Bleeding Disorders Flashcards
activation of coagulation cascade takes place in association with…
phospholipids (platelet/cell surface)
Ca
Cofactors
Nearly all coagulation proteins are produced where_____
Exception?
in the liver
vW n the endothelial cells
Name the Vit K ones…
2, 7, 9, 10, C, S
Deficiencies of which factors are not associated with bleeding tendencies
12, prekalikrein, HMW kininogen
How is coagulation inhibited?
- Plasminogen-Plasmin system breaks down fibrin polymerization, cleavage to plasmin by activators
- ANTITHROMBINS
- PROTEIN C + S
- C1 ESTERASE INHIBITOR, ALPHA 2 MACROGLOBULIN
PROTEIN C AND S INHIBIT…
FACTOR 5 AND FACTOR 8
Antithrombins inhibit the activity of…
thrombin
9a, 10a, 11s, 12a
Platelet structural features tested as…
Platelet factor 3
Thrombin activated ______. So what?
FACTOR 13
This is a fibrin-stabilizing factor that allows for cross linking. This make a clot resistant to solubilization in 6M urea
Importance of plasminogen activators
They induce the formation of active plasmin, which degrades several proteins, but especially plasminogen on fibrin
What is EACA?
a competitive inhibitor of plasminogen activators
Decreases fibrinolysis
Name two common drugs used as plasminogen activators therapeutically
Urokinase
Streptokinase
How does Heparin work?
potentiates anti-thrombin III
How does Coumadin work?
Interferes with Vit K carboxylation
What is DDAVP?
desmopressin acetate –> increases factor 8 levels transiently
What do patients get in fresh frozen plasma
Coag factors, no platelets
Normal Bleeding time
2-7 mintues
Which clotting factor being low can cause a low bleeding time
fibrinogen
INR is equivalent to which test
PT
Solubility in 6M urea is a test for…
Factor 8 stabilization
Ristocetin test is used to test
Specific aggregation of platelets due to vWF
Causes of non-thrombocytopenic purpuras?
Infections, Drug reactions, Scurvy, Ehlers Danlos
Infections that cause non-thrombocytopenic purpuras
Septicemia
Meningococcemia
Severe Measles
Rickettsia
Thrombocytopenia is a platelet count of…
under 100,000
Six causes of thrombocytopenia
- Bone Marrow Disease
- Ineffective megakeryopoesis (folate/B12)
- Immune Destruction
- Mechanical
- Hypersplenism (sequestration)
- Dilutional (from massive transfusion)
Cause of neonatal thrombocytopenia
PLA1 antigens can lead to destruction of fetal platelets by antibodies made in mother (like erythro. fetalis)
What is ITP? Secondary causes?
Platelets are destroyed by anti-platelet antibodies
SLE, AIDS, post-viral, drug therapy complication
Target antigens in ITP
IIb/IIIa and Ib/IX
Major form of immune damage in ITP?
mostly via IgG
Phagocytosis follows
Why do a splenectomy for ITP
Decrease antibody formation and sequestration
Clinical features of ITP
Women of CB age
Bruising, excessive bleeding, epistaxis
Treat w/ steroids
Pentad of symptoms of TTP
Fever, Thrombocytopenia, MAHA, Neurological deficits, renal failure
TTP leads to widespread formation of….
Hyaline thrombi in microcirculation
Dense platelet aggregates + fibrin
Large multimers of vWF/complex leading to microvascular thrombosis
How to distinguish HUS from TTP
Absence of neurological symptoms
Mostly a renal problem
Inheritance for hemophillia A
X linked
Inheritance for vW disease
autosomal dominant
What is Leiden Factor V
Arg–>Glu in Factor 5 makes resistant to protein C
Causes Deep vein thromboses
Other than Leiden Factor V, other important hereditary hypercoagu. disorders
Prothrombin Deficiency
Hyperhomocysteinurea
Protein C or S Deficiency
What is Heparin induced thrombocytopenia syndrome
Unfrax. heparin induces formation of antibodies to complexes of heparin and PF4
What is anti-phospholipid syndrome
Make anti-phospholipid antibodies in SLE
Cardiac valvular vegitations, repeated miscarriages
False positive for Syphilis
medication classically associated with hypercoagubility
oral contraceptives
What is ticlopidine
ADP antagonist
What is abciximab
monoclonal Ab to GpIIb-IIIa
How does TTP present differently than DIC
In DIC you use up all the coagulation factors
You need Factor ___ or the clot will stabilize in 6M urea
13
