Coagulation Disorders Flashcards by Arriane Cyrel (MTI)

: proteins that initiate the IP

XII, HK, PK

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denotes the time when plasma coagulation factors come in contact with tissue/artificial surfaces

CONTACT PHASE

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product of contact phase:

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Not significant in the body when deficient because there are still intrinsic activators of FIX

XII, HK, PK

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Presence or absence of these factors does not cause bleeding disorders because thrombin will still be generate independently = patient is asymptomatic = no manifestation of bleeding

XII, HK, PK

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Tested via in vivo testing (not by mixing studies)

XII, HK, PK

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The time it takes for free factors to activate is the time when the plasma will be adhering to tissue or artificial surfaces

CONTACT PHASE

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CONTACT PHASE FACTORS DEFICIENCY
autosomal recessive disorder

Factor XII (Hageman factor) Deficiency

Prekallikrein (Fletcher factor) Deficiency

HMWK (Fitzgerald/Flaujeac factor) Deficiency

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clinical findings: no bleeding disorder but manifested by excessive clotting (but rather thrombotic disorder)

Factor XII (Hageman factor) Deficiency

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laboratory findings: all normal except APTT (prolonged)

Factor XII (Hageman factor) Deficiency

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correction: adsorbed plasma, aged serum, fresh normal plasma (all reagent plasma with contact phase)

Factor XII (Hageman factor) Deficiency

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treatment: none

Factor XII (Hageman factor) Deficiency

Prekallikrein (Fletcher factor) Deficiency

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clinical findings: no bleeding disorder but manifested by excessive clotting

Prekallikrein (Fletcher factor) Deficiency

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laboratory findings: all normal except APTT (shortened)

Prekallikrein (Fletcher factor) Deficiency

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deficiency results to:
• poor contact phase reactions
• kinin formation deficiency
• defective fibrinolysis reaction

HMWK (Fitzgerald/Flaujeac factor) Deficiency

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APTT: normal to mildly prolonged (low deficiency)

HMWK (Fitzgerald/Flaujeac factor) Deficiency

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Thrombin will still be generated

Factor XII (Hageman factor) Deficiency

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Thrombotic (abnormal formation of clots): FXII, aside from activating FXI, activates plasminogen to plasmin → more fibrinolysis

Factor XII (Hageman factor) Deficiency

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CF stops the bleeding during injury → Coagulation cascade continues to activate = ↓ FXII = ↓ Plasmin = ↓Fibrinolysis = ↑ Clot formation = Thrombosis

Factor XII (Hageman factor) Deficiency

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even if it has nothing to do w/ bleeding disorders

Factor XII (Hageman factor) Deficiency

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Does not cause bleeding disorders; Asymptomatic

Factor XII (Hageman factor) Deficiency

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FXII will bring (?) (cofactor) to activate plasminogen to plasmin

Prekallikrein (Fletcher factor) Deficiency

Kallikrein

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↓ Kallikrein = (?) Clot formation = (?)

Prekallikrein (Fletcher factor) Deficiency

↑

Thrombosis

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(?) APTT: PK reacts with (?) = (?) contact phase activation; indicates (?) of PK

Prekallikrein (Fletcher factor) Deficiency

shortened

kaolin (activator)

speeds up

low deficiency

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(?) APTT: indicates a (?) of PK in the circulation

Prekallikrein (Fletcher factor) Deficiency prolonged severe deficiency or absence

Does not cause bleeding disorders

FXII Prekallikrein (Fletcher factor) Deficiency

Absence = Lacks cofactor

HMWK (Fitzgerald/Flaujeac factor) Deficiency

Inability to produce bradykinin (↓ inflammatory responses)

HMWK (Fitzgerald/Flaujeac factor) Deficiency

can also be a cofactor of FXII and K with activating plasminogen to plasmin

HMWK (Fitzgerald/Flaujeac factor) Deficiency

Prolonged: severe deficiency

HMWK (Fitzgerald/Flaujeac factor) Deficiency

Not significant in vitro; No haemorrhagic tendency

HMWK (Fitzgerald/Flaujeac factor) Deficiency

complete absence or total deficiency of the entire HWMK

Fitzgerald

presence of HWMK, but absence of kinogen (kinogen: deficient protein portion)

Flaujeac (William’s Trait)

"love of hemorrhage"

Hemophilias

are inherited bleeding disorders characterized by a deficiency of the antihemophilic factors.

Hemophilias

<1%

Severe

Spontaneous bleeding

Severe

1-5%

Moderate

Spontaneous bleeding is uncommon

Moderate

may bleed with surgery or trauma

Moderate

5-20%

Mild

No spontaneous bleeding

Mild

may bleed with major surgery or trauma

Mild

CONTACT PHASE FACTORS DEFICIENCY :

INHERITED INTRINSIC PATHWAY HEMORRHAGIC DISORDERS :

most common hemophilia

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

sex-linked disorder transmitted on the X chromosome by carrier women to their sons (50% affected)

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

activation of VIII:C: thrombin (IIa)

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

role: cofactor to FIX to form intrinsic tenase in activation of FX

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

clinical signs and symptoms: • severe GIT and intracranial hemorrhage • prone to hemarthrosis

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

laboratory findings: prolonged APTT

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

correction: aged plasma, fresh adsorbed plasma (any plasma w/ FVIII preent)

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

not corrected by: fresh serum (consumed during coagulation) or aged serum

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

treatment/therapy (same In VW because it sirculates in complex with VIII:C): • cryoprecipitate: to arrest bleeding • Prophylactic DDAVP (I-desamino-8-D arginine-vasopressin)

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

exist in the royal family (Queen Victoria); incest: sharing of genes

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

mother always carry a carrier gene; affected X chromosome carries Hemophilia A (H-A) or a defect in Factor VIII:C

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

normal distribution: o male: carries X from mother and Y from father o female: carries X from mother and X from father

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

in H-A: o X from mother can be passed to male offspring (higher chance of inheriting the trait due to one X chromosome coming from the mother only) o male linkage of the family: affected by H-A

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

activators of VIII:C:

residual thrombin, low level thrombin from the cascade

(blood trapped in the joints)

hemarthrosis

crippling and deformed hip, elbow, ankle, and shoulder due to continuous hemarthrosis

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

o used to differentiate hemophilia a from other hemophilias

severe GIT and intracranial hemorrhage

: with GIT bleeding and intracranial haemorrhage

FVIII

: without GIT bleeding and intracranial haemorrhage

FIX

VIII:C belongs in the intrinsic pathway

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

: to arrest bleeding

cryoprecipitate

cryoprecipitate Contains

VIII, vWF, fibrinogen, fibronectin

Effected for qualitative defect of VIII:C

cryoprecipitate

Effected for qunlitative defect of VIII:C

Prophylactic DDAVP

Prophylactic: to prevent after encounter

Prophylactic DDAVP

Administered after uncommon bleeding disorder

Prophylactic DDAVP

Analogous to VIII:C – increase and stimulate endothelium to release VIII:C complex o raise VIII:C by 3-6x fold

Prophylactic DDAVP

Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

What is the effect of DDAVP therapy?

What coagulation test will be prolonged? Hemophilia A/Classic Hemophilia (Factor VIII:C Deficiency)

Hemophilia B/Christmas disease (Factor IX Deficiency)

▪ sex-linked disorder characterized by a deficiency of Factor IX

Hemophilia B/Christmas disease (Factor IX Deficiency)

▪ second most common hemophilia

Hemophilia B/Christmas disease (Factor IX Deficiency)

▪ activation: XI, K, VII

Hemophilia B/Christmas disease (Factor IX Deficiency)

▪ role: to form intrinsic tenase in activation of FX

Hemophilia B/Christmas disease (Factor IX Deficiency)

▪ clinical findings: - mild to severe bleeding disorder - no GIT and intracranial involvement - severe conditions may be indistinguishable from Hemophilia A

Hemophilia B/Christmas disease (Factor IX Deficiency)

▪ laboratory findings: prolonged APTT

Hemophilia B/Christmas disease (Factor IX Deficiency)

▪ correction: aged serum (any reagent plasma w/ FIX)

Hemophilia B/Christmas disease (Factor IX Deficiency)

▪ not corrected by: adsorbed plasma (no prothrombin group)

Hemophilia B/Christmas disease (Factor IX Deficiency)

▪ treatment/therapy: • Factor IX commercial concentrate • Fresh frozen plasma

Hemophilia B/Christmas disease (Factor IX Deficiency)

IX can be activated by

XI, K, VII

o isolated from plasma

Factor IX commercial concentrate

o in blood donation: separation of packed rbc from plasma from donor and recipient →pooled plasma→isolation of FIX

Factor IX commercial concentrate

Hemophilia B/Christmas disease (Factor IX Deficiency) What coagulation test will be prolonged?

→ These are autosomal recessive disorders with no associated bleeding tendencies. Patients are more vulnerable to excessive clotting (THROMBOSIS)

Prekallikrein; HMWK; Factor XII deficiency

Prekallikrein; HMWK; Factor XII deficiency What coagulation test will be prolonged?

Autosomal recessive

II VII X V XIII

-Autosomal recessive -Autosomal dominant

Prothrombin deficiency

F VII deficiency

VII

F X deficiency

-Afibrinogenemia -Dysfibrinogenemia

Owren's disease Labile factor deficiency Parahemophilia

F XIII deficiency

XIII

Liver disease Vit. K deficiency Oral anticoagulant therapy

II VII X

Severe liver disease DIC Fibrinolysis

I V XIII

- inherited lack of fibrinogen

• Afibrinogenemia (recessive)

- severe bleeding symptoms

• Afibrinogenemia (recessive)

- inherited deficiency of fibrinogen

• Hypofibrinogenemia (dominant)

- bleeding symptoms correlate with fibrinogen concentration

• Hypofibrinogenemia (dominant)

Soft tissue bleeding

Factor VII (stable factor) deficiency

Soft tissue bleeding and chronic bruising

Factor X (StuartPrower) deficiency

Mild to moderate bleeding symptoms

Factor V (Owren disease, labile factor) deficiency

Mild bleeding symptoms

Factor II (prothrom bin) deficiency

• spontaneous bleeding

Factor XIII (fibrinstabilizing factor) deficiency

• delayed wound healing

Factor XIII (fibrinstabilizing factor) deficiency

• unusual scar formation

Factor XIII (fibrinstabilizing factor) deficiency

• increased incidence of spontaneous abortion

Factor XIII (fibrinstabilizing factor) deficiency

spontaneous bleeding of mucosa, intestines, and intracranial sites

Factor I (fibrinogen) deficiency

Prolonged PT

Factor VII (stable factor) deficiency

Prolonged PT, aPTT, and Stypven Time/RVV T

Factor X (StuartPrower) deficiency

Prolonged PT and aPTT

Factor V (Owren disease, labile factor) deficiency Factor II (prothrom bin) deficiency

• prolonged bleeding time (fibrinogen bridges do not form, platelet aggregation defect)

Factor I (fibrinogen) deficiency

• decreased fibrinogen concentration

Factor I (fibrinogen) deficiency

• prolonged PT, aPTT, and thrombin time

Factor I (fibrinogen) deficiency

• 5.0 M urea test abnormal

Factor XIII (fibrinstabilizing factor) deficiency

• PT and aPTT normal

Factor XIII (fibrinstabilizing factor) deficiency

• Enzymatic and immunologic studies can be done

Factor XIII (fibrinstabilizing factor) deficiency

only factor that prolongs PT when deficient; TF cannot be corrected in any way/uncorrecte d, VII – corrected Ca is involved in intrinsic tenase – APTT should also be prolonged

Factor VII (stable factor) deficiency

aged serum

Factor VII (stable factor) deficiency Factor X (StuartPrower) deficiency

adsorbed plasma (PT becomes normal)

Factor V (Owren disease, labile factor) deficiency

Not corrected by: adsorbed plasma (including other factor deficiencies in prothrombin group – II, IX, X)

Factor VII (stable factor) deficiency

Not corrected by: adsorbed plasma

Factor X (StuartPrower) deficiency

Treatment: • fresh frozen plasma • cryo-free or cryodepleted plasma

Factor V (Owren disease, labile factor) deficiency

Note: very labile in storage (w/ VIII)

Factor V (Owren disease, labile factor) deficiency

(to avoid disappearance of plasma ; raises FV levels and helps patient to demonstrate less symptoms)

fresh frozen plasma

: left after some blood clotting proteins (cryoprecipitate) have been removed from fresh frozen plasma

cryo-free or cryodepleted plasma

(provides purer and more adequate FV when defective;)

fresh frozen plasma

contains functional coag factor

cryoprep

Not in born; stimulated by external factors

Acquired Coagulation Disorders

▪ majority of these substances are antibodies that targets proteins

Inhibitory Substances

• stimulated by infusion of blood and the recipient rejects it, forming antibodies against it

Inhibitory Substances

• release of tumor substances (recognized by the body as foreign thus it starts to attack and affects the coagulation factors)

Inhibitory Substances

• common cause: autoimmune diseases (production of autoantibodies attacking one’s own cell; inhibits own coagulation factors)

Inhibitory Substances

▪ also attacks one’s own cell thus inhibiting coagulation factors

Inhibitory Substances

: directed to specific factors

▪ LA

: directed to anti-PPL

▪ APA

: directed to other coagulation factors

▪ Anticardiolipin antibodies

directed against platelet phospholipid and phospholipid protein complexes (main target)

A. Non-specific inhibitor

Laboratory: presence will prolong the PTT (due to lack of PPL) and dilute Russell viper venom test (problem w/ FX, which requires PPL in its activation)

A. Non-specific inhibitor

▪ directed against specific coagulation factors: • Factor VIII:C • Factor IX • Factor Xl

B. Specific factor Inhibitors/Circulating anticogulants

Presence of FSP/FDP – seen in

fibrinolysis

interfere with polymerization of fibrin strands when not cleared

FSP/FDP

should only be present once cleaved by plasmin in an excess manner

FSP/FDP

fragments are powerful anticoagulants and inhibitor of thrombin

FSP/FDP

Tested by: • Latex agglutination • Measurement of fibrin monomers (quantitative) • Platelet count • Fibrinogen level assays • PT and APTT (prolonged)

FSP/FDP

functional decrease (since liver is normal and only vit. K is deficient) of II, VII, IX, X, Protein C, S and Z (Vit K dependent proteins)

Causes: • antibiotic intake • decreased absorption • antagonistic drugs

Vit K Deficiency

also poses a problem w/ coauglation

Vit K Deficiency

• necessary for the glutamic acid conversion into a gamma carboxyglutamic acid to enable the prothrombin group (II, VII, IX, X) to bind with calcium for coagulation process

Vitamin K

o Vit K is produced by normal intestinal flora or normal flora in the GIT

antibiotic intake

o Deficiency in normal flora = Vit K deficiency

antibiotic intake

: Vit K is not processed in the liver; proteins are not passed in the liver and not processed well/broken down; problem in the liver; malabsorption of Vit K = Vit K deficiency

Obstructive jaundice

: Vit K antagonists

warfarin, Coumadin

▪ Breast-fed babies: more prone to vitamin K deficiency because breast milk is sterile, which allows no bacterial intestinal colonization to occur.

Vitamin K deficiency

▪ Laboratory: Prolonged PT (VII, X, II) and prolonged aPTT (IX, X, II)

Vitamin K deficiency

Vitamin K deficiency What coagulation test will be prolonged?

can result in decreased synthesis of proteins: • coagulation factors • fibrinolytic factors (Plasmin) • regulatory/inhibitory proteins (anti-thrombin III, Protein C, Protein Z)

Liver/Hepatic Disease

also causes impaired clearance of activated coagulation factors

Liver/Hepatic Disease

most profound deficiency: FVII

Liver/Hepatic Disease

Laboratory: • Screening tests (Prolonged): - PT - aPTT - Thrombin Clotting Time (TCT)

Liver/Hepatic Disease

: to diagnose congenital or acquired fibrinogen deficiency

Thrombin Clotting Time (TCT)

: major site of hemostatic protein synthesis

Liver

activated coagulation factors uncleared in the circulation: 1. TPA 2. FSP

Liver/Hepatic Disease

Normal: while coagulating, tissue plasminogen is prepared to bind w/ fibrin clot, making the clot dissolution on time and not delayed

TPA

remains uncleared in the circulation after activation of plasminogen due to decreased synthesis of the regulatory protein TPAI = ↓ inhibitory proteins = TPA remains activated = causes excessive fibrinolysis

TPA

FSP causes anticoagulation or cleaving of factor V, VIII, X, and I even without fibrin formation

Liver/Hepatic Disease

(most labile with liver disease, Vit K deficiency, and intake of oral anticoagulant)

FVII

Clinical: Soft tissue bleeding

Liver/Hepatic Disease

Correction: aged serum

Liver/Hepatic Disease

Not corrected by: adsorbed plasma (including other factor deficiencies in prothrombin group – II, IX, X)

Liver/Hepatic Disease

Liver/Hepatic Disease What coagulation test will be prolonged?

replacement of more than 1.5 L blood volume in 24 hours

Massive Transfusion

▪ results to DILUTION of coagulation factors and increased introduction of anticoagulants

Massive Transfusion

▪ excess citrate decreases ionized calcium needed by the blood to clot

Massive Transfusion

▪ most profound deficiency: V and VIII:C (labile factors upon storage)

Massive Transfusion

: used to preserve blood, but chelates and binds to calcium; does not directly cause bleeding

Citrate

in the bag used to transfuse the px could contaminate the blood and bind the Ca of the px

Citrate

• Main: due to liberation of thromboplastic substance (containing TF) that activates coagulation

Disseminated Intravascular Coagulation (DIC)

• activation of plasminogen through the contact phase, thus coagulation and fibrinolysis occur simultaneously and either may dominate

Disseminated Intravascular Coagulation (DIC)

• consumption of coagulation factors and platelets (platelets are trapped in the clot produced by coag factors)

Disseminated Intravascular Coagulation (DIC)

• RBC fragmentation (RBC - is affected due to clotting; does not flow well making it deformed and nonfuncitonal)

Disseminated Intravascular Coagulation (DIC)

• Increased in FDP and D-dimer (D-dimer: indication of excess fibrinolysis)

Disseminated Intravascular Coagulation (DIC)

Types of DIC

1. Acute DIC 2. Chronic DIC

▪ appears within a few hours

Acute DIC

▪ skin: purpura, gangrene, and bullae

Acute DIC

▪ mortality: 60-80%

Acute DIC

▪ less hemorrhage

Chronic DIC

▪ thrombotic events (can lead to vascular occlusion)

Chronic DIC

DIC Prolonged:

• TCT • PT • APTT

DIC Decreased:

• Fibrinogen (decreased 4-24 hours after onset) • Platelet • AT-III

DIC Increased:

• FSP • Fibrin monomers

DIC Positive:

• D-dimer test (due to presence of FSP)

DIC What coagulation test will be prolonged?

▪ acid mucopolysaccharide that acts together with antithrombin III to inhibit thrombin

Heparin

▪ used to treat thrombotic disorders caused by excess thrombin

Heparin

▪ half-life: 3 hours

Heparin

▪ antagonizes Vit K (factors are present but not functioning)

Coumarin Drugs: Warfarin

▪ causes Protein induced by vitamin K absence (PIVKA)

Coumarin Drugs: Warfarin

: powerful inhibitor of thrombin

Heparin together w/ antithrombin III

Easy bruising

II, VIII, IX

Delayed wound healing

I, XIII

Hematomas

II, VIII, IX

Umbilical cord bleeding

X, XIII

Mucosal bleeding/Ecch ymosis

II, VIII, IX, XI

Miscarriage

I, XIII

Hemarthrosis

VIII, IX, X

Thrombosis

Abnormal fibrinogens; LA; Inhibitor deficiencies

Postsurgical bleeding

I, II, V, VII, VIII, IX, X, XI, XIII

Asymptomati c

FXII, PK, HK

Intracranial bleeding

VII, VIII, IX, XIII

DISORDERS of Fibrinolysis

Primary fibrinolysis (fibrinogen lysis)

▪ referred to as “Pathologic Fibrinolysis of PF”

Primary fibrinolysis (fibrinogen lysis)

▪ pure form and unusual (lethal; life-threatening)

Primary fibrinolysis (fibrinogen lysis)

▪ Cause: release of excessive amount of plasminogen activators (TPA) in circulation from damaged/malignant cells or ruptured vein resulting to the conversion of plasminogen to plasmin in the absence of fibrin formation (Ex. metastatic carcinoma)

Primary fibrinolysis (fibrinogen lysis)

▪ Treatment: anti-fibrinolytic drugs/antiplasmin

Primary fibrinolysis (fibrinogen lysis)

TPA should only activate plasminogen when there is a detected fibrin formation

Primary fibrinolysis (fibrinogen lysis)

No clot formed, no activation of FI = activates independently due to excess ruptured/malignant cell

Primary fibrinolysis (fibrinogen lysis)

Problem: excess TPA (activation of plasmin)

Primary fibrinolysis (fibrinogen lysis)

▪ clot dissolution (excessive) results to increase FSP (spil products: D-dimer)/FDP (fragments: X and Y) that interfere with coagulation and platelet function Secondary fibrinolysis (fibrin lysis)

Secondary fibrinolysis (fibrin lysis)

▪ occurs in DIC (simultaneous clotting and fibrinolysis)

Secondary fibrinolysis (fibrin lysis)

Euglobulin Test markedly shortened

PRIMARY

Euglobulin Test normal to slightly shortened

SECONDARY

Platelet count > 100 x 109/L

PRIMARY

Platelet count < 100 x 109/L

SECONDARY

AT-III normal

PRIMARY

AT-III decreased (due to FSP)

SECONDARY

D-dimer Test negative

PRIMARY

D-dimer Test positive

SECONDARY

: compromises health and normal functioning of the body

PATHOLOGIC THROMBOSIS

▪ can be acquired or inherited

PATHOLOGIC THROMBOSIS

PATHOLOGIC THROMBOSIS risk factors include:

• Inherited/Congenital conditions • Acquired conditions

: related with congenital deficiencies in the regulatory proteins/inhibitors (antithrombin II, any antiplatelet reg proteins) and defective factors

• Inherited/Congenital conditions

: related with lifestyle such as age, smoking and other diseases (immunocompromised)

• Acquired conditions

▪ composed of platelets with small amounts of fibrin, red and white cells - “white clot”

Arterial thrombosis

Arterial thrombosis causes:

• hypertension • hyperviscosity • qualitative platelet abnormalities • atherosclerosis (accumulation of fats in blood vessels interfere with normal blood flow)

▪ composed of large amounts of fibrin and red cells

Venous thrombosis

▪ associated with slow blood flow, activation of coagulation, impairment of the fibrinolytic system, and deficiency of physiological inhibitors

Venous thrombosis

recurrent venous thrombosis

Antithrombin (AT) Deficiency

DIC, liver disease, nephrotic syndrome, oral contraceptives, and pregnancy

Antithrombin (AT) Deficiency

Not associated with thrombosis

Heparin Cofactor II Deficiency

thromboembolism

Protein C Deficiency

Vitamin K deficiency, liver disease, malnutrition, DIC, and warfarin therapy

Protein C Deficiency

vitamin K deficiency, liver disease, and DIC

Protein S Deficiency

factor V Leiden is not inactivated → excessive clot formation

Activated Protein C Resistance (Factor V Leiden)

increase in the concentration of plasma prothrombin

Prothrombin Mutations

Other Inherited Thrombotic Disorders

• Elevated activity levels of factor VIlI are associated with venous thrombosis embolism. • Factor XII deficiency • Dysfibrinogenemia; Hyperhomocysteinemia • Tissue factor pathway inhibitor (TFPI) deficiency

– principal inhibitor of thrombin

• AT-III

: recurrent deep venous thrombosis in anatomic sites (pulmonary embolism in lungs; thrombophlebitis in lower extremities)

• ↓ AT-III

• normal value in vivo: 85-125%

AT-III:

• moderate risk: 60-80%

AT-III:

• significant risk: 50-60%

AT-III:

• preferred sample for test: serum (reflects lower plasma AT-III level)

AT-III:

• normal value in serum: 70- 125%

AT-III:

prevent platelet activation and aggregation and are most effective in the treatment of the arterial diseases.

Antiplatelet Drugs

irreversibly affects platelet function by inhibiting the cyclooxygenase (COX) enzyme and thereby the formation of thromboxane A2 (TXA2).

Aspirin (acetylsalicylic acid)

: a potent activator of platelet

thromboxane A2 (TXA2)

Other antiplatelet drugs include

dipyridamole, thienopyridines, ticlopidine and clopidogrel

Acquired Thrombotic Disorders

• Lupus anticoagulant does not inhibit in vivo coagulation but may cause prolonged in vitro tests

1. Lupus Anticoagulant/ Antiphospholipid Syndrome

• Development of antibodies against heparinplatelet factor 4 complex.

2. HeparinInduced Thrombocytopenia

• This immune complex causes platelet activation, platelet microparticles, thrombocytopenia, and hypercoagulable state.

2. HeparinInduced Thrombocytopenia

▪ inhibit thrombin and fibrin formation

Anticoagulant Drugs

• the anticoagulant activity of heparin is enhanced by binding to AT.

1. Intravenous anticoagulant: Heparin

inactivates thrombin and factor Xa

• Heparin-AT complex

is monitored by APTT & activated Clotting time

• Heparin dosage

What is the treatment for heparin overdose?

• inhibit vitamin K-dependent factors and other vitamin K-dependent proteins.

2. Oral Anticoagulants: (Coumadin, Warfarin, Dicumarol)

• alter hepatic synthesis resulting to inability of the liver to carboxylate the glutamyl residue of the factors leading to their functional deficiency.

2. Oral Anticoagulants: (Coumadin, Warfarin, Dicumarol)

These factors/proteins formed are referred to as PIVKA/des-y-carboxy proteins.

2. Oral Anticoagulants: (Coumadin, Warfarin, Dicumarol)

crosses the placenta and is present in human milk.

• Coumadin (warfarin)

• Therapy is monitored by PT/international normalized ratio (INR).

2. Oral Anticoagulants: (Coumadin, Warfarin, Dicumarol)

What is the treatment for accidental warfarin poisoning?

- used to break down fibrin clots to restore vascular function and to prevent loss of tissues and organs

Thrombolytic Drugs

also used in acute arterial thrombosis for immediate thrombolysis

Thrombolytic Drugs

not fibrin specific (targets the whole clot in general)

Urokinase Streptokinase

used in the treatment of venous thromboembolism, MI, and thrombolysis of clotted catheters

Urokinase