Chapter 6: Hematology and Oncology

A 6-month-old boy presents to your office after his mother notices swelling and ecchymosis over his anterior right thigh. She does not recall any trauma to the area. The mother denies any history of bleeding problems, including during his circumcision. On physical examination the child has a large hematoma over his thigh. There are no obvious bony deformities and the child otherwise looks well. You suspect the child may have an inherited coagulation disorder.

Question 6.1.1 Which of the following statements is NOT correct?

A) Child abuse should be included in the differential diagnosis.

B) The child did not bleed during circumcision, so the possibility of hemophilia need not be considered.

C) A careful family history is important in the work-up.

D) Coagulation studies (PT, PTT) and CBC should be obtained.

Answer 6.1.1 The correct answer is "B." The absence of bleeding during circumcision in no way rules out hemophilia. Up to half of hemophiliac patients do not bleed after circumcision. Depending on the severity of factor deficiency, the diagnosis may not be made until the child is very active or even in adulthood, after surgery, etc.

Question 6.1.2 Which of the following is NOT TRUE about hemophilia A?

A) It is an X-linked disorder.

B) It is the result of factor VIII deficiency.

C) It generally leads to mucosal bleeding.

D) It occurs most often in males.

E) It can be treated with factor VIIa

Answer 6.1.2 The correct (and wrong) answer is "C." Hemophilia A is an X-linked deficiency of factor VIII, which presents with hematomas, bleeding, and hemarthrosis (and not generally mucosal bleeding or petechiae). Deficiency of factor IX, or hemophilia B, also known as "Christmas Disease," is also X-linked but is much less common. "D" deserves special mention. Hemophilia rarely occurs in females but can occur in two situations: (1) the female patient is a heterozygote who has early inactivation of the second X chromosome during embryogenesis or (2) if both parents are carriers—in which case the father would have the disease overtly. "E" is true. Factor VIIa can be used in most cases of hemophilia A and B to stop bleeding. It is mostly used in patients who have factor inhibitors in the blood (developed as a response to repeated exposure to factor VIII or factor IX [Christmas disease]).

Question 6.1.3 Which of the following is indicated when evaluating for a suspected inherited coagulopathy?

A) Prothrombin time (PT).

B) Partial thromboplastin time (PTT).

C) Platelet count.

D) PFA-100.

E) All of the above.

Answer 6.1.3 The correct answer is "E." The PTT is actually the most sensitive test for hemophilia. "D" deserves special mention. The PFA-100 (Platelet Function Analyzer) tests for (appropriately enough) platelet functioning and will be abnormal in diseases of platelet dysfunction, such as VWD.

You diagnose this patient with hemophilia A, and he grows up under your excellent tutelage. As a junior high school student, he attends summer camp for hemophiliacs in Transylvania. For some bizarre reason, the councilors decide to have the kids play tackle football (just in case you think we made this up, this scenario was seen by one of your authors while working in the emergency department (ED)—but not at the University of Iowa). The patient presents to the ED with bleeding into two of his joints.

Question 6.1.4 What is the initial step in the management of this patient's hemarthroses?

A) Joint aspiration.

B) Desmopressin.

C) Factor VIII infusion.

D) Heparin infusion.

E) Leeches.

Answer 6.1.4 The correct answer is "C." While joint aspiration and desmopressin may be helpful, this patient needs to be treated with factor VIII in order to stop the bleeding. Joint aspiration may play a role in preventing blood-induced arthritis, a risk with recurrent joint bleeds. Desmopressin is useful in some cases of VWD and in some mild cases of hemophilia. Desmopressin releases vWF from platelets transiently increasing circulating vWF. Antifibrinolytic therapy may also be of use: tranexamic acid or aminocaproic acid is commonly used to prevent clot breakdown.

Question 6.1.5 What factor level target is appropriate when treating this patient?

A) 5% to 10%

B) 30% to 40%.

C) 75% to 80%.

D) 100%.

Answer 6.1.5 The correct answer is "B." For a hemarthrosis or other "minor" bleeding, you should maintain a factor level of 30% to 40% for 72 hours. For more serious bleeding (intracranial, for example), maintain a level of 80% to 100% for 10 days.

Question 6.1.6 In 2015 (as opposed to 1992) which of the following likely scenarios may be seen in a patient with hemophilia?

A) Hemarthrosis with significant arthritis and joint dysfunction.

B) An extremely low risk of HIV/AIDS from multiple transfusions of FFP.

C) Maturational delay if antifactor antibodies are present.

D) Reduced risk of coronary artery disease (CAD).

E) All of the above are found with hemophilia.

Answer 6.1.6 The correct answer is "E." "A" is true. Patients still get recurrent hemarthrosis leading to arthritis and joint dysfunction. "B" is true. Screening and the use of recombinant factor VIII has led to a marked reduction in HIV in hemophiliacs from a high of 50% in the 1990s. Patients with hemophilia do have delayed maturation, especially if antifactor antibodies are present. And finally, they do have a reduced risk of CAD. This is also seen in carriers of hemophilia genes.

Note: In this chapter, objectives are listed after several short cases, so keep reading.

A 4-year-old girl is brought to you after she is noted to have small pink spots on her lower extremities and bleeding from her gums. She had a URI a couple of weeks ago. She also recently got her second dose of her MMR vaccine (mom particularly wants to make sure she is protected from the recent resurgence in measles and mumps). You note petechiae on her lower extremities and purpura in her oropharynx. The mother and patient deny any other bleeding. You obtain a CBC, which is normal except for a platelet count of 15,000/mm³. You suspect immune thrombocytopenic purpura (ITP, also known as idiopathic thrombocytopenic purpura).

Question 6.2.1 Which of the following may have led to this patient's ITP?

A) MMR vaccine.

B) Infection.

C) Food allergy.

D) Autoimmune hemolytic anemia.

E) A and B.

Answer 6.2.1 The correct answer is "E." Both infections and the MMR vaccine have been linked to ITP (not autism … got that? … not autism). Food allergy does not cause ITP and if you chose "D," time to study some more. An autoimmune hemolytic anemia is just that; an autoimmune hemolytic anemia. It is a different disease process entirely and typically presents with signs and symptoms of an anemia (pallor, fatigue, dyspnea, failure to thrive). Peripheral smear with a hemolytic process will typically show schistocytes, "bite cells" or even spherocytes; it depends on the etiology of the hemolysis (more later) This patient's CBC was normal aside from a low platelet count so answer "D" is not correct.

Question 6.2.2 Which of the following is NOT likely to lead to a sustained (let's say at least 2 days) increase in the patient's platelet count?

A) IVIG.

B) Steroids (e.g., prednisone).

C) Platelet transfusion.

D) Splenectomy.

Answer 6.2.2 The correct answer (and what will not yield a sustained increase in platelet count) is "C." Transfused platelets will just be chomped up by "Mr. Spleen." However, platelets can be used to temporize if a patient must go to the OR, etc. Most children can simply be observed. The only indication for treatment is bleeding. All of the treatments have a downside. Splenectomy is associated with a risk of sepsis. If possible, delay splenectomy until after the child is over 5 years old. Steroids may cause behavioral problems and long-term problems such as avascular necrosis. IVIG leads to a temporary increase in platelets that may last several weeks but can be associated with renal injury and anaphylaxis among other possible adverse effects.

Keep reading for the objectives … We swear there is a common theme and that we didn't forget them!

A 24-year-old female G1 P0 at 39 weeks of gestation presents to your office with a bruise on her anterior tibia, which she noticed after bumping into a coffee table. She has been healthy before and during her pregnancy and takes only prenatal vitamins. Her physical examination is unremarkable with the exception of an 8-cm bruise over her right anterior tibia. Her vital signs are normal. Her physical examination is remarkable for a gravid abdomen consistent with 39 weeks of gestation, fetal heart tones auscultated at 140 bpm, absence of right upper quadrant pain, and absence of peripheral edema. You obtain the following laboratory tests: CBC, which demonstrates white blood cell (WBC) 9,000/mm³, hemoglobin (Hgb) 11.8 g/dL, and platelet count 95,000/mm³; normal PTT and PT/INR; negative urinalysis; and normal liver enzymes.

Question 6.3.1 What is your next step?

A) Recommend immediate delivery by cesarean section as the infant likely has thrombocytopenia as well and is at high risk for intracranial hemorrhage.

B) Recommend immediate delivery by cesarean section as this disorder will likely progress to eclampsia.

C) Recommend close observation and reassure the patient that this is typically a self-limited condition.

D) Start prednisone, 1 mg/kg daily, and taper slowly over the next 6 weeks.

E) Recommend splenectomy as soon as possible after delivery.

Answer 6.3.1 The correct answer is "C." This patient likely has gestational thrombocytopenia, a condition that occurs in up to 5% of pregnant women. It is characterized by mild thrombocytopenia occurring in late gestation; the platelet count is usually >70,000/mm³ (two-thirds are between 130,000/mm³ and 150,000/mm³). The condition resolves after delivery and is not associated with severe neonatal thrombocytopenia. No specific change in routine obstetrical care is warranted, although the anesthesiologist placing an epidural may want a follow-up platelet count closer to the time of delivery.

Objectives (see, we told you we didn't forget them!): Did you learn to…

• Obtain a thorough bleeding history?

• Use laboratory testing to assist in the diagnosis of a bleeding disorder?

• Identify and treat common inherited bleeding disorders?

• Identify and treat common acquired bleeding disorders?

Which of the following conditions should be considered if both the PT and PTT are prolonged in a patient noted to be oozing from a surgical incision?

A) Severe liver disease, DIC, factor X deficiency.

B) Heparin effect, VWD, factor XII deficiency.

C) Warfarin effect, factor VII deficiency, vitamin K deficiency.

D) All of the above.

The correct answer is "A." The three factor deficiencies that may prolong both PT and PTT are II, V, and X. Both PTT and PT may be prolonged due to severe liver disease and DIC as well. Mild vitamin K deficiency or mild liver disease generally affects the PT only. Generally, heparin affects PTT, and warfarin affects PT. Remember that the newer agents (rivaroxaban, dabigatran, etc.) cause bleeding without prolonging the PT or PTT.

A 42-year-old gentleman presents to the ED with a gastrointestinal (GI) bleeding due to ibuprofen use. His Hgb is 6.8 g/dL and he is hemodynamically unstable at this point. You remember that blood actually increases mortality if used incorrectly.

Question 6.4.1 Which of the following is an indication for transfusion?

A) Hemodynamic instability in a trauma patient due to bleeding unresponsive to no less than 5 L of saline.

B) Preoperative Hgb of 7 to 8 g/dL with expected intraoperative blood loss.

C) Hemoglobin of 9.5 g/dL in a patient with angina.

D) A stable ICU patient with an Hgb of 8.7g/dL.

E) All of the above.

Answer 6.4.1 The correct answer is "B." In general, a restrictive policy for blood transfusion has been shown to improve outcomes. "A" is incorrect because blood should be given to the hemodynamically unstable trauma patient after at most 2 L of saline (and per new ATLS recommendations after 1 L of saline). "B" is correct. A restrictive preoperative transfusion policy limited transfusions to those with an Hb of <8 g/dL has shown survival benefit. "C" is incorrect. Transfusion should be considered in the patient with CAD only when the hemoglobin reaches 7 to 8 g/dL. Finally, "D" is incorrect. Transfusions should be withheld from a nonbleeding, hemodynamically stable ICU patient until the Hb reaches 7 g/dL. A more liberal transfusion policy is associated with higher mortality. As an aside, some would transfuse postoperative patients with an Hgb of less than 10 g/dL if they are at high risk for ischemic disease (ischemic bowel, CAD, etc.). Transfusion for indications other than these are not beneficial and have been proven harmful. See Table 6-1 for a list of transfusion indications.

You decide to transfuse one unit of packed red blood cells (PRBCs). After 30 minutes, the patient complains of dyspnea and back pain. Repeat examination of this patient reveals a diaphoretic man with a pulse of 130 and BP of 88/50. His lung fields are clear (initial vitals before the transfusion were a pulse of 110 and BP of 94/52.

Question 6.4.2 What is your next step?

A) Stop the blood transfusion and begin normal saline through the IV.

B) Increase the rate of transfusion.

C) Administer acetaminophen 650 mg PO.

D) Administer furosemide 40 mg IV.

E) Place a nasogastric tube for lavage.

Answer 6.4.2 The correct answer is "A." The transfusion must be stopped. The patient is exhibiting signs and symptoms of a hemolytic transfusion reaction, which is generally the result of an ABO incompatibility. Patients may exhibit nausea, flushing, dyspnea, oliguria, back pain, and hypotension. Other findings include markers of hemolysis: hemoglobinuria, elevated serum-free Hgb, reduced haptoglobin, and elevated bilirubin. Patients are positive for direct antiglobulin (Coombs) test. Therapy includes IV saline at a high enough rate to initiate a brisk diuresis and prevent Hgb from precipitating in the kidneys causing acute tubular necrosis.

A 56-year-old male presents to the ED with an acute abdomen, likely from a perforated diverticulum. He is taking warfarin for a DVT that occurred after a total knee arthroplasty. He weighs 65 kg. You are evaluating him for surgery and find the following laboratory results: Hgb 14.3 g/dL, platelet count 478,000/mm³, INR 3.5, and PTT 28 seconds.

Question 6.5.1 Which of the following statements about his preoperative management is correct?

A) Platelet transfusion perioperatively will produce the most immediate reduction in risk of bleeding from warfarin.

B) Fresh frozen plasma (FFP) transfusion will produce the most immediate reduction in risk of bleeding from warfarin.

C) Vitamin K administration orally will produce the most immediate reduction in risk of bleeding from warfarin.

D) Vitamin K administration subcutaneously will produce the most immediate reduction in risk of bleeding from warfarin.

E) Cryoprecipitate transfusion will produce the most immediate reduction in risk of bleeding from warfarin.

Answer 6.5.1 The correct answer is "B." The patient above would benefit most immediately from the administration of FFP. FFP contains all the soluble plasma proteins found in whole blood, including the vitamin K-dependent factors that are depleted by warfarin. If more sustained reversal is desired, the simultaneous administration of vitamin K is effective. The preferred route of administration of vitamin K is oral. Giving vitamin K IV is second best—lowers INR the same degree as oral vitamin K at 24 hours, but the IV route may be preferred in instances where GI absorption is questionable. Avoid vitamin K SQ or IM, which are less effective than PO and IV routes. The effects of FFP rarely last 24 hours; the effects of vitamin K are usually not apparent for 12 to 24 hours. The use of cryoprecipitate will not provide the appropriate factors depleted by warfarin. Cryoprecipitate contains vWF, factor VIII, factor XIII, and fibrinogen. Platelet transfusion would not benefit this patient since warfarin does not affect platelet function.

Objectives: Did you learn to…

• Decide when blood transfusion is appropriate?

• Recognize hemolytic transfusion reactions?

• Treat warfarin-induced hypocoagulability?

A 20-year-old female with acute myeloid leukemia completed her second cycle of consolidation chemotherapy 5 days ago. She presents to the ED complaining of fatigue and fever. She denies cough, dysuria, abdominal pain, sinus drainage, or redness around her Hickman catheter. Her physical examination reveals a temperature of 38.4°C, pulse 100 bpm, BP 120/58 mm Hg, and respirations 14 breaths per minute. Her examination is otherwise unremarkable, including no redness or tenderness at the Hickman site. Your magic crystal ball tells you she does not have a line infection. Her laboratory results reveal the following: WBC 200/mm³, Hgb 9 g/dL, hematocrit 27%, and platelet count 47,000/mm³. Blood cultures have been drawn.

Question 6.6.1 What is your next step, and what is your rationale?

A) Administer IV amphotericin B; a Candida urinary tract infection is most likely.

B) Administer IV cefepime; she requires empiric coverage for both Gram-negative and Gram-positive organisms.

C) Administer IV nafcillin; a Gram-positive bacterial infection is most likely and broader antibiotic coverage will encourage growth of resistant bacteria.

D) Administer IV vancomycin; she most likely has an MRSA sinus infection.

E) Close observation; there is no focus of infection and she looks well.

Answer 6.6.1 The correct answer is "B." This patient has a neutropenic fever, which is a medical emergency. Prompt treatment with broad-spectrum antibiotics has drastically improved the survival of patients with neutropenic fever. Neutropenia is usually defined as neutrophils plus bands (absolute neutrophil count, ANC) <500/mm³ or <1,000/mm³ when the nadir has not been reached. Most myelosuppressive chemotherapeutic agents produce a reduction in WBCs 4 to 10 days after completion and nadir at 10 to 14 days. Fever is defined as a single oral temperature >101°F (38.3°C) or a temperature >100.4^°F (38°C) persisting for 1 hour or more. This patient does not need vancomycin since the absence of a line infection was stipulated in the history (via crystal ball that always works in our experience). Broad-spectrum coverage of Gram-positive and Gram-negative organisms, including Pseudomonas, is the cornerstone of therapy with specific therapy for any localizing symptoms or risk signs. See Table 6-2 for common antibiotic regimens.

A 63-year-old male with a diagnosis of non–small-cell lung cancer, undergoing weekly chemotherapy and radiation to a left upper lobe mass, presents to your office. He complains of dull, nonradiating back pain in the lower thoracic/upper lumbar area. He denies trauma or any new activities. He has no associated weakness or paresthesias. He denies difficulties with bowel or bladder function.

Question 6.7.1 What is your initial diagnostic and/or therapeutic approach to this patient?

A) MRI of thoracic and lumbar spine.

B) Plain films of the thoracic and lumbar spine and a COX-2 inhibitor with a 2-week follow-up.

C) Plain films of the thoracic spine and NSAIDs.

D) Prescription for physical therapy and NSAIDs.

E) Urinalysis with culture and antibiotics.

Answer 6.7.1 The correct answer is "A." This is not your average back pain. Any patient with active malignancy complaining of back pain should be investigated for metastasis. While a plain film of the spine may be useful, the gold standard is MRI. The real emergency is spinal cord impingement. Spinal cord compression may occur from direct extension of metastatic disease from the vertebrae or extension from retroperitoneal or paravertebral disease. Frequently, the pain predates neurological symptoms, and because of the potential for severe, adverse outcomes, you want to catch the disease early to prevent chronic impairment.

The patient undergoes MRI of the spine, which demonstrates a lesion compressing the cord at L1.

Question 6.7.2 Which of the following is NOT an appropriate therapeutic modality?

A) Decompression surgery.

B) Dexamethasone 10 mg bolus IV, followed by 6 mg every 6 hours.

C) Observation with pain control (e.g., with morphine PCA).

D) Radiation therapy to the affected area.

Answer 6.7.2 The correct answer is "C." Patients with spinal cord compression who have aggressive interventions are more likely to retain function, including ambulation and bowel and bladder control. Steroids will help reduce edema surrounding the tumor and hopefully will relieve pressure on the cord. Radiation can often provide symptomatic relief and reduce the likelihood that the tumor will spread locally to impinge on the cord. Surgical decompression is another option. Of course, if this patient opted for a palliative care approach and had decided upon hospice, "C" might be appropriate, but he is still getting active therapy, and his remaining time could be spent with less pain and better function if one of the other options were chosen.

A 32-year-old woman presents to your office with complaints of dyspnea, constipation, menorrhagia, and fatigue that are new over the last few weeks. She has a distant history of Hodgkin lymphoma treated with chemotherapy and radiation to the chest. Her physical examination reveals a well-developed woman, who appears comfortable at rest with normal vital signs. She has no adenopathy and the remainder of her examination is unremarkable. Her CBC with WBC differential is normal.

Question 6.8.1 Which of these diagnoses can be absolutely ruled out based on this patient's history?

A) Coronary ischemia.

B) Hypothyroidism.

C) Lung cancer.

D) Relapse of the Hodgkin lymphoma.

E) None of the above.

Answer 6.8.1 The correct answer is "E." The point here is that patients with a history of Hodgkin lymphoma and chest radiation are at risk for a wide range of complications—even years after the disease has been successfully treated. Even though 80% of Hodgkin lymphoma patients have long-term disease-free survival, one in six patients can be expected to die from late effects of therapy. The key late effects of radiotherapy for Hodgkin lymphoma include secondary malignancy and accelerated cardiac disease at a younger age. Other delayed complications that have been associated with radiation therapy include thyroid dysfunction, pulmonary fibrosis, noncoronary atherosclerotic disease, and muscle atrophy.

Although coronary artery disease ("A") would be extremely unusual in a normal 32-year-old, a patient with a history of chest radiation has a relative risk of coronary disease of 5 to 10 times that of age-matched controls. "B," thyroid disease, is highly likely, with over 50% of patients treated with chest radiation requiring thyroid hormone replacement. A TSH would be adequate screening. There is a high risk for secondary malignancy, including breast cancer, lung cancer ("C"), leukemia, sarcoma, and non-Hodgkin lymphoma (NHL). Finally, you should always be concerned about recurrence ("D").

The patient has a normal chest radiograph and ECG. However, her TSH is markedly elevated, and you start her on levothyroxine. You plan to see her back in 8 weeks for re-evaluation and will provide additional counseling at that time.

Question 6.8.2 Which of the following preventive health issues is/are necessary to address at follow-up?

A) Early intervention by a fertility specialist if the patient desires pregnancy.

B) Smoking cessation.

C) Yearly mammograms.

D) All of the above.

E) None of the above.

Answer 6.8.2 The correct answer is "D." Female patients who were treated for Hodgkin lymphoma with chemotherapy and radiation prior to age 20 have up to a 35% incidence of breast cancer by the age of 40. The typical latency period is 15 years. National guidelines recommend that annual breast cancer screening of Hodgkin lymphoma survivors treated with chest irradiation should begin 5 to 8 years post-treatment, or age 40, whichever comes first. Breast cancer screening for these high-risk patients includes breast MRI in addition to mammography. Smokers with a history of Hodgkin lymphoma have a 20-fold increased chance of developing lung cancer when compared to nonsmokers with a history of Hodgkin lymphoma. Also, female patients with Hodgkin lymphoma have a 69% incidence of premature ovarian failure if treated for their cancer before the age of 29 and up to 96% if treated after the age of 30. While these statistics are improving with newer chemotherapy regimens, a patient should seek early referral to a fertility specialist if she desires pregnancy but is unable to conceive.

A 40-year-old male who has just received his first course of chemotherapy for non-Hodgkin lymphoma (NHL) presents to your ED complaining of weakness, cramps, and decreased urine output. He has no other medical problems and takes no medications except for prochlorperazine as needed for nausea. He has been eating and drinking well. His physical examination reveals a tired-appearing male, with normal vital signs. His head and neck examination reveals bilateral palpable cervical lymph nodes (2 cm). His lungs are clear in the upper lung fields with crackles bilaterally at the bases. Muscle strength is normal, and reflexes are 3+ and symmetric. He exhibits 6 beats of clonus at the ankles. Chest radiograph shows evidence of early pulmonary edema.

Question 6.9.1 What is the most likely set of laboratory values you will find for this patient (reference ranges: potassium 3.5 to 5 mg/dL, phosphate 2.4 to 4.1 mg/dL, uric acid 3.5 to 7.2 mg/dL, calcium 8.5 to 10.2 mg/dL).

A) Potassium 2.3 mEq/L, phosphorus 3.1 mg/dL, uric acid 4 mg/dL, calcium 9 mg/dL.

B) Potassium 2.6 mEq/L, phosphorus 6 mg/dL, uric acid 5 mg/dL, calcium 12 mg/dL.

C) Potassium 6.5 mEq/L, phosphorus 7 mg/dL, uric acid 18 mg/dL, calcium 6 mg/dL.

D) Potassium 6 mEq/L, phosphorus 6.8 mg/dL, uric acid 5 mg/dL, calcium 6.7 mg/dL.

E) Potassium 4.5 mEq/L, phosphorus 3.2 mg/dL, uric acid 9 mg/dL, calcium 8 mg/dL.

Answer 6.9.1 The correct answer is "C." This patient most likely has tumor lysis syndrome, which can occur in a patient with a highly responsive leukemia or a bulky lymphoma being treated with chemotherapy (it rarely occurs without treatment). Tumor lysis syndrome occurs when there is rapid release of intracellular contents into the bloodstream. It is characterized by high potassium, high phosphorus, high uric acid, and low calcium. Patients may experience renal failure, arrhythmias, fatigue, muscle cramps, and tetany.

The patient is found to have a creatinine of 8 mg/dL.

Question 6.9.2 What is the most likely cause of this patient's renal failure?

A) Dehydration.

B) Heart failure.

C) Hemoglobinuria.

D) Rhabdomyolysis related to chemotherapy.

E) Uric acid nephropathy.

Answer 6.9.2 The correct answer is "E." Patients with tumor lysis syndrome have renal failure secondary to uric acid nephropathy. This is caused by the precipitation of uric acid in the kidney, and it can be prevented by starting allopurinol prior to the administration of chemotherapy. Although dehydration ("A") is not the cause of renal failure, it certainly will exacerbate the situation.

Question 6.9.3 Which of the following is MOST LIKELY to help this patient's current condition?

A) Allopurinol 300 mg orally.

B) Calcium carbonate 500 mg orally.

C) Emergent hemodialysis.

D) IV D5W with 2 amps bicarbonate.

E) IV normal saline 200 mL/hr.

Answer 6.9.3 The correct answer is "C." The horses are already out of the barn, and in fact they're probably over the hills and through the woods. Allopurinol and oral calcium will not help this situation. The patient already has renal failure from his tumor lysis syndrome. While he may benefit from preventive measures, including aggressive hydration and allopurinol prior to undergoing chemotherapy, none of these measures are going to help his current renal failure. In addition, the patient may develop worsening pulmonary edema if given too much volume with IV fluids.

While awaiting hemodialysis, you should treat the patient's hyperkalemia. Treatment may include IV calcium gluconate, insulin and dextrose, and oral sodium polystyrene sulfonate (Kayexalate). Note that sodium bicarbonate for hyperkalemia has fallen out of favor. See Chapter 1 for more information on hyperkalemia.

Objectives: Did you learn to…

• Recognize and initiate treatment of some oncologic emergencies, including spinal cord compression, tumor lysis syndrome, and neutropenic fever?

• Recognize late complications of cancer and cancer therapy, including distant radiation and chemotherapy?

A 60-year-old gentleman presents to your office with complaints of fatigue. He has a history of alcoholic cirrhosis, diet-controlled diabetes, and hypertension and currently takes hydrochlorothiazide, enalapril, and monthly testosterone injections. He smokes two packs of cigarettes daily and consumes 6 to 8 beers nightly. His physical examination reveals an obese, ruddy-faced man with a temperature of 37°C, pulse 90 bpm, BP 164/80 mm Hg, and respirations 14 bpm. He is found to have a hematocrit of 54%.

Which of the following items in his history is LEAST likely to explain the elevated hematocrit?

A) Alcoholic cirrhosis.

B) Diabetes.

C) Antihypertensive medications.

D) Testosterone injections.

E) Smoking.

The correct answer is "B." Diabetes should not cause an elevated hematocrit and often causes anemia secondary to renal disease and reduced responsiveness to erythropoietin. Approach an elevated hematocrit with two questions: (1) Is it due to increased RBC mass or decreased plasma volume? (2) Is it primary erythrocytosis or secondary?

This patient has many potential secondary causes of an elevated hematocrit. "A," alcoholic cirrhosis can lead to hepatocellular carcinoma which, along with other malignancies, can result in overproduction of erythropoietin, causing an elevated hematocrit. Diuretics ("C") decrease plasma volume, causing an apparent elevation of hematocrit. Testosterone injections ("D") may cause polycythemia. Finally, he has a significant smoking history ("E") that may produce a secondary polycythemia due to hypoxia and cor pulmonale.

A 30-year-old female presents to your office for a routine visit. She was hospitalized for an appendectomy and at the time of surgery, her platelet count was found to be 1,400,000/mm³, which her surgeon felt was most likely reactive. She has no other past medical history, is asymptomatic, and exercises three times per week. You repeat the CBC, showing WBC 5000/mm³, Hgb 13 g/dL, and platelet count 800,000/mm³.

Question 6.10.1 What is your next step in managing this patient?

A) Anticoagulation with warfarin to a goal INR of 2 to 3.

B) Counseling against becoming pregnant.

C) Initiation of hydroxyurea 500 mg BID.

D) No further evaluation or follow-up necessary.

E) Observation and periodic evaluation of her CBC.

Answer 6.10.1 The correct answer is "E." This patient likely has essential thrombocythemia (ET), which is the most common myeloproliferative disorder in the United States. ET is more common in females. Patients are typically older when diagnosed with median age of 60. It is rare in children younger than 14 years of age. Patients with ET have a higher rate of mortality than matched controls due to risk of thrombosis (arterial > venous) and bleeding events. In order to diagnose ET, other causes of thrombocytosis (e.g., inflammation, iron deficiency, recent surgery, infection, bleeding, and malignancy) must be excluded. A bone marrow biopsy may be helpful in establishing the diagnosis by demonstrating adequate iron stores and ruling out chronic myelogenous leukemia (CML) or myelodysplasia.

"A" is incorrect. Warfarin would not be appropriate prophylactic therapy and would not be used unless the patient had a thromboembolic event. Aspirin can be used especially for the vasomotor symptoms associated with essential thrombocythemia (erythromeralgia [a burning pain in the hands and feet], acral paresthesias, headache, lightheadedness, etc.). Aspirin should also be considered if the platelet count is greater than 1.5 million. "B" is incorrect. Although patients with ET have a high rate of spontaneous abortion, many can have normal, healthy pregnancies. The patient should be counseled regarding pregnancy risks. "C" is also incorrect. The patient is at low risk for thromboembolic events (platelet count <1.5 million/mm³, young age, no comorbid illness, or prior events). Hydroxyurea could be considered if the patient was at high risk for thromboembolic events or symptomatic.

A 15-year-old female presents to your office complaining of fatigue. She reports menarche at age 13 and complains of heavy menses. Her physical examination reveals a well-developed, well-nourished, pale female. You find no hepatosplenomegaly. Her laboratory results reveal a WBC 6,000/mm³, Hgb 8.9 g/dL, hematocrit 27%, platelet count 400,000/mm³, MCV 72 fL, red blood cell distribution width (RDW) 16. You order more laboratory tests.

Question 6.11.1 What are the expected findings in this patient?

A) Increased iron, decreased ferritin, increased total iron binding capacity.

B) Decreased iron, decreased ferritin, decreased total iron binding capacity.

C) Increased iron, increased ferritin, increased total iron binding capacity.

D) Decreased iron, increased ferritin, decreased total iron binding capacity.

E) Decreased iron, decreased ferritin, increased total iron binding capacity.

Answer 6.11.1 The correct answer is "E." This patient likely has iron deficiency anemia related to her heavy menses. Iron deficiency anemia is characterized by anemia along with a decreased serum iron, decreased ferritin, increased total iron binding capacity (TIBC), and decreased transferrin saturation. The decrease in serum ferritin is proportional to the decrease in total body iron stores. Hypochromic microcytic RBCs are found on peripheral smear. See Table 6-3 for a general guide to the causes of anemia based on red cell indices.

You start iron supplementation therapy in this patient.

Question 6.11.2 Which of the following tests will be the first to indicate that you have instituted appropriate therapy and that the patient is responding?

A) Increase in hematocrit.

B) Increase in reticulocyte count.

C) Increase in serum-free Hgb.

D) Decrease in ferritin.

E) Decrease in transferrin saturation.

Answer 6.11.2 The correct answer is "B." The patient's reticulocyte count will increase first—before the hematocrit ("A"). This should start soon after treatment and maximize at 7 to 10 days. Pica (if present) should also resolve fairly early. "C" is incorrect. Only in exceptional circumstances (intravascular hemolysis) will there be free hemoglobin in the blood. "D" is incorrect because the ferritin is low in iron deficiency anemia and should increase with therapy. Finally, transferrin saturation ("E") should increase in patients once you start to treat their anemia, but the reticulocyte count increases first.

Question 6.11.3 How long should you continue iron supplementation once the patient's labs have normalized?

A) Stop immediately once anemia has resolved.

B) Continue 3 to 6 months after the anemia has resolved.

C) Continue for 1 year after the anemia has resolved.

D) Indefinite iron supplementation is indicated.

Answer 6.11.3 The correct answer is "B." Continue iron for 3 to 6 months once the anemia has resolved. Also address the underlying problem, in this patient her heavy periods, which may respond to hormonal contraception, tranexamic acid, etc.

The patient returns in 2 months but her labs, if anything, are worse than at first presentation. The patient swears that she has been taking the iron faithfully.

Question 6.11.4 Which of the following can lead to a failure of iron therapy for iron deficiency anemia?

A) Proton pump inhibitors (PPIs).

B) Incorrect diagnosis.

C) Oral antacids (e.g., calcium carbonate).

D) Atrophic gastritis, celiac disease, or Helicobacter pylori infection.

E) All of the above.

Answer 6.11.4 The correct answer is "E." Anything that neutralizes the stomach pH will interfere with absorption including PPIs, antacids, and loss of acid producing cells (e.g., pernicious anemia). Other GI diseases (celiac disease, H. pylori) can also interfere with iron absorption. Tea and some green leafy vegetables can also reduce iron absorption.

The patient returns to your office and finally admits she has not been able to take the iron because of side effects. Her hemoglobin is now down to 7.2 g/dL. She still feels fatigued. The patient will not agree to take any further iron orally. However, she is willing to consider other suggestions.

Question 6.11.5 What is your next step?

A) Encourage the patient to take the iron preparation along with calcium carbonate (Tums) to reduce the GI side effects.

B) Continue her prenatal vitamin only and encourage her to eat more red meat.

C) Give iron sucrose 200 mg IV weekly for 4 weeks.

D) Transfuse 2 units of PRBCs immediately.

Answer 6.11.5 The correct answer is "C." If oral iron preparations are not tolerated, IV iron preparations are available. Intramuscular preparations are best avoided due to pain at the injection site, skin discoloration, and risk for infection. The most commonly used options for IV replacement include iron dextran and iron sucrose. Iron dextran carries a risk of anaphylaxis in 0.6% to 2.3% of patients and other side effects in up to 25% of patients, including bronchospasm, flushing, headache, fever, urticaria, nausea, vomiting, hypotension, seizures, myalgias, arthralgias, and increased thromboembolic events. Iron sucrose has a lower incidence of side effects—typically nausea, constipation, diarrhea, or a transient minty taste—and may be given to patients who have had a previous reaction to iron dextran. "A" is incorrect because calcium will interfere with iron absorption. Not only that but also she has already said she would not take additional oral iron. "B" is incorrect because she needs more iron than can be provided through prenatal vitamins and her diet. Finally, "D" is incorrect as transfusion carries potential risks that could be avoided if she responds to IV iron replacement.

A 52-year-old woman with a history of rheumatoid arthritis is in your clinic for a 1-month follow-up after having a knee prosthesis removed secondary to a joint infection and osteomyelitis (Staphylococcal aureus). You obtain a CBC, revealing a WBC 8,000/mm³, Hgb 9.5 g/dL, hematocrit 28%, platelet count 450,000/mm³, and MCV 83 fL (normal). Serum iron levels are low with a normal serum transferrin receptor and increased ferritin.

Question 6.12.1 What is the most likely diagnosis?

A) Iron deficiency anemia due to rheumatoid arthritis.

B) Anemia of chronic disease due to rheumatoid arthritis and osteomyelitis.

C) Hemolytic anemia induced by antibiotics.

D) Acute blood loss during surgery.

E) Myelodysplastic syndrome (MDS) associated with rheumatoid arthritis.

Answer 6.12.1 The correct answer is "B." Anemia of chronic disease is a hypoproliferative anemia that occurs in the setting of chronic infection, inflammation, malignancy, heart failure, diabetes, and other serious health conditions. The anemia is usually mild and characterized by low serum iron, increased ferritin (remember that ferritin is an acute-phase reactant and these patients often have inflammation), decreased serum transferrin, normal (or low) serum soluble transferrin receptor level, and decreased transferrin saturation (see below for more on the soluble transferrin receptor). In addition, the reticulocyte count is typically low, the erythropoietin may be mildly elevated, and the peripheral smear may show hypochromic, microcytic RBCs or normochromic, normocytic RBCs. If differentiation between iron deficiency anemia and anemia of chronic disease is not apparent, a bone marrow biopsy can be obtained to assess iron stores.

A previously healthy 3-year-old female with a history of anorexia and irritability for 3 days is brought to your ED by her mother. On the day of admission, the child is difficult to arouse. You learn that her 6-year-old brother has had some difficulty reaching appropriate developmental milestones, and is a "fussy eater."

Physical examination reveals a slightly pale-appearing child, who responds to tactile stimuli but not to voice. Vitals are normal and her examination is unremarkable except for her decreased level of consciousness. Laboratory studies include a WBC 8,000/mm³, Hgb 10 g/dL, platelet count 300,000/mm³, and MCV 75 fL (microcytic). Her urine dipstick is normal, except for 1 + glucose; there are no ketones in the urine. Her blood chemistries are within normal limits, with the exception of a phosphorous of 2.0 mg/dL. Her peripheral blood smear shows red cells with coarse basophilic stippling.

Question 6.13.1 What is the best working diagnosis at this time?

A) Acute lead poisoning.

B) Anemia of chronic disease.

C) Early diabetic ketoacidosis (DKA).

D) Severe iron deficiency anemia.

E) Unrecognized bacteremia secondary to pyelonephritis.

Answer 6.13.1 The correct answer is "A." Lead poisoning should be considered in a child presenting with symptoms of encephalopathy and anemia with basophilic stippling on RBCs. Basophilic stippling occurs when ribosome precipitates litter the RBCs. Basophilic stippling can be seen in alcohol abuse, thalassemias, and heavy metal poisoning. "B," anemia of chronic disease, is unlikely because this illness is acute. "C," DKA, is unlikely because urine ketones are 99% sensitive for DKA and her urine ketones are normal. "D" is unlikely because there should be no neurologic symptoms associated with iron deficiency anemia. "E," pyelonephritis, is unlikely because the patient is afebrile and has a normal white count and negative urine. We could have tipped you off to the answer with a "Flint, Michigan" reference but that would have been no fun.

The patient's lead level is 70 mcg/dL. Because of your concern about acute lead intoxication and resulting encephalopathy, you decide to admit the child and treat her with dimercaprol.

Question 6.13.2 All of the following are true EXCEPT:

A) Dimercaprol should not be given if the child has a peanut allergy.

B) The child's diet should be monitored for adequate intake of calories, iron, and calcium.

C) The child's sibling should be tested, and arrangements should be made for close follow-up for both children.

D) The dose of dimercaprol should be tripled for patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Answer 6.13.2 The correct answer is "D." Dimercaprol is a lead chelator used to treat elevated lead levels. It is administered intramuscularly, is water insoluble, and must be given in a peanut oil vehicle. It may cause hemolysis in individuals with G6PD deficiency, so these patients should be monitored closely and not receive larger doses of dimercaprol. It is important to test siblings of an affected child, because the source of lead is often in the house. Close follow-up of affected children is essential to monitor for increasing blood lead levels after treatment, which may indicate the source of lead has not been removed. The absorption of lead can be made worse by malnutrition, iron deficiency, and poor intake of calcium. Iron deficiency frequently occurs in affected patients and may worsen anemia.

Another mainstream chelating agent is calcium disodium EDTA. It is recommended to use a combination of dimercaprol and EDTA for children with severe lead intoxication. Other chelating agents include d-penicillamine and succimer.

A 6-month-old male infant is brought to you for a well-baby check-up. His mother reports that the child has had difficulty with feeding, has frequent colds, and is often irritable. She has noted recurrent episodes of jaundice, especially when he is sick. His physical examination reveals a small child, faintly jaundiced. His temperature is 37.5°C, pulse 160 bpm, BP 85/50 mm Hg, and respirations 30 bpm. His abdomen is soft with palpable splenomegaly. The remainder of the examination is unremarkable. Laboratories reveal a WBC 13,000/mm³, Hgb 9 g/dL, platelet count 260,000/mm³, and MCV 60 fL (low). He is noted to have target cells on peripheral blood smear.

Question 6.14.1 Which one of the following is the most appropriate next step?

A) Order PT/PTT.

B) Order Hgb electrophoresis.

C) Transfuse with 1 unit of PRBCs.

D) Test for G6PD deficiency.

E) Test for sickle-cell anemia.

Answer 6.14.1 The correct answer is "B." The clinical and laboratory presentation is consistent with a hereditary hemoglobinopathy, most likely a thalassemia. The splenomegaly, significant anemia, target cells, and the profoundly low MCV are all suggestive of thalassemia; patients with thalassemia often have recurrent episodes of jaundice reflecting hemolysis. He has no history of abnormal bleeding, so "A" would not be indicated. Also, as the child does not appear to be in distress, "C" would be an incorrect answer. G6PD-deficient patients experience episodes of hemolytic anemia. Peripheral smear review at that time may reveal bite or blister cells, rather than target cells, so "D" is not the right answer. "E" is incorrect since the peripheral smear would reveal sickle cells if the patient had sickle disease.

Beta thalassemia major is confirmed by Hgb electrophoresis.

Question 6.14.2 Which of the following regarding his management is NOT true?

A) Untreated, mortality may approach 80% by 5 years of age.

B) Frequent blood transfusions may be required.

C) The condition will improve with age.

D) The child is likely to have growth retardation and delayed sexual maturation.

E) Without iron chelation therapy, there is a high incidence of mortality with this disease.

Answer 6.14.2 The correct answer is "C." Beta thalassemia refers to the disease state in which there are mutations in both genes that code for beta globin. Without treatment, mortality from thalassemia major approaches 80% by 5 years of age. Patients with beta thalassemia will eventually develop iron overload, even without blood transfusions. The use of transfusions and concurrent chelation therapy with deferoxamine has reduced long-term complications related to the disease. Deferasirox (Exjade), an oral chelating agent, is available as an alternative to deferoxamine. Bone marrow transplant can be curative. Beta thalassemia minor (or beta trait) is much less severe and occurs when only one of the genes is defective.

A woman brings her 10-week-old infant for evaluation. The child is colicky and irritable after feeding. She was born full term but has not been gaining weight appropriately. The patient's sister has sickle-cell trait, so you obtain an Hgb electrophoresis, which ultimately demonstrates SS genotype.

Question 6.15.1 Which of the following is INCORRECT regarding the child's care?

A) The patient should remain on prophylactic antibiotics until the age of 5 years due to a high risk of pneumococcal sepsis.

B) The child may develop splenomegaly and lymphadenopathy related to her disease.

C) The disease provides protection against infection with parvovirus.

D) The child may not develop pain crisis until she is older due to protection from HbF.

E) The child is likely to have a delay in puberty.

Answer 6.15.1 The correct answer is "C." The patient has homozygous SS sickle-cell disease. This child's mother should be counseled regarding the importance of continuing antibiotic prophylaxis until the age of 5 years because her child is at high risk for pneumococcal sepsis. Sickle-cell disease is protective against malaria, not parvovirus ("C"). In fact, parvovirus infection can be life-threatening in these patients due the development of aplastic anemia.

During infancy, children may be noted to have reticulocytosis, hemolytic anemia, and sickling by 10 to 12 weeks. At 5 to 6 months, splenomegaly may be noted, and lymphadenopathy may be prominent between 6 months and 5 years. The earliest pain crisis often involves hands and feet (dactylitis), and occurs after the HbF decreases to adult values; this usually does not occur until after the age of 4 years. The spleen involutes by 5 to 8 years. Puberty is delayed by an average of 2.5 years.

The child follows regularly with you for years, and she begins to develop more frequent pain crises in college. She is found to have an elevated C-reactive protein, increased LDH, and decreasing Hgb. You explain to her that some measures can be taken to reduce the frequency of pain crises.

Question 6.15.2 These measures include all of the following EXCEPT:

A) Initiation of hydroxyurea therapy.

B) Avoidance of hot showers.

C) Prompt treatment of infections.

D) Adequate hydration and nutrition.

E) Avoidance of emotional stress.

Answer 6.15.2 The correct answer is "B." Two main features of sickle-cell disease are shortened RBC survival and vasoocclusion due to poorly deformable RBC membranes. Pain episodes occur due to acute episodes of tissue hypoxemia and microinfarction. Crises can be precipitated by stress, fatigue, cold weather (not hot showers, which cause problems in multiple sclerosis patients), infection, dehydration, acidosis, and poor nutrition. The use of hydroxyurea promotes increased levels of HbF, and HbF is associated with decreased frequency and severity of pain crises.

Since you first met that little baby girl, 22 years have elapsed, and she is getting married—and you are getting old (the alternative is worse, of course). She is concerned about significant illness related to her disease. You counsel her regarding the most common causes of morbidity and mortality.

Question 6.15.3 All of the following statements are true EXCEPT:

A) ACS and pain crises are the most common causes for hospital admission for patients with sickle-cell disease.

B) Eighty percent of patients develop cholelithiasis by the age of 35 years.

C) Strokes may occur in 8% of patients by the age of 14 years, may be either symptomatic or clinically silent, and tend to be recurrent.

D) Heart failure, pulmonary fibrosis, pulmonary hypertension, and renal failure complicate fluid management, transfusions, and maintenance of adequate oxygenation.

E) Pregnancy should be avoided under any circumstance.

Answer 6.15.3 The correct answer is "E." The average life expectancy in patients with Hb SS is 42 years for men and 48 years for women. Maternal mortality occurs in about 1% of pregnancies. All of the rest are true including cerebrovascular events causing seizures and possible cognitive difficulty early in life. Of particular note, renal failure may be the cause of death in up to 10% of cases. Avascular necrosis and osteomyelitis (classically as a result of Salmonella infection), chronic skin ulcers, and priapism are also common.

Objectives: Did you learn to…

• Recognize the presentation and implication of essential thrombocytosis?

• Evaluate a patient with an elevated Hgb or platelet count?

• Obtain a thorough history in an anemic patient?

• Use laboratory parameters to identify the etiology of anemia?

• Initiate treatment of various causes of anemia?

• Identify certain anemias, especially iron deficiency, thalassemias, and sickle-cell disease, based on clinical and laboratory manifestations?

A 72-year-old gentleman is brought to your office because a home health nurse noted he was becoming progressively weaker and more fatigued. He has a history of celiac disease for which he follows a strict gluten-free diet, but he has not been eating well. He also has a history of a seizure disorder and takes phenytoin. His review of systems is positive for dyspnea on exertion and mild anorexia. He has no other symptoms.

Physical examination reveals a thin, pale-appearing man with normal vital signs. His conjunctivae are pale and his tongue is smooth, with moist mucosa and no oropharyngeal lesions. The remainder of the examination is unremarkable. A CBC reveals a WBC 4,500/mm³, Hgb 9 g/dL, hematocrit 28%, platelet count 140,000/mm³, MCV 102 fL, RDW 14, and B12 level 900 ng/L (normal).

Which of the following statements is most likely FALSE?

A) The patient may have a high homocysteine level.

B) The patient's condition could be made better with a trial of folate replacement.

C) The patient may have a low RBC folate level.

D) The patient's condition will likely require chronic blood transfusions.

E) The patient may have a normal serum folate level.

The correct answer is "D." This patient likely has folate deficiency, given a normal B12, macrocytic anemia, and risk factors for folate deficiency—old age, poor diet, avoidance of gluten (flour is normally fortified with folate), use of phenytoin, and possible malabsorption due to GI disease (celiac disease in this case, but also any other infiltrating or inflammatory process of the bowel). Dietary deficiency is uncommon in the United States due to supplementation of grain products with folate. Foods naturally high in folate include melons, bananas, leaf vegetables, asparagus, and broccoli. The recommended intake is 400 μg/day, and the body stores approximately a 4-month supply. If he has had recent adequate folate intake, the serum folate level may be normal, but the RBC folate will still be low, reflecting the deficiency (think of it as the HbA1C of folate).

To differentiate folate from B12 deficiency, check serum homocysteine and methylmalonate levels. Both will be elevated with B12 deficiency, while only homocysteine will be elevated in folate deficiency. Remember, you must exclude B12 deficiency before replacing folate because folate replacement can reverse the anemia but will permit progression of neurologic effects of B12 deficiency, so "B" is true.

A 47-year-old woman presents to your office complaining of tongue soreness, fatigue, and dyspnea with exertion. She denies unusual bleeding, weight loss, fevers, and night sweats. Her past medical history includes hypothyroidism, for which she takes levothyroxine. She does not drink alcohol or smoke. Physical examination reveals a tired-appearing woman with lemon-yellow colored skin, temperature 37°C, pulse 110 bpm, BP 120/74 mm Hg, and respirations 12 bpm. The examination is otherwise unremarkable. A CBC demonstrates a WBC count 4000/mm³, Hgb 9 g/dL, platelet count 140,000/mm³, and an MCV of 105 fL. Her B12 level is 100 pg/mL (normal >300 pg/mL) and folate 40 ng/mL.

Which of the following historical elements is LEAST likely to contribute to her condition?

A) History of working as a park ranger in Canada.

B) History of Zollinger–Ellison syndrome.

C) History of hypothyroidism.

D) History of new vegetarian diet started last month.

E) History of GI surgery.

The correct answer is "D." Most likely, this woman has pernicious anemia caused by B12 deficiency. Pernicious anemia is caused by immune destruction of parietal cells in the stomach, resulting in decreased absorption of B12. It typically develops in people over the age of 40 and is more common in people of northern European descent or in African Americans, as well as people with type A blood. Laboratory findings include antiparietal cell antibodies in 90% of affected patients (5% of normal individuals also have the antibody) and antibodies to intrinsic factor in 70% of patients. Individuals commonly have other autoimmune diseases such as thyroid disease, diabetes, and vitiligo. Individuals may complain of paresthesias, GI symptoms, sore tongue, or weight loss. The lemon-yellow appearance of the skin is due to anemia and mild jaundice.

Other causes of cobalamin (B12) deficiency include gastrectomy, Zollinger–Ellison syndrome (inability to alkalinize the small intestine), blind loop syndrome, bacterial overgrowth from previous surgery, and ingestion of undercooked fish infested with the tapeworm Diphyllobothrium latum (found in Canada, Alaska, and the Baltics—hence, the history of working as a park ranger). Although a strict vegetarian diet can cause B12 deficiency, there are sufficient stores to last 3 to 5 years (in other words, more than 1 month).

A 21-year-old college student is brought to the ED by his friends because of bizarre behavior. His friends state that he has been acting "a little odd" lately, but they are unaware of any drug abuse. He does drink alcohol but is not known as a binge drinker—at least not by modern NCAA Division I Drinking standards. His friends do not know his medical history but state he was taking a prescription drug for a "metabolic disorder," which he stopped several months ago. He is uncooperative, paranoid, and disoriented. You note brownish pigmentation of his corneas on physical examination. This may be the first—and last—case of Wilson disease you have ever seen.

Regarding this patient, which of the following is INCORRECT?

A) The patient has likely had episodes of hemolytic anemia in the past.

B) The patient has likely discontinued penicillamine.

C) The patient likely has an elevated ceruloplasmin level on blood test.

D) The patient likely has hepatolenticular degeneration.

E) The patient is at risk for hepatic failure.

The correct answer is "C." This patient likely has Wilson disease (an autosomal-recessive defect in cellular copper export), which presents with decreased levels of ceruloplasmin, increased liver enzymes, and signs of hemolysis (from the direct toxic effect of copper on the cell). Symptoms typically present in the teens and early 20s. Presenting symptoms may include Kayser–Fleischer rings (golden-brown pigmentation of the cornea), hemolytic anemia, or neurologic symptoms, often mimicking psychiatric illness. Treatment of the disease includes lifelong therapy with penicillamine or trientine (chelating agents), and should be considered even for asymptomatic individuals known to have the disease. By the way, pennies are primarily zinc and contain little copper.

A 50-year-old man presents to your office with low-back pain of 8 weeks duration. He denies any history of trauma or overexertion. He notes the pain is constant and does not improve with positioning. Also, he has noticed some fatigue. He has no other complaints.

Physical examination reveals a well-nourished male with normal vital signs. His neurologic examination is normal. On musculoskeletal examination, he has midline point tenderness over T12. Plain films reveal a compression fracture at T12. A serum total protein level is 9 mg/dL (elevated), but the remainder of an evaluation for endocrine causes of osteoporosis is normal.

All of the following are necessary for the diagnosis of this patient EXCEPT:

A) Bone scan.

B) Serum and urine protein electrophoresis with immunofixation.

C) Bone marrow aspirate and biopsy.

D) Quantitative immunoglobulins.

E) Skeletal survey.

The correct answer is "A." A spontaneous vertebral fracture in a 50-year-old male is definitely not normal. Multiple myeloma should be considered in patients with this presentation. Multiple myeloma is a clonal disorder of plasma cells. Risk factors include African-American race, male sex, and advancing age (median age of 60–65 at presentation). Work-up for the diagnosis of multiple myeloma requires a serum and urine protein electrophoresis with immunofixation ("B"). This will help to identify a monoclonal protein. Quantitative immunoglobulins ("D") will help to assess whether this patient has an elevation of immunoglobulins in the range required for the diagnosis of multiple myeloma. A skeletal survey ("E") and bone marrow biopsy ("C") complete the diagnostic work-up. A bone scan is not useful because the lytic lesions characteristic of multiple myeloma do not take up radioisotope.

On a routine insurance physical examination, a 55-year-old man was found to have a total protein of 9 g/dL (elevated). The remainder of his serum chemistries and his CBC were normal. He is active, feels well, and is not taking any medications. His physical examination is unremarkable. You order a serum and urine electrophoresis with immunofixation and quantitative immunoglobulins. He has a monoclonal spike with 1,400 g/dL of IgG kappa (elevated). His other immunoglobulins are within normal limits. A skeletal survey demonstrates no lytic lesions, and his bone marrow aspirate and biopsy demonstrate 6% plasma cells (normal is 1–4%). After the bone marrow biopsy, the hematologist sends him back to you for follow-up.

Question 6.16.1 What is your next step in the management of this patient?

A) Monitor blood, including serum immunoglobulins, every 3 to 6 months and, if stable after 1 year, annually thereafter.

B) Monitor blood, including serum immunoglobulins, every 4 weeks indefinitely.

C) Start on chemotherapy for multiple myeloma.

D) Obtain yearly bone marrow biopsy and skeletal survey.

E) No follow-up is necessary.

Answer 6.16.1 The correct answer is "A." This patient has monoclonal gammopathy of undetermined significance, or MGUS, which is found in up to 3% of asymptomatic older (over 50 years old) individuals (mostly Caucasian). A bone marrow biopsy indicating 10% plasma cells is required to make the diagnosis of multiple myeloma; this patient only has 6%. In addition, this patient has a normal CBC and is asymptomatic (no fatigue, bone pain suggestive of lesions, etc.). Thus, this patient has MGUS. Patients with MGUS typically do well, with only 1% per year progressing to multiple myeloma.

While patients should be reassured of the typically benign nature of this condition, up to 30% will have complications (multiple myeloma, amyloidosis, other myeloproliferative disorders). After several unchanged immunoglobulin levels and normal CBCs within the 6 months of the initial diagnosis, annual or biannual evaluation should be adequate. Any changes in the patient's condition, such as unexplained anemia, increased immunoglobulin levels, renal insufficiency, or bony pain, should prompt further evaluation. An increase in immunoglobulin does not necessarily mean the monoclonal protein is increasing, and a serum protein electrophoresis and immunofixation should be obtained. Repeat bone marrow biopsy is indicated only if the clinical picture is confusing.

A 63-year-old woman presents to your office with complaint of fatigue. She states she felt like she spent the winter taking antibiotics because she developed "one infection after the other." Prior to this past winter, she had been well and did not take any prescription drugs regularly. Physical examination demonstrates a slightly pale, thin woman. Her temperature is 37.5°C, pulse 90 bpm, BP 120/58 mm Hg, and respirations 12 bpm. Her oropharynx demonstrates purpuric lesions. Her abdominal examination shows no organomegaly, and the remainder of the physical examination is unremarkable.

You obtain blood tests: WBC 2,100/mm³, Hgb 8.4 g/dL, and platelet count 20,000/mm³. A bone marrow aspirate and biopsy are obtained, which demonstrate a hypercellular marrow with 4% blasts, 4% ringed sideroblasts, and megakaryocytes. You talk to the hematologist, who suspects that your patient has a myelodysplastic syndrome (MDS).

Question 6.17.1 Which of the following statements is INCORRECT?

A) The small number of blasts in the bone marrow indicates a good prognosis.

B) The patient cannot have MDS because she has pancytopenia.

C) The patient may benefit from administration of erythropoietin.

D) The patient may develop acute myeloid leukemia.

E) The patient's gender may result in a better prognosis.

Answer 6.17.1 The correct answer is "B." Patients with MDS can be pancytopenic. MDS includes a number of clonal stem cell disorders characterized by dysplasia and ineffective hematopoiesis of one or more cell lines. The disease is typically one of older adults, with a median age of 65 to 70 years at onset; however, a better prognosis is associated with age <60 years and female gender. There is an increased risk of MDS in smokers, those exposed to benzene or alkylating agents, and with some hereditary disorders. Prognosis depends on the number of blasts, the number of lineages affected, and cytogenetic abnormalities. Median survival ranges from 10 to 66 months, and progression to acute leukemia ranges from 6% to 33% of patients, depending on the subtype of MDS.

Depending on the age and overall performance status of the individual MDS patient, treatment can range from supportive care with blood or platelet transfusions, to treatment with granulocyte colony stimulating factor (GCSF), to chemotherapeutics such as azacytidine, or even to bone marrow transplantation.

Objectives: Did you learn to…

• Recognize the presentation of multiple myeloma?

• Identify MGUS?

• Identify pancytopenia as a presentation of MDS?

All of the following are accurate statements about neutrophil counts in children EXCEPT:

A) African-American children may have a normal ANC of 1,000/mm³.

B) Children over the age of 6 should be expected to have a normal ANC of 1,500 to 8,000/mm³.

C) Neonates typically have a normal ANC of <500/mm³ at birth.

D) Infants typically have 20% to 30% neutrophils on WBC differential.

E) Five-year-old children have 50% neutrophils on WBC differential.

The correct answer is "C." In the pediatric population, neutropenia is typically described as an ANC of <1,500/mm³. Up to 30% of African-American children have an asymptomatic ANC of <1,000/mm³ (e.g., no increased risk of infection). At birth, neutrophils make up the majority of the WBC differential, and this decreases to 20% to 30% after the first few days of life. At 5 years of age, neutrophils comprise approximately 50% of the differential, and this reaches 70% by puberty.

A 49-year-old male presents to your office complaining of joint pain, fatigue, and increased urination. There is a family history of cirrhosis of the liver, apparently not related to alcohol. He does not take any medications and does not smoke but drinks two glasses of wine each night. Physical examination reveals a thin male with tanned skin (in the dead of winter in Iowa, so he is either rich or sick, take your choice) and normal vital signs. His heart and lung examinations are unremarkable. The abdomen is soft, nontender, and nondistended, and his liver edge is palpable 2 cm below the costal margin. He has pain with range of motion in his hips, knees, and MTP joints. The remainder of the examination is unrevealing. Serum electrolytes are normal, but his glucose is 282 g/dL. His transaminases are elevated.

Question 6.18.1 Of the following, what is the most likely diagnosis?

A) Alcoholic hepatitis.

B) Colon cancer.

C) Hemochromatosis.

D) Vitamin B12 deficiency.

Answer 6.18.1 The correct answer is "C." This patient presents with a "classic" history of hemochromatosis. Symptoms start during or after the fifth decade of life, are initially mild, and progress slowly. "Bronze diabetes" (bronze or tan skin color due to iron deposition accompanied by hyperglycemia) is sometimes noted. Most organs can eventually be involved, but most commonly symptoms are due to liver, cardiac, joint, and testicular involvement. "A," alcoholic hepatitis, is a consideration, but his reported use is unlikely to result in disease. You also would not expect to see some of the other symptoms (e.g., diabetes and arthritis) in relation to alcoholic hepatitis. "B," colon cancer, is unlikely to present in this way. "D," vitamin B12 deficiency, typically presents with anemia and neurologic symptoms.

Question 6.18.2 Which of the following laboratory values are most consistent with this patient's presentation?

A) Decreased iron, decreased ferritin, decreased transferrin saturation.

B) Decreased iron, decreased ferritin, increased transferrin saturation.

C) Increased iron, decreased ferritin, increased transferrin saturation.

D) Increased iron, increased ferritin, decreased transferrin saturation.

E) Increased iron, increased ferritin, increased transferrin saturation.

Answer 6.18.2 The correct answer is "E." All of these iron studies (serum iron level, ferritin and transferrin saturation) are elevated in patients with hereditary hemochromatosis. A normal person maintains approximately 3 to 4 g of iron in the body. Normal individuals absorb about 1 mg/day of iron (10% of what is ingested), which is precisely balanced with loss through sweat, sloughing of cells, and GI losses. In hereditary hemochromatosis, 2 to 4 mg of iron is absorbed daily, resulting in the accumulation of iron.

The patient's diagnosis is confirmed, and you counsel him regarding his disease.

Question 6.18.3 All of the following statements are true EXCEPT:

A) This is an autosomal-dominant disease.

B) Affected females typically present later in life due to increased iron losses.

C) Patients may benefit from phlebotomy even after development of symptomatic disease.

D) Patients are susceptible to unusual infections.

E) Patients are at high risk for hepatocellular carcinoma.

Answer 6.18.3 The correct answer is "A." Hereditary hemochromatosis is an autosomal-recessive disorder. Approximately 10% of Caucasians are heterozygous, and 5/1,000 are homozygous for the gene mutation. Patients are at increased risk for infections due to Listeria, Vibrio vulnificus (sorry, no sushi!), and Yersinia enterocolitica. Affected females may present later in life due to increased iron losses from menstruation, pregnancy, and lactation.

Treatment includes phlebotomy or chelation therapy if phlebotomy is contraindicated. Patients should be monitored closely for development of hepatoma, since therapy does not reduce the risk of hepatocellular carcinoma once cirrhosis is present. Family members should be screened for the disease so they can be started on therapy early, in order to prevent the development of cirrhosis.

A 56-year-old man undergoes a laryngoscopy. In an outdated move that is generally not recommended now, his doctor used extra doses of benzocaine spray (like gallons of the stuff) to overcome a strong gag reflex. The patient tolerated the procedure well, but afterward he started to have cyanosis around the lips. You are now seeing him in the ED, and he has a bluish discoloration of his lips and fingertips and is complaining of a headache. You administer oxygen by nasal cannula with no improvement in his cyanosis. You draw venous blood for labs, and find that it has an unusual chocolate color.

Question 6.19.1 All of the following statements are likely to be true about this patient EXCEPT:

A) A measured arterial blood gas will demonstrate a normal PaO₂.

B) The pulse oximeter will show high-normal oxygen saturation.

C) The patient may require therapy with methylene blue.

D) The patient should not be treated with methylene blue if he has a history of G6PD deficiency.

E) Additional doses of benzocaine can be lethal.

Answer 6.19.1 The correct answer is "B." This patient has methemoglobinemia, which in his case was likely a result of the benzocaine spray. Methemoglobinemia results when iron in Hgb is oxidized from the ferrous to the ferric state and the Hgb becomes incapable of binding and transporting oxygen. The blood gas oxygen may look normal because the RBCs cannot release oxygen (and thus remain oxygenated). However, the pulse oximeter will show a low O₂ saturation. So, there is often a gap between what you see on the blood gas and what the pulse oximeter suggests.

In a normal patient, less than 1% of Hgb is found in the methemoglobin form. Depending on the percentage of methemoglobin, presentations will vary. At methemoglobin levels of 10% to 20%, patients present with cyanosis refractory to oxygen. The arterial blood gas may show a normal PaO₂ with low oxygen saturations. When methemoglobin levels are >30%, patients present with headache, dizziness, dyspnea, and tachypnea (signs of moderate hypoxemia). At >50%, patients develop stupor and obtundation (signs of severe hypoxemia), and levels >70% may be lethal.

Certain drugs such as nitroprusside, sulfonamides, some local anesthetics, and acetaminophen have been found to cause methemoglobinemia.

Treatment of methemoglobinemia is methylene blue. However, patients with G6PD deficiency should not be given methylene blue, and hyperbaric oxygen therapy should be considered instead. Remember, when patients have been exposed to cyanide, you want to cause methemoglobinemia. The exact mechanism by which this protects against cyanide is unknown, since patients begin to improve prior to the presence of methemoglobinemia.

A 16-year-old sub-Saharan African male presents to your office for progressive fatigue and dyspnea over the last few days. He also has some mild upper respiratory symptoms that are being "treated" with sulfamethoxazole—trimethoprim. (The doctor down the street is known to treat all respiratory infections with antibiotics.) On examination, you find a well-nourished male in no distress. He is afebrile but slightly tachycardic. You note mild scleral icterus and pallor of the palmar creases, but the remainder of the examination is unremarkable. A CBC shows normal WBC count and platelets, with Hgb 10.2 g/dL. On peripheral smear, "bite cells" and rare Heinz bodies are reported. The LDH and bilirubin are elevated and the serum haptoglobin is low, but the other serum chemistries are normal.

Question 6.20.1 Which of the following is the most likely diagnosis?

A) Hereditary spherocytosis.

B) G6PD deficiency.

C) Sickle-cell disease (homozygous).

D) Sickle-cell trait (heterozygous).

E) Iron deficiency anemia.

Answer 6.20.1 The correct answer is "B." The most likely cause of this patient's anemia is G6PD deficiency. He appears to have a hemolytic anemia, as evidenced by the elevated LDH, bite cells, elevated bilirubin, low haptoglobin, and the acute onset of symptoms. Heinz bodies are inclusions in red cells seen on peripheral smear within the first few days of an oxidative stress in patients with G6PD deficiency. Bite cells are formed as the red cells pass through the spleen and the Heinz bodies are removed. The other diagnoses are less likely. Hereditary spherocytosis ("A") is caused by an inherited defect in the red cell membrane, and episodes of hemolytic anemia may be brought on by environmental stress. However, patients generally have a baseline anemia, and spherocytes should be seen on peripheral smear. Sickle-cell disease and trait are discussed in more detail elsewhere. "E," iron deficiency anemia, does not generally present acutely and is not associated with findings of hemolysis.

Hemolytic anemia in G6PD deficiency is caused by oxidative stress on red cells, most commonly as the result of infection or administration of certain drugs.

Question 6.20.2 Which of the following can precipitate a hemolytic crisis in G6PD deficiency?

A) Sulfa antibiotics.

B) Fresh fava beans.

C) Nitrofurantoin.

D) Some antimalarial drugs.

E) All of the above.

Answer 6.20.2 The correct answer is "E." All of the above can cause a hemolytic crisis in G6PD deficiency. Multiple other drugs can be involved as well, including vitamin C, salicylates, isoniazid, and phenytoin.

Question 6.20.3 Which of the following is the most appropriate intervention for this patient with G6PD deficiency at this point?

A) Admit to the hospital and observe.

B) Admit to the hospital and transfuse 2 units of packed red cells.

C) Recommend supportive care and follow-up in a few days.

D) Recommend splenectomy and refer to a general surgeon.

Answer 6.20.3 The correct answer is "C." The hemolytic anemia of G6PD deficiency is self-limited and will resolve. This is because in most cases of G6PD deficiency, only about 25% of the RBCs (the older cells) are susceptible to oxidative stress. Severe episodes should be treated in the hospital setting, but most episodes can be managed as an outpatient. Patients should be educated on the drugs and stressors that may precipitate an episode of hemolytic anemia. Splenectomy may limit hemolysis in patients with more severe disease.

Objectives: Did you learn to…

• Describe symptoms and signs of hemochromatosis?

• Recognize complications related to iron overload?

• Describe findings and treatment of methemoglobinemia?

• Identify clinical and laboratory manifestations of G6PD deficiency and describe its management?

A 72-year-old man presents to your office for follow-up after a recent hospitalization for pneumonia. While he was in the hospital, he had an increased WBC with lymphocytosis. You repeat his CBC and find a WBC of 18,000/mm³, with 80% lymphocytes, Hgb of 14 g/dL, and a platelet count of 200,000/mm³. You review office records from a visit 1 year ago and find a WBC of 14,000/mm³ with 76% lymphocytes. You send his peripheral blood for flow cytometry, which is consistent with a diagnosis of chronic lymphocytic leukemia (CLL).

Which of the following statements about this patient is INCORRECT?

A) This patient is at risk for the development of hemolytic anemia.

B) This patient is at risk for serious infection.

C) This patient is likely to experience a relatively benign disease course.

D) This patient should be started on chemotherapy.

E) This patient may develop "B symptoms" (fever, night sweats, weight loss).

The correct answer is "D." CLL is characterized by progressive accumulation of long-lived lymphocytes. It is more common in men and tends to be a disease of older adults (median age at diagnosis is 65 years); however, up to 20% of cases occur in patients < 60 years of age. Diagnosis is made if a patient has >5,000/mm³ mature-appearing lymphocytes in the blood representing a clonal line. With the use of immunophenotyping, bone marrow biopsy is not necessary for diagnosis, but may be useful for prognosis.

This patient has a low-stage CLL (the only finding is lymphocytosis) and does not require immediate treatment with chemotherapy. He should be monitored every 6 to 12 months or sooner if he develops symptoms, such as infections, fatigue, bulky lymphadenopathy, or bleeding. Patients with CLL are at risk for developing autoimmune diseases, including hemolytic anemia, autoimmune thrombocytopenia, pure red cell aplasia, and autoimmune neutropenia.

A 46-year-old woman presents to your office for a preoperative evaluation. She is planning an elective hysterectomy for uterine fibroids. She has no significant past medical history. Her review of systems is positive only for sweats. Her physical examination is unremarkable except for a palpable spleen tip. You obtain a CBC, showing a WBC 50,000/mm³, Hgb 11 g/dL, and a platelet count 350,000/mm³. On her peripheral blood smear, she has mostly neutrophils and bands, with some metamyelocytes, myelocytes, and basophils as well.

All of the following are likely to be true EXCEPT:

A) The patient has an underlying infection with leukemoid reaction.

B) The patient has a balanced translocation between chromosomes 9 and 22.

C) The patient will likely develop progressive leukocytosis, fevers, anemia, and thrombocytopenia if untreated.

D) This condition may be treated with oral tyrosine kinase inhibitors.

The correct answer is "A." Although a leukemoid reaction is a possibility, it would be unusual to see a full range of maturation of myeloid cells (e.g., metamyelocytes and myelocytes) in the peripheral blood along with increased basophils and a palpable spleen. Rather, this patient likely has chronic myelogenous leukemia (CML), which is a clonal myeloproliferative disorder, characterized by the "Philadelphia chromosome" (translocation between chromosomes 9 and 22), which encodes for an abnormal tyrosine kinase protein. This protein is the target for the tyrosine kinase inhibitors, such as imatinib (Gleevec), which have resulted in significant improvement in survival. Patients with CML typically present between the ages of 40 and 60. Up to 40% of patients are asymptomatic at presentation. Others complain of weight loss, fatigue, abdominal pain, night sweats, and fever. Five-year overall survival can be up to 85% depending on the age at diagnosis.

You have a febrile 37-year-old male with a very high WBC count, most of which are blasts. Most likely, he has an acute leukemia. A bone marrow has not yet been done, and it is unknown if this is an acute myeloid leukemia or an acute lymphoblastic leukemia.

Which of the following statements is INCORRECT?

A) The patient's fever is likely due to the leukemic cells, and antibiotics should be started only if you identify a specific infection.

B) The patient is at risk for tumor lysis syndrome and should be started on allopurinol.

C) Aggressive inpatient chemotherapy is required for both the treatment of acute myeloid leukemia and acute lymphoblastic leukemia.

D) You should consult a hematologist/oncologist as soon as possible.

The correct answer is "A." Patients with acute leukemia and fever should be cultured, and antibiotics should be started as soon as possible since a fever is often the result of a concurrent infection. These patients should be kept well hydrated and given allopurinol to prevent tumor lysis syndrome, which can occur even without chemotherapy if the tumor burden is high enough. Treatment of acute leukemias requires intensive chemotherapy and should be started as soon as possible, so prompt evaluation by a hematologist/oncologist is imperative.

A 65-year-old male who is on quinine for leg cramps (a non–FDA-approved indication) is brought into the ED. Last night he was complaining of a headache, fever, and numbness on the right side of his face. This morning, he was acting erratically.

His physical examination demonstrates a confused male, with a temperature of 39°C, pulse 110 bpm, BP 180/94 mm Hg, and respirations 14 bpm. He has a few petechiae on his palate. He is tachycardic and lungs are clear to auscultation bilaterally. His abdomen is soft, without organomegaly. His neurologic examination is difficult to complete due to his inability to cooperate.

Laboratory findings include WBC 6,000/mm³, Hgb 8.4 g/dL, and platelet count 50,000/mm³. Schistocytes are noted on a peripheral blood smear.

Question 6.21.1 All of the following may be expected in this patient EXCEPT:

A) Creatinine of 3.2 mg/dL.

B) LDH of 640 IU/L.

C) Elevated haptoglobin.

D) Elevated indirect bilirubin.

E) Negative direct antiglobulin test (direct Coombs).

Answer 6.21.1 The correct answer is "C." An elevated haptoglobin would suggest the absence of active hemolysis. The presence of schistocytes suggests ongoing microangiopathic hemolysis, in this case due to thrombotic thrombocytopenic purpura (TTP). TTP is due to the lack of activity of the ADAMTS13 enzyme either via inheritance of a faulty enzyme (inherited) or via antibodies produced against the enzyme (acquired). It is classically described by a pentad of findings: microangiopathic hemolytic anemia (suggested by schistocytes on peripheral smear), thrombocytopenia, fever, renal insufficiency, and mental status changes. Not all five features need to be present for the diagnosis, but your patient seems to have the pentad. An otherwise unexplained microangiopathic hemolytic anemia in the presence of thrombocytopenia is enough to trigger treatment for TTP; fever, renal insufficiency and mental status changes are not necessary to make the presumptive diagnosis of TTP. The negative direct antiglobulin test (direct Coombs), "E," suggests that the hemolytic anemia is not due to an autoimmune process. Note that the patient is on quinine, one of the drugs that can cause TTP. Clopidogrel and ticlopidine can also cause TTP although it is less common with clopidogrel.

Question 6.21.2 Which of the following laboratory findings would you expect to see in this patient with TTP?

A) Normal PT/INR.

B) Elevated PTT.

C) Elevated fibrin degradation products.