Hematology

Question #9

A 50-year-old businessman presents to your office for an insurance examination. He smokes a pack of cigarettes a day, is moderately (20 lb) overweight, and has a history of hypertension treated with hydrochlorothiazide. Except for some job-related stresses, he feels well. Systems review is normal. Findings on physical exam are as follows: BP, 155/90; P, 92; T, 37.0 C; wt, 195 lb. Plethoric facies are noted, but examination of the heart, lungs, and abdomen is normal. Laboratory results are as follows: Hb, 18.5; HCT, 55; WBC, 6,800 with normal differential; platelets, 325,000; peripheral blood smear, normal; Na+, 140; K+, 3.2; Cr, 1.5; COHb, 4.2; RBC volume, 31 (upper limits of normal); plasma volume, 36 (low normal); Pao2, 94; Paco2, 42; pH, 7.41; HCO3, 24; Hb P50, normal; erythropoietin, 25.

Which of the following is the most likely diagnosis?

  1. Polycythemia vera
  2. Relative polycythemia
  3. Renal cell carcinoma
  4. Obstructive sleep apnea
  5. High-affinity hemoglobinopathy


Answer 1 is not correct. Answer 2 is correct.

Key Concept: Recognize the syndrome of relative polycythemia (Gaisbock's syndrome)

This patient has all of the classic features of relative polycythemia, also called stress erythrocytosis or Gaisbock's syndrome. Patients with this syndrome characteristically are 45 to 55 years of age (a bit younger than PRV patients), smokers, obese, and hypertensive. Modest increase in carboxyhemoglobin levels and diuretic therapy may contribute to the high-normal RBC masses and reduced plasma volumes, respectively, that are commonly seen in these patients. The absence of splenomegaly, leukocytosis, and thrombocytosis, as well as the high-normal erythropoietin, exclude polycythemia vera. Renal cell carcinoma (or other renal and hepatic lesions) should be considered in the differential but is not the most likely diagnosis, in light of the characteristic presentation for relative polycythemia. Sleep apnea should also be considered in the differential diagnosis, but the patient has no symptoms of excessive daytime somnolence. The normal P50 (the Po2 at which 50% of the hemoglobin is deoxygenated) excludes a hemoglobinopathy with increased oxygen affinity.

Question #10

A 78-year-old man presents for evaluation of progressive headache, dizziness, and weakness of 6 months' duration. Hot showers cause generalized pruritus. The past medical history and systems review are otherwise normal. He had a normal health maintenance examination 5 years ago, including routine laboratory studies. Physical examination shows the following: BP, 130/70; P, 70; T, 37.0 C; wt, 165 lb. The skin of the face is plethoric and dusky red. Heart and lungs are normal. A spleen tip is palpable 2 cm below the costal margin. There is no lymphadenopathy. The rest of the examination is normal. Laboratory results are as follows: Hb, 19.5; HCT, 65; WBC, 12,800, with normal differential; platelets, 525,000; peripheral blood smear, increased basophils, myelocytes, and metamyelocytes; Na+, 140; K+, 4.0; Cr, 1.0; uric acid, 10.5; Pao2, 94; Paco2, 42; pH, 7.41; ; HCO3, 24; erythropoietin, 5

Which of the following is the most likely diagnosis?

  1. Polycythemia vera
  2. Relative polycythemia
  3. Renal cell carcinoma
  4. Hypoxic polycythemia
  5. High-affinity hemoglobinopathy


Answer 1 is correct.

Key Concept: Diagnose polycythemia vera

The elevated hematocrit (> 60% in men, > 57% in women), splenomegaly, elevation and immaturity of other myeloid cell lines, and the reduced erythropoietin level are virtually diagnostic of polycythemia vera. These findings and the normal Pao2 level virtually exclude the other diagnostic options, especially since the question asks for the most likely diagnosis. Determination of the RBC mass is probably unnecessary in light of a markedly elevated hematocrit and reduced erythropoietin level. Other laboratory evidence of polycythemia vera would include elevations of leukocyte alkaline phosphatase (reduced in chronic myeloid leukemia), vitamin B12-binding capacity, vitamin B12 levels, and uric acid levels. Endogenous erythroid colonies are found in 97% of polycythemia vera patients. Note that a normal erythropoietin level does not exclude hypoxic polycythemia, though an elevated level is commonly seen in patients with disorders such as COPD and cyanotic congenital heart disease.

Question #11

For the patient described in Question 10, therapeutic weekly phlebotomy is initiated with a goal of reducing the hematocrit to a level of 40 to 45.

In addition to phlebotomy, which of the following therapeutic options also would be indicated at this time?

  1. Aspirin
  2. Anagrelide
  3. Radioactive phosphorus (32P)
  4. Busulfan
  5. Hydroxyurea


Answer 1 is not correct. Answer 5 is correct.

Key Concept: Know the appropriate therapy for patients with polycythemia vera

Myelosuppressive agents are indicated in patients with thrombotic risks (high platelets, age greater than 70 years, prior thrombosis) or in patients requiring frequent phlebotomy to maintain a hematocrit of 40 to 45. Compared with patients treated with phlebotomy and myelosuppressive drugs, patients managed with phlebotomy alone have an increased risk of thrombosis in the first 3 years after diagnosis. Hydroxyurea (usually in a dosage of 500 to 1,000 mg/day) is the preferred agent because of ease of administration, low cost, and low risk of secondary leukemia (compared with busulfan and 32P). Anagrelide will reduce the platelet count but is expensive and has not been shown to decrease the thrombotic risk. Aspirin, in conjunction with dipyridamole, failed to demonstrate a reduced risk of thrombosis in one study. Aspirin may also exacerbate the tendency toward peptic ulcer disease and iron deficiency anemia commonly seen in such patients; however, low-dose aspirin (81 mg/day) is commonly used in patients who have high platelet counts, thrombotic risk, and no bleeding history.

Question #12

A 50-year-old man is evaluated for impotence. His wife states that he has had progressive loss of interest in sex, personality change, and fatigue for 6 months. He has always been obese but has gained 25 lb in the past year since he discontinued smoking, after 30 pack-years. The patient has moved to a basement bedroom so that his wife and children can sleep without being awakened by his snoring. He claims to sleep soundly yet awakens feeling tired; he frequently falls asleep while watching TV or reading the paper and has occasionally even fallen asleep at the dinner table. He denies feelings of depression and complains only of feeling tired. Physical examination shows the following: BP, 140/80; P, 92; T, 37.0 C; wt, 265 lb. Office oximetry shows Sao2 to be 92% at rest and following a walk in the hallway. Except for obesity, the physical examination is normal. Laboratory findings are as follows: Hb, 18.5; HCT, 55; WBC, 4,600, with normal differential; platelets, 275,000; peripheral blood smear, normal; Na+, 142; K+, 4.2; Cr, 1.0; Hb P50, normal; erythropoietin, 55.

Which of the following is the most likely cause of the erythrocytosis in this patient?

  1. Polycythemia vera
  2. Relative polycythemia
  3. Familial erythrocytosis
  4. Hypoxic polycythemia (due to obstructive sleep apnea)
  5. High-affinity hemoglobinopathy


Answer 1 is not correct. Answer 4 is correct.

Key Concept: Diagnose hypoxic polycythemia in the face of a normal Sao2 or Pao2 level

The clinical stem is sketchy; the reader craves more historical and laboratory information. The patient could conceivably have one of the two rare causes of erythrocytosis offered (familial erythrocytosis, high-affinity hemoglobinopathy) or relative polycythemia. However, in the context of a multiple-choice question, little information is provided to support these diagnoses. The history provided is highly suggestive of obstructive sleep apnea, and this diagnosis is therefore the most likely cause of the erythrocytosis in this patient with an elevated erythropoietin level, no splenomegaly, and normal WBC and platelet counts. Further history (observed apneic episodes during sleep) and laboratory studies (arterial blood gases, pulmonary function studies, overnight oximetry, and polysomnography) would be appropriate at this time to confirm the suspected diagnosis. If these studies are negative, studies to investigate alternative diagnoses would be appropriate. Because the patient's hypoxia is intermittent (i.e., during sleep-disordered breathing) and because the patient apparently does not have severe COPD or cor pulmonale, the oxygen saturation and Pao2 levels can be normal during the day. The elevated erythropoietin level points to tissue hypoxia as a cause of the erythrocytosis.

Question #13

A 75-year-old woman has been treated for polycythemia vera for 10 years with phlebotomy and hydroxyurea. She has not required phlebotomy for 4 years, and the dose of hydroxyurea has been gradually reduced because of cytopenia. The hydroxyurea was discontinued 3 weeks ago. Physical examination reveals pallor and an enlarged spleen, palpable 12 cm below the left costal margin. Laboratory findings are as follows: Hb, 9.5; HCT, 25; WBC, 2,200; platelets, 55,000; blood smear, normal; Na+, 140; K+, 4.1; Cr, 1.2; peripheral blood smear, teardrop-shaped red cells, nucleated red cells, myelocytes, promyelocytes, and 1% myeloblasts.

What is the most likely cause of the anemia, thrombocytopenia, and leukopenia in this patient?

  1. Aplastic anemia
  2. Delayed myelosuppression from hydroxyurea
  3. Post-polycythemic myeloid metaplasia
  4. Transformation to acute myeloid leukemia
  5. Hypersplenism


Answer 1 is not correct. Answer 3 is correct.

Key Concept: Recognize the syndrome of myeloid metaplasia following polycythemia vera

Approximately 20% of patients with polycythemia vera (and the other myeloproliferative disorders) eventually develop myelofibrosis or myeloid metaplasia (MM), a process indistinguishable from agnogenic myeloid metaplasia (AMM). Myeloid metaplasia is caused by progressive fibrosis of the bone marrow and a shift of hematopoiesis from the marrow to the liver and spleen. Some of the largest spleens encountered in clinical medicine are seen in AMM and MM. These patients present with progressive cytopenia, and the smear shows characteristic teardrop-shaped red cells and a leukoerythroblastic picture. Although these patients can progress to acute myeloid leukemia, the presence of a small percentage of myeloblasts should not suggest the diagnosis of acute leukemia in this patient at this time.

Question #1

A 72-year-old man develops epistaxis that is difficult to control. He has no prior history of bleeding problems. Evaluation shows a platelet count of 158,000/l and normal bleeding time, PT, and TT. An elevated PTT is found that does not correct with a mixing study.

Which of the following would be appropriate treatment for uncontrollable bleeding in this patient?

  1. Discontinuance of aspirin
  2. Platelet infusion
  3. Porcine factor VIII infusion
  4. Cryoprecipitate infusion
  5. Prednisone, 60 to 100 mg/day


Answer 1 is not correct. Answer 3 is correct.

Key Concept: Recognize the presence of acquired clotting factor inhibitors

This patient has a bleeding problem that began in adulthood and suggests an acquired platelet or coagulation factor disorder. The prolongation of the PTT in the absence of other laboratory abnormalities suggests a problem in the intrinsic pathway of the clotting cascade. Presence of an inhibitor is confirmed by failure of the PTT to correct with a 1:1 mixing study. A factor VIII inhibitor would be the most common problem in this setting and is treated acutely with porcine factor VIII.

Question #2

A 28-year-old woman develops a rash on her legs. She has been tired for several weeks but has no other symptoms. On examination, she has a palpable spleen and lower extremity petechiae. Her platelet count is 55,000/l.

Which of the following tests is most likely to yield a diagnosis in this case?

  1. -HCG
  2. Monospot
  3. ETOH level
  4. ANA
  5. TSH


Answer 2 is correct.

Key Concept: Know the differential diagnosis of thrombocytopenia in a young woman, and recognize the importance of physical examination

Causes of thrombocytopenia in this young woman could include ITP, pregnancy, systemic lupus erythematosis, drug or alcohol use, infectious mononucleosis, HIV, varicella, Graves disease, and Hashimoto thyroiditis. Of these etiologies, only chronic ITP, chronic liver disease from alcohol abuse, and infectious mononucleosis would be accompanied by splenomegaly. In the absence of other signs of chronic liver disease, and given the patient's history, infectious mononucleosis would be the most likely diagnosis.

Question #3

A 68-year-old woman with coronary artery disease calls your nurse on Friday and reports bleeding of the gums, which is new for her. She takes baby aspirin and a beta blocker, as well as quinine for nocturnal leg cramps.

Which of the following would you advise this patient to do?

  1. Stop the quinine and make an appointment if the bleeding continues
  2. Make an urgent appointment for today for further evaluation
  3. See her dentist
  4. Stop the aspirin and make an appointment if the bleeding continues
  5. Make an appointment on Monday for further evaluation


Answer 1 is not correct. Answer 2 is correct.

Key Concept: Recognize the spectrum of drug-induced thrombocytopenia

Although most drug-induced thrombocytopenia is mild and rarely causes clinically significant bleeding, this patient warrants further evaluation. In addition to being associated with mild thrombocytopenia that resolves after discontinuance of the medication, quinine is associated with more severe thrombocytopenia, as well as hemolytic-uremic syndrome. This patient needs a further history and physical exam for evidence of bleeding; a peripheral smear to evaluate platelet count and look for microangiopathic changes; and a creatinine test.

Question #4

On routine blood studies, a 58-year-old man is found to have a platelet count of 690,000/l. He is asymptomatic and has normal red blood cell and white blood cell counts.

Which of the following would be an appropriate next step for this patient?

  1. Bone marrow biopsy to look for cause of thrombocytosis
  2. Starting aspirin, 325 mg/day
  3. Starting hydroxyurea therapy
  4. Watchful waiting for signs of bleeding or thrombosis, with serial platelet counts
  5. Starting prednisone, 30 to 60 mg/day


Answer 1 is not correct. Answer 4 is correct.

Key Concept: Recognize essential thrombocytosis and indications for therapy

The diagnosis of essential rather than reactive thrombocytosis is suggested in this patient by the absence of symptoms and the normal red and white blood cell counts. Bone marrow biopsy is not necessary. Aspirin should be initiated for symptoms such as digital discomfort but is not used routinely to prevent thrombosis and can promote bleeding in patients without symptoms. Hydroxyurea is used in symptomatic patients as well, and there is no threshold platelet count at which it is started in the absence of symptoms. Prednisone is not used in this disease.

Question #5

A 67-year-old woman has known chronic idiopathic thrombocytopenic purpura (ITP). In association with an upper respiratory tract infection, she develops gingival bleeding and has a platelet count of 25,000/l. She is treat-ed as an outpatient with prednisone, and her symptoms resolve. Five weeks after completing the prednisone, she remains asymptomatic and has a platelet count of 40,000/l.

Which of the following treatments would you choose for this patient at this time?

  1. Retreatment with prednisone to maintain a platelet count > 50,000/l
  2. Splenectomy
  3. Azathioprine
  4. IGIV
  5. Watchful waiting for bleeding episodes and intermittent platelet counts to ensure a level > 20,000/l


Answer 1 is not correct. Answer 5 is correct.

Key Concept: Understand treatment for chronic ITP

While children usually have acute ITP, the course is more likely to be chronic in adults. Exacerbations can occur at times of emotional stress, during viral illness, or with the development or worsening of other medical problems.

Prednisone is useful in acute exacerbations, and IGIV can be added in this setting if the patient has significant bleeding or sufficiently low platelet counts (< 20,000/l) to be at risk of intracranial hemorrhage. Splenectomy is very successful for producing remissions in patients who require prednisone between episodes, and azathioprine is reserved for splenectomized patients who remain steroid dependent or who cannot take steroids. In the absence of bleeding, there is no reason to increase this patient's platelet count to greater than 50,000/l.

Question #6

A 57-year-old man presents for evaluation of impotence. He is diabetic and complains of symptoms consistent with peripheral neuropathy. You decide that his symptoms are consistent with hemochromatosis.

Which of the following diagnostic tests should you order for this patient?

  1. Plasma ferritin
  2. Liver biopsy
  3. Transferrin saturation
  4. Bone marrow biopsy
  5. None of the above, because the patient's symptoms are not suggestive of hemochromatosis


Answer 1 is not correct. Answer 3 is correct.

Key Concept: Understand the best screening test for hemochromatosis

Hemochromatosis is a common, underdiagnosed, hereditary disease. In the United States, approximately 0.5% of the population is homozygous for this disorder. Hypogonadism, type II diabetes, and peripheral neuropathy are common presenting symptoms. Although a liver biopsy is the most definitive method for assessing the parenchymal iron overload characteristic of hemochromatosis, it is invasive and carries risk to the patient. Transferrin saturation is the best screening test for hemochromatosis. Values greater than 50% to 60% should prompt further investigation. Plasma ferritin provides a good indication of total body iron stores but may be elevated in a number of inflammatory, infectious, and malignant conditions. Bone marrow iron stores do not reflect parenchymal iron overload and therefore are not useful in the diagnosis of hemochromatosis.

Question #7

The man in Question 6 is diagnosed with hemochromatosis and begins phlebotomy.

What are your treatment goals for this patient?

  1. Continue phlebotomy until the cirrhosis seen on original liver biopsy has resolved
  2. Continue phlebotomy to maintain normal transferrin saturation and a ferritin level < 50 g/L
  3. Continue phlebotomy at an interval such that the hematocrit remains below 35
  4. Because the patient has too many complications of hemochromatosis, treatment will not change the course of his disease
  5. Because there is no effective treatment for hemochromatosis, educate the patient about the genetic aspects of the disease and screen his family for early detection


Answer 1 is not correct. Answer 2 is correct.

Key Concept: Understand the goals of therapy for hemochromatosis

Phlebotomy, removal of excess iron, is indicated in almost all patients with hemochromatosis. Appropriate phlebotomy can help slow the progression of the disease, preventing further complications. If the patient has cirrhosis at the time of diagnosis, the risk of hepatocellular carcinoma is not changed by phlebotomy, nor will the cirrhosis resolve. The goal of treatment is to reduce iron overload and maintain normal iron stores. The patient should not be made anemic; in fact, phlebotomy should be postponed if the patient is anemic. Normal transferrin saturation and a ferritin level less than 50 g/L are reasonable goals of therapy. Education about the genetic aspects of this condition is important for all patients.

Question #8

Which of the following signs and symptoms is most specific for iron deficiency anemia?

  1. Pagophagia
  2. Angular cheilitis
  3. Pale palmar creases
  4. Terry nails
  5. Atrophic glossitis


Answer 1 is correct.

Key Concept: Recognize history and physical exam findings that are relatively specific for iron deficiency anemia

Pale palmar creases can be seen in any form of anemia. Angular cheilitis and atrophic glossitis, although clues to iron deficiency anemia, can be seen in other non-anemia-related conditions. Koilonychia (spoon nails), not Terry nails, is the nail finding that is relatively specific for iron deficiency. Pagophagia, or the desire to eat ice, is also fairly specific for iron deficiency. Other forms of pica are seen in various types of anemia.

Question #9

A 35-year-old paraplegic woman has chronic osteomyelitis of the left hip secondary to decubitus ulcers. Her hematocrit has slowly fallen over the past year to 31.

What is the best indirect test to determine the cause of this patient's anemia?

  1. Serum iron
  2. Bone marrow biopsy
  3. Ferritin
  4. Transferrin saturation
  5. Transferrin receptor assay


Answer 1 is not correct. Answer 5 is correct.

Key Concept: Understand how to differentiate anemia of chronic disease from iron deficiency anemia

This woman has a chronic inflammatory condition and may have anemia of chronic disease or iron deficiency anemia secondary to menstrual blood loss or other site of bleeding. The best test to differentiate iron deficiency from anemia of chronic disease is a bone marrow biopsy, which would show an absence of stainable iron in the marrow. However, this direct measure is not without discomfort and risk and should be used only if indirect measures fail to identify the cause of the anemia. Serum iron and transferrin saturation will be low in both anemia of chronic disease and iron deficiency, and this patient's ferritin, an acute-phase reactant, is likely to be normal or high, given her underlying condition. The transferrin receptor concentration increases in iron deficiency but not in anemia of chronic disease and would be the best initial test to differentiate the two.

Question #10

In the absence of acute inflammation, infection, or malignancy, which is the most useful indirect test for iron deficiency?

  1. Serum iron
  2. Total iron-binding capacity
  3. Ferritin
  4. Bone marrow biopsy
  5. Transferrin saturation


Answer 1 is not correct. Answer 3 is correct.

Key Concept: Understand the best screening test for iron deficiency anemia in the absence of other complicating conditions

The pattern of low serum iron, transferrin saturation, and ferritin, combined with an elevated total iron-binding capacity, is very suggestive of iron deficiency. Of these indirect tests, a ferritin level below 12 g/L is the most specific for iron deficiency. A normal or high ferritin level does not eliminate the possibility of iron deficiency, but a value below this level is virtually diagnostic. Serum iron and transferrin saturation can be low in anemia of chronic disease, and total iron-binding capacity can be elevated in other conditions. Bone marrow biopsy, a direct measure of marrow iron stores, is the best diagnostic test but should be reserved for difficult diagnostic cases.

Question #1

A 26-year-old man presents with new-onset left lower extremity swelling and pain of 6 hours' duration. He takes no medications and has no history of trauma, immobilization, or prior thrombosis. His family history is remarkable for two "blood clots" in his mother. Compression ultrasonography confirms occlusive thrombus in the left superficial femoral vein.

Which of the following is the most appropriate sequence of interventions for this patient?

  1. Start heparin and warfarin immediately, send tests for the hypercoagulable state before warfarin reaches therapeutic levels, and discontinue heparin after the international normalized ratio (INR) reaches therapeutic levels
  2. Send tests for the hypercoagulable state, then start heparin and warfarin concurrently, and discontinue heparin after 5 days' overlap
  3. Send tests for the hypercoagulable state, then start heparin and warfarin concurrently, and discontinue heparin when the INR reaches therapeutic levels
  4. Start heparin and warfarin immediately, discontinue heparin after 5 days' overlap, and evaluate for the hypercoagulable state after warfarin therapy is completed
  5. Evaluate for the hypercoagulable state, but no anticoagulation is indicated for superficial thrombophlebitis


Answer 1 is not correct. Answer 4 is correct.

Key Concept: Understand the timing of workup and duration of therapy for patients presenting with a new DVT

A 26-year-old male presenting with new-onset thrombosis and a positive family history is highly suspicious for a hereditary hypercoagulable state and should be worked up for this. Because the levels of protein C and antithrombin III can be diminished in the setting of acute thrombosis and because heparin and warfarin also alter these levels, the optimal time for the workup is after the patient has completed therapy. Exceptions to this rule include the antiphospholipid antibody syndrome, in which early diagnosis can affect therapy and disorders for which specific genotypic tests are available (e.g., factor V Leiden), which will be accurate at any time. Because the INR (prothrombin time) is heavily dependent on factor VII, which has a short half-life, it rises fairly quickly after warfarin is begun. However, therapeutic anticoagulation may take several days longer because of the persistence of factor X and prothrombin. Overlapping heparin and warfarin by 5 days is thought to limit the risk of propagation of thrombus caused by delayed therapeutic anticoagulation. The confusingly named superficial femoral vein is in fact in the deep system and warrants therapy.

Question #2

A 34-year-old woman presents with transient aphasia and mild right hemiparesis. Symptoms have lasted about an hour and are resolving at the time of the exam. Her past history is remarkable for a prior deep vein thrombosis (DVT) of the leg while she was taking oral contraceptives and for two spontaneous abortions in the second trimester. Which of the following is the most likely diagnosis for this patient?

  1. Factor V Leiden
  2. Protein C deficiency
  3. Antiphospholipid antibody syndrome
  4. Antithrombin III deficiency
  5. Prothrombin mutation 20210A


Answer 1 is not correct. Answer 3 is correct.

Key Concept: Recognize clinical features suggestive of antiphospholipid antibody syndrome

This patient presents with symptoms of transient ischemic attack, an arterial thrombotic event. Of the disorders listed, only antiphospholipid antibody syndrome frequently manifests with arterial thrombosis. A history of recurrent late fetal loss is also quite suggestive of this diagnosis.

Question #3

A 47-year-old man weighing 60 kg presents with new-onset DVT without prior risk factors. I.V. heparin is started with a 5,000-unit bolus and infusion of 1,000 units an hour. Six hours later, his partial thromboplastin time (PTT) is only 38 seconds (normal is 24 to 32). He is rebolused with 1,500 units, and his infusion is increased to 1,200 units an hour. Six hours after the change, his PTT is 42 seconds.

What is the most likely underlying disorder in this patient?

  1. Factor V Leiden
  2. Protein C deficiency
  3. Antiphospholipid antibody syndrome
  4. Antithrombin III deficiency
  5. Prothrombin mutation 20210A


Answer 1 is not correct. Answer 4 is correct.

Key Concept: Recognize the manifestation of heparin resistance as a clinical feature of antithrombin III deficiency

This patient is manifesting heparin resistance: a minimal prolongation of the PTT despite therapeutic doses of heparin. Because heparin requires antithrombin III as a cofactor, patients with significant deficiency of antithrombin III occasionally do not respond to heparin alone. These patients require addition of antithrombin III concentrate or fresh frozen plasma to achieve therapeutic short-term anticoagulation with heparin. Warfarin remains effective in the long term, as its mechanism of action is independent of antithrombin III.

Question #4

A 58-year-old woman is 2 days' status post-total hip replacement. She has been receiving subcutaneous heparin as prophylaxis for DVT. You are asked to see the patient to evaluate new-onset dyspnea. On exam, the patient is tachypneic, tachycardic, and diaphoretic. She is agitated and complains of substernal chest pain. Chest exam reveals few bibasilar crackles. Cardiac, abdominal, and extremity exams are normal except for her surgical wounds, which seem to be healing well. Labs were sent before your arrival, and the results were pH, 7.47; Paco2, 31; Po2, 65; WBC, 11,500; Hb, 11.2; HCT, 33; platelets, 54,000; prothrombin time, 14 sec; INR, 1.1; PTT, 44 sec (normal 24-32; therapeutic range for heparin, 60-80); and chemistry panel, within normal limits. ECG reveals 2 mm ST depression in leads II, III, and aVf; and chest x-ray is normal.

Which of the following is the best course of action for this patient at this point?

  1. Bolus with I.V. heparin; begin heparin infusion; and arrange for urgent coronary angiography
  2. Bolus with I.V. heparin; begin heparin infusion; and arrange for urgent ventilation-perfusion scan
  3. Switch to low-molecular-weight heparin (LMWH) subcutaneously while arranging further diagnostic testing
  4. Stop all heparin, and bolus with I.V. methylprednisolone and diphenhydramine for allergic reaction to heparin
  5. Stop all heparin, and anticoagulate with hirudin while arranging further diagnostic testing


Answer 1 is not correct. Answer 5 is correct.

Key Concept: Recognize heparin-induced thrombocytopenia, and understand appropriate therapy

This patient is status post-hip surgery and has been receiving heparin for 2 days. She now presents with a clinical scenario that suggests pulmonary embolism or myocardial ischemia, or both, as well as a platelet count of 54,000. In this setting, one should be highly suspicious of heparin-induced thrombocytopenia, which can present with venous or arterial thrombosis. While the next diagnostic test is a matter of clinical judgment, the crucial first step is discontinuing all heparin, including I.V. flushes, and initiating anticoagulation with hirudin (a potent thrombin inhibitor derived from medicinal leeches). Other alternatives would be lepirudin or danaparoid. LMWH, unfortunately, is not considered safe in the setting of heparin-induced thrombocytopenia and would not be a good alternative in this setting.

Question #5

A 68-year-old man presents with new onset of right-sided DVT without apparent risk factors. Therapy is initiated, and the possibility of underlying cancer is raised. You are consulted regarding appropriate evaluation for occult malignancy. What would you recommend for this patient?

  1. Careful history, physical exam, routine blood counts and chemistries, chest x-ray (CXR), fecal occult blood testing (FOBT), and prostate-specific antigen (PSA); if these are not revealing, no further evaluation is necessary
  2. Careful history, physical exam, routine blood counts and chemistries, CXR, FOBT, and PSA; if these are not revealing, proceed with colonoscopy
  3. Careful history, physical exam, routine blood counts and chemistries, CXR, FOBT, and PSA; if these are not revealing, proceed with CT scan of the chest, abdomen, and pelvis
  4. Careful history, physical exam, routine blood counts and chemistries, CXR, FOBT, and PSA; if these are not revealing, proceed with bone scan


Answer 1 is correct.

Key Concept: Understand the appropriate extent of a malignancy workup that should be undertaken in a patient presenting with new-onset DVT

There is a documented association between malignancy and thrombosis; in a recent prospective trial, patients with idiopathic DVT had an 8% incidence of diagnosis of cancer in the following 2 years, with an odds ratio of 2.3. However, it has never been shown that an exhaustive workup for malignancy is cost-effective or beneficial. On the basis of a recent large cohort study, it has been recommended that the evaluation of idiopathic DVT be limited to a careful history, physical exam, CXR, routine blood counts and chemistries, FOBT, and possibly PSA in men and pelvic ultrasound in women. Further studies should be directed by this initial evaluation; if it is unrevealing, then additional tests will not likely help and may produce substantial psychological stress in the patient.