Coagulation Issues: Fibrinolysis & HIT: Helpful Graphics

Fibrinolysis

Fibrinolysis is the dissolution of the clot formation process involving the plasma protein plasminogen.  This system of enzymes dissolves blood clots by the lysis of fibrin.  Fibrinolysis plays a role as well in other biological processes such as tissue repair, macrophage activation and function, ovulation, and embryo implantation.  Fibrinolysis is mediated by plasmin and during blood coagulation, lysis of fibrin by plasmin results in derivation fragments of fibrin called fibrin degradation products (FDP).

Thrombocytopenia

Thrombocytopenia is a condition where the circulating platelet count falls below 50,000 platelets per microliter.  As a result of such low circulating platelet levels, people have bleeding tendencies similar to those experienced by hemophiliacs (deficiency of Factor VIII), except that bleeding occurs primarily from small capillaries and venules, as opposed to the larger vessels involved with hemophilia.  This condition is usually antibody mediated (idiopathic thrombocytopenia), and the cardiac patient can be impacted by either long term heparin therapy (heparin induced thrombocytopenia), or significant platelet loss and sequestration secondary to the extracorporeal circuit.

HIT

Heparin induced thrombocytopenia (HIT) complicates heparin therapy in about 2% to 5% of patients undergoing cardiopulmonary bypass.  While manifesting mildly without causing excessive bleeding in most patients, it has occasionally led to life threatening hemorrhage, acute arterial thrombosis, myocardial infarction, stroke and limb ischemia.  Recent studies found that this condition results from a specific IgG antiheparin antibody which binds to repeating antigenic determinants in heparin.  This antiheparin antibody in turn binds to the surface of the platelet.  There is no reliable method for predicting which patients will develop HIT.

Measurement

When plasmin breaks down fibrin, a number of soluble parts are produced. These are called fibrin degradation products (FDPs). FDPs compete with thrombin, and thus slow down clot formation by preventing the conversion of fibrinogen to fibrin. This effect can be seen in the thrombin clotting time (TCT) test, which is prolonged in a person that has active fibrinolysis.

FDPs, and a specific FDP, the D-dimer, can be measured using antibody-antigen technology. This is more specific than the TCT, and confirms that fibrinolysis has occurred. It is therefore used to indicate deep-vein thrombosis, pulmonary embolism, DIC and efficacy of treatment in acute myocardial infarction. Alternatively, a more rapid detection of fibrinolytic activity, especially hyperfibrinolysis, is possible with thromboelastometry (TEM) in whole blood, even in patients on heparin.

TEM is useful for near real-time measurement of activated fibrinolysis for at-risk patients, such as those experiencing significant blood loss during surgery. ^[4]

Testing of overall fibrinolysis can be measured by a euglobulin lysis time (ELT) assay. The ELT measures fibrinolysis by clotting the euglobulin fraction (primarily the important fibrinolytic factors fibrinogen, PAI-1, tPA, alpha 2-antiplasmin, and plasminogen) from plasma and then observing the time required for clot dissolution. A shortened lysis time indicates a hyperfibrinolytic state and bleeding risk. Such results can be seen in peoples with liver disease, PAI-1 deficiency or alpha 2-antiplasmin deficiency. Similar results are also seen after administration of DDAVP or after severe stress.^[5]