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During the winter months, a 65-year-old man presents with livedo reticularis and purple fingertips. Other symptoms include arthralgia and weakness. Renal impairment is present on laboratory testing. Which of the following is the most likely diagnosis?
The symptoms are typical of cryoglobulinemia. Cryoglobulins are antibodies that precipitate under cold conditions and are associated with several diseases. There are three main types of cryoglobulin syndromes based on the immunoglobulin composition of the precipitating antibody. Most cryoglobulinemic vasculitis is Type II or mixed and seen secondary to hepatitis C virus infection. Cold agglutinin disease would present with hemolytic anemia. The other syndromes would not generally be temperature sensitive.
A 34-year-old woman notices blue toes and a lacey rash on her knees when outside in the winter months. She has chronic hepatitis C virus infection. She has also noticed weakness, joint discomfort, and red spots on her legs. On examination, she has livedo reticularis-type skin on her thighs, and areas of palpable purpura on her toes. She has abnormal proteins detected in her serum. Which of the following is the most likely mechanism for the vessel
The syndrome is caused by cold-precipitable proteins (cryoglobulins) that are found in plasma or serum. These cryoproteins can be of three classes. Type 1 are single component (immunoglobulin G, M, or A [IgG, IgM, IgA]), Type 2 are called “mixed cryoglobulins” (usually IgG molecules complexed with IgM molecules having anti-IgG reactivity), and Type 3 are polyclonal immunoglobulins with antiimmunoglobulin activity. Cryoglobulinemia is small vessel vasculitis (not medium), and platelet aggregation is not an important mechanism for the vessel injury.
A 34-year-old man presents with symptoms of fatigue, weakness, nose bleeds, and palpitations with exertion. On examination he is pale, blood pressure 110/70 mm Hg, pulse 100/min, heart sounds are normal, lungs are clear, and he has multiple petechiae and bruises on his legs. His blood count is abnormal: hemoglobin 8.5 g/dL, white blood cells (WBCs) 4000/mL, platelets 50,000/mL, and there are blast cells in the peripheral blood. He is diagnosed with acute promyelocytic leukemia (AML-M3). Which of the following is a characteristic of this acute myelogenous leukemia?
Auer bodies are slender, pink, staining rods containing lysozyme, and are exclusively seen in AML. Although similar to normal azurophilic granules in content and staining properties, they are distinguished by their gigantic size. Special stains can enhance the detection of Auer bodies. They are only seen in a minority of cases. The Philadelphia chromosome is a feature of choric myelogenous leukemia (CML), and a high leukocyte alkaline phosphatase level is seen in patients with a high WBC due to a leukemoid reaction.
A 62-year-old man reports early satiety, fatigue, and generally feeling unwell. On examination he has a large spleen, appears pale, and the rest of the examination is normal. His blood count is abnormal; the WBC is 50,000/mL with increased mature granulocytes, hemoglobin 9.5 g/dL, and platelets 450,000/mL. Which of the following cytogenetic changes is most characteristic of his condition?
This is a case of chronic myelogenous leukemia. The reciprocal translocation involves the long arms of 22 and 9, and results in translocation of the ABL proto-oncogene from chromosome 9 adjacent to a portion of the BCR gene on chromosome 22. The resultant abnormal chromosome 22 is known as the Philadelphia (Ph1) chromosome.
An 18-year-old man is recently diagnosed with beta-thalassemia minor. His hemoglobin is 10.5g/dL, and he feels well. Which of the following findings is characteristic of this condition?
An increased amount of HbF or HbA2 would be expected. As beta-chains are decreased in beta-thalassemia, the excess alpha-chains combine with gamma- and delta-chains to make HbF and HbA2, respectively.
A patient with aplastic anemia receives a bone marrow transplant from a human lymphocyte antigen (HLA)-matched sister. Which of the following is the most likely complication of allogenic bone marrow transplantation?
Graft-versus-host disease is a frequent complication of hematopoietic cell transplantation. It is caused by a reaction of immunologically competent donor derived T cells that react with recipient tissue antigens. It can be acute or chronic. Numerous treatment regimens involving methotrexate, glucocorticoids, cyclosporine, and other drugs are used in treatment.
A 19-year-old man has had recurrent bleeding occur in his knee when playing contact sports. He has no history of spontaneous bleeding, but his brother had similar problems. Consultation with a specialist reveals that he has “mild” hemophilia A. Which of the following factor abnormalities is consistent with this diagnosis?
In hemophilia A, there are decreased levels of functioning factor VIII. This can be due to reduced amounts of normal VIII, the presence of a functionally abnormal protein, or a combination of both. The activated partial thromboplastin time (APTT) is prolonged, and the prothrombin consumption test is abnormal. The prothrombin time, thrombin clotting time, and bleeding time are usually normal.
A 63-year-old man presents with headaches, itching, and feeling unwell. He appears plethoric, and the remaining examination is normal. On laboratory investigations, he is found to have elevated hemoglobin of 20.5 g/dL, normal WBC, and normal platelet count. There is no palpable spleen or lymph nodes.
Hypernephroma, cerebellar hemangiomas, hepatoma, and giant uterine myomas are the tumors associated with secondary polycythemia. Endocrine disorders, hypoxia, and high-affinity hemoglobins can also cause secondary polycythemia.
A 19-year-old college student develops a severe sore throat, cervical lymphadenopathy, and atypical lymphocytes on blood film. A heterophil antibody test is positive.
Heterophil antibodies react against sheep red cells and are not absorbed out by the guinea pig kidney. They are positive in patients with infectious mononucleosis. In 90% of cases, liver enzymes are elevated. Examination of the blood film reveals a lymphocytosis with atypical lymphocytes.
A 7-year-old boy has severe microcytic anemia due to beta-thalassemia major (homozygous). He requires frequent blood transfusions (once every 6 weeks) to prevent the skeletal and developmental complications of thalassemia. Which of the following medications is also indicated in the treatment of patients requiring frequent blood transfusions?
Iron chelation with desferrioxamine will reduce the toxicity from iron overload if given regularly in high doses. The most lethal toxicity of iron load is iron infiltration of the myocardium, with resultant dysfunction and death.
A 45-year-old woman develops symptoms of shortness of breath on exertion, easy fatigue, and jaundice. On examination she is pale, and there is a palpable spleen, but no lymphadenopathy. Her hemoglobin is 9.0 g/dL, the reticulocyte count 9%, and the direct antibody test (Coombs’) is positive. Which of the following bone marrow findings is most likely to be seen in this patient?
Bone marrow examination is most likely to show increased erythroid-to-myeloid ratio. Erythroid hyperplasia is common to all hemolytic anemias, and megaloblastic features may develop unless folate is supplied.
A 23-year-old woman of Italian extraction is found to have a hypochromic microcytic anemia of 10 g/dL. In addition, there is a fair degree of anisocytosis, poikilocytosis, and targeting on the blood film. The WBC is 9500/mL, the platelet count is 240,000/mL, and the reticulocyte count is 7%. The spleen is palpated 5 cm below the left costal margin. Which of the following is the most appropriate treatment for her condition?
The present treatment of choice for thalassemia minor is purely supportive. Care is taken to watch for anemia during intercurrent illness, due to a regenerative crisis.
A 67-year-old man is complaining of fatigue. A routine complete blood count (CBC) reveals a platelet count of 850,000/mL, and the hemoglobin and WBC counts are normal. He reports no other symptoms, and his clinical examination is normal. Which of the following characteristics is most likely to be helpful in differentiating essential (primary) from reactive (secondary) thrombocytosis?
Reactive thrombocytosis is usually transitory, without thromboembolism, hemorrhage, splenomegaly, or leukocytosis. Causes of secondary thrombocytosis include chronic inflammatory disorders (e.g., rheumatoid arthritis), acute inflammatory disease, acute or chronic blood loss, and malignancy. Recovery from thrombocytopenia (“rebound”) can also result in very high platelets. A common cause is withdrawal from alcohol.
A 19-year-old man is found to have a decreased eosinophil count. Which of the following is the most likely cause?
Steroids cause decreased numbers of eosinophils to circulate, so that eosinophilia may be seen in Addison’s disease, for example. Beta-blockers may cause eosinophilia by blocking beta-adrenergic eosinopenia. Atopic and nonatopic chronic asthma are frequently associated with mild eosinophilia. Numerous allergic diseases, allergic rhinitis, atopic dermatitis, and urticaria can also cause eosinophilia. Parasites are the most common worldwide cause of eosinophilia, but other infections rarely cause it.
A 68-year-old man with aplastic anemia is due for another blood transfusion. He has had multiple blood transfusions in the past, but with the last transfusion, he developed fever and chills after the transfusion was started. Repeat cross-matching and testing at the time ruled out an acute hemolytic transfusion reaction. The next transfusion is ordered through a “filter” to prevent or minimize the febrile reaction. Which of the following mechanisms is most likely to explain the effect of the filter?
Febrile reactions to leukocytes may be severe and cause hypotension, especially in repeatedly transfused patients. Antibodies to platelets can also develop. Usually, at least seven transfusions are required to induce sensitization.
A 19-year-old man is found to have low hemoglobin on routine screening. He feels well at the present time, but in the past he has had two presentations to the hospital for severe abdominal and back pain that resolved on its own with no specific diagnosis. His blood film is shown in Fig. ; the hemoglobin is 10 mg/dL, mean corpuscular volume (MCV) 80 fL, and reticulocyte count 0.04 (4%). Which of the following is the most likely explanation for his previous episodes of abdominal pain?
The painful crisis seen in patients with sickle cell disease is due to vaso-occlusive disease where microvascular ischemic injury occurs to tissues. Acute illness, dehydration, and infections are common precipitants for this type of crisis. Because sickle cell anemia is a chronic hemolytic anemia, the reticulocyte is chronically elevated, except in aplastic crises, and erythrocyte life span is shortened. Infection is the most common precipitant of an aplastic crisis, particularly those caused by parvovirus B19. Sequestration crisis (hemoglobin level <6 mg/dL) is sudden massive pooling of red cells in the spleen resulting in hemodynamic instability. Hemolytic crisis is the sudden further reduction in red cell life span marked by falling hemoglobin, jaundice, and increased reticulocyte count.
A 23-year-old woman has symptoms of fatigue and not feeling well. She appears well and the physical examination is normal, but her hemoglobin is low at 9.8 g/dL with a mean corpuscular volume (MVC) of 76 fL. Her family history is positive for thalassemia. She also mentions a history of heavy menses in the past year. Which of the following would be most helpful in distinguishing thalassemia from one of pure iron deficiency anemia?
A serum ferritin determination would be most helpful. Iron stores in thalassemia are normal or increased. Some of the increase may be secondary to injudicious iron therapy
A 21-year-old woman is suspected of having mycoplasma pneumonia based on symptoms of a dry cough, fever, normal lung examination but abnormal chest x-ray with bilateral infiltrates. She is also anemic with hemoglobin of 10.5 g/dL, reticulocyte count 7%, and WBC 12,000/mL. Hemolytic anemia from cold agglutinins is suspected as the cause. Which of the following tests will confirm autoimmune causation as the cause of the anemia?
The diagnosis of autoimmune hemolytic anemia requires demonstration of immunoglobulin and/or complement in the patient’s RBC. The broad-spectrum Coombs’ test is an excellent screen.
A 59-year-old man presents to the emergency room with left face and arm weakness that lasts for 3 hours. He reports no other symptoms of palpitations, chest pain, or headache. Neurologic examination is now normal. A computerized tomography (CT) head, electrocardiogram (ECG), and laboratory workup are normal. He is started on clopidogrel, and referred for further evaluation as an outpatient. Which of the following is the most likely mechanism of action on platelet function from this medication?
Clopidogrel selectively inhibits platelet activation induced by ADP. It works as an ADP-receptor blocker. Other antiplatelet drugs such as ASA are COX-1 inhibitors, and dipyridamole modulates cAMP levels.
A 23-year-old woman has symptoms of leg swelling and discomfort, but no chest pain or shortness of breath. She has no risk factors for a blood clot. On examination, the left leg is swollen when compared to the right. Leg Doppler ultrasound is positive for deep vein thrombosis, and further investigations reveal decreased plasma antithrombin III (AT-III) levels. Which of the following is the most likely clinical effect from the low AT-III levels?
Heparin appears to act as catalyst in the inactivation of thrombin and factors XA, IXA, XIA, and by antithrombin III. However, not all patients with thrombosis and heparin resistance have antithrombin III deficiency.
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