 (female) Hemoglobin 14 gm/dL 13.8-17.2 gm/dL (male) 12.1-15.1 gm/dL (female) Platelets 41,000/mm3 130,000-400,000/mm3 PT 11.5 seconds 10.8-13.0 seconds PTT 30 seconds 25-41 seconds RBC 4.8 x 106/µl 4.5-5.7 x 106/µL (male) 3.9-5.0 x 106/µL (female) Question Highlights The patient's condition is most likely to be characterized by what? 1 Antiplatelet IgG 2 Decreased number of megakaryocytes 3 Spontaneous resolution 4 Requiring confirmation by bone marrow biopsy 5 Hemorrhagic death likely

Correct Answer: Antiplatelet IgG Antiplatelet IgG is seen with most patients with immune (idiopathic) thrombocytopenic purpura (ITP), which is the most likely diagnosis in this patient.

You are following up on laboratory results for your supervising physician while they are out of town. A bone marrow biopsy result for a 62-year-old man is noted. Bone Marrow aspiration (biopsy) Infiltration with small lymphocytes, B-cell. Coexpression of CD19, CD20, and CD5 Upon further chart review, you see that this patient presented to your clinic for review of abnormal health fair screening tests for his employment. The patient reported that he felt well in general, but he added that he could not exercise as vigorously as he could in the past; he attributed that to his aging. The table shows his complete blood count. Test Result Normal range Units WBC 98.4 3.6-9.0 K/μL RBC 4.78 4.18-5.22 M/ μL Hemoglobin 15.4 12.9-15.5 g/dL Hematocrit 45.2 34.6-50.1 % MCV 94.6 80.0-100.0 fL MCH 32.2 27.0-34.0 pg MCHC 34.1 30.0-37.0 g/dL RDW 11.7 11.0-17.0 % Platelets 392 140-440 K/μL MPV 9.9 6.5-12.0 fL WBC differential Neutrophils 5.70% 40-75% Lymphocytes 91% 20-50% Monocytes 2% 0-10% Eosinophils 1.20% 0-7% Basophils 0.10% 0-3% Question Highlights What pharmaceutical treatment should primarily be used to treat his condition, especially as it progresses? 1 Anticoagulants 2 Chemoimmunotherapy 3 Corticosteroids 4 Disease-modifying anti-rheumatic drugs (DMARDs) 5 Tumor necrosis factor (TNF) inhibitors

Correct Answer: Chemoimmunotherapy This patient's bone marrow result and presentation support a diagnosis of chronic lymphocytic leukemia (CLL), the most prevalent type of adult leukemia. CLL typically affects older individuals, and it can remain at a mild stage with minimal symptoms for years. In elderly patients with comorbidities, no treatment may be preferred. When treatment is desired and CLL is in early stages, chemoimmunotherapy is used. A variety of chemotherapeutic agents (such as chlorambucil, fludarabine, and cyclophosphamide) and monoclonal antibodies (primarily rituximab) may be chosen, based on the patient's CLL stage and genetics of his lymphocytes.

A 58-year-old man presents with a 4-month history of worsening fatigue. He has noted "enlarged nodes" along the right side of his neck; he has never noticed these nodes before and states they are bothersome due to having so many; they also seem to be getting bigger. Physical examination reveals multiple cervical lymphadenopathies involving both the posterior cervical and the superficial cervical lymph nodes on the right side. Labs obtained the day of presentation include abnormalities: a WBC count of 250,000/mm3 (normal: 5000-10,000 mm3), lymphocytes being 77% of circulating WBCs (normal: 20-40%), and a smear revealing small-but-mature-appearing lymphocytes. A subsequent bone marrow biopsy reveals variably infiltrated small mature lymphocytes. Philadelphia chromosome is negative. Question What is the most likely diagnosis? 1 Hairy cell leukemia (HCL) 2 Acute myeloid leukemia (AML) 3 Acute lymphoblastic leukemia (ALL) 4 Chronic lymphocytic leukemia (CLL) 5 Chronic myeloid leukemia (CML)

Correct Answer: Chronic lymphocytic leukemia (CLL) This patient most likely has chronic lymphocytic leukemia (CLL) due to the presenting symptoms, which include the patient's age (typically over 50, median 70), fatigue, and lymphadenopathy. Initial labs completed show an abnormally elevated white blood cell count with significant lymphocytosis; 75-98% of the cells are usually smaller (but mature-appearing) lymphocytes. Bone marrow biopsy is markedly infiltrated, with small (but mature) lymphocytes.

A 55-year-old man presents with a 1-week history of fatigue, night sweats, and abdominal fullness. On physical examination, you note a palpable spleen. You order a CBC; the results indicate a white blood count of 105,000 cells/mcL with a left shift of the myeloid series. The red blood cell count and morphology show anemia, and he has an elevated platelet count. To help confirm your suspicions, you order genetic studies, and the results come back with the BCR/ABL gene detected. Question Highlights What is the most likely diagnosis? 1 Chronic lymphocytic leukemia 2 Acute lymphoblastic leukemia 3 Chronic myelogenous leukemia 4 Acute myelogenous leukemia 5 Polycythemia vera

Correct Answer: Chronic myelogenous leukemia The clinical picture is suggestive of chronic myelogenous leukemia (CML). CML is a myeloproliferative disorder characterized by an overproduction of myeloid cells. Depending on disease progression, common findings include a strikingly high WBC (usually >100,000 cells/mm3), anemia, and an elevated platelet count (600,000-700,000 μL). A left shift of myeloid cells is noted. Definitive diagnosis is made by finding the BCR/ABL gene. CML has 3 stages: chronic, accelerated, and blastic. Symptoms (e.g., fever, night sweats, and tiredness) can appear at any point in the chronic phase.

A 17-year-old boy presents for a follow-up regarding fatigue and dizziness. After his initial presentation, he had some general blood work drawn, including a complete blood count (CBC), which shows a low hemoglobin and hematocrit. MCV is low. Question Highlights What detail from the patient's history would support your suspected diagnosis? 1 Heart palpitations 2 History of lymphoma 3 On doxycycline for 6 months 4 Craving to eat ice 5 Systemic lupus erythematosus

Correct Answer: Craving to eat ice In a patient who is anemic with a low mean corpuscular volume (MCV), the most likely diagnosis is iron deficiency anemia. Other causes of anemia with a low MCV would be thalassemia, sideroblastic anemia, anemia of chronic disease, and lead poisoning. Further lab testing (iron studies, reticulocyte count, and peripheral blood smear) would help differentiate these. Iron deficiency anemia is the most common form of anemia in the US and falls under the category of a microcytic anemia. A microcytic anemia is characterized by red blood cells with a MCV <80 fL. The patient's history of a craving to eat ice would support the diagnosis. Pica is described as persistent eating of non-nutritive substances for at least a month. Pica is more common in younger children than in older children or adults and can occur for a multitude of reasons. When the cravings are specifically for ice or dirt, this is sometimes associated with iron and/or zinc deficiencies. For this reason, the historical detail that he has been craving ice could be an indication that the cause of his anemia is iron deficiency. In many cases like this, the pica may disappear when oral iron is administered.

A 46-year-old woman underwent elective cholecystectomy. The attending nurse noted mild bleeding at the site of IV line and the incision site during dressing. The patient also reported bleeding from the gums and nose. Coagulation profiles revealed prolongation of aPTT, PT, and TT; decreased fibrinogen level; and increased levels of fibrinogen degradation product (FDP). Platelet count was also decreased. The patient was not experiencing any bleeding disorder before her hospitalization. Question What is the most likely cause of this patient's bleeding tendency? 1 Deficiency of clotting factors of the intrinsic pathway 2 Deficiency of clotting factors of the extrinsic pathway 3 Platelet functional defect 4 Disseminated intravascular coagulation 5 Underlying liver disease

Correct Answer: Disseminated intravascular coagulation Prolongation of aPTT, PT, and TT; decreased fibrinogen level; increased levels of FDP; and decreased platelet count indicate disseminated intravascular coagulation (DIC). DIC is an acquired syndrome characterized by bleeding from multiple sites, ecchymoses, mucosal bleeding, and depletion of platelets and clotting factors in the blood. The causes of DIC include infections (bacteria and their toxins, fungi, viruses, rickettsiae), obstetric and gynecological causes (such as abruptio placentae, abortions, eclampsia, amniotic fluid embolism), hemorrhagic shock, malignancy, snake venom, trauma, and transfusions. Diagnostic findings include coagulation abnormalities such as prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), decreased fibrinogen levels; increased levels of FDP; presence of D-dimer; and decreased platelet count. The mainstay of management involves treatment of the underlying cause. Blood products such as platelet concentrates, fresh frozen plasma, or cryoprecipitate can also be administered.

A 48-year-old previously healthy African American woman was involved in a severe motor vehicle accident, sustaining multiple injuries. She was stabilized in the emergency department but is now bleeding extensively from her laceration sites, her IV catheter site, and from mucous membranes. Laboratory results show thrombocytopenia, fragmented red blood cells, and low fibrinogen levels. Question Highlights What is the most likely diagnosis? 1 Factor V deficiency 2 Disseminated intravascular coagulation 3 Factor XI deficiency 4 Protein C and S deficiency 5 Acute idiopathic thrombocytopenia purpura

Correct Answer: Disseminated intravascular coagulation This patient's severe injuries triggered the mechanisms of disseminated intravascular coagulation (DIC). In DIC, traumatized or necrotic tissue releases tissue factor into the circulation, which triggers coagulation reactions. Thrombi and emboli develop. The thrombotic phase is followed by fibrinolysis. Hemorrhage results from depletion of coagulation factor and platelets. Diagnosis of DIC is made by thrombocytopenia, fragmented red blood cells, prolonged PT and PTT, decreased fibrinogen, and increased fibrin degradation products.

A 22-year-old man presents to his physician with swollen lymph nodes in the right axilla. He notes that he develops pain in the area after drinking alcohol. He has been feeling fatigued for the last few weeks and has lost weight without trying. Examination confirms lymphadenopathy in the right axilla. Biopsy of the region shows the presence of Reed Sternberg cells. Question What is the treatment of choice at this time? 1 Lenalidomide and prednisone 2 Doxorubicin, bleomycin, vinblastine, and dacarbazine 3 Radiation therapy 4 Stem cell transplant 5 Observation

Correct Answer: Doxorubicin, bleomycin, vinblastine, and dacarbazine The combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is the treatment of choice in Hodgkin's lymphoma. The patient's presentation of lymphadenopathy with the presence of Reed Sternberg cells on biopsy is classic for Hodgkin's lymphoma.

A 29-year-old African American woman and a 31-year-old African American man present for preconception counseling for sickle cell disease. The couple's complete blood count (CBC) and red cell indices are as follows: Female Patient Male Patient Hemoglobin 12.9 gm/dL 13.0 gm/dL HCT 43% 43% WBC 9.0 x 103/μL 8.0 x 103/μL Platelets 250 x 103/µl 220 x 103/μL Morphologic review of the peripheral blood smear from both patients shows normal red blood cell, platelet, and white blood cell morphology. Question Highlights What is the next step in their management? 1 Reassurance of normal RBC count and indices 2 Treatment of both candidates with hydroxyurea 3 Life adjustments for both with no pharmacotherapy indicated 4 Evaluation of both patients by hemoglobin electrophoresis 5 Repeat CBC in the woman only

Correct Answer: Evaluation of both patients by hemoglobin electrophoresis Electrophoresis is indicated next in these patients to detect a carrier state of sickle cell anemia. The CBC and microscopy are normal in both candidates, but this does not rule out the possibility of a carrier state of either sickle cell anemia or thalassemia (or other hemoglobinopathies). The ethnicity of both parents mandates their screening for hemoglobinopathies, particularly hemoglobin S. Hemoglobin electrophoresis on cellulose acetate is the preferred screening method for hemoglobin disorders. In candidates with abnormal hemoglobin, definitive diagnostic tests should be performed. The occurrence of sickle cell anemia can be prevented by the detection of those who may transmit the disorder through carrier-screening programs; they may then have genetic counseling and education about the options of not having children, having pregnancies monitored for the occurrence of sickle cell anemia in the fetus, or undergoing selective abortion.

An 11-year-old boy presents with a chronic history of mild hemolytic anemia, intermittent jaundice, and right upper quadrant pain. He denies any shortness of breath, muscle aches, or joint pain. Question Supplementation with what should be given to the patient as part of the treatment plan? 1Thiamine 2Cyanocobalamin 3Folic acid 4Niacin 5Riboflavin

Correct Answer: Folic Acid Folic acid should be given to patients who present with hemolytic anemias, such as those with hereditary spherocytosis as suggested in the above case. Hemolytic anemias cause reticulocytosis, which leads to an increased demand for folic acid in the formation of red blood cells. The treatment of choice for hereditary spherocytosis is splenectomy, as the spleen is responsible for sequestering and destroying the spherocytes, leading to hemolytic anemia.

A 29-year-old African American man develops dysuria and increased frequency of micturition. In the emergency room, he is found to have a urinary tract infection and is treated with Nitrofurantoin, as well as recommended to follow up with his primary care physician in the office. Over the next few days, the patient experiences fatigue, fever, jaundice, abdominal and back pain, and dark urine. Blood tests show Hb of 4 g/dL, reticulocyte count of 6%, and MCV of 93. Coombs test is negative and bilirubin is normal. Peripheral smear reveals cell fragments, microspherocytes, and blister or bite cells. Heinz bodies are also present. Question Based on these findings, what clinical entity is most likely? 1 Hereditary spherocytosis 2 Sickle cell anemia 3 Porphyria 4 G6PD deficiency 5 Autoimmune hemolytic anemia

Correct Answer: G6PD deficiency G6PD deficiency is a very common X-linked hemolytic disorder affecting millions worldwide. The highest incidence is among people of African, Asian, Kurdish Jewish, or Mediterranean descent. Glucose-6-phosphate dehydrogenase is an enzyme that is vital to the integrity of red cells. Deficient individuals are susceptible to hemolysis under oxidant stress caused by drugs like sulfa and antimalarials, infections, or noxious agents like fava beans. Oxidant stress causes denatured hemoglobin, resulting in Heinz bodies. During an acute event, as in this patient, rapid hemolysis causes acute anemia, hemoglobinuria (hence the dark urine), abdominal and back pain, jaundice, and even renal failure. G6PD levels are normal to low during an acute attack since the replacement reticulocytes are young and have adequate enzyme levels. G6PD level should be measured after an acute attack is over. Removing the precipitating agent and getting oxygen and rest is usually sufficient during an acute attack depending on the severity of anemia. This patient will most likely require hospital admission and blood transfusion due to severely low hemoglobin.

A 13-year-old African American boy presents with a 4-month history of increasing fatigue, pallor, exertional dyspnea, and depression. Past medical history is significant for an ischemic stroke due to sickle cell disease 6 years ago. Since his stroke, the boy has been receiving chronic red cell transfusion therapy, and subcutaneous iron chelation therapy started 3 years ago. On physical exam, pulse is 150 bpm, respirations are 20/min, blood pressure is 105/75 mm Hg, and O2 saturation by pulse oximetry is 92% on room air. In general, he appears ill; he is dyspneic and refuses to lie flat on the bed during his examination. Otherwise, he is cooperative with his exam. He is diaphoretic, with no rashes or skin abnormalities noted. His cardiovascular exam is significant for a 4/6 systolic ejection murmur and a gallop. His pulmonary exam demonstrates scattered expiratory wheezes throughout all lung fields. His liver is 4 cm below the right costal margin; no spleen is palpable. The remainder of his exam is unremarkable. Question Highlights You arrange for the patient to be transported to the hospital for admission. What combination of studies is most important for the initial evaluation and management of this patient? 1 Hemoglobin, liver function tests, hemoglobin electrophoresis, echocardiogram 2 Hemoglobin, ferritin, liver function tests, chest X-ray 3 Hemoglobin, arterial blood gas, hemoglobin electrophoresis, liver biopsy 4 Hemoglobin, ferritin, CT of the chest, echocardiogram 5 Hemoglobin, ferritin, liver function tests, chest X-ray, echocardiogram

Correct Answer: Hemoglobin, ferritin, liver function tests, chest X-ray, echocardiogram This patient's history and physical are most consistent with congestive cardiomyopathy due to iron overload. Patients receiving chronic red cell transfusions can develop complications of iron overload despite receiving adequate iron chelation therapy. Although all of the studies listed may be needed at some point during the evaluation and treatment of this patient, hemoglobin, ferritin, liver function tests, chest X-ray, and echocardiogram offer the most important information needed to confirm the diagnosis and better determine the immediate clinical stability of the patient.

A 12-year-old Jewish girl is brought in by her father. The father reports that the child started to bleed profusely following tooth extraction 2 hours ago. Further questioning reveals that there is a history of bleeding disorder in the child's maternal uncle and aunt. Examination reveals tachycardia and bleeding from the site of tooth extraction. Coagulation profile reveals prolonged activated partial thromboplastin time (aPTT), normal prothrombin time (PT) and thrombin time (TT), and deficiency of factor XI. The child was treated with fresh frozen plasma (FFP) and fibrin glue. Question Highlights What is the likely diagnosis? 1 Thrombocytopenia 2 Hemophilia B 3 Von Willebrand disease 4 Hemophilia A 5 Hemophilia C

Correct Answer: Hemophilia C Hemophilia C is an inherited autosomal disorder characterized by deficiency of factor XI, and it is common in the Ashkenazi or Iraqi Jewish population. Patients are usually asymptomatic. Spontaneous bleeds into joints, soft tissues, and muscles are rarely seen in Factor XI deficiency. Bleeding usually occurs after tooth extractions, trauma, or surgery, such as tonsillectomy. Hemophilia C should be suspected in patients with prolonged aPTT and a positive family history of lifelong bleeding disorders affecting both male and female family members. This condition is primarily treated with FFP and other adjunctive measures, such as fibrin glue and antifibrinolytics. Replacement with Factor XI concentrates can be done when available.

A 43-year-old woman presents with fever and cough, and she is found to have right lobar pneumonia with mild pleural effusion. She is admitted to the hospital for IV antibiotics and hydration. Not much of a medical history is obtained because she is quite confused on the first day and no family members are present. Based on her partial list of medications, it seems she has hypertension, systemic lupus erythematosus, and arthritis. Surgical history, family history, and allergies are unknown since this is her first visit to this hospital. Two IV lines are started, one in each arm: one for fluids, and the second for the two antibiotics. Other orders include nebulizer treatment every 4 hours, oxygen by nasal cannula, CXR in the morning, hep-lock second IV in between antibiotics, and a Foley catheter for strict urine output measurement; the catheter shows amber colored urine on admission. The patient improves gradually. By the second day, she is fully alert, oriented, and far less symptomatic. She is afebrile, but she still has a mild productive cough and occasional shortness of breath. On the same day, she also complains of left arm pain and has swelling of the entire arm with much tenderness diffusely, indicating possible upper extremity thrombosis. She is given a bolus of heparin and a heparin infusion is initiated. 5 days later, her labs show a Hb of 12 g/dL, WBC 11,000, down from 17,000, and platelet count of 56,000, down from 250,000 on admission. Her EKG is normal sinus rhythm, troponin is 0.1, CK 67 and CXR show decreased consolidation with resolving of pleural effusion. Question What is the most likely diagnosis? 1 Lupus anticoagulant 2 Oral contraceptive induced thrombosis 3 Trousseau's syndrome 4 Heparin-induced thrombocytopenia 5 Paroxysmal nocturnal hemoglobinuria (PNH)

Correct Answer: Heparin-induced thrombocytopenia Heparin-induced thrombocytopenia is a well-recognized complication of heparin therapy; it usually occurs 4-10 days after heparin treatment has started and is the result of the formation of antibodies against the heparin-platelet factor 4 complex. Heparin is an anticoagulant used in various conditions like deep vein thrombosis, pulmonary embolism, hemodialysis, during and after percutaneous coronary intervention procedures like angioplasty and stent placement, and in patients with disseminated intravascular coagulation. It is the anticoagulant of choice in pregnancy since warfarin is well known for its teratogenic effects. It can be used intravenously or subcutaneously. Its principle side effect is bleeding. In cases of overwhelming hemorrhage, protamine sulphate can be used as an antidote. Heparin-induced thrombocytopenia is associated with thrombocytopenia and thrombus formation. The treatment involves prompt discontinuation of heparin.

A 24-year-old man presents with a large painless mass above his right clavicle. He reports no change in its current size over the last 6 months. He denies excessive fatigue/malaise, weight loss, fevers, or chills. Physical exam reveals no hepatosplenomegaly or palpable cervical, axillary, or inguinal lymphadenopathy. Excisional biopsy of the mass is performed and the pathologist reports the presence of Reed-Sternberg cells. Question Highlights What is the most likely diagnosis? 1 Benign lymph node enlargement 2 Hodgkin's lymphoma 3 Non-Hodgkin's lymphoma 4 AIDS 5 Kikuchi disease

Correct Answer: Hodgkin's lymphoma The presence of abnormal B cells (Reed-Sternberg cells) is pathognomonic for Hodgkin's lymphoma. Although studies have shown a fivefold increase in the incidence of Hodgkin's lymphoma in HIV+ patients, the disease is not a defining disease of acquired immune deficiency syndrome (AIDS). Non-Hodgkin's lymphoma is likely to show a mixture of abnormal T and B cells on biopsy. Benign lymph node enlargement would have a normal biopsy result. Kikuchi disease presents with fever and cervical lymphadenopathy; it is more common in females. Biopsy results can show a necrotic foci with perinodal inflammation.

A 44-year-old Caucasian woman is admitted to the hospital with a severe nosebleed. The patient states that there was no history of trauma, and she has never had nosebleeds before. She also reports a history of upper respiratory infection (URI) symptoms 1 week ago. The patient's blood work is notable for a platelet count of 10,000/mm3. The patient is treated with steroids for her presumptive diagnosis. The patient's platelet count is refractory, and a splenectomy is performed. Question Highlights After a few months, what would you expect to see in this patient's peripheral blood smears? 1 Burr cells 2 Howell-Jolly bodies 3 Hypersegmented neutrophils 4 Schistocytes 5 Spherocytes

Correct Answer: Howell-Jolly bodies Howell-Jolly bodies are basophilic red cell inclusions commonly found in patients who have had a splenectomy. This patient had a splenectomy after being diagnosed with ITP. Howell-Jolly bodies are round basophilic-staining nuclear fragments of DNA in the red blood cell. This is also a classic finding in cases of sickle cell disease in which the spleen auto-infarcts.

A 59-year-old man starts to notice that he no longer has the energy for his morning jog. He starts to develop back pain, so he completely stops exercising, but this does not seem to help. He is always tired and seems to have a lot of aches and pains. One day, his back pain is particularly bad, so he sees his primary care physician. He also acknowledges constipation and polyuria. On physical exam, his doctor notes that he is pale. His laboratory tests are as follows: TEST RESULTS REFERENCE RANGE RBC 4.2 x 106/µl 4.5-5.7 x 106/µl (male) 3.9-5.0 x 106/µl (female) hematocrit 38 40-50 (male) 36-44 (female) hemoglobin 13 g/dL 13.8-17.2 g/dL (male) 12.1-15.1 g/dL (female) calcium 12 mg/100 mL 9-10.5 mg/100 mL ESR 40 mm/hr <30 mm/hr Comment: Rouleaux formation is seen An X-ray of the lumbar spine reveals "punched out" lesions. Question Highlights What immunoglobulin is most frequently elevated in this condition? 1 IgA 2 IgM 3 IgE 4 IgD 5 IgG

Correct Answer: IgG The correct response is IgG. This patient has signs and symptoms of multiple myeloma. Multiple myeloma is associated with lytic bone lesions. There can also be anemia (explaining the weakness and paleness) and hypercalcemia (explaining the polyuria and constipation). Rouleaux formation is commonly seen with multiple myeloma. Plasma cell neoplasms have particular biological and clinical attributes related to their ability to affect immunoglobulins. The most important of these tumors is multiple myeloma. The type of protein the cells produce helps determine the type of multiple myeloma and best treatment approach. IgG is usually present in the largest amounts, accounting for 60-70% of all multiple myeloma cases. The malignant cells in multiple myeloma are plasma cells.

A 56-year-old man presents with a painful lump on his neck that has been bothering him for the past 2 weeks. He denies other symptoms or recent illness. He has a past medical history of hypertension and kidney stones. Nursing staff reports that his temperature is 97.9°F, heart rate is 65, respirations 12, and blood pressure is 140/88. During your examination, you palpate an enlarged lymph node on his left suboccipital region that is soft and about 1 cm in size. The lymph node is non-movable, non-erythematous, and without warmth or fluctuance. Question Highlights What physical exam finding is most concerning? 1 Size of 1 cm 2 Soft consistency 3 Immobility 4 Tenderness 5 Suboccipital location

Correct Answer: Immobility Immobile or "fixed" lymph nodes are very concerning for malignancy. A normal lymph node is freely movable in the subcutaneous space.

A 24-year-old woman is evaluated in the endocrinology clinic. She is on 100 mcg of thyroxine per day for treatment of Hashimoto's thyroiditis and receives oral steroids for autoimmune adrenal insufficiency. In addition, she complains of fatigue, numbness, and tingling in her feet. When routine labs were drawn, the following values were noted: Hb: 9.9 g/dL MCV: 102 Iron indices: normal Folate: normal B12: low Parietal cell antibodies: high Question Highlights What would prevent the development of megaloblastic anemia in this patient? 1 Intramuscular injection of B12 2 Intravenous folate 3 Prescribed dose of oral folate 4 Small dose of oral B12 5 Prescribed dose of oral ferrous sulfate

Correct Answer: Intramuscular injection of B12 The condition being described above is pernicious anemia. The case gives clues to the diagnosis of B12 deficiency and, more specifically, pernicious anemia. Clues include the presence of other autoimmune conditions, macrocytic anemia, normal iron indices, and raised parietal cell antibodies. Pernicious anemia is characterized by failure to absorb oral B12, possibly due to lack of intrinsic factor. This results in a deficiency over time. The parietal cells are destroyed by autoantibodies. Healthcare providers treat pernicious anemia by replacing the missing vitamin B12 in the body. People who have pernicious anemia may need lifelong treatment. Goals of treatment include the following: preventing/treating the anemia and its signs and symptoms, preventing/managing complications that can occur, as well as treating the cause (if a cause can be found). Since the patient is having significant signs and symptoms of pernicious anemia, an injectable form of B12 would be certain to correct the deficiency.

A 7-year-old African American girl presents with a 6-hour history of severe pain in her hands and feet that started spontaneously. She has been having bouts of excruciating pain since she was 6 months old. She is an only child, and her parents have recently discovered that they are both carriers of her condition. On examination, her HR is 115 bpm and blood pressure is 90/50 mm Hg; she is also jaundiced. She has a mildly enlarged spleen but no source of infection. Laboratory investigations reveal hemoglobin of 8 g/dL. Question Highlights What treatment would be most appropriate? 1 Splenectomy 2 Ferrous sulfate 3 Antibiotics 4 Bone marrow transplant 5 Intravenous hydration

Correct Answer: Intravenous hydration The clinical picture is suggestive of a vaso-occlusive painful crisis in a patient with sickle cell disease. Intravenous hydration and aggressive pain management are the two main treatments for this condition. In tissues with reduced oxygen concentration, the hemoglobin S (Hb S) polymerizes into rods, giving the red blood cells the characteristic crescent appearance of sickles. These sickle cells are less pliable and more adherent to the vascular endothelium, which causes vaso-occlusion and premature destruction of the red cells by the spleen, resulting in hemolytic anemia. Clinical manifestations of the vaso-occlusion and tissue ischemia (painful crises) include acute pain in the long bones, hands, feet, joints, back, and abdomen. Other symptoms that arise as a result of end-organ damage by infarction include seizures, hemiplegia, cranial nerve palsies, coma, renal failure, retinal hemorrhages, and detachment. These painful crises can be precipitated by: infections dehydration hypoxia excessive exercise Treatment is symptomatic, as there is no definitive cure. Patients who present in a painful crisis should be hydrated orally or intravenously and given analgesics.

A 3-day-old male newborn starts to have mild epistaxis after vaginal delivery at home. The mother is a 38-year-old G2P2 who had diet-controlled gestational diabetes. She took a prenatal vitamin and iron supplement. Active labor lasted 3 hours. The midwife who examined the newborn after the delivery declared the newborn healthy. Since the delivery, the mother has been exclusively breastfeeding. The baby is eating every 1-2 hours and has had several wet diapers and 3 stools. Question Highlights What would be the most definitive treatment for this newborn's epistaxis? 1 Fresh frozen plasma 2 Whole blood transfusion 3 Direct pressure to nares 4 Intravenous vitamin K 5 Intravenous vitamin C

Correct Answer: Intravenous vitamin K This baby is at risk for hemorrhagic disease of the newborn because he was born at home and may not have had immediate and routine medical care. A decrease in factors II, VII, IX, and X normally occurs in all newborns by 48-72 hours. There is a gradual return to birth levels by 7-10 days of life. Routinely in a hospital setting, an intramuscular dose of vitamin K immediately after birth helps prevent hemorrhagic disease of the newborn. The disease is treated with an intravenous infusion of vitamin K, with improvement in coagulation defects within a few hours. Pressure and chemocautery will not correct the coagulation factors. Plasma and blood transfusions may be needed if the baby has a severe form of vitamin K deficiency and his PT fails to improve, or if the bleed is severe. Vitamin C administration plays no direct part in the immediate treatment of this scenario.

You are following up on laboratory results for your supervising physician while they are out of town. A bone marrow biopsy result for a 62-year-old man is noted. Bone Marrow aspiration (biopsy) Infiltration with small lymphocytes, B-cell. Coexpression of CD19, CD20, and CD5 On further chart review, you see that this patient presented to your clinic for review of abnormal health fair screening tests for his employment. The patient reported that he felt well in general, but he added that he could not exercise as vigorously as he could in the past; he attributed that to his aging. The table shows his complete blood count. Test Result Normal Range Units WBC 98.4 3.6-9.0 K/μL RBC 4.78 4.18-5.22 M/ μL Hemoglobin 15.4 12.9-15.5 g/dL Hematocrit 45.2 34.6-50.1 % MCV 94.6 80.0-100.0 fL MCH 32.2 27.0-34.0 pg MCHC 34.1 30.0-37.0 g/dL RDW 11.7 11.0-17.0 % Platelets 392 140-440 K/μL MPV 9.9 6.5-12.0 fL WBC differential Neutrophils 5.70% 40-75% Lymphocytes 91% 20-50% Monocytes 2% 0-10% Eosinophils 1.20% 0-7% Basophils 0.10% 0-3% Question Highlights If you were to review this patient's physical exam from his prior visit, what finding would you expect to see in his chart? 1 Ecchymoses 2 Jaundice 3 Large mass 4 Lymphadenopathy 5 Petechiae

Correct Answer: Lymphadenopathy This patient's bone marrow result and presentation support a diagnosis of chronic lymphocytic leukemia (CLL). Most patients are asymptomatic in the early stages of the disease; they might have vague symptoms, such as fatigue, decreased appetite, mild weight loss, and decreased exercise tolerance. The most common finding on physical exam is lymphadenopathy. Other findings such as hepatomegaly and splenomegaly are present in more advanced CLL. At later stages, in which the bone marrow is drastically affected and erythrocytes and platelets are altered, the patient may show pallor.

A 38-year-old woman of northern European origin is brought to the emergency room by her relatives who report abnormal behavior. The patient denies the accusation and reports numbness and a tingling sensation in both her hands and feet (gloves and stockings) and recurrent diarrhea. Physical examination shows an atrophic tongue (glossitis), and a neurologic examination reveals a loss of her sense of vibration and fine touch. Endoscopic examination shows atrophic gastric mucosa and fasting achlorhydria. Question Considering this patient's diagnosis, what test finding would you anticipate? 1 Negative gastric parietal cell antibody assay 2 Microcytic hypochromic red blood cells in peripheral blood film 3 Megaloblastic erythropoiesis in bone marrow 4 Negative Schilling test 5 Hyperchlorhydria

Correct Answer: Megaloblastic erythropoiesis in bone marrow This patient's exam findings and history make the diagnosis of pernicious anemia likely. Pernicious anemia causes megaloblastic anemia due to vitamin B12 deficiency. This is an autoimmune disease in which various types of antibodies are produced against gastric parietal cells and intrinsic factors (IF). Vitamin B12 is unable to be absorbed from the intestinal tract. Atrophy of gastric mucosa is seen in patients with pernicious anemia. Diagnostic laboratory test results include low serum B12 level and a peripheral blood film with macrocytic anemia. If a bone marrow sample was obtained, there would be megalobastic erthryopoesis in bone marrow.

A 70-year-old African American man with a PMH of HTN x 23 years and type 2 DM x 20 years was admitted to the hospital due to a high-grade fever, nausea, infection, and severe back pain. Nearly 2 years prior, while walking down his steps, he fell without incurring any apparent fractures. Since then, he has been experiencing mild back pain that worsens when coughing. Physical exam is significant for pallor and hepatosplenomegaly. Skin exam is normal. Lab reports reveal low red blood cell count but normal neutrophil and platelet count. Renal function is decreased. The serum protein electrophoresis reveals the presence of paraprotein. Bone marrow biopsy reveals 50% infiltration by plasma cells. Question Highlights What is the most likely diagnosis? 1 Multiple myeloma 2 Waldenström's macroglobulinemia 3 Monoclonal gammopathy of unknown significance 4 Primary amyloidosis 5 Polyclonal hypergammaglobulinemia

Correct Answer: Multiple myeloma Multiple myeloma is a malignant disorder of the plasma cells. The disease occurs very frequently in people over 60. Males are more frequently affected than females. In the patients with multiple myeloma, bone marrow biopsy shows heavy penetration with atypical plasma cells. The hallmark of myeloma is the finding of a paraprotein on serum protein electrophoresis (SPEP). The majority of patients have a monoclonal spike in the beta or gamma globulin region.

A 60-year-old man presents with sharp pain in his ribs and sternum; he has a history of allergies and has been sneezing frequently. Except for a heart rate of 120/min, the physical examination is normal. With the exception of a tonsillectomy as a child, his medical and surgical history is unremarkable. He has chronic seasonal allergies. Family history reveals nothing significant. Radiographs on the ribs and sternum reveal lytic lesions and a significant fracture of the sternum. Neurological examination is unremarkable. The laboratory results are shown in the table. Peripheral blood smear reveals rouleaux formation of RBCs. Bone marrow aspiration reveals large numbers of plasma cells. Tests Results Differential BUN 24 mg/dL Metas 0.30% Protein 12.0 g/dL Bands 3.20% Albumin 3.8 g/dL Segs 55.30% Uric acid 11.9 mg/dL Eos 4.00% Calcium 8.4 mEq/L Basos 0% Sodium 137 mmol/L Lymphs 34.00% Urinalysis Protein 4+ Monos 3.20% RBC 4.3 x 1012/L Platelets 380 x 109/L Hgb 12.4 g/dL Hct 0.35 MCV 82 fL MCHC 34% MCH 28 pg WBC 8.0 x 109/L Question What is the most likely diagnosis? 1 Burkitt's lymphoma 2 Acute lymphocytic leukemia 3 Multiple myeloma 4 Acute myeloblastic leukemia 5 Chronic lymphocytic leukemia

Correct Answer: Multiple myeloma Multiple myeloma is a neoplastic disorder characterized by a proliferation of myeloma (plasma cells) in the bone marrow and rouleaux formation of RBCs in the peripheral smear, typically occurring in older age. Anemia may be present. WBC and platelet count may be either normal or decreased. Both serum and urine protein may be elevated, with a large gap between total protein and serum albumin. Pancytopenia, coagulation abnormalities, hypercalcemia, and azotemia are common. Hypoalbuminemia, elevated alkaline phosphatase, and erythrocyte sedimentation rate may be present. A 24-hour urine protein electrophoresis demonstrates Bence Jones proteins. Radiographic findings include diffuse osteopenia, discrete lytic lesions, and fractures. Bone marrow aspiration is required for definitive diagnosis, which shows replacement of the marrow with plasma cells, which will produce large amounts of monoclonal immunoglobulin that can be demonstrated in the serum or urine.

A 65-year-old woman presents with pain in the back, chest, and at the right seventh rib. She appears to be quite pale, and she admits to fatigue. These symptoms have come on gradually over several weeks, with the back pain becoming the reason for consulting the physician. Physical examination reveals localized tenderness at the spine of T8 and ribcage with tenderness at the right seventh rib. CBC shows a normochromic normocytic anemia with hemoglobin of 8 g/dL. Peripheral smear shows marked rouleaux formation with normal platelet and white cell counts and morphology. Serum chemistry results include calcium elevation to 12.2 mg/dL with normal alkaline phosphatase. A dipstick urinalysis shows proteinuria. A bone marrow aspirate was dry. The bone marrow biopsy is pending. Plain film X-rays of the chest show a fracture of the right seventh rib and compression of the eighth vertebra. Question Highlights What is the most likely diagnosis? 1 Chronic lymphocytic leukemia 2 Chronic myelogenous leukemia 3 Multiple myeloma 4 Hairy cell leukemia 5 Myelofibrosis

Correct Answer: Multiple myeloma Skeletal pathology, likely pathologic fractures, along with rouleaux due to paraproteinemia, and hypercalcemia make the diagnosis of multiple myeloma unavoidable. Proteinuria may be due to free light chains.

A 2-month-old infant who is breastfeeding presents with low hemoglobin levels. The infant was born at home and the mother received no prenatal care; she did not, and does not, take any medications. Family history is unremarkable. On examination, the infant appears healthy. Question Highlights What is the underlying mechanism of low hemoglobin levels in this infant? 1 Folate deficiency 2 Vitamin K deficiency 3 Breastfeeding 4 Infection 5 Normal process

Correct Answer: Normal process Intrauterine hypoxia stimulates erythropoietin. Infants are born with high levels of hemoglobin and erythrocytes in their blood, which downregulates erythropoietin. A progressive drop in hemoglobin during the first 2-3 months of life is the signal to the infant's body to increase erythrocyte production. This is a normal process called physiologic anemia of infancy; no treatment is needed.

A 62-year-old man was diagnosed with multiple myeloma 1 year ago; he is currently hospitalized with intractable nausea and vomiting. Since he was asymptomatic at the time of diagnosis, he has not been treated for his cancer. His wife reports he has not eaten in several days, but he is constantly drinking water. He appears confused and lethargic. When adjusted for the albumin level, serum chemistries reveal an elevated level of calcium (12.0 mg/dL). Question Highlights What should the initial treatment of his hypercalcemia include? 1 Normal saline 2 Calcitonin 3 Pamidronate 4 Gallium nitrate 5 Dexamethasone

Correct Answer: Normal saline Hypercalcemia is present in about 1/3 of patients with multiple myeloma. It is usually associated with a large disease burden, and it is caused by excessive bone resorption by osteoclasts. Initial treatment involves the infusion of normal saline (3-6 liters per day) to promote renal excretion of calcium, usually in combination with diuretics to prevent fluid overload.

A 23-year-old woman presents with fatigue and the recent onset of a yellowing of her skin. Her physical examination is remarkable for the presence of splenomegaly. Laboratory results are as follows: TEST RESULTS REFERENCE RANGE Hematocrit 38 40-50 (male) 36-44 (female) Hemoglobin 12.6 g/dL 13.8-17.2 g/dL (male) 12.1-15.1 g/dL (female) RBC 3.3 x 106/µl 4.5-5.7 x 106/µl (male) 3.9-5.0 x 106/µl (female) MCHC 37 31-36 Platelets 258,000/mm3 130,000-400,000/mm3 WBC 5.4 x 103/mm3 4.0-11 x 103/mm3 Neutrophils 57 40-75% Lymphocytes 37 15-45% Monocytes 4 1-10% Eosinophils 2 1-6% Basophils 0 0-2% Comments: Red blood cells are spherocytes. Red blood cells demonstrate increased osmotic fragility. Question Where is the primary pathology in this patient's condition? 1 Heme 2 RBC membrane 3 α globin chain 4 β globin chain 5 Spleen

Correct Answer: RBC membrane The primary pathology is located within the red blood cell membrane that leads to the abnormal spherical shape of the cells. This patient has hereditary spherocytosis. Findings consistent with hereditary spherocytosis are spherocytes on the peripheral blood smear, anemia, an elevated MCHC, increased osmotic fragility, and splenomegaly. The abnormal red blood cells are subsequently removed by the spleen, resulting in increased hemolysis. Splenectomy can be used to treat hereditary spherocytosis. In approximately two-thirds of the cases, hereditary spherocytosis is inherited in an autosomal dominant manner.

A 28-year-old female administrator is referred to your office for further evaluation. She has noted swellings on her neck for the past 3 weeks. She denies any history of cough, fever, or night sweats. She reports she has been getting pruritus after taking alcohol. She is not on any medication and has no prior admissions. On examination, she is not pale and her vital signs are normal. She has a 2 cm rubbery non-tender left anterior cervical node and a 3 cm left posterior cervical node. No other nodes are palpable. The systemic examination is essentially normal. CT scans done of the chest, abdomen, and pelvis are normal. Reed-Sternberg cells are seen on a biopsy of the node. The ESR is 30 mm/hr. Question Based on the most likely diagnosis, what is the appropriate therapy? 1 Antiviral treatment 2 Corticosteroids 3 Surgical resection 4 Broad-spectrum antibiotics 5 Radiotherapy and chemotherapy

Correct Answer: Radiotherapy and chemotherapy The clinical presentation is suggestive of Hodgkin's lymphoma (HL), a malignant disease of the reticuloendothelial and lymphatic systems. Patients usually present with cervical, supraclavicular, or mediastinal lymphadenopathy. They also may have constitutional symptoms such as unexplained weight loss of >10% body weight, unexplained fever >38°C, and profuse night sweats. The presence of these symptoms is noted as "B" in staging, and their absence as "A." Other symptoms include malaise, anorexia, and severe pruritus. Pathological diagnosis is based on identification of Reed-Sternberg cells. Staging of Hodgkin's lymphoma helps determine the mode of treatment. Each treatment plan should be individualized, but a majority of HL stages are treated with radiotherapy and chemotherapy. Surgical resection typically does not play a role in treatment.

A 40-year-old woman undergoing a gynecologic workup for metromenorrhagia presents with a several-week history of fatigue and lightheadedness. Laboratory evaluation reveals a hemoglobin of 11 g/dL (12-16 g/dL), hematocrit of 34%, MCV of 70 fL (80-100 fL), and MCH of 24 pg (27-33 pg). Further studies reveal a ferritin level of 25 ng/mL (12-300 ng/mL), TIBC of 500 mcg/dL (250-450 mcg/dL), and an iron level of 45 mcg/dL (60-170 mcg/dL). The patient is diagnosed with iron deficiency anemia. She is prescribed ferrous sulfate 325 mg po tid. Several days later, she presents to the ER. She reports resting dyspnea and chest discomfort. Oxygen and nitroglycerin are given. Cardiac enzymes are pending. The patient's hematocrit is 23% with hemoglobin of 7.5. Question Highlights What treatment is most appropriate for this patient? 1 Addition of ascorbic acid 2 Increased dose of ferrous sulfate 3 Iron dextran IM or IV in the ER 4 Iron sucrose 200 mg IV in the ER 5 Red blood cell transfusion

Correct Answer: Red blood cell transfusion Red cell transfusion is the most appropriate treatment for this patient with symptomatic anemia. Anemia is defined as a decreased number of red blood cells. If the body is deficient in iron, a decrease in hemoglobin and (eventually) a reduced number of RBCs result. The body may become deficient in iron because of a decreased oral intake, increased loss (such as increased bleeding), or an increased iron requirement (e.g., pregnancy). Once iron deficiency anemia is confirmed through blood tests (decreased hemoglobin and hematocrit with a low MCV, MCH and MCHC, low iron level, increased transferrin level, low serum ferritin), treatment is planned.

A 16-year old girl on her high school's swim team focuses her exercise regimen on endurance rather than building muscle mass. While her menses are regular and moderate in quantity, she is concerned that she may become iron deficient and that this will negatively affect her endurance and athletic performance. She asked if she should begin an iron supplement. Past medical history was unremarkable, and there was no history of tobacco, alcohol, or recreational drug use. Growth and development have been normal, and immunizations are current. Vital signs are normal. Examination is unremarkable, consistent with Tanner stage V. Hematocrit, hemoglobin, and ferritin were normal. Question Highlights What would you recommend? 1 Iron supplements can increase endurance in moderate doses. 2 All menstruating adolescents should take an iron supplement. 3 She does not need an iron supplement. 4 Iron supplements have been banned by regulatory agencies. 5 Iron supplementation have no adverse effects.

Correct Answer: She does not need an iron supplement. Iron is an essential element required for hemoglobin formation, but there has been no demonstrated benefit of iron supplementation as a performance enhancer in the absence of iron deficiency (normal hemoglobin, hematocrit, and ferritin levels). This patient does not need an iron supplement. Decreased serum ferritin without iron deficiency anemia has not been shown to adversely affect performance and can usually be corrected by dietary modification. The iron requirement for a 16-year-old girl is approximately 15 mg/day. Good dietary sources of iron are lean meat, fish, poultry, eggs, green leafy vegetables and fortified whole grains.

An 11-month-old African American boy presents with an acute onset of anorexia, irritability, unexplained bruising, and jaundice. On examination, you note pale conjunctivae, icteric sclerae, and splenomegaly. Laboratory studies reveal decreased hemoglobin and hematocrit and a significantly elevated reticulocyte count. Hemoglobin electrophoresis reveals the presence of hemoglobin S. Question Highlights What is the most likely diagnosis? 1 Alpha-thalassemia 2 Beta-thalassemia 3 Sickle cell disease 4 Glucose-6-phosphate dehydrogenase (G6PD) deficiency 5 Hepatitis B

Correct Answer: Sickle cell disease Sickle cell disease is a disorder in which an autosomal recessive genetic defect induces abnormal production of the beta-globin subunit of hemoglobin, causing the normally biconcave disc to take the characteristic "sickle" shape. This abnormal hemoglobin is designated as hemoglobin S, and its presence can be confirmed by hemoglobin electrophoresis studies. Sickle cell disease has its onset during the first year of life when fetal hemoglobin (hemoglobin F) levels fall and the body is signaled to start producing adult hemoglobin (hemoglobin A). Affected patients often present with an acute onset of weakness, fatigue, irritability, anorexia, easy bleeding/bruising, and jaundice. Splenomegaly is usually noted on exam. Laboratory studies reveal a hemolytic anemia (low hemoglobin/hematocrit and a significantly elevated reticulocyte count) and hyperbilirubinemia due to the increased breakdown of red blood cell products.

A 6-year-old boy is brought to the emergency room with chest pain and signs of respiratory distress. His mother states he has been ill with an upper respiratory infection that suddenly worsened with temperature elevation. Physical examination reveals an increased P2 and systolic ejection murmur. Chest X-ray shows lobar infiltrates. Labs show a leukocyte count of 18,000/mm3, hemoglobin 7 g/dL, and reticulocytes 12%. Question Highlights What is the most likely cause of chest pain and respiratory distress? 1 Splenic sequestration 2 Myocardial infarction 3 Mycoplasma pneumonia 4 Sickle cell disease 5 Pneumocystis carinii infection

Correct Answer: Sickle cell disease Vaso-occlusive and aplastic crises and reticulocytosis (>5%) should always raise the suspicion of sickle cell disease. Chest pain and respiratory distress represent a typical vaso-occlusive complication of sickle cell disease. Sickle cell disease is caused by a molecular defect (substitution of valine for glutamic acid in the β-globin chain), causing production of Hgb S that distorts red cells into a sickle shape and shortens their lifespan. Overwhelming infection, particularly by encapsulated bacteria such as pneumococcus and Haemophilus influenzae, is a life-threatening problem. Streptococcus pneumoniae and Haemophilus influenzae type B tend to cause lobar chest X-ray pattern. Such infections can trigger painful and aplastic crises. Differentiation of vaso-occlusion (pulmonary infarct) and infection (pneumonia) does not alter treatment.

A 12-month-old African American boy presents with a 2-day history of irritability and refusal to bear weight. His mother denies any recent history of fever, vomiting, diarrhea, rash, or trauma. Family history is significant for a maternal uncle who had a stroke and died when he was 35. On exam, vital signs are stable. Patient is a well-developed well-nourished toddler who appears irritable but consolable. He is in no apparent distress, but he refuses to bear weight or play. The only significant findings on his exam are swollen hands and feet. CBC reveals WBC 18,000 mm3, with 40% neutrophils, 30% lymphocytes, and 1% monocytes. Hb is 8 g/dL and platelets are 400,000 mm3. Question What test would be helpful in making a diagnosis? 1 Urine analysis 2 Echocardiogram 3 CXR (AP/lateral) 4 Sickle cell solubility test 5 Blood culture

Correct Answer: Sickle cell solubility test The first manifestation of a pain crisis in an older infant or young toddler with sickle cell anemia is often hand-foot swelling (dactylitis). Pain crisis, which involves the small bones in the hands and feet, typically lasts for 2-7 days and is typically treated like other forms of sickle cell-associated pain crisis with hydration and analgesia. Screening for sickle cell disease, using the rapid and cost-efficient sickle cell solubility test (Sickledex), can quickly establish the diagnosis. Features of this patient's clinical presentation that support the diagnosis of sickle cell disease include ethnicity, chronic daily medication use (which is most likely oral penicillin prophylaxis to prevent bacteremia), family history of stroke with early demise, and blood count abnormalities. Other causes of swollen hands and feet can include nephrotic syndrome, urticaria, hereditary angioedema, vasogenic edema, cytotoxic edema, cardiac disease, bacteremia/sepsis, trauma, and deep venous thrombosis.

A 38-year-old woman gave birth to a healthy female neonate 3 months ago. Her pregnancy and vaginal delivery were unremarkable. Over the past 3 months, she developed increased oral bleeding with hemorrhagic bullae. Question Highlights Based on the most likely diagnosis, the presence of which of the following makes immune thrombocytopenic purpura less likely? 1 Splenomegaly 2 Petechiae 3 Megakaryocytosis 4 Increased bruising 5 Epistaxis

Correct Answer: Splenomegaly Immune thrombocytopenic purpura (ITP) does not typically cause an enlarged spleen despite the destruction of platelets in the spleen. If an enlarged spleen is identified, it should alert the clinician to consider other possible causes for the patient's thrombocytopenia. Typically, ITP is a diagnosis of exclusion once other hematologic abnormalities for thrombocytopenia are ruled out. In the majority of cases, it is found to be an autoimmune disorder with the creation of anti-platelet antibodies.

A 1-year-old boy appears to be physically underdeveloped. His vital signs are not remarkable. His parents are concerned about his health because he seems to be weak and lethargic. The parents are recent immigrants from southern Italy. A brief history check reveals that both parents have a history of mild anemia. The child is afebrile. A complete blood count (CBC) is ordered: red blood cell (RBC) count of 3.0x 1012/L; Hb of 8.0 gm/dL; Hct of 24%; peripheral smear showed 1+ basophilic stippling; hypochromia; and the presence of codocytes. Question What is the most likely diagnosis? 1 Thalassemia 2 Sickle cell anemia 3 Aplastic anemia 4 Megaloblastic anemia 5 Paroxysmal nocturnal hemoglobinuria

Correct Answer: Thalassemia Thalassemia is a hypochromic and microcytic anemia. It is an inherited disorder of hemoglobin synthesis characterized by a diminished synthesis of the beta chains and compensatory synthesis of alpha chains. The peripheral smear shows presence of codocytes and basophilic stippling of the RBCs. Beta-thalassemia is confirmed by hemoglobin electrophoresis. The genotype will determine the severity of the disease.

A 6-year-old girl is seen by her pediatrician because she has had frequent and prolonged bilateral nosebleeds. Her parents are concerned because there is a family history of a bleeding disorder that has an autosomal dominant pattern. Her father, paternal grandmother, and a paternal aunt are all affected. Bleeding time, platelet count and clotting time are normal. Ristocetin cofactor activity is found to be decreased. Coagulation factor assays show slight decrease in factor VIII but normal factor IX levels. Question Highlights What is the most probable diagnosis for this family? 1 Hemophilia A 2 Hemophilia B 3 Von Willebrand disease 4 Factor XIII deficiency 5 Primary thrombocythemia

Correct Answer: Von Willebrand disease Von Willebrand disease is inherited in an autosomal dominant manner, and males and females are equally affected. Typically, bleeding times are normal, ristocetin cofactor activity is decreased or normal, and factor VIII is low. All of these disorders are bleeding disorders, each caused by deficiencies of different clotting factors. Hemophilia A occurs when factor VIII is deficient, hemophilia B when factor IX is deficient, and von Willebrand disease when the von Willebrand factor is deficient or abnormal. All are clinically similar, and are characterized by prolonged or renewed bleeding after injuries, tooth extractions, or surgery. They should be suspected in individuals with deep muscle hematomas, intracranial bleeding in the absence of major trauma, unexplained GI bleeding or hematuria, recurrent and bilateral prolonged nosebleeds, and excessive bruising. In severe cases, joint bleeding is a frequent symptom. Age of diagnosis and severity of symptoms is dependent upon the level of normal functioning clotting factor present. Coagulation factor assays are used for diagnosis.

A 35-year-old woman presents with fatigue and yellowish coloration of her eyes and skin that started several weeks after non-eventful implantation of a prosthetic mechanical heart valve 6 weeks ago. She has a past history of severe aortic stenosis. Other past medical history is non-contributory. Physical examination reveals the presence of regurgitant murmur and subicterus. Laboratory results are: hemoglobin 7.0 g/dL; reticulocytes 21%; white blood cells 11,500/µL; platelets 80,000/µL; and undetected levels of haptoglobin. Lactate dehydrogenase, direct and indirect bilirubin levels are all elevated (3,100 U/L, 2.1 and 1.2 mg/dL, respectively). Peripheral blood smear shows burr and helmet cells (schistocytes) and polychromasia. Both direct and indirect Coombs tests are negative. You suspect microangiopathic hemolytic anemia. Question What is the next step in management? Answer Choices 1 Hemoglobin electrophoresis 2 Glucose-6-phosphate dehydrogenase deficiency 3 Echocardiography 4 Hepatitis B panel 5 Direct agglutination test

Echocardiography Anemia, reticulocytosis, and jaundice are the characteristics of hemolytic anemias. Red blood cell (RBC) survival is shortened and bone marrow increases erythroid production, resulting in increased reticulocytes. Elevated unconjugated bilirubin and lactate dehydrogenase levels and decreased (undetectable) haptoglobin is evidence of RBC breakdown. Microangiopathic hemolytic anemia occurs when the red cell membrane is damaged in circulation, leading to intravascular hemolysis and the appearance of schistocytes (fragmented erythrocytes). Hemolytic anemia due to mechanical damage is seen with prosthetic mechanical heart valves. The most important next step in the management of this patient will be to find out if there is a dysfunction of the prosthetic valve. Echocardiography will reveal the presence of significant leaking or valve dysfunction.

A 45-year-old man is evaluated for a 6-month history of palpitations, easy fatigability, and chest pain on exertion. He does not smoke or consume alcohol; he has no significant past medical history. His body weight has remained stable. He has spent the last 2 years traveling the world. His wife says that he eats "unhealthily." He is a strict vegan, consumes a lot of snacks, and has never taken any vitamin supplements. Examination shows a 5'7" male with a BMI of 19. His BP is 130/70 and pulse 90/min; his temperature is 98.4°F. Conjunctival pallor is present. Auscultation shows a grade 2/6 murmur ejection systolic murmur heard all over the precordium. Lab investigations are sent and are given below: Hb: 8.8 g/dL WBC: 6000/mm3 MCV: 72 Ferritin: low TIBC: elevated Stool occult blood: negative ESR: 8 mm/hour TSH: normal Question What is the most appropriate medical therapy? Oral Folate with B12 Intramuscular iron dextran Oral ferrous sulfate Packed red cell transfusion Erythropoietin injection

Oral Ferrous Sulfate The patient has iron deficiency anemia confirmed by the low MCV, low ferritin, and high TIBC. Stool occult blood being negative rules out GI blood loss as a cause, and normal ESR rules out chronic inflammatory conditions. The initial treatment of choice for iron deficiency anemia is an oral iron compound, commonly ferrous sulfate. Treatment is usually titrated to provide around 150-200 mg of elemental iron per day and is continued for 3-6 months after normalization of hemoglobin in order to replenish stores.

An 18-year-old woman presents with chronic fatigue and menorrhagia. Menorrhagia has been present since her first menstrual cycle, but it has recently become worse; she sometimes uses 20 tampons per day. About a year ago, she started using contraceptive pills but is now considering stopping using them because of migraine-like headaches. Her headaches are sometimes so severe that she has to take aspirin or other painkillers several times a day. The rest of her past medical history is unremarkable. Physical examination reveals pale skin and mucosa, pulse rate of 100 beats per minute, and a systolic ejection murmur 1/3 intensity over the precordium. Laboratory findings include white blood count 9 K, hemoglobin 10, platelet count 250 K, normal prothrombin time, slightly prolonged partial thromboplastin time, and normal fibrinogen. Her bleeding time is prolonged. Blood smear shows microcytic hypochromic anemia. Question Highlights What is the most likely diagnosis? Endometriosis 2 Ventricular septal defect 3 Von Willebrand disease 4 Hemolytic uremic syndrome 5 Hemophilia A

Von Willebrand Disease The cause of her fatigue is most probably anemia due to the blood loss. Having platelet-type of bleeding with normal PT and fibrinogen and prolonged PTT and bleeding time, she most likely has von Willebrand disease. Von Willebrand disease is the most common hereditary coagulation abnormality in humans, although it can also be acquired. Von Willebrand factor, which is deficient in this disease, is critical to the initial stages of blood clotting. Aspirin and many of the drugs used for pain can aggravate bleeding because they interfere with platelet function, but patients with von Willebrand disease can take acetaminophen for pain relief, as it does not inhibit platelet function.