Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (405 page)

Suggested Reading

Dupuis-Girod S, Bailly S, Plauchau H. Hereditary hemorrhagic telangiectasia: from molecular biology to patient care.
J Thromb Haemost.
2010;8:1447–1456.

HEMOSTATIC FAILURE IN CARDIOPULMONARY BYPASS SURGERY

   Definition and Etiology

Bleeding is a common complication in patients undergoing open heart surgery (approximately 30% of patients require red cell transfusions after CABG). The etiology of bleeding is multifactorial, as reflected in multiple laboratory abnormalities. Platelets, the fibrinolytic system, both the extrinsic and intrinsic coagulation pathways, and the complement system are activated, resulting in bleeding, and possibly thrombosis. The principal causes of bleeding in bypass surgery are excess heparin, fibrinolysis, and decrease in platelet number and function. Another cause of bleeding resulting in the need for transfusions are the antiplatelet and antithrombotic drugs used in addition to heparin: clopidogrel or prasugrel, anti-GPIIb/IIIa such as abciximab, and aspirin. Venous thromboembolism (DVT and PE) is often present but may be difficult to recognize.

   Laboratory Findings

   Hemostasis, platelet function, and fibrinolysis can be monitored by conventional techniques, or at the surgical room site, by a thromboelastogram.

   Thrombocytopathy (functional platelet defect): frequent occurrence due to platelet activation during bypass; exacerbated by the use of drugs that interfere with platelet function.

   Thrombocytopenia: platelets decline temporarily. By the end of surgery, their number is typically reduced by 40–60% due to hemodilution, activation, and consumption during bypass procedure. Occasionally, the decline may be more profound and compromise hemostasis.

   Hyperfibrinolysis: elevated fibrin(ogen) degradation products (FDP).

   Bleeding caused by heparin is frequently related to incomplete inactivation by protamine. “Heparin rebound” is a term that refers to delayed release of heparin from the lymphatic system after protamine has already been cleared from plasma. It may result in bleeding after completion of surgery. “Heparin resistance” may be secondary to antithrombin deficiency. Excessive infusion of protamine may itself result in bleeding.

   DIC: The concentrations of
D
-dimer and of fibrinopeptides A and B are increased.

THE COAGULOPATHY OF LIVER DISEASE

   Definition

A syndrome of excessive
bleeding,
occasionally
thrombosis
, resulting from severe liver disease. The coagulopathy is multifactorial, due to the liver’s many functions in hemostasis and thrombosis. Most coagulation factors are decreased, with the exception of fibrinogen, factor VIII, and von Willebrand factor (VWF). While fibrinogen becomes severely decreased in advanced liver disease, the latter two are often greatly increased. The VWF cleaving protease ADAMTS13 is reduced in liver cirrhosis. Naturally occurring anticoagulants (protein C, S, antithrombin) are decreased. These changes lead to rebalancing of coagulation and often to poor correlation between measured levels of clotting factors and clinical bleeding or thrombosis.

   Decreased synthesis in clotting factors → bleeding. Prekallikrein and factor VII are one of the earliest clotting proteins to be decreased in liver disease. Fibrinogen is one of the last ones.

   Decreased clearing of activated clotting factors (especially factor Xa) → tendency to DIC.