19 Hemostasis

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    Hemostasis

    Contents

    Overview of normal hemostasis 3Blood vessels 3Platelets 4Coagulation system 5

    Diagram of coagulation cascade 6Regulatory mechanisms 7Fibrinolysis 7

    Clinical considerations 8

    Laboratory evaluation of platelets 9Sample collection 9Tests to evaluate platelets

    CBC 9Bone marrow examination 9Platelet function tests

    Bleeding time (buccal mucosal bleeding time) 9Other tests 10

    Tests for immune-mediated disease 10

    Disorders of platelets 11Thrombocytopenia 11

    MechanismsIncreased destruction of platelets

    Immune-mediated thrombocytopenia 11Infection 11

    Increased consumptionDIC 11Vasculitis 13

    Decreased production 13Abnormal distribution 13Hemorrhage 13

    Tests 13Breed differences 14

    Thrombocytosis 14Mechanisms

    Reactive 14

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    Regenerative 14Decreased sequestration 14Essential thrombocythemia 14

    Platelet function disordersPrimary 14

    Glanzmanns thrombasthenia 14Others 14

    Secondary 15Von Willebrandd disease 15

    Laboratory evaluation of coagulation 16Sample collection 16Tests to evaluate coagulation

    Activated partial thromboplastin time (PTT) 16

    Activated clotting time (ACT) 16Prothrombin time (PT) 17PIVKA 17Thrombin time (TT) 17Fibrinogen 17Fibrin degradation products (FDPs) 18D-dimer 18

    Antithrombin (AT; ATIII) 18Specific factor assays 18

    Disorders of coagulation 19

    Vitamin K antagonism or deficiency 19DIC 20Coagulopathy associated with liver disease 20Inherited coagulation disorders

    Hemophilia A 20Hemophilia B 21Factor XII deficiency 21Others 21

    Bleeding associated with vascular disorders 21

    Blank table: Expected test results for different pathologic conditions 22

    Recommended reading 23

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    Overview of normal hemostasis

    Summary of major events in normal hemostasis:

    Formation of primary platelet plug (primary hemostasis)

    Formation of insoluble clot of cross-linked fibrin (secondary hemostasis)

    Clot retraction

    Fibrinolysis

    The main components of hemostasis are platelets, blood vessels, and thecoagulation system. They are highly interconnected, and bleeding disordersmay result if any of these systems are perturbed.

    GPIb

    platelet

    Fibrinogen

    receptor

    ( IIb3a)

    vWFFactor VIIIendothelium

    sub-endothel ial collagen

    plasmin

    FDPs/D-dimer

    activation of

    coagulation

    cascade

    fibrin

    ogen

    HemostasisHemostasis: The Big Picture: The Big Picture

    plateletthrombin fibrin

    Blood vessels

    Blood vessles have many key functions in hemostasis, including:

    Structural framework for hemostasis (subendothelial collagen)

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    Neuromechanical (vasoconstriction)

    Biochemical (endothelial synthesis and metabolism of key regulatorymolecules)

    Platelets

    Production regulated mainly by thrombopoietin (TPO)

    Lifespan= apx. 1 week

    Structure:

    o Flat disk shape when quiescent; spherical w/ pseudopodia whenactivated

    o Membrane invaginations form a network within the platelet (opencanalicular system) involved in release of contents, expansion ofsurface area when activated

    o Dense tubular system (modified endoplasmic reticulum) is a reservoirfor calcium

    o Alpha and dense granules contain many bioactive molecules, includingcalcium, ADP, fibrinogen, von Willebrands factor (vWF), histamine,serotonin

    o Cytoskeletal components maintain shape, mediate shape change, alsoinvolved in release of granule contents and receptor interactions

    o Surface receptors include GPIIb-IIIa (fibrinogen receptor, aka IIb3aintegrin) and GPIb (vWF receptor)

    Activation of platelets is triggered by soluble agonists (e.g., thrombin), orinsoluble agonists (e.g., collagen), followed by:

    o Adhesion to damaged blood vessel

    o Shape change and aggregation with other platelets

    o Release of bioactive substances (granule contents, TXA2)

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    o Viscous metamorphosis gel-like mass of platelets fused togetherand eventually incorporated into the clot

    Major functions of platelets:

    o Formation of platelet plug (primary hemostasis)

    o Localization of coagulation on platelet surface

    o Clot retraction

    o Also play a role in inflammation, wound healing

    Coagulation system

    The coagulation system involves interconnected pro- and anti-coagulantpathways that are maintained in a delicate balance to allow for:

    Rapid formation of an insoluble fibrin clot only when and where it isappropriate

    Eventual elimination of the clot

    Prevention of inappropriate clotting during normal homeostasis.

    Activation of the coagulation system involves linked enzymatic reactions aseries of conversions of inactive proenzymes to activated enzymes as well asother proteins, calcium, and platelet phospholipids. This process eventuallyresults in the formation ofthrombin, an enzyme that converts fibrinogen tofibrin. Fibrin is cross-linked to form a stable polymerized clot that alsoincorporates platelets.

    The coagulation system is conventionally considered to consist ofintrinsic,extrinsic, and common pathways this is an oversimplification, but helps with

    interpreting test results and localizing defects.

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    Intrinsic Pathway Extrinsic Pathway

    XII XIIa + PK + HMWK

    XI XIa

    IX IXa

    VIII VIIIa

    VIIa VII

    X Xa

    V Va

    Prothrombin (II) Thrombin (IIa)

    Fibrinogen Fibrin

    Cross linked fibrin

    XIIIa XIII

    Common

    Pathway

    (IXa + PL + VIIIa + Ca+2)

    (VIIa + Tissue factor + Ca+2 + PL )

    Calcium (Ca2+) and platelet phospholipid

    (PL) are cofactors for several reactions

    (Xa + Va + PL + Ca+2)

    Negatively charged surface (e.g., collagen)

    Tissue factor

    Activation of the intrinsic pathway begins with the activation of factor XII bycontact with a negatively charged surface. Once activated, factor XIIa quicklybinds and activates prekallikrein (PK), high molecular weight kininogen (HMWK),and factor XI forming a cohesive complex. The extrinsic pathway is initiated bythe release of tissue factor (TF) by damaged tissue or activated endothelial cellsand macrophages. Tissue factor binds factor VII forming an active complex thatnot only activates factor X but also factor IX of the intrinsic pathway. The intrinsicand extrinsic pathways have common endpoints that result in the activation offactor X, the beginning of the common pathway. Factors VIII and V arecofactors that accelerate coagulation; both are predominantly activated bythrombin. Factor XIII is also activated by thrombin and functions in the cross-

    linking of fibrin resulting in an insoluble clot. Platelet phospholipid (PL) isexpressed on activated platelet membranes and provides a structure upon whichcoagulation factor activation is greatly accelerated. Ca2+ links negatively chargedsurfaces of vitamin-K dependent factors to PL, positioning these enzymaticclotting factors for efficient reactions on their substrates; Ca2+ also facilitates thebinding of other factors.

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    Regulatory mechanisms are critical to the prevention of inappropriate orexcessive clotting, and eventual dissolution of the clot (fibrinolysis). Pro- andanti-coagulant pathways are normally maintained in a balance that avoids hyper-

    or hypocoagulable states. Anticoagulant and fibrinolytic pathways provide criticalchecks & balances these pathways are intitiated simultaneously withactivation of the coagulation system.

    Regulators of hemostasis include:

    Antithrombin (AT; also known as antithrombin III or ATIII) inactivatesthrombin; heparin potentiates activity of AT

    Protein C (w/ its cofactor, Protein S) inactivates Factors Va and VIIIa

    Thrombin in addition to its procoagulant and platelet activating activities,thrombin also:

    Converts plasminogen to plasmin, which lyses fibrin

    Activates Protein C

    Stimulates production of prostacyclin, a platelet inhibitor andvasodilator

    Thrombomodulin binds thrombin, promotes thrombin-Protein Cinteractions

    Tissue factor pathway inhibitor (TFPI) diminishes factor VIIa/TF complexactivity

    Fibrinolysis refers to dissolution of the fibrin clot, which results from the action ofplasmin on fibrin

    Inactive plasminogen is converted to plasmin by:

    Tissue plasminogen activator (tPA) and urokinase plasminogenactivator (uPA)

    Factor XIIa Thrombin

    Fibrin degradation products (FDPs; also known as fibrin split products,FSPs)

    Assays for FDPs used to detect inappropriate coagulation

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    FDPs can impair hemostasis by inhibiting fibrin polymerization andinhibiting platelets

    D-dimeris a specific type of FDP resulting from breakdown of cross-linked fibrin

    Regulators of fibrinolysis

    Inhibition of plasminogen

    Inhibition of plasmin

    Clinical considerations

    Signalment, history, clinical signs are important in evaluating the cause ofbleeding.

    Age, sex, breed may be important in distinguishing acquired v. hereditarydiseases

    History e.g., trauma, rodenticide exposure, family history of bleedingtendency

    Signs

    -

    Disorders of primary hemostasis typically result in small bleeds(e.g., petechiation, mild ecchymosis, bleeding from mucous membranes,bleeding immediately after venipuncture)

    -Disorders of secondary hemostasis typically result in big bleeds(e.g., hemorrhage into body cavities/joints, marked ecchymosis, largehematomas, delayed bleeding after venipuncture)

    Basic principles:

    Obtain diagnostic samples before initiating therapy

    Use appropriate collection and handling techniques (including using theright blood tube, filled properlyif youre not sure, check 1st with the lab)

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    Laboratory evaluation of platelets

    Sample collection

    Good venipuncture technique to avoid activating platelets, which maycause false test results (e.g., aggregation may cause false decrease inplatelet concentration)

    In most species, blood collected into an EDTA (purple top) tube for a CBCis fine for routine evaluation of platelets

    Some specialized platelet tests require collection of blood into sodiumcitrate (light blue top tube) or other anticoagulant

    Tests to evaluate platelets

    Complete blood count (CBC) In most clinical settings, the plateletconcentration (# per microliter) and mean platelet volume (MPV, expressed infL) values will be determined as part of the routine CBC, using an automatedhematology analyzer. The technology of these instruments continues toimprove.

    Estimating platelet number from a blood smear:

    est. # platelets/uL = [avg. #/HPF (100x objective)] x (20,000)

    Scan the feathered edge of the smear for platelet clumping (esp. commonin cats), which may cause a falsely low platelet count and platelet estimate

    MPV (fL) tends to increase with a regenerative response

    Platelet morphology (blood smear) evaluate size, shape, granularity ofplatelets; verify that values determined by automated counter areconsistent with the blood smear

    Bone marrow examination (aspirate for cytology and/or core biopsy forhistopathology) to assess thrombopoiesis, particularly in the case ofunexplained thrombocytopenia

    Tests to evaluate platelet function

    Bleeding time aka buccal mucosal bleeding time (BMBT) or templatebleeding time) assesses platelet plug formation by measuring time

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    interval between inflicting of standardized wound and cessation ofbleeding; usually performed on oral buccal mucosa

    -Prolonged time may be due to primary or secondary platelet functiondefect, von Willebrands disease, vascular defect, decreased number ofplatelets

    - Low sensitivity test

    - Reference interval is species- and site-dependent; can do a normalcontrol

    - Contraindicated in patient is thrombocytopenic (cannot interpret results)

    Other tests to characterize platelet function abnormalities some ofthese are only available through specialized laboratories

    -Clot retraction test crude test; results will be abnormal (lack of normalretraction) in some types of primary platelet function defects

    -PFA-100 instrument, simulates a damaged blood vessel uses wholeblood, measures time for a platelet plug to occlude an aperture

    - Platelet aggregometry assesses platelet aggregation in response tophysiologic agonists

    -Flow cytometry to assay for expression of surface molecules

    -Thromboelastography (TEG)global test of hemostasis thatevaluates platlets, coagulation, and fibrinolysis

    Tests for immune-mediated disease

    Flow cytometry detects immunoglobulin bound to the platelet surface,using a fluorescent-labeled antibody

    Immunofluorescent antibody (IFA) sometimes referred to as theantimegakaryocyte antibody test (AMAT), this test actually detects thepresence of immunoglobulin non-specifically: a smear of a bone marrowaspirate is incubated with a fluorescent-labeled antibody to species-specific immunoglobulin; positive staining of megakaryocytes supports adiagnosis of IMT.

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    Disorders of platelets

    A. Thrombocytopenia

    1. Signssevere thrombocytopenia (< 20,000/L) may result in spontaneoushemorrhage; uncomplicated mild or moderate thrombocytopenia typicallydoes not

    2. Mechanisms of thrombocytopenia

    a. Increased destruction of platelets

    i. Immune-mediated thrombocytopenia (IMT) usually severethrombocytopenia (often < 10,000 /L)

    Primary (idiopathic) IMT

    - Most commonly in young to middle-aged female dogs- Concurrent IMT and IMHA = Evans syndrome

    Secondary IMT

    - Drugs- Infection-

    Neoplasia- Vaccination?

    Isoimmune IMT (neonatal pigs, foals)

    ii. Infection

    FeLV

    A. platys

    b. Increased consumption of platelets

    i. Disseminated intravascular coagulation (DIC) usually moderate (>50,000/L) thrombocytopenia

    Definition: syndrome caused by continuous activation ofcoagulation and fibrinolysis, resulting in thrombosis of themicrovasculature and hemorrhage due to depletion of coagulationfactors and platelets; also called consumptive coagulopathy

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    Underlying disorder(s)

    Systemic activation of coagulation

    Intravascular Depletion of plateletsdeposition of fibrin & coagulation factors

    Thrombosis of small Bleeding& midsize vessels

    Organ failure

    Adapted from: M. Levi & H.T. Cate, NEJM, 341(8), 1999

    Laboratory diagnosis classically based on a triad of findings:

    - Thrombocytopenia- Prolonged coagulation time(s)- Decreased fibrinogen +/or increased fibrin degradation products

    However, DIC may occur in less fulminant forms that do not meet all ofthese diagnostic criteria. More complex scoring systems are used tocharacterize DIC in human medicine.

    Pathogenesis:

    - Release of thromboplastin (tissue factor) generation of thrombin- Defective inhibition of coagulation (e.g., ATIII, protein C)- Defective fibrinolysis (e.g., PAI-1)

    Always secondary to another disease process, for example:

    - Neoplasia- Sepsis- Endotoxemia- Shock- Heat stroke- Intravascular hemolysis- Obstetrical complications

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    DIC is a common condition in veterinary medicine

    ii. Vasculitis

    Inflammation & damage to blood vessels platelet adhesion andactivation

    Vasculitis may have various underlying causes (e.g., RMSF,immune-mediated)

    c. Decreased production of platelets

    - Immune-mediated destruction of precursors- Space occupation of the marrow

    -Drug-induced (e.g., chemotherapy, estrogen toxicity, chloramphenicol,streptomycin, sulfonamides)

    - Infection (e.g., Ehrlichia, FeLV, BVD, EIA)- Toxic (bracken fern poisoning in cattle)

    d. Abnormal distribution of platelets

    - Splenic sequestration of platelets

    e. Hemorrhage

    -Blood loss alone usually does not result in thrombocytopenia

    - If so, usually only mild decrease

    3. Test for thrombocytopenia (in addition to CBC):

    a. Bone marrow examination is indicated with any unexplained cytopenia,including thrombocytopenia

    - In cases of IMT, marrow usually has megakaryocyte hyperplasia- In cases of decreased production, typical bone marrow finding is

    megakaryocyte hypoplasia

    b. +/- additional tests as clinically indicated

    - Test for platelet-bound immunoglobulin (e.g., flow cytometry)- Tests for underlying or related disease

    - Immune-mediated disease (ANA, Coombs test)- Ehrlichia titers

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    - FeLV test- Coagulation panel

    4. Breed differences:

    Cavalier King Charles Spaniels often have macrothrombocytopenia (lowerthan normal numbers of abnormally large platelets)

    Greyhounds tend to have lower platelet numbers than other breeds (inaddition to RBC differences)

    B. Thrombocytosis

    1. Mechanisms of thrombocytosis:

    a. Reactive fairly common, non-specific

    - Inflammation- Iron deficiency

    b. Regenerative

    - Recovery from thrombocytopenia

    c. Decreased sequestration

    - Splenic contraction (esp. horses), splenectomy (transientthrombocytosis)

    d. Essential thrombocythemia

    - Leukemia of platelet precursors, extremely rare

    C. Platelet function disorders (aka thrombocytopathies, thrombopathies)

    1. Primary intrinsic platelet function defect

    -Glanzmanns thrombasthenia (Great Pyrenees, otterhounds; alsoreported in some horse breeds) absent, markedly decreased, orabnormal expression of fibrinogen receptor

    - Other rare conditions are also described in veterinary species

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    2. Secondary platelet function defects

    - IMT (may cause impaired function in addition to destruction)

    - Hyperglobulinemia (excess protein coats platelet surface)

    - Uremia (bleeding tendency correlates with severity of azotemia)

    - Drugs (e.g, NSAIDs or aspirin cause reversible or irreversible inhibition ofarachidonic acid metabolism)

    - Increased fibrinolytic products in plasma (increased production, as in DIC;decreased clearance, as in liver failure)

    3. von Willebrands disease (vWD) deficiency of von Willebrand factor(vWF), a soluble factor that mediates binding of platelets to collagen andstabilizes factor VIII; synthesized mainly by endothelium.

    vWD is often considered a platelet disorder, but technically it is notrather it is a disorder of a soluble factor that influences platelet function.

    - The most common canine heriditary bleeding disorder, also describedin most domestic species

    - Variable severity of disease:

    Type I: partial quantitative deficiency (

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    PTT, ACT often normal, may be prolonged if factor VIII level is lowenough

    Normal PT

    Specific assays for vWF require specialized laboratory

    Laboratory evaluation of coagulation

    Sample collection

    Most tests require citrated plasma

    Good venipuncture technique; studies indicate that is clinically acceptableto collect blood from an IV catheter if proper technique is used

    Plastic or siliconized syringes, tubes Anticoagulant

    - sodium citrate (light blue top) tube, except for ACT, FDP tests- ratio of anticoagulant:blood must be 1:9 need to fill the tube properly

    Tests to evaluate coagulation

    Activated partial thromboplastin time (aPTT orPTT)

    Required sample: citrated plasma

    Measures time for fibrin clot formation after addition of a contactactivator, calcium, and a substitute for platelet phospholipid

    Deficiencies/dysfunction in intrinsic and/or common coagulationpathway (all factors except for VII and XIII) will cause prolongation ofPTT

    Insensitive test prolongation requires 70% deficiency

    Other causes of prolongation include polycythemia (less plasma perunit volume, so excess amount of citrate available to chelate calcium),heparin therapy

    Activated clotting time (ACT)

    Required sample: non-anticoagulated whole blood in special ACT tube(diatomaceous earth as contact activator)

    Used in practice setting performed by warming sample to body temp,monitoring for clot formation; normal times are 60-90 seconds in dogs,< 165 seconds in cats

    Less sensitive version of PTT prolongation requires 95% deficiency

    Severe thrombocytopenia may cause prolongation

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    One stage prothrombin time (OSPT orPT)

    Required sample: citrated plasma

    Measures time for fibrin clot formation after addition of tissue factor(TF, thromboplastin), calcium, and a substitute for platelet phospholipid

    Deficiencies/dysfunction in extrinsic (factor VII) and/or commoncoagulation pathway will cause prolongation of PT

    Insensitive test prolongation requires 70% deficiency

    PIVKA (proteins induced by vitamin K antagonism or absence) test

    Required sample: citrated plasma

    PIVKA are inactive (uncarboxylated) vitamin-K dependent factors; anincrease in PIVKA is not specific for vitamin K antagonism, but may bethe earliest and most sensitive detector

    The name of this test is misleading because the one available inveterinary medicine is essentially a version of the PT using anespecially sensitive thromboplastin reagent

    Thrombin time (TT)

    Required sample: citrated plasma

    Measures time for fibrin clot formation after thrombin (factor IIa) is

    added; two kinds of assays with or without calcium Defects directly involving formation and/or polymerization of fibrin will

    prolong this test i.e., if the lesion is upstream of the conversion offibrinogen to fibrin, the TT will be normal

    Fibrinogen

    Required sample: citrated plasma

    Fibrinogen concentration measured based on time to clot formationafter addition of thrombin; this is essentially the same as the thrombin

    time, above, and is a more accurate method than the heat precipitationmethod

    Decreased fibrinogen may be due to increased consumption (DIC) ordecreased production (liver disease)

    Increased fibrinogen is associated with inflammation, renal disease,dehydration

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    Fibrin degradation products (FDPs)

    Required sample: special FDP tube (get from lab) Used in the practice setting (Thrombo-Wellcotest)

    Performed by adding blood to a special tube containing thrombin and atrypsin inhibitor (sample clots almost instantly in normal dogs andcats), and incubating two dilutions of serum (1:5 and 1:20) withpolystyrene latex particles coated with sheep anti-FDP antibodies(should be negative in normal dogs and cats, but positives have beenreported in normal cats)

    D-dimer test

    Required sample: citrated plasma Latex agglutination test

    Validated in dogs but not cats

    Assays for a specific type of FDP resulting from breakdown ofcrosslinked fibrin; often used as part of a DIC panel; can be used as anegative predictor to rule out pathologic thrombosis (e.g., pulmonarythromboembolism); will also be increased when there is appropriateclotting

    Antithrombin (AT; aka antithrombin III, ATIII)

    Required sample: citrated plasma Decreased due to decreased production (liver disease), loss (protein

    losing nephropathy or enteropathy), consumption (DIC), chronicheparin therapy

    Specific factor assays

    Required sample: citrated plasma

    Performed at specialized laboratories

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    Disorders of coagulation

    A. Vitamin K antagonism or deficiency

    1. Causes:

    Poisoning with coumarin derivatives (e.g., rodenticides, mycotoxin frommoldy sweetclover in cows)

    Fat malabsorption (uncommon) Dietary deficiency (rare) Antibiotics that cause decreased absorption or utilization by the liver

    2. Pathophysiology of rodenticide toxicity

    Vitamin K-dependent coaguation factors are II, VII, IX, and X;activation of these factors requires post-translational carboxylation;vitamin K is an essential cofactor for this reaction, and is oxidized (tovitamin K1 epoxide) in the process

    Anticoagulant rodenticides are vitamin K antagonists; they inhibit vitamin Kepoxide reductase, the enzyme that converts vitamin K back to its activeform; effect lasts until rodenticide is metabolized and cleared

    - examples: warfarin (1st generation), bromodiolone andbrodifacoum (2nd generation more potent, longer t1/2)

    Inactive factors

    (II, VII, IX, X, also

    Protein C and

    Protein S

    active factors

    (carboxylated)

    vitamin K (active) vitamin K epoxide (inactive)

    carboxylase

    XX = inactivation ofvitamin K epoxidereductase, the enzyme that maintains vitamin

    K in the active form

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    3. Laboratory features of rodenticide toxicity

    Factor VII has the shortest t1/2, so initially prolonged PT may be the only

    abnormality on the coagulation panel; eventually, PTT and ACT will alsobe prolonged

    PIVKA are inactive (uncarboxylated) vitamin-K dependent factors; they arecarboxylated to active form within 8-12 hours of vitamin K administration

    In uncomplicated cases, platelet count is usually within the referenceinterval

    B. DIC

    Definition, pathophysiology, diagnosis are covered above, in section onthrombocytopenia due to increased consumption of platelets. Note that

    coagulation factors are also depleted due to consumption in DIC.

    C. Coagulopathy associated with liver disease

    The liver is the site of synthesis and clearance of most clotting factors andinhibitors, and fibrinolytic agents and inhibitors (factor VIII produced mainly byendothelium, including hepatic sinusoids).

    Pathogenesis:

    Decreased synthesis of coagulation factors (except factor VIII), ATIII

    Production of abnormal coagulation factors Decreased clearance of FDPs, activated clotting factors These factors may lead to hypo- or hypercoagulable states

    D. Inherited coagulation disorders

    Many inherited disorders of coagulation have been reported in animals.Signalment may provide important information. Recall that PT and PTT arerelatively insensitive and may not be prolonged in an animal with a factordeficiency.

    Examples:

    1. Hemophilia A deficiency of factor VIII (not vWF)

    - Described in dogs, cats, horses, cattle- Mode of inheritance: X-linked recessive in dogs, horses- Variable severity of disease- Laboratory findings:

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    Normal platelet count, bleeding time

    PTT, ACT prolonged if deficiency is severe enough

    Normal PT

    Specific assay requires specialized laboratory (Cornell)

    2. Hemophilia B deficiency of factor IX

    Similar disease and inheritance pattern to Hemophilia A

    3. Factor XII deficiency

    The most common congenital bleeding disorder in cats

    Affected animals typically do not have clinical bleeding tendencies Prolonged PTT or ACT, other tests within normal limits

    4. Inherited deficiencies of most other coagulation factors have also beenreported (e.g., factor VII deficiency in beagles, factor XI deficiency in KerryBlue Terriers).

    Bleeding associated with vascular disorders

    Pathogenesis: failure to support collagen-platelet interactions and adhesion

    initiating hemostasis

    Causes:

    Vasculitis Collagen disorders (e.g., Ehler-Danos syndrome, reported in boxers,

    springer spaniels, cats)

    Clinical features are those of the underlying disorder, mucosal surface bleeding,prolonged bleeding time. These types of conditions generally require histologicevaluation.

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    Expected laboratory test results for different pathologic conditions

    ConditionPlateletcount

    BMBT PT ACT/PTT

    Fibrino-gen

    FDP/D-dimer

    AT

    Thrombocyto-penia

    *

    vWD

    Platelet functiondefect (1 or 2)

    DIC

    Vitamin Kantagonism/deficiency

    Severe liverdisease

    Extrinsicpathwaydeficiency

    Intrinsicpathwaydeficiency

    Commonpathwaydeficiency

    Fibrinogendeficiency/dysfunction

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    Recommended reading

    Stockham SL, Scott MA. 2008. Hemostasis. In Fundamentals of Veterinary

    Clinical Pathology, 2nd edition. Ames: Blackwell Publishing.

    Stockham SL, Scott MA. 2008. Platelets. In Fundamentals of VeterinaryClinical Pathology, 2nd edition. Ames: Blackwell Publishing.

    Topper MJ, Welles EG. 2003. Hemostasis. In Duncan & Prasses VeterinaryLaboratory Medicine: Clinical Pathology, edited by KS Latimer, EA Mahaffey,KW Prasse, 4th edition. Ames: Iowa State Press.