Hematology/Vasculitis

Question 1

Decreased activity of which enzyme causes sideroblastic anemia in patients taking isoniazid?

Answer 1

δ-aminolevulinate (ALA) synthase. Isoniazid inhibits the enzyme pyridoxine phosphokinase which normally converts pyridoxine (vitamin B6) to its active form, pyridoxal 5’ phosphate. Pyridoxal 5’ phosphate is a cofactor for δ-ALA synthase. Chloramphenicol and linezolid also can cause sideroblastic anemia. Sideroblastic anemia can also be caused by an X-linked deficiency in δ-ALA synthase, myelodysplastic syndrome, alcohol abuse and copper deficiency.

Question 2

What is polyarteritis nodosa (PAN)?

Answer 2

PAN is segmental, transmural, necrotizing inflammation of medium to small sized arteries. Renal artery involvement is often prominent. It usually involves the vessels of the kidneys, heart, liver and GI tract. The pulmonary arteries are usually spared. There is a propensity of bead-like aneurysm formation formation, especially in the mesenteric circulation. Cutaneous manifestations occur in up to one-third of patients, and include palpable purpura.

Question 3

What clotting factors does cryoprecipitate contain?

Answer 3

VIII, XIII, von Willebrand factor, and fibrinogen.

Question 4

What is rat poison?

Answer 4

“Super wafarin”, a long-acting 4-hydroxycoumarin derivative that depletes vitamin K-dependent clotting factors.

Question 5

What is a cavernous hemangioma?

Answer 5

Vascular malformations that often involve deeper tissues of the body, such as the liver and the brain. Gross examination shows a “mulberry-like” appearance due to their purple vascular clusters. On histology, they are composed of abnormal, dilated blood vessels with a thin adventitia lacking elastic fibers and smooth muscle. Because the walls lack these structural supports, they have a tendency to leak and hemorrhage.

Question 6

Which leukemias are patients with Down Syndrome most at risk for?

Answer 6

10 to 20 fold increased risk for acute lymphoblastic leukemia (ALL), and also have an increased risk for acute myelogenous leukemia (especially acute megakaryoblastic leukemia).

Question 7

Which two enzymes involved in heme biosynthesis are inhibited in lead poisoning?

Answer 7

δ-aminolevulinic acid (ALA) dehydratase and ferrochelatase. This causes sideroblastic anemia and basophilic stippling.

Question 8

What are 6 notable causes of sideroblastic anemia?

Answer 8

Myelodysplastic syndromes
Alcohol
Lead poisoning
Vitamin B6 deficiency
Copper deficiency
Isoniazid

Question 9

Why are patients at risk for hypocalcemia following massive blood transfusions?

Answer 9

Prior to storage, whole blood is generally mixed with solutions containing citrate anticoagulant. Infused citrate can chelate serum calcium, causing hypocalcemia. This most often occurs after massive transfusions of more than 5 or 6 liters over 24hrs.

Question 10

What is the inheritance pattern of C6PD deficiency?

Answer 10

X-linked recessive

Question 11

What does the oxygen-dissociation curve for a solution of dissociated beta hemoglobin subunits look like (without alpha subunits)?

Answer 11

Shifted left (looks like a myoglobin dissociation curve).

Question 12

What are characteristics of follicular lymphoma?

Answer 12

Second most common non-Hodgkin lymphoma. It is derived from follicular B cells and typically has a long, waxing and waning clinical course. Typically presents in middle-aged patients with painless lymph node enlargement or abdominal discomfort with an abdominal mass. Histology is notable for a mixture of cleaved and noncleaved follicle center cells in a nodular pattern. The majority of tumors have a t(14;18) translocation, resulting in overexpression of the bcl-2 oncogene that blocks programmed cell death.

Question 13

Why are patients with sickle cell disease at increased risk for megaloblastic anemia?

Answer 13

Due to increased erythrocyte turnover (hemolytic anemia), patients have increased folic acid requirements which puts them at risk for relative folic acid deficiency and megaloblastic anemia.

Question 14

Why do reticulocytes have a bluer appearance than mature RBCs on blood smear using a Wright-Giemsa stain?

Answer 14

They retain basophilic, reticular (mesh-like) network of residual rRNA.

Question 15

What cancer are patients with chronic lymphedema (e.g. post axillary lymph node dissection for breast cancer) at risk for?

Answer 15

Angiosarcoma, also known as Stewart-Treves syndrome.

Question 16

What are the symptoms of giant cell arteritis (GCA) and what is the pathological process?

Answer 16

Systemic symptoms (fever, fatigue, malaise, weight loss), headache, jaw claudication, visual disturbances (e.g. ischemic optic neuropathy), and polymyalgia rheumatica. Presents in patients >50 years of northern European descent.
It is due to a T-cell-mediated inflammatory process of medium-to-large arteries. It may occur diffusely but predominantly affects the arteries of the head and neck, especially the temporal lobe. Histologically it appears as granulomatous inflammation centered on the media with intimal thickening, elastic lamina fragmentation, and giant cell formation (histologically identical to Takayasu arteritis, which typically involves the aortic arch and affects primarily younger patients). Treated with glucocorticoids.

Question 17

What is Henoch-Schönlein purpura?

Answer 17

IgA immune complex-mediated vasculitis (Type III hypersensitivity reaction). Occurs following upper respiratory infections typically. It manifests as palpable purpura, arthralgias, abdominal pain, intussusceptions, renal disease similar to IgA nephropathy (hematuria).

Question 18

What are causes of schistocytes?

Answer 18

Traumatic RBC destruction: microangiopathic hemolytic anemia (e.g. hemolytic uremic syndrome [HUS], thrombotic thrombocytopenic purpura [TTP], disseminated intravascular coagulation [DIC], malignant hypertension, metastatic carcinoma) or mechanical damage (e.g. prosthetic valve, severely calcified valves).
HUS and TTP lie on a spectrum (HUS-TTP).

Question 19

What is the “chloride shift”?

Answer 19

The chloride content in venous blood is lower than in arterial blood. This is because carbonic anhydrase converts CO2 to HCO3- and H+ in RBCs. The bicarb diffuses out of the cell, so to maintain electrical neutrality, chloride diffuses into the cell.

Question 20

What is the criteria for diagnosis of Kawasaki disease (vasculitis of medium-sized arteries in young children of Asian ancestry most commonly)?

Answer 20

Fever ≥5 days plus 4 of the following:

1. Bilateral non-exudative conjunctival injection
2. Cervical lymphadenopathy
3. Mucositis (erythema of palantine mucosa, fissured erythematous lips, “strawberry” tongue).
4. Extremity changes (edema of hands and feet, erythema of palms and soles, desquamation of the fingertips [periungal]).
5. Rash (polymorphous [usually urticarial] erythematous rash on the extremities that spreads centripetally to the trunk)

Patients are at risk for development of coronary artery aneurysms.

Question 21

What is the growth pattern of cutaneous, strawberry-type capillary hemangiomas (benign) in newborns?

Answer 21

Initially, they will grow in proportion to the growth of the child, before eventually regressing in the majority of cases

Question 22

How do patients with von Willebrand disease present?

Answer 22

Lifelong history of mucosal bleeding (e.g. gingival bleeding, epistaxis, and/or menorrhagia). They typically have normal platelet levels, but typically have a prolonged bleeding time due to impaired platelet functioning.
Usually an autosomal dominant pattern of inheritance.

Question 23

What is eosinophilic granulomatosis with polyangiitis (Churg-Strauss)?

Answer 23

A small-to-medium vessel vasculitis that is characterized by late-onset asthma, rhinosinusitis, and eosinophilia. Asymmetric multifocal neuropathy (mononeuritis multiplex) is particularly common due to the vasculitis affecting the epineural vessels (e.g. wrist drop due to radial nerve involvement). Other common manifestations include skin nodules, migratory/transient pulmonary infiltrates, and paranasal sinus abnormalities. In addition to peripheral eosinophilia, a frequent laboratory finding is antibodies against neutrophil myeloperoxidase, which most commonly have a pattern of perinuclear staining (p-ANCA).

Question 24

What blood cancer predisposes patients to amyloidosis?

Answer 24

Multiple myeloma; due to the accumulation of monoclonal immunoglobulin light chains. AL amyloid is seen as “apple-green” birefringence with Congo red stain when viewed under polarized light. AL amyloidosis contributes to the development of renal failure in multiple myeloma. Amyloid is also deposited in the heart, tongue, and nervous system.

Question 25

What is the first-line treatment of menorrhagia in women with vWF deficiency?

Answer 25

Oral contraceptives.

Can also treat with desmopressin.

Question 26

What vasculitis is associated with hepatitis B infections?

Answer 26

Polyarteritis nodosa (PAN). PAN is usually idiopathic but is associated with hepatitis B infection in up to 30% of cases. In these cases, hepatitis B surface antigen/antibody complexes can be demonstrated in affected tissues.

Question 27

What two factors contribute to angiogenesis?

Answer 27

Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)

Question 28

What is the level (increased or decreased) of leukocyte (neutrophil) alkaline phosphatase in the setting of chronic myelogenous leukemia (CML)?

Answer 28

Decreased due to abnormal cells. Helps to distinguish from a leukemoid reaction which has normal or elevated levels.

Question 29

What tumor is pure red cell aplasia (PRCA) associated with?

Answer 29

A thymoma. PRCA is the decrease in RBC production with normal WBC production due to inhibition of erythropoietic precursors and progenitors by IgG autoantibodies and cytotoxic T lymphocytes.
PRCA can also be caused parvovirus B19 infections.

Question 30

What are Döhle bodies?

Answer 30

Light blue (basophilic) peripheral granules in neutrophils. Commonly seen in toxic systemic illness (e.g. sepsis) but can also occur with burns or myelodysplasia.

Question 31

What is hereditary hemorrhagic telangiectasia (aka Osler-Weber-Rendu syndrome)?

Answer 31

AD disorder of blood vessels. Findings: telangiectasias, recurrent epistaxis (nosebleeds), skin discoloration, ateriovenous malformations, GI bleeding, hematuria

Question 32

What is the underlying problem in thrombotic thrombocytopenic purpura?

Answer 32

Decreased ADAMTS13 activity leading to large vWF multimers and resulting diffuse microvascular platelet-rich thrombi

Question 33

What substance is secreted by endothelial cells that inhibits platelet aggregation?

Answer 33

Prostacyclin - inhibits platelet aggregation and adhesion to vascular endothelium, vasodilates vessels, increases permeability, and stimulates leukocyte chemotaxis.

Question 34

What is the function of c-Myc?

Answer 34

Transcription activator that controls cell proliferation, differentiation, and apoptosis

Question 35

What disease should be suspected in a patient with fatigability, constipation, back or rib pain, elevated serum protein, and renal failure.

Answer 35

Multiple myeloma: fatigability (anemia), constipation (hypercalcemia), bone pain (bone lysis), elevated serum protein (monoclonal proteins), renal failure (due to free light chain proteins accumulating in renal tubules forming casts)