Flashcards in Coagulation Deck (84):
process which spontaneously arrests the flow of blood from the vessels carrying blood under pressure. Causes bleeding to stop
A pathologic process in which one or more components of the normal hemostatic mechanism is activated wrong place, wrong time
the "plug" that seals off an injured artery or vein. most often referred to as a thrombus
what forms the hemostatic plug?
fibrin deposition and platelet plug
what limits and removes the hemostatic plug?
anti-coagulant and fibrin lysis
the precise study and diagnosis of disease
virchow's triad in thrombosis
endothelial injury, hyper coagulability, abnormal blood flow. Endothelial integrity is the most important factor.
what causes thrombosis?
too much clotting/platelet plug formation or too little anticoagulant/fibrinolytic activity
direction of thrombus movement (typically)?
towards the heart. Anterograde in veins and retrograde in arteries
clots occurring in the cardiac chambers and aorta
thrombi on the heart valves
lines of zahn
laminated appearance of thrombi due to the flow of blood over the clot (like rock sedimentation)
white layers in Lines of Zahn
platelets & fibrin (pink under microscope)
red layers in Lines of Zahn
most common in coronary, cerebral, and femoral arteries. commonly caused by endothelial injury (ruptured atherosclerotic plaque, vasculitis, trauma), white thrombus
most common in lower extremities (90%), upper extremities, pelvic plexi, portal/hepatic veins. caused by stasis, RBC trapping=red thrombus
two main features of thrombi
lines of zahn, attachment to endothelial wall
4 fates of thrombi
propagation, embolization, dissolution, recanalization
portion of/entire thrombus dislodges and travels via flow of blood to another site
fibrinolysis can result in breakdown
become organized via ingrowth of endothelial cells, smoot muscle cells and fibroblasts. new channels form and reestablish blood flow. occurs in older thrombi.
sits between bifurcation of two vessels.
venous thrombi complications
pulmonary embolus. thromboemboli are able to pass through large caliber vessels until they reach the smaller arteriolar and capillary bed of the lungs. (arterial thrombi are more likely to affect end organs)
difference between thrombi and postmortem clots?
in post mortem clots, the blood separates out into components (current jelly & chicken fat). no adhesion to wall. might fill vessels but don't over distend them. no lines of zahn.
definition of coagulation
forming and getting rid of fibrin clots
what comes in contact with blood when an artery is punctured?
collagen and tissue factor
a complex mechanism for producing a limited amount of thrombin quickly at a site of vascular injury
actions of thrombin
cleaves fibrinogen, activates platelets, activates 5a/8a/11a (positive feedback of itself), activates protein C (negative regulation of itself)
precursor of fibrin. activated to fibrin via thrombin protease
forms the mesh plug in clots
goal of clotting cascade
convert prothrombin (2) to thrombin (2a)
which of the clotting cascade factors are not proteases?
V, VIII (5,8)
Scaffold proteins in clotting cascade
5,8. assemble multiprotein complexes that greaty accelerate clotting rxns. substrates for thrombin.
clotting cascade number for thrombin
extrinsic tissue factor pathway in clotting cascade
tissue factor/7a complex activates 10a, which converts prothrombin to thrombin (2a). occurs on surface of cells.
mechanism of fibrin creation
thrombin (2a) converts fibrinogen to fibrin monomer, which then becomes polymer, which are then cross linked by 13a.
Tissue Factor Pathway Inhibitor (TFPI)
endogenous inhibitor of extrinsic pathway. shuts down the TF/7a/10a complex. Absence produces a prothrombotic state due to unrestrained thrombin generation.
Pathway of clotting cascade that occurs if TFPI is inhibiting the extrinsic tissue factor pathway
pathway 2 where Tissue Factor/7a complex activates 9a to activate 10a, using Ten-ase complex with factor 8a scaffold
Factor 8a, phospholipid, Ca2+ machinery that accelerates conversion to 10a via 9a.
Factor 5a, phospholipid, Ca2+ machinery that increases conversion to thrombin from prothrombin via 10a
Intrinsic/Contact Pathway of clotting cascade
involves kallikrein, HMWK, 12, 11
much slower process that doesn't require tissue presence
12a, 11a, 9a, 10a, 7a, 2a
11, 9, 7, 5 8, 10, 5, prothrombin, fibrinogen
when does coagulation begin?
when tissue factor/7a complex cleaves 10 to 10a
Factor 8 deficiency
Factor 9 deficiency
what solution is blood drawn into for clotting tests?
citrate solution because it is a negatively charged molecule that binds to Ca ions present in blood. reduces the free ca concentration below the level needed to accelerate coagulation
Basic way to prep for clot test
blood is treated with citrate, spun to sediment cells. Then Ca, initiator of clotting, and phospholipids are added
Prothrombin test (PT)
Tests the extrinsic pathway.
initiator of clotting is tissue factor. Start with tissue factor and measure time to fibrin. independent of patients own tissue factor
Normal range for prothrombin test
Internationalized Normalized Ratio for the PT
compensates for differences between labs and machinery. 1 is normal.
activated Partial Thromboplastin Time (aPTT)
no tissue factor is added (charged surface activates contact factors instead), so used to test intrinsic pathway. Charged accelerant is added (such as ground glass)
Normal range for aPTT
things that increase aPTT
inherited factor deficiencies, acquired deficiencies of factor/cofactors, lupus anticoagulant, factor antibodies, drug inhibitors
an antibody directed against phospholipid. slows aPTT, but doesn't signify a bleeding disorder
workup if long aPTT is obtained
need to know if an inhibitor is present or if there is a factor deficiency. Mix patient plasma 1:1 with normal plasma and repeat aPTT.
Normal long aPTT workup
signifies a factor deficiency. will always have at least 50% of factor when mixed with normal plasma, which will be enough for normal cascade. will need to conduct factor assays.
prolonged long aPTT workup
clotting factors are not missing, instead a dominant negative/inhibitor is present. could be lupus inhibitor, factor inhibitor, or other causes like drugs (heparin)
tissue factor deficiency
where are most clotting factors synthesized?
exceptions to clotting factors synthesized in hepatocytes
Factor 8 (liver, but not hepatocytes)
von Willebrand factor (megakaryocytes)
cofactor required for protease synthesis in liver for factors 2,7,9,10. necessary for post translational modification of glutamate to gamma carboxylated glutamate (Gla) residues
vitamin k dependent clotting factors
2,7,9,10, protein C
converted by vitamin k and carboxylase. sticks better to surface of cells. important in prothrombinase and ten-ase complexes that work on cell surface by attaching to negatively charged phospholipids
warfarin role in anticoagulation
inhibits the recycling of vitamin k. depletes the liver of it by locking it into epoxide form.
another name for warfarin
inhibits thrombin and 10a.
inhibits the ten-awe and prothrombinase complexes by inactivating factors 8a&5a
binds to anti-thrombin and makes it an even stronger inhibitor
factor V Leiden
mutation common to northern europeans. point mutation in factor 5 which affects cleavage site for protein C. Increases risk of thrombosis bc ten-awe remains overactive (prothrombotic state)
degrades clot. a protease that likes many substrates and is therefore present as plasminogen in the plasma
marker of clot production
Fibrin D Dimer (can only be created if fibrin has been cross linked)
where is tissue factor expressed?
expressed on the cell surfaces of vascular smooth muscle cells, activated monocytes, diseased endothelial cells. expression is regulated by trauma and TNF
serve as binding sites for the assembly of coagulation factor complexes, accelerating the conversion of prothrombin to thrombin and promoting clotting
factors tested by PT
7, 10, 5, 2, fibrinogen
intrinsic pathway scaffold
HMWK (high molecular weight kininogen)
12, PK, HMWK
accelerants in intrinsic pathway
work by increasing the surface area for formation of contact factor complexes
factors tested by aPTT
12, HMWK, PK, 11, 9, 8, 5, 10, 2, fibrinogen (anything other than 7)