Coagulation Disorders Flashcards
: proteins that initiate the IP
XII, HK, PK
denotes the time when plasma coagulation factors come in contact with tissue/artificial surfaces
CONTACT PHASE
product of contact phase:
IX
Not significant in the body when deficient because there are still intrinsic activators of FIX
XII, HK, PK
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
Tested via in vivo testing (not by mixing studies)
XII, HK, PK
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
CONTACT PHASE FACTORS DEFICIENCY
autosomal recessive disorder
Factor XII (Hageman factor) Deficiency
Prekallikrein (Fletcher factor) Deficiency
HMWK (Fitzgerald/Flaujeac factor) Deficiency
clinical findings: no bleeding disorder but manifested by excessive clotting (but rather thrombotic disorder)
Factor XII (Hageman factor) Deficiency
PK
laboratory findings: all normal except APTT (prolonged)
Factor XII (Hageman factor) Deficiency
correction: adsorbed plasma, aged serum, fresh normal plasma (all reagent plasma with contact phase)
Factor XII (Hageman factor) Deficiency
treatment: none
Factor XII (Hageman factor) Deficiency
Prekallikrein (Fletcher factor) Deficiency
clinical findings: no bleeding disorder but manifested by excessive clotting
Prekallikrein (Fletcher factor) Deficiency
laboratory findings: all normal except APTT (shortened)
Prekallikrein (Fletcher factor) Deficiency
deficiency results to:
• poor contact phase reactions
• kinin formation deficiency
• defective fibrinolysis reaction
HMWK (Fitzgerald/Flaujeac factor) Deficiency
APTT: normal to mildly prolonged (low deficiency)
HMWK (Fitzgerald/Flaujeac factor) Deficiency
Thrombin will still be generated
Factor XII (Hageman factor) Deficiency
Thrombotic (abnormal formation of clots): FXII, aside from activating FXI, activates plasminogen to plasmin → more fibrinolysis
Factor XII (Hageman factor) Deficiency
CF stops the bleeding during injury → Coagulation cascade continues to activate = ↓ FXII = ↓ Plasmin = ↓Fibrinolysis = ↑ Clot formation = Thrombosis
Factor XII (Hageman factor) Deficiency
even if it has nothing to do w/ bleeding disorders
Factor XII (Hageman factor) Deficiency
Does not cause bleeding disorders; Asymptomatic
Factor XII (Hageman factor) Deficiency
FXII will bring (?) (cofactor) to activate plasminogen to plasmin
Prekallikrein (Fletcher factor) Deficiency
Kallikrein
↓ Kallikrein = (?) Clot formation = (?)
Prekallikrein (Fletcher factor) Deficiency
↑
Thrombosis
(?) APTT: PK reacts with (?) = (?) contact phase activation; indicates (?) of PK
Prekallikrein (Fletcher factor) Deficiency
shortened
kaolin (activator)
speeds up
low deficiency
(?) 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
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
I
Prothrombin deficiency
II
F VII deficiency
VII
F X deficiency
X
-Afibrinogenemia
-Dysfibrinogenemia
I
Owren’s disease Labile factor deficiency Parahemophilia
V
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
- Acute DIC
- 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
- Lupus Anticoagulant/ Antiphospholipid Syndrome
• Development of antibodies against heparinplatelet factor 4 complex.
- HeparinInduced Thrombocytopenia
• This immune complex causes platelet activation, platelet microparticles, thrombocytopenia, and hypercoagulable state.
- HeparinInduced Thrombocytopenia
▪ inhibit thrombin and fibrin formation
Anticoagulant Drugs
• the anticoagulant activity of heparin is enhanced by binding to AT.
- 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.
- 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.
- Oral Anticoagulants: (Coumadin, Warfarin, Dicumarol)
These factors/proteins formed are referred to as PIVKA/des-y-carboxy proteins.
- 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).
- 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
