Hem/Onc Physiology Flashcards
What isotype are Anti-A, Anti-B, and Anti-Rh(D)
A and B are IgM
Anti-Rh(D) is IgG (can cross placenta and cause erythroblastosis fetalis)
Hemophilia A
Factor VIII
Hemophilia B
Factor IX
XIIa effects
Aside from the intrinsic pathway action of converting XI to XIa. It also turns Prekallikrein to kallikrein which converts plasminogen to plasmin and HMWK to Bradykinin.
What is HMWK
High molecular weight kininogen, which activates formation of XIIa
Bradykinin effects
Kinin cascade leads to increased vasodilation, permeability, and pain.
Plasmin does what
Breaks down fibrin clot and also turns C3 to C3a for complement cascade
How to think about the coagulation cascade
Extrinsic is simple: It’s 7 turned to 7a by tissue factor (thromboplastin) which activates 10.
Intrinsic: Collagen, basement membrane, and activated platelets turn 12 to 12a. Which forms 11 a, then 9a. 9a activates 10. You already know that 8 and 5 are components needed for the activation of the other stuff. Finally 10 activates 2 (prothrombin). 13 is at the end of it all and makes the clot super strong.
Difference in factors between PT and PTT
PT: 7–10–2–5
PTT: 12, 11, 9, 8, 10, 5, 2 (everything except 7)
Why does heparin only affect PTT
Is it that it affects everything in the intrinsic pathway?
ACE affect on bradykinin
Inactivates it
Vitamin K pathway
Oxidized vitamin K is reduced by Epoxide Reductase which matures II, VII, IX, X, C, and S.
Warfarin MOA
inhibits vitamin K epoxide reductase
What does vWF carry
VIII
Antithrombin does what
Primary targets are thrombin and factor Xa. Inhibits activated forms of factors 2, 7, 9, 10, 11, and 12
Factor V leiden
Can’t be inhibited by activated protein C
Warfarin necrosis MOA
starting warfarin makes you acutely hypercoagulable because protein C has a very short half life, which can lead to the skin necrosis
Protein C activation
Thrombin-Thrombomodulin complex. The activated protein C uses Protein S as a cofactor to cleave and ianctivate Va and VIIIa.
Fibrinolysis does what
Destruction of coagulation factors
Primary hemostasis pathway
- vWF binds to exposed collagen upon endothelial damage.
- Platelets bind vWF via GpIb receptor and release ADP and Ca2+
- ADP helps platelets adhere to endothelium. Also binding to ADp receptor induces GpIIb/IIIa expression at patelet surface.
- Fibrinogen binds GpIIb/IIIa receptors and links platelets
- Plug stops bleeding
Pro-aggregation factors
TXA2 (released by platelets)
Decreased blood flow
Inc. platelet aggregation
Anti-aggregation factors
PGI2 and NO (released by entothelial cells)
Inc. blood flow
Dec. platelet aggregation
Aspirin MOA
inhibits cyclooxygenase (TXA2 synthesis)
Clopidogrel MOA
irreversibly blocks ADP receptor. inhibits ADP-induced expression of GpIIb/IIIa
Ticlopidine MOA
Same as clopidogrel
Abciximab MOA
inhibits GpIIb/IIIa directly
Ristocetin MOA
activates vWF to bind to GpIb. Used to diagnose von Willebrand disease. Normal platelet aggregation response not seen in vWD.
GpIIb/IIIa MOA
It literally crosslinks two platelets together by finding a fibrinogen monomer.
Bernard-Soulier syndrome
GpIb deficiency
Glanzmann thrombasthenia
GpIIb/IIIa deficiency
COX MOA
turns arachidonic acid to TXA2
Platelets have what
vWF and fibrinogen
How does acute phase reactants increase ESR
Fibrinogen causes RBC aggregation
ESR elevated diseases
Infectious, autoimmune, malignant neoplasms, GI disease (ulcerative colitis), pregnancy
ESR decreased diseases
Polycythemia, sickle cell anemia, CHF, microcytosis, hypofibrinogenemia
