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91 Cards in this Set
- Front
- Back
Light Blue top tube
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-citrate (binds Ca2+)
-plasma (anticoagulant) -used for most coagulation assays |
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Primary Hemostasis vs. Secondary Hemostasis vs. Fibrinolysis
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-Primary = formation of platelet plug
-Secondary = formation of fibrin clot -Fibrinolysis = removal of fibrin clot |
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Assays for assessing Primary Hemostasis
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-Platelet function assessment
-von Willebrand Factor concentration |
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Assays for Assessing Secondary Hemostasis
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Assays for assessing blood clotting:
-PT (Prothrombin time) -PTT (Partial Thromboplastin Time) -Fibrinogen Concentration Assay for assessing inhibition of clotting: -AT (antithrombin activity) |
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Assays for Assessing Fibrinolysis
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-FDP (Fibrin/Fibrinogen Degredation Products)
-D-dimer (Fibrin Fragment D-dimer) |
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General hemostasis after an injury
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-vasoconstriction reducing blood flow to the area
-platelet aggregation to plug the hole -Fibrin formation to solidify the plug -Fibrinolysis to control fibrin formation and dissolve clots |
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Effect of a defect in platelet aggregation to plug the hole
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-Petechiae
-Ecchymosis |
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Effect in the ability to coagulate and have fibrin solidify the plug
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-Gross bleeding
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Effect of defective fibrinolysis
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-Thrombosis
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Assays for measuring Platelet Function
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-Buccal mucosal bleeding time
-clotting time |
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Difference between buccal mucosal bleeding time and clotting time
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-Buccal mucosal bleeding time (in vivo)
-Clotting time (in vitro) |
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What does a prolonged Buccal Mucosal Bleeding Time mean?
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-decreased platelet function (too few, not functional)
-vWF deficiency |
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Types of Clotting Times
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-PT
-PTT -ACT |
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What are PT & PTT assessing vs. ACT?
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-PT, PTT = time for fibrin clot
-ACT = time for blood clot |
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Reasons for increased time to form a fibrin or blood clot
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-dec. [clotting factor]
-inc. [clotting inhibitor] |
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Clot Retraction assay
-tube use |
-red top
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Clot retraction Assay
-how is the blood collected |
-into cold saline
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Clot Retraction Assay
-what does delayed retraction mean |
-dec. platelet conc.
-dec. platelet function -cold sample --> dec. enzyme activity |
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Clot retraction assay
-how long is it supposed to take to clot |
-30 mins
-60 min in horses |
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von Willebrand Factor
-composition |
-plasma glycoprotein
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von Willebrand Factor
-circulates with what clotting factor |
-Factor VIII
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von Willebrand Factor
-produced by |
-endothelial cells
-platelets and megakaryocytes (cats, people) |
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von Willebrand Factor
-function |
-bridge platelets to injured vessel wall
-platelet-platelet bridging (part of primary hemostasis) |
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Blood samples to test for vWF
-how to collect -how to ship |
-Plasma
-EDTA -citrated blood -ship frozen plasma overnight with cold packs |
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Why may vWF be falsely low
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-poor sample collection --> platelet clumps/clots
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vWF assays
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-ELISA
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vWF disease types
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-Type 1: All types of vWF multimers present but dec. [vWF]
-Type 2: Large vWF multimers are deficient (uncommon) -Type 3: No vWF present |
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Type 1 vWF deficiency
-dog breeds |
-Dobermans
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Type 2 vWF deficiency
-dog breeds |
-GSH
-GWH -Horses |
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Type 3 vWF deficiency
-dog breeds |
-Chesapeake Bay Retrievers
-Dutch Kooikers -Scottish terriers -Shetland sheepdogs -Border collies |
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Signs of dogs having vWF < 35%
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Defective primary hemostasis
-spontaneous mucosal bleeding -prolonged iatrogenic bleeding time (surgical, venipuncture) -prolonged buccal mucosal bleeding time (BMBT) |
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Extrinsic Coagulation
-aka -enzymes -evaluated by |
-aka: Tissue factor
-enzymes: VII -evaluated by: PT |
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Intrinsic Coagulation
-aka -enzymes -evaluated by |
-aka: Surface-induced
-enzymes: XII, XI, IX, VIII -evaluated by: PTT & ACT |
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Common Coagulation Pathway
-enzymes |
-X
-V -II -I |
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What does TT assess?
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-conversion of fibrinogen to fibrin with the addition of thrombin
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How is the Tissue Factor Pathway (Extrinsic) activated?
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TF released from:
-damaged tissue -monocytes, macrophages, endothelial cells activated by endotoxin and some inflammatory cytokines |
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Coagulation factors in vivo
-typically circulate as... |
-circulate as plasma zymogens (proenzymes) that act on other factors when activated
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Plasma zymogen half-life
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-short (hours)
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Coagulation factor IV
-aka |
-free Ca2+
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Coagulation factor II
-aka |
-Prothrombin
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Coagulation factor I
-aka |
-Fibrinogen
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Coagulation Factors produced by hepatocytes
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-XII
-XI -X -IX -VIII -VII -V -Prothrombin (II) -Fibrinogen (I) |
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How is the surface-induced (intrinsic) coagulation pathway initiated?
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-when contact coagulation factors HMWK, PK, and Factor XII contact negatively charged surfaces
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Negatively charged surfaces that will induce intrinsic coagulation
-in vivo -in vitro |
in vivo
-collagen in vitro -Kaolin -Diatomes -Glass |
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Ca2+ is needed as a cofactor for which coagulation enzymes
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-VII
-X -IX -II |
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Blood tubes to use to remove Ca2+ from coagulation cascade
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-Purple
-Light blue -Grey |
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Phospholipids are needed as cofactors in coagulation. Where do the phospholipids come from in vivo and in vitro?
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-in vivo: platelets
-in vitro: reagents |
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Citrate to blood ratio in a collection tube
-effect of too much citrate -effect of too little citrate |
-1 : 9
-too much: increased PTT &/or PT -too little: blood sample clots |
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Proper plasma sample collection technique for coagulation assay
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-mix blood with citrate in a 1:9 ratio (citrate:blood)
-centrifuge citrated blood within 1 hr -analyze citrated plasma within 4 hrs or freeze -if shipping, ship frozen overnight with ice |
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Why should centrifuged citrated blood be analyzed within 1 hr?
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-platelet poor plasma may begin to form clots by then
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Thromboplastin
-function |
-activator of coagulation activity
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Partial thromboplastin
-function |
-Procoagulant that is devoid of tissue factor
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How does PTT work?
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-add Partial Thromboplastin to Citrated plasma
-activation of factors XII and XI -incubated to prime the process and get it ready to clot with the addition of excess Ca2+ -Excess Ca2+ added -Fibrin forms --> (PTT) |
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How does PT work?
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-Thromboplastin with excess Ca2+ is added to citrated plasma
-Time until Fibrin is detected (PT) |
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Rules of Thumb for prolonged plasma clotting times
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-PTT prolonged if < 30% activity from 1 or more factors (XII, XI, IX, VIII, X, V, II)
PT prolonged if < 30% activity from 1 or more factors (VII, X, V, II) |
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Increased Thrombin Time generally means
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-decreased fibrinogen
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Prolonged PTT due to
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Deficiencies in the surface-induced pathway (intrinsic) or common pathway
-acquired ( > 1 factor) -hereditary (1 factor) Inhibitors of surface-induced (intrinsic) or common pathway |
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Acquired defects in the intrinsic/common pathway
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-hepatic disease (decreased production)
-Decreased Vit K recycling in hepatocytes -decreased Vit K absorbtion (biliary) -DIC -Pathway inhibition |
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What can cause decreased Vit K recycling by hepatocytes
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-rodenticide
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Inhibition of the intrinsic or common pathway can be caused by...
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-heparin
-FDPs -antibody to phospholipid -antibody to coagulation factors |
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Prolonged PT due to
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Deficiencies in the tissue factor (extrinsic) or common pathway
-acquired ( > 1 factor) -hereditary (1 factor) Inhibitors of tissue factor (extrinsic) or common pathway |
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Acquired deficiencies of the intrinsic/common pathway are:
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-dec. production (hepatic, Vit K)
-inc. activation/consumption (DIC) |
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Vit K dependent coagulation factors
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-II
-VII -IX -X |
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PIVKAs
-define |
-Proteins Induced by Vit K Antagonism, Absence or deficiency
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PIVKA
-importance |
-coagulation factors (II, VII, IX, X) cannot bind to Ca2+
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Prolonged PTT & PT due to Warfarin toxicity
-pathogenesis |
Ingestion & absorption of warfarin
-inhibition of the recycling of Vit. K by hepatocytes --less reduced Vit K for the carboxylation of Factors II, XII, IX, X ---Production of defective factors II, VII, IX, X (PIVKAs) that can't bind Ca2+ ----Reduced plasma VII activity (shortest half-life) -----Prolonged PT ----Reduced plasma factor II, IX, X activity -----Prolonged PT & PTT |
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Prolonged PT & PTT due to warfarin toxicity has a similar pathogenesis to
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-prolonged cholestasis
-malabsorption of Vit K |
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How Does the PIVKA test work?
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Thrombotest
-add special thromboplastin with TF, fibrinogen, factor V and excess Ca2+ to citrated plasma -time until fibrin is detected -has a greater diagnositic sensitivity for samples with decreased factors II, X, VII, IX |
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Thrombin Time
-definition |
-thrombin-induced conversion of fibrinogen to fibrin clot
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Thrombin Time
-dependent on |
-[Fibrinogen]
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Diseases causing hypofibrinogenemia
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Increased fibrinogen consumption
-Intravascular coagulation -Increased fibrinogenolysis |
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Physiologic inhibitor of coagulation
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-Antithrombin III (AT)
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Antithrombin binds to what factors?
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-IIa (thrombin)
-IXa -Xa |
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Coagulation factor used in the Antithrombin assay
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-Xa
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Tube to collect blood in for Antithrombin assay
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-green top (heparin)
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Describe how antithrombin works
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-AT is produced by hepatocytes
-AT binds with heparin sulfate, creating a receptor for Thrombin -AT-hep. complex binds Thrombin -Thrombin-AT complex removed by hepatocytes |
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Decreased Antithrombin activity can be due to:
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-Dec. production (dec. functional mass)
-Inc. loss (PLN) -Inc. consumption (DIC, Sepsis, Heparin administration) |
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What can happen if there is decreased inhibition of clotting?
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-more prone to forming thrombi in vessels
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Describe the 10ase assay
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-heparin binds to antithrombin
-the more antithrombin that gets bound, the more enzyme Xa will be inhibited |
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FDP
-defintion |
-Fibrinogen Degredation product
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What cleaves fibrin and fibrinogen to form FDPs
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-Plasmin
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Where does Plasmin come from?
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Tissue injury-->tissue releases t-PA --> plasminoen converted to plasmin
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Fibrinolysis
-pathogenesis |
Tissue injury (hypoxia, heat, neoplasia, infection....)
-release of T-PA --conversion of plasminogen to plasmin ---plasmin cleaves plasma fibrinogen to FDPs ----Inc. [FDPs] if the formation is greater than liver removal -activation of coagulation pathways --formation of fibrin in vessels -Release of T-PA --conversion of plasminogen to plasmin ---plasmin cleaves fibrin to FDPs and D-dimers ----inc. [FDPs] & [D-dimers] |
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FDP assay
-best blood sample to use |
-serum
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Increased FDP can be due to:
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-inc. fibrinolysis (DIC)
-inc. fibrinogenolysis (inc. plasmin activity) -dec. FDP clearance (liver, kidney, macrophages) |
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How does FDP act as an inhibitor?
-what are the effects |
Competes for fibrinogen-binding sites
-On thrombin: prolonged PT, PTT, TT, ACT, WBCT -On platelets: dec. platelet function |
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Consequence of high FDP in vivo
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-diffuse bleeding in DiC
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Causes of defects in Primary hemostasis
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-Thrombocytopenia
-vWF deficiency |
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Causes of defects in secondary hemostasis related to bleeding
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Coagulation factor deficiency:
-acquired (dec. production, inc. consumption) -hereditary Inhibitors (heparin, FDPs) |
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Causes of defects in secondary hemostasis related to thrombosis
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Decreased inhibitors (AT):
-dec. production -inc. loss -Inc. consumption |
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Causes of excessive fibrinolysis
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-Marked tissue damage --> Inc. Plasmin
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