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Flashcards in Coagulation Deck (84):
1

Hemostasis

process which spontaneously arrests the flow of blood from the vessels carrying blood under pressure. Causes bleeding to stop

2

Thrombosis

A pathologic process in which one or more components of the normal hemostatic mechanism is activated wrong place, wrong time

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hemostatic thrombus

the "plug" that seals off an injured artery or vein. most often referred to as a thrombus

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what forms the hemostatic plug?

fibrin deposition and platelet plug

5

what limits and removes the hemostatic plug?

anti-coagulant and fibrin lysis

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pathology

the precise study and diagnosis of disease

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virchow's triad in thrombosis

endothelial injury, hyper coagulability, abnormal blood flow. Endothelial integrity is the most important factor.

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what causes thrombosis?

too much clotting/platelet plug formation or too little anticoagulant/fibrinolytic activity

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direction of thrombus movement (typically)?

towards the heart. Anterograde in veins and retrograde in arteries

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mural thrombi

clots occurring in the cardiac chambers and aorta

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vegetations

thrombi on the heart valves

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lines of zahn

laminated appearance of thrombi due to the flow of blood over the clot (like rock sedimentation)

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white layers in Lines of Zahn

platelets & fibrin (pink under microscope)

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red layers in Lines of Zahn

RBCs

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arterial thrombi

most common in coronary, cerebral, and femoral arteries. commonly caused by endothelial injury (ruptured atherosclerotic plaque, vasculitis, trauma), white thrombus

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venous thrombi

most common in lower extremities (90%), upper extremities, pelvic plexi, portal/hepatic veins. caused by stasis, RBC trapping=red thrombus

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two main features of thrombi

lines of zahn, attachment to endothelial wall

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4 fates of thrombi

propagation, embolization, dissolution, recanalization

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thrombus propagation

continued growth

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thrombus embolization

portion of/entire thrombus dislodges and travels via flow of blood to another site

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thrombus dissolution

fibrinolysis can result in breakdown

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thrombus recanalization

become organized via ingrowth of endothelial cells, smoot muscle cells and fibroblasts. new channels form and reestablish blood flow. occurs in older thrombi.

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saddle embolus

sits between bifurcation of two vessels.

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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)

25

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.

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definition of coagulation

forming and getting rid of fibrin clots

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what comes in contact with blood when an artery is punctured?

collagen and tissue factor

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clotting cascade

a complex mechanism for producing a limited amount of thrombin quickly at a site of vascular injury

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actions of thrombin

cleaves fibrinogen, activates platelets, activates 5a/8a/11a (positive feedback of itself), activates protein C (negative regulation of itself)

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fibrinogen

precursor of fibrin. activated to fibrin via thrombin protease

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fibrin

forms the mesh plug in clots

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goal of clotting cascade

convert prothrombin (2) to thrombin (2a)

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which of the clotting cascade factors are not proteases?

V, VIII (5,8)

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Scaffold proteins in clotting cascade

5,8. assemble multiprotein complexes that greaty accelerate clotting rxns. substrates for thrombin.

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clotting cascade number for thrombin

2a

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extrinsic tissue factor pathway in clotting cascade

tissue factor/7a complex activates 10a, which converts prothrombin to thrombin (2a). occurs on surface of cells.

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mechanism of fibrin creation

thrombin (2a) converts fibrinogen to fibrin monomer, which then becomes polymer, which are then cross linked by 13a.

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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.

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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

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Ten-ase complex

Factor 8a, phospholipid, Ca2+ machinery that accelerates conversion to 10a via 9a.

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Prothrombinase complex

Factor 5a, phospholipid, Ca2+ machinery that increases conversion to thrombin from prothrombin via 10a

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Intrinsic/Contact Pathway of clotting cascade

involves kallikrein, HMWK, 12, 11

much slower process that doesn't require tissue presence

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Serine proteases

12a, 11a, 9a, 10a, 7a, 2a

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bleeding deficiencies

11, 9, 7, 5 8, 10, 5, prothrombin, fibrinogen

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when does coagulation begin?

when tissue factor/7a complex cleaves 10 to 10a

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Hemophilia A

Factor 8 deficiency

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Hemophilia B

Factor 9 deficiency

48

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

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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

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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

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Normal range for prothrombin test

10-12 seconds

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Internationalized Normalized Ratio for the PT

compensates for differences between labs and machinery. 1 is normal.

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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)

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Normal range for aPTT

28-35 seconds

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things that increase aPTT

inherited factor deficiencies, acquired deficiencies of factor/cofactors, lupus anticoagulant, factor antibodies, drug inhibitors

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lupus anticoagulant

an antibody directed against phospholipid. slows aPTT, but doesn't signify a bleeding disorder

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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.

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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.

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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)

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tissue factor deficiency

embryonic lethal

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where are most clotting factors synthesized?

hepatocytes

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exceptions to clotting factors synthesized in hepatocytes

Factor 8 (liver, but not hepatocytes)
von Willebrand factor (megakaryocytes)

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vitamin K

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

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vitamin k dependent clotting factors

2,7,9,10, protein C

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gamma carboxyglutamate

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

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warfarin role in anticoagulation

inhibits the recycling of vitamin k. depletes the liver of it by locking it into epoxide form.

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another name for warfarin

coumadin

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anti-thrombin

inhibits thrombin and 10a.

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protein C

inhibits the ten-awe and prothrombinase complexes by inactivating factors 8a&5a

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heparin

binds to anti-thrombin and makes it an even stronger inhibitor

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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)

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plasmin role

degrades clot. a protease that likes many substrates and is therefore present as plasminogen in the plasma

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marker of clot production

Fibrin D Dimer (can only be created if fibrin has been cross linked)

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epistaxis

nose bleed

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Ecchymosis

bruise

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hemarthrosis

joint bleeding

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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

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platelets

serve as binding sites for the assembly of coagulation factor complexes, accelerating the conversion of prothrombin to thrombin and promoting clotting

79

factors tested by PT

7, 10, 5, 2, fibrinogen

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intrinsic pathway scaffold

HMWK (high molecular weight kininogen)

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contact factors

12, PK, HMWK

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accelerants in intrinsic pathway

work by increasing the surface area for formation of contact factor complexes

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factors tested by aPTT

12, HMWK, PK, 11, 9, 8, 5, 10, 2, fibrinogen (anything other than 7)

84

what people have the most prolonged aPTT test times?

those with 12, HMWK, or PK deficiencies. But they don't have bleeding disorders! thrombin can produce 11 as well