Bleeding and Clotting

Question 1

What is primary and secondary hemostasis?

Answer 1

Primary stasis involves the formation of a platelet plug. Secondary hemostasis involves coagulation factors and development of a lattice network.

Question 2

How does DIC ensue (which stage is first, second?)?

Answer 2

The intrinsic and extrinsic coagulation systems are activated which causes escape of thrombin into the circulatory system causing an initial thrombosis stage.
-thrombosis is often masked and may not be seen clinically.

As platelets and clotting factors are depleted, bleeding ensues, which is the major feature of the disease.

Question 3

What is the treatment of DIC? (3)

Answer 3

Correct the underlying disorder (sepsis, bowel obstruction, etc.).

Heparin - not usually used unless overt thrombosis occurs.

Supportive care - platelet and factor replacement.

Question 4

What symptoms are associated with associated with TTP?

What additional symptoms makes it be HUS?

Answer 4

MAHA
Thrombocytopenia (<50K)
Fever
Neurologic symptoms

+ renal failure = HUS

Question 5

What is the “pathologic lesion” associated with TTP?

Answer 5

Hyaline thrombi which occlude the capillaries of almost every organ in the body.

Question 6

What are the 2 major forms of TTP (hereditary vs. acquired)?

Answer 6

Hereditary: mutation of ADAMTS13 gene.

Acquired: auto-antibodies directed against ADAMTS13 (linked to malignancy, immune disorders, etc.).

Question 7

What is the treatment for TTP? (2)

Answer 7

Treat the underlying disorder.

Plasmaphoresis - life-saving in virtually all cases.

**100% mortality if not treated.

Question 8

What test is abnormal in a patient with vWD?

Answer 8

Platelet aggregation tests, especially to Ristocetin.

Question 9

What are the 2 treatment options for vWD?

Answer 9

Cryoprecipitate - replaces vWF.

DDAVP - causes release of vWF from the epithelium.

Question 10

Qualitative platelet dysfunction may cause defects in… (3)

Answer 10

Uremia - impaired platelet adhesion.

Dysproteinemias - interface w/ platelet membrane function.

Autoimmune disorders - multiple abnormalities.

Question 11

Hereditary hemorrhagic telangiectasia is the only endothelial syndrome…

What is the pathogenesis of it?

What is the inheritance of it?

What gene is defective? On which chromosome?

What are the clinical features?

What is the treatment?

Answer 11

Associated with hemostatic complications.

Vessel walls are thinned with telangiectatic formations, AVMs and aneurysmal dilations throughout the body.

AD.

Endoglin gene (CD105) on chr. 9.

Telangiectasias - on skin, mucous membranes and viscera.
Bleeding to mild/inapparent trauma; most commonly *epistaxis.

It is usually benign. Surgery and laser photoablation can be done, but site selection must be careful.

Question 12

What are the major signs/symptoms of AT-III deficiency?

Answer 12

The symptoms vary from minimal to early death from recurrent emboli.
-recurrent LE thrombophlebitis and DVTs, venous insufficiency and chronic leg ulcers are seen.

50% of patients will have DVT/PE by age 30 y/o; pregnant women are at an even elevated risk!

Question 13

What is the treatment of AT-III deficiency? (3)

Answer 13

Prophylactic treatment with anticoagulation.

Patients with DVTs should get heparin, but at high doses.

AT-III replacement therapy is available for those with DVT who don’t respond to heparin.

Question 14

What is the function of protein C and protein S?

Answer 14

Protein C: inactivates factors V and VIII.

Protein S: cofactor for protein C.

Question 15

What are the symptoms of protein C and S deficiencies?

What is the indicated therapy?

Answer 15

Similar to AT-III deficiency - various symptoms, DVT/PE at young age, etc.

Warfarin to decrease risk of embolism.

Question 16

When is hypercoagulability the greatest in patients with protein C and S deficiencies?

Answer 16

At the initiation of Warfarin therapy. It depletes protein C and S prior to the other factors, resulting in a temporary increase in coagulability.

Question 17

How does a patient with factor V leiden risk for embolism change depending on zygosity?

What is the treatment?

Answer 17

Heterozygotes - increased risk for thromboembolic disease.
Homozygotes - excessively high risk for thromboembolic disease.

No prior episodes: monitor, DVT prophylaxis and risk reduction.
Prior episodes: consider lifelong anticoagulation.

Question 18

What is cause of Prothrombin 20210?

How is it treated?

Answer 18

G-A mutation resulting in increased activity for prothrombin and inability to deactivate prothrombin. Risk of thrombosis is very high!

Similar to FVL mutation: monitor, prophylaxis, anticoagulation, etc.

Question 19

What are a few symptoms/features of APS? (4)

What changes are seen with PTT?

Answer 19

Thromboembolic phenomena
Miscarraige
Thrombocytopenia
Cerebral ischemia and recurrent stroke (especially in young patients!)

Prolonged PTT.

Question 20

What are the 3 features needed for diagnosis of APS?

Answer 20

1. A prolonged PTT.
2. Lack of correction in mixing studies using normal plasma.
3. Neutralizing of inhibitor with excess phospholipid.

Question 21

What test is most specific than PTT to diagnose APS?

Answer 21

Dilute Russell viper venom time (DRVVT)

Question 22

What is the treatment of APS?

What about in pregnant women?

Answer 22

• In a patient without a history of thromboembolism, there is no evidence of benefit of use of anticoagulation.
• For those with a history, lifelong anticoagulation is indicated! Multiple positive tests over a 3-12 mo. period are required to make a diagnosis.

Heparin SC in pregnant women with APS.

Question 23

What is Homan’s sign?

Is it a good test?

Answer 23

Pain in calf or popliteal area on foot dorsiflexion.

Not really, there are lots of false positives and false negatives!

Question 24

What is Moses sign?

Answer 24

Pain with compression of the calf against the tibia, but NOT when squeezing the calf itself.

It is neither sensitive or specific for DVT.

Question 25

What is Lisker’s sign?

Answer 25

Pain with percussion of the anteromedial tibia.

Not specific or sensitive for DVT.

Question 26

What is Lowenberg’s sign?

Answer 26

BP cuff applied to mid-calf and pain elicited with inflation to 80 mmHg.

Not sensitive or specific for DVT.

Question 27

What is most commonly used to determine one’s risk profile for DVT or PE?

Answer 27

Wells criteria - one model for DVT, one for PE.

Question 28

What 5 primary malignancies most often cause DVT/PE?

Answer 28

Lung
Pancreas
Colon/rectum
Kidneys
Prostate

Question 29

What is Troussaeu’s syndrome?

Answer 29

A sign involving episodes of vessel inflammation due to blood clot which are recurrent or appearing in different locations over time. It is associated with cancer.

Question 30

What drugs may cause hypercoagulability? (3)

Answer 30

Tamoxifen - proestrogenic effects increase risk of DVT/PE and stroke.

Bevacizumab - may cause both arterial and venous thromboembolic issues.

Thalidomide, lenalidomide - may cause both arterial and venous thromboembolic issues.

Question 31

How does HF increase ones risk for hypercoagulability?

Answer 31

It may cause stasis forming intracardiac thrombi, due to reduced LV function and AFib.

Question 32

What type of HF results in the greatest risk for thrombi formation?

Answer 32

RSHF