Thrombophilia Flashcards
Thrombophilia
= hypercoag state
A decrease in what proteins are assc with an inherited thrombophilia?
antithrombin 3
protein C
protein S
An increase in what proteins/mutations are assc with an inherited thrombophilia?
Factor V Leiden prothrombin gene mut G20210 Factor 7, 8, 9, 11 vWF MTHFR gene
Why are Factor V Leiden pts hyper coagulable?
They are resistant to Protein C (makes them immortal)
*other than this, they clot normally
What can you expect the clinical history to be of a pt with an inherited hypercoag state?
thrombosis at early age
Family history of thrombosis
thrombosis at unusual site
T or F: one defect is enough to cause a person to form frequent thrombi
F: the body has redundancy/ability to compensate. It will take multiple deficiencies or risk factors
Why do oral contraceptives lead to a hypercoag state?
increases levels of estrogen inc risk for thrombosis by decreasing antithrombin 3 and increasing B-thromboglobulin
What are clinical presentations of antiphospholipid syndrome?
- fetal loss in 2nd trimester
thrombosis
long PTT
WHat is the pathogenesis of antiphospholipid syndrome?
Ab against membrane
- anti-cardiolipin, phosphatidyl serine, phosphatidic acid
- Beta 2 GPI and prothrombin have some role too
T or F: A person with antiphospholipid Ab syndrome will have a normal correction PTT
F: they have an Ab that will prolong the PTT even in the presence of normal plasma
What test will prove the presence of a lupus anti-coagulant?
correctional with hexagonal phase phospholipid
dilute russel viper venom test
**they will correct/have normal PTTs with these?
What part of the clotting cascade is the lupus anti-coag Ab syndrom/lupus anti-coag?
X–> Xa +V +prothrombin–> thrombin
What do you need in order to Dx antiphospholipid syndrome?
at least 1 clotting assay test
at least 1 Ab present
What effect does dipyridamole have on a platelet?
inhibits them by inhib phospho-diesterase
*stops the breakdown of cAMP to AMP = Inc cAMP = inhibits platelets
What effect does abciximab have on a platelet?
Ab to GpIIb/IIIa to inhibit platelet activation
Stasis causes _____
thrombosis
What is the difference between a white and red thrombi?
white: arterial, high blood flow
red: venous, stasis
What acts near the endothelium to inhibit thrombosis?
- antithrombin 3 inactivates thrombin, Xa, 9a
- thromodulin binds thrombin
- heparin-like molecule
- PGI2 and NO secretion
Describe the effect that HIT has on the platelet count
drop 5-7 days after heparin admin
*drop in 24 hrs if previous heparin historm
In terms of tx, what do you do when you suspect HIT?
STOP HEPARIN
use direct thrombin inhibitor (hirudin, argatroban, bivalirudin, dabigatran)
How is HIT ab detected?
ELISA
What is the pathogenesis of HIT?
Ab to heparin-PF4 complex resulting in activation of platelets
What is the complication of HIT?
thrombosis
How is hirudin cleared?
kidney
