Diagnosis and Management of Bleeding and Clotting Disorders Flashcards
history of epistaxis and gingival bleeding should make you think of what?
mucosal bleeding–> platelet disorder until proven otherwise
if you see spontaneous hemarthrosis in a question stem, what is the diagnosis until proven otherwise?
hemophilia (factor VIII or factor IX deficiency)
what does a primary hemostatic deficiency consist of?
platelet disorders
what does a secondary hemostatic deficit consist of?
coagulation factor deficiency or inhibitor
what are the three main components to hemostasis?
platelets, plasma proteins, and the vessel wall
testing for vWF, how do you test to see if there is enough?
test for the antigen
testing for vWF, how do you test to see if it binds to platelets?
test for cofactor
testing for vWF, how do you test to see if it protects/enables FVIII?
test for FVIII
what defines a Type 1 vWD? (vWF antigen level, vWF activity, vWF antigen/activity ratio, and Factor VIII levels)
vWF antigen: decreased, vWF activity: decreased, vWF antigen/activity ratio: normal, and factor VIII: normal
how do you treat Type 1 vWD? with minor bleeding
desmopression (temporarily)- it allows release of vWF from endothelial cells/platelets
what are the side effects of desmopressin?
flushing, hypotension, HYPONATREMIA
how do you treat type 1 vWD with major bleeding?
plasma derived or recombinant vWF
what disease types of vWD are autosomal dominant?
type 1, type 2A and type 2B- so it is the most common types you’ll see
what is a heavy menstrual bleeding defined as?
by a change of pad/tampon every hour and clots >1 cm
When trying to diagnose hemophilia, why do we get a genetic test?
it can help predict disease severity (certain mutations are associated with more significant bleeding) and it eliminates other diseases in the differential
what is something that could help you distinguish between vWD and hemophilia A?
a normal bleeding time in hemophilia versus von willebrand disease (vWD typically has an increased bleeding time because it is a platelet disorder)
which types of von willebrand disease have significantly decreased FVIII levels?
type 2N and type 3
what is the inheritance pattern of hemophilia A?
x-linked recessive (can hide in family members (aka they are carriers without knowing))
What is the management of hemophilia: prevention?
prevention: avoid bleeding in acute and chronic situations, set a baseline activity
what is the treatment of hemophilia?
goal isn’t to cure the disease, but to increase factor activity to achieve hemostasis–> most standard therapy is recombinant FVIII
what is an example of recombinant FVIII and what is the downfall to this medication?
Emicizumab: binds to FIXa and X- it is an effective prophylactic drug, but it is so costly
what is likely if the mixing study shows failure to correct?
an inhibitory antibody is likely and it is unlikely to be a deficiency in a clotting factor
How do you treat acquired hemophilia A?
if they have low titers–> you administer FVIII to get that up to allow the common pathway to occur; if they have high titers–> you given them Factor VII- you just bypass the entire intrinsic pathway until you can address the inhibition with immunosuppression
what is the key to treating acquired hemophilia?
address the inhibition with immunosuppression
what are the characteristics of acquired hemophilia A?
often seen in older adults, can occur postpartum (or even during pregnancy), often associated with autoimmune disease (RA/ SLE), and may be seen in malignancy
What components make up virchow’s triad?
venous stasis, endothelial injury, and hypercoaguability
what contributes to venous stasis?
intra-operative period, post-operative period, travel
what contributes to endothelial injury?
trauma, implanted devices, catheters
what contributes to hypercoagulability?
genetic mutations, nephrotic syndrome, hyper-viscosity due to malignancy, autoimmune/ inflammatory disease, contraceptives, and cigarette smoking
what are sites for proximal DVTs?
iliac, femoral , and popliteal veins
what are the sites for distal DVTs?
below the knee, popliteal vein is not involved!
what are the reasons for a provoked DVT?
surgery, hospital admission, malignancy, auto-immune disease, estrogen therapy
what are the reasons for an unprovoked DVT?
there are no identifiable environmental events
a saddle PE leads to heart failure because why?
you have increased pressure on the right ventricle, you get right ventricular strain and ballooning into the left ventricle and you get hypotension
how do you diagnose a thromboembolism?
Lab test: d-dimer; radiography: ultrasound for DVT and CT angiogram for PE
you do not order a d-dimer on everybody. So when do you order one?
if the patient’s history is not super convincing, but you still need to rule out a VTE- you only order it on people with low probability
what is d-dimer?
the degradation of products of cross-linked fibrin
d-dimer has a high negative predictive value. What does this mean?
if D-dimer is negative, you are not dealing with a thromboembolic phenomenon
what is the gold standard test for a DVT?
compression ultrasound
what is the gold standard for imagining for a PE?
CT angiogram
if for some reason a patient cannot tolerate a CT angiogram, which imaging modality should be ordered?
ventilation/perfusion (V/Q) scan
what is the downfall of a V/Q scan?
you can’t 100% diagnose a blood clot- it is just going to look for a mismatch between ventilation and perfusion
What does a protein C deficiency highlight?
a hypercoagulable state
mesenteric vein thrombosis should make you think what?
hypercoagulable state
what is the role of Proteins C and S?
they block the sites at VIII and V to inhibit the clotting cascade
where are proteins c and s synthesized?
in the liver
what does deficiency of proteins c or s cause?
thrombophilia (the inhibition is removed, so you just keep having this viscous cycle of clotting, which promotes thrombophilia)
what is a paradoxical embolism?
passage of an embolus from the venous circulation to the arterial circulation
how do you diagnose a paradoxical embolism?
with a transesophageal echocardiography (TEE) with bubble study
what allows for a paradoxical embolism to occur?
a patent foramen ovale (PFO)
what is the most common cause of strokes in patients under the age of 55?
a patent foramen ovale
How does heparin work?
it inhibits factors II, IX, X, and XI
what are 3 examples of Factor Xa inhibitors?
rivaroxaban, apixaban, and endoxaban
what is an example of a direct thrombin inhibitor?
dabigatran
how does warfarin work?
it inhibits vitamin K dependent factors ( II, VII, IX, X)
which drugs are now considered safer and better than warfarin?
rivaroxaban and apixaban
how long do you need to be anticoagulated?
it depends- provoked thromboembolism with no underlying conditions or enduring risk factors: anticoagulate for 3-6 months; however, if you have more than 2 spontaneous thromboses, you are going to have indefinite or lifelong anticoagulation
how long do you anticoagulate if you have a patient that has 1 spontaneous thrombosis at an unusual site (such as the mesentery or cerebral venous)?
indefinite or lifelong anticoagulation is required
when might anticoagulation be contraindicated? and what is the treatment options for these patients?
metastatic brain cancer with a high risk of bleeding or intracranial hemorrhage or they have a thrombocytopenia with high risk of bleeding; an inferior vena cava filter would be the least evil of all options
