Diagnosis and Management of Bleeding and Clotting Disorders

Question 1

history of epistaxis and gingival bleeding should make you think of what?

Answer 1

mucosal bleeding–> platelet disorder until proven otherwise

Question 2

if you see spontaneous hemarthrosis in a question stem, what is the diagnosis until proven otherwise?

Answer 2

hemophilia (factor VIII or factor IX deficiency)

Question 3

what does a primary hemostatic deficiency consist of?

Answer 3

platelet disorders

Question 4

what does a secondary hemostatic deficit consist of?

Answer 4

coagulation factor deficiency or inhibitor

Question 5

what are the three main components to hemostasis?

Answer 5

platelets, plasma proteins, and the vessel wall

Question 6

testing for vWF, how do you test to see if there is enough?

Answer 6

test for the antigen

Question 7

testing for vWF, how do you test to see if it binds to platelets?

Answer 7

test for cofactor

Question 8

testing for vWF, how do you test to see if it protects/enables FVIII?

Answer 8

test for FVIII

Question 9

what defines a Type 1 vWD? (vWF antigen level, vWF activity, vWF antigen/activity ratio, and Factor VIII levels)

Answer 9

vWF antigen: decreased, vWF activity: decreased, vWF antigen/activity ratio: normal, and factor VIII: normal

Question 10

how do you treat Type 1 vWD? with minor bleeding

Answer 10

desmopression (temporarily)- it allows release of vWF from endothelial cells/platelets

Question 11

what are the side effects of desmopressin?

Answer 11

flushing, hypotension, HYPONATREMIA

Question 12

how do you treat type 1 vWD with major bleeding?

Answer 12

plasma derived or recombinant vWF

Question 13

what disease types of vWD are autosomal dominant?

Answer 13

type 1, type 2A and type 2B- so it is the most common types you’ll see

Question 14

what is a heavy menstrual bleeding defined as?

Answer 14

by a change of pad/tampon every hour and clots >1 cm

Question 15

When trying to diagnose hemophilia, why do we get a genetic test?

Answer 15

it can help predict disease severity (certain mutations are associated with more significant bleeding) and it eliminates other diseases in the differential

Question 16

what is something that could help you distinguish between vWD and hemophilia A?

Answer 16

a normal bleeding time in hemophilia versus von willebrand disease (vWD typically has an increased bleeding time because it is a platelet disorder)

Question 17

which types of von willebrand disease have significantly decreased FVIII levels?

Answer 17

type 2N and type 3

Question 18

what is the inheritance pattern of hemophilia A?

Answer 18

x-linked recessive (can hide in family members (aka they are carriers without knowing))

Question 19

What is the management of hemophilia: prevention?

Answer 19

prevention: avoid bleeding in acute and chronic situations, set a baseline activity

Question 20

what is the treatment of hemophilia?

Answer 20

goal isn’t to cure the disease, but to increase factor activity to achieve hemostasis–> most standard therapy is recombinant FVIII

Question 21

what is an example of recombinant FVIII and what is the downfall to this medication?

Answer 21

Emicizumab: binds to FIXa and X- it is an effective prophylactic drug, but it is so costly

Question 22

what is likely if the mixing study shows failure to correct?

Answer 22

an inhibitory antibody is likely and it is unlikely to be a deficiency in a clotting factor

Question 23

How do you treat acquired hemophilia A?

Answer 23

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

Question 24

what is the key to treating acquired hemophilia?

Answer 24

address the inhibition with immunosuppression

Question 25

what are the characteristics of acquired hemophilia A?

Answer 25

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

Question 26

What components make up virchow's triad?

Answer 26

venous stasis, endothelial injury, and hypercoaguability

Question 27

what contributes to venous stasis?

Answer 27

intra-operative period, post-operative period, travel

Question 28

what contributes to endothelial injury?

Answer 28

trauma, implanted devices, catheters

Question 29

what contributes to hypercoagulability?

Answer 29

genetic mutations, nephrotic syndrome, hyper-viscosity due to malignancy, autoimmune/ inflammatory disease, contraceptives, and cigarette smoking

Question 30

what are sites for proximal DVTs?

Answer 30

iliac, femoral , and popliteal veins

Question 31

what are the sites for distal DVTs?

Answer 31

below the knee, popliteal vein is not involved!

Question 32

what are the reasons for a provoked DVT?

Answer 32

surgery, hospital admission, malignancy, auto-immune disease, estrogen therapy

Question 33

what are the reasons for an unprovoked DVT?

Answer 33

there are no identifiable environmental events

Question 34

a saddle PE leads to heart failure because why?

Answer 34

you have increased pressure on the right ventricle, you get right ventricular strain and ballooning into the left ventricle and you get hypotension

Question 35

how do you diagnose a thromboembolism?

Answer 35

Lab test: d-dimer; radiography: ultrasound for DVT and CT angiogram for PE

Question 36

you do not order a d-dimer on everybody. So when do you order one?

Answer 36

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

Question 37

what is d-dimer?

Answer 37

the degradation of products of cross-linked fibrin

Question 38

d-dimer has a high negative predictive value. What does this mean?

Answer 38

if D-dimer is negative, you are not dealing with a thromboembolic phenomenon

Question 39

what is the gold standard test for a DVT?

Answer 39

compression ultrasound

Question 40

what is the gold standard for imagining for a PE?

Answer 40

CT angiogram

Question 41

if for some reason a patient cannot tolerate a CT angiogram, which imaging modality should be ordered?

Answer 41

ventilation/perfusion (V/Q) scan

Question 42

what is the downfall of a V/Q scan?

Answer 42

you can't 100% diagnose a blood clot- it is just going to look for a mismatch between ventilation and perfusion

Question 43

What does a protein C deficiency highlight?

Answer 43

a hypercoagulable state

Question 44

mesenteric vein thrombosis should make you think what?

Answer 44

hypercoagulable state

Question 45

what is the role of Proteins C and S?

Answer 45

they block the sites at VIII and V to inhibit the clotting cascade

Question 46

where are proteins c and s synthesized?

Answer 46

in the liver

Question 47

what does deficiency of proteins c or s cause?

Answer 47

thrombophilia (the inhibition is removed, so you just keep having this viscous cycle of clotting, which promotes thrombophilia)

Question 48

what is a paradoxical embolism?

Answer 48

passage of an embolus from the venous circulation to the arterial circulation

Question 49

how do you diagnose a paradoxical embolism?

Answer 49

with a transesophageal echocardiography (TEE) with bubble study

Question 50

what allows for a paradoxical embolism to occur?

Answer 50

a patent foramen ovale (PFO)

Question 51

what is the most common cause of strokes in patients under the age of 55?

Answer 51

a patent foramen ovale

Question 52

How does heparin work?

Answer 52

it inhibits factors II, IX, X, and XI

Question 53

what are 3 examples of Factor Xa inhibitors?

Answer 53

rivaroxaban, apixaban, and endoxaban

Question 54

what is an example of a direct thrombin inhibitor?

Answer 54

dabigatran

Question 55

how does warfarin work?

Answer 55

it inhibits vitamin K dependent factors ( II, VII, IX, X)

Question 56

which drugs are now considered safer and better than warfarin?

Answer 56

rivaroxaban and apixaban

Question 57

how long do you need to be anticoagulated?

Answer 57

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

Question 58

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)?

Answer 58

indefinite or lifelong anticoagulation is required

Question 59

when might anticoagulation be contraindicated? and what is the treatment options for these patients?

Answer 59

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