The Problem of Transfusion Therapy for the Bleeding Chronic Liver Disease Patient Akram Al-Hilali 2009
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What is Chronic Liver (?Disease (CLD The clinical state arising from gross decompensation of hepatocyte and hepatic lobe with regards to synthetic, detoxifying and metabolic functions. Final stage : ESLD August 6, 2014
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Why do ?need
CLD patients Transfusion
• Bleeding from local defects – Complications of portal hypertension
• Coagulopathy – A very complicated syndrome of coagulation and antithrombotic factor defects. Is this really correlated with severity of clinical bleeding?
• Splenomegaly – Anemia – Thrombocytopenia
• Secondary anemia August 6, 2014
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The local defect portal circulation
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Portal Hypertension
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Consequences of Portal hypertension • Splenomegaly. • Varices at the lower part of the esophagus and upper part of the stomach fundus. • Varices at the lower part of the rectum- hemorrhoids August 6, 2014
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Coagulation Factors Deficiency
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Fibrinolysis in CLDtPA • Increased tPA activity in plasma, due to poor clearance by the liver. • Decreased PAI in liver, though antigen level in blood is normal or raised. • Probably PAI is released fast from liver due to ↑tPA. • Decreased plasminogen in blood. ↓production or ↑consumption? • Normal level of aVII, in spite of low FVII in blood suggests an ongoing process of activation and thrombosis, DIC. • Monocytes release more TF in cirrhosis. • Result is an ongoing fibrinolytic process in blood. • All kinds of chronic liver disease share these findings. August 6, 2014
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FIBRINOLYTIC PROCESS
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Fibrinolysis- TAFI • TAFI (Thrombin-activatable fibrinolysis inhibitor) is a liver factor. • It is markedly reduced in liver cirrhosis • As a result, fibrinolysis is increased • Its level was found to be inversely related to survival Gresele P. et al. Thromn Res 2008, 126:6, 763-8
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TAFI deficiency
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Other hemostatic problems
• Diminished FXII and FXI- synthesis defect. • Low fibrinogen, basically a finding in terminal cases. Level may become very low. This is due to fibrinolysis, but partly a synthetic defect. • Dysfibrinogenemia, leading to defective fibrin. • Low FXIII • Low α2 antiplasmin. • High FDP’s • Coagulopathy of massive transfusion. • Some coagulation authorities deny that coagulopathy is a major player in CLD bleeding.* *PM Mannucci,2006. J. of Thromb Haemost, 4:721-23 August 6, 2014
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Platelets defect • Low count due to splenomegaly, not usually significant. Up to 65% of cases. • Count drops further with DIC and consumption. • Abnormal function in CLD due to an intrinsic abnormality as well as high FDP’s • Prolonged bleeding time is well correlated with bleeding after needle biopsy in CLD August 6, 2014
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How to Manage? ?Prophylaxis • No place for regular prophylactic correction of coagulation. • Correction only when patient is going for an invasive procedure. • Measures to help vessel-based hemostasis: β blockers, vaso-active agents, banding and sclerotherapy • Invasive procedures should be restricted to the very essential and urgent. • Preoperative discussion, consultation and planning August 6, 2014
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How to manage? Invasive procedure • Coagulation is to be corrected only within 2-3 hours prior to procedure. It will be corrected to a little higher than normal by 2-4 FFP units. • Correction is to continue throughout the procedure. • Monitoring labs during procedure. August 6, 2014
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How to manage? Acute spontaneous bleeding • Red cell transfusion, as necessary. • FFP liberally, very fast infusion. At least 20 ml/min. • Cryoprecipitate supplement for fibrinogen
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Management of uncontrolled bleeding • Bleeding from a local cause: attention to the bleeding spot. • Continue vessel measures: β blockers, vasoactive agents, banding and sclerotherapy. • Correction of coagulation may become impossible by FFP alone in late stages. • Cryoprecipitate: one unit for every 3 or 4 FFP. • Factor concentrate : Prothrombin Complex • Recombinant aVII • Surgical intervention to deal with the bleeding may make situation worse August 6, 2014
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• • • •
Management of uncontrolled bleeding?Can we stop
Ethical issue. Family and consent. FVII and FXII assays- limits TAFI assay, when it becomes available in routine labs. • MELD score • Can patient be considered NFR, but transfusion continued? Local measures are proving more important than correcting coagulation. If they are utilized blood components can go on. • Consultation group August 6, 2014
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KFAF Hospital- Jeddah study • Retrospective study over 3 years. • Transfusion to chronic liver disease patients • All kinds of hepatitisassociated cirrhosis • Total patients transfused 4400. • CLD patients transfused 63 (1.43%) Presented at the Annual Scientific Meeting of the Australia and New Zealand Society of Blood Transfusion-Melbourne-Oct 2004
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.Jeddah
study-contd
CLD patients received : • 9.97% of total FFP transfused • 3.04% of total PRBC transfused. • 2.92% of total PC transfused • 5.8% of total Cryprecipitate transfused during the 3-year period. • Total transfusion episodes was 109.
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.Jeddah
study- Contd
• 28 patients (44.4%) died during the period. • 8 of them had cancer • One patient received a total of >180 of all components and died • He did not match another patient in author’s practice, who received 220 units and died. • Death from hepatic coma, renal failure, ARDS and multi-organ failure August 6, 2014
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End-stage Liver Disease (ESLD)-Prognostic score MELD scoring System 3.78[Ln serum bilirubin (mg/dL(] + 11.2[Ln INR] + 9.57[Ln serum creatinine (mg/dL(] + 6.43
Interpretation of the score For hospitalized patients, the 3 month mortality is: – 40 or more - 100% mortality – 30-39 - 83% mortality – 20-29 - 76% mortality – 10-19 - 27% mortality – <10 - 4% mortality Originally designed for post hepato-systemic shunt patients August 6, 2014
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?ANY CUT-OFF VALUES • Factor VII assay less than 7%, as checked before any transfusion. • FXII assay of less than 12% before any transfusion. • MELD score above 40 • In actual hepatic coma at presentation • In shock at presentation. August 6, 2014
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