Bleeding Disorders (Rosenthal) Flashcards
a measure of the sensitivity of the thromboplastin a laboratory is using (thromboplastin = enzyme that converts prothrombin –> thrombin)
international normalized ratio (INR)
clotting factors that make up the intrinsic pathway in the coagulation cascade
12, 11, 9, 8
_______ measures the functionality of the intrinsic pathway while _______ measures the functionality of the extrinsic pathway.
partial thromboplastin time (PTT); prothrombin time (PT)
how is a mixing study used to determine the cause of a clotting problem?
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.
lack of this factor may be due to disseminated intravascular coagulation (DIC), liver disease, or (rarely) congenital absence
fibrinogen
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
d-dimer
test used to measure platelet activation time, which when markedly reduced may indicate platelet deficit or von Willebrand disease
PFA-100
what type of disorder do people with petechiae normally have?
platelet disorders
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
chronic immune thrombocytopenic purpura
prototypic drug that causes thrombocytopenia (though many others have been implicated as well)
quinine
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
D. Platelets are formed from megakaryocytes, who share a common myeloid progenitor with erythrocytes.
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 ______.
thrombosis
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.
acute immune thrombocytopenic purpura
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
C. Renal dysfunction is the 5th sign associated with this disease, as thrombi clog up the caillaries in the glomerulus.
what is the deficiency that causes thrombocytic thrombocytopenic purpura?
deficiency of the protease ADAMTS13, that cleaves ultra-large von Willebrand multimers, leading to clustering of these multimers into thrombus forming aggregates.
drug that blocks the adenosine diphosphate (ADP) receptor preventing platelet aggregation, and is used following MI or stroke
clopidogrel
cofactor in the intrinsic pathway whose deficiency would result in a long partial thromboplastin time
factor 8
what complication of factor VIII replacement therapy is seen in 5-15% of patients?
they form an antibody to it
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
E. Patients with hemophIlia A have abnormal PTT only - PT and PFA-100 are normal.
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
A. Hemophilia B is caused by factor iX deficiency, due to either failed synthesis or a defective product.
deficiency of this factor leads to prolonged PTT but is benign with no bleeding risk
factor 12
made in endothelial cells and serves as initial adherence point of platelets to the endothelium by its binding to glycoprotein 1b
von Willebrand Factor
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
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
condition characterized by inappropriate release of tissue factor, leading to depletion of platelets and coag factors and widespread microvascular thrombosis
diseminated intravascular coagulation (DIC)
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
B. Also, tPA and Factor 8 are increased, all due to endothelial cell activation.
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
E.
D-dimer and fibrin degradation products (FDPs) would actually increase, due to the widespread clotting and breakdown of clots.
which clotting factors are vitamin K dependent?
2, 7, 9, 10
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
antiphosholipid antibody syndrome
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
lupus anticoagulant; may or may not occur in the presence of SLE
factor V leiden results from a mutation that prevents factor V from being cleaved by what anticoagulant factor, leading to thrombophilia?
protein C
