Thrombophilia

Question 1

Thrombophilia

Answer 1

= hypercoag state

Question 2

A decrease in what proteins are assc with an inherited thrombophilia?

Answer 2

antithrombin 3
protein C
protein S

Question 3

An increase in what proteins/mutations are assc with an inherited thrombophilia?

Answer 3

Factor V Leiden
prothrombin gene mut G20210
Factor 7, 8, 9, 11
vWF
MTHFR gene

Question 4

Why are Factor V Leiden pts hyper coagulable?

Answer 4

They are resistant to Protein C (makes them immortal)

*other than this, they clot normally

Question 5

What can you expect the clinical history to be of a pt with an inherited hypercoag state?

Answer 5

thrombosis at early age
Family history of thrombosis
thrombosis at unusual site

Question 6

T or F: one defect is enough to cause a person to form frequent thrombi

Answer 6

F: the body has redundancy/ability to compensate. It will take multiple deficiencies or risk factors

Question 7

Why do oral contraceptives lead to a hypercoag state?

Answer 7

increases levels of estrogen inc risk for thrombosis by decreasing antithrombin 3 and increasing B-thromboglobulin

Question 8

What are clinical presentations of antiphospholipid syndrome?

Answer 8

• fetal loss in 2nd trimester
  thrombosis
  long PTT

Question 9

WHat is the pathogenesis of antiphospholipid syndrome?

Answer 9

Ab against membrane

• anti-cardiolipin, phosphatidyl serine, phosphatidic acid
• Beta 2 GPI and prothrombin have some role too

Question 10

T or F: A person with antiphospholipid Ab syndrome will have a normal correction PTT

Answer 10

F: they have an Ab that will prolong the PTT even in the presence of normal plasma

Question 11

What test will prove the presence of a lupus anti-coagulant?

Answer 11

correctional with hexagonal phase phospholipid

dilute russel viper venom test

**they will correct/have normal PTTs with these?

Question 12

What part of the clotting cascade is the lupus anti-coag Ab syndrom/lupus anti-coag?

Answer 12

X–> Xa +V +prothrombin–> thrombin

Question 13

What do you need in order to Dx antiphospholipid syndrome?

Answer 13

at least 1 clotting assay test

at least 1 Ab present

Question 14

What effect does dipyridamole have on a platelet?

Answer 14

inhibits them by inhib phospho-diesterase

*stops the breakdown of cAMP to AMP = Inc cAMP = inhibits platelets

Question 15

What effect does abciximab have on a platelet?

Answer 15

Ab to GpIIb/IIIa to inhibit platelet activation

Question 16

Stasis causes _____

Answer 16

thrombosis

Question 17

What is the difference between a white and red thrombi?

Answer 17

white: arterial, high blood flow
red: venous, stasis

Question 18

What acts near the endothelium to inhibit thrombosis?

Answer 18

• antithrombin 3 inactivates thrombin, Xa, 9a
• thromodulin binds thrombin
• heparin-like molecule
• PGI2 and NO secretion

Question 19

Describe the effect that HIT has on the platelet count

Answer 19

drop 5-7 days after heparin admin

*drop in 24 hrs if previous heparin historm

Question 20

In terms of tx, what do you do when you suspect HIT?

Answer 20

STOP HEPARIN

use direct thrombin inhibitor (hirudin, argatroban, bivalirudin, dabigatran)

Question 21

How is HIT ab detected?

Answer 21

ELISA

Question 22

What is the pathogenesis of HIT?

Answer 22

Ab to heparin-PF4 complex resulting in activation of platelets

Question 23

What is the complication of HIT?

Answer 23

thrombosis

Question 24

How is hirudin cleared?

Answer 24

kidney

Question 25

How is argatroban cleared?

Answer 25

liver

Question 26

What is bivalirudin approved for?

Answer 26

use in coronary angioplasty but has been used in HIT tx

Question 27

What is notable about dabigatran?

Answer 27

oral DTI, is irreversible/does not have an”antidote”