Hematology: Thrombosis

Front 1

Hypercoagulable state

Back 1

Imbalanced hemostasis--> more procoagulant/clotting activity (or, less anticoagulant activity).

Front 2

Thrombosis

Back 2

Inappropriate formation of a plt. and/or fibrin clot that obstruct blood vessels known as thrombus (thrombi)--> ischemia & necrosis.

Front 3

Thrombophilia

Back 3

- Predisposition to thrombosis.
- Secondary to a congenital or acquired d/o.

Front 4

Embolus

Back 4

- A piece of thrombotic material & travel through circulation.
- Lodging at a distant site, obstructing (embolism) blood flow--> ischemia & necrosis or cell death.

Front 5

Thromboembolism

Back 5

Blockage that originates form a thrombus

Front 6

Etiology

Back 6

- Physical, bilogical, or chemical events that release prothrombotic mediators from damaged blood vessels (or, surpression of antithrombotic substances)
- Inappropriate/uncontrolled plt. activation
- Uncontrolled triggering of the plasma coagulation sx.
- Inadequate control of coagulaton &/or impaired fibrinolysis.

Front 7

Venous thrombosis

Back 7

- Caused by coagulation sx imbalances.
- DVT, PE
- 1:1000/year

Front 8

Arterial thrombosis

Back 8

- Mechanism: atherosclerotic plaque formation in the vessel walls.
- Caused 80% of heart attack (myocardial infarct); 85% of strokes (cerebral infarct).

Front 9

Acquired thrombosis

Back 9

Risk factors:
- Age, immobilization, oral contraceptives, pregnancy, smoking, inflammation.
Associated w/ systemic dz:
- MPD- ET, PV; cancer; leukemia- APL, AML--> DIC
Double Hit: congenital + acquired--> synergistic effects

Front 10

Thrombosis: Lab evaluation

Back 10

- Recommended to perform assays 14 days after anticoagulation therapy is d/c'd.

Front 11

Antiphospholipid (APL) antibodies.

Back 11

- Family of Ig that bind protein-PL complexes.
- Non-specific inhibitors: may bind a variety of protein- PL complex.

Front 12

Lupus Anticoagulant (LA)

Back 12

- IgG immunoglobulins directed against several phospholipid protein complexes.
- Prolong the phospholipid dependent PTT rxn.

Front 13

Test systems that are sensitive to LA & must fulfill the requirements.

Back 13

- Prolonged PL dependent clot formation (i.e. aPTT).
- Mixing study: failure to correct prolonged aPTT by mixing w/ normal PPP (plt poor plasma <10,000/uL).
- Correction of the prolonged screen by addition of excess PL.
- Exclusion of other coagulopathies.

Front 14

Lupus Anticoagulant (LA) lab evaluation.

Back 14

- Mixing study is necessary: LA vs. specific inhibitors & factor deficiency
- 1st: perform thrombin time to r/o heparin as a cause of prolonged PTT.
- If thrombin time w/in the normal limits (no heparin), Pt's PPP is mixed 1:1 w/ pooled normal plasma--> perform PTT.
- If the result of the mixture w/in 10% of the pooled normal plasma= CORRECTION OCCURED= factor deficiency?
- Next, incubate pt. PPP & pooled normal PPP for 1-2hrs at 37 Celsius.
- Factor deficiency if PTT remains corrected.
- Suspect LA if the initial 1:1 mixture remains uncorrected.
- Confirmation analysis: new aliquot of pt. PPP is added to high PL rgt.--> shortening of PTT by at least 8 seconds= LA.
- Possible presence of anti-factor antibody if the initial 1:1 mixture= normal & incubated mixture= uncorrected.

Front 15

Dilute Russell's Viper Venom Time (dRVVT)

Back 15

- Sensitive to LA and Coumadin/Warfarin effect.
- dRVVT is neutralized by LA--> prolonged test.
- High PL rgt. corrects the prolongation= confirm LA.

Front 16

Antithrombin (AT) assay

Back 16

- Bind to heparin; inhibit thrombin, factors 10, 9, & 11.
- AT deficiency can be acquired (liver dz, prolonged heparin therapy, oral contraceptives, DIC) or congenital.

Front 17

Protein C & S assays

Back 17

- Natural anticogualnt pathway
- Heterozygous deficiencies--> increased risk of recurrent DVT & PE.

Front 18

Heparin Induced Thrombocytopenia (HIT).

Back 18

- Adverse effect of unfractioned heparin therapy.
- Also called HIT w/ thrombosis (HITT)
- Detection of antibodies to the PF4-heparin complex.
- Suspected when plt count <150 X 10^3/uL (or by 50% in pts w/ previous thrombocytopenia).
- D/c heparin therapy & proceed w/ alternate anticoagulant.

Front 19

HIT laboratory tests

Back 19

- Screening: kit & heparin induced antibody immunoassay
- Reference method: 14C serotonin release assay
- Endothelial damage--> activated plts release serotonin (delta granules)--> vasoconstriction