DIT review - Heme 1 Flashcards
What steps of the coagulation cascade do Protein C and S work on?
Protein C inhibits the activating factors VIII and V
Protein S is a cofactor for Protein C
What is responsible for the activation of Kallikrein
- Factor XIIa converts prekalikrein to kallikrein
What are the 2 functions of kallikrein
- Kallikrein cleaves plasminogen to plasmin
- Plasmin breaks down the fibrin mesh
- So factor XIIa is a regulator to make sure the coagulation cascade doesn’t go too crazy
- Kallikrein converts high molecular weight kininogen (HMWK) to bradykinin
What is the function of bradykinin
- Bradykinin has 3 functions:
- Vasodilation
- Increased vascular permeability
- Pain mediator
- This is why coagulation and inflammation are interconnected’
- ACE is responsible for degrading bradykinin
- So bradykinin can cause angioedema in patients taking ACEI
- ACE is responsible for degrading bradykinin
What are the deficient factors in Hemophilia A, B, and C
- Hemophilia A
- Deficiency of factor VIII
- Increases PTT (no effect on PT or INR)
- Hemophilia B
- Deficiency of factor IX
- Increases PTT (no effect on PT or INR)
- Hemophilia C
- Deficiency of factor XI
- Increases PTT (no effect on PT or INR)
Describe the role of Vitamin K in the coagulation cascade, including the Vitamin-K dependent factors
- Vitamin K acts as a cofactor to gamma glutamyl transferase in the liver for activation of certain factors
- Vitamin K must first be reduced by liver epoxide reductase
- Warfarin inhibits epoxide reductase
- Vitamin K must first be reduced by liver epoxide reductase
- Vitamin K-dependent factors:
- Factors II, VII, IX, X, C, and S
- THINK: diSCo started in 1972
What is the defect in Factor V Leiden
- Mutation that makes Factor Va resistant to inactivation by protein C
- Guanine to Adenosine point mutation
- Increased coagulation
Describe prothrombin mutation
- Prothrombin G20210A mutation
- Mutation on prothrombin gene causes increased production of prothrombin (II)
- Predisposes to thrombosis
Describe Anti-thrombin defiency
- Unable to inactivate thrombin
- Patients often resistant to Heparin, or must be given a larger dose
Describe Protein C and S deficiency
- Unable to inactivate factors V and VIII
Describe the pathophysiology behind Heparin-induced thrombocytopenia
- Heparin binds to platelet factor 4
- Antibodies form against this complex
- Antibody-heparin-PF4 complex can then destroy platelets, and their fragments will activate remaining platelets
- Leads to thrombocytopenia and hypercoagulable state
What is the MOA of Heparin
Binding and activation of Anti-thrombin III, so that there is inactivation of thrombin (II) and factor X
What drug is used to reverse the effects of Heparin
Protamin sulfate (Sketchy = protected area)
It is positively charged and will bind to negatively-charged Heparin, and inhibit it
What is the suffix of LMWH drugs?
“-parin”
What is the difference between Unfractionated heparin and LMWH
LMWH only increases inhibtion of Factor X, not thrombin (II)
LMWH effects are not inhibited by protamine sulfate
LMWH has greater bioavailability and longer half life
Does not require PTT monitoring
MOA of Fondaparinux
Same MOA of LMWH
Binds and activates Anti-thrombin III, inhibiting factor X
Not reversed by protamine sulfate
What are drug names of direct thrombin (II) inhibitors?
- BivaliRUDIN - No IntRUDIN sign
- ArGATROban - big gators
- DabiGATRAN - big gators
What are drug names of Factor Xa inhibitors
- RivaroXaBAN - banned foXes sign
- ApiXaBAN - banned foXes sign
What is used to measure effects of Heparin and Warfarin
Heparin - PTT
Warfarin - PT/INR
What is the mechanism behind Warfarin-induced skin necrosis
Due to early hyper-coagulable state due to depletion of protein C and S
What is used to reverse effects of Warfarin
Vitamin K supplement and fresh frozen plasma (to replace clotting factors)
What is the MOA of fibrinolytics
Activate the conversion of plasminogen to plasmin
Plasmin degrades fibrin clots
What are some of the fibrinolytic drugs
Recombinant tPA
Alteplase, Reteplase, Tenecteplase (“-teplase” = toy playset)
What drugs are used in the reversal of fibrinolytic therapy?
Aminocaproic acid (teacher putting cap on paint)
Trasexamic acid (teacher with exams)
