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Hypercoagulable state


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mass of clot free in blood
blockage of blood vessel
Ischemic necrosis
death due to lack of blood flow
necrotic area
Why are thrombus formations life threatening?
Clots may dislodge/cause occlusion or infarct.
Why are thrombi life-saving?
1. Stop bleeding
2. Maintains homeostasis
What factors pre-dispose a patient to thrombosis?
1. Injury to endothelium
2. Altered blood flow
3. Altered hemostatic systems
4. Proteins
5. Platelets
What are 5 therapeutic measures for thrombosis?
1. Low dose heparin
2. Full dose coumadin
3. Aspirin
4. Stockings
5. Physical therapy
2 Inhibitors of Fibrinolysis
4 Inhibitors of Coagulation
-Protein C
-Protein S
Activator of Fibrinolysis
Plasmin activation
Activator of Coagulation
-Coag factors
8 Risk factors for Thrombosis
4 Challenges causing Thrombosis
1. Injury
2. Pregnancy
3. Surgery
4. Medications
What general lab results accompany thrombosis?
1. History
2. PT/PTT - normal to sl. low
3. NORMAL bleeding time
4. NORMAL platelet count
What are the 4 more common hereditary disorders of hypercoagulation?
1. Protein C defic.
2. Protein S defic.
3. ATIII defic.
4. APC resistance
What are the similar features of the four hereditary disorders?
1. All autosomal dominant
2. All cause DVT
Which disorders have earliest onset?
Proteins C/S - at birth in homozygotes
Which disorders have earliest onset at adolescence?
Proteins C/S - heterozygotes
ATIII - Heterozygotes
When does APC resistance become apparent in patients?
Homozygotes - age 10-40
Heterozygotes - about 40
Which disorder can cause:
-Superfic. thrombophlebitis
-Purpura fulminans
Super-thrmbophleb = Protein S
purpura fulminans = Protein C
What's the only difference btwn PRotein C/S disorders?
-S causes pulmonary embolism and thrombophlebitis
-C causes purpura fulminans.
-Homozygous C is fatal
What causes PRotein S deficiency?
-Congenital - genetics
-Acquired - Vit K defic, Liver disease
Why does warfarin/coumadin therapy induce protein s/c deficiency?
They have shorter t1/2's than other factors, so decrease faster; leaves patient at risk for thrombosis.
-What does Factor V leiden deficiency cause?
-What causes it?
-APC resistance
-Congenital - genetics
What is the main problem in APC resistance?
-A point mutation of factor five; unable to be inactivated by APC.
What 2 types of screening tests are used for APC resistance?
1. Clot based - PT/APTT
2. Chromogenic
What test is used to confirm APCR?
PCR on isolated DNA
What is the principle of the aPTT for Fx V leiden?
-Fx V deficient plasma + Pt.
-If prolonged, Fx V is ok
-If not, Fx V is resistant.
What type of APCR is more common; hetero or homozygous?
Homozygous - 50-100%
Hetero = 5-10%
What are 7 results of Thrombosis?
1. Deep vein thrombosis
2. pulmonary embolism
3. recurrent pregnancy loss
4. Myocardial infarct
5. CVA
6. Phlebitis
7. Post-op thrombosis
What are the 3 main lab criteria for diagnosing LA?
-Abnormal PT
-Prolonged PTT that doesn't correct
-Pos drVVT
What is the LA basically?
An Antiphospholipid Antibody.
What are non-lupus causes of anticardiolipin antibody?
-immune thrombocytopenic purpura
What are the 2 more common causes of deep vein thrombosis?
-LA - 8-14%
-Factor V Leiden 40-50%
-Protein S = 5%
-PC/ATIII = 3%
why are the pt/ptt prolonged in LA states?
-They inhibit clotting in vitro by attacking actin; but not in vivo.
What are 3 types of tests for LA?
1. Increased phospholipid (sta-clot)
2. Decreased phospholipid
3. Specific Elisas for IgG/M
What is the basic principle of the StaClot procedure?
1. 2 tubes incubated; one w/ hexagonal phase phospholipid.
2. Run aPTT on both; the HPE will neutralize LA if present
3. Compare clotting times.
What tests specifically detect LA's?
-LA screen
-LA confirm
What is the reagent in LA tests?
Dilute Russell's viper venom
What is the principle of the DRVVT LA-screen?
-Viper venom activates Fx X
-Bypasses VII/factors above 9/8 in intrinsic.
-Specific b/c less affected by factor deficiencies or inhibitors.
What happens in the LA confirm?
-More procoag phospholipid is put in to neutralize LA.
-Polybrene also added for heparin resistance.
Why would heparin interfere with LA testing?
Of course the PPT would be prolonged and uncorrected.
What's another name for inhibitor assays?
mixing studies
what is the principle of mixing studies?
-mix suspect plasma w/ PPP.
-If it doesnt correct, or is prolonged after incubation, confirm w/ factor assays.
-Increased phospholipid test
-Decreased phospholipid test
Incr = StaClot
Decr = LA COnfirm
So when do we test for inhibitors?
When PT/PTT are prolonged by:
-other factor inhibitors
If PT AND aPTT are abnormal and uncorrectable:
contamination, probly heparin
What 3 therapeutic agents given to patients with LA?
-LMWH if pregnant
What 2 miscellaneous thrombotic disorders must i know?
1. Hyperhomocysteinemia
2. Prothrombin mutations
What causes hyperhomocystin?
-Vascular toxin
What should i remember about prothrombin mutations?
-Test with PCR
-Lifelong Warfarin therapy
If not a factor disorder or circulating anticoagulant, what can alter fibrinolysis?
1. Plasminogen deficiency
2. Dysfibrinogenemia
3. Increased PAI-1
what is PAI-1?
Tissue plasminogen activator inhibitor - keeps the activation of plasminogen in check.
What causes plasminogen deficiency?
Autosomoal dominant inheritance.
How is plasminogen deficiency tested for?
Functional antigen assay

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