Coagulation Flashcards
Which interaction leads to adhesion? Which leads to aggregation?
Adhesion between GPIba:vWF
Aggregation between GPIIb/IIIa:Fibrinogen
What are some molecules that bind receptors on passing platelets for recruitment/activation?
5-HT and ADP
What are the vitamin K dependent cofactors?
II, VII, IX and X
Protein C & Protein S
What screening tests should be done for mucosal bleeding (nosebleeds, menorrhagia)?
Platelet defect and vWF
What screening tests should be done for deep bleeding (joints, muscles, intracranial)?
Factor deficiency tests
Thrombocytopenia due to decreased production
Vit B12 deficiency, marrow failure or disease
Thrombocytopenia non-immune mediated
blood film often abnormal (DIC)
Thrombocytopenia immune mediated–Fab mediated
Blood film usually normal (ITP)
Thrombocytopenia immune mediated–Non-fab mediated
Heparin induced thrombocytopenia (Fc mediated)
Immune complex disease (HIV)
TTP (autoantibody to ADAMTS13–>deficiency)
Transient autoimmune disease about 10 days after heparin therapy
Heparin-induced Thrombocytopenia
Auto-antibodies to PF4:Heparin
Congenital absence of GPIb
Bernard Soulier Syndrome
Failure of adhesion
Congenital absence of GPIIb/IIIa
Glanzman’s Thrombasthenia
Failure of platelets to aggregate
Autoimmune production of IgG against platelet antigens (eg GPIIb/IIIa) –> consumed by splenic macrophages
Immune Thrombocytopenic Purpura
What are some differences between the acute and chronic form of ITP?
Acute: usually in children, weeks after viral infection/immunization; self-limiting
Chronic: usually adults (women of child-bearing age), less likely to recover –> txt: corticosteroids, IVIG, Rituximab, last resort splenectomy
Platelets consumed in formation of microthrombi –> RBCs are sheared as they cross microthrombi (hemolytic anemia with schistocytes)
Microangiopathic hemolytic anemia
TTP
HUS
What is the PFA-100 lab test?
Screens for platelet and vWF function
Membrane is coated with collagen, blood is drawn through membrane, vWF sticks to collagen, platelets stick to vWF and eventually clog the hole –> measure the time to occlusion
What causes TTP?
An acquired auto-antibody or congenital mutation to ADAMTS13 that results in large uncleaved multimers that lead to abnormal platelet adhesion –> develop microthrombi
What form of E. coli will put you at risk for HUS?
O157:H7
What is added to a prothrombin time?
Tissue factor, phospholipid and calcium to citrated plasma
What is added in a PTT?
Surface activator, phospholipid and calcium to citrated plasma
What does it mean if the clotting time corrects with a 1:1 mix test?
A factor deficiency is likely
If it does not correct than it is likely an inhibitor
How is hemophilia inherited?
X linked recessive
What are some things that may cause vitamin K deficiency?
Drugs (warfarin, antibiotics that decrease bowel flora)
Malabsorption or dietary deficiency
Liver disease
Newborns
What will the labs look like in someone who has vWF deficiency?
Increased bleeding time
Increased PTT
Normal PT
What is the pathophysiology behind vWF deficiency?
vWF normally stabilizes factor VIII – deficiency ruins this and decreased the half life of factor VIII
What is a treatment for vWF deficiency?
Desmopressin (Increases vWF release from Weibel Palade bodies)
Treatment for heparin induced thrombocytopenia
Stop heparin
Start direct thrombin inhibitor
Which factors does antithrombin inactivate?
IIa and Xa
Which factors does Protein C inactivate?
Va and VIIIa
Widespread microthrombi result in ischemia and infarction –> consumption of platelets and factors results in bleeding (IV and mucosal sites)
DIC
Mutated form of factor V that lacks the cleavage site for deactivation by protein C
Factor V Leiden – VENOUS thrombotic risk factor
Arg 506 replaced with Gln
what increases the risk of warfarin skin necrosis?
Protein C deficiency
Antibodies against phospholipids that damage cells leading to the formation of clots in arteries and veins
Antiphospholipid Antibody Syndrome
What are some antiphospholipid antibodies to test for?
Anti-cardiolipin
Lupus anticoagulant
Some syndromes associated with DIC?
Malignancy Amniotic fluid Fat embolism Acute hemolytic process Heparin assoc thrombocytopenia Sepsis
what might Purpura Fulminans be a presenting symptom for?
Meningococcal sepsis
Severe protein C deficiency in a newborn
What is hemophilia C?
Deficiency in factor XI affecting men and women equally
What is the clinical pentad of TTP?
Thrombocytopenia Microangiopathic hemolytic anemia (schistocytes/RBC fragments) Renal insufficiency Neurological symptoms Fever
