The Coagulopathy of Chronic Liver Disease

Coagulopathy of Chronic Liver disease

Clinical bleeding
Decreased levels of procoagulants

except factor 8 and vW factor

Also parallel decrease in anti-coagulants

protien C, antithrombin

Laboratory testing

Prothrombin time APTT Poor correlation to bleeding post procedure Liver biopsies etc Also poor correlation with spontaneous bleeding- GI bleeds Correction of clotting factors ie recombinant F 7 fail to control clinical bleeding even if PT shortened

Laboratory testing

Rebalanced coagulation 2 to parallel reduction in both pro and anti coagulants Thrombin generation shown to be similar to healthy subjects PTT measurementLack of thrombomodulin (Protein C activator) in vitro

Laboratory testing
PT expressed as INR used for prognostication- MELD score Validated for patients on Vitamin K anatgonists Not standardized for liver disease Need for alternative system using calibration based on plasma of people with CLD

Relative deficiency of pro and anti coagulant factors Fragile balance Can tip towards thrombosis or bleeding depending on other risk factors

Role of platelets

Attach to damaged vessel walls Interact with vW factor, promoting aggregation Thrombocytopenia common in CLD High levels of vW factor restores platelet adhesion Low levels of ADAMTS 13 further contributes to restored plt function Platelet count of 60 equivalent thrombin generation to lower limit of normal subjects

Not naturally 'autoanticoagulated' Increased risk of thrombosis esp in portal venous system Increased risk of peripheral vein thrombosisDVT > PEs retrospective studies

Lack of evidence of correcting coagulation with plasma products pre-procedure

Increased life expectancy in pts with CLD Increasing episodes of thrombosis Need for thromboprophylaxis Surgery, immobilization, malignancies Contradicts current clinical practice Need for further studies

Portal vein Thrombosis

Common in advanced CLD 8 to 25% LMWH or Vit K antagonists used May need to treat varices prior

Portal vein Thrombosis

Portal vein thombosis worsens post transplantation prognosis Primary prevention in pts awaiting transplant LMWH vs Vit K antagonists Reduction of protien C levels by Warfarin?increases risk of thrombus Trials underway ?new direct thrombin inhibitors preferable ?Role of regular anti-platelet usage to prevent arterial thrombus

Conclusions

Not autoanticoagulated

Lab tests do not reflect 'in vivo' Not for routine correction unless clinical condition warrants Risk of thrombus- need for prophylaxis Need for more studies- warfarin, aspirin

Management of bleeding

Investigate for other causes- infections, renal failure etc Platelet transfusion only if plts <50,000. Aim target >70,000 FFP- therauptic effect is transient and with risks Cryoppt if fibrinigen <10mg/dl- aim normal levels Tranexamic acid, epsilon amino caproic acid help, but increase risk of thrombosis

Management of bleeding
DDAVP- no benefit in variceal bleeding or liver surgery Recombinant factor 7a- transient effect need multiple doses Expensive Topical agents- fibrin glue, cyanoacryates, thrombin products Surgical procedures to reduce blood loss- thermal, radiofrequency ablation, hydrojet dissection, maintaining low CVP, reducing portal pressures