Bleeding Disorders (Rosenthal)

Question 1

a measure of the sensitivity of the thromboplastin a laboratory is using (thromboplastin = enzyme that converts prothrombin –> thrombin)

Answer 1

international normalized ratio (INR)

Question 2

clotting factors that make up the intrinsic pathway in the coagulation cascade

Answer 2

12, 11, 9, 8

Question 3

_______ measures the functionality of the intrinsic pathway while _______ measures the functionality of the extrinsic pathway.

Answer 3

partial thromboplastin time (PTT); prothrombin time (PT)

Question 4

how is a mixing study used to determine the cause of a clotting problem?

Answer 4

patient’s sample is mixed with an equal volume of normal plasma - if the blood clots, that means the problem was factor deficiency, corrected by the normal sample. If the blood does not clot, that means the patient’s making some kind of inhibitor (e.g., antibody) that continues to interfere with the clotting ability.

Question 5

lack of this factor may be due to disseminated intravascular coagulation (DIC), liver disease, or (rarely) congenital absence

Answer 5

fibrinogen

Question 6

assay that detects excess generation of cross-linked fibrin by plasmin, which is evidence of blood clot degradation, and is useful for detecting DIC, VT and PE

Answer 6

d-dimer

Question 7

test used to measure platelet activation time, which when markedly reduced may indicate platelet deficit or von Willebrand disease

Answer 7

PFA-100

Question 8

what type of disorder do people with petechiae normally have?

Answer 8

platelet disorders

Question 9

an adult disease, usually in women ages 20-40 years, with a gradual onset of moderate thrombocytopenia; may treat with steroids and IVIG, as well as splenectomy in persistent cases

Answer 9

chronic immune thrombocytopenic purpura

Question 10

prototypic drug that causes thrombocytopenia (though many others have been implicated as well)

Answer 10

quinine

Question 11

Which of the following statements regarding platelets is FALSE?

A. They live in the circulation for 7-10 days

B. Abnormalities are often quantitative rather than qualitative

C. They typically cause mucocutaneous bleeds

D. They are formed in the bone marrow from erythrocytes

E. They range in number from 150k - 450k/microliter

Answer 11

D. Platelets are formed from megakaryocytes, who share a common myeloid progenitor with erythrocytes.

Question 12

heparin induced thrombocytopenia is caused by an antibody against heparin and platelet factor 4, and it causes platelet aggregation (not reduction) which may lead to life-threatening ______.

Answer 12

thrombosis

Question 13

a disease in children that usually presents abruptly following viral illness, and resolves on its own after a couple of weeks; may be treated with steroids and IVIG.

Answer 13

acute immune thrombocytopenic purpura

Question 14

All of the following are part of the pentad of clinical features of thrombotic thrombocytopenia purpura EXCEPT:

A. microangiopathic hemolytic anemia (fragmented cells AKA schistocytes)

B. neurologic abnormalities

C. liver dysfunction

D. fever

E. clotting in small vessels

Answer 14

C. Renal dysfunction is the 5th sign associated with this disease, as thrombi clog up the caillaries in the glomerulus.

Question 15

what is the deficiency that causes thrombocytic thrombocytopenic purpura?

Answer 15

deficiency of the protease ADAMTS13, that cleaves ultra-large von Willebrand multimers, leading to clustering of these multimers into thrombus forming aggregates.

Question 16

drug that blocks the adenosine diphosphate (ADP) receptor preventing platelet aggregation, and is used following MI or stroke

Answer 16

clopidogrel

Question 17

cofactor in the intrinsic pathway whose deficiency would result in a long partial thromboplastin time

Answer 17

factor 8

Question 18

what complication of factor VIII replacement therapy is seen in 5-15% of patients?

Answer 18

they form an antibody to it

Question 19

Which of these is NOT a characteristic of hemophilia A?

A. Though there is delayed bleeding from small wounds because of functioning platelets, death occurs from bleeding into vital areas

B. Causes joint destruction and muscle atrophy

C. It is the most common hereditary disease in which there is severe bleeding

D. Most severe versions of this disorder are caused by an inversion mutation in the X chromosome
E. Lab abnormalities include abnormal PTT, abnormal PT and normal PFA-100

Answer 19

E. Patients with hemophIlia A have abnormal PTT only - PT and PFA-100 are normal.

Question 20

Which of the following is NOT a characteristic of hemophilia B?

A. It is caused by factor VIII deficiency

B. It is less common than hemophilia A

C. Symptoms are milder than hemophilia A

D. It is sex-linked

E. It shows prolonged PTT

Answer 20

A. Hemophilia B is caused by factor iX deficiency, due to either failed synthesis or a defective product.

Question 21

deficiency of this factor leads to prolonged PTT but is benign with no bleeding risk

Answer 21

factor 12

Question 22

made in endothelial cells and serves as initial adherence point of platelets to the endothelium by its binding to glycoprotein 1b

Answer 22

von Willebrand Factor

Question 23

Which of the following statements regarding von Willebrand disease is FALSE?

A. it is a relatively common autosomal dominant disease, with the exception of the extremely rare subtype III, which is autosomal recessive

B. people with the disease have mucocutaneous bleeding

C. people with the disease have decreased vWF antigen but relatively normal factor VIII

D. people with the disease have prolonged PFA-100 closure time due to lack of adherence of platelets

E. most people have subtype I, which shows moderatate quantitative reduction in vWF levels as opposed to subtype II which shows qualitative defects

Answer 23

C. People with von Willebrand disease have decreased vWF and factor VIII, since vWF is its carrier protein.

Treatment includes avoidance of aspirin as well as administration of DDAVP (desmopressin) or humate P, which contains both vWF and factor 8

Question 24

condition characterized by inappropriate release of tissue factor, leading to depletion of platelets and coag factors and widespread microvascular thrombosis

Answer 24

diseminated intravascular coagulation (DIC)

Question 25

All of the following are decreased in patients with liver disease EXCEPT:

A. platelets

B. von Willebrand factor

C. thrombopoietin

D. proteins C and S

E. fibrinogen

Answer 25

B. Also, tPA and Factor 8 are increased, all due to endothelial cell activation.

Question 26

Which of the following would NOT be a laboratory finding in a person with DIC?

A. fragmented red blood cells on peripheral smear

B. decreased fibrinogen

C. decreased platelet count

D. increased PT and PTT

E. decreased D-dimer

Answer 26

E.

D-dimer and fibrin degradation products (FDPs) would actually increase, due to the widespread clotting and breakdown of clots.

Question 27

which clotting factors are vitamin K dependent?

Answer 27

2, 7, 9, 10

Question 28

most common cause of acquired thrombophilia characterized by the development of antibodies against plasma proteins - most notably Beta2 glycoprotein 1 - leading to venous and arterial thrombosis, recurrent fetal loss, and thrombocytopenia

Answer 28

antiphosholipid antibody syndrome

Question 29

antibody that prolongs phospholipid dependent coagulation tests (i.e., PTT) but actually leads to increased risk of clotting that does not correct with mixing study

Answer 29

lupus anticoagulant; may or may not occur in the presence of SLE

Question 30

factor V leiden results from a mutation that prevents factor V from being cleaved by what anticoagulant factor, leading to thrombophilia?

Answer 30

protein C