HEMATOLOGY Flashcards

Question 1

Q

In a patient who presents with pallor, which of the following disorders would you consider if work-up reveals a reticulocyte index of > 2.5?

a. Aplastic Anemia
b. Hemoglobinopathy
c. Iron deficiency anemia
d. Vitamin B12 Deficiency

Answer

A

In the first branch point of the classification of anemia, a reticulocyte production index >2.5 indicates that hemolysis is most likely. A reticu¬locyte production index <2.5 indicates either a hypoproliferative anemia or maturation disorder.

The correct answer is: Hemoglobinopathy

Question 2

Q

A 47-year-old female with no known comorbidities came into your clinic because of elevated hemoglobin (165 mg/dL) and hematocrit (58%) levels found on routine blood exam. You measured her RBC mass and found out that it was elevated, but her serum EPO levels were below normal. What mutation does this patient most likely have?

a. BCR-ABL mutation
b. JAK2 mutation
c. NPM1 mutation
d. PML-RARA mutation

Answer

A

In approaching patients with polycythemia, the first step is to document the presence of an increased red cell mass using the principle of isotope dilution by administering 51Cr-labeled autologous red blood cells to the patient and sampling blood radioactivity over a 2-h period. If the red cell mass is normal (<36 mL/kg in men, <32 mL/kg in women), the patient has spurious or relative polycythemia. If the red cell mass is increased (>36 mL/kg in men, >32 mL/kg in women), serum EPO levels should be measured.

If EPO levels are low or unmeasurable, the patient most likely has polycythemia vera. A mutation in JAK2 (Val617Phe), a key member of the cytokine intracellular signaling pathway, can be found in 90–95% of patients with polycythemia vera.

The correct answer is: JAK2 mutation

Question 3

Q

How much iron is needed to replace red cells lost through senescence daily?

a. 1 mg
b. 5 mg
c. 10 mg
d. 20 mg

Answer

A

Because each milliliter of red cells contains 1 mg of elemental iron, the amount of iron needed to replace those red cells lost through senescence amounts to 20 mg/d (assuming an adult with a red cell mass of 2 L). Any additional iron required for daily red cell production comes from the diet.
Normally, an adult male will need to absorb at least 1 mg of elemental iron daily to meet needs, while females in the childbearing years will need to absorb an average of 1.4 mg/d. The amount of iron required from the diet to replace losses averages ∼10% of body iron content a year in men and 15% in women of childbearing age.

The correct answer is: 20 mg

Question 4

Q

At which stage of iron deficiency does microcytic cells first appear on peripheral blood smear?

a. Negative iron balance
b. Iron – deficient erythropoiesis
c. Iron – deficiency anemia
d. At serum ferritin of 100

Answer

A

By definition, marrow iron stores are absent when the serum ferritin level is <15 μg/L. As long as the serum iron remains within the normal range, hemoglobin synthesis is unaffected despite the dwindling iron stores. Once the transferrin saturation falls to 15–20%, hemoglobin synthesis becomes impaired. This is a period of iron-deficient erythropoiesis. Careful evaluation of the peripheral blood smear reveals the first appearance of microcytic cells, and if the laboratory technology is available, one finds hypochromic reticulocytes in circulation. Gradually, the hemoglobin begins to fall, reflecting iron-deficiency anemia. The transferrin saturation at this point is <10–15%.

The correct answer is: Iron – deficient erythropoiesis

Question 5

Q

A 28yo female patient who appeared pale and cachectic due to a fad diet came into your clinic. Work-up shows absence of marrow iron stores, serum ferritin of 17 ug/L, and total iron binding capacity of 370. RBC morphology is normal. At which stage of iron deficiency does the patient belong?

a. Normal
b. Negative iron balance
c. Iron – deficient erythropoiesis
d. Iron – deficiency anemia

Answer

A

The correct answer is: Negative iron balance

Question 6

Q

A 61yo female consulted at your clinic due to pallor and her CBC result shows a hemoglobin of 9.2 g/dL with note of microcytic and hypochromic RBCs. She complains of intermittent joint pains and has no other comorbidities. Which of the following should be first ruled out in this patient?

a. Anemia of chronic disease
b. Bone marrow aplasia
c. Peptic ulcer disease
d. Renal disease

Answer

A

A cardinal rule is that the appearance of iron deficiency in an adult male or post-menopausal female means gastrointestinal blood loss until proven otherwise. The fact that the patient complains of intermittent joint pains is also a clue that she may be taking NSAIDs that could also contribute to her peptic ulcer disease.

The correct answer is: Peptic ulcer disease

Question 7

Q

Which is the most convenient laboratory test to estimate iron stores?

a. Serum apoferritin levels
b. Serum ferritin levels
c. Serum hepcidin levels
d. Serum transferrin levels

Answer

A

Under steady-state conditions, the serum ferritin level correlates with total body iron stores; thus, the serum ferritin level is the most convenient laboratory test to estimate iron stores. The normal value for ferritin varies according to the age and gender of the individual. Adult males have serum ferritin values averaging 100 μg/L, while adult females have levels averaging 30 μg/L.

The correct answer is: Serum ferritin levels

Question 8

Q

In a patient with iron-deficiency anemia, which of the following is expected to be elevated?

a. Marrow sideroblasts
b. RBC protoporphyrin
c. Serum ferritin
d. Transferrin saturation

Answer

A

Protoporphyrin is an intermediate in the pathway to heme synthesis. Under conditions in which heme synthesis is impaired, protoporphyrin accumulates within the red cell. This reflects an inadequate iron supply to erythroid precursors to support hemoglobin synthesis. Normal values are <30 μg/dL of red cells. In iron deficiency, values >100 μg/dL are seen. The most common causes of increased red cell protoporphyrin levels are absolute or relative iron deficiency and lead poisoning.

The correct answer is: RBC protoporphyrin

Question 9

Q

In the differential diagnosis of a hypochromic, microcytic anemia, which of the following would have low serum iron, normal or increased ferritin, and a low transferrin saturation or total iron binding capacity?

a. Inflammation
b. Iron deficiency
c. Sideroblastic anemia
d. Thalassemia

Answer

A

The distinction between true iron deficiency anemia and anemia of inflammation (AI) is among the most common diagnostic problems encountered by clinicians. Usually, AI is normocytic and normochromic but is sometimes microcytic. The iron values usually make the differential diagnosis clear, as the ferritin level is normal or increased and the percent transferrin saturation and TIBC are typically below normal.

The correct answer is: Inflammation

Question 10

Q

A 35-year-old female with no known comorbidities consulted your clinic due to abdominal discomfort, mild nausea, and occasional vomiting. She notes that these symptoms started when she started taking her “vitamins.” Which of the following would be the most likely cause?

a. Ascorbic Acid
b. Calcium + Vitamin D
c. Ferrous sulfate
d. Vitamin B complex

Answer

A

Of the complications of oral iron therapy, gastrointestinal distress is the most prominent and is seen in at least 15–20% of patients. Abdominal pain, nausea, vomiting, or constipation may lead to noncompliance. Although small doses of iron or iron preparations with delayed release may help somewhat, the gastrointestinal side effects are a major impediment to the effective treatment of a number of patients.

The correct answer is: Ferrous sulfate

Question 11

Q

A 38-year-old male with chronic glomerulonephritis who is on maintenance hemodialysis had an anaphylactic reaction to parenteral iron infusion and was adequately managed. What should be done with regards to his iron supplementation?

a. Erythropoietin should be increased to compensate for the lack of iron
b. He should be shifted to oral iron therapy
c. Iron therapy is contraindicated for this patient
d. Other parenteral iron preparations maybe safely given

Answer

A

In administering any intravenous iron preparation, anaphylaxis is a concern. Anaphylaxis is much rarer with the newer preparations. The factors that have correlated with an anaphylactic-like reaction include a history of multiple allergies or a prior allergic reaction to an iron preparation.

Generalized symptoms appearing several days after the infusion of a large dose of iron can include arthralgias, skin rash, and low-grade fever. These may be dose-related, but they do not preclude the further use of parenteral iron in the patient. To date, patients with sensitivity to one iron preparation have been safely treated with other parenteral iron preparations.

The correct answer is: Other parenteral iron preparations maybe safely given

Question 12

Q

Which of the following characterizes anemia of chronic inflammation?

a. Hepcidin decreases iron absorption and release from storage sites
b. IL-1 and TNF increases the response of the erythroid marrow to EPO
c. Serum ferritin is decreased threefold over basal levels
d. The bone marrow is hyperproliferative

Answer

A

Typically, serum ferritin values increase threefold over basal levels in the face of inflammation. IL-1, acting through accessory cell release of interferon γ (IFN-γ), suppresses the response of the erythroid marrow to EPO—an effect that can be overcome by EPO administration in vitro and in vivo. In addition, tumor necrosis factor (TNF), acting through the release of IFN-β by marrow stromal cells, also suppresses the response to EPO.
Hepcidin, made by the liver, is increased in inflammation via an IL-6 mediated pathway, and acts to suppress iron absorption and iron release from storage sites. The overall result is a chronic hypoproliferative anemia with classic changes in iron metabolism.

The correct answer is: Hepcidin decreases iron absorption and release from storage sites

Question 13

Q

A 35-year-old patient went to your clinic for consult. He has poorly controlled type 2 diabetes mellitus for 8 years, and upon reviewing his laboratory results you saw that his creatinine and BUN have been constantly elevated for the past 4 years. You also noted that his latest Hemoglobin is 89 mg/dL. The patient recently had an EGD – Colonoscopy done which were normal. No masses or bleeding was noted. Which of the following is the most likely primary cause of this patient’s anemia?

a. Decreased iron absorption from the diet
b. Decreased response to EPO stimulation
c. Failure of EPO production
d. Failure to utilize iron stores

Answer

A

The anemia is primarily due to a failure of EPO production by the diseased kidney and a reduction in red cell survival. Assessment of iron status provides information to distinguish the anemia of CKD from the other forms of hypoproliferative anemia (Table 93-6) and to guide management. Patients with the anemia of CKD usually present with normal serum iron, TIBC, and ferritin levels.

The correct answer is: Failure of EPO production

Question 14

Q

A 57-year-old male was admitted due to chest pain and was managed as a case of acute coronary syndrome – ST elevation myocardial infarction. On the third hospital day, he had upper GI bleeding and his hemoglobin went down to 92 mg/dL. An esophagogastroduodenoscopy was done and bleeding was effectively controlled. What would be the best management for his anemia?

a. Repeat CBC the following day
b. Add oral iron supplement
c. Start EPO injections
d. Blood transfusion

Answer

A

In general, patients without serious underlying cardiovascular or pulmonary disease can tolerate hemoglobin levels above 7–8 g/dL and do not require intervention until the hemoglobin falls below that level. Patients with more physiologic compromise may need to have their hemoglobin levels kept above 11 g/dL. Usually, a unit of packed red cells increases the hemoglobin level by 1 g/dL.

Rational Use of Blood Products CPG page 28

The correct answer is: Blood transfusion

Question 15

Q

A new staff nurse on duty asks you how long one unit of PRBC should be transfused. You know that blood transfusion should be completed after how many hours since commencement?

a. 4 hours
b. 5 hours
c. 6 hours
d. 8 hours

Answer

A

Complete transfusion within 4 hours of commencement.

The correct answer is: 4 hours

Question 16

Q

A 55-year-old male with chronic kidney disease (CKD) secondary to diabetic nephropathy who is on maintenance hemodialysis for the past 3 years consulted your clinic. You found out that his hemoglobin level is 9.2 g/dL and is asymptomatic. You plan to start erythropoietin (EPO) together with iron therapy. What is the usual dose of EPO in patients with CKD?

a. 50-150 U/kg once a week intravenously
b. 50-150 U/kg once a week subcutaneously
c. 50-150 U/kg three times a week intravenously
d. 50-150 U/kg three times a week subcutaneously

Answer

A

In patients with CKD, the usual dose of EPO is 50–150 U/kg three times a week intravenously. Hemoglobin levels of 10–12 g/dL are usually reached within 4–6 weeks if iron levels are adequate; 90% of these patients respond.

The correct answer is: 50-150 U/kg three times a week intravenously

Question 17

Q

A 23-year-old female was admitted due to acute onset of severe pain and tenderness of the different muscles of both upper and lower extremities which last for a few hours, sometimes longer. This started when she was treated for a urinary tract infection last week. On further probing, you found out that this episode has already happened for the 5th time this year. A review of her CBC shows that her hemoglobin is 8.5 g/dL, and her RBC morphology is shown on the figure below.
What is considered the mainstay of therapy for this patient?

a. Aggressive analgesia
b. Oxygen support
c. Start hydroxyurea
d. Vigorous but careful hydration

Answer

A

Figure: The elongated and crescent-shaped red blood cells seen on this smear represent circulating irreversibly sickled cells. Target cells and a nucleated red blood cell are also seen.

The management of an acute painful crisis includes vigorous but careful hydration, thorough evaluation for underlying causes (such as infection), and aggressive analgesia administered by a standing order and/or patient-controlled analgesia (PCA) pump. The most significant advance in the therapy of sickle cell anemia has been the introduction of hydroxyurea as a mainstay of therapy for patients with severe symptoms.

Hydroxyurea (10–30 mg/kg per day) increases fetal hemoglobin and may also exert beneficial effects on RBC hydration, vascular wall adherence, and suppression of the granulocyte and reticulocyte counts; dosage is titrated to maintain a white cell count between 5000 and 8000/μL. White cells and reticulocytes may play a major role in the pathogenesis of sickle cell crisis, and their suppression may be an important side benefit of hydroxyurea therapy.

The correct answer is: Start hydroxyurea

Question 18

Q

A 48-year-old male who works in a chemical factory came in due to severe headache and dizziness. You noticed that he has a characteristic bluish-brown muddy color, but his PaO2 is 95%. What is an effective emergency therapy?

a. Ascorbic acid IM
b. Intubate patient immediately
c. Mannitol intravenously
d. Methylene blue intravenously

Answer

A

Methemoglobin is generated by oxidation of the heme iron moieties to the ferric state, causing a characteristic bluish brown muddy color resembling cyanosis. The characteristic muddy appearance of freshly drawn blood can be a critical clue. The best diagnostic test is methemoglobin assay, which is usually available on an emergency basis.

Methemoglobinemia often causes symptoms of cerebral ischemia at levels >15%; levels >60% are usually lethal. Intravenous injection of 1 mg/kg of methylene blue is effective emergency therapy. Milder cases and follow-up of severe cases can be treated orally with methylene blue (60 mg three to four times each day) or ascorbic acid (300–600 mg/d).

The correct answer is: Methylene blue intravenously

Question 19

Q

A 25-year-old female patient with B-thalassemia major was admitted to the ER due to severe anemia. You ordered blood transfusion and upon reviewing her records, you realized that she would be receiving her 7th unit of PRBC this year. Which of the following parenteral medications is also indicated?

a. Ascorbic acid
b. Deferasirox
c. Deferoxamine
d. Sodium bicarbonate

Answer

A

A unit of packed RBCs contains 250–300 mg iron (1 mg/mL). The iron assimilated by a single transfusion of 2 units of packed RBCs is thus equal to a 1- to 2-year oral intake of iron. Iron accumulates in chronically transfused patients because no mechanisms exist for increasing iron excretion: an expanded erythron causes especially rapid development of iron overload because accelerated erythropoiesis promotes excessive absorption of dietary iron. Vitamin C should not be supplemented because it generates free radicals in iron excess states. The decision to start long-term transfusion support should also prompt one to institute therapy with iron-chelating agents.
Deferoxamine (Desferal) is for parenteral use. Its iron-binding kinetics require chronic slow infusion via a metering pump. Deferasirox is an oral iron-chelating agent. Single daily doses of 20–30 mg/kg deferasirox produced reductions in liver iron concentration comparable to deferoxamine in long-term transfused adult and pediatric patients.

The correct answer is: Deferoxamine

Question 20

Q

A 72-year-old female patient who has Type 1 Diabetes Mellitus (controlled by insulin) came into your clinic for consult due to pallor. She has also been having anorexia and some paresthesia. To rule out upper GI bleeding as the cause of anemia, an esophagogastroduodenoscopy was done which showed no masses, ulcers, nor bleeding. Gastric biopsy showed atrophy of all layers of the body and fundus, with loss of glandular elements and replacement of mucous cells with a mixed inflammatory cell infiltrate.
Her hemoglobin was 8.7 g/dL with an elevated mean corpuscular volume (MCV). Which of the following should be given to the patient?
a. Cobalamin
b. Ferrous sulfate
c. Folic acid
d. Thiamine

Answer

A

PA may be defined as a severe lack of IF due to gastric atrophy. The ratio of incidence in men and women among whites is ~1:1.6, and the median age of onset is 70–80 years, with only 10% of patients being <40 years of age. The disease occurs more commonly than by chance in close relatives and in persons with other organ-specific autoimmune diseases, for example, thyroid diseases, vitiligo, hypoparathyroidism, Type 1 diabetes, and Addison’s disease. A single endoscopic examination is recommended if PA is diagnosed.

Gastric biopsy usually shows atrophy of all layers of the body and fundus, with loss of glandular elements, an absence of parietal and chief cells and replacement by mucous cells, a mixed inflammatory cell infiltrate, and perhaps intestinal metaplasia.

Replenishment of body stores should be complete with six 1000-μg IM injections of hydroxocobalamin given at 3- to 7-day intervals. More frequent doses are usually used in patients with cobalamin neuropathy, but there is no evidence that they produce a better response. Allergic reactions are rare and may require desensitization or antihistamine or glucocorticoid cover. For maintenance therapy, 1000 μg hydroxocobalamin IM once every 3 months is satisfactory.

Because a small fraction of cobalamin can be absorbed passively through mucous membranes even when there is complete failure of physiologic IF-dependent absorption, large daily oral doses (1000–2000 μg) of cyanocobalamin are used in PA for replacement (especially in Canada and Sweden) and maintenance of normal cobalamin status in, for example, food malabsorption of cobalamin.

The correct answer is: Cobalamin

Question 21

Q

Your 32-year-old female patient who is a known hypertensive recently got pregnant with her first baby. Her BP is controlled with her current medications. You advised her to also schedule an appointment with her obstetrician however the next available slot for check-up is after 4 weeks. At this point, which of the following would you give her to prevent megaloblastic anemia?

a. Folic acid 200ug OD
b. Folic acid 300ug OD
c. Folic acid 400ug OD
d. Folic acid 500ug OD

Answer

A

Folic acid, 400 μg daily, should be given as a supplement before and throughout pregnancy to prevent megaloblastic anemia and reduce the incidence of NTDs, even in countries with fortification of the diet. In women who have had a previous fetus with an NTD, 5 mg daily is recommended when pregnancy is contemplated and throughout the subsequent pregnancy.

The correct answer is: Folic acid 400ug OD

Question 22

Q

Among the causes of hemolytic anemia, which of the following is acquired and is associated with intracorpuscular defects?

a. Hemoglobinopathies
b. Hemolytic uremic syndrome
c. Microangiopathic destruction
d. Paroxysmal nocturnal hemoglobinuria

Answer

A

Hereditary causes correlate with intracorpuscular defects because these defects are due to inherited mutations; the one exception is PNH because the defect is due to an acquired somatic mutation. Similarly, acquired causes correlate with extracorpuscular factors because mostly these factors are exogenous; the one exception is familial hemolytic-uremic syndrome (HUS; often referred to as atypical HUS) because here an inherited abnormality allows complement activation to be excessive, with bouts of production of membrane attack complex capable of destroying normal red cells.

The correct answer is: Paroxysmal nocturnal hemoglobinuria

Question 23

Q

A 23 year-old-female presented with a chief complaint of left upper quadrant abdominal pain that has slowly progressed over the last two weeks. Upon examination, you noted that she has pale palpebral conjunctivae, and splenomegaly. Her laboratory results also showed elevated unconjugated bilirubin. Upon review of her laboratories, which of the following would mainly indicate that there is an erythropoietic response by the bone marrow?

a. Elevated ferritin
b. Elevated LDH
c. Elevated MCV
d. Elevated reticulocyte

Answer

A

The main sign of the erythropoietic response by the bone marrow is an increase in reticulocytes (a test all too often neglected in the initial workup of a patient with anemia). Usually the increase will be reflected in both the percentage of reticulocytes (the more commonly quoted figure) and in the absolute reticulocyte count (the more definitive parameter).

The correct answer is: Elevated reticulocyte

Question 24

Q

A 26-year-old female was admitted due to jaundice which was first noted 3 weeks prior. Physical examination shows an enlarged spleen, and ultrasound reveals the presence of gallstones. The patient was also noted to have normocytic anemia, with an elevated mean corpuscular hemoglobin concentration. Her peripheral blood smear is shown below. What is the main diagnostic test that needs to be done?

a. Electrophoresis
b. Osmotic fragility
c. Prothrombin time
d. Western blot

Answer

A

Image: Hereditary spherocytosis

In vitro studies revealed that the red cells were abnormally susceptible to lysis in hypotonic media; indeed, the presence of osmotic fragility became the main diagnostic test for Hereditary spherocytosis. The main clinical findings are jaundice, an enlarged spleen, and often gallstones; indeed, it may be the finding of gallstones in a young person that triggers diagnostic investigations. decompensation.

The anemia is usually normocytic, with the characteristic morphology that gives the disease its name. An increased mean corpuscular hemoglobin concentration (MCHC >34) on an ordinary blood count report should raise the suspicion of HS, because HS is almost the only condition in which this abnormality occurs.

The correct answer is: Osmotic fragility

Question 25

Q

A 38-year-old female with G6PD deficiency came into your clinic with a chief complaint of dysuria for 5 days. She has no history of fever. A urinalysis done shows pus of 20-30. Which of the following antibiotics could be safely given?

a. Ciprofloxacin
b. Co-amoxiclav
c. Cotrimoxazole
d. Nitrofurantoin

Answer

A

The correct answer is: Co-amoxiclav

Question 26

Q

A 32-year-old female patient with SLE was admitted due to dyspnea and cough and was managed as a case of community-acquired pneumonia. Piperacillin-tazobactam was started and on the third hospital day, her condition was improving. On the fourth hospital day, she started to complain of abdominal pain and developed jaundice. Physical examination shows pale palpebral conjunctivae, icteric sclerae, and an enlarged spleen.

Coombs test turned out positive with the presence of IgG, and her hemoglobin has gone down to 5.5 g/dL from a baseline of 12.4 g/dL upon admission. Which of the following interventions should be done?

a. Perform splenectomy STAT
b. Start Prednisone (1 mg/kg per day)
c. Start Rituximab (anti-CD20)
d. Transfuse ABO-matched but incompatible blood

Answer

A

Auto-immune hemolytic anemia: The onset is often abrupt and can be dramatic. The hemoglobin level may drop, within days, to as low as 4 g/dL; the massive red cell removal will produce jaundice; and sometimes the spleen is enlarged. When this triad is present, the suspicion of AIHA must be high. Severe acute AIHA can be a medical emergency. The immediate treatment almost invariably includes transfusion of red cells.

This may pose a special problem because many or all of the blood units cross-matched may be incompatible. In these cases, it is often correct, if paradoxical, to transfuse ABO-matched but incompatible blood: the rationale being that the transfused red cells will be destroyed no less—but no more—than the patient’s own red cells, and in the meantime the patient stays alive.

Whenever the anemia is not immediately life threatening, blood transfusion should be withheld (because compatibility problems may increase with each unit of blood transfused), and medical treatment started immediately with prednisone (1 mg/kg per day), which will produce a remission promptly in at least one-half of patients. Rituximab (anti-CD20), previously regarded as second-line treatment, is increasingly being used at a relatively low dose together with prednisone as part of first-line treatment.

For patients who do relapse or are refractory to medical treatment, one may have to consider splenectomy: this procedure does not cure the disease, but it can produce significant benefit by removing a major site of hemolysis, thus improving the anemia and/or reducing the need for other therapies (e.g., the dose of prednisone); of course splenectomy is not free of risk, as it entails increased risk of sepsis and of thrombosis.

The correct answer is: Transfuse ABO-matched but incompatible blood

Question 27

Q

A 27-year-old male patient came into your clinic due to one episode of urinating “blood” instead of urine in the morning. He has no other symptoms nor comorbidities and physical examination is unremarkable. His CBC shows pancytopenia. You referred him to a hematologist who did a flow cytometry which showed absence of CD59 and CD55 on his red blood cells. Which of the following is mandatory as part of his supportive treatment?

a. Anticoagulant prophylaxis
b. Ferrous sulfate
c. Folic acid
d. Long term glucocorticoids

Answer

A

This is a classic case of paroxysmal nocturnal hemoglobinuria to which the management by supportive treatment is very important. Folic acid supplements (at least 3 mg/d) are mandatory; the serum iron should be checked periodically, and iron supplements should be administered as appropriate. Transfusion of filtered red cells should be used whenever necessary, which, for some patients, means quite frequently.

Long-term glucocorticoids are not indicated because there is no evidence that they have any effect on chronic hemolysis; in fact, they are contraindicated because their side effects are considerable. A short course of prednisone may be useful when an inflammatory process exacerbates hemolysis. Any patient who has had venous thrombosis or who has a genetically determined thrombophilic state in addition to PNH should be on regular anticoagulant prophylaxis.

The correct answer is: Folic acid

Question 28

Q

A 31-year-old female patient who was managed as a case of ruptured ectopic pregnancy at the ER was referred to you by OB for the management of shock. Her BP was 60 palpatory, heart rate was 114 bpm, and respiratory rate was 21. You saw that her hemoglobin result was 11.9 g/dL. What is the next step?

a. Correct hypovolemia and repeat CBC
b. Investigate and resolve the source of the bleeding
c. Start broad-spectrum antibiotics
d. Start IV crystalloids since plasma may interfere with hemostasis

Answer

A

As an emergency response, baroreceptors and stretch receptors will cause release of vasopressin and other peptides, and the body will shift fluid from the extravascular to the intravascular compartment, producing hemodilution; thus, the hypovolemia gradually converts to anemia.

In an acute hemorrhage situation, plasma may be preferred to saline for volume expansion since dilution of clotting factors with crystalloid may interfere with hemostasis.

The correct answer is: Correct hypovolemia and repeat CBC

Question 29

Q

Which of the following entities may present with pancytopenia and is associated with a hypocellular bone marrow?

a. Aplastic anemia
b. Hairy cell leukemia
c. HIV infection
d. Myelofibrosis

Answer

A

The correct answer is: Aplastic anemia

Question 30

Q

A 26-year-old female patient was admitted due to pallor. She feels apparently well but has petechiae and ecchymoses all throughout her body. She has no lymphadenopathy nor splenomegaly. Bone marrow aspirate shows mainly fat under the microscope. The mother asks you about the patient’s prognosis. You tell her that the major prognostic determinant is the:

a. Blood count result
b. Bone marrow biopsy result
c. Patient’s signs and symptoms
d. Presence of lymphadenopathy or splenomegaly

Answer

A

This is a case of aplastic anemia. The major prognostic determinant is the blood count. Severe disease historically has been defined by the presence of two of three parameters: absolute neutrophil count <500/μL, platelet count <20,000/μL, and corrected reticulocyte count <1% (or absolute reticulocyte count <60,000/μL).

The correct answer is: Blood count result

Question 31

Q

A 27-year-old female patient was admitted due to pallor. She was then diagnosed to have severe aplastic anemia later in the disease course. Which of the following would be the best treatment for this patient?

a. Erythropoietin and G-CSF injections
b. Hematopoietic stem cell transplant
c. Systemic glucocorticoids
d. Transfusion of compatible blood from family members

Answer

A

HSCT is the best therapy for the younger patient with a fully histocompatible sibling donor. Glucocorticoids are not of value as primary therapy. In transplant candidates, transfusion of blood from family members should be avoided so as to prevent sensitization to histocompatibility antigens. Hematopoietic growth factors (HGFs) such as erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) are not effective in aplastic anemia, probably because endogenous blood levels in patients are extremely high.

The correct answer is: Hematopoietic stem cell transplant

Question 32

Q

A 37-year-old-male was admitted due to pallor. He also has tenderness and pain in the joints of the distal lower and upper extremities for 3 weeks. He has no other known comorbidities. On physical exam, he had pale palpebral conjunctivae, anicteric sclerae, no lymphadenopathies, no palpable masses on the abdomen. His joints felt warm but were not swollen. The rest of the physical exam was unremarkable. His laboratories show a hemoglobin of 7.2 g/dL, WBC and platelet counts are normal, and ANA is normal.

A bone marrow biopsy was done and revealed the presence of giant pronormoblasts. Which of the following treatment should be given?

a. Azathioprine
b. Cyclophosphamide
c. Cyclosporine
d. IVIg therapy

Answer

A

The presence of giant pronormoblast in a background of red cell aplasia on bone marrow biopsy is the cytopathic sign of B19 parvovirus infection. For persistent B19 parvovirus infection, almost all patients respond to intravenous immunoglobulin therapy. The majority of patients with idiopathic PRCA respond favorably to immunosuppression: glucocorticoids, cyclosporine, ATG, azathioprine, and cyclophosphamide are effective.

The correct answer is: IVIg therapy

Question 33

Q

A 43-year-old patient was admitted due to anemia and had an admitting impression of myelodysplatic syndrome (MDS). A clinical clerk rotating in internal medicine asks you about MDS. Which of the following will you teach him?

a. Fever and weight loss usually point to a myelodysplastic process
b. MDS is a disease of young adults, with a mean age of onset at 40 years old
c. No single characteristic feature of marrow morphology distinguishes MDS
d. Therapy-related MDS portends a good prognosis

Answer

A

MDS is a disease of the elderly; the mean age at onset is older than 70 years. Fever and weight loss should point to a myeloproliferative rather than myelodysplastic process. No single characteristic feature of marrow morphology distinguishes MDS, but the following are commonly observed: dyserythropoietic changes (especially nuclear abnormalities) and ringed sideroblasts in the erythroid lineage; hypogranulation and hyposegmentation in granulocytic precursors, with an increase in myeloblasts; and megakaryocytes showing reduced numbers of or disorganized nuclei.
The number of blasts, and marrow fibrosis are all poor prognostic indicators. The outlook in therapy related MDS, regardless of type, is extremely poor, and most patients will progress within a few months to refractory AML.

The correct answer is: No single characteristic feature of marrow morphology distinguishes MDS

Question 34

Q

A 32-year-old female was admitted due to abdominal pain and jaundice for 2 weeks. History reveals no fever but claims that she has intermittent episodes of erythema and burning pain on the the extremities. Physical examination reveals hepatomegaly and splenomegaly. Further work-up shows leukocytosis and thrombocytosis, hepatitis profile is negative, but her imaging studies shows hepatic venous thrombosis. Which of the following should be done to establish the diagnosis?

a. Bone marrow biopsy
b. Cytogenetic analysis
c. JAK2 V617F assay
d. Liver biopsy

Answer

A

This case represents Polycythemia Vera. Hepatic venous thrombosis (Budd-Chiari syndrome) is particularly common in young women and may be catastrophic if sudden and complete obstruction of the hepatic vein occurs. Indeed, PV should be suspected in any patient who develops hepatic vein thrombosis. Erythema, burning, and pain in the extremities, a symptom complex known as erythromelalgia, is another complication of thrombocytosis in PV due to increased platelet stickiness. Today, however, the assay for JAK2 V617F has superseded other tests for establishing the diagnosis of PV.

The correct answer is: JAK2 V617F assay

Question 35

Q

Which of the following symptoms distinguish polycythemia vera (PV) from other causes of erythrocytosis?

a. Aquagenic pruritus
b. Erythromelalgia
c. Ocular migraine
d. No symptom is specific for PV

Answer

A

With the exception of aquagenic pruritus, no symptoms distinguish PV from other causes of erythrocytosis.

The correct answer is: Aquagenic pruritus

Question 36

Q

A 27-year-old female patient with polycythemia vera was admitted for her periodic phlebotomy. What is the target hemoglobin level to avoid thrombotic complications in this patient?

a. < 140 g/L
b. < 130 g/L
c. < 120 g/L
d. < 110 g/L

Answer

A

Thrombosis due to erythrocytosis is the most significant complication and often the presenting manifestation; maintenance of the hemoglobin level at ≤140 g/L (14 g/dL; hematocrit <45%) in men and ≤120 g/L (12 g/dL; hematocrit <42%) in women is mandatory to avoid thrombotic complications. Phlebotomy serves initially to reduce hyperviscosity by reducing the red cell mass to normal while further expanding the plasma volume.

The correct answer is: < 120 g/L

Question 37

Q

A 35-year-old male patient consulted due to abdominal pain which started 2 months prior, with progressively increasing severity. Physical examination shows that the abdomen is distended with massive splenomegaly and mild hepatomegaly. Blood counts show hemoglobin of 8.2 g/dL and leukocytes of 27,000 /uL. A peripheral blood smear was done (see figure below).

A bone marrow biopsy showed hypercellularity with increased megakaryocytes with large dysplastic nuclei. Bone marrow transplantation was offered however the patient refused due to lack of funds and donor. Which of the following is effective in reducing splenomegaly and alleviating constitutional symptoms in this patient while also prolonging survival?

a. Prednisone
b. Ruxolitinib
c. Splenectomy
d. Thalidomide

Answer

A

Figure: Teardrop-shaped red blood cells indicative of membrane damage from passage through the spleen, a nucleated red blood cell, and immature myeloid cells indicative of extramedullary hematopoiesis are noted. This peripheral blood smear is related to any cause of extramedullary hematopoiesis.

This represents a case of Primary Myelofibrosis. A blood smear will show the characteristic features of extramedullary hematopoiesis: teardrop-shaped red cells, nucleated red cells, myelocytes, and promyelocytes; myeloblasts may also be present. The JAK2 inhibitor, ruxolitinib, has proved effective in reducing splenomegaly and alleviating constitutional symptoms in a majority of advanced PMF patients while also prolonging survival, although it does not significantly influence the JAK2 V617F neutrophil allele burden. Allogeneic bone marrow transplantation is the only curative treatment for PMF and should be considered in younger patients and older patients with high risk disease.

The correct answer is: Ruxolitinib

Question 38

Q

A 21-year-old male patient consulted due to a 2-month history of fatigue, anorexia, and weight loss. He had a history of stage 2 germ cell tumor 2 years prior which was treated with orchiectomy and chemotherapy. Physical examination revealed mild hepatomegaly, splenomegaly, but no testicular mass or lymphadenopathies. CBC showed mild normocytic, normochromic anemia, leukocyte of 16,000/uL, and platelet count of 110,000/uL. You suspected a diagnosis of Acute Myeloid Leukemia probably secondary to previous chemotherapy. To establish this diagnosis, the marrow or blood blast count should generally be?

a. > 5%
b. > 10%
c. > 20%
d. > 30%

Answer

A

Marrow (or blood) blast count of ≥20% is required to establish the diagnosis of AML, except for AML with the recurrent genetic abnormalities t(15;17), t(8;21), inv(16), or t(16;16).

The correct answer is: > 20%

Question 39

Q

In a patient being treated for Acute Myeloid Leukemia, which of the following portends a relatively good prognosis?

a. AML 2o to chemotherapy for other malignancies
b. High presenting leukocyte count
c. Presence of cytopenia upon diagnosis
d. t(15;17) cytogenetic rearrangement

Answer

A

Patients with t(15;17) have a very good prognosis (~85% cured). Cytopenia is a clinical feature associated with a lower complete remission (CR) rate and shorter survival time. AML developing after treatment with cytotoxic agents for other malignancies is usually difficult to treat successfully. Other factors independently associated with worse outcome are a poor performance status that influences ability to survive induction therapy and a high presenting leukocyte count that in some series is an adverse prognostic factor for attaining a CR.

The correct answer is: t(15;17) cytogenetic rearrangement

Question 40

Q

A 62-year-old male patient is currently admitted for generalized fatigue with intermittent fever and diaphoresis for 1 month. Physical examination shows clear breath sounds, with mild hepatomegaly and splenomegaly. CBC shows mild anemia, leukocytosis, and thrombocytopenia. Chest x-ray shows the absence of infiltrates. His peripheral blood smear shows this image.

What is the most likely diagnosis?

a. Acute myeloid leukemia
b. Chronic myeloid leukemia
c. Essential thrombocytosis
d. Polycythemia vera

Answer

A

Figure: Leukemic myeloblast containing an Auer rod.
In AML, the cytoplasm often contains primary (nonspecific) granules, and the nucleus shows fine, lacy chromatin with one or more nucleoli characteristic of immature cells. Abnormal rod-shaped granules called Auer rods are not uniformly present, but when they are, AML is virtually certain.

The correct answer is: Acute myeloid leukemia

Question 41

Q

A 39-year-old female patient diagnosed to have acute myeloid leukemia is currently admitted for chemotherapy. Upon seeing her at the ER, she gives you her recently cytogenetic analysis results which shows t(15;17)(q22;q12) cytogenetic rearrangement with the PML-RARA fusion product. Which of the following has been shown to dramatically improve prognosis for this patient?

a. Cytarabine
b. Daunorubicin
c. Tretinoin
d. Hydroxyurea

Answer

A

This describes a case of acute promyelocytic leukemia (APL). The prognosis of APL patients has changed dramatically with the introduction of tretinoin (ATRA), an oral drug that induces the differentiation of leukemic cells bearing the t(15;17), where disruption of the RARA gene encoding a retinoid acid receptor occurs.

The correct answer is: Tretinoin

Question 42

Q

A 61 year-old-male was admitted with a chief complaint of generalized fatigue for almost 2 months which was accompanied by weight loss and early satiety. Physical examination showed pale palpebral conjunctivae, clear breath sounds, no abdominal pain or masses noted. He then mentions to you that he was seen by a hematologist before and shows you a cytogenetic analysis result which reveals translocation between the long arms of chromosome 9 and 22. What would be your treatment of choice?

a. ATRA
b. Cytarabine
c. Hydroxyurea
d. Imatinib

Answer

A

The t(9;22)(q34.1;q11.2) is present in >90% of classical CML cases. With TKI therapy, the estimated 10-year survival in CML is 85%. Imatinib 400 mg orally daily, nilotinib 300 mg orally twice a day (on an empty stomach), dasatinib 100 mg orally daily, and bosutinib 400 mg orally daily are approved for frontline therapy of CML.

The correct answer is: Imatinib

Question 43

Q

In patients with chronic myeloid leukemia, what is the most common physical finding?

a. Hepatomegaly
b. Lymphadenopathy
c. Pallor
d. Splenomegaly

Answer

A

Splenomegaly is the most common physical finding, occurring in 20–70% of patients depending on health care screening frequency. Other less common findings include hepatomegaly (5–10%), lymphadenopathy (5–10%), and extramedullary disease (skin or subcutaneous lesions).

The correct answer is: Splenomegaly

Question 44

Q

A 62-year-old male patient diagnosed with chronic myeloid leukemia, on maintenance treatment, was admitted due to fever, generalized body malaise, and loss of appetite. CBC showed anemia, leukocytosis, and increased blasts and basophils. Which of the following would suggest progression to accelerated phase of CML?

a. Hemoglobin of 8.5 g/dL
b. Peripheral basophils 15%
c. Peripheral blasts 10%
d. Platelet count of 90 x 109/L

Answer

A

Criteria of accelerated-phase CML, historically associated with median survival of <1.5 years, include the presence of 15% or more peripheral blasts, 30% or more peripheral blasts plus promyelocytes, 20% or more peripheral basophils, cytogenetic clonal evolution (presence of chromosomal abnormalities in addition to Ph), and thrombocytopenia < 100 x 109/L (unrelated to therapy).

The correct answer is: Platelet count of 90 x 109/L

Question 45

Q

What is the main therapeutic endpoint in the management of CML and is usually measured by 12 months of imatinib therapy?

a. Complete cytogenetic response
b. Disappearance of signs / symptoms
c. Improved functional capacity
d. Normalization of CBC parameters

Answer

A

Achievement of complete cytogenetic response by 12 months of imatinib therapy and its persistence later, the only consistent prognostic factor associated with survival, is now the main therapeutic endpoint in CML. Failure to achieve a complete cytogenetic response by 12 months or occurrence of later cytogenetic or hematologic relapse are considered as treatment failure and an indication to change therapy.

The correct answer is: Complete cytogenetic response

Question 46

Q

A 32-year-old female comes to your clinic for a wellness check -up. She was diagnosed with acute lymphoid leukemia 5 years ago and is currently in remission. You review her laboratory results knowing that she will still be in complete hematologic remission when the blast cells in her marrow is:

a. <3%
b. <5%
c. <10%
d. <20%

Answer

A

The correct answer is: <5%

Question 47

Q

A 55-year-old male with no known comorbidities and is asymptomatic came in for consult because of his CBC results that revealed a normal WBC with a differential count showing lymphocytosis. You then found out that his paternal uncle has a history of chronic lymphocytic leukemia. What would be your next diagnostic step?

a. Bone marrow aspiration and biopsy
b. CT scan of the chest, abdomen, and pelvis
c. Flow cytometry on the peripheral blood
d. Serum protein electrophoresis studies

Answer

A

CLL is one of the most familial-associated malignancies, and the first-degree relative of a CLL patient has an 8.5-fold elevated risk of developing CLL than the general population.

CLL is most commonly diagnosed on routine blood work demonstrating an elevated lymphocyte count in asymptomatic individuals, although some patients present with symptoms and require early therapy. When noting either an elevated total white blood cell (WBC) count with lymphocytic predominance or a normal WBC with a differential showing a lymphocytosis, the next step is to perform flow cytometry on the peripheral blood.

In CLL, this will reveal the typical immunophenotype that includes the typical B-cell markers CD19, CD20, CD22, CD23, the T-cell marker CD5 (CD5 is also expressed on the B1 subset of B cells that typically has unmutated immunoglobulin and responds to antigens independent of cognate T-cell help), and dim surface immunoglobulin of either kappa or lambda type.

The correct answer is: Flow cytometry on the peripheral blood

Question 48

Q

To prevent morbidity and death from infectious complications in patients with chronic lymphocytic leukemia, which of the following is recommended?

a. Pneumococcal vaccine should be avoided because adequate immune response is poor (58% in one study)
b. Prophylactic IVIg has been shown to improve survival and decrease bacterial infections in patients with hypogammaglobulinemia
c. Prophylaxis for Pneumocystis pneumonia is indicated for at least 6 months following therapy to allow recovery of functional T cells
d. Varicella zoster vaccine is recommended due to the risk of viral reactivation in immunocompromised host

Answer

A

Infections are a leading cause of both disease-related morbidity and death in patients with CLL, with ~30–50% of deaths in CLL patient attributed to infection. For many nucleoside analog-based chemotherapy regimens used in CLL, prophylaxis for Pneumocystis pneumonia is indicated for at least 6 months following therapy to allow recovery of functional T cells. Because of the abnormalities in cellular and humoral immunity, vaccine responses in CLL are limited in many patients, especially in the later stages of disease. In one study, one dose of 13-valent pneumococcal vaccine produced an adequate immune response in only 58% of patients compared with 100% in age-matched controls.

Despite the known limitations, vaccination against influenza and pneumococcal pneumonia is recommended in CLL. Live vaccines, such as the varicella zoster vaccine, should be avoided because of the small risk of viral reactivation with an immunocompromised host. While administration of prophylactic intravenous immunoglobulin (IVIg) has not been shown to improve survival, it has been shown to reduce the number of minor or moderate bacterial infections, and thus is indicated in patients with hypogammaglobulinemia who suffer from recurrent infections or have pulmonary bronchiectasis.

The correct answer is: Prophylaxis for Pneumocystis pneumonia is indicated for at least 6 months following therapy to allow recovery of functional T cells

Question 49

Q

A 62-year-old male patient with chronic lymphocytic leukemia arrives at the emergency department with a chief complaint of intermittent fever for 1 month. This was accompanied by fatigue, weight loss, night sweats, and a rapidly progressive lymphadenopathies at the cervical area. You suspect Richter’s transformation. What would be the first diagnostic step?

a. Bone marrow aspiration biopsy
b. Peripheral blood smear
c. 18FDG -PET/CT scan
d. Needle biopsy of the cervical lymphadenopathy

Answer

A

Clinical signs of Richter’s transformation include rapid progression in adenopathy, often in a specific area, and constitutional symptoms including fatigue, night sweats, fever, and weight loss. LDH is usually high. In suspected cases, the first step is 18FDG-PET/CT (fluorodeoxyglucose– positron emission tomography combined with computed tomography) scan to localize an area for biopsy. Standardized uptake values (SUV) <5 is consistent with CLL and can rule out Richter’s transformation in many cases. SUV >5 are suspicious for Richter’s transformation, with SUV ≥10 very concerning. Excisional biopsy is diagnostic. Needle biopsy should be discouraged.

The correct answer is: 18FDG -PET/CT scan

Question 50

Q

Which of the following clinical indications does the use of G-CSF in patients undergoing chemotherapy have no benefit?

a. Patient has pre-existing neutropenia or active infection
b. Patients with poor performance status
c. Probability of febrile neutropenia is > 10%
d. If prolonged neutropenia (even without fever) delays therapy

Answer

A

The correct answer is: Probability of febrile neutropenia is > 10%

Question 51

Q

What is the most common cause of thrombocytopenia (eHPIM 20TH ED p. 823)?

a. Drug-induced thrombocytopenia
b. Infection-induced thrombocytopenia
c. Idiopathic immune thrombocytopenia
d. Congenital thrombocytopenia

Answer

A

The correct answer is: Drug-induced thrombocytopenia

Question 52

Q

Which of the following patients with thrombocytopenia and respective peripheral blood smear findings would warrant a bone marrow biopsy?

a. A 28-year-old pregnant patient with findings of helmet cells and basophilic red blood cells
b. A 39-year-old woman being treated with ceftriaxone for bacterial pneumonia with zero platelets on high power field
c. A 50-year-old man with mucocutaneous bleeding and with giant platelets
d. A 68-year-old man with fatigue and petechiae with macrocytes and platelets of varying size

Answer

A

A. A 28-year-old pregnant patient with findings of helmet cells and basophilic red blood cells (schistocytes sine qua non for TTP, eHPIM 20TH ED pp. 826-827)
B. A 39-year-old woman being treated with ceftriaxone for bacterial pneumonia with zero platelets on high power field (drug-induced thrombocytopenia, hold causative agent first, Table 111-1, eHPIM 20TH ED p. 823-824)
C. A 50-year-old man with mucocutaneous bleeding and with giant platelets (ITP, eHPIM 20TH ED p. 825)
D. A 68-year-old man with fatigue and petechiae with macrocytes and platelets of varying size (can be MDS - needs BMA, eHPIM 20TH ED p. 823)

The correct answer is: A 68-year-old man with fatigue and petechiae with macrocytes and platelets of varying size

Question 53

Q

A 76-year-old female had total hip replacement and has been on heparin anticoagulation for the past 7 days. She developed left leg pain, swelling, warmth and tenderness. Lower extremity duplex scan revealed acute thrombosis in the left common femoral and superficial femoral veins. Her platelet count dropped by 50% from baseline. Which of the following is true regarding this condition (eHPIM 20TH ED p. 825)?

a. Most patients develop this condition 7-21 days following first exposure to the drug
b. Thrombocytopenia is not usually severe, with platelet counts usually above 20,000 / uL
c. This condition is associated with bleeding as much as with thrombosis
d. The frequency is higher with low molecular weight heparin than with unfractionated heparin

Answer

A

Drug-induced thrombocytopenia due to heparin differs from that seen with other drugs in two major ways.
1. The thrombocytopenia is not usually severe, with nadir counts rarely <20,000/μL.
2. Heparin-induced thrombocytopenia (HIT) is not associated with bleeding and, in fact, markedly increases the risk of thrombosis.
HIT can occur after exposure to low-molecular-weight heparin (LMWH) as well as unfractionated heparin (UFH), although it is more common with the latter. Most patients develop HIT after exposure to heparin for 5–14 days.

The “4T’s” have been recommended to be used in a diagnostic algorithm for HIT:
• thrombocytopenia,
• timing of platelet count drop,
• thrombosis and other sequelae such as localized skin reactions,
• and other causes of thrombocytopenia not evident.
Application of the 4T scoring system is very useful in excluding a diagnosis of HIT but will result in over-diagnosis of HIT in situations where thrombocytopenia and thrombosis due to other etiologies are common, such as in the intensive care unit.

The correct answer is: Thrombocytopenia is not usually severe, with platelet counts usually above 20,000 / uL

Question 54

Q

In the 76-year-old female patient who underwent total hip replacement and developed lower extremity DVT despite being on heparin anticoagulation for the past 7 days, which test strongly associates with the condition when positive (eHPIM 20TH ED p. 825)?

a. ELISA with PF4/polyanion complex as the antigen
b. ELISAs specific for IgG
c. Heparin induced platelet aggregation assay
d. 14 C-Serotonin release assay

Answer

A

LABORATORY TESTING FOR HIT
• ELISA with PF4/polyanion complex as the antigen – most widely available; low specificity for HIT
• IgG-specific ELISAs - increased specificity but may decrease sensitivity
• Platelet activation assay, most commonly the serotonin release assay - lower sensitivity but higher specificity than the ELISA.
• However, HIT remains a clinical diagnosis.

The correct answer is: 14 C-Serotonin release assay

Question 55

Q

Which is true regarding management of patients with HIT (eHPIM 20TH ED p. 825)?

a. Common complications of thrombosis and bleeding may occur even after discontinuation of causative agent
b. Stopping the anticoagulant and switching to the other form of heparin will prevent complications
c. Argatroban is effective and indicated for prevention and treatment of thrombotic events
d. Patients with higher anti-heparin/PF4 antibody titers may have a higher risk of bleeding

Answer

A

Heparin-induced thrombocytopenia (HIT) is not associated with bleeding and, in fact, markedly increases the risk of thrombosis.

Patients requiring anticoagulation should be switched from heparin to an alternative anticoagulant. HIT antibodies cross-react with LMWH, and these preparations should not be used in the treatment of HIT.

The direct thrombin inhibitor (DTI) argatroban is effective in HITT.

Patients with higher anti-heparin/PF4 antibody titers may have a higher risk of thrombosis.

The correct answer is: Argatroban is effective and indicated for prevention and treatment of thrombotic events

Question 56

Q

The 45-year-old female who developed thrombocytopenia while on heparin, with high anti-heparin/PF4 antibody titers, is now being prepared for discharge. Her current platelet count is 155,000/uL, and her lower extremity duplex studies are clear. Which of the following is recommended when initiating warfarin as anticoagulation (eHPIM 20TH ED p. 825)?

a. Overlap warfarin with the other form of heparin other than the one that caused her condition
b. Fondaparinux should not be used together with warfarin
c. She may take warfarin for a few days to a month
d. Rivaroxaban is an established alternative to warfarin in this scenario

Answer

A

Because of the high rate of thrombosis in patients with HIT, anticoagulation should be considered, even in the absence of thrombosis. In patients without thrombosis, the duration of anticoagulation needed is undefined. An increased risk of thrombosis is present for at least 1 month after diagnosis; however, most thromboses occur early, and whether thrombosis occurs later if the patient is initially anticoagulated is unknown. Options include continuing anticoagulation until a few days after platelet recovery or for 1 month.

Introduction of warfarin alone in the setting of HIT or HITT may precipitate thrombosis, particularly venous gangrene, presumably due to clotting activation and severely reduced levels of proteins C and S. Warfarin therapy, if started, should be overlapped with a DTI or fondaparinux and started after resolution of the thrombocytopenia and lessening of the prothrombotic state.

Evidence for use of an oral direct Xa inhibitor in this setting is growing, but more data are needed to establish efficacy.

The correct answer is: She may take warfarin for a few days to a month

Question 57

Q

A 23-year-old lady came in for pre-employment check-up. Other than occasional gum bleeding, her history and physical examination were essentially normal. Her CBC showed platelet count of 25,000 / uL, with no other notable abnormalities. Which of the following diagnostic test result is expected for this patient (eHPIM 20TH ED p. 825 – 826)?

a. Peripheral blood smear with large platelets
b. Antibodies to heparin/PF4 (+)
c. ADAMTS13 activity levels of <10%
d. Bone marrow biopsy with 20% blast cells

Answer

A

A case of ITP
A. Peripheral blood smear with large platelets
B. Antibodies to heparin/PF4 (+) (HIT)
C. ADAMTS13 activity levels of <10% (TTP)
D. Bone marrow biopsy with 20% blast cells (leukemia)

The correct answer is: Peripheral blood smear with large platelets

Question 58

Q

What initial treatment is most appropriate for a 38-year-old male with spontaneous bruising and unremarkable CBC except for platelet count of 10,000 / uL (eHPIM 20TH ED p. 826)?

a. Eltrombopag
b. Intravenous gamma globulin
c. Prednisone
d. Rho(D) immune globulin

Answer

A

The correct answer is: Prednisone

Question 59

Q

A 76-year-old male came in for 1-week-history of low back pain and right shoulder pain with one episode of hematuria. He was in his usual state of health prior to the onset of symptoms. His physical examination was remarkable only for petechiae. His work-up showed hemoglobin of 100 g/dL, wbc count of 6.8 x 103 / uL, and platelet count of 10,400 / uL. His blood smear showed normal RBCs and WBCs. His blood type was B
(-). Hemolysis work up was negative. Abdominal ultrasound showed unremarkable spleen and liver. FOBT was positive. What is the recommended management in addition to high-dose glucocorticoids (eHPIM 20TH ED p. 826)?
a. Eltrombopag
b. Intravenous gamma globulin
c. Rho(D) immune globulin
d. Rituximab

Answer

A

A case of severe ITP
A. Eltrombopag (relapse or unresponsive to other meds)
B. Intravenous gamma globulin
C. Rho(D) immune globulin (for Rh (+))
D. Rituximab (refractory ITP)

The correct answer is: Intravenous gamma globulin

Question 60

Q

A 52-year-old female presented with very low platelet counts and large platelets on peripheral blood smear more than 6 months ago. Despite receiving conventional therapies and undergoing splenectomy, her platelet count is still at 5,000/ uL. What is a reasonable therapeutic option (eHPIM 20TH ED p. 826)?

a. Eltrombopag
b. Intravenous gamma globulin
c. Prednisone
d. Rho(D) immune globulin

Answer

A

A. Eltrombopag (effective in raising platelet counts in patients with ITP and are recommended for adults at risk of bleeding who relapse after splenectomy)

The correct answer is: Eltrombopag

Question 61

Q

What congenital disease is characterized by decreased metalloprotease activity that cleaves the von Willebrand factor (eHPIM 20TH ED p. 826-827)?

a. Evans syndrome
b. Moschcowitz syndrome
c. Upshaw-Schulman syndrome
d. Von Willebrand disease

Answer

A

A. Evans syndrome (combined autoimmune hemolytic anemia with ITP)
B. Moschcowitz syndrome (TTP)
C. Upshaw-Schulman syndrome (inherited TTP - deficiency of, or antibodies to, the metalloprotease ADAMTS13, which cleaves VWF)
D. Von Willebrand disease (deficiency in the VWF)

The correct answer is: Upshaw-Schulman syndrome

Question 62

Q

A 48-year-old male was brought in for decreased sensorium. On examination, he was febrile, had lower extremity purpura and had dark-colored urine on insertion of Foley catheter. He has anemia, thrombocytopenia and renal failure on work-up. What would be the most likely finding in his peripheral blood smear (eHPIM 20TH ED pp. 826-827)?

a. Giant platelets
b. Schistocytes
c. Platelets of varying size
d. Hypochromic red blood cells

Answer

A

A case of TTP (fever, microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, renal failure)
B. Schistocytes (sine qua non)

TTP was first described in 1924 by Eli Moschcowitz and characterized by a pentad of findings that include microangiopathic hemolytic anemia, thrombocytopenia, renal failure, neurologic findings, and fever. The PT and aPTT are characteristically normal. ADAMTS13 activity levels of <10% are more clearly associated with idiopathic (antibody-mediated) TTP.

Findings to support the TTP diagnosis include an increased lactate dehydrogenase and indirect bilirubin, decreased haptoglobin, and increased reticulocyte count, with a negative direct antiglobulin test. The peripheral smear should be examined for evidence of schistocytes.

The correct answer is: Schistocytes

Question 63

Q

A 42-year-old female came in for headache, visual disturbance and paresthesia. She has had weakness and malaise for months, worsening within the last four days. She had no episodes of overt bleeding or diarrhea, but has noted her urine to be darker in color. Labs done recently showed anemia, thrombocytopenia and increased creatinine levels. Which diagnostic picture is characteristic of the clinical picture (eHPIM 20TH ED pp. 826-827)?

a. Pancytopenia with hypochromic, microcytic red blood cells and large platelets
b. Hyperbilirubinemia with predominance of direct bilirubin
c. Elevated LDH and reticulocyte count and positive direct Coombs test
d. Normal prothrombin time and activated partial thromboplastin time

Answer

A

A case of TTP (fever, microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, renal failure)
A. Pancytopenia with hypochromic, microcytic red blood cells and large platelets (schistocytes)
B. Hyperbilirubinemia with predominance of direct bilirubin (indirect bilirubin)
C. Elevated LDH and reticulocyte count and positive direct Coombs test (negative direct Coombs test)
D. Normal prothrombin time and activated partial thromboplastin time

TTP was first described in 1924 by Eli Moschcowitz and characterized by a pentad of findings that include microangiopathic hemolytic anemia, thrombocytopenia, renal failure, neurologic findings, and fever. The PT and aPTT are characteristically normal. ADAMTS13 activity levels of <10% are more clearly associated with idiopathic (antibody-mediated) TTP.

Findings to support the TTP diagnosis include an increased lactate dehydrogenase and indirect bilirubin, decreased haptoglobin, and increased reticulocyte count, with a negative direct antiglobulin test. The peripheral smear should be examined for evidence of schistocytes.

The correct answer is: Normal prothrombin time and activated partial thromboplastin time

Question 64

Q

In a severely thrombocytopenic patient with fever and neurological symptoms, moderate schistocytes in the peripheral blood smear and ADAMST13 activity of < 5%, which is true regarding management (eHPIM 20TH ED p. 826-827)?

a. Prednisone is the cornerstone of initial therapy
b. Plasma exchange is used as an adjunct to glucocorticoid therapy
c. Rituximab has the most evidence in efficacy in a refractory case
d. Eculizumab can improve or preserve renal function

Answer

A

A case of TTP
A. Prednisone is the cornerstone of initial therapy (ITP)
B. Plasma exchange is used as an adjunct to glucocorticoid therapy (Plasma exchange is mainstay treatment for TTP)
C. Rituximab has the most evidence in efficacy in a refractory case
D. Eculizumab can improve or preserve renal function (in aHUS)

The correct answer is: Rituximab has the most evidence in efficacy in a refractory case

Answer 65

A

A. Fever, microangiopathic hemolytic anemia, thrombocytopenia, neurologic decline, renal dysfunction (TTP)
B. Fever, microangiopathy, thrombocytopenia, consumptive coagulopathy (DIC)
C. Bloody diarrhea, irritability, renal failure, thrombocytopenia and anemia (HUS)
D.Renal failure, anemia, mild thrombocytopenia, ADAMST13 activity of > 10% (aHUS)

The correct answer is: Bloody diarrhea, irritability, renal failure, thrombocytopenia and anemia

Answer 66

A

A case of HUS
Treatment of HUS is primarily supportive. Plasma infusion or plasma exchange has not been shown to alter the overall course.

The correct answer is: Treatment is primarily supportive

Answer 67

A

A case of HUS
In patients with aHUS, eculizumab, a humanized monoclonal antibody against C5 that blocks terminal complement, has efficacy in resolution of HUS and improving or preserving renal function. Patients with aHUS may initially be treated with plasma exchange, until the ADAMTS13 level is returned and the diagnosis more clear, since aHUS remains a diagnosis of exclusion. However, plasma exchange has not been shown to affect clinical outcomes in aHUS.

The correct answer is: Eculizumab effectively resolves the condition

Answer 68

A

SPLENECTOMY
ITP
• For patients who relapse after glucocorticoids are tapered
• An important treatment option; but, more patients are now noted to go into remission over time.
o Observation, if the platelet count is high enough, or intermittent treatment with anti-Rh0(D) or IVIgG, or initiation of treatment with a TPO receptor agonist may be a reasonable approach to see if the ITP will resolve
TTP
• Plasma exchange remains the mainstay of treatment of TTP
• Successful in refractory or relapsing TTP, together with rituximab, vincristine, and cyclophosphamide
Vaccination against encapsulated organisms (especially pneumococcus, but also meningococcus and Haemophilus influenzae, depending on patient age and potential exposure) is recommended prior

The correct answer is: For cases of ITP, TPO receptor agonists may decrease the need for splenectomy

Answer 69

A

Von Willebrand Disease Type 1

The correct answer is: Desmopressin

Answer 70

A

A case of Von Willebrand Disease
A. ADAMTS13 activity levels of <10% (TTP)
B. Factor XIII activity normal (decreased)
C. Fibrinogen decreased (normal)
D. Von Willebrand antigen decreased

The correct answer is: Von Willebrand antigen decreased

Answer 71

A

A. More men than women are affected by von Willebrand disease (men and women affected equally - https://www.cdc.gov/ncbddd/vwd/facts.html)
B. Bleeding associated with von Willebrand disease occurs without delay from inciting event (possible even weeks after surgery - https://emedicine.medscape.com/article/206996-clinical)
C. Most common signs include nosebleeds and hematomas
D. Bleeding symptoms typically worsen with the use of oral contraceptives (Birth control pills can increase the levels of VWF and factor VIII in the blood and reduce menstrual blood loss - https://www.cdc.gov/ncbddd/vwd/facts.html)

The correct answer is: Most common signs include nosebleeds and hematomas

Answer 72

A

A Antifibrinolytic agents with desmopressin can be used as prophylaxis for tonsillectomy for mild to moderate disease
B. Regular infusions of von Willebrand factor are recommended for patients with severe disease as prophylaxis for bleeding (some patients can develop antibodies to infused factor; if replacement is needed, virally inactivated VWF-plasma-derived and recombinant factor concentrates can be used)
C. Subcutaneous desmopressin is the recommended therapy over intranasal or intravenous administration (all forms can be used in VWD)
D. Nonsteroidal anti-inflammatory drugs (NSAIDs) can be given to patients with the disease, over aspirin (avoid drugs that inhibit platelet aggregation)

The correct answer is: Antifibrinolytic agents with desmopressin can be used as prophylaxis for tonsillectomy for mild to moderate disease

Answer 73

A

B. Hematuria (risk of ureteral obstruction)

The correct answer is: Hematuria

Answer 74

A

The most common presenting symptom is petechiae (more for platelet disorders, vasculitis)
B. Men and women are similarly affected by this disease (X-linked recessive, affects males mostly, female carriers)
C. Mild hemophilia may be diagnosed late in life, after a traumatic challenge
D. The pectorals and the abdominal muscles are the ones most commonly affected (flexor groups of the arms, gastrocnemius)

The correct answer is: Mild hemophilia may be diagnosed late in life, after a traumatic challenge

Answer 75

A

A. It is due to heterogeneous mutations in the F9 gene (F8)
B. It is the most common inherited condition of factor deficiency
C. It affects females predominantly, majority of whom are symptomatic (X-linked recessive, affects males)
D. Its patient population mostly have no family history of the disease (majority with family history)

The correct answer is: It is the most common inherited condition of factor deficiency

Answer 76

A

A. The most common hemophilia A mutation involves the inversion of the intron 1 sequence (intron 22)
B. The most common hemophilia A mutation is present in 40% of cases of severe hemophilia
C. There are only less than 100 different mutations identified for hemophilia (more than 500)
D. Current technologies cannot identify women with the genetic mutation for hemophilia (advances in molecular diagnosis now
permit precise identification of mutations, allowing accurate diagnosis of women carriers)

The correct answer is: The most common hemophilia A mutation is present in 40% of cases of severe hemophilia

Answer 77

A

Clinically, hemophilia A and hemophilia B are indistinguishable.

The disease phenotype correlates with the residual activity of FVIII or FIX and can be classified as severe (<1%), moderate (1–5%), or mild (6–30%).

In the severe and moderate forms, the disease is characterized by bleeding into the joints (hemarthrosis), soft tissues, and muscles after minor trauma or even spontaneously.

Patients with mild disease experience infrequent bleeding that is usually secondary to trauma.

The correct answer is: < 5%

Answer 78

A

A case of hemophilia
A. Platelet count of 100,000 / uL (NV: 150,000 – 400,000 / uL) (should be normal)
B. Prothrombin time of 20 seconds (NV: 11-13.5 seconds) (should be normal)
C. International normalized ratio of 2.5 (NV: 0.8 – 1.2) (should be normal)
D. Activated partial thromboplastin time of 48 seconds (NV: 30-40 seconds)

The correct answer is: Activated partial thromboplastin time of 48 seconds (NV: 30-40 seconds)

Answer 79

A

A. Most common bleeding manifestations are the recurrent hemarthroses in mild hemophilia (severe hemophilia)
B. Bleeding in joints mainly involve the knees, ankles, metatarsophalangeal joints, wrist, and interphalangeal joints (mainly large joints: knees, elbows, ankles, shoulders, and hips)
C. Recurrent bleeding into a joint can result in progressive joint deformity that requires surgery
D. Muscle contracture can result from recurrent hematomas into the muscles of distal parts of the limbs (to avoid pain, the patient may adopt a fixed position, leading to contractures)

The correct answer is: Recurrent bleeding into a joint can result in progressive joint deformity that requires surgery

Answer 80

A

Bleeding into the oropharyngeal spaces, central nervous system (CNS), or retroperitoneum is life threatening and requires immediate therapy. Retroperitoneal hemorrhages can accumulate large quantities of blood with formation of masses with calcification and inflammatory tissue reaction (pseudotumor syndrome) and also result in damage to the femoral nerve. Pseudotumors can also form in bones, especially long bones of the lower limbs.

Hematuria is frequent among hemophilia patients, even in the absence of genitourinary pathology. It is often self-limited and may not require specific therapy.

The correct answer is: Hematuria without genitourinary pathology

Answer 81

A

A. Severe spontaneous bleeding complications occur in patients with undetectable activity on factor IX assay (severe: < 1%, eHPIM p. 831)
B. Coagulation correction can be delayed pending diagnostic test results in suspected hemophilia B patients (Do not delay indicated coagulation correction for test results)
C. A normal activated partial thromboplastin time rules out hemophilia B (aPTT is relatively insensitive, mild and moderate disease may have normal aPTT - https://emedicine.medscape.com/article/779434-workup)
D. Ultrasonography is useful in evaluating bone and cartilage (UTZ for joints)

The correct answer is: Severe spontaneous bleeding complications occur in patients with undetectable activity on factor IX assay

Answer 82

A

A. Prophylactic oral antibiotics is routinely prescribed in all patients prior to any dental procedure (case to case basis)
B. Annual standardized evaluation, including screening for inhibitors, is recommended
C. Intravenous factor concentrate reverses established joint damage in patients with moderate hemophilia (timely administration can prevent chronic arthropathy and deformities)
D. All forms of bleeding require admission in a hospital for management (home infusion therapy, ambulatory replacement therapy)

The correct answer is: Annual standardized evaluation, including screening for inhibitors, is recommended

Answer 83

A

B. Factor levels of 30–50% (Mild bleeds such as uncomplicated hemarthroses or superficial hematomas require initial therapy with factor levels of 30–50%.)

The correct answer is: Factor levels of 30–50%

Answer 84

A

A. 15-25% (Additional doses to maintain levels of 15–25% for 2 or 3 days are indicated for severe hemarthroses, especially when these episodes affect the “target joint.”)

The correct answer is: 15-25%

Answer 85

A

FIX dose (IU) = (Target FIX levels – FIX baseline levels) × body weight (kg) × 1 unit/kg

The correct answer is: 6000 IU

Answer 86

A

FVIII dose (IU) = (Target FVIII levels – FVIII baseline levels) × body weight (kg) × 0.5 unit/kg
Prophylactic replacement for surgery is aimed at achieving normal factor levels (100%) for a period of 7–10 days; replacement can then be tapered depending on the extent of the surgical wounds.

The correct answer is: 3750 IU

Answer 87

A

FVIII dose (IU) = (Target FVIII levels – FVIII baseline levels) × body weight (kg) × 0.5 unit/kg
Large hematomas, or bleeds into deep muscles, require factor levels of 50% or even higher if the clinical symptoms do not improve, and factor replacement may be required for a period of 1 week or longer.
Cryoprecipitate is enriched with FVIII protein (each bag contains ~80 IU of FVIII)

The correct answer is: 25

Answer 88

A

DDAVP is a synthetic vasopressin analog that causes a transient rise in FVIII and von Willebrand factor (VWF), but not FIX, through a mechanism involving release from endothelial cells. Patients with moderate or mild hemophilia A should be tested to determine if they respond to DDAVP before a therapeutic application.

DDAVP does not improve FVIII levels in severe hemophilia A patients because there are no stores to release.

The correct answer is: FVIII 24%

Answer 89

A

Oral Antifibrinolytic Drugs
ε-amino caproic acid (EACA) or tranexamic acid

Controls local bleeding in the gums, in the gastrointestinal tract, and during oral surgery

Not indicated to control hematuria because of the risk of formation of an occlusive clot in the lumen of genitourinary tract structures

The correct answer is: Hematuria

Answer 90

A

Possible patient with inhibitor
HEMOPHILIA PATIENTS WITH INHIBITOR FORMATION
The clinical diagnosis of an inhibitor is suspected when patients do not respond to factor replacement at therapeutic doses. Inhibitors increase both morbidity and mortality in hemophilia. The formation of alloantibodies to FVIII or FIX is currently the major complication of hemophilia treatment.

The high-risk group for inhibitor formation includes severe deficiency (>80% of all cases of inhibitors), familial history of inhibitor, African descent, mutations in the FVIII or FIX gene resulting in deletion of large coding regions, or gross gene rearrangements. Inhibitors usually appear early in life, at a median of 2 years of age, and after 10 cumulative days of exposure. However, intensive replacement therapy such as for major surgery, intracranial bleeding, or trauma increases the risk of inhibitor formation for patients of all ages and degree of clinical severity, which requires close laboratory monitoring in the following weeks.

The laboratory test required to confirm the presence of an inhibitor is an aPTT with a mix (with normal plasma). In most hemophilia patients, 1:1 mix with normal plasma completely corrects prolonged aPTT. In inhibitor patients, the PTT is abnormally prolonged because the inhibitor neutralizes the FVIII clotting activity of the normal plasma.

The correct answer is: Abnormally prolonged PTT

Answer 91

A

Possible patient with inhibitor
THERAPY FOR HEMOPHILIA PATIENTS WITH INHIBITORS
Therapy has two goals: the control of acute bleeding episodes and the eradication of the inhibitor.

For the control of bleeding episodes, low responders, those with titer <5 BU, respond well to high doses of human FVIII (50–100 U/kg), with minimal or no increase in the inhibitor titers.

However, high-responder patients, those with initial inhibitor titer >5 BU or an anamnestic response in the antibody titer to >5 BU, even if low titer initially, do not respond to FVIII. The control of bleeding episodes in high-responder patients can be achieved by using concentrates enriched for prothrombin, FVII, FIX, FX (prothrombin complex concentrates [PCCs] or activated PCCs [aPCCs]), and recombinant activated factor VII (FVIIa) known as “bypass agents”.
•For FIX inhibitor patients, high doses of FIX can be used (<5 BU); however, allergic or anaphylactic reactions are common in FIX inhibitors, thus the use of bypass products should be used to treat or prevent bleeding as well as for those cases of high titer inhibitors.
•For eradication of the inhibitory antibody, immunosuppression alone is not effective. The most effective strategy is the immune tolerance induction (ITI) based on daily infusion of missing protein until the inhibitor disappears, typically requiring periods >1 year, with success rates of ∼60%. The management of patients with severe hemophilia and inhibitors resistant to ITI is challenging. The use of anti-CD20 monoclonal antibody (rituximab) combined with ITI was thought to be effective. Although this therapy may reduce the inhibitor titers in some cases, sustained eradication is uncommon.

The correct answer is: Recombinant activated factor VII

Answer 92

A

ELDERLY HEMOPHILIA PATIENTS
Elderly hemophilia patients have different problems compared to the younger generation; they have more severe arthropathy and chronic pain, due to suboptimal treatment, and high rates of HCV and/or HIV infections.

Early data indicate that mortality from coronary artery disease is lower in hemophilia patients than the general male population. The underlying hypocoagulability probably provides a protective effect against thrombus formation, but it does not prevent atherogenesis. Similar to the general population, these patients are exposed to cardiovascular risk factors such as age, obesity, and smoking. Moreover, physical inactivity, hypertension, and chronic renal disease are commonly observed in hemophilia patients. In HIV patients on combined antiretroviral therapy, there may be a further increase in the risk of cardiovascular disease. Therefore, these patients should be carefully considered for preventive and therapeutic approaches to minimize the risk of cardiovascular disease. Excessive replacement therapy should be avoided, and it is prudent to slowly infuse factor concentrates. Continuous infusion of clotting factor is preferable to bolus dosing in patients with cardiovascular risk factors undergoing invasive procedures. The management of an acute ischemic event and coronary revascularization should include the collaboration of hematologists and internists. The early assumption that hemophilia would protect against occlusive vascular disease may change in this aging population.

Cancer is a common cause of mortality in aging hemophilia patients because they are at risk for HIV- and HCV-related malignancies. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and a common cause of death in HIV-negative patients. The recommendations for cancer screening for the general population should be the same for age-matched hemophilia patients. Among those with high-risk HCV, a semiannual or annual ultrasound and a-fetoprotein are recommended for HCC. Screening for urogenital neoplasm in the presence of hematuria or hematochezia may be delayed due to the underlying bleeding disease, thus preventing early intervention. Multidisciplinary interaction should facilitate the attempts to ensure optimal cancer prevention and treatment recommendations for those with hemophilia.

The correct answer is: More severe arthropathy and chronic pain due to suboptimal treatment

Answer 93

A

HEMOPHILIA CARRIERS
Usually hemophilia carriers, with factor levels of ~50% of normal, have not been considered to be at risk for bleeding. However, a wide range of values (22–116%) have been reported due to random inactivation of the X chromosomes (lyonization). Therefore, it is important to measure the factor level of carriers to recognize those at risk of bleeding and to optimize preoperative and postoperative management. During pregnancy, both FVIII and FIX levels increase gradually until delivery. FVIII levels increase approximately two- to threefold compared to nonpregnant women, whereas an FIX increase is less pronounced. After delivery, there is a rapid fall in the pregnancy-induced rise of maternal clotting factor levels. This represents an imminent risk of bleeding that can be prevented by infusion of factor concentrate to levels of 50–70% for 3 days in the setting of vaginal delivery and up to 5 days for cesarean section. In mild cases, the use of DDAVP and/or antifibrinolytic drugs is recommended.

The correct answer is: Carriers who will be giving birth should have infusion of factor concentrate

Answer 94

A

A. Hemodynamic complications are common in chronic DIC (acute DIC)
B. Massive bleeding is the predominant cause of organ failure (hypercoagulability causing occlusion in the microcirculation)
C. Purpura fulminans is predominantly seen in the elderly (young children)
D. Thrombosis of large vessels and cerebral embolism occur

The correct answer is: Thrombosis of large vessels and cerebral embolism occur

Answer 95

A

A. Peripheral blood smear can show schistocytes
B. PT / PTT are expected to be normal (increased)
C. Level of fibrin degradation products is expected to be less than the reference value (increased)
D. Every other day lab determination since changes are not expected to be dramatic (repeated over a period of 6–8 h, drastic changes can occur)

The correct answer is: Peripheral blood smear can show schistocytes

Answer 96

A

A case of low grade, compensated DIC
A. Normal plasma levels of FDP (elevated)
B. Normal d-dimer (elevated)
C. Normal PT/PTT
D. Normal or low fibrinogen levels (normal or elevated in relation to chronic inflammatory disorder)

The correct answer is: Normal PT/PTT

Answer 97

A

A. Laboratory parameters in severe liver disease do not change dramatically
B. Patients with severe liver disease are not at risk for thrombosis (Cumulative clinical experience has demonstrated risk for thrombosis, especially those with advanced liver disease)
C. Severe liver disease does not cause elevated levels of FDP (elevated)
D. Severe liver disease consumes coagulation factors rather than decreases production (deficient synthesis of procoagulant factors and enhanced fibrinolysis)

The correct answer is: Laboratory parameters in severe liver disease do not change dramatically

Answer 98

A

D. Replacement with clotting factor concentrates (Clotting factor concentrates are not recommended for control of bleeding in DIC because of the limited efficacy afforded by replacement of single factors and the high risk of products containing traces of
aPCCs that further aggravate the disease)

The correct answer is: Replacement with clotting factor concentrates

Answer 99

A

The use of antifibrinolytic drugs, EACA, or tranexamic acid to prevent fibrin degradation by plasmin may reduce bleeding episodes in patients with DIC and confirmed hyperfibrinolysis.

However, these drugs can increase the risk of thrombosis, and concomitant use of heparin is indicated.

Patients with acute promyelocytic leukemia or those with chronic DIC associated with giant hemangiomas are among the few patients who may benefit from this therapy.

The correct answer is: Antifibrinolytic drugs

Answer 100

A

IRON DEFICIENCY ANEMIA

Answer 101

A

MEGALOBLASTIC ANEMIA

Answer 102

A

SPHEROCYTOSIS

Answer 103

A

HOWELL-JOLLY BODIES

Answer 104

A

SICKLE CELL ANEMIA

Answer 105

A

The correct answer is: Serum ferritin levels

Answer 106

A

The correct answer is: RBC protoporphyrin

Answer 107

A

The correct answer is: Inflammation

Answer 108

A

The correct answer is: Hydroxyurea

Answer 109

A

The correct answer is: 4 hours

Answer 110

A

The correct answer is: t(15;17) cytogenetic rearrangement

Answer 111

A

The correct answer is: Splenomegaly

Answer 112

A

The correct answer is: Complete cytogenetic response

Answer 113

A

The correct answer is: Hematuria

Answer 114

A

The correct answer is: It is the most common inherited condition of factor deficiency

Answer 115

A

The correct answer is: Desmopressin

Answer 116

A

The correct answer is: Treatment is primarily supportive

Answer 117

A

The correct answer is: Prednisone

Answer 118

A

The correct answer is: 18FDG -PET/CT scan

Answer 119

A

The correct answer is: <5%

Answer 120

A

The correct answer is: Imatinib

Answer 121

A

The correct answer is: > 20%

Answer 122

A

The correct answer is: Aquagenic pruritus

Answer 123

A

The correct answer is: No single characteristic feature of marrow morphology distinguishes MDS

Answer 124

A

The correct answer is: Blood count result

Answer 125

A

The correct answer is: Co-amoxiclav

Answer 126

A

The correct answer is: Paroxysmal nocturnal hemoglobinuria

Answer 127

A

The correct answer is: Cobalamin

Answer 128

A

The correct answer is: Deferoxamine

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