10c- Intro to Hemostasis- Clotting Disorders Flashcards
What are 2 factors that promote thrombosis and what are some examples of each?
- Endothelial Injury
- trauma, surgery, fracture, burn, ulcerated atherosclerotic plaques, vasculites, smoking, sepsis
- Abnormal blood flow
- atherosclerosis, prolonged bed rest, atrial fibrilation, myocardial infarct, prosthetis heart valves, aneurysms
What are 6 inherited hypercoagulability states?
Factor 5 Leiden
Prothrombin 20210A mutation
Hyperhomocysteinemia
dysfibrinogenemia
Protein C deficiency (also acquired)
Prtein S deficiency (also acquired)
at3 deficiency (also acquired)
What are some acquired hypercoagulability factors?
malignancy,
estrogens,
antiphospholipid antibody syndrome,
heparin-induces thrombocytopenia,
disseminated intravascular coagulation (DIC),
thrombotic thrombocytopenic purpura,
paroxysmal nocturnal hemoglobinuria,
myeloproliferative neoplasms
Which 3 thrombophilia risk factors can be both acquired or inherited? Are they more commonly acquired or inherited?
protein C, S, at3 deficiencies
hyperhomocysteinemia
dysfibrinogenemia
what are 3 sources of thrombi?
- Venous
- sites of stasis, travel in direction of blood flow , DVT in leg veins, may travel through heart to pulmonary veins (PE)
- Heart: atrial or ventricular walls or valve leaflets
- right heart: embolus may detach and travel into lung
- left heart: embolus may detach and travel into systemis arterial circulation
- Arterial
- develop at sites of endothelial injury, turbulence,
- travel retrograde, atherosclerotic plaque (abdominal aorta, carotid artery)
Which thrombi diseases usually occur in veins and which in arteries?
What is Factor 5 Leiden? What causes it?
- most common inherited predisposition to thrombosis (venous)
- single point mutation in F5 gene which is the cleavage site for protein C
- heterozygous: 2-15% of caucasians are hetero, 5-7X risk
- homozygous: 50X risk for thrombosis
- most pts won’t have thrombosis unless coupled with other risk factors
- Activated protein C resisitance= mutated F5 is resistant to protein C inactivation so protein F5 is active longer and promotes clotting
How do we test for Factor V Leiden? Who should we not test?
Molecular analysis (PCR, microarray) for mutation (cheap automated)
Don’t test for thrombophilia in adult patients with venous thromboembolism (VTE) occuring in the setting of major transient risk factors (surgery, trauma, or prolonged immobility)
What is the significance of the Prothrombin 20210A mutation
- it is the 2nd most common inherited predisposition for thrombosis (venous)
- single base pair mutation in prothrombin (F2) gene
- heterozygous vs homozygotes
- heterozygotes have 2-3X risk for thrombosis and 2-4% of caucasians are heteros
- homoszygote state is rare
- unclear mechanism of hypercoagulability, but may be related to elevated prothrombin levels
- diagnosis: molecular analysis for gene mutation
What does it mean to say someone is a double heterozyote?
Heterozygote for factor V leiden and prothrombin gene mutation
they are at a greater risk of thrombosis
How does someone get an ATIII, Protein C and Protein S deficiency? What is it associated with?
- inherited forms
- 5-15% of family thrombosis, risk increases after puberty and present in adolescence/young adulthood
- acquired forms
- consumptive (recent clot, DIC), decreased synthesis (liver failure, vitamin K deficiency)
How do we assess for protein C and protein S deficiencies in lab? WHen should we not assess?
ATIII, Protein C and S activities, Protein S free antigen
Do not test levels during active clotting bc the tests are not analytically accurate during an active clot
What happes with antiphospholpid antibody syndrome? What is ti assocaited with? What are the 2 kinds? What does it cause in vitro and how is that different in vivo?
acquire antibodies against various phospholipid complexes
associated with arterial, venous thrombosis with high recurrence rates and repeat miscarriages (DVTs, chronic PES, stroke, renal failure, interference with placenta growth/devo)
Primary ( no known association) secondary (associated with lupus)
in vitro: inhibit clotting, in vivio promote clotting
What are the 2 criteria for diagnsing antiphospholipid antibody syndrome?
Positive laboratory test (only need 1)
- lupus anticoagulant test
- antiphospholipid antibody ELISA
Positive clinical finding
- thrombosis
- recurrent miscarriage
What are the 2 laboratory evaluations for antiphospholipid anitbody syndrome?
Lupus anticoagulant
- functional assessment
- prolongation of clotting based tests
Anti-cardiolipin, anti- B2 glycoprotein
- ELISA
What are antiphospholipid antibodies used to diagnose (LA)? what 4 things lead to the diagnosis? What would tests results would you expect?
antiphospholipid antibody syndrome!
- Prolongation of 1 clotting assay, sensitive to lupus anticoagulants (dRVVT, aPTT; NOT PT)
- Failure to correct on mixing study
- correction of a clotting time with addition of excess phospholipid
- presistently present> 12 wks
**aPTT prolonged, 1:1 mix aPTT prolnged, aPTT with excess PLs normal**
What is the pathophysiology of HIT?
Drug induced antibody production
antibodies made against heparin-PF4 complex (IgGs)
immune complexes bind to platelets through Fc receptor
platelets activate and initiate clot formation
What is the 4Ts system for measuring risk of HIT? Is a high or low score equivalent to high risk? What criteria need to be met to be considered high risk?
high score=high risk! scale of 0-2
To score a 2:
Thrombocytopenia-extent of fall in platelet count: >50% fall or nadir> 20*10^9
Timing-onset of fall in platelet count or thrombosis in relation to inititaion of heparin: after 5-10 days or <1 day within recent heparin exposure
Thrombosus or other sequelae- proven new thrombosis; skin necrosis; acute systemic reaction after intravenous unfractionated heparin bolus
Other causes of thrombocytopenia- none evident
What are thrombotic microangiopathies? What are 3 symptoms?
disease characterized by widespread thrombi deposition in the microvasculature
- Hemolytic anemia (MAHA)
- Organ dysfunction
- Thrombocytopenia due to consumptiion
What is Thrombotic Thrombocytopenic Purpura? (TTP) What symptoms are associated? Who gets it?
Deficiency of metalloproteinase, ADMTS
- usually autoimmune= ADAMTS13 antibodies
- leads to too large vWF multimers
Classic pentad: fever, renal and neurologic impairment, thrombocytopenia, MAHA
acquired MUCH more than congenital, 30-50 y/o, female>male
What does TTP lead to?
Platelet activation and thrombi formation
The big vWF factor multimers are BIG and STICKY so they form clots and stick to things that they shouldn’t!
What would laboratory evaluation of TTP show?
Red cell fragments (schistocytes; circled)
decreased platelets
decreased ADAMTS13 levels (initiate treatment before this lab is back!)
How do we treat TTP?
must be inititated rapidly!
plasma exchange (remove antibodies, resupply ADAMTS-13)
What is atypical HUS associated with? What makes it atypical?
associated with complement defects
atypical because no bloody diarrhea, may be episodic w recurrent flairs of activity
familial cases usually do not precent concurrently,
progression to renal failure is more common
***don’t need to know details but they are pictured
What is DIC associated with?
It is not a primary disease
it is associated with severe illnesses (sepsis, trauma, obstetric complications, fat emoblus, cancer (acute promyelocytic leukemia), burns, ischemia)
due to relase of tissue factor and endothelial injury
Summary! Fill in the chart :)
