thrombotic disorders

thrombosis

actual formation of a clot

thrombophilia

increased risk of developing a clot

thrombotic disorder

condition resulting from thrombosis formation

venous thromboses

Red thrombi

• decreased blood flow allows coagulation cascade

• red cells get trapped in the fibrin mesh

• occurs more in lower limbs

• 80-90% of defects in coag proteins/platelets

arterial thromboses

white thrombi

• damaged endothelium and high blood flow allows platelet activation and coagulation cascade

• platelets trap leukocytes

• obstruct the artery

• induces ischemia

• 65% associated with coagulation protein/platelet defects

acquired thrombosis risk factors

• trauma, surgery, inflammation, infection, cancer

• immobilization

• stasis

• smoking

• obesity

• hypertension, poor diet, high cholesterol

• pregnancy

• HRT

• oral contraceptives

multi hit theory

most risk factors have small impact

• the risk for a thrombotic event is increased when 2 or more factors are combined

factor V leiden

activated protein c resistance

• mutation in factor 5 causes APC resistance

• autosomal dominant

• most common inherited in caucasians

• RCR test for point mutation

protein c or s deficiency

• reduced APC function leads to excessive clotting

• factors 5 and 8 go unchecked

• diagnose with functional assays and antigen assays to measure total or free protein levels

Prothrombin G20210A

• guanine is subbed with adenine

• leads to elevated factor 2 levels

• generates more thrombin

• most common in spain

• diagnose with molecular testing for mutation

• not detectable with PT/APTT

antithrombin defiency

• naturally occuring SERPIN anticoagulant

• enhanced by heparin

• autosomal dominant

• funtional activity assay and antigen assay to diagnose

anti-phospholipid antibodies

• autoantibodies target protein bound to phospholipids in cell membrane

• increases risk of thrombosis not bleeding

• most common cause of acquired thrombophilia

what are the common antiphospholipid antibodies?

• lupus anticoagulant

• anticardiolipin antiboiotics

• anti-beta 2 glycoprotein I

what are the key tests that lead to antiphospholipid antibodies?

• inhibits phospholipid dependent testing

• prolonged APTT

• fails to correct in mixing studies

when shoudl you test for HT?

not close to a thrombotic event

not on warfarin or heparin therapy

testing for HT

• not done on all patients

• costly

• confirmation of event with imaging

when is PT/APTT most useful?

when bleeding is suspected

• except with APL syndrome

what are the clot busting drugs for emergencies?

TPA

urokinase

streptokinase

initial treatment options

• heparin is immediately effective

• continue until warfarin works

routine/ongoing treatments

oral anticoagulants

what are the oral anticoagulants?

• warfarin

• DOAC

• aspirin