‘COMGULATION ABNORMALITIES: BLEEDING AND THROMBOSIS INTRODUCTION Problems in hemostasis frequently arise in critically ill patients and are often complex due to the various effects of sepsis, multiple organ failure, indwelling catheters, im planted devices, and the simultaneous administration of multiple drugs. What follows is a clinical approach to the hemostatic problems frequently encountered in these patients. BASIC COAGULATION Three components are necessary for normal clot formation: 1) intact vascular wail endothelium 2) a normal clotting cascade and 3) platelets of adequate number and function. .Although none of these portions of the clotting system works in isolation, most clotting disorders affect specific parts of one of these three components. While abnormalities of the vascular wall do result in clinical coagulation disorders, they are rare and not usually of concern in critical care disorders. Therefore, physicians in intensive care settings most often face disorders of the clotting cascade or platelet number or function. Most physicians who are not required to confront coagulation problems on a routine basis are unlikely to be comfortable referring to the clotting cascade when analyzing clinical problems; however, the classical clotting cascade, shown in Figure 1, does provide’ information which is useful at the bedside. The left side of the cascade, known as the intrinsic pathway, begins with factor XII, and ends with the breakdown of fibrinogen which is also known as factor I. A more useful way to remenber this is to refer to this part of the cascade as the PIT system since the activated partial thromboplastin time is a measure of its function. The right side of the cascade, known as the extrinsic pathway, is activated at factor VII and proceeds also through the clotting of fibrinogen. This part of the cascade may be thought of as the PT system since the prothrombin time is a measure of its function.Notice should ke taken that the portion of the cascade from factor X through fibrinogen is common to both pathways and is referred to as the common pathway. Additional clinical insights are gained by the knowledge that factor VII is only in the PT pathway and factors XII, XI, IX and VIII are only in the PTT pathway. Consequently, anything that decreases the level o£ one of the clotting factors beneath a critical value or inhibits one of the steps in the cascade will slow the corresponding pathway or pathways and therefore prolong the PT and/or the PIT depending on whether the factor or step involved is in the extrinsic pathway (PT prolonged), intrinsic pathway (PTT prolonged), or common pathway (PT and PTT prolonged). A second way for prolongation of the PT and PTT to ocour is if two factors, one in each arm of the cascade above the common pathway, are similarly affected. Platelets also are involved in a complicated biochemical reaction sequence which causes platelet adhesion, aggregation, and plug formation to occur in association with the clotting cascade and the vascular endothelium. Receptors for several of the clotting factors are found on the surface of platelets; von Willebrand factor, produced in vascular endothelial cells, is important for platelet adhesion, and fibrinogen is necessary to form a stable platelet plug. Despite this, most platelet problems in critial care are due to thrombocytopenia and platelet dysfunction is a much less frequent problem. Therefore, for evaluation of platelet problems a simple platelet count is the most useful test. For platelet function “abnormalities platelet adhesion and platelet aggregation tests can be obtained, but a template bleeding time in our experience, despite recent statements questioning its validity, still provides useful information when applied in appropriate clinical settings and if done by trained personnel. “APPROACH TO BLEEDING General .. oWhen.bleeding-occurs a PT, PTT, and platelet count usually are obtained as an initial work-up. Just as important is an evaluation of the patient‘s clinical situation and history to avoid requesting unnecessary, and nore costly, sophisticated clotting tests. Obviously if the patient has had recent surgery or trauma, anatomic bleeding must be considered. In some cases other structural lesions may also be bleeding such as an ulcer or tumor and need to be considered before assuming that a coagulopathy is present.When a history is taken, asking a patient or the family general questions concerning any past bleeding problems will usually be fruitless. Specific questions concerning intra- operative or post-operative bleeding with special attention to dental extractions and tonsillectomy are much more helpful and may result in positive findings when patients have previously denied bleeding problems. A history of menorrhagia or easy bruising may aiso be helpful although many persons report a history of these problems without having a coagulation defect. Clotting Factor Analysis In analyzing PT and PTT results, most patient‘s problens fit into categories which can easily be recognized with a basic understanding of the coagulation cascade as outlined above. TABLE 1. CAUSES OF A PROLONGED PT ONLY 1) Early Vitamin K deficiency 2) Recent Coumadin initiation 3) Mild liver disease 4) Congenital deficiency of factor VII (rare) Finding the PT to be prolonged and the PTT to be normal points to a deficiency of factor VII since it is the only factor in the PT system not in the PIT system. Vitamin K-dependent factor VII has a half-life of only about 6 hours and in critically il] patients frequently reaches low levels rapidly when there has been poor oral intake, there are antibiotics destroying vitamin K-producing bovel flora, and there has been no parenteral administration of vitamin K. When Coumadin has been started, the factor VII tends to be the first factor level to fall and therefore may cause only a PT prolongation until the other vitamin K-dependent factors II, IX, and X are depressed. At that point the PTT will also be prolonged since the latter factors are in the PTT system. Thus despite the fact that the PT is used to monitor Coumadin therapy, the additional finding of a long PTT does not by itself indicate that @ coagulopathy is present, Early liver disease may prolong the PT but in liver disease of any severity a loss of factor V production should soon prolong the PIT as well. Congenital deficiency of factor VII is a rare disorder which is included to make the point that when only factor VII is absent, the PT is long and the PIT should be normal.