Section 2: Anemia_Hemolytic

Question 2

All forms of hemolytic anemia present with the sudden onset of weakness and fatigue associated with anemia.

What are the features of hemolytic anemia?

Answer 2

• Elevated indirect bilirubin level
• Elevated reticulocyte count
• Elevated LDH level
• Decreased haptoglobin level
• Abnormal peripheral smear (schistocytes, helmet cells, fragmented cells)
• Hemoglobinuria
• Hemosiderinuria (metabolic, oxidized product of hemoglobin in the urine)

CCS Tip: In a case of hemolysis, order a peripheral smear, LDH, bilirubin level, reticulocyte count, and haptoglobin level on the first CCS screen

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5083-5089). Kaplan Publishing. Kindle Edition.

Question 3

A complete physical examination is very important for the sickle cell case.

List the first management steps.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5095-5101). Kaplan Publishing. Kindle Edition.

Answer 3

• Oxygen
• Fluids
• Analgesics
• Antibiotics
• Then perform a complete physical examination

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5095-5101). Kaplan Publishing. Kindle Edition.

Question 4

Possible physical examination findings in sickle cell anemia

Answer 4

• HEENT: Retinal infarction
• CV: Flow murmur from anemia
• Abdomen: Splenomegaly in children; absence of spleen in adults
• Chest: Rales or consolidation from infection or infarction
• Extremities: Skin ulcers (unclear etiology in sickle cell) and aseptic necrosis of hip
• Neurological: Stroke, current or previous

Question 5

Rx of SCA

Answer 5

Next best step: Oxygen, hydration with normal saline continuously, and pain medications

If a fever is present: Give ceftriaxone, levofloxacin, or moxifloxacin with the first screen. Fever in a patient with sickle cell disease is an emergency because the patient has no spleen

• Hence, for a question of “Most urgent next step?” answer antibiotics when fever is present. This is more important than waiting for results of testing
• If it is a CCS question, answer blood cultures, urinalysis, reticulocyte count, CBC, and chest x-ray with the first screen as well, but if fever is present, do not wait for results.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5102-5115). Kaplan Publishing. Kindle Edition.

Question 6

When to do exchange blood transfusion in SCA?

Answer 6

• Eye: Visual disturbance from retinal infarction
• Lung: Pulmonary infarction leading to pleuritic pain and abnormal x-ray
• Penis: Priapism from infarction of prostatic plexus of veins
• Brain: Stroke

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5102-5115). Kaplan Publishing. Kindle Edition.

Question 7

A patient admitted for sickle cell crisis has a drop from her usual hematocrit of 34 to 26 over 2 days in the hospital. The reticulocyte count is 2 percent.

What is the diagnosis?

What is the most accurate test?

What is the treatment?

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5116-5125). Kaplan Publishing. Kindle Edition.

Answer 7

Sudden drops in the hematocrit in sickle cell patients or those with hemoglobinopathy can be caused by parvovirus B19 or folate deficiency

Sickle cell patients should universally be on folate replacement.

If the patient is on replacement therapy, then the diagnosis shifts to parvovirus B19, which is an infection that invades the marrow and stops production of cells at the level of the pronormoblast.

The most accurate diagnostic test is PCR for DNA of the parvovirus. This is more accurate than IgM or IgG antibody testing or bone marrow.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5116-5125). Kaplan Publishing. Kindle Edition.

Question 8

Rx of autoimmune hemolysis

Answer 8

Steroids (prednisone)

If recurrent: splenectomy

The antibodies found in Coombs test are also called “warm antibodies,” which are IgG. Only IgG antibodies respond to steroids and splenectomy

CCS Tip: If the case describes severe hemolysis not responsive to prednisone or repeated blood transfusion, use intravenous immunoglobulins as the best therapy to stop acute episodes of hemolysis.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5152-5157). Kaplan Publishing. Kindle Edition.

Question 9

Rx for parvovirus B19 induced anemic crisis in SCA

Answer 9

Transfusion and intravenous immunoglobulins

Question 10

List the post-discharge prescription for a SCA patient

Answer 10

Folate replacement

Pneumococcal vaccination

Hydroxyurea to prevent further crisis if they happen > 4 times per year

Question 11

CF of SCD

Answer 11

Visual disturbances

Hematuria

Isosthenuria (inability to concentrate or dilute the urine)

UTI

Question 12

Autoimmune Hemolysis - Look for other autoimmune diseases in the history, such as SLE or rheumatoid arthritis. Other clues are a history of chronic lymphocytic leukemia (CLL), lymphoma, or medications such as penicillin, alpha-methyldopa, quinine, or sulfa drugs.

List the diagnostic tests for autoimmune hemolysis

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5141-5148). Kaplan Publishing. Kindle Edition.

Answer 12

LDH

Indirect bilirubin level

Reticulocyte count will be elevated

Haptoglobin level can be decreased in both intravascular and extravascular forms of hemolysis

Peripheral smear: May show spherocytes

Most accurate diagnostic test: Coomb’s test

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5141-5148). Kaplan Publishing. Kindle Edition.

Question 13

Rx of autoimmune hemolysis

Answer 13

Best initial therapy: Steroids, such as prednisone

If the case describes recurrent episodes of hemolysis, splenectomy is the most effective therapy.

The antibodies found in Coombs test are also called “warm antibodies,” which are IgG. Only IgG antibodies respond to steroids and splenectomy.

CCS Tip: If the case describes severe hemolysis not responsive to prednisone or repeated blood transfusion, use intravenous immunoglobulins as the best therapy to stop acute episodes of hemolysis.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5150-5157). Kaplan Publishing. Kindle Edition.

Question 14

Cold-Induced Hemolysis (Cold Agglutinins)

1. Causes or predisposing factors
2. Is Coomb’s test positive or negative
3. Which other test can be done
4. Response to Rx

Answer 14

1. Mycoplasma or Epstein-Barr virus is in the history
2. Standard Coombs test is negative.
3. Complement test is positive
4. There is no response to steroids, splenectomy, or intravenous immunoglobulins. Treat with rituximab.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5158-5172). Kaplan Publishing. Kindle Edition.

Question 15

Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency

Sudden onset of hemolysis, which can be quite severe, is seen. As an X-linked disorder, hemolysis from G6PD deficiency is much more often described in males.

List the causes of bleeding in G6PD deficiency

Answer 15

Infection

Oxidizing drugs, such as:

• Sulfa medication
• Primaquine
• Dapsone

Fava bean ingestion may also be in the history.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5158-5172). Kaplan Publishing. Kindle Edition.

Question 16

G6PD deficiency:

Best initial test

Most accurate test

Rx

Answer 16

Heinz bodies test, bite cells

G6PD level after 2 months

Avoid oxidant stress

Heinz bodies are collections of oxidized, precipitated hemoglobin embedded in the red cell membrane. Bite cells appear when pieces of the red cell membrane have been removed by the spleen.

On the day of the hemolysis, the most deficient cells have been destroyed, and the level of G6PD is normal.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5178-5179). Kaplan Publishing. Kindle Edition.

Question 17

CF of hereditary spherocytosis

Answer 17

Recurrent episodes of hemolysis

Splenomegaly

Bilirubin gallstones

Elevated mean corpuscular hemoglobin concentration (MCHC)

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5188-5190). Kaplan Publishing. Kindle Edition.

Question 18

Hereditary spherocytosis:

• Most accurate test
• Rx

Answer 18

• Osmotic fragility test
• Splenectomy

Question 19

Hemolytic Uremic Syndrome (HUS) and Thrombotic Thrombocytopenic Purpura (TTP)

Look for E. coli 0157: H7 in the history for HUS. Medications such as ticlopidine predispose to TTP.

Diagnostic Testing

Rx

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5196-5214). Kaplan Publishing. Kindle Edition.

Answer 19

There is no specific diagnostic test for these

Usually resolves on their own. If serious, plasmapheresis

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5196-5214). Kaplan Publishing. Kindle Edition.

Question 20

HUS and TTP

List classisc triad and pentad for HUS and TTP respectively

Answer 20

HUS triad: ART

• Intravascular hemolysis with abnormal smear (A: Autoimmune hemolysis)
• Elevated BUN and creatinine (R: Renal failure)
• Thrombocytopenia (T: Thrombocytopenia)

TTP pentad (FAT RN) also has the following:

• Intravascular hemolysis with abnormal smear (A: Autoimmune hemolysis)
• Elevated BUN and creatinine (R: Renal failure)
• Thrombocytopenia (T: Thrombocytopenia)
• Fever (F: Fever)
• Neurological abnormalities (N: Neurological issues)

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5196-5214). Kaplan Publishing. Kindle Edition.

Question 21

Paroxysmal Nocturnal Hemoglobinuria (PNH)

CF

Most common cause of death

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5221-5222). Kaplan Publishing. Kindle Edition.

Answer 21

CF

• Pancytopenia
• Recurrent episodes of dark urine, particularly in the morning

The most common cause of death is large vessel venous thrombosis, such as portal vein thrombosis.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5222-5236). Kaplan Publishing. Kindle Edition.

Question 22

PNH

Which conditions can it transform into?

Answer 22

Aplastic anemia

Acute myelogenous leukemia (AML)

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5222-5236). Kaplan Publishing. Kindle Edition.

Question 23

PNH

Diagnostic test

Rx

Answer 23

Most accurate test: CD 55 and CD 59 antibody (also known as decay accelerating factor)

Older screening tests that are not as accurate: the sugar-water test and Ham’s test. These are tests for the activation of complement, which leads to hemolysis

The best initial treatment is with glucocorticoids, such as prednisone. Transfusion-dependent patients with severe illness are treated with eculizumab.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5222-5236). Kaplan Publishing. Kindle Edition.

Question 24

A pregnant woman comes with weakness and elevated liver function tests. She is in her 35th week of pregnancy. The prothrombin time is normal. The smear of blood shows fragmented red cells. Platelet count is low. What is the treatment?

a. Transfuse platelets
b. Plasmapheresis
c. Fresh frozen plasma
d. Delivery of the baby
e. Prednisone

Answer 24

D. Deliver the baby with the HELLP syndrome. HELLP syndrome stands for hemolysis, elevated liver function tests, and low platelets. This disorder is idiopathic and can be distinguished from DIC by the normal coagulation studies, such as the prothrombin time and aPTT.

Eculizumab inhibits C-5 and prevents complement activation. PNH is treated with eculizumab.

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5234-5246). Kaplan Publishing. Kindle Edition.

Question 25

Methemoglobinemia

The key to recognizing this condition is that the patient presents with shortness of breath for no clear reason with clear lungs on exam and a normal chest x-ray. Methemoglobinemia is blood locked in an oxidized state that cannot pick up oxygen.

Causes of methemoglobinemia

Rx

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5248-5261). Kaplan Publishing. Kindle Edition

Answer 25

• Nitroglycerin
• Amyl nitrate
• Nitroprusside
• Dapsone
• Any of the anesthetic drugs that end in -caine (e.g., lidocaine, bupivicaine, tetracaine)

Treat with methylene blue

Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5248-5261). Kaplan Publishing. Kindle Edition.

Question 26

**Transfusion Reactions** Match the most likely diagnoses with each of the following cases: a. ABO incompatibility b. Transfusion-related acute lung injury (TRALI) or “leukoagglutination reaction” c. Urticarial reaction d. IgA deficiency e. Febrile nonhemolytic reaction f. Minor blood group incompatibility **Case 1**: Twenty minutes after a patient receives a blood transfusion, the patient becomes short of breath. There are transient infiltrates on the chest x-ray. All symptoms resolve spontaneously. **Case 2**: As soon as a patient receives a transfusion, he becomes hypotensive, short of breath, and tachycardic. The LDH and bilirubin levels are normal. **Case 3**: During a transfusion, a patient becomes hypotensive and tachycardic. She has back and chest pain, and there is dark urine. The LDH and bilirubin are elevated, and the haptoglobin level is low. **Case 4**: A few days after a transfusion, a patient becomes jaundiced. The hematocrit does not rise with transfusion, and he is generally without symptoms. **Case 5**: A few hours after a transfusion, a patient becomes febrile with a rise in temperature of about 1 degree. There is no evidence of hemolysis. Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5262-5284). Kaplan Publishing. Kindle Edition.

Answer 26

**Case 1: B.** TRALI presents with acute shortness of breath from antibodies in the donor blood against recipient white cells. There is no treatment, and it resolves spontaneously. **Case 2: D.** IgA deficiency presents with anaphylaxis. In the future, use blood donations from an IgA deficient donor or washed red cells. **Case 3: A.** ABO incompatibility presents with acute symptoms of hemolysis while the transfusion is occurring. **Case 4: F.** Minor blood group incompatibility to Kell, Duffy, Lewis, or Kidd antigens or Rh incompatibility presents with delayed jaundice. There is no specific therapy. **Case 5: E.** Febrile nonhemolytic reactions result in a small rise in temperature and need no therapy. These reactions are against donor white cell antigens. They are prevented by using filtered blood transfusions in the future to remove the white cell antigens. Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5288-5290). Kaplan Publishing. Kindle Edition. Fischer, Conrad (2012-09-22). Master the Boards: USMLE Step 3 (Kaplan Medical Usmle Master the Boards Step 3) (Kindle Locations 5279-5287). Kaplan Publishing. Kindle Edition.

Question 27

A healthy 6-year-old African-American girl is brought to the physician for a routine follow-up visit. She has sjckle cell disease. She is asymptomatic, and has never had a sickle cell crisis. She is not taking any medications. Her mother also has sickle cell disease. Her physical examination is normal. which of the following complications is most likely to occur in this patient? A. Splenic infacrtion B. Bone infarction C. Splenic sequestration D. Stroke E. Acute coronary ischemia

Answer 27

**C**. In children, the most common initial symptom of sickle cell disease is dacyilytis, which develops in 40% of patients. Splenic sequestration is the second most common, and oocurs in about 20% of patients. Other complications, such as ischemic events, are not as frequent, and are seen mainly in the adult population